The functional categories of 627 ups, identified with GO enrichment analysis.
The above three terms can be defined as follows
\nwith
where
The above approach can be extended onto the mechanical problem of free vibration by replacing the linear form of (44) by the virtual work of the inertia forces [26]. These forces are:
In the case of electrostatic dielectricity, the local problems of the equilibrated residual method take the form [23]:
\nwith the bilinear and linear forms,
Taking into considerations the below definitions:
\nwhere
Above
The adaptive strategy for the complex problems of elasticity is based on the Texas Three-Step Strategy [24]. The latter strategy consists in solution of the global problem thrice on the so-called initial, intermediate and final meshes. The intermediate mesh is obtained from the initial one based on the initial mesh estimated values of element errors and the
The above four-step strategy can be easily extended onto the complex dielectric problems. It has to account only for the boundary layer phenomenon within the modification step, as two other phenomena do not appear in the problems of dielectrics. Other steps do not change.
\nIn this section of the chapter we consider the main difficulties in generalization of the hierarchical models, hierarchical approximations, equilibration residual method of error estimation and three- or four-step adaptive strategies, presented in the previous sections for the problems of elasticity and dielectricity, onto coupled problems of piezoelectricity.
\nThe first task here is to compose the elastic and dielectric models, defined with (28) and (33), respectively, into one consistent hierarchy of the piezoelectric media. Our proposition on how to perform this task follows from the main feature of both component hierarchies which are characterized with the independently changing orders
which determines the hierarchy P of piezoelectric models
is valid in the limit, the ordering of the coupled electro-mechanical solutions measured in the energy norm is not unique due to different signs of the strain (or elastostatic)
where
The most general case of the
It should be noticed that the monotonic character of the co-energy of the consecutive approximate solutions is not guaranteed here due to the coupled character of the electro-mechanical field.
\nPractical realization of the above concepts of hierarchical modelling and approximations is implemented by means of the
The normalized versions of the prismatic adaptive elements are presented above, where the 3D-based solid (or hierarchical shell), transition (an example of) and first-order shell mechanical elements are combined with the three-dimensional (or 3D-based symmetric-thickness) dielectric elements. In the figure the normalized coordinates are defined as
Piezoelectric solid/three-dimensional (top), transition/three-dimensional (middle), shell/three-dimensional (bottom) elements.
In order to generalize the equilibrated residual method for piezoelectricity the local elastic (44) and dielectric (47) problems have to be replaced with the coupled stationary problems describing the electro-mechanical equilibrium:
\nwhere
Definitions (45), (48) and (55) allow to rewrite (54) in the finite element language:
\nThe main disadvantage of the local solutions
The simplified solutions of the above two decoupled problems is suggested for serving the approximated error assessment of the coupled field.
\n\nIn the case of the coupled free-vibration problem we propose to apply the same approach as for the purely elastic vibrations. This means that the inertia forces introduced in Subsection 4.4 have to replace the volume and surface forces in the first equations (56) and (57). The element constitutive stiffness matrix
The main problem with the piezoelectricity in the context of adaptivity control of the three- or four-step
With this assumption in mind we generalize the adaptive scheme applied successfully for the complex elastic structures [28]. It can also be adopted for the dielectricity problems. The generalization is presented in Figure 2 in the form of a block diagram, where
Four-step
In the presented chapter we showed how to generalize hierarchical modelling,
We suggest to combine the hierarchical models for complex elastic structures with the analogous models of dielectricity in order to obtain all coupled combinations of the component mechanical and electric models. In the case of the approximations, we suggest to apply the common
In the error estimation, we propose to decouple the mechanical and electric fields in the local problems of the residual approach.
\nOur four-step
The support of the Polish Scientific Research Committee (now the National Science Centre) under the research grant no. N N504 5153 040 is thankfully acknowledged.\n
E – the hierarchy of dielectric models,
\x3c!--
Ubiquitination is one of the important protein post-translational modifications (PTMs) in human body, in which ubiquitin, a 76-amino-acid protein with a molecular weight of 8.5 KDa, is covalently attached its C-terminus to the ε-amino group of the substrate protein lysine residue through a multi-step enzymatic reaction cascade catalyzed by ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3) [1]. As substrate proteins commonly contain multiple lysine residues, there are a variety of ubiquitination forms such as monoubiquitination (only one ubiquitin attached to a protein), multiubiquitination (several lysine residues of substrate proteins were tagged with single ubiquitin), and polyubiquitination (a polyubiquitin chain is derived from subsequent ubiquitin covalently attached to lysine residues or N-terminus of the former ubiquitin) [2]. It is worth noting that the ubiquitin itself also has seven lysine residues to greatly complicate the topology of the polyubiquitin chain. Different ubiquitination forms perform different functions, such as monoubiquitination or multiubiquitination has been shown to be required for the entry of certain cargo proteins into vesicles at different stages of the secretory/endocytic pathway, while lysine-48 ubiquitin chain is mainly related to proteasome [3]. Like other PTMs, ubiquitination is a reversible reaction, and there are over 100 deubiquitination enzymes that regulate this process [4]. Ubiquitination coordinates with deubiquitination to regulate a broad host of cellular processes, including DNA repair, cell differentiation, signal transduction, enzymatic activity regulation, assembly of multiprotein complexes, protein trafficking, and autophagy [5]. Therefore, abnormal ubiquitination is associated with many diseases, including cancer, neurodegenerative disease, infection, and immune disorders [6]. Considering the importance of ubiquitination in tumorigenesis, different components of ubiquitin-proteasome system could be regarded as targets for discovery of anti-tumor drugs. With the application of first and second therapeutic proteasome inhibitors, such as Bortezomib (FDA has approved it for multiple myeloma and mantle cell lymphoma) [7] and Carfilzomib (FDA has approved it for relapsed and refractory multiple myeloma) [8], more and more anti-tumor drugs targeting UPS have been developed and approved by FDA, such as thalidomide, lenalidomide, and pomalidomide for treatment of multiple myeloma [9, 10].
