The potential contribution of aberrant cathepsin K expression to gastric cancer pathogenesis.

The role of cathepsin K (CTSK) expression in the pathogenesis and progression of gastric cancer (GC) remains unclear. Hence, the primary objective of this study is to elucidate the precise expression and biological role of CTSK in GC by employing a combination of bioinformatics analysis and in vitro experiments. Our findings indicated a significant upregulation of CTSK in GC. The bioinformatics analysis revealed that GC patients with a high level of CTSK expression exhibited enrichment of hallmark gene sets associated with angiogenesis, epithelial-mesenchymal transition (EMT), inflammatory response, KRAS signaling up, TNFα signaling via KFκB, IL2-STAT5 signaling, and IL6-JAK-STAT3 signaling. Additionally, these patients demonstrated elevated levels of M2-macrophage infiltration, which was also correlated with a poorer prognosis. The results of in vitro experiments provided confirmation that the over-expression of CTSK leads to an increase in the proliferative and invasive abilities of GC cells. However, further evaluation was necessary to determine the impact of CTSK on the migration capability of these cells. Our findings suggested that CTSK has the potential to facilitate the initiation and progression of GC by augmenting the invasive capacity of GC cells, engaging in tumor-associated EMT, and fostering the establishment of an immunosuppressive tumor microenvironment (TME).

Exploring the Causal Effects of Mineral Metabolism Disorders on Telomere and Mitochondrial DNA: A Bidirectional Two-Sample Mendelian Randomization Analysis.

The aim of this study was to assess the causal relationships between mineral metabolism disorders, representative of trace elements, and key aging biomarkers: telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN). Utilizing bidirectional Mendelian randomization (MR) analysis in combination with the two-stage least squares (2SLS) method, we explored the causal relationships between mineral metabolism disorders and these aging indicators. Sensitivity analysis can be used to determine the reliability and robustness of the research results. The results confirmed that a positive causal relationship was observed between mineral metabolism disorders and TL (p < 0.05), while the causal relationship with mtDNA-CN was not significant (p > 0.05). Focusing on subgroup analyses of specific minerals, our findings indicated a distinct positive causal relationship between iron metabolism disorders and both TL and mtDNA-CN (p < 0.05). In contrast, disorders in magnesium and phosphorus metabolism did not exhibit significant causal effects on either aging biomarker (p > 0.05). Moreover, reverse MR analysis did not reveal any significant causal effects of TL and mtDNA-CN on mineral metabolism disorders (p > 0.05). The combination of 2SLS with MR analysis further reinforced the positive causal relationship between iron levels and both TL and mtDNA-CN (p < 0.05). Notably, the sensitivity analysis did not indicate significant pleiotropy or heterogeneity within these causal relationships (p > 0.05). These findings highlight the pivotal role of iron metabolism in cellular aging, particularly in regulating TL and sustaining mtDNA-CN, offering new insights into how mineral metabolism disorders influence aging biomarkers. Our research underscores the importance of trace element balance, especially regarding iron intake, in combating the aging process. This provides a potential strategy for slowing aging through the adjustment of trace element intake, laying the groundwork for future research into the relationship between trace elements and healthy aging.

New insights from bidirectional Mendelian randomization: causal relationships between telomere length and mitochondrial DNA copy number in aging biomarkers.

Mitochondrial DNA (mtDNA) copy number and telomere length (TL) are dynamic factors that have been linked to the aging process in organisms. However, the causal relationship between these variables remains uncertain. In this research, instrumental variables (IVs) related to mtDNA copy number and TL were obtained from publicly available genome-wide association studies (GWAS). Through bidirectional Mendelian randomization (MR) analysis, we examined the potential causal relationship between these factors. The forward analysis, with mtDNA copy number as the exposure and TL as the outcome, did not reveal a significant effect (B=-0.004, P>0.05). On the contrary, upon conducting a reverse analysis, it was found that there exists a positive causal relationship (B=0.054, P<0.05). Sensitivity analyses further confirmed the reliability of these results. The outcomes of this study indicate a one-way positive causal relationship, indicating that telomere shortening in the aging process may lead to a decrease in mtDNA copy number, providing new perspectives on their biological mechanisms.

Causal Associations between Gut Microbiota and Different Types of Dyslipidemia: A Two-Sample Mendelian Randomization Study.

