PD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression.

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.

Clinical analysis of 314 patients with high-grade squamous intraepithelial lesion who underwent total hysterectomy directly: a multi-center, retrospective cohort study.

OBJECTIVE: To identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL. METHOD: The clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading. RESULT: 1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2-59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244-12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78-23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947-14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892-11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good. CONCLUSION: There is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

Effects of UV-B Radiation Exposure on Transgenerational Plasticity in Grain Morphology and Proanthocyanidin Content in Yuanyang Red Rice.

The effect of UV-B radiation exposure on transgenerational plasticity, the phenomenon whereby the parental environment influences both the parent's and the offspring's phenotype, is poorly understood. To investigate the impact of exposing successive generations of rice plants to UV-B radiation on seed morphology and proanthocyanidin content, the local traditional rice variety 'Baijiaolaojing' was planted on terraces in Yuanyang county and subjected to enhanced UV-B radiation treatments. The radiation intensity that caused the maximum phenotypic plasticity (7.5 kJ·m-2) was selected for further study, and the rice crops were cultivated for four successive generations. The results show that in the same generation, enhanced UV-B radiation resulted in significant decreases in grain length, grain width, spike weight, and thousand-grain weight, as well as significant increases in empty grain percentage and proanthocyanidin content, compared with crops grown under natural light conditions. Proanthocyanidin content increased as the number of generations of rice exposed to radiation increased, but in generation G3, it decreased, along with the empty grain ratio. At the same time, biomass, tiller number, and thousand-grain weight increased, and rice growth returned to control levels. When the offspring's radiation memory and growth environment did not match, rice growth was negatively affected, and seed proanthocyanidin content was increased to maintain seed activity. The correlation analysis results show that phenylalanine ammonialyase (PAL), cinnamate-4-hydroxylase (C4H), dihydroflavonol 4-reductase (DFR), and 4-coumarate:CoA ligase (4CL) enzyme activity positively influenced proanthocyanidin content. Overall, UV-B radiation affected transgenerational plasticity in seed morphology and proanthocyanidin content, showing that rice was able to adapt to this stressor if previous generations had been continuously exposed to treatment.

Cell-free Nucleic Acid as Promising Diagnostic Biomarkers for Gastric Cancer: a Systematic Review.

Background: Gastric cancer (GC) is a common malignancy with early detection being crucial for survival. Liquid biopsy analysis using cell-free nucleic acid is a preferred method for detection. Hence, we conducted a systematic review to assess the diagnostic efficacy of cell-free nucleic acid markers for GC. Methods: We searched PubMed and ISI Web of Science databases for articles that conformed to our inclusion and exclusion criteria from 2012 to 2022. The following information was abstracted: first author, year of publication, country/region, age, male proportion, tumor stage for cases, specimen type, measurement method, targeted markers and diagnostic related indicators (including sensitivity, specificity, AUC, P-value). Results: Fifty-eight studies examined cell-free RNAs (cfRNAs) with a total of 62 individual circulating markers and 7 panels in serum or plasma, while 21 studies evaluated cell-free DNAs (cfDNAs) with 29 individual circulating markers and 7 panels. For individual cfRNAs, the median (range) sensitivity and specificity were 80% (21% - 98%) and 80% (54% - 99%), respectively. The median (range) sensitivity and specificity for cfRNA panels were 86% (83% - 90%) and 75% (60% - 98%), respectively. In comparison, the median (range) sensitivity and specificity reported for individual cfDNAs were 50% (18% - 96%) and 93% (57% - 100%), respectively, while cfDNA panels had a median (range) sensitivity and specificity of 85% (41% - 92%) and 73.5% (38% - 90%), respectively. The meta results indicate that cfRNA markers exhibit high sensitivity (80%) and low specificity (80%) for detecting GC, while cfDNA markers have lower sensitivity (59%) but higher specificity (92%). Conclusions: This review has demonstrated that cell-free nucleic acids have the potential to serve as useful diagnostic markers for GC. Given that both cfRNA and cfDNA markers have shown promising diagnostic performance for GC, the combination of the two may potentially enhance diagnostic efficiency.

