Glycosylation Targeting: A Paradigm Shift in Cancer Immunotherapy.

Immunotherapy has shown great potential in cancer treatment. However, even with the intervention of techniques such as immune checkpoint inhibitor therapy, tumors can still achieve immune escape, leading to a low response rate. Abnormal glycosylation is a widely recognized hallmark of cancer. The development of a complex "glyco-code" on the surface of tumor cells can potentially influence the immune system's ability to monitor tumors and can impact the anti-tumor immune response. Therefore, abnormal glycosylation has emerged as a promising target for immunotherapy. Many recent studies have shown that targeted glycosylation can reshape the tumor microenvironment (TME) and promote the immune response, thereby improving the response to immunotherapy. This review summarizes how glycosylation affects anti-tumor immune function in the TME and synthesizes the latest research progress on targeted glycosylation in immunotherapy. It is hoped that by elucidating the basic laws and biological connotations of glycosylation, this review will enable researcher to thoroughly analyze the mechanism of its influence on the immune metabolic regulation network, which will provide a theoretical tool for promoting the clinical application of glycosylation codes.

Is neoadjuvant chemotherapy necessary for T2N0-1M0 hormone receptor-positive/HER2-negative breast cancer patients undergoing breast-conserving surgery?

INTRODUCTION: For HR-positive/HER2-negative patients who can undergo breast-conserving surgery (BCS) but have a tumor size of 2-5 cm or 1-3 lymph node metastases, neoadjuvant chemotherapy (NAC) is still controversial. METHODS: Patients with T2N0-1M0 HR-positive/HER2-negative BC who underwent BCS between 2010 and 2017 were selected from the SEER database. Propensity score matching (PSM) was used to minimize the influence of confounding factors. The overall survival (OS) and breast cancer-specific survival (BCSS) of patients were estimated by Kaplan‒Meier curves and Cox proportional hazard models. Independent prognostic factors were included to construct a nomogram prediction model. RESULTS: A total of 6475 BC patients were enrolled, of whom 553 received NAC and 5922 received adjuvant chemotherapy (AC). In the T2N0-1M0 population and T2N1M0 subgroup, AC patients before PSM had better OS and BCSS than NAC patients. After PSM, there was no significant difference in OS or BCSS between the two groups. However, in the T2N0M0 subgroup, there was no difference in survival between the AC and NAC groups before and after PSM. Stratified analysis revealed that for complete response (CR) patients, survival was roughly equivalent between the NAC and AC groups. However, the survival of no response (NR) and partial response (PR) patients was significantly worse than that of AC patients. Cox analysis revealed that radiotherapy after BCS was an independent protective factor for OS. NAC is an independent risk factor for NR and PR patients. The nomogram has good prediction efficiency. CONCLUSION: NAC before BCS is not necessary for T2N0-1M0 HR-positive/HER2-negative BC patients.

Water Catchers within Sub-Nano Channels Promote Step-by-Step Zinc-Ion Dehydration Enable Highly Efficient Aqueous Zinc-Metal Batteries.

Zinc metal suffers from violent and long-lasting water-induced side reactions and uncontrollable dendritic Zn growth, which seriously reduce the coulombic efficiency (CE) and lifespan of aqueous zinc-metal batteries (AZMBs). To suppress the corresponding harmful effects of the highly active water, a stable zirconium-based metal-organic framework with water catchers decorated inside its sub-nano channels is used to protect Zn-metal. Water catchers within narrow channels can constantly trap water molecules from the solvated Zn-ions and facilitate step-by-step desolvation/dehydration, thereby promoting the formation of an aggregative electrolyte configuration, which consequently eliminates water-induced corrosion and side reactions. More importantly, the functionalized sub-nano channels also act as ion rectifiers and promote fast but even Zn-ions transport, thereby leading to a dendrite-free Zn metal. As a result, the protected Zn metal demonstrates an unprecedented cycling stability of more than 10 000 h and an ultra-high average CE of 99.92% during 4000 cycles. More inspiringly, a practical NH4V4O10//Zn pouch-cell is fabricated and delivers a capacity of 98 mAh (under high cathode mass loading of 25.7 mg cm-2) and preserves 86.2% capacity retention after 150 cycles. This new strategy in promoting highly reversible Zn metal anodes would spur the practical utilization of AZMBs.