The determination of a causal association between gut microbiota and a range of dyslipidemia remains uncertain. To clarify these associations, we employed a two-sample Mendelian randomization (MR) analysis utilizing the inverse-variance weighted (IVW) method. This comprehensive analysis investigated the genetic variants that exhibited a significant association (p < 5 × 10-8) with 129 distinct gut microbiota genera and their potential link to different types of dyslipidemia. The results indicated a potential causal association between 22 gut microbiota genera and dyslipidemia in humans. Furthermore, these findings suggested that the impact of gut microbiota on dyslipidemia regulation is dependent on the specific phylum, family, and genus. Bacillota phylum demonstrated the greatest diversity, with 15 distinct genera distributed among eight families. Notably, gut microbiota-derived from the Lachnospiraceae and Lactobacillaceae families exhibit statistically significant associations with lipid levels that contribute to overall health (p < 0.05). The sensitivity analysis indicated that our findings possess robustness (p > 0.05). The findings of our investigation provide compelling evidence that substantiates a causal association between the gut microbiota and dyslipidemia in the human body. It is noteworthy to highlight the significant influence of the Bacillota phylum as a crucial regulator of lipid levels, and the families Lachnospiraceae and Lactobacillaceae should be recognized as probiotics that significantly contribute to this metabolic process.

Synthesis of pyrano[3,2-c]quinolones and furo[3,2-c]quinolones via acid-catalyzed tandem reaction of 4-hydroxy-1-methylquinolin-2(1H)-one and propargylic alcohols.

Two acid-catalyzed tandem reactions between 4-hydroxy-1-methylquinolin-2(1H)-one and propargylic alcohols are described. Depending mainly on the propargylic alcohol used, these tandem reactions proceed via either a Friedel-Crafts-type allenylation followed by 6-endo-dig cyclization sequence to form pyrano[3,2-c]quinolones or a Friedel-Crafts-type alkylation and 5-exo-dig ring closure sequence to afford furo[3,2-c]quinolones in moderate-to-high yields. The pyrano[3,2-c]quinolones products could be further transformed to tetracyclic 4,9-dihydro-5H-cyclopenta[lmn]phenanthridin-5-one derivatives.

KIF22 Promotes Development of Pancreatic Cancer by Regulating the MEK/ERK/P21 Signaling Axis.

The study is aimed at exploring the potential biological process and molecular mechanism of KIF22 involved in the development and progression of pancreatic cancer. First, we used the GEPIA database and tissue qRT-PCR to examine the expression of KIF22 mRNA in pancreatic cancer. Meanwhile, immunohistochemistry revealed the presence of KIF22 in 71 pancreatic cancer tissues versus 30 paracarcinoma tissues. Then, we also explored the relationship between KIF22 expression level and clinical prognosis. Furthermore, in pancreatic cancer cells, we silenced KIF22 by transfecting KIF22 SiRNA, and we investigated the effect of KIF22 on the proliferation of pancreatic cancer cells with MTT and colony formation assays. Finally, we used Gene Set Enrichment Analysis (GSEA) to look at the effect of KIF22 on the cell cycle regulation of pancreatic cancer cells, and we used Western blot to look at the relationship between KIF22 and the phosphorylated MEK1/2, ERK1/2 (p-MEK1/2, p-ERK1/2), and the cyclin-dependent kinase inhibitor (P21). In this study, we found that KIF22 was highly expressed in pancreatic cancer tissues, and patients with high expression of KIF22 demonstrated significantly worse clinical prognosis outcomes (P < 0.05). When the KIF22 gene was silenced in pancreatic cancer cells (PANC-1 and MIA PaCa-2), the cells' ability to proliferate was significantly reduced. Furthermore, GSEA confirmed that KIF22 is involved in cell cycle regulation in pancreatic cancer patients (FDR = 0.00158, P < 0.0001). Besides, the level of KIF22 expression was positively correlated with Ki67 (r = 0.8043, P < 0.0001), and KIF22 can promote the transmutation of G1/S. The expression of p-MEK1/2 and p-ERK1/2 was significantly downregulated, while P21 expression was significantly upregulated (P < 0.05). According to our findings, KIF22 is highly expressed in pancreatic cancer and demonstrates a poor clinical prognosis. It regulates the cell cycle via the MEK/ERK/P21 signaling axis and promotes the development of pancreatic cancer.

