Anti-inflammatory germacrane-type sesquiterpene lactones from Vernonia sylvatica.

Nine new germacranolides, sylvaticalides A-H (1-9), and three known analogues (10-12) were isolated from the aerial part of Vernonia sylvatica. Their structures were established using comprehensive spectroscopic analysis, including high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. Their absolute configurations were determined by X-ray diffraction experiments. The anti-inflammatory activities of all isolated compounds were assessed by evaluating their inhibitory effects on the nuclear factor kappa B (NF-κB) pathway, which was activated by lipopolysaccharide (LPS)-stimulated human THP1-Dual cells, and the interferon-stimulated gene (ISG) pathway, activated by STING agonist MSA-2 in the same cell model. Compounds 1, 2 and 6 showed inhibitory effects on the NF-κB and ISG signaling pathways, with IC50 values ranging from 4.12 to 10.57 µmol·L-1.

Revealing the mechanism of ethyl acetate extracts of Semen Impatientis against prostate cancer based on network pharmacology and transcriptomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Prostate cancer (PCa) is the most common malignancy of the male genitourinary system and currently lacks effective treatment. Semen Impatientis, the dried ripe seed of Impatiens balsamina L., is described by the Chinese Pharmacopoeia as a traditional Chinese medicine (TCM) and is used in clinical practice to treat tumors, abdominal masses, etc. In our previous study, the ethyl acetate extracts of Semen Impatientis (EAESI) was demonstrated to be the most effective extract against PCa among various extracts. However, the biological effects of EAESI against PCa in vivo and the specific antitumor mechanisms involved remain unknown. AIM OF THE STUDY: In this study, we aimed to investigate the antitumor effect of EAESI on PCa in vitro and in vivo by performing network pharmacology analysis, transcriptomic analysis, and experiments to explore and verify the underlying mechanisms involved. MATERIALS AND METHODS: The antitumor effect of EAESI on PCa in vitro and in vivo was investigated via CCK-8, EdU, flow cytometry, and wound healing assays and xenograft tumor models. Network pharmacology analysis and transcriptomic analysis were employed to explore the underlying mechanism of EAESI against PCa. Activating transcription factor 3 (ATF3) and androgen receptor (AR) were confirmed to be the targets of EAESI against PCa by RT‒qPCR, western blotting, and rescue assays. In addition, the interaction between ATF3 and AR was assessed by coimmunoprecipitation, immunofluorescence, and nuclear-cytoplasmic separation assays. RESULTS: EAESI decreased cell viability, inhibited cell proliferation and migration, and induced apoptosis in AR+ and AR- PCa cells. Moreover, EAESI suppressed the growth of xenograft tumors in vivo. Network pharmacology analysis revealed that the hub targets of EAESI against PCa included AR, AKT1, TP53, and CCND1. Transcriptomic analysis indicated that activating transcription factor 3 (ATF3) was the most likely critical target of EAESI. EAESI downregulated AR expression and decreased the transcriptional activity of AR through ATF3 in AR+ PCa cells; and EAESI promoted the expression of ATF3 and exerted its antitumor effect via ATF3 in AR+ and AR- PCa cells. CONCLUSIONS: EAESI exerts good antitumor effects on PCa both in vitro and in vivo, and ATF3 and AR are the critical targets through which EAESI exerts antitumor effects on AR+ and AR- PCa cells.

Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment.

