A new prognostic model based on gamma-delta T cells for predicting the risk and aiding in the treatment of clear cell renal cell carcinoma.

BACKGROUND: ccRCC is the prevailing form of RCC, accounting for the majority of cases. The formation of cancer and the body's ability to fight against tumors are strongly connected to Gamma delta (γδ) T cells. METHODS: We examined and analyzed the gene expression patterns of 535 individuals diagnosed with ccRCC and 72 individuals serving as controls, all sourced from the TCGA-KIRC dataset, which were subsequently validated through molecular biology experiments. RESULTS: In ccRCC, we discovered 304 module genes (DEGRGs) that were ex-pressed differentially and linked to γδ T cells. A risk model for ccRCC was constructed using 13 differentially DEGRGs identified through univariate Cox and LASSO regression analyses, which were found to be associated with prognosis. The risk model exhibited outstanding performance in both the training and validation datasets. The comparison of immune checkpoint inhibitors and the tumor immune microenvironment between the high- and low-risk groups indicates that immunotherapy could lead to positive results for low-risk patients. Moreover, the inhibition of ccRCC cell proliferation, migration, and invasion was observed in cell culture upon knocking down TMSB10, a gene associated with different types of cancers. CONCLUSIONS: In summary, we have created a precise predictive biomarker using a risk model centered on γδ T cells, which can anticipate clinical results and provide direction for the advancement of innovative targeted therapies.

Synthesis and photophysical properties of dinuclear N-heterocyclic carbene (NHC) copper(I) complexes and their application to photoluminescent light-emitting diodes and anti-counterfeiting.

Here, a series of dinuclear N-heterocyclic carbene (NHC) copper(I) complexes having 3,3'-(1,4-phenylenebis(methylene))bis(1-(pyridin-2-yl)-1H-imidazolylidene as bis-NHC ligand and bis[(2-diphenylphosphino)phenyl]ether (POP) as auxiliary ligand have been successfully prepared, and their photophysical properites were investigaged experimentally and theocitcally. The resulting complexes all exhibited intense green to yellow emission that originated from the thermally activated delayed fluorescence (TADF) with a high photoluminescence quantum yield of up to 0.67 and longer excited-state lifetimes on the microsecond time scale in the solid state. Green and yellow light-emitting diode (LED) devices based on Cu(I) complexes have successfully achieved good color rendering indices. Moreover, the anti-counterfeiting patterns and QR codes made of Cu(I) complexes have been applied to clothing, banknotes, books and glass plates with excellent anti-counterfeiting effects.

Causal inference between rheumatoid arthritis and prostate cancer.

It is unclear if the association between rheumatoid arthritis (RA) and a higher risk of prostate cancer (Pca) reflects a causal relationship. We conducted a meta-analysis and used the Mendelian randomization method (MR) to evaluate the association between RA and Pca risk. A meta-analysis and subgroup analysis of the incidence of Pca in patients with RA was conducted. To determine whether genetically elevated RA levels were causally linked to Pca, two MR samples were employed. To eliminate gender-related bias, we conducted a stratified analysis of the GWAS data for RA by gender, specifically including 140,254 males. Additional MR analysis was also performed to determine potential confounding factors influencing the association between genetically susceptible RA and Pca. In total, 409,950 participants were enrolled in 20 trials to investigate the Pca risk in patients with RA. The meta-analysis suggested that RA was unrelated to the Pca risk (SIR = 1.072, 95% CI, 0.883-1.261). However, a subgroup analysis showed that low smoking rates might increase the Pca risk in patients with RA by 24%. The MR analysis showed that increased genetic susceptibility to RA was related to a high Pca risk (OR = 36.20, 95%CI = 1.24-1053.12, P = 0.037). The causality estimation of MR-Egger, Weighted mode, Simple mode, and Weighted median method were similar in direction and magnitude. Although our meta-analysis found no correlation between RA and Pca risk, MR analyses supported a causal relationship between genetic susceptibility to RA and increased prostate risk. Early attention to Pca risk in patients with RA may be important for improving prognosis and mortality in such patients. Further research is needed to determine the etiology of RA attributed to Pca and its underlying mechanisms.

CD44 Is Associated with Poor Prognosis of ccRCC and Facilitates ccRCC Cell Migration and Invasion through HAS1/MMP9.

