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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, which invades a cell through binding to the ACE2 receptor and TMPRSS2 priming. Patients with severe disease predominantly present with pneumonia-related symptoms. However, evidence suggests that COVID-19 infection also has implications for the urogenital tract. Thus, urogenital organs should be considered when treating COVID-19.

Prostate cancer is the second most common cancer in men worldwide 1 . Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients 2 , 3 . However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1 . Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease. Genomic, transcriptomic and DNA methylation data from tissue samples from 208 Chinese patients with prostate cancer define the landscape of alterations in this population, and comparison with data from Western cohorts suggests that the disease may stratify into different molecular subtypes.

Atrazine (ATZ), as a widely used triazine herbicide, is an environmental endocrine disruptor (EDC) that can cause many health problems. Therefore, we conducted this study based on the evidence of rats and mice to figure out the characteristics of ATZ damage to the reproductive system and further evaluate its health effects on the human. PRISMA’s guidelines were followed according to the principles recommended by the Cochrane Handbook for Systematic Review. Health assessment was performed using the OHAT approach. Our new data were obtained from randomized controlled trials in rats designed in accordance with toxicological guidelines. Exposure to ATZ was significantly associated with decreased testosterone production (SMD = − 0.90, 95% CI − 1.27 to − 0.53), and reduced absolute weights of testis (SMD = − 0.41, 95% CI − 0.61 to − 0.22) and other reproductive organs. The damaging effect of sperm quality was also observed clearly, which included reduction of sperm count both in epididymis (SMD = − 2.32, 95% CI − 2.83 to − 1.81) and testis (SMD = − 1.01, 95% CI − 1.37 to − 0.64), decrease in sperm motility (SMD = − 8.86, 95% CI − 10.88 to − 6.83), and increase in sperm abnormality. Subgroup analysis revealed consistency across different species, life stage, and dosage. In addition, we found that ATZ exposure at a daily dose of 120 mg/kg during adolescence could cause decrease in weight gain and histological damage to the testis. The gene expression levels of Nrf2/HO-1 and Bcl-2/caspase signaling pathways in testis tissues were changed significantly. The results of this SR indicated that exposure to ATZ was associated with impairment of male reproductive system in rodents regardless of species, exposure life stage, and dosage. It is believed that ATZ exposure may have similar effects on male reproductive system of human beings. Pathways related to oxidative stress and apoptosis may be the mechanism leading to testicular damage in rats treated with ATZ.

The prediction of harmful effects can guide research on the health hazards of environmental pollutants. The development of a computer-aided drug design in pharmacological technology and omics database remarkably facilitates the prediction of the possible harmful effects of hazardous substances. In this study, the pharmacophore target database based on molecular structure served as a bridge between pollutants and genes and combined with the omics database and molecular pathway enrichment technology to predict the potential prostatic cancer-promoting effect of dibutyl phthalate. Cell experiments and gene expression were carried out to verify the previous prediction, and the characteristics of harmful effects were further explored. Low concentrations of dibutyl phthalate may have androgen-independent prostate cancer-promoting effects, which may put patients receiving androgen deprivation therapy in danger. This study suggests the potential negative effects of phthalates on prostate cancer and a method for predicting harmful effects on the basis of pharmacology technology. Graphical abstract