\nLung squamous cell carcinoma (LUSC) is a common type of lung cancer without a clear molecular mechanism. Currently, surgery, radiation, and chemotherapy have made significant advances in lung cancer treatment, especially targeted drug therapy; for example, epidermal growth factor receptor (EGFR) mutation or EML4-ALK fusion-based targeted therapies have improved the survival time of patients with lung adenocarcinoma (LUAD). However, targeted therapy and early-stage diagnosis are still a big clinical challenge in LUSC patients [11]. Although FGFR1 amplification and DDR2 mutation have been nominated as “druggable” targets in LUSC patients, the clinical efficacies of the corresponding drugs are still under clinical trials [12, 13]. Considering that abnormal ubiquitination will lead to the occurrence of a variety of tumors and the widespread clinical applications of anti-tumor drugs for the ubiquitin-proteasome pathway in recent years, the study of quantitative ubiquitinomics in LUSC tissues may provide the direction for the development of biomarkers and new targeted drugs.
\nHigh-resolution liquid chromatography in combination with tandem mass spectrometry (LC-MS/MS) has been used as a power tool for large-scale identification of various PTMs such as ubiquitination, phosphorylation, acetylation, and N-glycosylation [14]. The challenge of the use of LC-MS/MS to identify endogenous ubiquitination sites on a large scale is the fact that ubiquitination is a low abundance event
This book chapter mainly reviewed ubiquitinated proteins (UPs) and differentially ubiquitinated proteins (DUPs) in ubiquitin-proteasome-system (UPS) in LUSC, and emphasized the potential regulatory role of ubiquitination in UPS, which offers scientific data for further research on the regulatory mechanism of ubiquitination on UPS, the molecular mechanism of UPS abnormality in tumor development, and the development of anti-tumor drugs targeting UPS.
\nHuman LUSC tissues (n = 5) and tumor-adjacent control lung tissues (n = 5) were surgically removed from patients, immediately stored in liquid nitrogen (−196°C), and then stored in freezer (−80°C). Clinical characteristics of each sample were described previously [19]. LUSC tissues (750 mg, equally mixed 5 tumor tissues) and control tissues (750 mg, equally mixed 5 control tissues) were washed 5 times with 3 mL 0.9% NaCl to clean blood on the surface of the tissues. The washed tissues (LUSC; or controls) were homogenized with urea lysis buffer [2 M thiourea, 7 M urea, 1 mM protein inhibitor PMSF, and 100 mM dithiothreitol(DTT)], sonicated, and centrifuged (15,000 g, 20 min, and 4°C). The supernatant was the extracted protein sample. The protein content was tested with Brandford method. The detailed procedure of protein extraction was described previously [19].
\nAn amount of DTT (final concentration = 10 mM) was added to each extracted protein sample, which was mixed (600 rpm, 1.5 h, and room temperature). An amount of iodoacetamide (final concentration = 50 mM) was added to the DTT-treated protein sample, which was incubated (dark, 30 min). The uranyl acetate (UA) was diluted to 2 M with 50 mM Tris HCl buffer (pH 8.0) and added to each protein sample. An amount of trypsin was added to each protein sample (trypsin:protein = 1:50 at wt:wt), and then incubated (37°C, 15–18 h). A volume of 10% trifluoroacetic acid (TFA; final concentration = 0.1%) was added, and pH was adjusted to ≤ 3 to stop digestion. Each tryptic peptide sample was purified with C18 cartridges and then lyophilized. The lyophilized tryptic peptides were resolved with 1.4 mL immunoaffinity purification (IAP) buffer that contained 50 mM NaCl, 10 mM Na2HPO4, 50 mM MOPS/NaOH, and pH 7.2. The anti-K-ε-GG antibodies against ubiquitin remnant motif (K-ε-GG) (Cell Signal Technology) were used to enrich the ubiquitinated peptides, followed by purification with C18 STAGE Tips. The purified ubiquitinated peptide sample was used for MS/MS analysis. The detailed experimental procedure was described previously [19].
\nThe prepared ubiquitinated peptide sample was analyzed with LC-MS/MS in the Easy nLC and Q Exactive mass spectrometer (Thermo Scientific). The MS/MS data for each sample were used to search protein database using MaxQuant 1.5.3.17 software to identify ubiquitinated proteins and ubiquitination sites and quantify the abundance of ubiquitination. The detailed procedure was described previously [19].
\nFor UPs and DUPs, DAVID software (version 6.8, https://david.ncifcrf.gov/) was used to carry out the gene ontology (GO) enrichment analysis, including cellular components (CCs), molecular functions (MFs), and biological processes (BPs), and group those proteins into different functional clusters [20]. The statistically significant pathways were mined with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The KEGG online service tool KOBAS (http://kobas.cbi.pku.cn) was used to annotate the KEGG database description of each protein [21].
\nTo identify protein lysine-ubiquitinated sites and quantify the level of ubiquitination in human LUSC tissues, proteins were extracted and digested into peptides with trypsin. Lysine-ubiquitinated peptides were immunoaffinity-enriched with commercially specific anti-K-ε-GG antibodies and analyzed with high-resolution LC-MS/MS. In total, 1209 lysine-ubiquitinated sites in 627 unique proteins were identified. These proteins containing ubiquitinated lysine residues were defined as UPs. Figure 1 showed two representative MS/MS spectra of the ubiquitinated peptides 425ETNLDSLPLVDTHSK*R440 from vimentin (P08670; K* = ubiquitinated lysine residue) (Figure 1A), and 633RPVK*DGGGTNSITVR647 from multidrug resistance-associated protein 1 (P33527; K* = ubiquitinated lysine residue) (Figure 1B). All other ubiquitinated sites and ubiquitinated proteins were identified with the same MS/MS method. The differentially ubiquitinated peptides were determined with amino acid sequences, ratio(tumor/control) > 2.0 or < 0.5, and p-value < 0.05. Proteins containing this type of ubiquitinated peptides were defined as DUPs. Totally, 400 DUPs with 654 ubiquitinated sites were identified in LUSC tissues vs. tumor-adjacent control lung tissues [19].