BACKGROUND: Prostate cancer (PCa) is the most prevalent genitourinary malignancy in men, with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. The immune microenvironment and metabolic alterations have crucial implications for the tumorigenesis and progression of PCa. Therefore, identifying metabolic genes associated with the immune microenvironment holds promise for predicting BCR and improving PCa prognosis. METHODS: In this study, ssGSEA and hierarchical clustering analysis were first conducted to evaluate and group PCa samples, followed by the use of the ESTIMATE and CIBERSORT algorithms to characterize the immunophenotypes and tumor microenvironment. The differential metabolic genes (MTGs) between groups were utilized to develop a prognostic-related signature. The predictive performance of the signature was assessed by principal component analysis (PCA), receiver operating characteristic (ROC) curve analysis, survival analysis, and the TIDE algorithm. A miRNA-MTGs regulatory network and predictive nomogram were constructed. Moreover, the expression of prognostic MTGs in PCa was detected by RT‒qPCR. RESULTS: PCa samples from the TCGA cohort were separated into two groups: the immune-low group and immune-high group. Forty-eight differentially expressed MTGs between the groups were identified, including 37 up-regulated and 11 down-regulated MTGs. Subsequently, CEL, CYP3A4, and PDE6G were identified as the genes most strongly associated with the BCR of PCa patients and these genes were utilized to establish the MTGs-based prognostic signatures. PCA, ROC curves analysis, Kaplan-Meier survival analysis, and the nomogram all showed the good predictive ability of the signature regardless of clinical variables. Furthermore, the MTGs-based signature was indicated as a potential predictive biomarker for immunotherapy response. Nine miRNAs involved in the regulation of prognostic MTGs were determined. In addition to the CEL gene, the PDE6G and CYP3A4 genes were expressed at higher levels in PCa samples. CONCLUSIONS: The MTGs-based signature represents a novel approach with promising potential for predicting BCR in PCa patients.

Comparison of cytokine levels in prostatic secretion between the IIIa and IIIb subtypes of prostatitis.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as National Institutes of Health (NIH) type III prostatitis, is a common disorder with an unclear etiology and no known curative treatments. Based on the presence or absence of leukocytes in expressed prostatic secretion (EPS), CP/CPPS is classified further into IIIa (inflammatory) and IIIb (noninflammatory) subtypes. However, the severity of symptoms is not entirely consistent with the white blood cell (WBC) count. Following the preliminary finding of a link between inflammatory cytokines and CP/CPPS, we performed this clinical study with the aim of identifying cytokines that are differentially expressed according to whether the prostatitis subtype is IIIa or IIIb. We found that granulocyte colony-stimulating factor (G-CSF), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) levels were significantly elevated and interferon-inducible protein-10 (IP-10) and platelet-derived growth factor-BB (PDGF-BB) levels were downregulated in the EPS of patients with type IIIa prostatitis. In a word, it is a meaningful study in which we investigate the levels of various cytokines in EPS according to whether prostatitis is the IIIa or IIIb subtype. The combination of G-CSF, IL-18, MCP-1, IP-10, and PDGF-BB expression levels could form a basis for classification, diagnosis, and therapeutic targets in clinical CP/CPPS.

Exploring a ferroptosis and oxidative stress-based prognostic model for clear cell renal cell carcinoma.

Background: Ferroptosis is a newly defined cell death process triggered by increased iron load and tremendous lipid reactive oxygen species (ROS). Oxidative stress-related ferroptosis is of great important to the occurrence and progression of clear cell renal cell carcinoma (ccRCC), which is particularly susceptibility to ferroptosis agonist. Therefore, exploring the molecular features of ferroptosis and oxidative stress might guide the clinical treatment and prognosis prediction for ccRCC patients. Methods: The differentially expressed ferroptosis and oxidative stress-associated genes (FPTOSs) between normal renal and ccRCC tissues were identified based on The Cancer Genome Atlas (TCGA) database, and those with prognostic significances were applied to develop a prognostic model and a risk scoring system (FPTOS_score). The clinical parameter, miRNA regulation, tumor mutation burden (TMB), immune cell infiltration, immunotherapy response, and drug susceptibility between two FPTOS-based risk stratifications were determined. Results: We have identified 5 prognosis-associated FPTOSs (ACADSB, CDCA3, CHAC1, MYCN, and TFAP2A), and developed a reliable FPTOS_socre system to distinguish patients into low- and high-risk groups. The findings implied that patients from the high-risk group performed poor prognoses, even after stratified analysis of various clinical parameters. A total of 30 miRNA-FPTOS regulatory pairs were recognized to identify the possible molecular mechanisms. Meanwhile, patients from the high-risk group exhibited higher TMB levels than those from the low-risk groups, and the predominant mutated driver genes were VHL, PBRM1 and TTN in both groups. The main infiltrating immune cells of high- and low-risk groups were CD8+ T cells and resting mast cells, respectively, and patients from the high-risk groups showed preferable drug responsiveness to anti-PD-1 immunotherapy. Eventually, potential sensitive drugs (cisplatin, BI-D1870, and docetaxel) and their enrichment pathways were identified to guide the treatment of ccRCC patients with high-risk. Conclusion: Our study comprehensively analyzed the expression profiles of FPTOSs and constructed a scoring system with considerable prognostic value, which would supply novel insights into the personalized treatment strategies and prognostic evaluation of ccRCC patient.

