Associations of serum aminotransferase and the risk of all-cause and cause-specific mortality in Chinese type 2 diabetes: a community-based cohort study.

OBJECTIVE: Investigating the associations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with all-cause, cardiovascular disease (CVD) and cancer mortality in a large cohort of community-dwelling patients with type 2 diabetes mellitus (T2DM). DESIGN: Community-based prospective cohort study conducted between 2013 and 2014. SETTING: 44 selected townships in Changshu and Huai'an City, Jiangsu province, China. PARTICIPANTS: 20340 participants with T2DM were recruited in Jiangsu province, China. METHODS: We use Cox proportional hazard models to estimate the HR and 95% CIs of associations of serum ALT and AST levels with all-cause and cause-specific mortality. Restricted cubic splines were used to explore the dose-response relationships between ALT and AST levels with mortality. RESULTS: ALT and AST levels were inversely associated with CVD mortality, compared with the lowest quintile (Q1), the multivariable HRs of the highest quintile (Q5) was 0.82 (95% CI: 0.66 to 1.01, p for trend=0.022) and 0.78 (95% CI: 0.63 to 0.96, p for trend=0.022), respectively. Furthermore, the HRs for ALT levels in all-cause mortality were 0.90 (95% CI: 0.79 to 1.01, p for trend=0.018), and the HRs for AST levels in cancer mortality were 1.29 (95% CI: 1.02 to 1.63, p for trend=0.023). Stronger inverse effects of ALT and AST levels on all-cause mortality were observed in the older subgroup and in those with dyslipidaemia (all p for interaction <0.05). Further analysis based on gender showed that the associations between serum aminotransferases and the mortality risk were more significant in women and substantially attenuated in men. CONCLUSION: Our findings suggested patients with T2DM with lower levels of ALT and AST had an increased risk of CVD mortality, which needs confirmation in future clinical trials.

Association of gamma-glutamyl transferase concentrations with all-cause and cause-specific mortality in Chinese adults with type 2 diabetes.

BACKGROUND: Evidence links gamma-glutamyl transferase (GGT) to mortality in the general population. However, the relationship of GGT with all-cause and cause-specific mortality risk has been little explored in type 2 diabetes mellitus (T2DM) patients. METHODS: We recruited 20 340 community-dwelling T2DM patients between 2013 and 2014 in Jiangsu, China. Cox regression models were used to assess associations of GGT with all-cause and specific-cause mortality. Restricted cubic splines were used to analyze dose-response relationships between GGT and mortality. Stratified analysis was conducted to examine potential interaction effects by age, sex, smoking status, body mass index (BMI), diabetes duration, and dyslipidemia. RESULTS: During a median follow-up period of 7.04 years (interquartile range: 6.98-7.08), 2728 deaths occurred, including 902 (33.09%) due to cardiovascular disease (CVD), and 754 (27.58%) due to cancer. GGT concentrations were positively associated with all-cause, CVD, and cancer mortality. Multivariable hazard ratios (HRs) for the highest (Q5) vs. the lowest quintile (Q1) were 1.63 (95% confidence intervals [CI]: 1.44-1.84) for all-cause mortality, 1.87 (95% CI: 1.49-2.35) for CVD mortality, and 1.43 (95% CI: 1.13-1.81) for cancer mortality. Effect modification by BMI and dyslipidemia was observed for all-cause mortality (both p for interaction <.05), and HRs were stronger in the BMI <25 kg/m2 group and those without dyslipidemia. CONCLUSIONS: Our findings suggest that, in Chinese T2DM patients, elevated serum GGT concentrations were associated with mortality for all-cause, CVD, and cancer, and further research is needed to elucidate the role of obesity, nonalcoholic fatty liver disease, and lipids in this association.

Circulating liver function markers and the risk of COPD in the UK Biobank.

Objective: To investigate the associations of circulating liver function marker levels with the risk of chronic obstructive pulmonary disease (COPD). Methods: We leveraged the data of 372,056 participants from the UK Biobank between 2006 and 2010. The assessed circulating liver function markers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), albumin (ALB), and total protein (TP). Incident COPD was identified through linkage to the National Health Service registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up period of 12.3 (interquartile range:11.4-13.2) years, we documented 10,001 newly diagnosed COPD cases. Lower levels of ALT, TBIL, ALB, and TP and higher levels of GGT and ALP were nonlinearly associated with elevated COPD risk. The HR (95% CI) for decile 10 vs. 1 was 0.92 (0.84-1.01) for ALT, 0.82 (0.75-0.89) for TBIL, 0.74 (0.67-0.81) for ALB, 0.96 (0.88-1.04) for TP, 1.45 (1.31-1.62) for GGT, and 1.31 (1.19-1.45) for ALP. Restricted cubic spline analyses suggested a U-shaped relationship between AST levels and COPD risk (P for nonlinearity <0.05). Conclusion: We observed that all seven circulating liver function markers were nonlinearly associated with the risk of COPD, indicating the importance of liver function in COPD.