BACKGROUND: In many solid tumors, CD44 has been identified as a cancer stem cell marker as well as an important molecular in cancer progression and metastasis, making it attractive for potential therapeutic applications. However, our knowledge of the biological function and mechanism of CD44 in clear cell renal cell carcinoma (ccRCC) is limited. METHODS: In this study, the expression, prognostic values and functional enrichment analysis of CD44 in ccRCC were analyzed using public databases. Quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemical (IHC) assays were taken to detect CD44 expression in ccRCC tissues. The effects of CD44 on the proliferation, migration and invasion of ccRCC cells were investigated by gain-of-function and loss-of-function experiments. Subcutaneous models further confirmed the role of CD44 in tumor growth. The relationship between CD44, HAS1 and MMP9 was investigated to uncover the regulatory mechanism of CD44 in ccRCC. RESULTS: CD44 was significantly upregulated in ccRCC and associated with poor overall survival (OS). Based on the functional enrichment analysis and PPI network, we found that CD44 had associations with ECM interaction and focal adhesion pathway. Clinical ccRCC sample validation revealed that CD44 mRNA and protein expression were significantly increased in ccRCC tissues, and strong CD44 staining was observed in four metastatic ccRCC cases. In vitro experiments showed that CD44 overexpression promoted cell proliferation, migration and invasion. In vivo experiments also demonstrated that CD44 overexpression accelerated tumor formation in mice. Finally, we found that CD44 regulates the expression of HAS1 in ccRCC, which is essential for the secretion of MMP9 and cell migratory ability. CONCLUSION: The upregulation of CD44 mRNA and protein expressions in ccRCC is indicative of unfavorable clinical prognoses. The CD44/HAS1/MMP9 axis is believed to exert a significant influence on the regulation of ECM degradation and ccRCC metastasis.

ATAD2 promotes glycolysis and tumor progression in clear cell renal cell carcinoma by regulating the transcriptional activity of c-Myc.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urogenital tract. Given that ccRCC is often resistant to radiotherapy and traditional chemotherapy, the clinical treatment of patients with ccRCC remains a challenge. The present study found that ATAD2 was significantly upregulated in ccRCC tissues. In vitro and in vivo experiments showed that the inhibition of ATAD2 expression mitigated the aggressive phenotype of ccRCC. ATAD2 was also associated with glycolysis in ccRCC. Interestingly, we found that ATAD2 could physically interact with c-Myc and promote the expression of its downstream target gene, thereby enhancing the Warburg effect of ccRCC. Overall, our study emphasizes the role of ATAD2 in ccRCC. The targeted expression or functional regulation of ATAD2 could be a promising method to reduce the proliferation and progression of ccRCC.

Systemic lupus erythematosus and prostate cancer risk: a pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Current observational studies suggest that there may be a causal relationship between systemic lupus erythematosus (SLE) and prostate cancer (PC). However, there is contradictory evidence. This study aimed to investigate and clarify the association between SLE and PC. METHODS: We searched PubMed, Embase, Web of Science, and Scopus until May 2022. A meta-analysis was conducted on the standard incidence rate (SIR) and 95% CI. Subgroup analysis was performed based on the follow-up duration, study quality, and appropriate SLE diagnosis. Mendelian randomization (MR) of the two samples was used to determine whether genetically elevated SLE was causal for PC. Summary MR data were obtained from published GWASs, which included 1,959,032 individuals. The results were subjected to sensitivity analysis to verify their reliability. RESULTS: In a meta-analysis of 79,316 participants from 14 trials, we discovered that patients with SLE had decreased PC risk (SIR, 0.78; 95% CI, 0.70-0.87) significantly. The MR results showed that a one-SD increase in genetic susceptibility to SLE significantly reduced PC risk (OR, 0.9829; 95% CI, 0.9715-0.9943; P = 0.003). Additional MR analyses suggested that the use of immunosuppressants (ISs) (OR, 1.1073; 95% CI, 1.0538-1.1634; P < 0.001), but not glucocorticoids (GCs) or non-steroidal anti-inflammatory drugs (NSAIDs), which were associated with increased PC risk. The results of the sensitivity analyses were stable, and there was no evidence of directional pleiotropy. CONCLUSIONS: Our results suggest that patients with SLE have a lower risk of developing PC. Additional MR analyses indicated that genetic susceptibility to the use of ISs, but not GCs or NSAIDs, was associated with increased PC risk. This finding enriches our understanding of the potential risk factors for PC in patients with SLE. Further study is required to reach more definitive conclusions regarding these mechanisms.