Identification of a novel senescence-associated signature to predict biochemical recurrence and immune microenvironment for prostate cancer.

Background: Prostate cancer (PCa) is an age-associated malignancy with high morbidity and mortality rate, posing a severe threat to public health. Cellular senescence, a specialized cell cycle arrest form, results in the secretion of various inflammatory mediators. In recent studies, senescence has shown an essential role in tumorigenesis and tumor development, yet the extensive effects of senescence in PCa have not been systematically investigated. Here, we aimed to develop a feasible senescence-associated prognosis model for early identification and appropriate management in patients with PCa. Method: The RNA sequence results and clinical information available from The Cancer Genome Atlas (TCGA) and a list of experimentally validated senescence-related genes (SRGs) from the CellAge database were first obtained. Then, a senescence-risk signature related with prognosis was constructed using univariate Cox and LASSO regression analysis. We calculated the risk score of each patient and divided them into high-risk and low-risk groups in terms of the median value. Furthermore, two datasets (GSE70770 and GSE46602) were used to assess the effects of the risk model. A nomogram was built by integrating the risk score and clinical characteristics, which was further verified using ROC curves and calibrations. Finally, we compared the differences in the tumor microenvironment (TME) landscape, drug susceptibility, and the functional enrichment among the different risk groups. Results: We established a unique prognostic signature in PCa patients based on eight SRGs, including CENPA, ADCK5, FOXM1, TFAP4, MAPK, LGALS3, BAG3, and NOX4, and validated well prognosis-predictive power in independent datasets. The risk model was associated with age and TNM staging, and the calibration chart presented a high consistency in nomogram prediction. Additionally, the prognostic signature could serve as an independent prediction factor due to its high accuracy. Notably, we found that the risk score was positively associated with tumor mutation burden (TMB) and immune checkpoint, whereas negatively correlated with tumor immune dysfunction and exclusion (TIDE), suggesting that these patients with risk scores were more sensitive to immunotherapy. Drug susceptibility analysis revealed differences in the responses to general drugs (docetaxel, cyclophosphamide, 5-Fluorouracil, cisplatin, paclitaxel, and vincristine) were yielded between the two risk groups. Conclusion: Identifying the SRG-score signature may become a promising method for predicting the prognosis of patients with PCa and tailoring appropriate treatment strategies.

Water-in-Water Emulsions Stabilized by Silica Janus Nanosheets.

Water-in-water (w/w) emulsions have been recognized for their broad applications in foods, cosmetics, and biomedical engineering. In this work, silica Janus nanosheets (JNs) with polyacrylic acid (PAA) chains grafted on one surface via crushing functional silica foams, and used silica JNs as Pickering stabilizer to produce stable water-in-water (w/w) emulsions from the aqueous two-phase system (ATPS) containing methacrylic acid (MAA) and NaCl are prepared. The interfacial area of w/w emulsions increases linearly with the concentration of silica JNs, and the interfacial coverage of nanosheets is calculated to be about 98%. After polymerizing w/w emulsions prepared from MAA/NaCl ATPS, it is found that silica JNs are entrapped at the interface of w/w emulsions with the smooth PAA-grafted surface located toward MAA-rich phase due to their specific interaction. These results show that functional silica JNs can be used as a promising amphiphilic Pickering stabilizer to produce well-defined w/w emulsions for numerous application fields.

Rate and Mechanism of Electrochemical Formation of Surface-Bound Hydrogen on Pt(111) Single Crystals.

