A study of diabetes-induced erectile dysfunction treated with human umbilical cord mesenchymal stem cells.

The present study aimed to assess the value of human umbilical cord mesenchymal stem cells (hUC-MSCs) for the treatment of diabetes-induced erectile dysfunction (DMED). We established a type 1 diabetes model through intra-abdominal streptozotocin injection. After 10 weeks, an apomorphine test was performed to screen the rats for erectile dysfunction (ED). The rats were divided into three groups: normal control group (n = 10), DMED group (n = 9) and DMED+hUC-MSC group (n = 9). After 4 weeks of hUC-MSC therapy, erectile function was evaluated by intracavernous pressure measurements, and penile tissue collagen and smooth muscle were examined by haematoxylin-eosin and Masson's trichrome staining. In addition, western blotting, immunohistochemistry and RT-PCR analysis of TLR4, VEGF and eNOS were performed. The results showed that hUC-MSC treatment restored erectile function (p < .05) and reversed the smooth muscle/collagen ratio changes of DMED rats (p < .05). Furthermore, hUC-MSC treatment inhibited the expression of TLR4 (p < .05) and enhanced VEGF and eNOS expression (p < .05). In conclusion, hUC-MSC treatment restored the erectile function of diabetic rats by inhibiting TLR4, improving corpora cavernosa fibrosis, and increasing VEGF and eNOS expression.

The indicative effects of apolipoproteins on organic erectile dysfunction: bridging Mendelian randomization and case-control study.

The existing research on the association between apolipoproteins (Apos) and erectile dysfunction (ED) primarily relies on observational studies and does not distinguish between organic and psychogenic causes when diagnosing ED. It is difficult to believe that Apos play a role in psychogenic ED. To address these issues, our study explored the causal relationship between lipoproteins and ED using Mendelian randomization (MR) analysis and differentiate between organic and psychogenic ED through the use of nocturnal penile tumescence and rigidity (NPTR) monitoring. Multivariate MR analysis revealed significant causal associations between high-density lipoprotein (HDL), Apo A1, and Apo B/A1 with ED (OR and 95% CI were 0.33 (0.14-0.78), 3.58 (1.52-8.43), and 0.30 (0.13-0.66)). we conducted statistical and analytical analyses on the data of 212 patients using multivariate analyses and receiver operating characteristic (ROC) curves. Patients with organic ED had significantly lower levels of HDL, Apo A1 and Apo A1/B, whereas patients with organic ED had considerably higher levels of Apo B and low-density lipoprotein (LDL). The diagnostic value of Apos in predicting the risk of organic ED was evaluated using ROC curves. The results indicated that Apo A1 and Apo A1/B demonstrated good predictive value. HDL, Apo A1, and Apo A1/B have been identified as risk factors for ED in our study. Furthermore, our research highlights the significance of Apo A1 and Apo A1/Apo B in the development of organic ED and suggests their potential use as indicators to assess the risks associated with organic ED.

Three-dimensional S-scheme heterojunction by integration of purple tungsten oxide nanowires and cadmium sulfide nanospheres for effective photocatalytic hydrogen generation.

The practical photocatalytic application of cadmium sulfide (CdS) has been significantly constrained by fast carrier recombination and significant photocorrosion. Therefore, we developed a three-dimensional (3D) step-by-step (S-scheme) heterojunction using the coupling interface between purple tungsten oxide (W18O49) nanowires and CdS nanospheres. The photocatalytic hydrogen evolution rate of optimized W18O49/CdS 3D S-scheme heterojunction can reach 9.7 mmol·h-1·g-1, 7.5 and 16.2 times greater than pure CdS (1.3 mmol·h-1·g-1) and 10 wt%-W18O49/CdS (mechanical mixing, 0.6 mmol·h-1·g-1), proving that the tight S-scheme heterojunction constructed by the hydrothermal method can efficiently enhance the carrier separation. Notably, the apparent quantum efficiency (AQE) of W18O49/CdS 3D S-scheme heterojunction approaches 7.5% and 3.5% at 370 nm and 456 nm, respectively, which is 7.5 and 8.8 times than pure CdS (1.0% and 0.4%). The produced W18O49/CdS catalyst also has relative stability of structure and hydrogen production. Additionally, the H2 evolution rate of W18O49/CdS 3D S-scheme heterojunction is 1.2 times greater than 1 wt%-platinum (Pt)/CdS (8.2 mmol·h-1·g-1), which indicates that the W18O49 can effectively replace the precious metal for boosting the hydrogen production rate.

