Ultralight Flexible Collagen Fiber Based Aerogels Derived from Leather Solid Waste for High Electromagnetic Interference Shielding.

Designing and developing high-performance shielding materials against electromagnetic interference is of utmost importance due to the rapid advancement of wireless telecommunication technologies. Such materials hold both fundamental and technological significance. A three-stage process is presented for creating ultralight, flexible aerogels from biomass to shield against electromagnetic interference. Collagen fibers sourced from leather solid waste are used for: (i) freeze-drying preparation of collagen fibers/poly(vinyl alcohol) (PVA) aerogels, (ii) adsorption of silver nanowires (AgNWs) onto collagen fiber/PVA aerogels, and (iii) Hydrophobic modification of collagen fiber/PVA/AgNWs aerogels with 1H, 1H, 2H, 2H-perfluorodecyltriethoxysilane (POTS). Scanning electron microscopy studies reveal that an interweaving of AgNWs and collagen fiber/PVA porous network has formed a conductive network, exhibiting an electrical conductivity of 103 S·m-1. The electromagnetic interference shielding effectiveness reached more than 62 dB, while the density was merely 5.8 mg/cm3. The collagen fiber/PVA/AgNWs/POTS aerogel displayed an even better electromagnetic shielding efficiency of 73 dB and water contact angle of 147°. The study results emphasize the distinctive capacity of leather solid waste to generate cost-effective, ecofriendly, and highly efficient electromagnetic interference shielding materials.

Superaerophilic/Superaerophobic NiFe-LDHs Electrode for Enhancing Overall Water Splitting in Alkaline Media.

Overall water splitting, as a critical approach to producing green hydrogen, is greatly impeded by the mass transfer of gaseous bubbles and dissolved gas molecules. Herein, a bifunctional superaerophilic/superaerophobic (SAL/SAB) NiFe layered-double-hydroxides (LDHs) electrode has been developed, which can drive H2 and O2 bubbles out of the reaction system by asymmetric Laplace pressure and accelerate dissolved gases diffusion through reducing their diffusion distance. Consequently, the SAL/SAB NiFe-LDHs electrode exhibits excellent HER activity with an overpotential of -76 mV at -10 mA cm-2 and outstanding oxygen evolution reaction activity with an overpotential of 253 mV at 100 mA cm-2. The bifunctional SAL/SAB NiFe-LDHs electrode is further utilized in overall water splitting, which can achieve 10 mA cm-2 with a cell voltage of 1.54 V. This work provides an efficient strategy to improve the efficiency of overall water splitting and can stimulate new electrode design in various gas-involved processes.

Identification of key genes affecting sperm motility in chicken based on whole-transcriptome sequencing.

Sperm motility is an important index for the evaluation of semen quality. Improving sperm motility is important to improve reproductive performance, promote breeding process, and reduce production cost. However, the molecular mechanisms regulating sperm motility in chickens remain unclear. In this study, histological observation and whole-transcriptome analysis were performed on testicular tissue of chickens with high and low sperm motility. Histological observations showed that roosters with high sperm motility exhibited better semen quality than those with low sperm motility. In addition, the germinal epithelial cells of roosters with low sperm motility were loosely arranged and contained many vacuoles. RNA-seq results revealed the expression of 23,033 mRNAs, 2,893 lncRNAs, and 515 miRNAs in chicken testes. Among them, there were 417 differentially expressed mRNAs (DEmRNAs), 106 differentially expressed lncRNAs (DElncRNAs), and 15 differentially expressed miRNAs (DEmiRNAs) between high and low sperm motility testes. These differentially expressed genes were involved in the G protein-coupled receptor signaling pathway, cilia structure, Wnt signaling, MAPK signaling, GnRH signaling, and mTOR signaling. By integrating the competitive relationships between DEmRNAs, DElncRNAs, and DEmiRNAs, we identified the regulatory pathway of MSTRG.3077.3/MSTRG.9085.1-gga-miR-138-5p-CADM1 and MSTRG.2290.1-gga-miR-142-3p-GNAQ/PPP3CA as crucial in the modulation of chicken sperm motility. This study provides new insights into the function and mechanism of ceRNAs in regulating sperm motility in chicken testes.