Huangqi-Honghua Combination Prevents Cerebral Infarction with Qi Deficiency and Blood Stasis Syndrome in Rats by the Autophagy Pathway.

BACKGROUND: Cerebral ischemia/reperfusion injury (CI/RI) contributes to the process of autophagy. Huangqi-Honghua combination (HQ-HH) is a traditional Chinese medicine (TCM) combination that has been widely used in the treatment of cerebrovascular diseases in China. The role of autophagy in HQ-HH-mediated treatment of CI/RI is unclear. METHODS: Sprague-Dawley (SD) rats were used to establish the middle cerebral artery occlusion (MCAO) with QDBS syndrome model and evaluate the function of HQ-HH in protecting against CI/RI. RESULTS: HQ-HH significantly improved the neuronal pathology and reduced infarct volume, neurological deficits, and whole blood viscosity in rats with CI/RI. Western blot results showed that the expression of autophagy marker proteins LC3II/LC3I and Beclin1 in the HQ-HH group was significantly lower than that in the model group, while the expression of p62 was significantly higher in the HQ-HH group as compared with the model group. There were no significant differences in PI3K, Akt, and mTOR levels between the HQ-HH group and the model group; however, p-PI3K, p-Akt, and p-mTOR were significantly upregulated. In addition, HQ-HH also changed the composition and function of intestinal flora in MCAO + QDBS model rats. CONCLUSION: HQ-HH protects from CI/RI, and its underlying mechanism may involve the activation of the PI3K-Akt-mTOR signaling pathway, relating to the changes in the composition of intestinal flora.

Bioinformatic Evidence Reveals that Cell Cycle Correlated Genes Drive the Communication between Tumor Cells and the Tumor Microenvironment and Impact the Outcomes of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive cancer type with poor prognosis; thus, there is especially necessary and urgent to screen potential prognostic biomarkers for early diagnosis and novel therapeutic targets. In this study, we downloaded target data sets from the GEO database, and obtained codifferentially expressed genes using the limma R package and identified key genes through the protein-protein interaction network and molecular modules, and performed GO and KEGG pathway analyses for key genes via the clusterProfiler package and further determined their correlations with clinicopathological features using the Oncomine database. Survival analysis was completed in the GEPIA and the Kaplan-Meier plotter database. Finally, correlations between key genes, cell types infiltrated in the tumor microenvironment (TME), and hypoxic signatures were explored based on the TIMER database. From the results, 11 key genes related to the cell cycle were determined, and high levels of these key genes' expression were focused on advanced and higher grade status HCC patients, as well as in samples of TP53 mutation and vascular invasion. Besides, the 11 key genes were significantly associated with poor prognosis of HCC and also were positively related to the infiltration level of MDSCs in the TME and the HIF1A and VEGFA of hypoxic signatures, but a negative correlation was found with endothelial cells (ECs) and hematopoietic stem cells. The result determined that 11 key genes (RRM2, NDC80, ECT2, CCNB1, ASPM, CDK1, PRC1, KIF20A, DTL, TOP2A, and PBK) could play a vital role in the pathogenesis of HCC, drive the communication between tumor cells and the TME, and act as probably promising diagnostic, therapeutic, and prognostic biomarkers in HCC patients.

Network pharmacology-based prediction of the active compounds and mechanism of Buyang Huanwu Decoction for ischemic stroke.

Buyang Huanwu Decoction (BYHWD) is used to promote blood circulation and is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. However, the mechanism and active compounds of BYHWD used to treat ischemic stroke are not well understood. The current study aimed to identify the potential active components of BYHWD and explore its mechanism using network pharmacology and bioinformatics analyses. The compounds of BYHWD were obtained from public databases. Oral bioavailability and drug-likeness were screened using the absorption, distribution, metabolism and excretion (ADME) criteria. Components of BYHWD, alongside the candidate targets of each component and the known therapeutic targets of ischemic stroke were collected. A network of target gene compounds and cerebral ischemia compounds was established using network pharmacology data sources. The enrichment of key targets and pathways was analyzed using STRING and DAVID databases. Moreover, three of key targets [IL6, VEGFA and hypoxia-inducible-factor-1α (HIF-1α)] were verified using western blot analysis. Network analysis determined 102 compounds in seven herbal medicines that were subjected to ADME screening. A total of 42 compounds as well as 79 genes formed the principal pathways associated with ischemic stroke. The 16 key compounds identified were baicalein, beta-carotene, baicalin, kaempferol, luteolin, quercetin, hydroxysafflor yellow A, isorhamnetin, bifendate, formononetin, calycosin, astragaloside IV, stigmasterol, sitosterol, Z-ligustilide, and dihydrocapsaicin. The core genes in this network were IL6, TNF, VEGFA, HIF-1α, MAPK1, MAPK3, JUN, STAT3, IL1B and IL10. Furthermore, the TNF, IL17, apoptosis, PI3K-Akt, toll-like receptor, MAPK, NF-κB and HIF-1 signaling pathways were identified to be associated with ischemic stroke. Compared with the control group (no treatment), BYHWD significantly inhibited the expression of IL6 and increase the expression of HIF-1α and VEGFA. Network pharmacology analyses can help to reveal close interactions between multi-components and multi-targets and enhance understanding of the potential effects of BYHWD on ischemic stroke.

