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Background: Circular RNAs (circRNA) have a vital role in the progression of cancers. For instance, circTP63 is upregulated in prostate cancer (PCa) tissues compared with adjacent normal tissues. However, the role of circTP63 in prostate cancer is still unclear. Methods: qRT-PCR assays were applied to detected the expression of circTP63 and miR-421 in PCa samples. Functionally, CCK-8, apoptosis assay, and transwell migration and invasion assays were used to explore the role of circTP63 in PCa progression. Mechanistically, the interaction between circTP63 and miR-421 were verified using qRT-PCR and dual-luciferase report assay. Western blot, qRT-PCR, and dual-luciferase report assay were applied to detect the interaction between miR-421 and VAMP associated protein A (VAPA). And xenograft animal model was used to detect the role of circTP63 in vivo. Results: circTP63 was upregulated and miR-421 was downregulated in PCa tissues. Functional assays revealed that circTP63 promoted the proliferation and metastasis of PCa cells in vitro. In addition, the inhibition effect of circTP63 knockdown could be rescued by miR-421 inhibition or VAPA overexpression. Mechanistically, circTP63-mediated PCa progression through directly binding to miR-421, and subsequently releasing the VAPA. In vivo, silencing of circTP63 significantly impaired PCa progression. Conclusion: In summary, our study identified circTP63 as an oncogenic circRNA, which could be a promising diagnostic and therapeutic target for PCa treatment.

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OBJECTIVE: To evaluate the clinical efficacy and safety of bevacizumab combined with apatinib in the treatment of advanced metastatic gastric cancer, providing insights for treatment decisions. METHODS: We conducted a single-center retrospective study involving patients with metastatic gastric cancer treated with apatinib, with or without bevacizumab, between August 2018 and April 2021 at Nanchang Medical College. Data on efficacy, adverse events, response rates, and quality of life were collected and compared. RESULTS: No significant differences were observed in complete remission, partial response, stable disease, disease progression, objective response rate, or disease control rate between the groups (all P>0.05). The median progression-free survival was 9.23 months in the control group and 9.94 months in the observation group (P=0.587). Median overall survival (OS) was 19.64 months in the control group and 26.44 months in the observation group (P=0.187). Univariate and multivariate analyses identified combination therapy with apatinib and bevacizumab, primary lesion resection, and number of metastatic organs as independent prognostic factors for OS. Scores for role, emotional, somatic, cognitive, and social functions were significantly higher in the observation group post-intervention (all P<0.05). CONCLUSIONS: In patients with advanced metastatic gastric cancer, combined therapy with bevacizumab and apatinib significantly improved OS, enhanced response rates, and increased rates of early and maximal tumor shrinkage.

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Biosynthesis and biodegradation of microorganisms critically underpin the development of biotechnology, new drugs and therapies, and environmental remediation. However, most uncultured microbial species along with their metabolic capacities in extreme environments, remain obscured. Here we unravel the metabolic potential of microbial dark matters (MDMs) in four deep-inland hypersaline lakes in Xinjiang, China. Utilizing metagenomic binning, we uncovered a rich diversity of 3030 metagenome-assembled genomes (MAGs) across 82 phyla, revealing a substantial portion, 2363 MAGs, as previously unclassified at the genus level. These unknown MAGs displayed unique distribution patterns across different lakes, indicating a strong correlation with varied physicochemical conditions. Our analysis revealed an extensive array of 9635 biosynthesis gene clusters (BGCs), with a remarkable 9403 being novel, suggesting untapped biotechnological potential. Notably, some MAGs from potentially new phyla exhibited a high density of these BGCs. Beyond biosynthesis, our study also identified novel biodegradation pathways, including dehalogenation, anaerobic ammonium oxidation (Anammox), and degradation of polycyclic aromatic hydrocarbons (PAHs) and plastics, in previously unknown microbial clades. These findings significantly enrich our understanding of biosynthesis and biodegradation processes and open new avenues for biotechnological innovation, emphasizing the untapped potential of microbial diversity in hypersaline environments.