Can neoadjuvant systemic therapy provide additional benefits for T1 HER2+ breast cancer patients: a subgroup analysis based on different high-risk signatures.

INTRODUCTION: Neoadjuvant systemic therapy (NAST) is vital in the management of HER2-positive (HER2+) breast cancer. Nevertheless, the indications for NAST in tumors <2 cm remain controversial. METHOD: A total of 7961 patients were screened from the Surveillance, Epidemiology, and End Result database. Independent prognostic factors were identified using multivariate Cox analysis. Subgroup analyses and Kaplan-Meier analyses were used to simulate whether NAST would provide a survival benefit with different high-risk characteristics. Nomograms were constructed, and an internal validation cohort was employed. RESULTS: Of the 7961 included patients, 1137 (14.3%) underwent NAST. In the total population, NAST was associated with poorer overall survival (OS) and breast cancer-specific survival (BCSS) (OS: P = 0.00093; BCSS: P  <  0.0001). Multivariate Cox analysis confirmed that NAST markedly affected the prognosis of enrolled patients. Besides, a direct association between T, N, age, subtype, and prognosis was observed. Subgroup analyses yielded in these three subgroups, T1c, hormone receptor-negative, and 61-69 years of age, NAST and AST had comparable OS, while NAST possessed worse BCSS. Notably, even in the N3, we still did not observe any additional benefit of NAST. The calculated C-index of 0.72 and 0.73 confirmed the predictability of the nomograms. The AUCs exhibit consistency in the training and validation cohorts. CONCLUSION: Our findings suggest that NAST does not provide additional benefit to patients with T1 HER2+ breast cancer, even in the presence of lymph node metastasis, T1c, or hormone receptor negativity. This study facilitates the implementation of individualized management strategies.

PIK3CA mutation-driven immune signature as a prognostic marker for evaluating the tumor immune microenvironment and therapeutic response in breast cancer.

PURPOSE: Gene mutations drive tumor immune microenvironment (TIME) heterogeneity, in turn affecting prognosis and immunotherapy efficacy. PIK3CA is the most frequently mutated gene in breast cancer (BC), yet its relevance to BC prognosis remains controversial. Herein, we sought to determine the impact of PIK3CA mutation-driven immune genes (PDIGs) on BC prognosis in relation to TIME heterogeneity. METHODS: PIK3CA mutation characteristics were compared and verified between the TCGA-BRCA dataset and a patient cohort from our hospital. PIK3CA mutation-driven differentially expressed genes were identified for consensus clustering and weighted gene co-expression network analysis to select the modules most relevant to the immune subtype. Thereafter, the two were intersected to obtain PDIGs. Univariate Cox, LASSO, and multivariate Cox regression analyses were sequentially performed on PDIGs to obtain a PIK3CA mutation-driven immune signature (PDIS), which was then validated using the Gene Expression Omnibus (GEO) database. Differences in functional enrichment, mutation landscape, immune infiltration, checkpoint gene expression, and drug response were compared between different risk groups. RESULTS: PIK3CA mutation frequencies in the TCGA and validation cohorts were 34.49% and 40.83%, respectively. PIK3CA mutants were significantly associated with ER, PR, and molecular BC subtypes in our hospital cohort. The PDIS allowed for effective risk stratification and exhibited prognostic power in TCGA and GEO sets. The low-risk patients exhibited greater immune infiltration, higher expression of common immune checkpoint factors, and lower scores for tumor immune dysfunction and exclusion. CONCLUSION: The PDIS can be used as an effective prognostic model for predicting immunotherapy response to guide clinical decision-making.

Construction and Validation of a Nomogram Predicting the Overall Survival Benefit of Unilateral Breast Cancer Patients Undergoing Contralateral Prophylactic Mastectomy.