L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma.

The survival of tumor cells in the bloodstream, and vasculature adhesion at metastatic sites are crucial for tumor metastasis. Perivascular invasion aids tumor cell self-renewal, survival, and formation of metastases by facilitating readily available oxygen, nutrients, and endothelial-derived paracrine factors. Renal cell carcinoma (RCC) is among the most prevalent tumors of the urinary system, and the formation of venous tumor thrombus (VTT) is a characteristic feature of RCC. We observed high expression of L1CAM in the VTT with vessel wall invasion. L1CAM promotes the adhesion, migration, and invasion ability of RCC and enhances metastasis by interacting with ITGA5, which elicits activation of signaling downstream of integrin α5ß1. L1CAM promotes ADAM17 transcription to facilitate transmembrane ectodomain cleavage and release of soluble L1CAM. In response to soluble L1CAM, vascular endothelial cells release several cytokines and chemokines. Endothelial-derived CXCL5 and its receptor CXCR2 promote the migration and intravasation of RCC toward endothelial cells suggesting that crosstalk between endothelial cells and tumor cells has a direct guiding role in driving the metastatic spread of RCC. LICAM plays a crucial role in the invasive ability of RCC, and regulation of L1CAM expression may contribute therapeutically to preventing RCC progression.

TPM2 attenuates progression of prostate cancer by blocking PDLIM7-mediated nuclear translocation of YAP1.

BACKGROUND: Prostate cancer (PCa) is a common malignant tumor of the genitourinary system. Clinical intervention in advanced PCa remains challenging. Tropomyosins 2 (TPM2) are actin-binding proteins and have been found as a biomarker candidate for certain cancers. However, no studies have explored the role of TPM2 in PCa and its regulatory mechanism. METHODS: TPM2 expression was assessed in Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) PCa patient dataset. The effect of TPM2 on PCa progression was assessed in vitro and in vivo by quantifying proliferation, migration, invasion and tumor growth assays, and the mechanism of TPM2 in PCa progression was gradually revealed by Western blotting, immunoprecipitation, and immunofluorescence staining arrays. RESULTS: TPM2 was found to be severely downregulated in tumor tissues of PCa patients compared with tumor-adjacent normal tissues. In vitro experiments revealed that TPM2 overexpression inhibited PCa cell proliferation, invasion and androgen-independent proliferation. Moreover, TPM2 overexpression inhibited the growth of subcutaneous xenograft tumors in vivo. Mechanistically, this effect was noted to be dependent on PDZ-binding motif of TPM2. TPM2 competed with YAP1 for binding to PDLIM7 through the PDZ-binding motif. The binding of TPM2 to PDLIM7 subsequently inhibited the nuclear transport function of PDLIM7 for YAP1. YAP1 sequestered in the cytoplasm phosphorylated at S127, resulting in its inactivation or degradation which in turn inhibited the expression of YAP1 downstream target genes. CONCLUSIONS: This study investigated the role of TPM2, PDLIM7, and YAP1 in PCa progression and castration resistance. TPM2 attenuates progression of PCa by blocking PDLIM7-mediated nuclear translocation of YAP1. Accordingly, targeting the expression or functional modulation of TPM2, PDLIM7, or YAP1 has the potential to be an effective therapeutic approach to reduce PCa proliferation and prevent the progression of castration-resistant prostate cancer (CRPC).

Association between soft drink consumption types and risk of lung cancer and all-cancer: A prospective study of PLCO data.