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Antimicrobial resistance (AMR) poses a global health threat to aquatic environments and its propagation is a hot topic. Therefore, deactivating antibiotic-resistant bacteria (ARB) and removing antibiotic resistance genes (ARGs) from water is crucial for controlling AMR transmission. Peracetic acid (PAA), which is known for its potent oxidizing properties and limited by-product formation, is emerging as a favorable disinfectant for water treatment. In this study, we aimed to assess the efficacy of pre-exposure to PAA followed by UV treatment (PAA-UV/PAA) compared with the simultaneous application of UV and PAA (UV/PAA). The focus was on deactivating vancomycin-resistant Enterococcus faecalis (VREfs), a typical ARB in water. Pre-exposure to PAA significantly enhanced the efficacy of subsequent UV/PAA treatment. At a UV fluence of 7.2 mJ cm-2, the PAA-UV/PAA method achieved a 6.21 log reduction in VREfs, surpassing the 1.29 log reduction observed with UV/PAA. Moreover, compared to UV/PAA, PAA-UV/PAA showed increased efficacy with longer pre-exposure times and higher PAA concentrations, maintaining superior performance across a broad pH range and in the presence of humic acid. Flow cytometry analysis indicated minimal cellular membrane damage using both methods. However, the assessments of superoxide dismutase (SOD) activity and adenosine triphosphate content revealed that PAA-UV/PAA induced greater oxidative stress under similar UV irradiation conditions, leading to slower bacterial regrowth. Specifically, SOD activity in PAA-UV/PAA surged to 3.06 times its baseline, exceeding the 1.73-fold increase under UV/PAA conditions. Additionally, pre-exposure to PAA amplified ARGs degradation and reduced resistance gene leakage, effectively mitigating the spread of AMR. Pre-exposure to 200 µM PAA for 10 and 20 min enhanced vanB gene removal efficiency by 0.14 log and 1.29 log, respectively. Our study provides a feasible approach for optimizing UV/PAA disinfection for efficient removal of ARB and ARGs.

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Glycyl-tRNA synthetase (GARS1) is differentially expressed across cancers. In this study, the value of GARS1 in the diagnosis and prognosis of various cancers was comprehensively evaluated by multiple omics integrative pan-cancer analysis and experimental verification. Through Kaplan-Meier, ROC and multiple databases, we explored GARS1 expression and prognostic and diagnostic patterns across cancers. The GARS1 relative reaction network was identified in PPI, GO, KEGG, methylation models and the genetic mutation atlas. Further research on the GARS1 value in bladder urothelial carcinoma (BLCA) was conducted by regression and nomogram models. We further analyzed the correlation between GARS1 and immune markers and cells in BLCA. Finally, in vitro experiments were used to validate GARS1 the oncogenic function of GARS1 in BLCA. We found that GARS1 was highly expressed across cancers, especially in BLCA. GARS1 expression was correlated with poor survival and had high diagnostic value in most tumor types. GARS1 is significantly associated with tRNA-related pathways whose mutation sites are mainly located on tRNA synthetase. In addition, Upregulation of GARS1 was connected with immune cell infiltration and five key MMR genes. M2 macrophages, TAMs, Th1 and T-cell exhaustion, and marker sets associated with GARS1 expression indicated specific immune infiltration in BLCA. Finally, in vitro experiments validated that GARS1 expression promotes BLCA cell proliferation and metastasis and inhibits apoptosis. Overall, GARS1 can be a novel prognostic and immunological biomarker through multiple omics integrative pan-cancer analysis. The expression of GARS1 in BLCA was positively correlated with specific immune infiltration, indicating that GARS1 might be related to the tumor immune microenvironment.