BACKGROUND: Currently, research on the prognostic factors of unilateral breast cancer (UBC) patients receiving contralateral prophylactic mastectomy (CPM) is limited. This study aimed to construct a new nomogram to predict these patients' overall survival (OS). METHODS: In this retrospective study, 88,477 patients who underwent CPM or unilateral mastectomy (UM) were selected from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier curves and Cox regression analyses were used to determine the difference in the impact of the 2 surgical methods on the prognosis. Multivariate Cox analysis was used to determine the best prognostic variable and construct a nomogram. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the discrimination capability and clinical effectiveness of the nomogram. RESULTS: The prognosis of patients receiving CPM and UM was significantly different. The DCA curves indicated that the nomogram could provide more excellent clinical net benefits for these patients. The NRI and IDI of the nomogram demonstrated that its performance was better than that of the classical tumor-node-metastasis (TNM) staging system. CONCLUSION: This study developed and validated a practical nomogram to predict the OS of UBC patients undergoing CPM, which provided a beneficial tool for clinical decision-making management.

Chelating Additive Regulating Zn-Ion Solvation Chemistry for Highly Efficient Aqueous Zinc-Metal Battery.

Aqueous zinc-metal batteries (AZMBs) usually suffered from poor reversibility and limited lifespan because of serious water induced side-reactions, hydrogen evolution reactions (HER) and rampant zinc (Zn) dendrite growth. Reducing the content of water molecules within Zn-ion solvation sheaths can effectively suppress those inherent defects of AZMBs. In this work, we originally discovered that the two carbonyl groups of N-Acetyl-ϵ-caprolactam (N-ac) chelating ligand can serve as dual solvation sites to coordinate with Zn2+, thereby minimizing water molecules within Zn-ion solvation sheaths, and greatly inhibit water-induced side-reactions and HER. Moreover, the N-ac chelating additive can form a unique physical barrier interface on Zn surface, preventing the harmful contacting with water. In addition, the preferential adsorption of N-ac on Zn (002) facets can promote highly reversible and dendrite-free Zn2+ deposition. As a result, Zn//Cu half-cell within N-ac added electrolyte delivered ultra-high 99.89 % Coulombic efficiency during 8000 cycles. Zn//Zn symmetric cells also demonstrated unprecedented long life of more than 9800 hours (over one year). Aqueous Zn//ZnV6O16 ⋅ 8H2O (Zn//ZVO) full-cell preserved 78 % capacity even after ultra-long 2000 cycles. A more practical pouch-cell was also obtained (90.2 % capacity after 100 cycles). This method offers a promising strategy for accelerating the development of highly efficient AZMBs.

Prognostic value and mode selection of locoregional treatment in Stage-IV breast cancer patients.

PURPOSE: This study aimed to assess the actual prognostic significance of different locoregional treatment (LRT) (surgery and radiotherapy) modalities for stage-IV  breast cancer (BC) patients and construct a competing risk nomogram to make precise predictions of the breast cancer-specific death (BCSD) risk among LRT recipients. METHODS: A total of 9279 eligible stage-IV BC patients from the Surveillance Epidemiology and End Results (SEER) database were included in this study. Initially, we evaluated the impact of LRT on survival both before and after the propensity score matching (PSM). Then, we used the Cox hazard proportional model and competing risk model to identify the independent prognostic factors for LRT recipients. Based on the screened variables, a comprehensive nomogram was established. RESULTS: Kaplan-Meier curves demonstrated that LRT significantly prolonged overall survival (OS) and breast cancer-specific survival (BCSS) (P < 0.001). In addition, patients treated with surgery combined with postoperative radiotherapy (PORT) possessed the optimal survival (P < 0.001). Regardless of the surgical modalities, primary tumor resection combined with radiotherapy could ameliorate the prognosis (P < 0.05). Subgroup analysis showed that in patients with T2-T4 stage, PORT had a survival benefit compared with those undergoing surgery combined with preoperative radiotherapy (PRRT) and surgery only. Based on the screened independent prognostic factors, we established a comprehensive nomogram to forecast BCSD in 1 year, 2 years and 3 years, which showed robust predictive ability. CONCLUSION: PORT was associated with a lower BCSD in stage-IV BC patients. The practical nomogram could provide a precise prediction of BCSD for LRT recipients, which was meaningful for patients' individualized management.