Identification of key genes related to intramuscular fat deposition in Beijing-You chicken by mRNA and miRNA transcriptome analysis.

Intramuscular fat (IMF) is an important factor affecting chicken quality. However, the age-related mechanism of IMF deposition has not yet been elucidated. In this study, the IMF, phospholipids (PL), triglycerides (TG), and fatty acid (FA) content in the breast muscle of Beijing-You chicken (BJY) at 1, 56, 98, and 120 d of age was measured, and mRNA and miRNA sequencing was integrated to explore the regulatory genes of IMF deposition. The results showed that the IMF content of BJY at 1 d of age was significantly higher than that at later stage of birth (P < 0.05). The transcriptome sequencing results showed that 7, 225 differentially expressed genes (DEGs) and 243 differentially expressed miRNAs (DE-miRNAs) were identified. The cluster analysis showed that the expression of DEGs and DE-miRNAs at 1 d of age was significantly different from that at later stages of birth. Furthermore, a potential mRNA-miRNA regulatory network related to IMF deposition was established by weighted gene co-expression network analysis (WGCNA); gga-miR-29c-3p-PIK3R1, gga-miR-6701-3p-PTEN, gga-miR-363-3p-PTEN, gga-miR-1563-WWP1, gga-miR-449c/d-5p-TRAF6, and gga-miR-6701-3p-BMPR1B were identified as key mRNA-miRNA pairs for the regulation of IMF deposition. These results will help elucidate the mechanism of IMF formation mediated by miRNAs in chickens, and provide a theoretical foundation for the genetic improvement of broiler meat quality.

Bioinspired Underwater Superoleophilic Two-Dimensional Surface with Asymmetric Oleophobic Barriers for Unidirectional and Long-Distance Oil Transport.

Unidirectional and long-distance liquid transport is critically important to a range of practical applications, e.g., water harvesting, microfluidics, and chemical reactions. Great efforts have been made on liquid manipulation; most of which, however, are limited in the air environment. It is still a great challenge to achieve unidirectional and long-distance oil transport in an aqueous environment. Herein, we have successfully fabricated an underwater superoleophilic two-dimensional surface (USTS) with asymmetric oleophobic barriers to arbitrarily manipulate oil in aqueous medium. The behavior of oil on USTS was carefully investigated, of which the unidirectional spreading capability was originated from the anisotropic spreading resistance resulted from the asymmetric oleophobic barriers. Accordingly, an underwater oil/water separation device has been developed, which can achieve continuous and efficient oil/water separation and further prevent the secondary pollution caused by oil volatilization.

Identification of Key Genes Affecting Flavor Formation in Beijing-You Chicken Meat by Transcriptome and Metabolome Analyses.

The flavor of chicken meat is influenced by muscle metabolites and regulatory genes and varies with age. In this study, the metabolomic and transcriptomic data of breast muscle at four developmental stages (days 1, 56, 98, and 120) of Beijing-You chickens (BJYs) were integrated and 310 significantly changed metabolites (SCMs) and 7,225 differentially expressed genes (DEGs) were identified. A Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that SCMs and DEGs were enriched in amino acid, lipid, and inosine monophosphate (IMP) metabolism pathways. Furthermore, genes highly associated with flavor amino acids, lipids, and IMP were identified by a weighted gene co-expression network analysis (WGCNA), including cystathionine ß-synthase (CBS), glycine amidinotransferase (GATM), glutamate decarboxylase 2 (GAD2), patatin-like phospholipasedomain containing 6 (PNPLA6), low-specificity L-threonine aldolase (ItaE), and adenylate monophosphate deaminase 1 (AMPD1) genes. A regulatory network related to the accumulation of key flavor components was constructed. In conclusion, this study provides new perspectives regarding the regulatory mechanisms of flavor metabolites in chicken meat during development.

CBS-H2S axis preserves the intestinal barrier function by inhibiting COX-2 through sulfhydrating human antigen R in colitis.