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BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors marked a milestone in the breast cancer treatment. Due to the potential impact of adverse effects on treatment decisions and patient outcomes, careful consideration of the varying toxicities of CDK4/6 inhibitors is crucial, as three inhibitors-palbociclib, abemaciclib, and ribociclib-have been approved with differences in adverse event profiles. However, limitations in clinical trials call for urgent real-world safety studies to evaluate and compare the risk of adverse events (AEs) among these CDK4/6 inhibitors. Therefore, this study aimed to analyze AEs of CDK4/6 inhibitors and provide insights for clinical drug selection, using real world database. METHODS: The AEs of CDK4/6 inhibitors in the FDA Adverse Event Reporting System (2015-2022) were analyzed. Four disproportionality methods were used to detect safety signals: reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Neural Network Propagation, and Multi-Item Gamma Poisson Shrinker. Venn analysis was used to compare and select common and specific AEs. RESULTS: This study included 73,042 patients treated with palbociclib, 25,142 with ribociclib, and 7563 with abemaciclib. All three inhibitors had 27 common AEs. Palbociclib exhibited the highest ROR for hematologic toxicities, while ribociclib showed the highest ROR for macrocytosis, nail disorders, and hepatic lesions. Abemaciclib displayed the highest ROR for mucosal toxicity. Common signals for both palbociclib and ribociclib included hematologic toxicities, decreased immune responsiveness, and aphthous ulcers. Myelosuppression, oral pain, and pseudocirrhosis were common signals for palbociclib and abemaciclib. Anemia, hepatotoxicity, and pneumonitis were observed as common signals for ribociclib and abemaciclib. Furthermore, specific AEs associated with palbociclib included fatigue, alopecia, and stomatitis. For ribociclib, specific AEs included electrocardiogram QT prolongation, thrombocytopenia, and decreased hemoglobin. Abemaciclib was specifically linked to diarrhea, vomiting, and interstitial lung disease. CONCLUSION: Our analysis revealed that palbociclib showed a higher risk of hematologic toxicity. Ribociclib showed higher risks of hepatotoxicity, nephrotoxicity, and QT prolongation. Abemaciclib showed higher risks of hepatotoxicity, gastrointestinal effects, interstitial lung disease, and thrombosis. These findings provide valuable insights for CDK4/6 inhibitor selection.

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Astragalus polysaccharide-containing 3D-printed scaffold shows great potential in traumatic skin repair. This study aimed to investigate its repairing effect and to combine it with proteomic technology to deeply resolve the related protein expression changes. Thirty SD rats were divided randomly into three groups (n = 10 per group): the sham-operated group, the model group and the scaffold group. Subsequently, we conducted a comparative analysis on trauma blood perfusion, trauma healing rate, histological changes, the expression of the YAP/TAZ signalling pathway and angiogenesis-related factors. Additionally, neonatal skin tissues were collected for proteomic analysis. The blood perfusion volume and wound healing recovery in the scaffold group were better than that in the model group (p < 0.05). The protein expression of STAT3, YAP, TAZ and expression of vascular-related factor A (VEGFA) in the scaffold group was higher than that in the model group (p < 0.05). Proteomic analysis showed that there were 207 differential proteins common to the three groups. Mitochondrial function, immune response, redox response, extracellular gap and ATP metabolic process were the main groups of differential protein changes. Oxidative phosphorylation, metabolic pathway, carbon metabolism, calcium signalling pathway, etc. were the main differential metabolic pathway change groups. Astragalus polysaccharide-containing 3D-printed scaffold had certain reversals of protein disorder. The Astragalus polysaccharide-containing 3D-printed scaffold may promote the VEGFs by activating the YAP/TAZ signalling pathway with the help of STAT3 into the nucleus, accelerating early angiogenesis of the trauma, correcting the protein disorder of the trauma and ultimately realizing the repair of the wound.

