Efficiency of bladder-sparing strategies for bladder cancer: an umbrella review.

Bladder preservation (BP) has emerged as a clinical alternative to radical cystectomy (RC) for alleviating the substantial physical and psychological burden imposed on localized bladder cancer patients. Nevertheless, disparities persist in the comparative evaluations of BP and RC. We aimed to address the disparities between BP and RC. An umbrella review and meta-analysis were conducted to explore these disparities. We extracted data from meta-analyses and randomized controlled trials (RCTs) selected after searching PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Review Manager 5.4.0 and R x64 4.1.3 were used to evaluate the collected data. Our study included 11 meta-analyses and 3 RCTs. In terms of progression-free survival, all the meta-analyses reported that patients with localized bladder cancer who underwent BP exhibited outcomes comparable to those who underwent RC. Meta-analyses regarding the outcomes of cancer-specific survival (CSS) and overall survival (OS) are controversial. To solve these issues, we conducted a pooled analysis of CSS data, which supported the similarity of CSS between BP and RC with no significant heterogeneity [odds ratio (OR): 1.2; 95% confidence interval (CI): 0.71-2.02; I2 = 26%]. Similarly, the pooled OS results extracted from three RCTs indicated the comparability of OS between BP and RC with no significant heterogeneity (OR: 1.12; 95% CI: 0.41-3.07; I2 = 33%). A combination of umbrella review and meta-analysis results suggested that BP had survival rates comparable to those of RC. We suggest that BP may be a more eligible therapy than RC for patients with localized muscle-invasive bladder cancer. This conclusion warrants further validation through randomized controlled trials.

The implications of single-cell RNA-seq analysis in prostate cancer: unraveling tumor heterogeneity, therapeutic implications and pathways towards personalized therapy.

In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments in the current era, particularly the emerging integration of single-cell and spatiotemporal transcriptomics, have enabled a detailed molecular comprehension of the complex regulation of cell fate. The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine. Currently, single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors. Starting from the perspective of RNA sequencing technology, this review outlined the significance of single-cell RNA sequencing (scRNA-seq) in prostate cancer research, encompassing preclinical medicine and clinical applications. We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies, as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis, treatment, and drug resistance characteristics of prostate cancer. These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer. Furthermore, we explore the potential clinical applications stemming from other single-cell technologies in this review, paving the way for future research in precision medicine.

An endothelial-related prognostic index for bladder cancer patients.

BACKGROUND: Within the tumor microenvironment, endothelial cells hold substantial sway over bladder cancer (BC) prognosis. Herein, we aim to elucidate the impact of endothelial cells on BC patient outcomes by employing an integration of single-cell and bulk RNA sequencing data. METHODS: All data utilized in this study were procured from online databases. R version 3.6.3 and relevant packages were harnessed for the development and validation of an endothelial-associated prognostic index (EPI). RESULTS: EPI was formulated, incorporating six genes (CYTL1, FAM43A, GSN, HSPG2, RBP7, and SLC2A3). EPI demonstrated significant prognostic value in both The Cancer Genome Atlas (TCGA) and externally validated dataset. Functional results revealed a profound association between EPI and endothelial cell functionality, as well as immune-related processes. Our findings suggest that patients with low-risk EPI scores are more likely to respond positively to immunotherapy, as indicated by immune checkpoint activity, immune infiltration, tumor mutational burden, stemness index, TIDE, and IMvigor210 analyses. Conversely, individuals with high-risk EPI scores exhibited heightened sensitivity to cisplatin, docetaxel, and gemcitabine treatment regimens. CONCLUSION: We have effectively discerned pivotal genes from the endothelial cell perspective and constructed an EPI for BC patients, thereby offering promising prospects for precision medicine.

Effects of main active components of rosemary on growth performance, meat quality and lipid metabolism in finishing pigs.