\nRepresentative MS/MS spectra of ubiquitinated peptides 425ETNLDSLPLVDTHSK*R440 from vimentin (P08670) (A) and 633RPVK*DGGGTNSITVR647 from multidrug resistance-associated protein 1 (MRP1) (P33527) (B). K* = ubiquitinated lysine residue. Reproduced from Lu et al. [
GO functional enrichment analyses of 627 UPs and 400 DUPs were carried out according to BPs, MFs, and CCs. GO enrichment result-based cluster analysis grouped those UPs into seven clusters (Table 1), and DUPs into 10 clusters (Table 2).
\nCategory | \nGO term | \np -value | \n
---|---|---|
\n | \n | |
GOTERM_MF_DIRECT | \nCadherin binding involved in cell-cell adhesion | \n1.43E-29 | \n
GOTERM_CC_DIRECT | \nCell-cell adherens junction | \n3.72E-29 | \n
GOTERM_BP_DIRECT | \nCell-cell adhesion | \n1.13E-23 | \n
\n | \n | |
GOTERM_BP_DIRECT | \nWnt signaling pathway, planar cell polarity pathway | \n5.78E-11 | \n
GOTERM_BP_DIRECT | \nRegulation of cellular amino acid metabolic process | \n4.14E-09 | \n
GOTERM_BP_DIRECT | \nStimulatory C-type lectin receptor signaling pathway | \n4.43E-09 | \n
GOTERM_BP_DIRECT | \nNIK/NF-kappa B signaling | \n1.37E-08 | \n
GOTERM_BP_DIRECT | \nTumor necrosis factor-mediated signaling pathway | \n2.96E-08 | \n
GOTERM_BP_DIRECT | \nNegative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle | \n3.70E-08 | \n
GOTERM_BP_DIRECT | \nPositive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition | \n9.13E-08 | \n
GOTERM_BP_DIRECT | \nAnaphase-promoting complex-dependent catabolic process | \n1.52E-07 | \n
GOTERM_BP_DIRECT | \nT cell receptor signaling pathway | \n9.74E-07 | \n
GOTERM_BP_DIRECT | \nPositive regulation of canonical Wnt signaling pathway | \n1.13E-06 | \n
GOTERM_BP_DIRECT | \nNegative regulation of canonical Wnt signaling pathway | \n1.57E-05 | \n
\n | \n | |
GOTERM_CC_DIRECT | \nProteasome regulatory particle, base subcomplex | \n1.29E-08 | \n
GOTERM_CC_DIRECT | \nNuclear proteasome complex | \n1.70E-08 | \n
GOTERM_CC_DIRECT | \nCytosolic proteasome complex | \n1.21E-07 | \n
GOTERM_MF_DIRECT | \nProteasome-activating ATPase activity | \n1.70E-07 | \n
GOTERM_BP_DIRECT | \nPositive regulation of RNA polymerase II transcriptional preinitiation complex assembly | \n3.45E-06 | \n
GOTERM_MF_DIRECT | \nTBP-class protein binding | \n3.27E-05 | \n
GOTERM_BP_DIRECT | \nPositive regulation of proteasomal protein catabolic process | \n9.97E-05 | \n
\n | \n | |
GOTERM_BP_DIRECT | \nSRP-dependent cotranslational protein targeting to membrane | \n3.56E-08 | \n
GOTERM_BP_DIRECT | \nViral transcription | \n7.74E-08 | \n
GOTERM_BP_DIRECT | \nNuclear-transcribed mRNA catabolic process, nonsense-mediated decay | \n1.92E-07 | \n
GOTERM_BP_DIRECT | \nTranslational initiation | \n6.60E-06 | \n
GOTERM_CC_DIRECT | \nRibosome | \n3.32E-05 | \n
GOTERM_MF_DIRECT | \nStructural constituent of ribosome | \n1.68E-03 | \n
\n | \n | |
GOTERM_CC_DIRECT | \nHaptoglobin-hemoglobin complex | \n9.95E-05 | \n
\n | \n | |
GOTERM_BP_DIRECT | \nNucleotide-excision repair, DNA damage recognition | \n6.40E-04 | \n
\n | \n | |
GOTERM_CC_DIRECT | \nHemoglobin complex | \n4.59E-03 | \n
The functional categories of 627 ups, identified with GO enrichment analysis.