INTRODUCTION: Lipopolysaccharide (LPS) causes lesions of the epithelial barrier, which allows translocation of pathogens from the intestinal lumen to the host's circulation. Hydrogen sulfide (H2S) regulates multiple physiological and pathological processes in colonic epithelial tissue, and CBS-H2S axis involved in multiple gastrointestinal disorder. However, the mechanism underlying the effect of the CBS-H2S axis on the intestinal and systemic inflammation in colitis remains to be illustrated. OBJECTIVES: To investigate the effect of CBS-H2S axis on the intestinal and systematic inflammation related injuries in LPS induced colitis and the underlying mechanisms. METHODS: Wild type and CBS-/+ mice were used to evaluate the effect of endogenous and exogenous H2S on LPS-induced colitis in vivo. Cytokine quantitative antibody array, western blot and real-time PCR were applied to detect the key cytokines in the mechanism of action. Biotin switch of S-sulfhydration, CRISPR/Cas9 mediated knockout, immunofluorescence and ActD chase assay were used in the in vitro experiment to further clarify the molecular mechanisms. RESULTS: H2S significantly alleviated the symptoms of LPS-induced colitis in vivo and attenuated the increase of COX-2 expression. The sulfhydrated HuR increased when CBS express normally or GYY4137 was administered. While after knocking kown CBS, the expression of COX-2 in mice colon increased significantly, and the sulfhydration level of HuR decreased. The results in vitro illustrated that HuR can increase the stability of COX-2 mRNA, and the decrease of COX-2 were due to increased sulfhydration of HuR rather than the reduction of total HuR levels. CONCLUSION: These results indicated that CBS-H2S axis played an important role in protecting intestinal barrier function in colitis. CBS-H2S axis increases the sulfhydration level of HuR, by which reduces the binding of HuR with COX-2 mRNA and inhibited the expression of COX-2.

Preliminary development of Health Literacy Evaluation Scale for Pupils / 中国学校卫生

Objective@#To preliminarily develop Health Literacy Scale for pupils, providing a tool for dynamic monitoring and related health literacy research among pupils.@*Methods@#Through policy and literature review, the health literacy evaluation index system of pupils was established. Through two rounds of expert consultation, the evaluation index system and scale item pool of three levels in primary school were formed, and "Evaluation Scale 1.0" was developed. Through two panel discussions, health education experts, teachers and students were invited to provide advices on the content, expression and structure of scale 1.0, turning it into "Evaluation Scale 2.0", and completing the preliminary development of the scale.@*Results@#The health literacy assessment index system of primary school students includes three levels，including level-1 was Grade 1-2, level-2 was Grade 3-4,level-3 was Grade 5-6, covering two level indexes. The scale for primary school students contained five horizontal dimensions and four vertical dimensions. In the Delphi consultation, the response rate was 100%, and the authority coefficient was 0.85. After item selection and modification, the final version of level-1, level-2 and level-3 scales contained 36, 44 and 50 items respectively.@*Conclusion@#The development of Health Literacy Evaluation Scale for pupils has high applicability and practical value.

Absorption-Dominant, Low-Reflection Multifunctional Electromagnetic Shielding Material Derived from Hydrolysate of Waste Leather Scraps.

High-performance flexible conductive films are highly promising for the development of wearable devices, artificial intelligence, medical care, etc. Herein, a three-step procedure was developed to produce electromagnetic interference (EMI) shielding, Joule heating, and a hydrophobic nanofiber film based on hydrolysate of waste leather scraps (HWLS): (i) electrospinning preparation of the HWLS/polyacrylonitrile (PAN)/zeolitic imidazolate framework-67 (ZIF-67) nanofiber film, (ii) carbonization of the HWLS/PAN/ZIF-67 nanofiber film, and (iii) coating of the carbon nanofiber@cobalt (Co@CNF) nanofiber film with perfluorooctyltriethoxysilane (POTS). The X-ray diffraction results showed that metal nanoparticles and amorphous carbon had obvious peaks. The micromorphology results showed that metal nanoparticles were coated with carbon nanofibers. The conductivity and shielding efficiency of the carbon nanofiber film with 250 µm thickness could reach 45 S/m and 49 dB, respectively, and absorption values (A > 0.5) were higher than reflection (R) values for the Co@CNF nanofiber film, which indicated that the contribution of absorption loss was more significant than that of reflection loss. Ultrafast electrothermal response performances were also achieved, which could guarantee the normal functioning of films in cold conditions. The water contact angle of the Co@CNF@POTS nanofiber film was ∼151.3°, which displayed a self-cleaning property with water-proofing and antifouling. Absorption-dominant and low-reflection EMI shielding and electrothermal films not only showed broad application potential in flexible wearable electronic devices but also provided new avenues for the utilization of leather solid waste.