Rosemary extracts have been widely used as feed additives in recent years. This study aimed to investigate the effects of rosmarinic acid (RA) and ursolic acid (UA), the main active components of rosemary, on growth performance, meat quality and lipid metabolism in finishing pigs. A total of 72 finishing pigs (Landrace; initial age of 150 d) were randomly divided into 3 treatments with 8 replicates of 3 pigs each, and fed a basal diet or diet containing 500 mg/kg of RA or UA. The results showed that dietary supplementation of RA or UA had no significant effect on the growth performance and carcass traits of finishing pigs (P > 0.05). However, both RA and UA significantly increased the triglyceride (TG) level in soleus muscle (P < 0.001). Supplementation of RA increased the expression of genes related to lipogenesis and transport including fatty acid synthase (FAS) (P < 0.001), sterol regulatory element binding protein-1c (SREBP1c) (P < 0.001) and peroxisome proliferator-activated receptor γ (PPARγ) (P < 0.05), while UA increased the expression of fatty acid transport protein 1 (FATP1), a gene related to lipid uptake (P < 0.05). However, RA reduced the expression of adipogenesis-related gene acetyl-coenzyme A carboxylase α (ACCα) (P < 0.01). Characterization of cecal microbiota indicated that RA increased the microbial richness (chao 1, P < 0.001) and diversity (observed species, P < 0.01). Further analysis of the genera revealed that RA increased the relative abundance of Bacteroides and g-UCG-005 (P < 0.05), and UA enriched Prevotella (P < 0.001). Correlation analysis showed that g-UCG-005 was positively correlated with the expression of FAS, carnitine palmitoyl transferase 1B (CPT1B), SREBP1c and PPARγ (P < 0.01). In conclusion, dietary supplementation of RA or UA may increase fat deposition in muscle of finishing pigs by regulating lipid metabolism and gut microbiota.

An SCN1A gene missense variant in a Chinese Tujia ethnic family with genetic epilepsy with febrile seizures plus.

Genetic epilepsy with febrile seizures plus (GEFSP) is a familial epileptic syndrome that is genetically heterogeneous and inherited in an autosomal dominant form in most cases. To date, at least seven genes have been reported to associate with GEFSP. This study aimed to identify the disease-causing variant in a Chinese Tujia ethnic family with GEFSP by using whole exome sequencing, Sanger sequencing, and in silico prediction. A heterozygous missense variant c.5725A>G (p.T1909A) was identified in the sodium voltage-gated channel alpha subunit 1 gene (SCN1A) coding region. The variant co-segregated with the GEFSP phenotype in this family, and it was predicted as disease-causing by multiple in silico programs, which was proposed as the genetic cause of GEFSP, further genetically diagnosed as GEFSP2. These findings expand the genetic and phenotypic spectrum of GEFSP and should contribute to genetic diagnoses, personalized therapies, and prognoses.

New Insights of Biological Functions of Natural Polyphenols in Inflammatory Intestinal Diseases.

The intestine is critically crucial for nutrient absorption and host defense against exogenous stimuli. Inflammation-related intestinal diseases, including enteritis, inflammatory bowel disease (IBD), and colorectal cancer (CRC), are heavy burdens for human beings due to their high incidence and devastating clinical symptoms. Current studies have confirmed that inflammatory responses, along with oxidative stress and dysbiosis as critical pathogenesis, are involved in most intestinal diseases. Polyphenols are secondary metabolites derived from plants, which possess convincible anti-oxidative and anti-inflammatory properties, as well as regulation of intestinal microbiome, indicating the potential applications in enterocolitis and CRC. Actually, accumulating studies based on the biological functions of polyphenols have been performed to investigate the functional roles and underlying mechanisms over the last few decades. Based on the mounting evidence of literature, the objective of this review is to outline the current research progress regarding the category, biological functions, and metabolism of polyphenols within the intestine, as well as applications for the prevention and treatment of intestinal diseases, which might provide ever-expanding new insights for the utilization of natural polyphenols.