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BACKGROUND: Spinal muscular atrophy (SMA) is a neurodegenerative disorder. Although prior studies have investigated the metabolomes of SMA in various contexts, there is a gap in research on cerebrospinal fluid (CSF) metabolomics compared to healthy controls. CSF metabolomics can provide insights into central nervous system function and patient outcomes. This study aims to investigate CSF metabolite profiles in untreated SMA patients to enhance our understanding of SMA metabolic dysregulation. METHODS: This case control study included 15 SMA patients and 14 control subjects. CSF samples were collected, and untargeted metabolomics was conducted to detect metabolites in SMA and control groups. RESULTS: A total of 118 metabolites abundance were significantly changed between the SMA and control groups. Of those, 27 metabolites with variable importance for the projection (VIP) ≥ 1.5 were identified. The top 5 differential metabolites were N-acetylneuraminic acid (VIP = 2.38, Fold change = 0.43, P = 5.49 × 10-5), 2,3-dihydroxyindole (VIP = 2.33, Fold change = 0.39, P = 1.81 × 10-4), lumichrome (VIP = 2.30, Fold change = 0.48, P = 7.90 × 10-5), arachidic acid (VIP = 2.23, Fold change = 10.79, P = 6.50 × 10-6), and 10-hydroxydecanoic acid (VIP = 2.23, Fold change = 0.60, P = 1.44 × 10-4). Cluster analysis demonstrated that the differentially metabolites predominantly clustered within two main categories: protein and amino acid metabolism, and lipid metabolism. CONCLUSIONS: The findings highlight the complexity of SMA, with widespread effects on multiple metabolic pathways, particularly in amino acid and lipid metabolism. N-acetylneuraminic acid may be a potential treatment for functional improvement in SMA. The exact mechanisms and potential therapeutic targets associated with metabolic dysregulation in SMA require further investigation.

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The United States Food and Drug Administration (FDA) has been warning about the psychiatric disorders associated with montelukast (MTK) for years. To study the characteristics of the presence of MTK-associated adverse events (AEs), we obtained data from the FDA Adverse Event Reporting System database and used a case (MTK) vs. non-case (all other drugs) analysis to investigate the safety signals in a disproportionality study. 27,507 reported AEs from January 2004 to December 2022 were analyzed. Disproportionality analysis shows that psychiatric, respiratory, thoracic, and mediastinal disorders as well as social circumstances are the most commonly reported AEs. In addition, our study found several unreported AEs, such as increased systolic blood pressure, diastolic dysfunction, hypothyroidism, obesity, bursitis, and polycystic ovaries. The timing of AE occurrence indicates that MTK-associated AEs are mainly acute effects. Most importantly, we found that 60.1% of patients reporting AEs in the category of psychiatric disorders were younger than 18 years. In summary, we revealed an age-preference pattern of psychiatric AEs in patients prescribed MTK. Our study is helpful for physicians and health professionals to better evaluate the value and risk of MTK and to achieve the goal of optimal patient care.

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Background: Circadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between PER and CRY polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity. Methods: A total of 221 preterm infants of gestational age <34 weeks were included in this study (160 in the response group and 61 in the non-response group). The propensity score matching method was used to perform a 1:1 matching for all premature infants, and the general characteristics and clinical outcomes of the two groups were compared. The association between polymorphisms of the circadian transcription repressors PER and CRY and caffeine citrate treatment response in infants with apnea of prematurity was analyzed with co-dominant, dominant, recessive, and over-dominant models, as well as analysis of alleles. Generalized multifactor dimensionality reduction (GMDR) analysis was used to analyze the interaction between the PER and CRY genes. Results: After propensity score matching, 45 preterm infants were included in each of the response and non-response groups, and there were no statistically significant differences in general characteristics between the two groups (P > 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (P = 0.043), retinopathy of prematurity (ROP) (P = 0.035), and invasive ventilation (P = 0.027), and their duration of oxygen use (P = 0.041) was longer. When corrected for false discovery rate, the PER3 rs228669 recessive model (P FDR = 0.045) and the over-dominant model (P FDR = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12-0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64-10.66). GMDR analysis revealed an interaction between the PER and CRY genes (P < 0.05). Conclusions: Circadian rhythms may play a role in the response of premature infants to caffeine citrate, and polymorphisms of the PER and CRY genes may influence the effectiveness of caffeine citrate treatment for apnea of prematurity.