GBP2 facilitates the progression of glioma via regulation of KIF22/EGFR signaling.

Identifying the mechanism of glioma progression is critical for diagnosis and treatment. Although studies have shown that guanylate-binding protein 2(GBP2) has critical roles in various cancers, its function in glioma is unclear. In this work, we demonstrate that GBP2 has high expression levels in glioma tissues. In glioma cells, depletion of GBP2 impairs proliferation and migration, whereas overexpression of GBP2 enhances proliferation and migration. Regarding the mechanism, we clarify that epidermal growth factor receptor (EGFR) signaling is regulated by GBP2, and also demonstrate that GBP2 interacts directly with kinesin family member 22(KIF22) and regulates glioma progression through KIF22/EGFR signaling in vitro and in vivo. Therefore, our study provides new insight into glioma progression and paves the way for advances in glioma treatment.

2D graphene/FeOCl heterojunctions with enhanced tribology performance as a lubricant additive for liquid paraffin.

The purpose of this study is to prepare graphene/FeOCl (G/FeOCl) heterojunctions via a microwave-pyrolysis approach and probe into the synergistic lubrication of G with FeOCl in liquid paraffin (LP). The morphology and chemical composition of specimens were analysed by utilizing scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS) techniques. The tribological property of G/FeOCl was determined, and the interaction between the G/FeOCl heterojunction and friction pair was carried out through simulation calculations. The results indicated that neither G nor FeOCl significantly improved the lubrication performance of LP. However, together with FeOCl, G as lubrication additives greatly improved the lubrication performance of LP. Under the load of 1.648 GPa, the mean friction coefficient and wear scar diameter of LP containing 0.20 wt% G/FeOCl were 66.1% and 44.7% inferior to those of pure LP, respectively. Scanning electron microscopy (SEM) and elemental mapping analyses of worn scars revealed the formation of G/FeOCl layer tribofilms that prevent direct contact between metals. In addition, the high interfacial energy between graphene and FeOCl calculated based on first-principles density functional theory (DFT) further confirmed that graphene and FeOCl simultaneously form friction films with wear resistance and wear reduction effect at the friction interface, which is consistent with the experimental results. This study, therefore, provides a pathway for low-friction lubricants by deploying G/FeOCl two-dimensional material systems.

Overexpression of CBS/H2S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44.

BACKGROUND: The role of hydrogen sulfide (H2S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H2S refers to pro-cancer action at lower doses and anti-cancer effect at higher concentrations. We hypothesized that overexpression of cystathionine-beta-synthase (CBS)/H2S exerts an inhibitory effect on colon cancer cell proliferation and metastasis. METHODS: Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), clone-formation and sphere formation assay. Cell migration was evaluated by transwell migration assay. Intracellular H2S was detected by H2S probe. Chromatin immunoprecipitation (ChIP) analysis was carried out to examine DNA-protein interaction. Cell experiments also included western blotting, flow cytometry, immunohistochemistry (IHC) and immunofluorescence analysis. We further conducted in vivo experiments to confirm our conclusions. RESULTS: Overexpression of CBS and exogenous H2S inhibited colon cancer cell proliferation and migration in vitro. In addition, overexpression of CBS attenuated tumor growth and liver metastasis in vivo. Furthermore, CD44 and the transcription factor SP-1 was probably involved in the inhibitory effect of CBS/H2S axis on colon cancer cells. CONCLUSIONS: Overexpression of CBS and exogenous provision of H2S inhibited colon cancer cell proliferation and migration both in vivo and in vitro. Molecular mechanisms might involve the participation of CD44 and the transcription factor SP-1.