Highly Stable Aqueous Zinc Metal Batteries Enabled by an Ultrathin Crack-Free Hydrophobic Layer with Rigid Sub-Nanochannels.

Aqueous zinc-metal batteries (AZMBs) have received tremendous attentions due to their high safety, low cost, environmental friendliness, and simple process. However, zinc-metal still suffer from uncontrollable dendrite growth and surface parasitic reactions that reduce the Coulombic efficiency (CE) and lifetime of AZMBs. These problems which are closely related to the active water are not well-solved. Here, an ultrathin crack-free metal-organic framework (ZIF-7x -8) with rigid sub-nanopore (0.3 nm) is constructed on Zn-metal to promote the de-solvation of zinc-ions before approaching Zn-metal surface, reduce the contacting opportunity between water and Zn, and consequently eliminate water-induced corrosion and side-reactions. Due to the presence of rigid and ordered sub-nanochannels, Zn-ions deposits on Zn-metal follow a highly ordered manner, resulting in a dendrite-free Zn-metal with negligible by-products, which significantly improve the reversibility and lifespan of Zn-metals. As a result, Zn-metal protected by ultrathin crack-free ZIF-7x -8 layer exhibits excellent cycling stability (over 2200 h) and extremely-high 99.96% CE during 6000 cycles. The aqueous PANI-V2 O5 //ZIF-7x -8@Zn full-cell preserves 86% high-capacity retention even after ultra-long 2000 cycles. The practical pouch-cell can also be cycled for more than 120 cycles. It is believed that the simple strategy demonstrated in this work can accelerate the practical utilizations of AZMBs.

Weakly supervised label propagation algorithm classifies lung cancer imaging subtypes.

Aiming at the problems of long time, high cost, invasive sampling damage, and easy emergence of drug resistance in lung cancer gene detection, a reliable and non-invasive prognostic method is proposed. Under the guidance of weakly supervised learning, deep metric learning and graph clustering methods are used to learn higher-level abstract features in CT imaging features. The unlabeled data is dynamically updated through the k-nearest label update strategy, and the unlabeled data is transformed into weak label data and continue to update the process of strong label data to optimize the clustering results and establish a classification model for predicting new subtypes of lung cancer imaging. Five imaging subtypes are confirmed on the lung cancer dataset containing CT, clinical and genetic information downloaded from the TCIA lung cancer database. The successful establishment of the new model has a significant accuracy rate for subtype classification (ACC = 0.9793), and the use of CT sequence images, gene expression, DNA methylation and gene mutation data from the cooperative hospital in Shanxi Province proves the biomedical value of this method. The proposed method also can comprehensively evaluate intratumoral heterogeneity based on the correlation between the final lung CT imaging features and specific molecular subtypes.

Comprehensive analysis of nicotinamide metabolism-related signature for predicting prognosis and immunotherapy response in breast cancer.