A Network Pharmacology Approach to Predict the Proangiogenesis Mechanism of Huangqi-Honghua Herb Pair after Cerebral Ischemia.

OBJECTIVE: Huangqi-Honghua herb pair is known for its medicinal value to treat Qi deficiency and blood stasis syndrome with a long history in clinical practice. To understand its possible mechanism in a systematic study, a network pharmacological method was addressed. METHODS: Detailed information on the HH compounds was obtained from two public databases, and oral bioavailability (OB) and drug-like (DL) of the compounds were evaluated. A correlation between HH compounds, its potential targets, and known targets was extrapolated, and the herb-compound-target-disease (H-C-T-D) network was established. Next, the pathway enrichment and essential genes were analyzed. Then, three key genes (VEGFA, VEGFR2, and eNOS), highly associated with angiogenesis, were screened and verified through western blot assay. RESULTS: Out of 276 compounds, 21 HH compounds and 78 target genes regulating the major pathways associated with CI in the network are analyzed. The bioactive compounds in HH were active in various signal transduction pathways such as the toll-like receptor signaling pathway, VEGF signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway are important pathways that may regulate anti-inflammatory, antiapoptotic, immune correlation, and antioxidative effects. The core genes are PTGS2, TNF, NOS2, IL6, BCL2, IL1B, SOD2, NOS3, SOD1, MMP9, and VEGFA. The in vitro results suggested that HH treatment could significantly elevate the expression of proangiogenic genes such as VEGFA, VEGFR2, and eNOS compared with OGD groups. CONCLUSIONS: Our results predict that HH may regulate the expression of VEGFA, VEGFR2, and eNOS via the VEGF and HIF-1 signaling pathway to promote angiogenesis and alleviate cerebral ischemia injury.

Self-supported nickel-doped molybdenum carbide nanoflower clusters on carbon fiber paper for an efficient hydrogen evolution reaction.

Developing an efficient, stable and low-cost noble-metal-free electrocatalyst for the hydrogen evolution reaction (HER) is an effective way to alleviate the energy crisis. Herein, we report a simple and facile approach to synthesize self-supported Ni-doped Mo2C via a molten salt method. By optimizing the content of Ni, the concentration of Ni(NO3)2, and the annealing time, self-supported nanoflower-like electrocatalysts composed of ultrathin nanosheets on carbon fiber paper (CFP) can be achieved. Such a fluffy and porous nanoflower-like structure has a large specific surface area, which can expose many active sites, and promote charge transfer; moreover, all of the above is beneficial for improving the HER performance. Density functional theory (DFT) calculations reveal that the doping of Ni leads to a down shift of the value of the d band center (εd), so that the adsorbed hydrogen (Hads) is easier to desorb from the catalyst surface, thus leading to an enhanced intrinsic catalytic activity of Ni doped Mo2C based catalysts. As a result, Mo2C-3 M Ni(NO3)2/CFP with a nanoflower-like structure prepared at 1000 °C for 6 h exhibits the best electrocatalytic performance for the HER in 0.5 M H2SO4, with a low overpotential of 56 mV (at j = 10 mA cm-2) and a Tafel slope (27.4 mV dec-1) comparable to that of commercial Pt/C (25.8 mV dec-1). The excellent performance surpasses most of the noble-metal-free electrocatalysts. In addition, the outstanding long-term durability of Mo2C-3 M Ni(NO3)2/CFP is demonstrated by showing no obvious fluctuations during 35 h of the HER testing. This work provides a simple and facile strategy for the preparation of nanoelectrocatalysts with high specific surface areas and high catalytic activities, both of which promote an efficient HER.