Cancer-associated fibroblast related gene signature in Helicobacter pylori-based subtypes of gastric carcinoma for prognosis and tumor microenvironment estimation in silico analysis.

Introduction: Gastric cancer (GC) remains the major constituent of cancer-related deaths and a global public health challenge with a high incidence rate. Helicobacter pylori (HP) plays an essential role in promoting the occurrence and progression of GC. Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the tumor microenvironment (TME), which is related to the metastasis of GC. However, the regulation mechanisms of CAFs in HP-related GC are not elucidated thoroughly. Methods: HP-related genes (HRGs) were downloaded from the GSE84437 and TCGA-GC databases. The two databases were combined into one cohort for training. Furthermore, the consensus unsupervised clustering analysis was obtained to sort the training cohort into different groups for the identification of differential expression genes (DEGs). Weighted correlation network analysis (WGCNA) was performed to verify the correlation between the DEGs and cancer-associated fibroblasts which were key components in the tumor microenvironment. The least absolute shrinkage and selection operator (LASSO) was executed to find cancer-associated fibroblast-related differential expression genes (CDEGs) for the further establishment of a prognostic model. Results and discussion: In this study, 52 HP-related genes (HRGs) were screened out based on the GSE84437 and TCGA-GC databases. A total of 804 GC samples were analyzed, respectively, and clustered into two HP-related subtypes. The DEGs identified from the two subtypes were proved to have a relationship with TME. After WGCNA and LASSO, the CAFs-related module was identified, from which 21 gene signatures were confirmed. Then, a CDEGs-Score was constructed and its prediction efficiency in GC patients was conducted for validation. Overall, a highly precise nomogram was established for enhancing the adaptability of the CDEGs-Score. Furthermore, our findings revealed the applicability of CDEGs-Score in the sensitivity of chemotherapeutic drugs. In general, our research provided brand-new possibilities for comprehending HP-related GC, evaluating survival, and more efficient therapeutic strategies.

Ferroptosis-related gene signatures in neuroblastoma associated with prognosis.

Background: Ferroptosis, a form of regulatory cell death, has been linked to the development of various tumors. Peripheral neuroblastoma (NB) is one of the most common extracranial solid tumors in children, and it has been proposed that regulating tumor cell ferroptosis may be a future treatment for NB. However, it is unclear how ferroptosis contributes to NB development. Methods: Expression data were collected from two independent cohorts (GEO and Arrayexpress databases). Univariate Cox analysis, multivariate Cox analysis, and the least absolute shrinkage and selection operator (Lasso) algorithm were applied to create a prognostic signature, whose performance was quantified using the area under the receiver operating characteristic curve (AUC) and Kaplan-Meier curves. A prognostic meta-analysis was used to test the suitability and stability of the FRG signature. Drug sensitivity analyses were performed using the data collected from Cell Miner™. Results: PROM2, AURKA, STEAP3, CD44, ULK2, MAP1LC3A, ATP6V1G2, and STAT3 are among the eight genes in the FRG prognostic signature, all of which were highly expressed in stage 1 NB, except AURKA. Furthermore, the high-risk group, which was stratified by signature, had a lower overall survival rate than the low-risk group. GSEA revealed that high-risk groups have more biological processes related to ferroptosis. Conclusion: Ferroptosis-related genes are expressed differently between stages 1 and 4 NB. The FRG signature successfully stratified NB patients into two risk groups and can accurately predict the overall survival in NB. In addition, we found that the gene AURKA might have the potential to be a prognostic marker in NB.

TMED2/9/10 Serve as Biomarkers for Poor Prognosis in Head and Neck Squamous Carcinoma.