Ubiquitin-specific protease 54 regulates GLUT1-mediated aerobic glycolysis to inhibit lung adenocarcinoma progression by modifying p53 degradation.

Lung adenocarcinoma (LUAD) is one of the most prevalent types of cancer. Ubiquitination is crucial in modulating cell proliferation and aerobic glycolysis in cancer. The frequency of TP53 mutations in LUAD is approximately 50%. Currently, therapeutic targets for wild-type (WT) p53-expressing LUAD are limited. In the present study, we systemically explored the expression of ubiquitin-specific protease genes using public datasets. Then, we focused on ubiquitin-specific protease 54 (USP54), and explored its prognostic significance in LUAD patients using public datasets, analyses, and an independent cohort from our center. We found that the expression of USP54 was lower in LUAD tissues compared with that in the paracancerous tissues. Low USP54 expression levels were linked to a malignant phenotype and worse survival in patients with LUAD. The results of functional experiments revealed that up-regulation of USP54 suppressed LUAD cell proliferation in vivo and in vitro. USP54 directly interacted with p53 protein and the levels of ubiquitinated p53 were inversely related to USP54 levels, consistent with a role of USP54 in deubiquitinating p53 in p53-WT LUAD cells. Moreover, up-regulation of the USP54 expression inhibited aerobic glycolysis in LUAD cells. Importantly, we confirmed that USP54 inhibited aerobic glycolysis and the growth of tumor cells by a p53-mediated decrease in glucose transporter 1 (GLUT1) expression in p53-WT LUAD cells. Altogether, we determined a novel mechanism of survival in the p53-WT LUAD cells to endure the malnourished tumor microenvironment and provided insights into the role of USP54 in the adaptation of p53-WT LUAD cells to metabolic stress.

Gas-Amplified Metalloimmunotherapy with Dual Activation of Pyroptosis and the STING Pathway for Remodeling the Immunosuppressive Cervical Cancer Microenvironment.

The immunosuppressive microenvironment of cervical cancer significantly hampers the effectiveness of immunotherapy. Herein, PEGylated manganese-doped calcium sulfide nanoparticles (MCSP) were developed to effectively enhance the antitumor immune response of the cervical cancer through gas-amplified metalloimmunotherapy with dual activation of pyroptosis and STING pathway. The bioactive MCSP exhibited the ability to rapidly release Ca2+, Mn2+, and H2S in response to the tumor microenvironment. H2S disrupted the calcium buffer system of cancer cells by interfering with the oxidative phosphorylation pathway, leading to calcium overload-triggered pyroptosis. On the other hand, H2S-mediated mitochondrial dysfunction further promoted the release of mitochondrial DNA (mtDNA), enhancing the activation effect of Mn2+ on the cGAS-STING signaling axis and thereby activating immunosuppressed dendritic cells. The released H2S acted as an important synergist between Mn2+ and Ca2+ by modulating dual signaling mechanisms to bridge innate and adaptive immune responses. The combination of MCSP NPs and PD-1 immunotherapy achieved synergistic antitumor effects and effectively inhibited tumor growth. This study reveals the potential collaboration between H2S gas therapy and metalloimmunotherapy and provides an idea for the design of nanoimmunomodulators for rational regulation of the immunosuppressive tumor microenvironment.

Association between vitamin B2 intake and prostate-specific antigen in American men: 2003-2010 National Health and Nutrition Examination Survey.

BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.

The Impact of Impurity Gases on the Hydrogen Embrittlement Behavior of Pipeline Steel in High-Pressure H2 Environments.