The formation of surface-bound hydrogen from one proton and one electron plays an enabling role in renewable hydrogen production. Quantifying the surface-bound hydrogen formation, however, requires decoupling the delicate interplay of numerous processes. We study cyclic voltammetry (CV) at fast scan rates to characterize the rate constant for the surface-bound hydrogen formation (also known as underpotential deposition hydrogen, UPD Had). We find that the formation of Had on Pt(111) single crystals is ∼100× faster in acid than in base. Reaction-order analysis indicates that the formation of Had occurs as a standard proton-coupled electron transfer (PCET) reaction in acid, whereas in base, it displays a pH-independent rate constant, indicating the presence of a chemical step such as the reorganization of interfacial water. Our results provide a methodology for quantifying the interfacial PCET kinetics and reveal the mechanistic nature of the UPD Had formation as the reason the hydrogen evolution electrocatalysis on Pt is faster in acid than in base.

Withaphysalins from Medicinal and Edible Physalis minima and Their Anti-inflammatory Activities.

Physalis minima is a medicinal and edible plant in China. In this study, 22 new withaphysalins, including a novel 1(10 → 6)abeo-14ß-hydroxy one (1) and other 15 unusual 14ß-hydroxy ones (3-4, 6-17, 19), were isolated from the whole herbs of P. minima together with two known analogues (23-24). Their structures were established by extensive analysis of high-resolution electrospray ionization mass spectrometry, IR, and 1D and 2D NMR spectroscopic data. Their absolute configurations were determined by electronic circular dichroism (ECD) spectra and single-crystal X-ray crystallographic analyses, together with DFT NMR calculations. All isolated compounds were evaluated for their anti-inflammatory activity via measuring the colorimetric reporter of the secreted embryonic alkaline phosphatase gene driven by an IFN-ß minimal promoter fused to five copies of the NF-κB consensus transcriptional response element and three copies of the c-Rel binding site in LPS-stimulated human THP1-Dual cells. Compounds 2, 5, 6, 9, 10, 11, and 20 showed significant anti-inflammatory effects with IC50 values in the range of 3.01-13.39 µM. Among them, compounds 2 and 10 showed better anti-inflammatory effects to inhibit the secretion of IL-6, IL-1ß, and TNF-α in LPS-stimulated THP1-Dual cells.

Evaluation of mid- and long-term impact of COVID-19 on male fertility through evaluating semen parameters.

Background: The coronavirus disease 2019 (COVID-19) has spread worldwide with alarming levels of spread and severity. The distribution of angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) from bioinformatics evidence, the autopsy report for COVID-19 and the published study on sperm quality indicated COVID-19 could have a negative impact on male fertility. However, whether the negative impact of COVID-19 on male fertility is persistent remains unknown, which requires long-term follow-up investigation. Methods: Semen samples were collected from 36 male COVID-19 patients with a median recovery time of 177.5 days and 45 control subjects. Then, analysis of sperm quality and alterations of total sperm number with recovery time were performed. Results: There was no significant difference in semen parameters between male recovered patients and control subjects. And the comparisons of semen parameters between first follow-up and second follow-up revealed no significant difference. In addition, we explored the alterations of sperm count with recovery time. It showed that the group with recovery time of ≥120 and <150 days had a significantly lower total sperm number than controls while the other two groups with recovery time of ≥150 days displayed no significance with controls, and total sperm number showed a significant decline after a recovery time of 90 days and an improving trend after a recovery time of about 150 days. Conclusions: The sperm quality of COVID-19 recovered patients improved after a recovery time of nearly half a year, while the total sperm number showed an improvement after a recovery time of about 150 days. COVID-19 patients should pay close attention to the quality of semen, and might be considered to be given medical interventions if necessary within about two months after recovery, in order to improve the fertility of male patients as soon as possible.

Facile and scalable synthesis of functional Janus nanosheets - A polyethoxysiloxane assisted surfactant-free high internal phase emulsion approach.