Category | \nGO term | \np-value | \n
---|---|---|
\n | \n | |
GOTERM_MF_DIRECT | \nCadherin binding involved in cell-cell adhesion | \n3.11E-18 | \n
GOTERM_CC_DIRECT | \nCell-cell adherens junction | \n2.24E-17 | \n
GOTERM_BP_DIRECT | \nCell-cell adhesion | \n1.23E-13 | \n
\n | \n | |
GOTERM_CC_DIRECT | \nProteasome accessory complex | \n4.60E-12 | \n
GOTERM_BP_DIRECT | \nAntigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent | \n1.59E-11 | \n
GOTERM_BP_DIRECT | \nRegulation of cellular amino acid metabolic process | \n3.49E-09 | \n
GOTERM_BP_DIRECT | \nNIK/NF-kappaB signaling | \n5.35E-09 | \n
GOTERM_BP_DIRECT | \nNegative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle | \n1.27E-08 | \n
GOTERM_BP_DIRECT | \nStimulatory C-type lectin receptor signaling pathway | \n1.85E-08 | \n
GOTERM_BP_DIRECT | \nPositive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition | \n2.83E-08 | \n
GOTERM_BP_DIRECT | \nAnaphase-promoting complex-dependent catabolic process | \n4.43E-08 | \n
GOTERM_BP_DIRECT | \nTumor necrosis factor-mediated signaling pathway | \n8.37E-08 | \n
GOTERM_BP_DIRECT | \nPositive regulation of canonical Wnt signaling pathway | \n1.04E-07 | \n
GOTERM_BP_DIRECT | \nT cell receptor signaling pathway | \n2.37E-07 | \n
GOTERM_BP_DIRECT | \nFc-epsilon receptor signaling pathway | \n4.90E-07 | \n
GOTERM_BP_DIRECT | \nProtein polyubiquitination | \n7.65E-07 | \n
GOTERM_BP_DIRECT | \nNegative regulation of canonical Wnt signaling pathway | \n4.36E-06 | \n
\n | \n | |
GOTERM_CC_DIRECT | \nProteasome regulatory particle, base subcomplex | \n4.88E-10 | \n
GOTERM_CC_DIRECT | \nNuclear proteasome complex | \n1.00E-09 | \n
GOTERM_CC_DIRECT | \nCytosolic proteasome complex | \n7.28E-09 | \n
GOTERM_MF_DIRECT | \nProteasome-activating ATPase activity | \n1.54E-08 | \n
GOTERM_BP_DIRECT | \nPositive regulation of RNA polymerase II transcriptional preinitiation complex assembly | \n3.41E-07 | \n
GOTERM_MF_DIRECT | \nTBP-class protein binding | \n2.10E-06 | \n
GOTERM_BP_DIRECT | \nPositive regulation of proteasomal protein catabolic process | \n1.05E-05 | \n
GOTERM_BP_DIRECT | \nProtein catabolic process | \n1.41E-04 | \n
\n | \n | |
GOTERM_BP_DIRECT | \nRegulation of ventricular cardiac muscle cell action potential | \n1.11E-03 | \n
GOTERM_MF_DIRECT | \nCell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication | \n5.30E-03 | \n
\n | \n | |
GOTERM_CC_DIRECT | \nHaptoglobin-hemoglobin complex | \n2.43E-05 | \n
GOTERM_CC_DIRECT | \nEndocytic vesicle lumen | \n1.71E-04 | \n
GOTERM_MF_DIRECT | \nHaptoglobin binding | \n1.10E-03 | \n
GOTERM_BP_DIRECT | \nPositive regulation of cell death | \n1.90E-02 | \n
GOTERM_CC_DIRECT | \nHemoglobin complex | \n1.97E-02 | \n
GOTERM_MF_DIRECT | \nOxygen transporter activity | \n2.90E-02 | \n
GOTERM_BP_DIRECT | \nOxygen transport | \n3.43E-02 | \n
\n | \n | |
GOTERM_BP_DIRECT | \nSRP-dependent cotranslational protein targeting to membrane | \n9.85E-05 | \n
GOTERM_BP_DIRECT | \nNuclear-transcribed mRNA catabolic process, nonsense-mediated decay | \n5.83E-04 | \n
GOTERM_BP_DIRECT | \nViral transcription | \n1.69E-03 | \n
GOTERM_BP_DIRECT | \nTranslational initiation | \n5.82E-03 | \n
GOTERM_CC_DIRECT | \nRibosome | \n3.40E-02 | \n
\n | \n | |
GOTERM_MF_DIRECT | \nVoltage-gated anion channel activity | \n5.30E-03 | \n
GOTERM_MF_DIRECT | \nPorin activity | \n5.30E-03 | \n
GOTERM_CC_DIRECT | \nPore complex | \n1.11E-02 | \n
GOTERM_BP_DIRECT | \nAnion transport | \n3.02E-02 | \n
GOTERM_BP_DIRECT | \nRegulation of anion transmembrane transport | \n4.34E-02 | \n
\n | \n | |
GOTERM_BP_DIRECT | \nDaunorubicin metabolic process | \n1.00E-02 | \n
GOTERM_BP_DIRECT | \nDoxorubicin metabolic process | \n1.00E-02 | \n
\n | \n | |
GOTERM_BP_DIRECT | \nNucleotide-excision repair, DNA damage recognition | \n1.00E-02 | \n
GOTERM_BP_DIRECT | \nGlobal genome nucleotide-excision repair | \n2.47E-02 | \n
\n | \n | |
GOTERM_MF_DIRECT | \nNeutral amino acid transmembrane transporter activity | \n1.82E-02 | \n
GOTERM_BP_DIRECT | \nNeutral amino acid transport | \n2.62E-02 | \n
The functional categories of 400 DUPs, identified with GO enrichment analysis. Modified from Lu et al. [19], with permission from Springer publisher open access article, copyright 2020.
Among GO enrichment results of 627 UPs, many biological processes, molecular functions, and cellular components related to UPS were significantly enriched, including negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle, and positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition in cluster 2, and proteasome-activating ATPase activity, positive regulation of proteasomal protein catabolic process, cytosolic proteasome complex, nuclear proteasome complex, and proteasome regulatory base complex in cluster 3 (Table 1). Interestingly, DUPs were also significantly enriched in the similar biological processes, molecular functions, and cellular components, including proteasome accessory complex, negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle, positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition, and protein polyubiquitination in cluster 2, and proteasome-activating ATPase activity, positive regulation of proteasomal protein catabolic process, cytosolic proteasome complex, nuclear proteasome complex, and proteasome regulatory base complex in cluster 3 (Table 2). These findings clearly demonstrated that many ubiquitinated proteins were involved in UPS system, and differential ubiquitination occurred in UPS system in LUSC, implying that ubiquitination participated in the regulation of UPS, and abnormal ubiquitination might play an important role in the development of LUSC.