Background: Breast cancer (BC) is the most common malignancy among women. Nicotinamide (NAM) metabolism regulates the development of multiple tumors. Herein, we sought to develop a NAM metabolism-related signature (NMRS) to make predictions of survival, tumor microenvironment (TME) and treatment efficacy in BC patients. Methods: Transcriptional profiles and clinical data from The Cancer Genome Atlas (TCGA) were analyzed. NAM metabolism-related genes (NMRGs) were retrieved from the Molecular Signatures Database. Consensus clustering was performed on the NMRGs and the differentially expressed genes between different clusters were identified. Univariate Cox, Lasso, and multivariate Cox regression analyses were sequentially conducted to develop the NAM metabolism-related signature (NMRS), which was then validated in the International Cancer Genome Consortium (ICGC) database and Gene Expression Omnibus (GEO) single-cell RNA-seq data. Further studies, such as gene set enrichment analysis (GSEA), ESTIMATE, CIBERSORT, SubMap, and Immunophenoscore (IPS) algorithm, cancer-immunity cycle (CIC), tumor mutation burden (TMB), and drug sensitivity were performed to assess the TME and treatment response. Results: We identified a 6-gene NMRS that was significantly associated with BC prognosis as an independent indicator. We performed risk stratification according to the NMRS and the low-risk group showed preferable clinical outcomes (P < 0.001). A comprehensive nomogram was developed and showed excellent predictive value for prognosis. GSEA demonstrated that the low-risk group was predominantly enriched in immune-associated pathways, whereas the high-risk group was enriched in cancer-related pathways. The ESTIMATE and CIBERSORT algorithms revealed that the low-risk group had a higher abundance of anti-tumor immunocyte infiltration (P < 0.05). Results of Submap, IPS, CIC, TMB, and external immunotherapy cohort (iMvigor210) analyses showed that the low-risk group were indicative of better immunotherapy response (P < 0.05). Conclusions: The novel signature offers a promising way to evaluate the prognosis and treatment efficacy in BC patients, which may facilitate clinical practice and management.

BMPR1B Polymorphisms (rs1434536 and rs1970801) are Associated With Breast Cancer Susceptibility in Northwest Chinese Han Females: A Case-Control Study.

BACKGROUND: Bone morphogenetic proteins receptor type 1B (BMPR1B) was a multifunctional signaling molecule and its abnormal expression associated with poorer prognosis. We aimed to explore the relationship between BMPR1B polymorphisms and breast cancer susceptibility among northwest population. METHODS: A total of 450 healthy controls and 434 patients with breast cancers were recruited in this study. Two candidate polymorphisms, rs1434536 and rs1970801 were genotyping using Sequenom MassArray technique. Expression quantitative trait loci analysis in the GTEx portal was adopted to determine the correlation between the rs1434536 and rs1970801 polymorphism and level of BMPR1B expression. RESULTS: We found that the T allele of rs1434536 was associated with an increased susceptibility of breast cancer [CT+TT vs. CC: adjusted OR (95% CI) = 1.35(1.02-1.78), Padjusted= 0.034; CT vs. CC adjusted OR (95% CI) = 1.39(1.03-1.87), Padjusted= 0.029]. For rs1970801, carrying minor allele T was significantly associated with an increased risk of breast cancer [GT+TT vs. GG: adjusted OR (95% CI) = 1.52(1.14-2.01), Padjusted= 0.004; GT vs. GG adjusted OR (95% CI) = 1.56(1.15-2.09), Padjusted= 0.004]. Stratified analyses found statistical significance existing in women under 49 years of age, BMI less than 24 kg/m2, and premenopausal women for both rs1434536 and rs1970801. Expression quantitative trait loci analysis in the GTEx portal proved that the minor alleles of rs1434536 T and rs1970801 T was significantly associated with higher expression level of BMPR1B. CONCLUSION: BMPR1B polymorphisms (rs1434536 and rs1970801) may increase susceptibility to breast cancer in Chinese Han women.

An Odorant Receptor from the Proboscis of the Cotton Bollworm Helicoverpa armigera (Lepidoptera: Noctuidae) Narrowly Tuned to Indole.

Helicoverpa armigera is a serious agricultural pest with polyphagous diets, widespread distribution, and causing severe damage. Among sixty-five candidate ORs in H. armigera, the co-receptor HarmOrco and three specific ORs with partial sequences were identified to be expressed in the proboscis by our previous work, whereas their exact function is not known yet. In this study, we first confirmed the expression of these ORs in the proboscis by full-length cloning, which obtained the complete coding region of HarmOrco, OR24, and OR30. We then performed functional identification of HarmOR24 and OR30 by co-expressing them respectively with HarmOrco in Xenopus oocytes eukaryotic expression system combined with two-electrode voltage-clamp physiology. By testing the response of HarmOR24/OR30-expressing oocytes against eighty structural-divergent compounds, respectively, HarmOR30 was characterized to narrowly tune to indole and showed a specific tuning spectrum compared to its ortholog in Spodoptera littoralis. As indole is a distinctive herbivore-induced plant volatile and floral scent component, HarmOR30 might play roles in foraging and mediating the interactions between H. armigera with its surrounding environment.