Hydrophobic, flexible electromagnetic interference shielding films derived from hydrolysate of waste leather scraps.

With the rapid development of wireless telecommunication technologies, it is of fundamental and technological significance to design and engineer high-performance shielding materials against electromagnetic interference (EMI). Herein, a three-step procedure is developed to produce hydrophobic, flexible nanofiber films for EMI shielding and pressure sensing based on hydrolysate of waste leather scraps (HWLS): (i) electrospinning preparation of HWLS/polyacrylonitrile (PAN) nanofiber films, (ii) adsorption of silver nanowires (AgNWs) onto HWLS/PAN nanofiber films, and (iii) coating of HWLS/PAN/AgNWs nanofiber films with polydimethylsiloxane (PDMS). Scanning electron microscopy studies show that AgNWs are interweaved with HWLS/PAN nanofibers to form a conductive network, exhibiting an electrical conductivity of 105 S m-1 and shielding efficiency of 65 dB for a 150 µm-thick HWLS/PAN/AgNWs film. The HWLS/PAN/AgNWs/PDMS film displays an even better electromagnetic shielding efficiency of 80 dB and a water contact angle of 132.5°. Results from this study highlight the unique potential of leather solid wastes for the production of high-performance, environmentally friendly, and low-cost EMI shielding materials.

FRAT1 promotes the angiogenic properties of human glioblastoma cells via VEGFA.

Glioblastoma is a common central nervous system tumor and despite considerable advancements in treatment patient prognosis remains poor. Angiogenesis is a significant prognostic factor in glioblastoma, anti­angiogenic treatments represent a promising therapeutic approach. Vascular endothelial growth factor A (VEGFA) is a predominant regulator of angiogenesis and mounting evidence suggests that the Wnt signaling pathway serves a significant role in tumor angiogenesis. As a positive regulator of the Wnt/ß­catenin signaling pathway, frequently rearranged in advanced T­cell lymphomas­1 (FRAT1) is highly expressed in human glioblastoma and is significantly associated with glioblastoma growth, invasion and migration, as well as poor patient prognosis. Bioinformatics analysis demonstrated that both VEGFA and FRAT1 were highly expressed in most tumor tissues and associated with prognosis. However, whether and how FRAT1 is involved in angiogenesis remains to be elucidated. In the present study, the relationship between FRAT1 and VEGFA in angiogenesis was investigated using the human glioblastoma U251 cell line. Small interfering RNAs (siRNAs) were used to silence FRAT1 expression in U251 cells, and the mRNA and protein expression levels of VEGFA, as well as the concentration of VEGFA in U251 cell supernatants, were determined using reverse transcription­quantitative PCR, western blotting and ELISA. A tube formation assay was conducted to assess angiogenesis. The results demonstrated that siRNA knockdown significantly decreased the protein expression levels of FRAT1 in U251 cells and markedly decreased the mRNA and protein expression levels of VEGFA. Furthermore, the concentration of VEGFA in the cell supernatant was significantly reduced and angiogenesis was suppressed. These results suggested that FRAT1 may promote VEGFA secretion and angiogenesis in human glioblastoma cells via the Wnt/ß­catenin signaling pathway, supporting the potential use of FRAT1 as a promising therapeutic target in human glioblastoma.

The CBS-H2S axis promotes liver metastasis of colon cancer by upregulating VEGF through AP-1 activation.

