Comprehensive assessment of the association between tumorinfiltrating immune cells and the prognosis of renal cell carcinoma

BACKGROUND According to current statistics,renal cancer accounts for 3%of all cancers world-wide.Renal cell carcinoma(RCC)is the most common solid lesion in the kidney and accounts for approximately 90%of all renal malignancies.Increasing evi-dence has shown an association between immune infiltration in RCC and clinical outcomes.To discover possible targets for the immune system,we investigated the link between tumor-infiltrating immune cells(TIICs)and the prognosis of RCC.AIM To investigate the effects of 22 TIICs on the prognosis of RCC patients and iden-tify potential therapeutic targets for RCC immunotherapy.METHODS The CIBERSORT algorithm partitioned the 22 TIICs from the Cancer Genome Atlas cohort into proportions.Cox regression analysis was employed to evaluate the impact of 22 TIICs on the probability of developing RCC.A predictive model for immunological risk was developed by analyzing the statistical relationship between the subpopulations of TIICs and survival outcomes.Furthermore,multi-variate Cox regression analysis was used to investigate independent factors for the prognostic prediction of RCC.A value of P<0.05 was regarded as statistically significant.RESULTS Compared to normal tissues,RCC tissues exhibited a distinct infiltration of im-mune cells.An immune risk score model was established and univariate Cox regression analysis revealed a significant association between four immune cell types and the survival risk connected to RCC.High-risk individuals were correlated to poorer outcomes according to the Kaplan-Meier survival curve(P=1E-05).The immunological risk score model was demonstrated to be a dependable predictor of survival risk(area under the curve=0.747)via the receiver operating characteristic curve.According to multivariate Cox regression analysis,the immune risk score model independently predicted RCC patients'prognosis(hazard ratio=1.550,95%CI:1.342–1.791;P<0.001).Finally,we established a nomogram that accurately and comprehensively forecast the survival of patients with RCC.CONCLUSION TIICs play various roles in RCC prognosis.The immunological risk score is an independent predictor of poor survival in kidney cancer cases.

Exploring the potential mechanisms of impairment on genitourinary system associated with coronavirus disease 2019 infection:Bioinformatics and molecular simulation analyses

Objective:The novel coronavirus(severe acute respiratory syndrome coronavirus 2)has been spreading worldwide since December 2019,posing a serious danger to human health and socioeconomic development.A large number of clinical trials have revealed that coronavirus disease 2019(COVID-19)results in multi-organ damage including the urogenital system.This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis.Methods:We used multiple publicly available databases to explore the expression patterns of angiotensin-converting enzyme 2(ACE2),transmembrane serine protease 2(TMPRSS2),and CD147 in major organs in the healthy and disease-specific populations,particularly the genitourinary organs.Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2,TMPRSS2,CD147,cytokine receptors,and cytokine interacting proteins in genitourinary organs,such as the bladder,kidney,prostate,and testis.Additionally,gene set enrichmentanalysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer.Results:The results revealed that ACE2,TMPRSS2,and CD147 were highly expressed in normal urogenital organs.Then,they were also highly expressed in multiple tumors and chronic kidney diseases.Additionally,ACE2,TMPRSS2,and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing.Cytokine receptors and cytokine interacting proteins,especially CCL2,JUN,and TIMP1,were commonly highly expressed in urogenital organs.Finally,gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19.Conclusion:Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives,which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.

Polycystic ovary syndrome patients with high BMI tend to have functional disorders of androgen excess:a prospective study

Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome （PCOS）. There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index （BMI）, total testosterone （TT）, modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin （SHBG）, homeostasis model assessment-estimated insulin resistance （HOMA-IR） and free androgen index （FAI） between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyper- androgenism had significantly higher BMI （P 〈 0.05）, but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong pre-dictor of hyperandrogenism in PCOS.

New insights into SET protein during mouse spermatogenesis

Spermatogenesis is a complex, unique process that takes place in the testis. It consists of a set of events including mitotic （from spermatogonia to primary spermatocytes） and meiotic divisions （from primary spermatocytes to early round spermatids）, and spermiogenesis, a differentiation step from early round spermatids to testicular spermatozoa Although spermatogenesis is known as a well autocrine- and paracrine-regulated process, some proteins involved in its regulation remain to be determined. Related to this, the recent study conducted by Dai et al. have shed light on the relevant function of SET protein, a protein phosphatase 2A （PP2A） inhibitor, also known as I2PP2A, or TAF-Ib. This protein, identified for the first time in 1992, has been described to be involved in multiple cell functions, such as control of cell cycle and apoptosis, gene transcription, epigenetic regulation, and nucleosome assembly. Apart from these functions, it is worth noting that SET has been to be involved in the regulation found in theca cells, where appears of androgen biosynthesis, and in mature oocytes, where plays a key role in the segregation of sister chromatids during the second meiotic division SET protein inhibits PP2A by enhancing lyase activity of P450c17, a substrate for PP2A when it is Serand Thr-phosphorylated. PP2A function in reproductive physiology is not restricted to gamete production （i.e. spermatogenesis and oogenesis）, but this protein is also involved in human sperm capacitation.

Blastoids generated purely from embryonic stem cells both in mice and humans

Dear Editor,Embryonic stem cells(ESCs)and trophoblast stem cells(TSCs)are derived from blastocysts(Lu et al.,2001).Blastocyst-like structures(blastoids)are self-assembled structures formed by a combination of ESCs and TSCs(Rivron et al.,2018).To increase the success rate of blastoid formation and its similarity with the features of blastocysts,some reports showed that blastoid could also be derived from a combination of three cell lines,ESCs,TSCs,and extraembryonic endoderm cells(XENs),or novel type of stem cells(Sozen et al.,2018;Weatherbee et al.,2023:Wu et al.,2023;Zhang et al.,2023;Zhang et al.,2019).

The RING finger protein family in health and disease

Ubiquitination is a highly conserved and fundamental posttranslational modification(PTM)in all eukaryotes regulating thousands of proteins.The RING(really interesting new gene)finger(RNF)protein,containing the RING domain,exerts E3 ubiquitin ligase that mediates the covalent attachment of ubiquitin(Ub)to target proteins.Multiple reviews have summarized the critical roles of the tripartite-motif(TRIM)protein family,a subgroup of RNF proteins,in various diseases,including cancer,inflammatory,infectious,and neuropsychiatric disorders.Except for TRIMs,since numerous studies over the past decades have delineated that other RNF proteins also exert widespread involvement in several diseases,their importance should not be underestimated.This review summarizes the potential contribution of dysregulated RNF proteins,except for TRIMs,to the pathogenesis of some diseases,including cancer,autoimmune diseases,and neurodegenerative disorder.Since viral infection is broadly involved in the induction and development of those diseases,this manuscript also highlights the regulatory roles of RNF proteins,excluding TRIMs,in the antiviral immune responses.In addition,we further discuss the potential intervention strategies targeting other RNF proteins for the prevention and therapeutics of those human diseases.