The use of hydrogen-blended natural gas presents an efficacious pathway toward the rapid, large-scale implementation of hydrogen energy, with pipeline transportation being the principal method of conveyance. However, pipeline materials are susceptible to hydrogen embrittlement in high-pressure hydrogen environments. Natural gas contains various impurity gases that can either exacerbate or mitigate sensitivity to hydrogen embrittlement. In this study, we analyzed the mechanisms through which multiple impurity gases could affect the hydrogen embrittlement behavior of pipeline steel. We examined the effects of O2 and CO2 on the hydrogen embrittlement behavior of L360 pipeline steel through a series of fatigue crack growth tests conducted in various environments. We analyzed the fracture surfaces and assessed the fracture mechanisms involved. We discovered that CO2 promoted the hydrogen embrittlement of the material, whereas O2 inhibited it. O2 mitigated the enhancing effect of CO2 when both gases were mixed with hydrogen. As the fatigue crack growth rate increased, the influence of impurity gases on the hydrogen embrittlement of the material diminished.

Potential Role of MAP3K14 in Hepatocellular Carcinoma: A Study Based on Comprehensive Bioinformatical Analysis and Validation.

According to reports, MAP3K14 is considered an oncogene and is aberrantly expressed in various types of tumor cells. Its abnormal expression is closely associated with the occurrence and progression of various cancers. MAP3K14 also plays a significant role in the development of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma and its connection to tumor stem cells. The prognostic value of MAP3K14 in HCC, as well as its potential functions and roles, requires further elucidation. We evaluated the potential role of MAP3K14 in HCC based on data mining from a range of public databases. The bioinformatics analysis of TCGA, GEO, TIMER, cBioportal, Kaplan-Meier plotter, MethSurv, ENCORI and CellMiner databases was carried out. The expression of MAP3K14 protein in HCC was detected by immunohistochemical method. The mRNA and protein expression levels of MAP3K14 in tumor tissues were higher than those in normal tissues (p < 0.05). The expression of MAP3K14 was correlated with Pathologic T stage (p=0.026), Pathologic stage (p=0.032), Tumor status (p=0.024) and AFP (p=0.002). HCC patients with high expression of MAP3K14 had poor overall survival (OS), progression free survival (PFS) and recurrence free survival (RFS). Multivariate Cox regression analysis showed that the Pathologic stage (p < 0.001) and MAP3K14 expression levels (p < 0.05) is an independent prognostic factor affecting the survival of patients with liver cancer. GO/KEGG analysis suggested that key biological processes (PI3K-Akt signaling pathway) may be the mechanism promoting HCC development. In addition, MAP3K14 was significantly correlated with the infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (p < 0.05). MAP3K14 is up-regulated in HCC and is closely related to the prognosis of HCC patients. MAP3K14 may serve as a potential biomarker for poor prognosis of HCC.

Squalene Epoxidase: Its Regulations and Links with Cancers.

Squalene epoxidase (SQLE) is a key enzyme in the mevalonate-cholesterol pathway that plays a critical role in cellular physiological processes. It converts squalene to 2,3-epoxysqualene and catalyzes the first oxygenation step in the pathway. Recently, intensive efforts have been made to extend the current knowledge of SQLE in cancers through functional and mechanistic studies. However, the underlying mechanisms and the role of SQLE in cancers have not been fully elucidated yet. In this review, we retrospected current knowledge of SQLE as a rate-limiting enzyme in the mevalonate-cholesterol pathway, while shedding light on its potential as a diagnostic and prognostic marker, and revealed its therapeutic values in cancers. We showed that SQLE is regulated at different levels and is involved in the crosstalk with iron-dependent cell death. Particularly, we systemically reviewed the research findings on the role of SQLE in different cancers. Finally, we discussed the therapeutic implications of SQLE inhibitors and summarized their potential clinical values. Overall, this review discussed the multifaceted mechanisms that involve SQLE to present a vivid panorama of SQLE in cancers.

Predicting central cervical lymph node metastasis in papillary thyroid carcinoma with Hashimoto's thyroiditis: a practical nomogram based on retrospective study.