BACKGROUND: The main therapy for colon cancer with liver metastasis is chemotherapy based on 5-fluorouracil combined with targeted drugs. However, acquired drug resistance and severe adverse reactions limit patients' benefit from standard chemotherapy. Here, we investigate the involvement of endogenous hydrogen sulfide (H2S) in liver metastasis of colon cancer and its potential value as a novel therapeutic target. METHODS: We used the CRISPR/Cas9 system to knockdown CBS gene expression in colon cancer cell lines. PCR arrays and proteome arrays were applied to detect the transcription and protein expression levels, respectively, of angiogenesis-related genes after knockdown. The molecular mechanism was investigated by western blot analysis, RT-qPCR, immunofluorescence staining, ChIP assays and dual-luciferase reporter assays. A liver metastasis mouse model was adopted to investigate the effect of targeting CBS on tumour metastasis in vivo. RESULTS: Knockdown of CBS decreased the metastasis and invasion of colon cancer cells and inhibited angiogenesis both in vivo and in vitro. Tissue microarray analysis showed a positive correlation between CBS and VEGF expression in colon cancer tissues. Further analysis at the molecular level validated a positive feedback loop between the CBS-H2S axis and VEGF. CONCLUSIONS: Endogenous H2S promotes angiogenesis and metastasis in colon cancer, and targeting the positive feedback loop between the CBS-H2S axis and VEGF can effectively intervene in liver metastasis of colon cancer.

Two Similar Signatures for Predicting the Prognosis and Immunotherapy Efficacy of Stomach Adenocarcinoma Patients.

BACKGROUND: Globally, stomach adenocarcinoma (STAD)'s high morbidity and mortality should arouse our urgent attention. How long can STAD patients survive after surgery and whether novel immunotherapy is effective are questions that our clinicians cannot escape. METHODS: Various R packages, GSEA software, Metascape, STRING, Cytoscape, Venn diagram, TIMER2.0 website, TCGA, and GEO databases were used in our study. RESULTS: In the TCGA and GEO, macrophage abundance of STAD tissues was significantly higher than that of adjacent tissues and was an independent prognostic factor, significantly related to the overall survival (OS) of STAD patients. Between the high- and low- macrophage abundance, we conducted differential expression, univariate and multivariate Cox analysis, and obtained 12 candidate genes, and finally constructed a 3-gene signature. Both low macrophage abundance group and group D had higher TMB and PD-L1 expression. Furthermore, top 5 common gene-mutated STAD tissues had lower macrophage abundance. Macrophage abundance and 3 key genes expression were also lower in the Epstein-Barr Virus (EBV) and HM-indel STAD subtypes and significantly correlated with the tumor microenvironment score. The functional enrichment and ssGSEA revealed 2 signatures were similar and closely related to BOQUEST_STEM_CELL_UP, including genes up-regulated in proliferative stromal stem cells. Hsa-miR-335-5p simultaneously regulated 3 key genes and significantly related to the expression of PD-L1, CD8A and PDCD1. CONCLUSION: macrophage abundance and 3-gene signature could simultaneously predict the OS and immunotherapy efficacy, and both 2 signatures had remarkable similarities. Hsa-miR-335-5p and BOQUEST_STEM_CELL_UP might be novel immunotherapy targets.

SPARC enhances 5-FU chemosensitivity in gastric cancer by modulating epithelial-mesenchymal transition and apoptosis.

Previous studies have shown that secreted protein acidic and rich in cysteine (SPARC) proteins can inhibit the development of cancer cells in various ways, such as by inhibiting angiogenesis and inhibiting cell proliferation. In fact, SPARC proteins may have an effect on the chemoresistance of gastric cancer cells to 5-Fluorouracil (5-FU), which needs further research in the future. Therefore, the purpose of this study was to explore the relationship between SPARC proteins and the chemosensitivity of gastric cancer cells to 5-FU. In vitro, after SPARC protein levels were regulated by plasmid, siRNA and human recombinant SPARC protein transfection in MGC-803, SGC-7901 and BGC-823 cells, we detected epithelial-mesenchymal transition (EMT), apoptosis markers and cell viability after 5-FU treatment. In vivo, we implanted BGC-823 cells with stable SPARC overexpression into nude mice. Tumour size was measured to assess the effect of SPARC protein on tumour formation and 5-FU chemosensitivity. In SGC-7901 and BGC-823 cells, both endogenous and exogenous upregulation of SPARC protein levels decreased cell viability, destroyed cytoskeletal F-actin, inhibited cell migration, and downregulated a series of transcription factors to inhibit cell EMT; it also upregulated cell apoptosis-related proteins to promote cell apoptosis. However, we obtained opposite results in SPARC knockdown MGC-803 cells. In vivo, compared with the control group, the group engrafted with BGC-823 cells stably overexpressing SPARC had a significant smaller tumour size. After 5-FU treatment, the new tumour gradually decreased in size. Our results show that the SPARC protein could enhance 5-FU chemosensitivity in gastric cancer cell lines by inhibiting EMT and promoting cell apoptosis.