\nKEGG pathway network analysis of 627 UPs revealed 47 statistically significant ubiquitination-mediated signaling pathway alterations (P < 0.05 and FDR < 0.05) (Figure 2), among which were included two UPS-related pathways—ubiquitin-mediated proteolysis pathway (hsa04120) and proteasome complex (hsa03050).
\nStatistically significant KEGG pathways enriched from 627 UPs. Those UPs were significantly enriched in 47 KEGG pathways (p < 0.05 and FDR < 0.05), among which were included two UPS-related pathways—ubiquitin-mediated proteolysis pathway (hsa04120) and proteasome complex (hsa03050). The darker dot means the more significant enrichment, and the size of the dot represents the number of UPs enriched in the pathway.
Ubiquitin-mediated proteolysis pathway showed the detailed process of protein ubiquitination, which involved multiple types of E1s, E2s, and E3s. This study found that one E1 (UBE1), two E2s (UBE2N, and UBE2O), and six E3s (ITCH, HUWE1, UBE4B, PML, CUL4A, and CUL5) were ubiquitinated in LUSC (Figure 3). These six E3s belonged to different subfamilies, in which ITCH and HUWE1 belonged to HECT type E3, UBE4B belonged to U-box type E3, PML belonged to single RING-finger type E3, and both CUL4A and CUL5 belonged to multi subunit RING-finger type E3. E1s, E2s, and E3s are the important enzymes to catalyze the occurrence of ubiquitination in a protein. The ubiquitination of these enzymes definitely affects the quitination process of a protein. Currently, studies on these enzymes have focused on their roles in the ubiquitination process, and the effects of PTMs on these enzymes are poorly understood. There are relatively few studies on the ubiquitination of these nine enzymes. For example, ubiquitinated PML (P29590, identified in this study) was mediated by multiple E3s, leading to subsequent proteasomal degradation [22, 23]. Self-ubiquitination of ITCH (Q96J02, identified in this study) through lysine-63 linkages showed an auto-regulatory mechanism controlling ITCH cytoplasmic-nuclear shuffling [24]. Therefore, the effects of the currently known ubiquitination on these enzymes are only the tip of the iceberg. However, one should also realize that this study found ubiquitination of cullin proteins such as Cul4A and Cul5, while cullin proteins can also be modified by NEDD8 to form NEDDylation. It is well known that the use of the K-ε-GG antibody cannot discriminate between proteins modified with ubiquitin and the related proteins NEDD8 and ISG15. Therefore, for deep investigation of this identified ubiquitination of E3s Cul4A and Cul5 in LUSC in the future, additional experiments are needed to discriminate E3s Cul4A and Cul5 that were modified by ubiquitin, NEDD8, or ISG15 [22].
\nUPs identified in ubiquitin-mediated proteolysis pathway (hsa04120). Pink rectangle means the ubiquitinated proteins, and green rectangle means nonubiquitinated proteins. The pathway node in the right panel corresponds to the pink rectangle in the left diagram. Protein access number is the Swiss-Prot accession number. Modified sites refer to ubiquitinated lysine (K). Ratio (T/N) = ratio of tumors to controls. Asterisk (*) represents there is no quantitative intensity on this modification site in both the tumor and the control group.
Proteasome was a pivotal component for ubiquitin-mediated proteolysis. The 26S proteasome was a complex including two 19S regulatory particles (PA700) and one 20S core particle. The 20S degradation complex contained two α rings (7 subunits, α1-α7) and two β rings (7 subunits, β1-β7). These α rings and β rings together formed a hollow ground circle. The tube-like structure was highly conserved from archaea to mammals [25]. Among them, the α ring was located in the outer layer of the cylinder-like structure, which mainly acted on the recognition of the substrate; the β ring was located in the inner layer of the cylinder-like structure, and was mainly responsible for catalyzing the degradation of the substrate [26, 27]. Three subunits that played a catalytic role were located on the inner surface of the β-ring molecule, exhibiting cysteine protease-like activity, trypsin-like activity, and chymotrypsin-like activity [26, 27]. The 19S regulatory complex contained 19 different subunits, which were divided into two parts: “base” and “lid” [28]. Among them, the base part formed the proximal part of the 19S regulatory complex, which was connected to the alpha ring of the 20S degradation complex, and the lip part formed the distal end. The base section contained 6 ATPase-dependent subunits (Rpt1-Rpt6) and 2 ATPase-independent subunits (Rpn1 and Rpn2) [28]. Usually, Rpn10 and Rpn13 were also classified as the base [26]. The lid part consisted of Rpn3, Rpn5-Rpn9, and Rpn11-Rpn12 subunits [28]. The 19S regulatory complex recognized ubiquitin-labeled target proteins (Rpn10 and Rpn13) and before the target protein entered the 20S degradation complex, deubiquitinated the target protein (Rpn11) and opened the folded structure of the target protein [28]. This study discovered five UPs (Rpn3, Rpn5, Rpn6, Rpn10, and Rpn12) in PA700 (Lid), and seven UPs (Rpn13, Rpt1, Rpt2, Rpt3, Rpt4, Rpt5, and Rpt6) in PA700 (Base) in LUSC. No UPs were identified in 20S core particle in LUSC (Figure 4).