Diet/sugar-free soft drinks are considered to be healthier than regular soft drinks. However, few studies have examined the relationship between the types of soft drinks (regular and diet/sugar-free) and lung cancer (LC)/all-cancer (AC) risk. In this study, we comprehensively assessed the influence of the type of soft drink consumption on LC/AC risk based on the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Multivariable Cox proportional hazards and competing risks Fine-Gray regression models adjusted for relevant confounders were used to estimate hazard ratios (HRs) and subdistribution HRs for different types of soft drink consumption. In the PLCO population, female subgroup, and the ever/current smoker subgroup, consumption of both regular and diet soft drinks was associated with a significantly reduced risk of LC compared with no soft drinks at all. For the non-lung cancer (NLC) risk, consumption of only diet soft drinks had a significant positive association for the total population and female subgroup. Based on our findings, it was suggested that partial replacement of regular soft drinks with diet soft drinks might be beneficial to LC prevention, especially for females and ever/current smokers. Additionally, completely replacing regular soft drinks with diet soft drinks might be detrimental to NLC prevention, especially for females.

Metabolic Obesity Phenotypes and Risk of Lung Cancer: A Prospective Cohort Study of 450,482 UK Biobank Participants.

(1) Background: The association between metabolic obesity phenotypes and incident lung cancer (LC) remains unclear. (2) Methods: Based on the combination of baseline BMI categories and metabolic health status, participants were categorized into eight groups: metabolically healthy underweight (MHUW), metabolically unhealthy underweight (MUUW), metabolically healthy normal (MHN), metabolically unhealthy normal (MUN), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). The Cox proportional hazards model and Mendelian randomization (MR) were applied to assess the association between metabolic obesity phenotypes with LC risk. (3) Results: During a median follow-up of 9.1 years, 3654 incident LC patients were confirmed among 450,482 individuals. Compared with participants with MHN, those with MUUW had higher rates of incident LC (hazard ratio (HR) = 3.24, 95% confidence interval (CI) = 1.33-7.87, p = 0.009). MHO and MHOW individuals had a 24% and 18% lower risk of developing LC, respectively (MHO: HR = 0.76, 95% CI = 0.61-0.95, p = 0.02; MHO: HR = 0.82, 95% CI = 0.70-0.96, p = 0.02). No genetic association of metabolic obesity phenotypes and LC risk was observed in MR analysis. (4) Conclusions: In this prospective cohort study, individuals with MHOW and MHO phenotypes were at a lower risk and MUUW were at a higher risk of LC. However, MR failed to reveal any evidence that metabolic obesity phenotypes would be associated with a higher risk of LC.

Associations of genetic risk, BMI trajectories, and the risk of non-small cell lung cancer: a population-based cohort study.

BACKGROUND: Body mass index (BMI) has been found to be associated with a decreased risk of non-small cell lung cancer (NSCLC); however, the effect of BMI trajectories and potential interactions with genetic variants on NSCLC risk remain unknown. METHODS: Cox proportional hazards regression model was applied to assess the association between BMI trajectory and NSCLC risk in a cohort of 138,110 participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. One-sample Mendelian randomization (MR) analysis was further used to access the causality between BMI trajectories and NSCLC risk. Additionally, polygenic risk score (PRS) and genome-wide interaction analysis (GWIA) were used to evaluate the multiplicative interaction between BMI trajectories and genetic variants in NSCLC risk. RESULTS: Compared with individuals maintaining a stable normal BMI (n = 47,982, 34.74%), BMI trajectories from normal to overweight (n = 64,498, 46.70%), from normal to obese (n = 21,259, 15.39%), and from overweight to obese (n = 4,371, 3.16%) were associated with a decreased risk of NSCLC (hazard ratio [HR] for trend = 0.78, P < 2×10-16). An MR study using BMI trajectory associated with genetic variants revealed no significant association between BMI trajectories and NSCLC risk. Further analysis of PRS showed that a higher GWAS-identified PRS (PRSGWAS) was associated with an increased risk of NSCLC, while the interaction between BMI trajectories and PRSGWAS with the NSCLC risk was not significant (PsPRS= 0.863 and PwPRS= 0.704). In GWIA analysis, four independent susceptibility loci (P < 1×10-6) were found to be associated with BMI trajectories on NSCLC risk, including rs79297227 (12q14.1, located in SLC16A7, Pinteraction = 1.01×10-7), rs2336652 (3p22.3, near CLASP2, Pinteraction = 3.92×10-7), rs16018 (19p13.2, in CACNA1A, Pinteraction = 3.92×10-7), and rs4726760 (7q34, near BRAF, Pinteraction = 9.19×10-7). Functional annotation demonstrated that these loci may be involved in the development of NSCLC by regulating cell growth, differentiation, and inflammation. CONCLUSIONS: Our study has shown an association between BMI trajectories, genetic factors, and NSCLC risk. Interestingly, four novel genetic loci were identified to interact with BMI trajectories on NSCLC risk, providing more support for the aetiology research of NSCLC. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov , NCT01696968 .