Identification of a combined apoptosis and hypoxia gene signature for predicting prognosis and immune infiltration in breast cancer.

BACKGROUND: Breast cancer (BC) is the most common malignant tumor worldwide. Apoptosis and hypoxia are involved in the progression of BC, but reliable biomarkers for these have not been developed. We hope to explore a gene signature that combined apoptosis and hypoxia-related genes (AHGs) to predict BC prognosis and immune infiltration. METHODS: We collected the mRNA expression profiles and clinical data information of BC patients from The Cancer Genome Atlas database. The gene signature based on AHGs was constructed using the univariate Cox regression, least absolute shrinkage and selection operator, and multivariate Cox regression analysis. The associations between risk scores, immune infiltration, and immune checkpoint gene expression were studied using single-sample gene set enrichment analysis. Besides, gene signature and independent clinicopathological characteristics were combined to establish a nomogram. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the potential functions of AHGs. RESULTS: We identified a 16-AHG signature (AGPAT1, BTBD6, EIF4EBP1, ERRFI1, FAM114A1, GRIP1, IRF2, JAK1, MAP2K6, MCTS1, NFKBIA, NFKBIZ, NUP43, PGK1, RCL1, and SGCE) that could independently predict BC prognosis. The median score of the risk model divided the patients into two subgroups. By contrast, patients in the high-risk group had poorer prognosis, less abundance of immune cell infiltration, and expression of immune checkpoint genes. The gene signature and nomogram had good predictive effects on the overall survival of BC patients. GO and KEGG analyses revealed that the differential expression of AHGs may be closely related to tumor immunity. CONCLUSION: We established and verified a 16-AHG BC signature which may help predict prognosis, assess potential immunotherapy benefits, and provide inspiration for future research on the functions and mechanisms of AHGs in BC.

A Mutation-Related Long Noncoding RNA Signature of Genome Instability Predicts Immune Infiltration and Hepatocellular Carcinoma Prognosis.

Background: Long noncoding RNAs (lncRNAs) have been discovered to play a regulatory role in genomic instability (GI), which participates in the carcinogenesis of various cancers, including hepatocellular carcinoma (HCC). We endeavored to establish a GI-derived lncRNA signature (GILncSig) as a potential biomarker and explore its impact on immune infiltration and prognostic significance. Methods: Combining expression and somatic mutation profiles from The Cancer Genome Atlas database, we identified GI-related lncRNAs and conducted functional analyses on co-expressed genes. Based on Cox regression analysis, a GILncSig was established in the training cohort (n = 187), and an independent testing patient cohort (n = 183) was used to validate its predictive ability. Kaplan-Meier method and receiver operating characteristic curves were adopted to evaluate the performance. The correlation between GI and immune infiltration status was investigated based on the CIBERSORT algorithm and single sample gene set enrichment analysis. In addition, a comprehensive nomogram integrating the GILncSig and clinicopathological variables was constructed to efficiently assess HCC patient prognosis in clinical applications. Results: A total of 88 GI-related lncRNAs were screened out and the functional analyses indicated diversified effects on HCC progression. The GILncSig was established using four independent lncRNAs (AC116351.1, ZFPM2-AS1, AC145343.1, and MIR210HG) with significant prognostic value (p < 0.05). Following evaluation with the GILncSig, low-risk patients had significantly better clinical outcomes than high-risk patients in the training cohort (p < 0.001), which was subsequently validated in the independent testing cohort. High-risk group exhibited more immunocyte infiltration including B cells memory, macrophages M0 and neutrophils and higher expression of HLA gene set and immune checkpoint genes. Compared to existing HCC signatures, the GILncSig showed better prognosis predictive performance [area under the curve (AUC) = 0.709]. Furthermore, an integrated nomogram was constructed and validated to efficiently and reliably evaluate HCC patient prognosis (3-years survival AUC = 0.710 and 5-years survival AUC = 0.707). Conclusion: The GILncSig measuring GI and impacting immune infiltration serves as a potential biomarker and independent predictor of HCC patient prognosis. Our results highlight further investigation of GI and HCC molecular mechanisms.