\nUPs identified in proteasome complex (hsa03050). Pink rectangle means the ubiquitinated subunits, and green rectangle means non-ubiquitinated subunits. The pathway node in the right panel corresponds to the pink rectangle in the left diagram. Protein access number is the Swiss-Prot accession number. Modified sites refer to ubiquitinated lysine (K). Ratio (T/N) = ratio of tumors to controls. T+/N− indicates that this modification site has quantitative intensity only in tumor group, while T−/N+ means this modification site has quantitative intensity only in control group. Asterisk (*) represents there is no quantitative intensity on this modification site in both the tumor and the control group.
KEGG pathway network analysis of 400 DUPs revealed 39 statistically significant ubiquitination-mediated signaling pathway alterations (P < 0.05 and FDR < 0.05) (Figure 5), including one UPS-related pathway – proteasome complex (hsa03050).
\nStatistically significant KEGG pathways enriched from 400 DUPs. Those DUPs were significantly enriched in 39 KEGG pathways (p < 0.05 and FDR < 0.05), including one UPS-related pathway – proteasome complex. The darker dot means the more significant enrichment, and the size of the dot represents the number of DUPs enriched in the pathway. Reproduced from Lu et al. [
In proteasome complex, this study discovered 4 DUPs (Rpn3, Rpn5, Rpn10, and Rpn6) in PA700 (Lid), and 7 DUPs (Rpn13, and Rpt1-Rpt6) in PA700 (Base). Their ubiquitination levels were significantly increased at residues K74 (Ratio = 5.16) in Rpn10, K34 (Ratio = 2.27) in Rpn13, K293 (T+/N−) in Rpt2, K46 (Ratio = 4.96) in Rpt1, K372 (T+/N−) in Rpt5, K273 (T+/N−) in Rpt4, K346 (T+/N−), K330 (T+/N−) and K290 (T+/N−) in Rpt6, K194 (T+/N−), K328 (T+/N−) and K62 (Ratio = 2.37) in Rpt4, K273 (T+/N−) in Rpn3, K32 (T+/N−) in Rpn6, and K147 (T+/N−) in Rpn5. The ubiquitination level was decreased at residue K53 (Ratio = 0.33) in Rpt5 (Figure 6).
\nDUPs identified in proteasome complex (hsa03050). The red rectangle means the intensities of all identified ubiquitination sites in one protein were increased, and yellow rectangle means at least two ubiquitination sites in a protein with inconsistent ubiquitination intensities. The pathway node in the right panel corresponds to the red and yellow rectangle in the left diagram. Protein access number is the Swiss-Prot accession number. Modified sites refer to ubiquitinated lysine (K). Ratio (T/N) = ratio of tumors to controls. T+/N− indicates that this modification site has quantitative intensity only in tumor group, while T−/N+ means this modification site has quantitative intensity only in control group. Reproduced from Lu et al. [
The proteasome was a pivotal component of UPS to degrade the short-lived regulatory proteins and remove the damaged soluble proteins [29]. Consequently, dysfunction of proteasome might decrease the capability of protein degradation, thus resulting in the increased level of misfolded and damaged proteins, which was closely related to tumorigenesis [30]. The 26S proteasome had one 20S subunit and two 19S regulatory caps. Two 19S caps were necessary to maintain the normal functions of 20S subunit. For example, Rpn 13 in 19S base cap and Rpn 10 in 19S head cap were the recognition-receptors of the ubiquitinated proteins [31, 32]. Further, PTMs (such as phosphorylation, acetylation, myristoylation, and ubiquitination) had been detected in those subunits to greatly complicate the mechanisms of the modulation of proteasome activity. For example, Rpn 10 was mono-ubiquitinated to recruit substrate protein and interact with the shuttle factor of proteasome in drosophila [33, 34]. The multiple ubiquitinations in 19S cap of proteasome such as Rpn 1, Rpn 10, and Rpn 13 were necessary to autophage proteasome [35]. Our study [19] discovered three non-ATPase subunits (PSMD3, PSMD11, and PSMD12), and three ATPase subunits (PSMC1, PSMC4, and PSMC6) were differentially ubiquitinated in 19S regulatory cap of proteasome in LUSC tissues. It clearly demonstrated that these ubiquitinations in 19S regulatory caps might influence the structure and functions of the proteasome complex. Some studies found that PSMD11 was necessary to assemble proteasome complex and elevate the activity of proteasome in embryonic stem cells [36]. Acetylation [37], phosphorylation [38], and SUMO [39] had been reported to occur in PSMD11, and our study first discovered that PSMD11 was ubiquitinated at residue K32 in LUSC tissues but not in control lung tissues [19]. Currently, few literature studies are found regarding the study on the relationship of ubiquitination and function of proteasome subunits. However, the abnormal ubiquitination of proteasome subunits might cause the functional abnormalities of proteasome complex in LUSC tissues and further lead to the imbalance of synthesis and degradation of intracellular proteins. These findings offer the new clues to deeply study and understand the regulation of UPS functions in LUSC.
\nLabel-free quantitative ubiquitinomics was an effective approach to identify ubiquitinated proteins and ubiquitination sites and quantifies the levels of ubiquitination in human LUSC tissues. In total, 627 UPs and 400 DUPs were identified, providing the first (differential) ubiquitinome profile based on fresh human LUSC tissues. GO and KEGG analyses of UPs and DUPs revealed the statistically significant ubiquitination-mediated molecular network alternations, among which several proteins in two UPS-related pathways (ubiquitin-mediated proteolysis pathway, and proteasome complex) underwent ubiquitination in LUSC. Furthermore, 11 subunits of proteasome complex were differentially ubiquitinated in LUSC. These findings demonstrated that ubiquitination was widely present in UPS in LUSC. At the same time, abnormal ubiquitination might affect the functions of the proteasome to promote tumorigenesis and development. This book chapter focused on the status of protein ubiquitination in UPS-related pathways in human LUSC tissues, and provided the scientific data for the elucidation of the specific molecular mechanisms of abnormal ubiquitination during canceration and the development of anti-tumor drugs targeting UPS for lung cancer.