Simultaneously enhancing the photovoltaic parameters of ternary organic solar cells by incorporating a fused ring electron acceptor.

The ternary strategy has been recognized as an effective method to improve the photovoltaic performance of organic solar cells (OSCs). In ternary OSCs, the complementary or broadened absorption spectrum, optimized morphology, and enhanced photovoltaic performance could be obtained by selecting a third rational component for the host system. In this work, a fused ring electron acceptor named BTMe-C8-2F, which possesses a high-lying lowest unoccupied molecular orbital (LUMO) energy level and a complementary absorption spectrum to PM6:Y6, was introduced to a PM6:Y6 binary system. The ternary blend film PM6:Y6:BTMe-C8-2F showed high and more balanced charge mobilities, and low charge recombination. Therefore, the OSC based on the PM6:Y6:BTMe-C8-2F (1 : 1.2 : 0.3, w/w/w) blend film achieved the highest power conversion efficiency (PCE) of 17.68%, with an open-circuit voltage (VOC) of 0.87 V, a short-circuit current (JSC) of 27.32 mA cm-2, and a fill factor (FF) of 74.05%, which are much higher than the binary devices of PM6:Y6 (PCE = 15.86%) and PM6:BTMe-C8-2F (PCE = 11.98%). This work provides more insight into the role of introducing a fused ring electron acceptor with a high-lying LUMO energy level and complementary spectrum for simultaneously enhancing the VOC and JSC to promote the performance of ternary OSCs.

Experimental demonstration of 201.6-Gbit/s coherent probabilistic shaping QAM transmission with quantum noise stream cipher over a 1200-km standard single mode fiber.

A probabilistic shaping (PS) quadrature amplitude modulation (QAM) based on Y-00 quantum noise stream cipher (QNSC) has been proposed. We experimentally demonstrated this scheme with data rate of 201.6Gbit/s over a 1200-km standard single mode fiber (SSMF) under a 20% SD-FEC threshold. Accounting for the 20% FEC and 6.25% pilot overhead, the achieved net data rate is ∼160Gbit/s. In the proposed scheme, a mathematical cipher (Y-00 protocol) is utilized to convert the original low-order modulation PS-16 (22 × 22) QAM into ultra-dense high-order modulation PS-65536 (28 × 28) QAM. Then, the physical randomness of quantum (shot) noise at photodetection and amplified spontaneous emission (ASE) noise from optical amplifiers are employed to mask the encrypted ultra-dense high-order signal for further improving the security. We further analyze the security performance by two metrics known in the reported QNSC systems, namely the number of masked signals (NMS) of noise and the detection failure probability (DFP). Experimental results show it is difficult or even impossible to extract transmission signals from quantum or ASE noise for an eavesdropper (Eve). We believe that the proposed PS-QAM/QNSC secure transmission scheme has the potential to be compatible with existing high-speed long-distance optical fiber communication systems.

Identification of endothelial-related molecular subtypes for bladder cancer patients.

Background: Bladder cancer (BC) is a disease with significant heterogeneity and poor prognosis. The prognosis and therapeutic response of BC patients are significantly influenced by endothelial cells in the tumor microenvironment. In order to understand BC from the perspective of endothelial cells, we orchestrated molecular subtypes and identified key genes. Methods: Single-cell and bulk RNA sequencing data were extracted from online databases. R and its relative packages were used to analyze these data. Cluster analysis, prognostic value analysis, function analysis, immune checkpoints, tumor immune environment and immune prediction were conducted. Results: Five endothelial-related genes (CYTL1, FAM43A, HSPG2, RBP7, and TCF4) divided BC patients in the TCGA, GSE13507, and GSE32894 datasets into two clusters, respectively. In prognostic value analysis, patients in the cluster 2 were substantially associated with worse overall survival than those in the cluster 1 according to the results of TCGA, GSE13507 and GSE32894 datasets. In the results of functional analysis, the endothelial-related clusters was enriched in immune-related, endothelial-related and metabolism-related pathways. Samples in the cluster 1 had a statistically significant increase in CD4+ T cells and NK-cell infiltration. Cluster 1 was positively correlated with the cancer stem score and tumor mutational burden score. The results of immune prediction analysis indicated that 50.6% (119/235) of patients in the cluster 1 responded to immunotherapy, while the response rate in the cluster 2 decreased to 16.7% (26/155). Conclusion: In this study, we categorized and discovered distinctive prognosis-related molecular subtypes and key genes from the perspective of endothelial cells at the genetic level by integrating single-cell and bulk RNA sequencing data, primarily to provide a roadmap for precision medicine.