Carbonic anhydrase inhibition, antioxidant activity against alveolar epithelial cells and antibacterial effect against Klebsiella pneumoniae enabled by synthesized silica nanoparticles through laser ablation technique.

Silica (SiO2) nanoparticles (NPs) were synthesized by laser ablation method and were characterized by TEM and DLS techniques. Afterwards, their inhibition activity against carbonic anhydrase (CA) isoforms (CA I and CA II) was explored by experimental and theoretical analysis. Also, the protective effect of SiO2 NPs against H2O2-induced oxidative stress in alveolar epithelial cells (A549) were assessed by measurement of MTT, ROS level, CAT and SOD activity and GSH content. Finally, the NPs were screened for their antimicrobial activity using the MICs method against the Klebsiella pneumoniae. The result showed that the synthesized NPs have a size of around 40 nm. The inhibition activity by comparing IC50 values with acetazolamide as a positive control revealed that SiO2 NPs in comparison with acetazolamide served as potent inhibitors against CA isoforms which was also confirmed by docking studies. The cellular assays indicated that the SiO2 NPs with a concentration of 20 µg/mL stimulated a significant antioxidant activity against H2O2-induced oxidative cell damage through activation of CAT and SOD, an increase in the GSH content and reducing the level of ROS. The synthesize NPs also showed a good inhibition effect against Klebsiella pneumoniae as compared to Sulfamethoxazole as a positive control. In conclusion, this data may provide some useful information on the development of some platforms for pneumonia treatment and management.

Self-healing solid polymer electrolyte based on imine bonds for high safety and stable lithium metal batteries.

Due to their low flammability, good dimensional stability and chemical stability, solid polymer electrolytes are currently attracting extensive interest for building lithium metal batteries. But severe safety issues such as cracks or breakage, resulting in short circuits will prevent their widespread application. Here, we report a new design of self-healing solid polymer electrolyte (ShSPE) based on imine bonds, fabricated from varying amounts of polyoxyethylenebis(amine) and terephthalaldehyde through a simple Schiff base reaction. Moreover, adding diglycidyl ether of bisphenol A improves the flexibility and high stretchability of the polymer electrolyte. The polymer networks exhibit good thermal stability and excellent self-healing characteristics. The ShSPE with the highest NH2-PEG-NH2 content (ShSPE-3) has an improved lithium ion transference number of 0.39, and exhibits an electrochemical stability up to 4.5 V vs. Li/Li+. ShSPE-3 shows the highest ionic conductivity of 1.67 × 10-4 S cm-1 at 60 °C. Besides, the interfacial stability of ShSPE-3 is promoted and the electrolyte membrane exhibits good cycling performance with LiFePO4, and the LiFePO4/Li cell exhibits an initial discharge capacity of 141.3 mA h g -1. These results suggest that self-healing solid polymer electrolytes are promising candidates for high safety and stable lithium metal batteries.

Synthesis of tetrahydro-ß-carbolines from 2-indolylmethyl azides and propargylic alcohols.

A facile and efficient route to tetrahydro-ß-carbolines from 2-indolylmethyl azides and propargylic alcohols via acid-catalyzed dehydrative annulation reactions is described. This reaction proceeds through a cascade sequence of Friedel-Crafts-type alkylation followed by intramolecular "Click" reaction, involving the formation of multiple chemical bonds in a single operation with excellent atom-economy and broad functional group tolerance.

Sex Difference of Ribosome in Stroke-Induced Peripheral Immunosuppression by Integrated Bioinformatics Analysis.