Background: In papillary thyroid carcinoma (PTC) patients with Hashimoto's thyroiditis (HT), preoperative ultrasonography frequently reveals the presence of enlarged lymph nodes in the central neck region. These nodes pose a diagnostic challenge due to their potential resemblance to metastatic lymph nodes, thereby impacting the surgical decision-making process for clinicians in terms of determining the appropriate surgical extent. Methods: Logistic regression analysis was conducted to identify independent risk factors associated with central lymph node metastasis (CLNM) in PTC patients with HT. Then a prediction model was developed and visualized using a nomogram. The stability of the model was assessed using ten-fold cross-validation. The performance of the model was further evaluated through the use of ROC curve, calibration curve, and decision curve analysis. Results: A total of 376 HT PTC patients were included in this study, comprising 162 patients with CLNM and 214 patients without CLNM. The results of the multivariate logistic regression analysis revealed that age, Tg-Ab level, tumor size, punctate echogenic foci, and blood flow grade were identified as independent risk factors associated with the development of CLNM in HT PTC. The area under the curve (AUC) of this model was 0.76 (95% CI [0.71-0.80]). The sensitivity, specificity, accuracy, and positive predictive value of the model were determined to be 88%, 51%, 67%, and 57%, respectively. Conclusions: The proposed clinic-ultrasound-based nomogram in this study demonstrated a favorable performance in predicting CLNM in HT PTCs. This predictive tool has the potential to assist clinicians in making well-informed decisions regarding the appropriate extent of surgical intervention for patients.

Mid-term clinical outcomes of totally endoscopic repair for mitral regurgitation in Barlow's disease.

OBJECTIVE: This study aimed to confirm the safety and feasibility of totally endoscopic repair for mitral regurgitation (MR) in Barlow's disease. METHODS: From June 2018 to December 2022, 21 consecutive Barlow's disease patients (aged 33 ± 12 years; 57.1% male) underwent totally endoscopic mitral valve (MV) repair with leaflets folding, multiple artificial chordae implantation and ring annuloplasty. The safety and feasibility of this technique was evaluated by its mid-term clinical outcomes. RESULTS: There was no operative death or complications. The mean cardiopulmonary bypass (CPB) time was 190 ± 41 (128-267) min, and the aortic cross-clamp time was 145 ± 32 (66-200) min. The average number of artificial chordae implantation was 2.9 ± 0.7 (1-4) pairs. The mean MV coaptation length was 1.4 ± 0.3 (0.8-1.8) cm, and the median transvalvular gradient was 1 [interquartile range (IQR), 1-2] mmHg. During a median follow-up time of 24 (IQR, 10-38) months, all patients showed persistent effective valve function with no significant MR or systolic anterior motion. CONCLUSIONS: Totally endoscopic repair was a safe, effective, and reproducible procedure with satisfied mid-term clinical outcomes for MR in Barlow's disease. However, further randomized and long-term follow-up studies were warranted to determine its clinical effects.

The beneficial effect of α-lipoic acid on spinal cord injury repair in rats is mediated through inhibition of oxidative stress: A transcriptomic analysis.

BACKGROUND: Oxidative stress is a crucial factor contributing to the occurrence and development of secondary damage in spinal cord injuries (SCI), ultimately impacting the recovery process. α-lipoic acid (ALA) exhibits potent antioxidant properties, effectively reducing secondary damage and providing neuroprotective benefits. However, the precise mechanism by which ALA plays its antioxidant role remains unknown. METHODS: We established a model of moderate spinal cord contusion in rats. Experimental rats were randomly divided into 3 distinct groups: the sham group, the model control group (SCI_Veh), and the ALA treatment group (SCI_ALA). The sham group rats were exposed only to the SC without contusion injury. Rats belonging to SCI_Veh group were not administered any treatment after SCI. Rats of SCI_ALA group were intraperitoneally injected with the corresponding volume of ALA according to body weight for three consecutive days after the surgery. Subsequently, three days after SCI, spinal cord samples were obtained from three groups of rats: the sham group, model control group, and administration group. Thereafter, total RNA was extracted from the samples and the expression of three sets of differential genes was analyzed by transcriptome sequencing technology. Real-time PCR was used to verify the sequencing results. The impact of ALA on oxidative stress in rats following SCI was assessed by measuring their total antioxidant capacity and hydrogen peroxide (H2O2) content. The effects of ALA on rat recovery following SCI was investigated through Beattie and Bresnahan (BBB) score and footprint analysis. RESULTS: The findings from the transcriptome sequencing analysis revealed that the model control group had 2975 genes with altered expression levels when compared to the ALA treatment group. Among these genes, 1583 were found to be upregulated while 1392 were down-regulated. Gene ontology (GO) displayed significant enrichment in terms of functionality, specifically in oxidative phosphorylation, oxidoreductase activity, and signaling receptor activity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway was enriched in oxidative phosphorylation, glutathione metabolism and cell cycle. ALA was found to have multiple benefits for rats after SCI, including increasing their antioxidant capacity and reducing H2O2 levels. Additionally, it was effective in improving motor function (such as 7 days after SCI, the BBB score for SCI_ALA was 8.400 ± 0.937 compared to 7.050 ± 1.141 for SCI_Veh) and promoting histological recovery after SCI (The results of HE demonstrated that the percentage of damage area in was 44.002 ± 6.680 in the SCI_ALA and 57.215 ± 3.964 in the SCI_Veh at the center of injury.). The sequence data from this study has been deposited into Sequence Read Archive (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242507). CONCLUSION: Overall, the findings of this study confirmed the beneficial effects of ALA on recovery in SCI rats through transcriptome sequencing, behavioral, as well histology analyses.