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BACKGROUND: Metastatic colorectal cancer (mCRC) is a common malignancy whose treatment has been a clinical challenge. Cancer-specific survival (CSS) plays a crucial role in assessing patient prognosis and treatment outcomes. However, there is still limited research on the factors affecting CSS in mCRC patients and their correlation. AIM: To predict CSS, we developed a new nomogram model and risk grading system to classify risk levels in patients with mCRC. METHODS: Data were extracted from the United States Surveillance, Epidemiology, and End Results database from 2018 to 2023. All eligible patients were randomly divided into a training cohort and a validation cohort. The Cox proportional hazards model was used to investigate the independent risk factors for CSS. A new nomogram model was developed to predict CSS and was evaluated through internal and external validation. RESULTS: A multivariate Cox proportional risk model was used to identify independent risk factors for CSS. Then, new CSS columns were developed based on these factors. The consistency index (C-index) of the histogram was 0.718 (95%CI: 0.712-0.725), and that of the validation cohort was 0.722 (95%CI: 0.711-0.732), indicating good discrimination ability and better performance than tumor-node-metastasis staging (C-index: 0.712-0.732). For the training set, 0.533, 95%CI: 0.525-0.540; for the verification set, 0.524, 95%CI: 0.513-0.535. The calibration map and clinical decision curve showed good agreement and good potential clinical validity. The risk grading system divided all patients into three groups, and the Kaplan-Meier curve showed good stratification and differentiation of CSS between different groups. The median CSS times in the low-risk, medium-risk, and high-risk groups were 36 months (95%CI: 34.987-37.013), 18 months (95%CI: 17.273-18.727), and 5 months (95%CI: 4.503-5.497), respectively. CONCLUSION: Our study developed a new nomogram model to predict CSS in patients with synchronous mCRC. In addition, the risk-grading system helps to accurately assess patient prognosis and guide treatment.

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When it comes to enzyme stability and their application in organic solvents, enzyme biocatalysis has emerged as a popular substitute for conventional chemical processes. However, the demand for enzymes exhibiting improved stability remains a persistent challenge. Organic solvents can significantly impacts enzyme properties, thereby limiting their practical application. This study focuses on Lipase Thermomyces lanuginose, through molecular dynamics simulations and experiments, we quantified the effect of different solvent-lipase interfaces on the interfacial activation of lipase. Revealed molecular views of the complex solvation processes through the minimum distance distribution function. Solvent-protein interactions were used to interpret the factors influencing changes in lipase conformation and enzyme activity. We found that water content is crucial for enzyme stability, and the optimum water content for lipase activity was 35 % in the presence of benzene-water interface, which is closely related to the increase of its interfacial activation angle from 78° to 102°. Methanol induces interfacial activation in addition to significant competitive inhibition and denaturation at low water content. Our findings shed light on the importance of understanding solvent effects on enzyme function and provide practical insights for enzyme engineering and optimization in various solvent-lipase interfaces.

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BACKGROUND: ThePhosphoinositide 3-kinases (PI3Ks) family plays a crucial role intumorigenesis. Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibitingPI3Kδ) were developed to target the PI3K pathway. However, the toxicity limitstheir application to some extent. It's necessary to investigate the adverseeffects (AEs) of these inhibitors. RESEARCH DESIGNAND METHODS: We conducted acomparative analysis of the safety signals of AEs in PI3K inhibitors usingdisproportionality analysis in the FDA Adverse Event Reporting System database(FAERS). RESULTS: Our studyidentified significant safety signals for metabolic disorders with all PI3Kinhibitors. Notable safety signals for gastrointestinal disorders were observedwith most PI3K inhibitors, with the exception of copanlisib. Common AEs shared amongall PI3K inhibitors included colitis and dehydration. Alpelisib displayedunique AEs associated with metabolic disorders, whereas copanlisib exhibitedidiosyncratic AEs linked to cardiac and vascular disorders. Stevens-Johnsonsyndrome emerged as a common severe adverse event (SAE) among alpelisib,copanlisib, and idelalisib, while febrile neutropenia was prevalent amongcopanlisib, duvelisib, and idelalisib. Intestinal perforation was solelyassociated with alpelisib. CONCLUSIONS: The safety profiles of the five PI3K inhibitorsvary concerning adverse events. These findings could guide drug selection andinform future prospective research.