Ischemic stroke (IS) greatly threatens human health resulting in high mortality and substantial loss of function. Recent studies have shown that the outcome of IS has sex specific, but its mechanism is still unclear. This study is aimed at identifying the sexually dimorphic to peripheral immune response in IS progression, predicting potential prognostic biomarkers that can lead to sex-specific outcome, and revealing potential treatment targets. Gene expression dataset GSE37587, including 68 peripheral whole blood samples which were collected within 24 hours from known onset of symptom and again at 24-48 hours after onset (20 women and 14 men), was downloaded from the Gene Expression Omnibus (GEO) datasets. First, using Bioconductor R package, two kinds of differentially expressed genes (DEGs) (nonsex-specific- and sex-specific-DEGs) were screened by follow-up (24-48 hours) vs. baseline (24 hours). 30 nonsex-specific DEGs (1 upregulated and 29 downregulated), 79 female-specific DEGs (25 upregulated and 54 downregulated), and none of male-specific DEGs were obtained finally. Second, bioinformatics analysis of female-specific DEGs was performed. Gene Ontology (GO) functional annotation analysis shows that DEGs were mainly enriched in translational initiation, cytosolic ribosome, and structural constituent of ribosome. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that the top 6 enrichment pathways are ribosome, nuclear factor--kappa B (NF-kappa B) signaling pathway, apoptosis, mineral absorption, nonalcoholic fatty liver disease, and pertussis. Three functional modules were clustered in the protein-protein interaction (PPI) network of DEGs. The top 10 key genes of the PPI network constructed were selected, including RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2. Sex difference of ribosome in stroke-induced peripheral immunosuppression may be the potential mechanism of sex disparities in outcome after IS, and women are more likely to have stroke-induced immunosuppression. RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2 may be novel prognostic biomarkers and potential therapeutic targets for IS.

Prognostic and Predictive Value of Cadherin 11 for Patients with Gastric Cancer and Its Correlation with Tumor Microenvironment: Results from Microarray Analysis.

Gastric cancer is a disease characterized by inflammation, and epithelial-to-mesenchymal transition (EMT) and tumor-associated macrophages (TAMs) both play a vital role in epithelial-driven malignancy. In the present study, we performed an integrated bioinformatics analysis of transcriptome data from multiple databases of gastric cancer patients and worked on a biomarker for evaluating tumor prognosis. We found that cadherin 11 (CDH11) is highly expressed not only in gastric cancer tissues but also in EMT molecular subtypes and metastatic patients. Also, we obtained evidence that CDH11 has a significant correlation with infiltrating immune cells in the tumor microenvironment (TME). Our findings reflected that CDH11 likely plays an important role in tumor immune escape and could provide a prognostic biomarker and potential therapeutic target for patients with gastric cancer.

Understanding Protection Mechanisms of Graphene-Encapsulated Silicon Anodes with Operando Raman Spectroscopy.

Carbon-coated silicon micro- and nanostructures have been widely used as composite anodes for lithium-ion batteries combining the benefits of high theoretical capacity of Si and better conductivity of carbon. To optimize structures that allow the Si volume expansion without losing the electrical connection, a detailed carbon protection mechanism is desired. We fabricate a network of interconnected sandwich branches with a silicon thin film encapsulated between a porous 3-dimensional graphene foam and graphene drapes (so-called a graphene ensemble). This prototype binder-free anode, of great mechanical strength and composed of only silicon and few-layer graphene, provides distinct signals under operando Raman spectroscopy. During electrochemical cycles, the graphene G peak shows variation of peak position and intensity, while the 2D peak experiences a negligible shift from limited deformation. Silicon displays excellent structural reversibility under the sandwich protection, validating the functions of graphenic carbon coating. This specific graphene ensemble can also serve as an experimental scaffold for mechanical and chemical analysis of many active materials.

The efficacy and safety of capecitabine-based versus S-1-based chemotherapy for metastatic or recurrent gastric cancer: a systematic review and meta-analysis of clinical randomized trials.