DBDNMF: A Dual Branch Deep Neural Matrix Factorization method for drug response prediction.

Anti-cancer response of cell lines to drugs is in urgent need for individualized precision medical decision-making in the era of precision medicine. Measurements with wet-experiments is time-consuming and expensive and it is almost impossible for wide ranges of application. The design of computational models that can precisely predict the responses between drugs and cell lines could provide a credible reference for further research. Existing methods of response prediction based on matrix factorization or neural networks have revealed that both linear or nonlinear latent characteristics are applicable and effective for the precise prediction of drug responses. However, the majority of them consider only linear or nonlinear relationships for drug response prediction. Herein, we propose a Dual Branch Deep Neural Matrix Factorization (DBDNMF) method to address the above-mentioned issues. DBDNMF learns the latent representation of drugs and cell lines through flexible inputs and reconstructs the partially observed matrix through a series of hidden neural network layers. Experimental results on the datasets of Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) show that the accuracy of drug prediction exceeds state-of-the-art drug response prediction algorithms, demonstrating its reliability and stability. The hierarchical clustering results show that drugs with similar response levels tend to target similar signaling pathway, and cell lines coming from the same tissue subtype tend to share the same pattern of response, which are consistent with previously published studies.

Correlation between anti-müllerian hormone in polycystic ovarian syndrome with metformin: a systematic review and meta-analysis.

OBJECTIVE: This study aims to examine the short-term effects of oral metformin (MET) on serum anti-müllerian hormone (AMH) levels and to verify its impact on AMH concentrations in women with polycystic ovary syndrome (PCOS). METHODS: The literature search, extending from January 2000 to April 2023, was conducted using databases such as PubMed, Embase, and the Cochrane Central, resulting in the inclusion of 20 studies. These selected studies, evaluated for quality using the Newcastle-Ottawa Scale, investigated changes in AMH levels before and after treatment, with durations ranging from less than three months to over six months. The reported outcomes were quantified as standardized mean differences (SMD) with 95% confidence intervals (CI). This comprehensive systematic review and meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42023420705. The statistical analyses were performed using Review Manager 5.4.1. RESULTS: ① The study incorporated 20 articles, consisting of 12 prospective studies, 7 randomized controlled trials (RCT), and 1 cross-sectional study. ② Serum AMH levels in patients with PCOS diminish subsequent to the oral administration of MET. ③ Across the spectrum of studies analyzed, a pronounced degree of heterogeneity is evident, potentially ascribed to differential parameters including body mass index (BMI), daily pharmacological dosages, the temporal extent of treatment regimens, criteria of PCOS, and detection Methods. ④ The impact of MET on AMH levels exhibits a dose-responsive trend, with escalating doses of MET being associated with progressively greater declines in AMH concentrations in the patient population. ⑤ For women with PCOS receiving MET therapy, a minimum treatment duration of three months may be necessary to observe a reduction in serum AMH levels. CONCLUSIONS: The results of this meta-analysis indicate that MET treatment exerts a suppressive effect on serum AMH levels in women with PCOS. It appears that a treatment duration of at least three months is required to achieve a significant decrease in AMH concentrations. Furthermore, the influence of MET on AMH is dose-dependent, with higher doses correlating with more pronounced reductions in AMH levels among the patients studied.

Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor, and the role of carbohydrate sulfotransferase 11 (CHST11) in this cancer remains unclear. Here, by using bioinformatics methods, we comprehensively analyzed the relationship between CHST11 and clinical significance, immune infiltration, functional enrichment, m6A methylation, and protein-protein interaction networks. We found that CHST11 expression was significantly higher in ccRCC samples than in normal tissues. Additionally, CHST11 levels correlated with the clinicopathological features of ccRCC patients and functioned as a prognostic factor for patient survival. Functional analysis revealed the involvement of CHST11 in metabolic pathways. Immune infiltration and m6A methylation analysis suggested the association of CHST11 with immune cell abundance in the tumor microenvironment and specific methylation patterns in ccRCC. The in vitro analysis of the clinical samples and ccRCC cell lines demonstrated that the overexpression of CHST11 promotes ccRCC cell proliferation, migration, and invasion, while its suppression has the opposite effect. Thus, CHST11 may play a remarkable role in the occurrence and progression of ccRCC. Functionally, CHST11 promotes the aggressiveness of ccRCC cells. These findings provide insights into the role of CHST11 in ccRCC progression.Registry and the Registration No. of the study/trial: No. 2021K034.

Efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients with KRAS mutations: A network meta-analysis.

OBJECTIVE: Previous studies have shown that immune checkpoint inhibitors can improve the survival of patients with advanced non-small cell lung cancer with KRAS mutations; however, there is a lack of comparisons between treatment regimens associated with immune checkpoint inhibitors, and our study aims to compare several treatment parties to find a more effective treatment regimen. METHOD: A comprehensive literature search was conducted across multiple databases, namely PubMed, Web of Science, Embase, and Cochrane Library, to identify relevant studies. The screened studies were thoroughly examined, and data were collected to establish a Bayesian framework. The study focused on two primary endpoints: overall survival (OS) and progression-free survival (PFS). Data analysis and graphical plotting using R software and Revman (version 5.3). It is worth mentioning that the study protocol was registered with the International Prospective Registry for Systematic Reviews, ensuring transparency and adherence to predetermined protocols (CRD42022379595). RESULT: In total, our analysis included six RCTs involving 469 patients with KRAS mutations. Among these patients, 224 received chemotherapy, while 245 were treated with immune checkpoint inhibitors. Meta-analysis results showed that the addition of ICIs could significantly improve OS and PFS (0.69, 95% CI 0.55, 0.86; 0.57, 95% CI 0.42, 0.77). The results of the network meta-analysis showed that Pembrolizumab could improve OS (HR 0.42, 95% CI 0.22-0.80) and Pembrolizumab emerged as the most effective treatment option for enhancing OS in patients (SUCRA 65.03%). Additionally, pembrolizumab in combination with chemotherapy showed improvement in PFS (HR 0.47, 95% CI 0.29-0.76). CONCLUSION: Our analysis found that among advanced NSCLC patients with KRAS gene mutations, first-line treatment with pembrolizumab alone demonstrated greater efficacy. Similarly, second-line treatment with nivolumab alone was found to be more effective in this patient population. However, the sample size of this study was limited, Therefore, additional clinical data is necessary to validate this finding in subsequent research.

Sterigmatocystin induces autophagic and apoptotic cell death of liver cancer cells via downregulation of XIAP.