Development and validation of a disulfidptosis and M2 TAM-related classifier for bladder cancer to explore tumor subtypes, immune landscape and drug treatment.

BACKGROUND: Disulfidptosis, as a new mode of programmed cell death, is closely associated with tumorigenesis. Meanwhile, M2 tumor-associated macrophage (TAM) plays an important role in tumor progression. Here, we propose to combine these two perspectives to detect novel disulfidptosis and M2 TAM-related biomarkers in bladder cancer (BCa) to identify various tumor subtypes, construct prognostic features, reveal immune and somatic mutational landscapes, and screen for drugs in BCa. METHODS: We used weighted gene co-expression network analysis (WGCNA) to mine M2 TAM-related genes. Consensus unsupervised clustering was performed to identify potential tumor subtypes. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were utilized to build the risk model. We then explored the immune cell, immune function, immune checkpoint expression patterns and somatic mutational landscape in clusters and risk groups. In addition, we performed sensitivity analysis for anti-cancer drugs. RESULTS: We identified 3057 M2 TAM-related genes and intersected them with disulfidptosis-related genes to obtain 95 disulfidptosis and M2 TAM-related genes (DMRGs). In terms of tumor subtypes, two molecular clusters were identified. Cluster 1 showed stronger immunogenicity and higher tumor mutational burden (TMB). We also predicted 50 drugs with high sensitivity in cluster 1. On the basis of risk grouping, the high-risk group had poor overall survival in the training, test, and validation groups. Ten screened anti-cancer drugs were more sensitive in the high-risk group. A nomogram predicting survival of BCa patients was also established. CONCLUSION: By combining two hotspot perspectives, disulfidptosis and M2 TAM, we provide a valuable risk score signature for establishing individualized treatment regimens and drug choices. The risk score may serve as an independent risk factor for BCa patients.

Intracavitary Chemotherapy after kidney-Sparing Therapy for Upper Tract Urothelial Carcinoma: A Meta-Analysis.

PURPOSE: Intracavitary chemotherapy is one of the current treatment options for kidney-sparing treatment of upper tract urothelial carcinoma (UTUC). The purpose of this meta-analysis was to assess the efficacy and safety of intracavitary perfusion. METHODS: We carefully selected publications for study from four databases (Embase, PubMed, Web of Science, and Scopus) up to January 2023. The R 4.0.4 software was used to calculate the pooled ratio and its 95% confidence intervals (95% CIs). The I2 score was used to test heterogeneity, and the funnel plot was used to estimate the publication bias. RESULTS: Thirty-four studies with a total of 788 patients were included in this study. The overall survival at a median follow-up of 26.3 months was 87.2% (95% CI 0.80-0.93). The cancer-specific survival at a median follow-up of 30 months was 94.1% (95% CI 0.89-0.98). At a median follow-up of 30 months, the recurrence rate of UTUC was 27.5% (95% CI 0.21-0.34). By subgroup analysis, we found that the recurrence rate in patients with T1 / Ta stage was 35.1% and CIS stage 29.0%. The recurrence rates of BCG, Mitomycin C, and Mitomycin Gel (UGN101) were 31.2%, 41.3% and 12.9%, respectively. The recurrence rates for anterograde and retrograde perfusion were 28.5% and 21.8%, respectively. CONCLUSION: With the advent of new drugs, including UGN101, patients with UTUC have a better prognosis. Therefore, kidney preservation therapy for patients with UTUC would be promising.

Identification of bicalutamide resistance-related genes and prognosis prediction in patients with prostate cancer.