Inhibition of N-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication.

Cancer suppression through the inhibition of N-acetyltransferase 10 (NAT10) by its specific inhibitor Remodelin has been demonstrated in a variety of human cancers. Here, we report the inhibitory effects of Remodelin on prostate cancer (PCa) cells and the possible associated mechanisms. The prostate cancer cell lines VCaP, LNCaP, PC3, and DU145 were used. The in vitro proliferation, migration, and invasion of cells were measured by a cell proliferation assay, colony formation, wound healing, and Transwell assays, respectively. In vivo tumor growth was analyzed by transplantation into nude mice. The inhibition of NAT10 by Remodelin not only suppressed growth, migration, and invasion in vitro, but also the in vivo cancer growth of prostate cancer cells. The involvement of NAT10 in DNA replication was assessed by EdU labeling, DNA spreading, iPOND, and ChIP-PCR assays. The inhibition of NAT10 by Remodelin slowed DNA replication. NAT10 was detected in the prereplication complex, and it could also bind to DNA replication origins. Furthermore, the interaction between NAT10 and CDC6 was analyzed by Co-IP. The altered expression of NAT10 was measured by immunofluorescence staining and Western blotting. Remodelin markedly reduced the levels of CDC6 and AR. The expression of NAT10 could be altered under either castration or noncastration conditions, and Remodelin still suppressed the growth of in vitro-induced castration-resistant prostate cancers. The analysis of a TCGA database revealed that the overexpression of NAT10, CDC6, and MCM7 in prostate cancers were correlated with the Gleason score and node metastasis. Our data demonstrated that Remodelin, an inhibitor of NAT10, effectively inhibits the growth of prostate cancer cells under either no castration or castration conditions, likely by impairing DNA replication.

Deciphering the role of extracellular polymeric substances in the regulation of microbial extracellular electron transfer under low concentrations of tetracycline exposure: Insights from transcriptomic analysis.

Low concentrations of antibiotics can regulate the formation of electroactive biofilms, however, the underlying mechanisms, especially the composition and spatial distribution of extracellular polymeric substances (EPS) and their effects on extracellular electron transfer (EET) process, have not been fully deciphered. Here, the response of EPS of Geobacter sulfurreducens biofilm to low concentrations of tetracycline (µg L-1 to mg L-1) was explored, and the impact of such EPS variations on EET efficiency was further elucidated by transcriptomic analysis. Results showed that 0.05 mg L-1 of tetracycline achieved both beneficial quantitative and spatial regulation of redox-active proteins and non-conducting exopolysaccharides in EPS, while higher concentrations induced negative effects. Moreover, 1 mg L-1 of tetracycline upregulated multiple exopolysaccharide biosynthesis-related genes, indicating a stress response for cell-protection, while 0.05 mg L-1 of tetracycline upregulated most direct EET-related gene expressions, resulting in the promoted EET efficiency. Furthermore, 0.05 mg L-1 of tetracycline selectively enriched Geobacter (45.55% vs 19.55% in control, respectively) from mixed inoculum. This research provides a new insight of how antibiotics at low concentrations regulated EET process through modulation of EPS.

Prediction of acute kidney injury after cardiac surgery: model development using a Chinese electronic health record dataset.