XIAP, or the X-linked Inhibitor of Apoptosis Protein, is the most extensively studied member within the IAP gene family. It possesses the capability to impede apoptosis through direct inhibition of caspase activity. Various kinds of cancers overexpress XIAP to enable cancer cells to avoid apoptosis. Consequently, the inhibition of XIAP holds significant clinical implications for the development of anti-tumor medications and the treatment of cancer. In this study, sterigmatocystin, a natural compound obtained from the genus asperigillus, was demonstrated to be able to induce apoptotic and autophagic cell death in liver cancer cells. Mechanistically, sterigmatocystin induces apoptosis by downregulation of XIAP expression. Additionally, sterigmatocystin treatment induces cell cycle arrest, blocks cell proliferation, and slows down colony formation in liver cancer cells. Importantly, sterigmatocystin exhibits a remarkable therapeutic effect in a nude mice model. Our findings revealed a novel mechanism through which sterigmatocystin induces apoptotic and autophagic cell death of liver cancer cells by suppressing XIAP expression, this offers a promising therapeutic approach for treating liver cancer patients.

Inhibition of Verticillium Wilt in Cotton through the Application of Pseudomonas aeruginosa ZL6 Derived from Fermentation Residue of Kitchen Waste.

To isolate and analyze bacteria with Verticillium wilt-resistant properties from the fermentation residue of kitchen wastes, as well as explore their potential for new applications of the residue. A total of six bacterial strains exhibiting Verticillium wilt-resistant capabilities were isolated from the biogas residue of kitchen waste fermentation. Using a polyphasic approach, strain ZL6, which displayed the highest antagonistic activity against cotton Verticillium wilt, was identified as belonging to the Pseudomonas aeruginosa. Bioassay results demonstrated that this strain possessed robust antagonistic abilities, effectively inhibiting V. dahliae spore germination and mycelial growth. Furthermore, P. aeruginosa ZL6 exhibited high temperature resistance (42o C), nitrogen fixation, and phosphorus removal activities. Pot experiments revealed that P. aeruginosa ZL6 fermentation broth treatment achieved a 47.72% biological control effect compared to the control group. Through activity tracking and protein mass spectrometry identification, a neutral metalloproteinase (Nml) was hypothesized as the main virulence factor. The mutant strain ZL6ΔNml exhibited a significant reduction in its ability to inhibit cotton Verticillium wilt compared to the strain P. aeruginosa ZL6. While the inhibitory activities could be partially restored by a complementation of nml gene in the mutant strain ZL6CMΔNml. This research provides a theoretical foundation for the future development and application of biogas residue as biocontrol agents against Verticillium wilt and as biological preservatives for agricultural products. Additionally, this study presents a novel approach for mitigating the substantial amount of biogas residue generated from kitchen waste fermentation.

Spatio-temporal distribution of cadmium levels in Chinese population and its potential risk factors.

Cadmium (Cd), a ubiquitous heavy metal, exists in numerous environmental matrices and has severe adverse effects on various human organs and tissues. This research evaluates blood and urine Cd levels in the Chinese population through data mining using Monte Carlo simulation (MCS). A total of 168 scientific studies (120 on urine and 48 on blood) published between January 1980 and December 2020, reflecting a population of 109,743 individuals in China, were included in the study. The results indicate that the blood and urine Cd levels in the Chinese population exhibited a peak from 1990 to 1995 and remained stable after 1995, averaging 1.21 µg/L of blood Cd (BCd) and 0.61 µg/L of urine Cd (UCd). The spatial trend of Cd levels varied significantly. Shandong, Zhejiang, Heilongjiang, and Guangdong provinces were identified as the top provinces with high Cd levels, which were related to factors such as tobacco sales, E-waste amounts, and contaminated rice. Additionally, the study highlights that BCd concentrations are highest among preschool-aged individuals, whereas school-age and adolescent groups exhibit the lowest levels. However, no significant difference existed among the different age groups. Males showed significantly higher Cd levels than females in the general population. Moreover, exposure to smoking, drinking, and staple food preferences had an impact on Cd levels. Furthermore, this comprehensive study, using biological monitoring and data mining, provides valuable information on Cd pollution levels in the Chinese population. It presents a statistical analysis that can aid decision-makers in implementing effective measures to control potential Cd pollution and improve the health of vulnerable populations.