Background: Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death in men. Androgen deprivation therapy (ADT) has become the first-line therapy for inhibiting PCa progression; however, nearly all patients receiving ADT eventually progress to castrate-resistant prostate cancer. Therefore, this study aimed to identify hub genes related to bicalutamide resistance in PCa and provide new insights into endocrine therapy resistance. Methods: The data were obtained from public databases. Weighted correlation network analysis was used to identify the gene modules related to bicalutamide resistance, and the relationship between the samples and disease-free survival was analyzed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed, and hub genes were identified. The LASSO algorithm was used to develop a bicalutamide resistance prognostic model in patients with PCa, which was then verified. Finally, we analyzed the tumor mutational heterogeneity and immune microenvironment in both groups. Results: Two drug resistance gene modules were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that both modules are involved in RNA splicing. The protein-protein interaction network identified 10 hub genes in the brown module LUC7L3, SNRNP70, PRPF3, LUC7L, CLASRP, CLK1, CLK2, U2AF1L4, NXF1, and THOC1) and 13 in the yellow module (PNN, PPWD1, SRRM2, DHX35, DMTF1, SALL4, MTA1, HDAC7, PHC1, ACIN1, HNRNPH1, DDX17, and HDAC6). The prognostic model composed of RNF207, REC8, DFNB59, HOXA2, EPOR, PILRB, LSMEM1, TCIRG1, ABTB1, ZNF276, ZNF540, and DPY19L2 could effectively predict patient prognosis. Genomic analysis revealed that the high- and low-risk groups had different mutation maps. Immune infiltration analysis showed a statistically significant difference in immune infiltration between the high- and low-risk groups, and that the high-risk group may benefit from immunotherapy. Conclusion: In this study, bicalutamide resistance genes and hub genes were identified in PCa, a risk model for predicting the prognosis of patients with PCa was constructed, and the tumor mutation heterogeneity and immune infiltration in high- and low-risk groups were analyzed. These findings offer new insights into ADT resistance targets and prognostic prediction in patients with PCa.

Identifying hub genes and common biological pathways between COVID-19 and benign prostatic hyperplasia by machine learning algorithms.

Background: COVID-19, a serious respiratory disease that has the potential to affect numerous organs, is a serious threat to the health of people around the world. The objective of this article is to investigate the potential biological targets and mechanisms by which SARS-CoV-2 affects benign prostatic hyperplasia (BPH) and related symptoms. Methods: We downloaded the COVID-19 datasets (GSE157103 and GSE166253) and the BPH datasets (GSE7307 and GSE132714) from the Gene Expression Omnibus (GEO) database. In GSE157103 and GSE7307, differentially expressed genes (DEGs) were found using the "Limma" package, and the intersection was utilized to obtain common DEGs. Further analyses followed, including those using Protein-Protein Interaction (PPI), Gene Ontology (GO) function enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Potential hub genes were screened using three machine learning methods, and they were later verified using GSE132714 and GSE166253. The CIBERSORT analysis and the identification of transcription factors, miRNAs, and drugs as candidates were among the subsequent analyses. Results: We identified 97 common DEGs from GSE157103 and GSE7307. According to the GO and KEGG analyses, the primary gene enrichment pathways were immune-related pathways. Machine learning methods were used to identify five hub genes (BIRC5, DNAJC4, DTL, LILRB2, and NDC80). They had good diagnostic properties in the training sets and were validated in the validation sets. According to CIBERSORT analysis, hub genes were closely related to CD4 memory activated of T cells, T cells regulatory and NK cells activated. The top 10 drug candidates (lucanthone, phytoestrogens, etoposide, dasatinib, piroxicam, pyrvinium, rapamycin, niclosamide, genistein, and testosterone) will also be evaluated by the P value, which is expected to be helpful for the treatment of COVID-19-infected patients with BPH. Conclusion: Our findings reveal common signaling pathways, possible biological targets, and promising small molecule drugs for BPH and COVID-19. This is crucial to understand the potential common pathogenic and susceptibility pathways between them.

Metabolic syndrome-related prognostic index: Predicting biochemical recurrence and differentiating between cold and hot tumors in prostate cancer.