HYPOTHESIS: Janus nanosheets, which have two surfaces of different functionalities, exhibit unique interfacial properties. In this work, we propose a facile and scalable technique for preparation of silica-based Janus nanosheets, which is based on formation of high internal phase water-in-oil emulsions stabilized solely by alkyl-substituted polyethoxysiloxanes due to their hydrolysis-induced interfacial activity. EXPERIMENTS: Janus nanosheets are then obtained by crushing the silica foams converted from such emulsions. The morphology of Janus nanosheets is investigated by field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The chemical structure of functional silica materials is characterized by Fourier transform infrared spectroscopy (FT-IR). The asymmetric structure of silica nanosheets is observed by confocal laser scanning microscopy. FINDINGS: The resulting nanosheets have a rough hydrophobic surface and a smooth hydrophilic one, and are capable of stabilizing Pickering oil-in-water emulsions. Remarkably, pH-responsiveness of emulsions can be attained using the nanosheets whose hydrophilic surface is substituted with amino groups. Fast oil-water separation is achieved by the Janus nanosheets, which has been demonstrated by the nanosheets with a polystyrene-coated hydrophobic surface. This work paves a new avenue for large-scale production of functional silica-based Janus nanosheets suitable for numerous promising applications.

A Mitochondrial Dysfunction and Oxidative Stress Pathway-Based Prognostic Signature for Clear Cell Renal Cell Carcinoma.

Mitochondria not only are the main source of ATP synthesis but also regulate cellular redox balance and calcium homeostasis. Its dysfunction can lead to a variety of diseases and promote cancer and metastasis. In this study, we aimed to explore the molecular characteristics and prognostic significance of mitochondrial genes (MTGs) related to oxidative stress in clear cell renal cell carcinoma (ccRCC). A total of 75 differentially expressed MTGs were analyzed from The Cancer Genome Atlas (TCGA) database, including 46 upregulated and 29 downregulated MTGs. Further analysis screened 6 prognostic-related MTGs (ACAD11, ACADSB, BID, PYCR1, SLC25A27, and STAR) and was used to develop a signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses showed that the signature could accurately distinguish patients with poor prognosis and had good individual risk stratification and prognostic potential. Stratified analysis based on different clinical variables indicated that the signature could be used to evaluate tumor progression in ccRCC. Moreover, we found that there were significant differences in immune cell infiltration between the low- and high-risk groups based on the signature and that ccRCC patients in the low-risk group responded better to immunotherapy than those in the high-risk group (46.59% vs 35.34%, P = 0.008). We also found that the expression levels of these prognostic MTGs were significantly associated with drug sensitivity in multiple ccRCC cell lines. Our study for the first time elucidates the biological function and prognostic significance of mitochondrial molecules associated with oxidative stress and provides a new protocol for evaluating treatment strategies targeting mitochondria in ccRCC patients.

Exploration of Redox-Related Molecular Patterns and the Redox Score for Prostate Cancer.

Redox homeostasis is the key to cell survival, and its imbalance can promote the occurrence and progression of tumors. However, it remains unclear whether these redox-related genes (RRGs) have potential roles in the tumor microenvironment, immunotherapy, and drug sensitivity. Here, we performed a systematic and comprehensive analysis of 489 prostate cancer (PC) samples from The Cancer Genome Atlas database and 214 PC samples from 8 datasets in the Gene Expression Omnibus database to determine redox modification patterns and the redox scoring system for PC. We identified two modification patterns (Redox_A and Redox_B) in PC using unsupervised consensus clustering based on 1410 differential expression RRGs. We then compared the prognostic value, tumor microenvironment characteristics, immune cell infiltration, and molecular characteristics of the two patterns. The Redox_A pattern was significantly enriched in the carcinogenic activation signaling pathways and had a poor prognosis, while the Redox_B pattern was mainly enriched in a variety of metabolic and redox pathways and had a good prognosis. Next, redox-related characteristic genes were extracted from these two patterns, and a scoring system (Redox_score) was constructed to evaluate PC patients. Further analysis indicated that lower Redox_score patients had a better prognosis, while higher Redox_score patients had a higher tumor mutation burden, driver gene mutation rate, and immune checkpoint inhibitor gene expression. We also found that higher Redox_score patients were more responsive to anti-PD-1 immunotherapy. Moreover, Redox_score was determined to be significantly correlated with anticancer drug sensitivity and resistance. Our study provides a comprehensive analysis of redox modifications in PC and reveals new patterns of PC based on RRGs, which will provide insights into the complex mechanisms of PC and develop more effective individualized therapeutic strategies.

A Mid-to-Long Term Comprehensive Evaluation of Psychological Distress and Erectile Function in COVID-19 Recovered Patients.