Disease Burden and Attributable Risk Factors of Ovarian Cancer From 1990 to 2017: Findings From the Global Burden of Disease Study 2017.

Aim: We aimed to estimate the disease burden and risk factors attributable to ovarian cancer, and epidemiological trends at global, regional, and national levels. Methods: We described ovarian cancer data on incidence, mortality, and disability-adjusted life-years as well as age-standardized rates from 1990 to 2017 from the Global Health Data Exchange database. We also estimated the risk factors attributable to ovarian cancer deaths and disability-adjusted life-years. Measures were stratified by region, country, age, and socio-demographic index. The estimated annual percentage changes and age-standardized rates were calculated to evaluate temporal trends. Results: Globally, ovarian cancer incident, death cases, and disability-adjusted life-years increased by 88.01, 84.20, and 78.00%, respectively. However, all the corresponding age-standardized rates showed downward trends with an estimated annual percentage change of -0.10 (-0.03 to 0.16), -0.33 (-0.38 to -0.27), and -0.38 (-0.32 to 0.25), respectively. South and East Asia and Western Europe carried the heaviest disease burden. The highest incidence, deaths, and disability-adjusted life-years were mainly in people aged 50-69 years from 1990 to 2017. High fasting plasma glucose level was the greatest contributor in age-standardized disability-adjusted life-years rate globally as well as in all socio-demographic index quintiles and most Global Disease Burden regions. Other important factors were high body mass index and occupational exposure to asbestos. Conclusion: Our study provides valuable information on patterns and trends of disease burden and risk factors attributable to ovarian cancer across age, socio-demographic index, region, and country, which may help improve the rational allocation of health resources as well as inform health policies.

Antioxidant Gene Signature Impacts the Immune Infiltration and Predicts the Prognosis of Kidney Renal Clear Cell Carcinoma.

Background: Oxidative stress is related to oncogenic transformation in kidney renal clear cell carcinoma (KIRC). We intended to identify a prognostic antioxidant gene signature and investigate its relationship with immune infiltration in KIRC. Methods: With the support of The Cancer Genome Atlas (TCGA) database, we researched the gene expression and clinical data of KIRC patients. Antioxidant related genes with significant differences in expression between KIRC and normal samples were then identified. Through univariate and multivariate Cox analysis, a prognostic gene model was established and all patients were divided into high- and low-risk subgroups. Single sample gene set enrichment analysis was adopted to analyze the immune infiltration, HLA expression, and immune checkpoint genes in different risk groups. Finally, the prognostic nomogram model was established and evaluated. Results: We identified six antioxidant genes significantly correlated with the outcome of KIRC patients as independent predictors, namely DPEP1 (HR = 0.97, P < 0.05), GSTM3 (HR = 0.97, P < 0.05), IYD (HR = 0.33, P < 0.05), KDM3B (HR = 0.96, P < 0.05), PRDX2 (HR = 0.99, P < 0.05), and PRXL2A (HR = 0.96, P < 0.05). The high- and low-risk subgroups of KIRC patients were grouped according to the six-gene signature. Patients with higher risk scores had poorer prognosis, more advanced grade and stage, and more abundance of M0 macrophages, regulatory T cells, and follicular helper T cells. There were statistically significant differences in HLA and checkpoint gene expression between the two risk subgroups. The performance of the nomogram was favorable (concordance index = 0.766) and reliably predicted the 3-year (AUC = 0.792) and 5-year (AUC = 0.766) survival of patients with KIRC. Conclusion: The novel six antioxidant related gene signature could effectively forecast the prognosis of patients with KIRC, supply insights into the interaction between cellular antioxidant mechanisms and cancer, and is an innovative tool for selecting potential patients and targets for immunotherapy.

Identification of an immune-related RNA-binding protein signature to predict survival and targeted therapy responses in liver cancer.