Background: The prostate, as an endocrine and reproductive organ, undergoes complex hormonal and metabolic changes. Recent studies have shown a potential relationship between metabolic syndrome and the progression and recurrence of prostate cancer (PCa). This study aimed to construct a metabolic syndrome-related prognostic index (MSRPI) to predict biochemical recurrence-free survival (BFS) in patients with PCa and to identify cold and hot tumors to improve individualized treatment for patients with PCa. Methods: The Cancer Genome Atlas database provided training and test data, and the Gene Expression Omnibus database provided validation data. We extracted prognostic differentially expressed metabolic syndrome-related genes (DEMSRGs) related to BFS using univariate Cox analysis and identified potential tumor subtypes by consensus clustering. The least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression were used to construct the MSRPI. We further validated the predictive power of the MSRPI using KaplanMeier survival analysis and receiver operating characteristic (ROC) curves, both internally and externally. Drug sensitivity was predicted using the half-maximal inhibitory concentration (IC50). Finally, we explored the landscape of somatic mutations in the risk groups. Results: Forty-six prognostic DEMSRGs and two metabolic syndrome-associated molecular clusters were identified. Cluster 2 was more immunogenic. Seven metabolic syndrome-related genes (CSF3R, TMEM132A, STAB1, VIM, DUOXA1, PILRB, and SLC2A4) were used to construct risk equations. The high-risk index was significantly associated with a poor BFS, which was also validated in the validation cohort. The area under the ROC curve (AUC) for BFS at 1-, 3-, and 5- year in the entire cohort was 0.819, 0.785, and 0.772, respectively, demonstrating the excellent predictive power of the MSRPI. Additionally, the MSRPI was found to be an independent prognostic factor for BFS in PCa. More importantly, MSRPI helped differentiate between cold and hot tumors. Hot tumors were associated with the high-risk group. Multiple drugs demonstrated significantly lower IC50 values in the high-risk group, offering the prospect of precision therapy for patients with PCa. Conclusion: The MSRPI developed in this study was able to predict biochemical recurrence in patients with PCa and identify cold and hot tumors. MSRPI has the potential to improve personalized precision treatment.

Comparative efficacy of second-generation androgen receptor inhibitors for treating prostate cancer: A systematic review and network meta-analysis.

Introduction: Second-generation androgen receptor inhibitors (SGARIs), namely enzalutamide, apalutamide, and darolutamide, are good for improving survival outcomes in prostate cancer patients, but some researchers have shown that using SGARIs increases side effects, which complicates clinicians' choice of. Therefore, we performed this network meta-analysis to assess the efficacy and toxicity of several SGARIs in the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), non-metastatic castration-resistant prostate cancer (nmCRPC), and metastatic castration-resistant prostate cancer (mCRPC). Methods: We searched PubMed, EMBASE and Cochrane Library databases from January 2000 to December 2022 to identify randomized controlled studies associated with SGARIs. We use Stata 16.0 and R 4.4.2 for data analysis, hazard ratio (HR) with 95% confidence intervals (CI) were used to assess the results. Results: This meta-analysis included 7 studies with a total of 9488 patients. In mHSPC, enzalutamide and darolutamide had a positive effect on overall survival (OS) (HR, 0.70; 95% CI, 0.59-0.82), but we did not find a difference in their efficacy to improve OS (HR, 1.19; 95% CI, 0.75-1.89). Also in nmCRPC, enzalutamide, apalutamide and darolutamide were beneficial for metastasis-free survival (MFS) (HR, 0.32; 95% CI, 0.25-0.41). Compared to darolutamide, enzalutamide (HR, 0.71; 95% CI, 0.54-0.93) and apalutamide (HR, 0.68; 95% CI, 0.51-0.91) prolonged MFS, but there was no difference in efficacy between enzalutamide and apalutamide (HR, 0.97; 95% CI, 0.73-1.28). Finally in mCRPC, there was no significant difference in indirect effects on OS between pre- and post-chemotherapy enzalutamide (HR, 0.89; 95% CI, 0.70-1.13). However, using enzalutamide before chemotherapy to improve radiographic progression-free survival (rPFS) was a better option (HR, 2.11; 95% CI, 1.62-2.73). Conclusion: The SGARIs used in each trial were beneficial for the primary endpoint in the study. Firstly there was no significant difference in the effect of enzalutamide and darolutamide in improving OS in patients with mHSPC. Secondly improving MFS in patients with nmCRPC was best achieved with enzalutamide and apalutamide. In addition both pre- and post-chemotherapy use of enzalutamide was beneficial for OS in mCRPC patients, but for improving rPFS pre-chemotherapy use of enzalutamide should be preferred.The INPLASY registration number of this systematic review is INPLASY202310084.