BACKGROUND: Acute kidney injury (AKI) is a major complication following cardiac surgery that substantially increases morbidity and mortality. Current diagnostic guidelines based on elevated serum creatinine and/or the presence of oliguria potentially delay its diagnosis. We presented a series of models for predicting AKI after cardiac surgery based on electronic health record data. METHODS: We enrolled 1457 adult patients who underwent cardiac surgery at Nanjing First Hospital from January 2017 to June 2019. 193 clinical features, including demographic characteristics, comorbidities and hospital evaluation, laboratory test, medication, and surgical information, were available for each patient. The number of important variables was determined using the sliding windows sequential forward feature selection technique (SWSFS). The following model development methods were introduced: extreme gradient boosting (XGBoost), random forest (RF), deep forest (DF), and logistic regression. Model performance was accessed using the area under the receiver operating characteristic curve (AUROC). We additionally applied SHapley Additive exPlanation (SHAP) values to explain the RF model. AKI was defined according to Kidney Disease Improving Global Outcomes guidelines. RESULTS: In the discovery set, SWSFS identified 16 important variables. The top 5 variables in the RF importance matrix plot were central venous pressure, intraoperative urine output, hemoglobin, serum potassium, and lactic dehydrogenase. In the validation set, the DF model exhibited the highest AUROC (0.881, 95% confidence interval [CI] 0.831-0.930), followed by RF (0.872, 95% CI 0.820-0.923) and XGBoost (0.857, 95% CI 0.802-0.912). A nomogram model was constructed based on intraoperative longitudinal features, achieving an AUROC of 0.824 (95% CI 0.763-0.885) in the validation set. The SHAP values successfully illustrated the positive or negative contribution of the 16 variables attributed to the output of the RF model and the individual variable's effect on model prediction. CONCLUSIONS: Our study identified 16 important predictors and provided a series of prediction models to enhance risk stratification of AKI after cardiac surgery. These novel predictors might aid in choosing proper preventive and therapeutic strategies in the perioperative management of AKI patients.

Identification of KIF23 as a Prognostic Biomarker Associated With Progression of Clear Cell Renal Cell Carcinoma.

About 3% of adult cancers are caused by renal cell carcinoma (RCC) and its pathogenesis remains elusive. Among RCC, clear cell renal cell carcinoma (ccRCC) is the predominant histological subtype. Resistance to conventional treatments leaves few treatment options for advanced ccRCC. Although the transcriptome profile of primary ccRCC has been comprehensively summarized, the transcriptome profile of metastatic ccRCC is still lacking. In this study we identified a list of metastasis-related genes and constructing a metastasis-associated prognostic gene signature. By analyzing data from GSE85258 and GSE105288 datasets, 74 genes were identified as metastasis-related genes. To construct prognostic features, we downloaded the expression data of ccRCC from the Cancer Genome Atlas (TCGA). Metastasis-associated genes were initially selected through the LASSO Cox regression analysis and 12 metastasis-related were included to construct prognostic model. Transcriptome profile, patient prognosis, and immune cell infiltration characteristics differed between low- and high-risk groups after grouping according to median risk score. Through explored the functions of differentially expressed genes (DEGs) between the two groups. Kinesin family member 23 (KIF23) was identified as a prognostic marker in ccRCC patients. Furthermore, inhibition of KIF23 expression reduced the proliferation, migration and invasion of ccRCC cells. We further demonstrated that KIF23 promote nuclear translocation of ß-catenin in ccRCC cells, which provides novel insight into the functions and molecular machinery of KIF23 in ccRCC.

Heterogeneity of Treatment Effects for Intensive Blood Pressure Therapy by Individual Components of FRS: An Unsupervised Data-Driven Subgroup Analysis in SPRINT and ACCORD.