Background: Head and neck squamous carcinoma (HNSC) is one of the most common malignant tumors with high incidence and poor prognosis. Transmembrane emp24 structural domain (TMED) proteins are involved in protein transport and vesicle budding processes, which have implicated various malignancies' progression. However, the roles of TMEDs in HNSC, especially in terms of development and prognosis, have not been fully elucidated. Methods: We applied TIMER 2.0, UALCAN, GEPIA 2, Kaplan-Meier plotter, GEO, The Human Protein Atlas (HPA), cBioPortal, Linkedomics, Metascape, GRNdb, STRING, and Cytoscape to investigate the roles of TMED family members in HNSC. Results: Compared with normal tissues, the mRNA expression levels of TMED1/2/4/5/7/8/9/10 were significantly increased in the TCGA HNSC dataset. And we combined GEPIA 2 and Kaplan-Meier Plotter to select TMED2/9/10 with prognostic value. Then we detected the levels of mRNA in the GEO HNSC database and the protein expression in HPA. It was found that the mRNA and protein expression levels of TMED2/9/10 were increased in HNSC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMED2/9/10 and their co-expressed genes promoted the malignant behavior of tumors by participating in biological processes such as intracellular transferase complex, protein transport, focal adhesion, intracellular protein processing. Single-cell analysis and immune infiltration analysis suggested that immune responses of cancer-associated fibroblasts and endothelial cells might be associated with prognosis. Finally, the transcription factors-genes network and protein-protein functional interaction network pointed to genes such as X-box binding protein 1 (XBP1) and TMED7, which might cooperate with TMED2/9/10 to change the progression of HNSC. Conclusions: Our study implied that TMED2/9/10 and related genes mightjointly affect the prognosis of HNSC, providing specific clues for further experimental research, personalized diagnosis strategies, and targeted clinical therapy for HNSC.

Binary Plasmonic Assembly Films with Hotspot-Type-Dependent Surface-Enhanced Raman Scattering Properties.

Tuning and controlling the plasmon coupling of noble metal nanoparticles are significant for enhancing their near-field and far-field responses. In this work, a novel heterogeneous plasmonic assembly with a controllable hot spot model was proposed by the conjugation of Au nanospheres (NSs) and Au@Ag core-shell nanocube (NC) films. Three hotspot configurations including point-to-point type, point-to-facet type, and facet-to-facet type were fabricated and transformed simply by adjusting the doping ratio of nanoparticles in the co-assembly film. Expectedly, the localized surface plasmon resonance (LSPR) property and surface-enhanced Raman scattering (SERS) performance of the binary assembly film exhibit distinct diversity due to the change in the hotspot conformation. Interestingly, the point-to-facet hotspot in hybrid assembly films can provide the most extraordinary enhancement for SERS behavior compared with single-component Au NS and Au@Ag NC plasmonic assemblies, which is further confirmed by the finite-different time-domain simulation results of dimer nanostructures. In addition, the two-dimensional binary assemblies of Au NS doping in Au@Ag NCs with excellent sensitivity and high reproducibility were successfully applied in the identification of ketamine. This work opens a new avenue toward the fabrication of plasmonic metal materials with collective LSPR properties and sensitive SERS behavior.

ER stress modulates apoptosis in A431 cell subjected to EtNBSe-PDT via the PERK pathway.

Photodynamic therapy (PDT) is a promising modality against various cancers including squamous cell carcinoma (SCC) with which the induction of apoptosis is an effective mechanism. Here, we initially describe the preclinical activity of 5-ethylamino-9-diethylaminobenzo [a] phenoselenazinium(EtNBSe)-mediated PDT treatment in SCC. Results of our studies suggest that EtNBSe-PDT provokes a cellular state of endoplasmic reticulum (ER) stress triggering the PERK/ eIF2α signaling pathway and induces the appearance of apoptosis in A431 cells at the meantime. With ER stress inhibitor 4-PBA or eIF2α inhibitor ISRIB, suppressing the EtNBSe-PDT induced ER stress substantially promotes apoptosis of A431 cells. Furthermore, we demonstrate that ATF4, whose expression is ER-stress-inducible and elevated in response to the PERK/eIF2α signaling pathway activation, contributes to cytoprotection against EtNBSe-PDT induced apoptosis. In a mouse model bearing A431 cells, EtNBSe shows intense phototoxicity and when associated with decreased ER stress, EtNBSe-PDT ameliorates tumor growth. Taken together, our study reveals an antagonistic activity of ER stress against EtNBSe-PDT treatment via inhibiting apoptosis in A431 cells. With further development, these results provide a proof-of-concept that downregulation of ER stress response has a therapeutic potential to improve EtNBSe-PDT sensitivity in SCC patients via the promotion of induced apoptosis.

N-Doped porous graphitic carbon with multi-flaky shell hollow structure prepared using a green and 'useful' template of CaCO3 for VOC fast adsorption and small peptide enrichment.

High N-doped porous graphitic carbons (S-NPGCs) with multi-flaky shell hollow structure were prepared by using CaCO3 as a green/useful template. S-NPGCs exhibit very fast adsorption for toluene (31 times that of HKUST-1) and effectively selective enrichment of small peptides with high inhibitory activity of angiotensin converting enzymes.