\nThe authors acknowledge the financial supports from the Shandong First Medical University Talent Introduction Funds (to X.Z.), the Hunan Provincial Hundred Talent Plan (to X.Z.), and the National Natural Science Foundation of China (Grant No. 81572278 to X.Z.).
\nWe declare that we have no financial and personal relationships with other people or organizations.
X.Z. conceived the concept, designed the book chapter, wrote and critically revised the book chapter, coordinated, and was responsible for the correspondence work and financial support. M.L. designed and wrote the book chapter.
\nDUPs | differentially ubiquitinated proteins |
E1 | ubiquitin-activating enzyme |
E2 | ubiquitin-conjugating enzyme |
E3 | ubiquitin ligase |
GO | gene ontology |
KEGG | kyoto encyclopedia of genes and genomes |
LC | liquid chromatography |
LUSC | lung squamous cell carcinoma |
LUAD | lung adenocarcinoma |
MS | mass spectrometry |
MS/MS | tandem mass spectrometry |
PTM | post-translational modification |
PPPM | predictive, preventive and personalized medicine |
UPs | ubiquitinated proteins |
UPS | ubiquitin-proteasome system |
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Bearings are a key factor in their design and development. The aim of the present research work is the development of the support system for a typical microturbine intended for power generation. To this goal, the present chapter defines the typical requirements of the machine and, afterward, describes the different technologies available to develop the support system of a reliable microturbine. Conventional (rolling element and oil-film) supports and cutting-edge (magnetic, aerodynamic, and aerostatic) bearings are reviewed. Particularly, their suitability to the operating conditions is compared by means of a literature review and elaboration of the relevant data. By analyzing all this information, a new concept for the design of a micro-GT support system is devised. Instead of using a single type of bearing as usual, the new system includes different types in order to take advantage of the best characteristics of each one and, simultaneously, to minimize the effects of the relevant flaws. The innovative support system requires a suitable bearing arrangement, which is compared with the conventional ones. 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This system consists of a rotor, a shaft, a cover, and a base. The author derives a meaningful electromagnetic force by using the singular value decomposition. The author develops a control system using the proportional‐integral‐derivative controller to control the position of the rotor and regulate the two gimbal angles of the rotor. The author gives the numerical simulation and experimental results on the control of the electromagnetic levitation system.",book:{id:"5523",slug:"bearing-technology",title:"Bearing Technology",fullTitle:"Bearing Technology"},signatures:"Yonmook Park",authors:[{id:"2861",title:"Dr.",name:"Yonmook",middleName:null,surname:"Park",slug:"yonmook-park",fullName:"Yonmook Park"}]},{id:"55312",doi:"10.5772/67144",title:"Design Aspects of the Bearing Supports",slug:"design-aspects-of-the-bearing-supports",totalDownloads:1665,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter examines different types of bearing supports. Technical parameters of different types of bearing supports are presented. The effectiveness of some types of bearings is determined. General approach for the calculation of bearing overall dimensions is considered.",book:{id:"5523",slug:"bearing-technology",title:"Bearing Technology",fullTitle:"Bearing Technology"},signatures:"Ismagilov Flur Rashitovich, Vavilov Vyacheslav Evgenievich and D.V.\nGusakov",authors:[{id:"192044",title:"Dr.",name:"Viacheslav",middleName:null,surname:"Vavilov",slug:"viacheslav-vavilov",fullName:"Viacheslav Vavilov"},{id:"192050",title:"Prof.",name:"Flur",middleName:null,surname:"Ismagilov",slug:"flur-ismagilov",fullName:"Flur Ismagilov"},{id:"197037",title:"Ph.D.",name:"Denis",middleName:null,surname:"Gusakov",slug:"denis-gusakov",fullName:"Denis Gusakov"}]}],mostDownloadedChaptersLast30Days:[{id:"53926",title:"Condition Monitoring and Fault Diagnosis of Roller Element Bearing",slug:"condition-monitoring-and-fault-diagnosis-of-roller-element-bearing",totalDownloads:2724,totalCrossrefCites:6,totalDimensionsCites:7,abstract:"Rolling element bearings play a crucial role in determining the overall health condition of a rotating machine. An effective condition-monitoring program on bearing operation can improve a machine’s operation efficiency, reduce the maintenance/replacement cost, and prolong the useful lifespan of a machine. This chapter presents a general overview of various condition-monitoring and fault diagnosis techniques for rolling element bearings in the current practice and discusses the pros and cons of each technique. The techniques introduced in the chapter include data acquisition techniques, major parameters used for bearing condition monitoring, signal analysis techniques, and bearing fault diagnosis techniques using either statistical features or artificial intelligent tools. 