Novel compound heterozygous variants in the USH2A gene associated with autosomal recessive retinitis pigmentosa without hearing loss.

Background: Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies characterized by the primary degeneration of rod photoreceptors and the subsequent loss of cone photoreceptors because of cell death. It is caused by different mechanisms, including inflammation, apoptosis, necroptosis, pyroptosis, and autophagy. Variants in the usherin gene (USH2A) have been reported in autosomal recessive RP with or without hearing loss. In the present study, we aimed to identify causative variants in a Han-Chinese pedigree with autosomal recessive RP. Methods: A six-member, three-generation Han-Chinese family with autosomal recessive RP was recruited. A full clinical examination, whole exome sequencing, and Sanger sequencing, as well as co-segregation analysis were performed. Results: Three heterozygous variants in the USH2A gene, c.3304C>T (p.Q1102*), c.4745T>C (p.L1582P), and c.14740G>A (p.E4914K), were identified in the proband, which were inherited from parents and transmitted to the daughters. Bioinformatics analysis supported the pathogenicity of the c.3304C>T (p.Q1102*) and c.4745T>C (p.L1582P) variants. Conclusions: Novel compound heterozygous variants in the USH2A gene, c.3304C>T (p.Q1102*) and c.4745T>C (p.L1582P), were identified as the genetic causes of autosomal recessive RP. The findings may enhance the current knowledge of the pathogenesis of USH2A-associated phenotypes, expand the spectrum of the USH2A gene variants, and contribute to improved genetic counseling, prenatal diagnosis, and disease management.

A novel endothelial-related prognostic index by integrating single-cell and bulk RNA sequencing data for patients with kidney renal clear cell carcinoma.

Background: Endothelial cells in the tumor microenvironment play an important role in the development of kidney renal clear cell carcinoma (KIRC). We wanted to further identify the function of endothelial cells in KIRC patients by integrating single-cell and bulk RNA sequencing data. Methods: Online databases provide the original data of this study. An endothelial-related prognostic index (ERPI) was constructed and validated by R version 3.6.3 and relative packages. Results: The ERPI consisted of three genes (CCND1, MALL, and VWF). Patients with high ERPI scores were significantly correlated with worse prognosis than those with low ERPI scores in the TCGA training group, TCGA test group, and GSE29609 group. A positive correlation was identified between the ERPI score and poor clinical features. The results of functional analysis indicated that ERPI was significantly associated with immune-related activities. We suggested that patients with high ERPI scores were more likely to benefit from immunotherapy based on the results of immune checkpoints, tumor microenvironment, stemness index, and TCIA, while patients with low ERPI scores were sensitive to gemcitabine, docetaxel, paclitaxel, axitinib, pazopanib, sorafenib, and temsirolimus according to the results of the "pRRophetic" algorithm. Therefore, this ERPI may help doctors choose the optimal treatment for patients with KIRC. Conclusion: By integrating single-cell and bulk RNA sequencing data from KIRC patients, we successfully identified the key genes from the perspective of endothelial cells in the tumor microenvironment and constructed ERPIs that had positive implications in precision medicine.

lncRNA SSTR5-AS1 Predicts Poor Prognosis and Contributes to the Progression of Esophageal Cancer.