BACKGROUND: Few studies have answered the guiding significance of individual components of the Framingham risk score (FRS) to the risk of cardiovascular disease (CVD) after antihypertensive treatment. This study on the systolic blood pressure intervention trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes blood pressure trial (ACCORD-BP) aimed to reveal previously undetected association patterns between individual components of the FRS and heterogeneity of treatment effects (HTEs) of intensive blood pressure control. METHODS: A self-organizing map (SOM) methodology was applied to identify CVD-risk-specific subgroups in the SPRINT (n = 8,773), and the trained SOM was utilized directly in 4,495 patients from the ACCORD. The primary endpoints were myocardial infarction (MI), non-myocardial infarction acute coronary syndrome (non-MI ACS), stroke, heart failure (HF), death from CVD causes, and a primary composite cardiovascular outcome. Cox proportional hazards models were then used to explore the potential heterogeneous response to intensive SBP control. RESULTS: We identified four SOM-based subgroups with distinct individual components of FRS profiles and the CVD risk. For individuals with type 2 diabetes mellitus (T2DM) in the ACCORD or without diabetes in the SPRINT, subgroup I characterized by male with the lowest concentrations for total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol measures, experienced the highest risk for major CVD. Conversely, subgroup III characterized by a female with the highest values for these measures represented as the lowest CVD risk. Furthermore, subgroup II, with the highest systolic blood pressure (SBP) and no antihypertensive agent use at baseline, had a significantly greater frequency of non-MI ACS under intensive BP control, the number needed to harm (NNH) was 84.24 to cause 1 non-MI ACS [absolute risk reduction (ARR) = -1.19%; 95% CI: -2.08, -0.29%] in the SPRINT [hazard ratio (HR) = 3.62; 95% CI: 1.33, 9.81; P = 0.012], and the NNH of was 43.19 to cause 1 non-MI ACS (ARR = -2.32%; 95% CI: -4.63, 0.00%) in the ACCORD (HR = 1.81; 95% CI: 1.01-3.25; P = 0.046). Finally, subgroup IV characterized by mostly younger patients with antihypertensive medication use and smoking history represented the lowest risk for stroke, HF, and relatively low risk for death from CVD causes and primary composite CVD outcome in SPRINT, however, except stroke, a low risk for others were not observed in ACCORD. CONCLUSION: Similar findings in patients with hypertensive with T2DM or without diabetes by multivariate subgrouping suggested that the individual components of the FRS could enrich or improve CVD risk assessment. Further research was required to clarify the potential mechanism.

Efficient degradation of refractory pollutant in a microbial fuel cell with novel hybrid photocatalytic air-cathode: Intimate coupling of microbial and photocatalytic processes.

A microbial fuel cell-photocatalysis system with a novel photocatalytic air-cathode (MFC-PhotoCat) was proposed for synergistic degradation of 2,4,6-trichlorophenol (TCP) with simultaneous electricity generation. Stable electricity generation of 350 mV was achieved during 130 days of operation. Besides, 50 mg L-1 TCP was completely degraded within 72 h, and the rate constant of 0.050 h-1 was 1.8-fold higher than MFC with air-cathode without N-TiO2 photocatalyst. Degradation pathway was proposed based on the intermediates detected and density functional theory (DFT) calculation, with two open-chain intermediates (2-chloro-4-keto-2-hexenedioic acid and hexanoic acid) detected. Furthermore, hierarchical cluster and PCoA revealed significant shifts of microbial community structures, with enriched exoelectrogen (55.2% of Geobacter) and TCP-degrading microbe (7.1% of Thauera) on the cathode biofilm as well as 61.8% of Pseudomonas in the culture solution. This study provides a promising strategy for synergic degradation of recalcitrant contaminants by intimate-coupling of MFC and photocatalysis.

Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Protects the Growth and Survival of Cancer Cells.

The cGAS (GMP-AMP synthase)-mediated senescence-associated secretory phenotype (SASP) and DNA-induced autophagy (DNA autophagy) have been extensively investigated in recent years. However, cGAS-mediated autophagy has not been elucidated in cancer cells. The described investigation revealed that active DNA autophagy but not SASP activity could be detected in the BT-549 breast cancer cell line with high micronucleus (MN) formation. DNA autophagy was identified as selective autophagy of free genomic DNA in the cytoplasm but not nucleophagy. The process of DNA autophagy in the cytosol could be initiate by cGAS and usually cooperates with SQSTM1-mediated autophagy of ubiquitinated histones. Cytoplasmic DNA, together with nuclear proteins such as histones, could be derived from DNA replication-induced nuclear damage and MN collapse. The inhibition of autophagy through chemical inhibitors as well as the genomic silencing of cGAS or SQSTM1 could suppress the growth and survival of cancer cells, and induced DNA damage could increase the sensitivity to these inhibitors. Furthermore, expanded observations of several other kinds of human cancer cells indicated that high relative DNA autophagy or enhancement of DNA damage could also increase or sensitize these cells to inhibition of DNA autophagy.

Correction to: Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells.

The article "Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells", written by "Yaqian Wu, Yanan Cao, Haijing Liu, Mengfei Yao, Ningning Ma and Bo Zhang", was originally published electronically on the publisher's internet portal https://link.springer.com/article/10.1007/s11010-020-03776-w on 11 June 2020 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on 6 July 2020 to © Springer Science+Business Media, LLC, part of Springer Nature 2020 and the article is forthwith distributed under the terms of copyright. The original article has been corrected.