BACKGROUND: Gastric cancer (GC), particularly unresectable, metastatic, or recurrent GC, has been characterized by unfavorable prognosis. This meta-analysis of clinical randomized phase II trials was conducted to systematically evaluate the efficacy and safety of capecitabine-based versus S-1-based chemotherapy for metastatic or recurrent GC. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library databases to identify studies eligible for the present analysis. Data were collected from inception to June 20th, 2019. Outcomes included objective response rate (ORR); 6-, 12-, and 18-month progression-free survival (PFS); 1-, 2-, and 3-year overall survival (OS); and adverse events. A meta-analysis was conducted using a random-effects model, and a sensitivity analysis was conducted to examine whether the results of the meta-analysis were robust. Risk ratio (RR) or hazard ratio (HR) with 95% confidence interval (CI) was reported as the main evaluation parameters. RESULTS: Six eligible studies with 561 subjects were included in the present meta-analysis. There was no significant difference between S-1-based and capecitabine-based chemotherapy in ORR (RR =1.17, 95% CI: 0.95-1.44, P=0.13, I2 =0%); 6-month (HR =0.94, 95% CI: 0.77-1.14, I2 =0%), 12-month (HR =0.89, 95% CI: 0.61-1.31, I2 =0%), and 18-month PFS (HR =1.02, 95% CI: 0.55-1.91, I2 =0%); 1-year (HR =0.99, 95% CI: 0.83-1.18, I2 =0%), 2-year (HR =0.90, 95% CI: 0.58-1.42, I2 =0%), and 3-year OS (HR =1.08, 95% CI: 0.50-2.34, I2 =0%). However, the capecitabine-based chemotherapy had a higher incidence in all grades of hand-foot syndrome (HFS) (RR =3.41, 95% CI: 1.98-5.90, P<0.01, I 2 =39%) and grades 3-4 neutropenia (RR =1.62, 95% CI: 1.05-2.51, P=0.03, I2 =0%). CONCLUSIONS: In terms of efficacy, capecitabine-based chemotherapy and S-1-based chemotherapy had similar short-term outcomes. Regarding safety, we recommend S-1-based chemotherapy for patients with metastatic or recurrent GC prior to capecitabine-based treatment.

Could CTSK and COL4A2 be specific biomarkers of poor prognosis for patients with gastric cancer in Asia?-a microarray analysis based on regional population.

BACKGROUND: In the purpose of identifying reliable biomarkers for evaluating prognosis, monitoring recurrence and exploring new therapeutic targets, it is quite necessary to screen for the genetic changes and potential molecular mechanisms of the occurrence and development of gastric cancer (GC) from the aspects of race and region. METHODS: Target datasets were retrieved from Gene Expression Omnibus (GEO) database with "gastric cancer" as the key word, and corresponding data was downloaded. The differentially expressed genes (DEGs) were obtained by using limma R package, and the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for DEGs were analyzed in Enirchr database. Protein-protein interaction (PPI) network and molecular module were also constructed through STRING database and Cytoscape software. Survival analyses were completed for DEGs in GEO and Kaplan-Meier plotter database via cross validation. Finally, the correlation between gene expression and the infiltration cell levels in tumor microenvironment (TME) was explored based on the tumor immune estimation resource (TIMER) database. RESULTS: Five GC-related microarray datasets were selected and used for differential analysis, and 222 DEGs were identified. GO analyses of DEGs were mainly involved in cell metabolism and the formation of extracellular matrix (ECM). The top enriched pathways of DEGs were protein digestion and absorption, ECM-receptor interaction, focal adhesion (FA), PI3K-Akt signaling pathway. Survival analyses of DEGs revealed that the expression levels of CTSK and COL4A2 were significantly associated with poor prognosis of GC patients in Asian. Specifically, the high expression of CTSK had a closely related to the infiltration level of inflammatory cell in TME. CONCLUSIONS: CTSK and COL4A2 could play a critical role in the pathogenesis of GC and act as the promising prognostic biomarkers. CTSK could induce the formation of immunosuppressive TME and promote the immune escape of GC cells.

Novel BP/BiOBr S-scheme nano-heterojunction for enhanced visible-light photocatalytic tetracycline removal and oxygen evolution activity.

Designing heterojunction photocatalysts with strong interfacial interaction and matched band structure is an effective way to reduce the recombination of photogenerated carriers. Herein, the exfoliated black phosphorus (BP) nanosheets were coupled with BiOBr nanosheets having higher Fermi level, and thereby it constructed a novel layered BP/BiOBr nano-heterojunction with chemically bonding, larger contact interface and unique band structures. BiOBr nanosheets were self-assembled on the surface of BP nanosheets by a facile liquid-phase ultrasound combined with solvothermal method. The photocatalytic performance for tetracycline (TC) degradation, oxygen evolution and H2O2 production rate of Sol-10BP/BiOBr was 7.8, 7.0 and 2.6 times than that of pure BiOBr, respectively. The in-situ generated H2O2 and OH became the main active species of mineralization and decomposition of TC. The novel S-scheme two-dimensional BP/BiOBr nano-heterojunction for boosting spatial charge separation retained the useful holes-electrons with higher redox ability, which was very beneficial for producing more OH, H2O2 and O2, and the photocatalytic activity was greatly improved.