Esophageal cancer (ESCA), as a common cancer worldwide, is a main cause of cancer-related mortality. Long noncoding RNAs (lncRNAs) have been shown in an increasing number of studies to be capable of playing an important regulatory function in human malignancies. Our study is aimed at delving into the prognostic value and potential function of lncRNA SSTR5-AS1 (SSTR5-AS1) in ESCA. The gene expression data of 182 ESCA samples from TCGA and 653 nontumor specimens from GTEx. The expressions of SSTR5-AS1 were analyzed. We investigated whether there was a correlation between the expression of SSTR5-AS1 and the clinical aspects of ESCA. In order to compare survival curves, the Kaplan-Meier method together with the log-rank test was utilized. The univariate and multivariate Cox regression models were used to analyze the data in order to determine the SSTR5-AS1 expression's significance as a prognostic factor in ESCA patients. In order to investigate the level of SSTR5-AS1 expression in ESCA cells, RT-PCR was utilized. CCK-8 trials served as a model for the loss-of-function tests. In this study, we found that the expressions of SSTR5-AS1 were increased in ESCA specimens compared with nontumor specimens. According to the ROC assays, high SSTR5-AS1 expression had an AUC value of 0.7812 (95% CI: 0.7406 to 0.8217) for ESCA. Patients who had a high level of SSTR5-AS1 expression had a lower overall survival rate than those who had a low level of SSTR5-AS1 expression. In addition, multivariate analysis suggested that SSTR5-AS1 was an independent predictor of overall survival for ESCA patients. Moreover, RT-PCR experiments indicated that SSTR5-AS1 expression was distinctly increased in three ESCA cells compared with HET1A cells. CCK-8 experiments indicated that silence of SSTR5-AS1 distinctly inhibited the proliferation of ESCA cells. Overall, ESCA patients with elevated SSTR5-AS1 had a worse chance of survival, suggesting it could be used as a prognostic and diagnostic biomarker for ESCA.

M7G-related molecular subtypes can predict the prognosis and correlate with immunotherapy and chemotherapy responses in bladder cancer patients.

BACKGROUND: N7-methylguanosine (m7G) is closely associated with tumor prognosis and immune response in many cancer types. The correlation between m7G and bladder cancer (BC) needs further study. We aimed to orchestrate molecular subtypes and identify key genes for BC from the perspective of m7G. METHODS: RNA-seq and clinical data of BC patients were extracted from TCGA and GSE13507 datasets. The patients were subtyped by "ConsensusClusterPlus" and "limma." The clusters were validated by the Kaplan‒Meier curves, univariable and multivariate Cox regression models, the concordance index, and calibration curves. The immunotherapy response was evaluated by immune checkpoints, immune infiltration, TIDE score, and IMvigor210 cohort. Genomics of Drug Sensitivity in Cancer was utilized to predict the chemotherapy response between the clusters. RESULTS: The m7G-related cluster was ultimately established by EIF4G1, NUDT11, NUDT10, and CCNB1. The independent prognostic value of the m7G-related cluster was validated by the TCGA and GSE13507 datasets. The cluster was involved in immune-associated pathways, such as neutrophil degranulation, antigen processing cross-presentation, and signaling by interleukins pathways. Meanwhile, cluster 2 was positively correlated with many immune checkpoints, such as CD274, CTLA4, HAVCR2, LAG3, PDCD1, and PDCD1LG2. The cluster 2 was significantly correlated with a higher TIDE score than the cluster 1. Furthermore, in the IMvigor210 cohort, patients in the cluster 1 had a higher response rate than those in the cluster 2. Patients in the cluster 2 were sensitive to many chemotherapies. CONCLUSIONS: We successfully determined molecular subtypes and identified key genes for BC from the perspective of m7G, thereby providing a roadmap for the evolution of immunotherapy and precision medicine.