BACKGROUND: The psychological and sexual health of different populations are negatively affected during the coronavirus disease 2019 (COVID-19) pandemic. However, little is known about psychological distress and erectile function of male recovered patients with COVID-19 in the long term. AIM: We aimed to evaluate psychological distress and erectile function of male recovered patients with COVID-19 in the mid-to-long terms. METHODS: We recruited 67 eligible male recovered patients with COVID-19 and followed them up twice within approximately 6 months of recovery time. The psychological distress and erectile function were assessed by validated Chinese version of paper questionnaires. OUTCOMES: The primary outcomes were Symptom Checklist 90 questionnaire for psychological distress and International Index of Erectile Function-5 for erectile function. RESULTS: In the first visit, COVID-19 patients with a median recovery time of 80 days mainly presented the following positive symptoms: Obsessive-Compulsive, additional items (ADD), Hostility, Interpersonal Sensitivity, Depression, and Somatization; while the dimension scores in Somatization, Anxiety, ADD, and Phobia were higher than Chinese male norms. Besides, the prevalence of erectile dysfunction (ED) in the first-visit patients was significantly higher than Chinese controls. In the second visit, the primary psychological symptoms of COVID-19 patients with a median recovery time of 174 days were Obsessive-Compulsive, ADD, Interpersonal Sensitivity, and Hostility, while all dimensions scores of Symptom Checklist 90 were lower than Chinese male norms. Moreover, second-visit patients had no significant difference with Chinese controls in ED prevalence. In addition, it suggested that GSI was the independent risk factor for ED in the regression analysis for the first-visit patients. CLINICAL IMPLICATIONS: The study showed the changes of psychological symptoms and erectile function in COVID-19 recovered patients, and provided reference on whether psychological and sexual supports are needed after a period of recovery. STRENGTHS AND LIMITATIONS: To our knowledge, it is the first study to comprehensively evaluate the psychological distress and erectile function of COVID-19 recovered patients in the mid-to-long terms. The main limitations were the low number of analyzed participants, and the psychological distress and erectile function of healthy Chinese men over the same period were not evaluated, and the psychological and sexual related data of participants prior to COVID-19 were not available. Additionally, there was a selection bias in comparing COVID-19 patients with healthy controls. CONCLUSION: With less impact of COVID-19 event, the impaired erectile function and psychological distress improved in COVID-19 recovered patients with a recovery time of nearly half a year. Hu B, Ruan Y, Liu K, et al. A Mid-to-Long Term Comprehensive Evaluation of Psychological Distress and Erectile Function in COVID-19 Recovered Patients. J Sex Med 2021;18:1863-1871.

Synthesis and Biological Evaluation of C-17-Amino-Substituted Pyrazole-Fused Betulinic Acid Derivatives as Novel Agents for Osteoarthritis Treatment.

A series of pyrazole-fused betulinic acid (BA) derivatives were designed and synthesized by replacing the carboxyl group at C-17 with aliphatic amine, amide, and urea groups. The suppressive effects of the compounds on osteoclast (OC) formation and inflammatory cytokine production were evaluated on murine macrophages, RAW264.7 cells, conditioned with receptor activator for nuclear factor-κB ligand (RANKL)/macrophage colony stimulating factor (M-CSF) or lipopolysaccharide (LPS), respectively. Results showed that, compared with betulinic acid, most of these compounds exhibited significant improvements in inhibitory potency. Compound 25 exhibited distinguished activities on inhibiting OC differentiation with an IC50 value of 1.86 µM. Meanwhile, compound 25, displaying the most promising suppression on IL-1ß secretion from RAW264.7 cells, was further found to possess therapeutic effects in the sodium monoiodoacetate (MIA)-induced osteoarthritis rat model. Dose-dependent benefits were observed in MIA-elicited rats with ameliorated joint pain as well as decreased cartilage damage and bone changes after compound 25 treatment.

Identification of the Functions and Prognostic Values of RNA Binding Proteins in Bladder Cancer.