Background Sunitinib resistance is one of the main reasons for the poor prognosis of clear renal cell carcinoma (ccRCC). Moreover, Stress granules (SGs) was found to enhance the stress adaptation capability of tumor cells, becoming an important mechanism for drug resistance in various cancers. Methods We developed sunitinib-resistant patient-derived xenograft (PDX) and organoid (PDO) models to investigate sunitinib resistance in ccRCC. Proteomic analysis identified UBAP2L as a key mediator of this resistance. To explore its role in stress granule formation and sunitinib resistance, we conducted both in vitro and in vivo studies. We further elucidated the regulatory mechanisms of UBAP2L O-GlcNAcylation using immunoprecipitation, mass spectrometry, modification-based proteomics, RNA sequencing (RNA-seq), and RNA immunoprecipitation sequencing (RIP-seq). Results In this study, enrichment of UBAP2L was elucidated to be significantly associated with sunitinib-resistant ccRCC patient-derived xenograft (PDX) model. Functional experiments showed that UBAP2L protected ccRCC from apoptosis and promoted ccRCC prolifecation and angiogenesis upon sunitinib treatment, thus enhancing drug resistance of ccRCC cells. Furthermore, mechanistic investigation demonstrated that O-GlcNAcylation of UBAP2L promoted its protein stability via inhibiting TRIM37-mediated ubiquitination and it regulated stress granule formation, thereby enhancing the mRNA stability of Melk and activating the PI3K signaling pathways. Conclusions These results validated the significant roles of O-GlcNAcylation of UBAP2L in ccRCC sunitinib resistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of ccRCC. Graphical abstract

Backgrounds This article aimed to explore the prognostic and immunological roles of AXL gene in clear cell renal cell carcinoma (ccRCC) for overall survival (OS) and to identify the LncRNA/RBP/AXL mRNA networks. Methods AXL-related gene expression matrix and clinical data were obtained from The Cancer Genome Atlas (TCGA) dataset and AXL-related pathways were identified by gene set enrichment analysis (GSEA). We performed univariate/multivariate Cox regression analysis to evaluate independent prognostic factors and the relationships between AXL and immunity were also investigated. Results The outcomes of us indicated that the AXL mRNA expression was up-regulated in ccRCC samples and high expression of AXL was associated with worse OS in TCGA dataset (P < 0.01). Further external verification results from HPA, UALCAN, ICGC dataset, GSE6344, GSE14994, and qRT-PCR remained consistent (all P < 0.05). AXL was also identified as an independent prognostic factor for ccRCC by univariate/multivariate Cox regression analysis (both P < 0.05). A nomogram including AXL expression and clinicopathological factors was established by us and GSEA results found that elevated AXL expression was associated with the JAK-STAT, P53, WNT, VEGF and MAPK signaling pathways. In terms of immunity, AXL was dramatically linked to tumor microenvironment, immune cells, immune infiltration, immune checkpoint molecules and tumor mutational burden (TMB). As for its potential mechanisms, we also identified several LncRNA/RBP/AXL mRNA axes. Conclusions AXL was revealed to play prognostic and immunological roles in ccRCC and LncRNA/RBP/AXL mRNA axes were also identified by us for its potential mechanisms.

Background/Aims: Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. Methods: Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors. Cell apoptosis was detected by flow cytometry and western blot. Radiation-induced DNA double strand break was measured by the staining of γ-H2AX. In addition, autophagy was detected by western blot, immunofluorescence staining, and electron microscopy. Results: The treatment with chloroquine alone inhibited the proliferation of bladder cancer cells in a dose-dependent manner. Low cytotoxic concentrations of chloroquine enhanced the radiation sensitivity of bladder cancer cells with a sensitization enhancement ratio of 1.53 and 1.40. Chloroquine also obviously weakened the repair of radiation-induced DNA damage. A combination of radiation and chloroquine enhanced the apoptosis rate of EJ and T24 cells and down-regulated the expression of Bcl-2 while up-regulating the expression of caspase-3. Additionally, the relevant markers of autophagy were obviously increased in the combined group, meaning that chloroquine inhibited autophagy induced by irradiation. Furthermore, subcutaneous xenograft tumors displayed that the combination of radiation and chloroquine could impede tumorigenesis in vivo. Conclusion: In summary, these results provided support that by inhibiting autophagy and activating apoptosis, chloroquine might be a potentially promising radiosensitizer in the radiation therapy of bladder cancer.