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PURPOSE: Teprotumumab is the only drug approval by The US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED), which targets the insulin-like growth factor-1 receptor. This study aimed to identify potential safety signals of teprotumumab by analyzing post-marketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023. METHODS: The case/non-case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered three or more. RESULTS: Total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), deafness permanent (ROR [95% CI] = 1552.35 [789.07-3053.98]), deafness bilateral (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycaemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]) and amenorrhoea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals of teprotumumab. CONCLUSIONS: This study identified ear and labyrinth disorders, reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue.

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Background: Bladder cancer is a prevalent malignancy with significant clinical implications. Small Ubiquitin-like Modifier (SUMO) pathway related genes (SPRG) have been implicated in the development and progression of cancer. Methods: In this study, we conducted a comprehensive analysis of SPRG in bladder cancer. We analyzed gene expression and prognostic value of SPRG and developed a SPRG signature (SPRGS) prognostic model based on four genes (HDAC4, TRIM27, EGR2, and UBE2I) in bladder cancer. Furthermore, we investigated the relationship between SPRGS and genomic alterations, tumor microenvironment, chemotherapy response, and immunotherapy. Additionally, we identified EGR2 as a key SPRG in bladder cancer. The expression of EGR2 in bladder cancer was detected by immunohistochemistry, and the cell function experiment clarified the effect of knocking down EGR2 on the proliferation, invasion, and migration of bladder cancer cells. Results: Our findings suggest that SPRGS hold promise as prognostic markers and predictive biomarkers for chemotherapy response and immunotherapy efficacy in bladder cancer. The SPRGS prognostic model exhibited high predictive accuracy for bladder cancer patient survival. We also observed correlations between SPRG and genomic alterations, tumor microenvironment, and response to chemotherapy. Immunohistochemical results showed that EGR2 was highly expressed in bladder cancer tissues, and its overexpression was associated with poor prognosis. Knockdown of EGR2 inhibited bladder cancer cell proliferation, invasion, and migration. Conclusion: This study provides valuable insights into the landscape of SPRGS in bladder cancer and their potential implications for personalized treatment strategies. The identification of EGR2 as a key SPRG and its functional impact on bladder cancer cells further highlights its significance in bladder cancer development and progression. Overall, SPRGS may serve as important prognostic markers and predictive biomarkers for bladder cancer patients, guiding treatment decisions and improving patient outcomes.

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Background: Kidney cancer is a prevalent malignancy with an increasing incidence worldwide. Blood cell indices and inflammation-related markers have shown huge potential as biomarkers for predicting cancer incidences, but that is not clear in kidney cancer. Our study aims to investigate the correlations of blood cell indices and inflammation-related markers with kidney cancer risk. Methods: We performed a population-based cohort prospective analysis using data from the UK Biobank. A total of 466,994 participants, free of kidney cancer at baseline, were included in the analysis. The hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk were calculated using Cox proportional hazards regression models. Restricted cubic spline models were used to investigate nonlinear longitudinal associations. Stratified analyses were used to identify high-risk populations. The results were validated through sensitivity analyses. Results: During a mean follow-up of 12.4 years, 1,710 of 466,994 participants developed kidney cancer. The Cox regression models showed that 13 blood cell indices and four inflammation-related markers were associated with kidney cancer incidence. The restricted cubic spline models showed non-linear relationships with kidney cancer. Finally, combined with stratified and sensitivity analyses, we found that the mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet distribution width (PDW), systemic immune-inflammation index (SII), and product of platelet count and neutrophil count (PPN) were related to enhanced kidney cancer risk with stable results. Conclusion: Our findings identified that three blood cell indices (MCHC, RDW, and PDW) and two inflammation-related markers (SII and PPN) were independent risk factors for the incidence of kidney cancer. These indexes may serve as potential predictors for kidney cancer and aid in the development of targeted screening strategies for at-risk individuals.