Post-transcriptional regulation plays a leading role in gene regulation and RNA binding proteins (RBPs) are the most important posttranscriptional regulatory protein. RBPs had been found to be abnormally expressed in a variety of tumors and is closely related to its occurrence and progression. However, the exact mechanism of RBPs in bladder cancer (BC) is unknown. We downloaded transcriptomic data of BC from the Cancer Genome Atlas (TCGA) database and used bioinformatics techniques for subsequent analysis. A total of 116 differentially expressed RBPs were selected, among which 61 were up-regulated and 55 were down-regulated. We then identified 12 prognostic RBPs including CTIF, CTU1, DARS2, ENOX1, IGF2BP2, LIN28A, MTG1, NOVA1, PPARGC1B, RBMS3, TDRD1, and ZNF106, and constructed a prognostic risk score model. Based on this model we found that patients in the high-risk group had poorer overall survival (P < 0.001), and the area under the receiver operator characteristic curve for this model was 0.677 for 1 year, 0.697 for 3 years, and 0.709 for 5 years. Next, we drew a nomogram based on the risk score and other clinical variables, which showed better predictive performance. Our findings contribute to a better understanding of the pathogenesis, progression and metastasis of BC. The model of these 12 genes has good predictive value and may have good prospects for improving clinical treatment regimens and patient prognosis.

Development of an Individualized Ubiquitin Prognostic Signature for Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common tumor type in genitourinary system and has a poor prognosis. Ubiquitin dependent modification systems have been reported in a variety of malignancies and have influenced tumor genesis and progression. However, the molecular characteristics and prognostic value of ubiquitin in ccRCC have not been systematically reported. In our study, 204 differentially expressed ubiquitin related genes (URGs) were identified from The Cancer Genome Atlas (TCGA) cohort, including 141 up-regulated and 63 down-regulated URGs. A total of seven prognostic related URGs (CDCA3, CHFR, CORO6, RNF175, TRIM72, VAV3, and WDR72) were identified by Cox regression analysis of differential URGs and used to construct a prognostic signature. Kaplan-Meier analysis confirmed that high-risk patients had a worse prognosis (P = 1.11e-16), and the predicted area under the receiver operating characteristic (ROC) curves were 0.735 at 1 year, 0.702 at 3 years, and 0.744 at 5 years, showing good prediction accuracy. Stratified analysis showed that the URGs-based prognostic signature could be used to evaluate tumor progression in ccRCC. Further analysis confirmed that the signature is an independent prognostic factor related to the prognosis of ccRCC patients, which may help to reveal the molecular mechanism of ccRCC and provide potential diagnostic and prognostic markers for ccRCC.

Integrated Analysis to Identify a Redox-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma.

The imbalance of the redox system has been shown to be closely related to the occurrence and progression of many cancers. However, the biological function and clinical significance of redox-related genes (RRGs) in clear cell renal cell carcinoma (ccRCC) are unclear. In our current study, we downloaded transcriptome data from The Cancer Genome Atlas (TCGA) database of ccRCC patients and identified the differential expression of RRGs in tumor and normal kidney tissues. Then, we identified a total of 344 differentially expressed RRGs, including 234 upregulated and 110 downregulated RRGs. Fourteen prognosis-related RRGs (ADAM8, CGN, EIF4EBP1, FOXM1, G6PC, HAMP, HTR2C, ITIH4, LTB4R, MMP3, PLG, PRKCG, SAA1, and VWF) were selected out, and a prognosis-related signature was constructed based on these RRGs. Survival analysis showed that overall survival was lower in the high-risk group than in the low-risk group. The area under the receiver operating characteristic curve of the risk score signature was 0.728 at three years and 0.759 at five years in the TCGA cohort and 0.804 at three years and 0.829 at five years in the E-MTAB-1980 cohort, showing good predictive performance. In addition, we explored the regulatory relationships of these RRGs with upstream miRNA, their biological functions and molecular mechanisms, and their relationship with immune cell infiltration. We also established a nomogram based on these prognostic RRGs and performed internal and external validation in the TCGA and E-MTAB-1980 cohorts, respectively, showing an accurate prediction of ccRCC prognosis. Moreover, a stratified analysis showed a significant correlation between the prognostic signature and ccRCC progression.