The Hippo pathway participates in development of numerous tumors through regulating tissue growth and cell fate. This study aimed to detect the association between the genetic variants in Hippo pathway genes and bladder cancer risk in a Chinese population. A case–control study of 580 cases and 1101 controls was performed to evaluate the association of single nucleotide polymorphisms (SNPs) in 39 candidate genes involved in the Hippo pathway with bladder cancer risk. A logistic regression model was used to assess the effects of SNPs on bladder cancer susceptibility. Candidate gene expression in human bladder cancer samples was detected using The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) datasets. We found that SNP rs755813 in WWC1 was significantly associated with a decreased risk of bladder cancer [odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.66–0.88, P = 3.63 × 10–4], which was more common in patients with low grade and non-muscle invasive tumors. Younger subjects (age ≤ 65) (OR = 0.70, 95% CI = 0.56–0.86), females (0.35, 0.23–0.52) and non-smokers (0.72, 0.58–0.88) showed a pronounced association between the rs755813 C allele and risk of bladder cancer by stratified analysis. The WWC1 was upregulated in bladder cancer tissues according to TCGA and GEO datasets. These findings indicated that genetic variant of WWC1 gene in Hippo signaling pathway contributes to the decreased risk of bladder cancer in the Chinese population and may have the protective effect against the development of bladder cancer.

Background Renal clear cell carcinoma (ccRCC) is the most prevalent tumors worldwide. Discovering effective biomarkers is essential to monitor the prognosis and provide alternative clinical options. SPTBN1 is implicated in various cancerous processes. However, its role in ccRCC remains unelucidated. This study intends to explore the biological function and mechanism of SPTBN1 in ccRCC. Methods Single-cell and bulk RNA-seq, tissue microarray, real-time quantitative PCR, and western blotting were applied to verify the expression and predictive value of SPTBN1 in ccRCC. Gain or loss of functional ccRCC cell line models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Actinomycin D experiment, RNA immunoprecipitation (RIP), specific inhibitors, and rescue experiments were carried out to define the molecular mechanisms. Results SPTBN1 was down-regulated in ccRCC and knockdown of SPTBN1 displayed a remarkably oncogenic role both in vitro and in vivo; while overexpressing SPTBN1 reversed this effect. SPTBN1 mediated ccRCC progression via the pathway of glutamate pyruvate transaminase 2 (GPT2)-dependent glycolysis. The expression of GPT2 was significantly negatively correlated with that of SPTBN1. As an RNA binding protein SPTBN1, regulated the mRNA stability of GPT2. Conclusion Our research demonstrated that SPTBN1 is significantly down-regulated in ccRCC. SPTBN1 knockdown promotes ccRCC progression via activating GPT2-dependent glycolysis. SPTBN1 may serve as a therapeutic target for the treatment of ccRCC.

Background Cell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive roles of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasize its associations with immunity. Methods The RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was adopted to explore CDCA7 associated signaling pathways. Univariate and multivariate Cox regression analyses were carried out to assess independent prognostic factors. Furthermore, roles of CDCA7 in human immunity were also investigated. Results Our results suggested that CDCA7 was overexpressed in ccRCC and its elevated expression was related to shorter OS (P < 0.01). Univariate and multivariate Cox regression analyses identified CDCA7 as an independent prognostic factor (both P < 0.05). The prognostic nomogram integrating CDCA7 expression level and clinicopathologic variables was constructed to predict 1-, 3- and 5-year OS. GSEA indicated that high CDCA7 expression was related to the apoptosis pathway, cell cycle pathway, JAK-STAT pathway, NOD like receptor pathway, P53 pathway, T cell receptor pathway and toll like receptor pathway, etc. Moreover, CDCA7 was significantly related to microsatellite instability (MSI, P < 0.001) and tumor mutational burden (TMB, P < 0.001). As for immunity, CDCA7 was remarkably associated with immune infiltration, tumor microenvironment, immune checkpoint molecules and immune pathways. Conclusions CDCA7 could serve as an independent prognostic factor for ccRCC and it was closely related to MSI, TMB, and immunity.