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This methodology is based on conventional vibration analysis techniques, however, it is, non-invasive, low cost, and easier to implement. Bearing fault detection and identification in induction machines is of utmost importance in order to avoid unexpected breakdowns and even a catastrophic event. Thus, bearing fault characteristic components are extracted combining summation of phase currents, prewhitening, spectral kurtosis and squared envelope spectrum analysis. Experimental results with a 0.37 W, 60 Hz, and three-phase induction machine demonstrated the methodology effectiveness.",book:{id:"5523",slug:"bearing-technology",title:"Bearing Technology",fullTitle:"Bearing Technology"},signatures:"Valeria Cristina Maria Nascimento Leite, Jonas Guedes Borges da\nSilva, Germano Lambert Torres, Giscard Francimeire Cintra Veloso,\nLuiz Eduardo Borges da Silva, Erik Leandro Bonaldi and Levy Ely de\nLacerda de Oliveira",authors:[{id:"112971",title:"Prof.",name:"Germano",middleName:null,surname:"Lambert-Torres",slug:"germano-lambert-torres",fullName:"Germano Lambert-Torres"},{id:"112977",title:"Prof.",name:"Luiz Eduardo",middleName:null,surname:"Borges Da Silva",slug:"luiz-eduardo-borges-da-silva",fullName:"Luiz Eduardo Borges Da Silva"},{id:"117413",title:"Dr.",name:"Erik",middleName:"Leandro",surname:"Bonaldi",slug:"erik-bonaldi",fullName:"Erik Bonaldi"},{id:"117672",title:"Dr.",name:"Levy Ely",middleName:null,surname:"Oliveira",slug:"levy-ely-oliveira",fullName:"Levy Ely Oliveira"},{id:"192256",title:"Dr.",name:"Valéria",middleName:"Cristina Maria Nasscimento",surname:"Leite",slug:"valeria-leite",fullName:"Valéria Leite"},{id:"192864",title:"Dr.",name:"Jonas",middleName:null,surname:"Guedes Borges Da Silva",slug:"jonas-guedes-borges-da-silva",fullName:"Jonas Guedes Borges Da Silva"},{id:"192909",title:"Prof.",name:"Giscard",middleName:null,surname:"Giscard Francimeire Cintra Veloso",slug:"giscard-giscard-francimeire-cintra-veloso",fullName:"Giscard Giscard Francimeire Cintra Veloso"}]},{id:"53968",title:"Electromagnetic Levitation System for Active Magnetic Bearing Wheels",slug:"electromagnetic-levitation-system-for-active-magnetic-bearing-wheels",totalDownloads:1621,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In this chapter, the author presents an electromagnetic levitation system for active magnetic bearing wheels. This system consists of a rotor, a shaft, a cover, and a base. The author derives a meaningful electromagnetic force by using the singular value decomposition. The author develops a control system using the proportional‐integral‐derivative controller to control the position of the rotor and regulate the two gimbal angles of the rotor. The author gives the numerical simulation and experimental results on the control of the electromagnetic levitation system.",book:{id:"5523",slug:"bearing-technology",title:"Bearing Technology",fullTitle:"Bearing Technology"},signatures:"Yonmook Park",authors:[{id:"2861",title:"Dr.",name:"Yonmook",middleName:null,surname:"Park",slug:"yonmook-park",fullName:"Yonmook Park"}]},{id:"55312",title:"Design Aspects of the Bearing Supports",slug:"design-aspects-of-the-bearing-supports",totalDownloads:1665,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter examines different types of bearing supports. Technical parameters of different types of bearing supports are presented. The effectiveness of some types of bearings is determined. General approach for the calculation of bearing overall dimensions is considered.",book:{id:"5523",slug:"bearing-technology",title:"Bearing Technology",fullTitle:"Bearing Technology"},signatures:"Ismagilov Flur Rashitovich, Vavilov Vyacheslav Evgenievich and D.V.\nGusakov",authors:[{id:"192044",title:"Dr.",name:"Viacheslav",middleName:null,surname:"Vavilov",slug:"viacheslav-vavilov",fullName:"Viacheslav Vavilov"},{id:"192050",title:"Prof.",name:"Flur",middleName:null,surname:"Ismagilov",slug:"flur-ismagilov",fullName:"Flur Ismagilov"},{id:"197037",title:"Ph.D.",name:"Denis",middleName:null,surname:"Gusakov",slug:"denis-gusakov",fullName:"Denis Gusakov"}]},{id:"53984",title:"Comparative Analysis of Bearings for Micro-GT: An Innovative Arrangement",slug:"comparative-analysis-of-bearings-for-micro-gt-an-innovative-arrangement",totalDownloads:2913,totalCrossrefCites:4,totalDimensionsCites:6,abstract:"Microgas turbines are a widespread technology in cogenerative and propulsion applications. Bearings are a key factor in their design and development. The aim of the present research work is the development of the support system for a typical microturbine intended for power generation. To this goal, the present chapter defines the typical requirements of the machine and, afterward, describes the different technologies available to develop the support system of a reliable microturbine. Conventional (rolling element and oil-film) supports and cutting-edge (magnetic, aerodynamic, and aerostatic) bearings are reviewed. Particularly, their suitability to the operating conditions is compared by means of a literature review and elaboration of the relevant data. By analyzing all this information, a new concept for the design of a micro-GT support system is devised. Instead of using a single type of bearing as usual, the new system includes different types in order to take advantage of the best characteristics of each one and, simultaneously, to minimize the effects of the relevant flaws. The innovative support system requires a suitable bearing arrangement, which is compared with the conventional ones. The conceptual design of the innovation is completed by a discussion of its advantages, drawbacks, and prospective improvements.",book:{id:"5523",slug:"bearing-technology",title:"Bearing Technology",fullTitle:"Bearing Technology"},signatures:"Fabrizio Stefani, Andrea Perrone, Luca Ratto and Ramon\nFrancesconi",authors:[{id:"20899",title:"Dr.",name:"Fabrizio",middleName:null,surname:"Stefani",slug:"fabrizio-stefani",fullName:"Fabrizio Stefani"},{id:"194300",title:"Dr.",name:"Andrea",middleName:null,surname:"Perrone",slug:"andrea-perrone",fullName:"Andrea Perrone"},{id:"194301",title:"Dr.",name:"Luca",middleName:null,surname:"Ratto",slug:"luca-ratto",fullName:"Luca Ratto"},{id:"194302",title:"Dr.",name:"Ramon",middleName:null,surname:"Francesconi",slug:"ramon-francesconi",fullName:"Ramon Francesconi"}]}],onlineFirstChaptersFilter:{topicId:"822",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:333,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:11,numberOfPublishedChapters:144,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:126,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:13,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. 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