A wrinkled nanosurface causes accelerated protein unfolding revealing its critical role in nanotoxicity.

Wrinkles are often found to have a strong influence on the properties of nanomaterials and have attracted extensive research interest. However, the consequences of the use of wrinkled nanomaterials in biological systems remain largely unknown. Here, using molecular dynamics simulations, we studied the interactions of a wrinkled graphene with proteins, using the villin headpiece (HP35) as the representative model. Our results clearly revealed that the wrinkle, especially the wrinkle corner, showed stronger binding affinity to HP35 than the planar surface where HP35 experienced accelerated and more severe unfolding. This is because the transverse translocation of the aromatic residues of the protein is highly confined at the wrinkle corner. The movement of other parts of the protein causes unfolding of the protein secondary structure and releases hydrophobic residues to bind to graphene, causing complete denaturation. Further free energy analyses revealed that this is attributed to the stronger binding affinity of residues to the wrinkle corner than to the planar surface. The present findings provide a deeper understanding of the effect of graphene wrinkles on protein stability. This finding may be generalized to other types of biomolecules and may also guide the design of biomedical nanomaterials through surface structural engineering.

Long noncoding RNAs regulated spermatogenesis in varicocele-induced spermatogenic dysfunction.

OBJECTIVES: To evaluate the expression, potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the pathogenesis of varicocele (VC)-induced spermatogenic dysfunction. MATERIALS AND METHODS: We established a rat model with left experimental VC and divided rats into the sham group, the VC group, and the surgical treatment group (each group, n = 10). Haematoxylin and eosin (HE) staining and sperm quality were analysed to evaluate spermatogenesis function. LncRNA expression profiles were analysed using lncRNA-Seq (each group n = 3) and validated using quantitative real-time polymerase chain reaction (each group n = 10). Correlation analysis and gene target miRNA prediction were used to construct competing endogenous RNA network. The regulated signalling pathway and spermatogenic dysfunction of differentially expressed lncRNAs (DE lncRNAs) were validated by Western blot. RESULTS: HE detection and sperm quality analysis showed that VC could induce spermatogenic dysfunction. Eight lncRNAs were upregulated and three lncRNAs were downregulated in the VC group compared with the sham group and surgical treatment group. The lncRNA of NONRATG002949.2, NONRATG001060.2, NONRATG013271.2, NONRATG022879.2, NONRATG023424.2, NONRATG005667.2 and NONRATG010686.2 were significantly negatively related to sperm quality, while NONRATG027523.1, NONRATG017183.2 and NONRATG023747.2 were positively related to sperm quality. The lncRNAs promote spermatogenic cell apoptosis and inhibit spermatogonia and spermatocyte proliferation and meiotic spermatocytes by regulating the PI3K-Akt signalling pathway. CONCLUSION: DE lncRNAs may be potential biomarkers for predicting the risk of spermatogenic dysfunction in VC and the effect of surgical repair. These DE lncRNAs promote spermatogenic dysfunction by regulating the PI3K-Akt signalling pathway.

A monomolecular platform with varying gated photochromism.

In the development of modern high-performance photoelectric materials, the gated photochromic materials have attracted wide attention. However, the integration of varying signal regulations into gated photochromism to construct efficient photochromic materials is still an urgent necessity. Herein, we designed and synthesized a new gated photoswitching DTEP based on a Schiff base with a diarylethene core. The photochromic properties of compound DTEP can be regulated to different degrees by multiple stimuli, including UV/visible light, Cu2+ and Ni2+. The compound DTEP showed different response abilities to Cu2+ and Ni2+, due to the diverse complexation modes between DTEP and Cu2+ as well as Ni2+. The photochromic properties of compound DTEP could be inhibited completely by the introduction of Cu2+ to form a 1 : 1 complexation, while the weak gated photochromism could be found from the DTEP-Ni2+ complex in a 1 : 2 stoichiometry. Relying on such varying degrees of gated photochromic properties, a new molecular logic circuit was constructed to undertake complicated logical operations.