RNA-binding proteins (RBPs) play crucial roles in multiple cancers. However, very few RBPs and their association with immune genes have been systematically studied in liver cancer (LC). We aimed to identify an immune-related RBP signature to predict the survival of LC patients. Bioinformatics methods were used to identify differentially expressed, immune-related, and prognostic RBPs and to develop an immune-related RBP signature based on data from the Cancer Genome Atlas (TCGA) cohort. We obtained eight differentially expressed, immune-related, and prognostic RBPs to construct a risk signature. The signature could effectively distinguish between high- and low-risk patients, and its predictive capacity was validated in the International Cancer Genomics Consortium (ICGC) cohort. We speculated that the high-risk group was more sensitive to targeted therapy. The immune-related RBP signature is an independent prognostic biomarker for LC patients and can expand the application of targeted therapy through patient stratification.

Association of folate intake and plasma folate level with the risk of breast cancer: a dose-response meta-analysis of observational studies.

Epidemiological studies showing the correlation between folate and the breast cancer risk have revealed inconsistent results. Hence, we conducted a dose-response meta-analysis of observational studies to obtain more reliable conclusions. We searched PubMed and Embase for studies published before April 2019 and identified 39 studies on folate intake and 12 studies on plasma folate level. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were extracted to estimate the breast cancer risk. Folate intake was inversely correlated with the breast cancer risk when the highest and lowest categories (OR = 0.85, 95% CI = 0.79-0.92) were compared, and the dose-response result showed that folate intake had a linear correlation with the breast cancer risk. Moreover, a higher folate intake correlated with a lower breast cancer risk in premenopausal women (OR = 0.80, 95% CI = 0.66-0.97), but not in postmenopausal women (OR = 0.94, 95% CI = 0.83-1.06). However, plasma folate levels were not correlated with the breast cancer risk (OR = 0.98, 95% CI = 0.82-1.17). Folate intake was negatively correlated with the breast cancer risk; however, its practical clinical significance requires further study. Furthermore, additional folate supplements should be considered carefully.

Fluorescence-enhanced p19 proteins-conjugated single quantum dot with multiplex antenna for one-step, specific and sensitive miRNAs detection.

Ideal methods for miRNA detection should be rapid and amplification-free in the mix-and-measure format. Here we report a novel FRET strategy based on fluorescence-enhanced p19 proteins-conjugated single quantum dot (QD) with multiplex antenna for one-step, specific and sensitive miRNAs quantitative analysis. It is simple in design and operation, and possesses high sensitivity and selectivity. In the strategy, RNA-binding viral p19 proteins-conjugated quantum dot (p19-QD) with high fluorescence and multiplex antenna was designed, and exploited for the capture recognition element and the donor. In the presence of target miRNAs, the p19-QD would tightly capture the miRNA-21-antimiRNA-21 duplex (dsRNA) formed in solution by hybridization of the specific antimiRNA-21-Cy3 probe (receptor) to the single-stranded miRNA-21 target. The FRET detection system between QD and Cy3 was constructed, and the signal read-out was measured. Conversely, in the absence of target miRNA-21, the p19-QD refuse to capture the free single-stranded antimiRNA-21-Cy3 probe (receptor), the FRET between quantum dot and Cy3 is deterred, thereby providing a low-background signal to improve sensitivity. Benefiting from the high affinity and specificity of p19 protein for duplex RNA and the fluorescence enhancement of donor p19-QD by the passivation and protection from p19 protein, a detection limit as low as 0.6 fM was achieved without employing any amplification techniques and pre-concentration or purification steps. The performance can be achieved by only one-step incubation without additional reagents and washing steps, thus greatly reducing the operating difficulty and saving time. Moreover, the fluorescence-enhanced p19-QD conjugate-based FRET strategy avoids the specific design in the number of the bases for interval in the DNA-QD conjugate-based FRET system using DNA strands as the FRET linker, and improves the FRET efficiency. Furthermore, it has been successfully applied to analyze the content of miRNA-21 in breast cancer cell. The results indicated that, the strategy will become a sensitive and reliable miRNAs quantification method in biomedical research and early clinical diagnostics.