Endogenous hydrogen sulfide regulates xCT stability through persulfidation of OTUB1 at cysteine 91 in colon cancer cells.

Increased xCT and transsulfuration pathway has been associated with metabolic reprogramming of colorectal cancer. However, the correlation between these 2 events and the underlying molecular mechanism remains obscure. xCT expression was determined in tissue microarrays of colorectal cancer. RNA sequencing and functional assays in vitro was adopted to delineate the involvement of transsulfuration pathway in the proper function of xCT in maintaining the chemoresistant phenotype. The synthetic lethality of blocking xCT and the transsulfuration pathway was investigated both in vitro and in vivo. The up-regulation of the transsulfuration pathway after inhibiting xCT in colon cancer cells was evident and exogenous H2S partially reversed the loss of chemoresistance phenotype after inhibiting xCT. Mechanistically, CTH derived H2S increased the stability of xCT through persulfidation of OTU domain-containing ubiquitin aldehyde-binding protein 1 at cysteine 91. AOAA and Erastin resulted in synthetic lethality both in vitro and in vivo, which was mediated through increased ferroptosis and apoptosis. Our findings suggest that a reciprocal regulation exists between xCT and the transsulfuration pathway, which is a targetable metabolic vulnerability. Mechanistically, CTH derived H2S increased the stability of xCT through persulfidation of OTU domain-containing ubiquitin aldehyde-binding protein 1 at cysteine 91.

The aging-related risk signature in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. The opening of the TCGA and GEO databases has promoted the progress of CRC prognostic assessment, while the aging-related risk signature has never been mentioned. METHODS: R software packages, GSEA software, Venn diagram, Metascape, STRING, Cytoscape, cBioPortal, TIMER and GeneMANIA website were used in this study. RESULTS: Aging-related gene sets, GO_AGING, GO_CELL_AGING and GO_CELLULAR_SENESCENCE, were activated significantly in CRC tissues. We constructed an aging-related risk signature using LASSO COX regression in training group TCGA and validated in testing group GSE39582. The risk score was significantly associated with the overall survival of CRC patients, whose stability was clarified by stratified survival analysis and accuracy was demonstrated using the ROC curve. The risk score was significantly increased in the advanced stage, T3-4, N1-3 and M1 and positively correlated with the richness of immune cell infiltration in the tumor microenvironment. We further investigated the molecular characteristics of 15 hub genes at the DNA and protein levels and performed GSEA between high- and low-risk groups. CONCLUSIONS: The aging-related signature is a reliable prognostic analysis model and can predict the severity and immune cell infiltration of CRC patients.

Identification of 6 Hub Proteins and Protein Risk Signature of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer death in the United States and the third most common cancer globally. The incidence of CRC tends to be younger, and we urgently need a reliable prognostic assessment strategy. METHODS: Protein expression profile and clinical information of 390 CRC patients/samples were downloaded from the TCPA and TCGA database, respectively. The Kaplan-Meier, Cox regression, and Pearson correlation analysis were applied in this study. RESULTS: Based on the TCPA and TCGA database, we screened 6 hub proteins and first constructed protein risk signature, all of which were significantly associated with CRC patients' overall survival (OS). The risk score was an independent prognostic factor and significantly related with the size of the tumor in situ (T). 6 hub proteins were differentially expressed in cancer and normal tissues and in different CRC stages, which were validated at the ONCOMINE database. Next, 40 coexpressed proteins of 6 hub proteins were extracted from the TCPA database. In the protein-protein interaction (PPI) network, HER1, HER2, and CTNNB1 were at the center. Function enrichment analysis illustrated that 46 proteins were mainly involved in the EGFR (HER1) tyrosine kinase inhibitor resistance pathway. CONCLUSION: Studies indicated that 6 hub proteins might be considered as new targets for CRC therapies, and the protein risk signature can be used to predict the OS of CRC patients.