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BACKGROUND: Predictive biomarkers and models of immune checkpoint inhibitors (ICIs) have been extensively studied in non-small cell lung cancer (NSCLC). However, evidence for many biomarkers remains inconclusive, and the opaqueness of machine learning models hinders practicality. We aimed to provide compelling evidence for biomarkers and develop a transparent decision tree model. METHODS: We consolidated data from 3,288 ICI-treated patients with NSCLC across real-world multicenter, public cohorts and the Choice-01 trial (ClinicalTrials.gov: NCT03856411). Over 50 features were examined for predicting durable clinical benefits (DCBs) from ICIs. Noteworthy biomarkers were identified to establish a decision tree model. Additionally, we explored the tumor microenvironment and peripheral CD8+ programmed death-1 (PD-1)+ T cell receptor (TCR) profiles. FINDINGS: Multivariate logistic regression analysis identified tumor histology, PD-ligand 1 (PD-L1) expression, tumor mutational burden, line, and regimen of ICI treatment as significant factors. Mutation subtypes of EGFR, KRAS, KEAP1, STK11, and disruptive TP53 mutations were associated with DCB. The decision tree (DT10) model, using the ten clinicopathological and genomic markers, showed superior performance in predicting DCB in the training set (area under the curve [AUC] = 0.82) and consistently outperformed other models in test sets. DT10-predicted-DCB patients manifested longer survival, an enriched inflamed tumor immune phenotype (67%), and higher peripheral TCR diversity, whereas the DT10-predicted-NDB (non-durable benefit) group showed an enriched desert immune phenotype (86%) and higher peripheral TCR clonality. CONCLUSIONS: The model effectively predicted DCB after front-/subsequent-line ICI treatment, with or without chemotherapy, for squamous and non-squamous lung cancer, offering clinicians valuable insights into efficacy prediction using cost-effective variables. FUNDING: This study was supported by the National Key R&D Program of China.

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Phase-modulator-generated laser for Raman transition is widely used in atom gravimeters to simplify a system and improve robustness. However, the induced additional sidebands (ASBs) lead to systematic errors in gravity measurement. This work presents a novel, to our knowledge, method to generate an optical single-sideband (OSSB) laser for Raman transition through phase modulation based on a Faraday anomalous dispersion atomic filter (FADOF). The experimental result indicates that it can reduce the additional sidebands with a signal-to-noise ratio (SNR, the intensity ratio of carrier and unwanted sidebands) of better than 50 dB, and the phase shift caused by ASBs is demonstrated to be effectively suppressed from 358.8 to 2.2 mrad. Furthermore, this system has already been applied on an atom gravimeter to achieve a primary gravity measurement. It shows that the FADOF-based Raman laser system is a new scheme for a compact atom absolute gravimeter.

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Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a crucial enzyme in glycolysis, an essential metabolic pathway for carbohydrate metabolism across all living organisms. Recent research indicates that phosphorylating GAPDH exhibits various moonlighting functions, contributing to plant growth and development, autophagy, drought tolerance, salt tolerance, and bacterial/viral diseases resistance. However, in rapeseed (Brassica napus), the role of GAPDHs in plant immune responses to fungal pathogens remains unexplored. In this study, 28 genes encoding GAPDH proteins were revealed in B. napus and classified into three distinct subclasses based on their protein structural and phylogenetic relationships. Whole-genome duplication plays a major role in the evolution of BnaGAPDHs. Synteny analyses revealed orthologous relationships, identifying 23, 26, and 26 BnaGAPDH genes with counterparts in Arabidopsis, Brassica rapa, and Brassica oleracea, respectively. The promoter regions of 12 BnaGAPDHs uncovered a spectrum of responsive elements to biotic and abiotic stresses, indicating their crucial role in plant stress resistance. Transcriptome analysis characterized the expression profiles of different BnaGAPDH genes during Sclerotinia sclerotiorum infection and hormonal treatment. Notably, BnaGAPDH17, BnaGAPDH20, BnaGAPDH21, and BnaGAPDH22 exhibited sensitivity to S. sclerotiorum infection, oxalic acid, hormone signals. Intriguingly, under standard physiological conditions, BnaGAPDH17, BnaGAPDH20, and BnaGAPDH22 are primarily localized in the cytoplasm and plasma membrane, with BnaGAPDH21 also detectable in the nucleus. Furthermore, the nuclear translocation of BnaGAPDH20 was observed under H2O2 treatment and S. sclerotiorum infection. These findings might provide a theoretical foundation for elucidating the functions of phosphorylating GAPDH.

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Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.