No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: A perspective and urogenital evaluation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been spreading all over the world since December 2019. However, medical information regarding the urogenital involvement in recovered COVID-19 patients is limited or unknown. OBJECTIVES: To comprehensively evaluate urogenital involvement in recovered COVID-19 patients. MATERIALS AND METHODS: Men aged between 20 years and 50 years who were diagnosed with SARS-CoV-2 infection and recovered when the study was conducted were enrolled in our study. Demographic and clinical characteristics, and history of hospitalization were collected and analyzed. Urine, expressed prostatic secretions (EPSs), and semen samples were collected for SARS-CoV-2 RNA detection. Semen quality and hormonal profiles were analyzed. RESULTS: Among 74 male recovered COVID-19 patients, 11 (14.9%) were asymptomatic, classified into mild type, and 31 (41.9%) were classified into moderate type. The remaining patients (32/74, 43.2%) had severe pneumonia. No critically ill recovered COVID-19 patient was recruited in our cohort. The median interval between last positive pharyngeal swab RT-PCR test and semen samples collection was 80 days (IQR, 64-93). The median age was 31 years (IQR, 27-36; range, 21-49), and the median body mass index (BMI) was 24.40 (IQR, 22.55-27.30). Forty-five (61.6%) men were married, and 28 (38.4%) were unmarried. Fifty-three (72.6%) patients denied cigarette smoking, 18 (24.7%) were active smokers, and 2 of them were past smokers. The majority of our participants (53/74, 72.6%) did not consume alcohol. Fever occurred in most of the patients (75.3%), and 63 of them had abnormal chest CT images. Only one patient complained of scrotal discomfort during the course of COVID-19, which was ruled out orchitis by MRI (data not shown). A total of 205 samples were collected for SARS-CoV-2 detection (74 urine samples, 70 semen samples, and 61 EPS samples). However, viral nucleic acid was not detected in body fluids from the urogenital system. In terms of hormonal profiles, the levels of FSH, LH, testosterone, and estradiol were 5.20 [4.23] mIU/mL, 3.95 [1.63] mIU/mL, 3.65 [1.19] ng/mL, and 39.48 [12.51] pg/mL, respectively. And these values were within the normal limits. The overall semen quality of recovered COVID-19 patients was above the lower reference limit released by the WHO. While compared with healthy control, sperm concentration, total sperm count, and total motility were significantly declined. In addition, different clinical types of COVID-19 have no significant difference in semen parameters, but total sperm count showed a descending trend. Interestingly, subjects with a longer recovery time showed worse data for sperm quality. Small sample size and lacking semen parameters before the infection are the major limitations of our study. DISCUSSION AND CONCLUSIONS: To the best of our knowledge, it is the largest cohort study with longest follow-up for urogenital evaluation comprehensively so far. Direct urogenital involvement was not found in the recovered COVID-19 male patients. SARS-CoV-2 RNA was undetectable in the urogenital secretions, and semen quality declined slightly, while hormonal profiles remained normal. Moreover, patients with a long time (≥90 days) since recovery had lower total sperm count. Great attention and further study should be conducted and follow-up on the reproductive function in the following months.

An eleven metabolic gene signature-based prognostic model for clear cell renal cell carcinoma.

In this study, we performed bioinformatics and statistical analyses to investigate the prognostic significance of metabolic genes in clear cell renal cell carcinoma (ccRCC) using the transcriptome data of 539 ccRCC and 72 normal renal tissues from TCGA database. We identified 79 upregulated and 45 downregulated (n=124) metabolic genes in ccRCC tissues. Eleven prognostic metabolic genes (NOS1, ALAD, ALDH3B2, ACADM, ITPKA, IMPDH1, SCD5, FADS2, ACHE, CA4, and HK3) were identified by further analysis. We then constructed an 11-metabolic gene signature-based prognostic risk score model and classified ccRCC patients into high- and low-risk groups. Overall survival (OS) among the high-risk ccRCC patients was significantly shorter than among the low-risk ccRCC patients. Receiver operating characteristic (ROC) curve analysis of the prognostic risk score model showed that the areas under the ROC curve for the 1-, 3-, and 5-year OS were 0.810, 0.738, and 0.771, respectively. Thus, our prognostic model showed favorable predictive power in the TCGA and E-MTAB-1980 ccRCC patient cohorts. We also established a nomogram based on these eleven metabolic genes and validated internally in the TCGA cohort, showing an accurate prediction for prognosis in ccRCC.