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.

Co-inoculation of fungi and desert cyanobacteria facilitates biological soil crust formation and soil fertility.

The inoculation of cyanobacteria for enriching soil nutrients and forming biological soil crusts (BSCs) is considered an effective means to restore degraded soil. However, there are limited studies on the application of co-inoculation of fungi and cyanobacteria for degraded soil remediation. In this study, a high exopolysaccharide-secreting fungi Zh2 was isolated from lichen BSCs in Hobq Desert, and co-inoculated with a cyanobacterial strain identified as Phormidium tenue in different proportions to form BSCs on sand during a 35 days incubation period. Results revealed significant differences in crust biomass and soil properties among crusts with different cyanobacterial/fungal inoculation ratios. Microbial biomass, soil nutrient content and enzyme activities in crusts co-inoculated with cyanobacteria and fungi were higher than those inoculated with cyanobacteria and fungi alone. The inoculation of cyanobacteria contributed to the fulvic-like accumulation, and the inoculated fungi significantly increased the humic-like content and soil humification. Redundancy analysis showed that the inoculation of cyanobacteria was positively correlated with the activities of urease and phosphatase, and the content of fulvic-like. Meanwhile, the inoculation of fungi was positively correlated with the contents of total carbon, total nitrogen and humic-like, the activities of catalase and sucrase. Cyanobacteria and fungi play distinct roles in improving soil fertility and accumulating dissolved organic matter. This study provides new insights into the effects of cyanobacteria and fungi inoculations on the formation and development of cyanobacterial-fungus complex crusts, offering a novel method for accelerating induced crust formation on the surface of sand.

Establishment of bladder cancer spheroids and cultured in microfluidic platform for predicting drug response.

Cisplatin-containing combination chemotherapy has been used as the standard treatment for bladder cancer patients at advanced stage. However, nearly 50% of patients are nonresponders. To guide the selection of more effective chemotherapeutic agents, a bladder cancer spheroids microfluidic drug sensitivity analysis system was established in this study. Bladder cancer spheroids were established and successfully cultured in a customized microfluidic device to assess their response to different chemotherapeutic agents. The in vitro drug sensitivity results were also compared to patient-derived xenograft (PDX) models and clinical responses of patients. As a result, bladder cancer spheroids faithfully recapitulate the histopathological and genetic features of their corresponding parental tumors. Furthermore, the in vitro drug sensitivity outcomes of spheroids (n = 8) demonstrated a high level of correlation with the PDX (n = 2) and clinical response in patients (n = 2). Our study highlights the potential of combining bladder cancer spheroids and microfluidic devices as an efficient and accurate platform for personalized selection of chemotherapeutic agents.

An efficient and simple approach to remove Cd(II) in aqueous solution by using rice straw biochar: performance and mechanisms.

In recent years, cadmium pollution in water environment has become an environmental problem that could not be ignored. As a porous carbon rich solid material, biochar is an environment-friendly new material because of its ultra-high adsorption capacity and strong chemical stability. In this study, rice straw biochar (RS-Biochar) was successfully prepared at different temperatures for removal of Cd(II) from aqueous solution. Through a series of characterization and adsorption experiments, the adsorption principle of Cd(II) by RS-Biochar was deeply studied. The results showed that RS-Biochar prepared at 600 °C (BioC600) has high specific surface area (232.6 m2/g) and shows high Cd(II) removal rate of 91.23% with the maximum Cd(II) adsorption capacity of 8.62 mg/g. The Langmuir model fit well to describe the adsorption process of Cd(II) on the BioC600. The mechanism analysis showed that hydroxyl and carboxyl groups on the biochar surface were concerned in the removal of Cd(II). The formation of CdCO3 in the adsorption process was also be proven. Importantly, RS-Biochar could be conveniently produced with needed scale, displaying a promising approach for remediating Cd(II)-contaminated water environment and a huge application potential.

Orthostatic Hypotension Promotes the Progression From Mild Cognitive Impairment to Dementia in Type 2 Diabetes Mellitus.

CONTEXT: In type 2 diabetes mellitus (T2DM), orthostatic hypotension (OH) is associated with cognition, but the mechanisms governing the link between OH and cognition are still unclear. OBJECTIVE: We sought to analyze Alzheimer's disease (AD) biomarkers and the part of complement proteins in modulating the association of OH with cognitive impairment and examine whether OH could accelerate the clinical progression of mild cognitive impairment (MCI) to dementia in T2DM. METHODS: We recruited patients with T2DM with MCI and collected general healthy information and blood samples. Complement proteins of astrocyte-derived exosomes were isolated and AD biomarkers of neuronal cell-derived exosomes isolated were quantified by enzyme-linked immunosorbent assay. Cognitive assessments were performed at patient enrollment and follow-up. RESULTS: Mediation analysis showed that the influence of OH on cognition in T2DM was partly mediated by baseline AD biomarkers and complement proteins. Cox proportional-hazards regression proved the OH group had a higher risk of developing dementia compared to the T2DM without OH group. CONCLUSION: In T2DM with MCI patients, AD biomarkers and complement proteins mediate the effects of OH on cognitive impairment and OH may be a risk factor of progression from MCI to dementia in T2DM.

Value of digital rectal examination in patients with suspected prostate cancer: a prospective cohort analysis study.

Background: Digital rectal examination (DRE) is a straightforward, cost-effective, practical, and time-honored physical examination method that plays a valuable role in the detection of prostate cancer (PCa). Nevertheless, with the advent of the prostate-specific antigen (PSA) era, the necessity of performing DRE has become a subject of debate. Our aim was to investigate the diagnostic efficacy and adjunctive role of DRE in a population (Prostate Imaging Reporting and Data System (PI-RADS), PI-RADS ≥3 or PSA ≥4 ng/mL) suspected of PCa. Methods: Five hundred and ninety-seven patients with suspected PCa requiring referral for biopsy were prospectively enrolled consecutively from February 2020 to May 2021. All patients received DRE and corresponding clinical diagnosis by a urologist before biopsy. According to the collected clinical and pathological information, the diagnostic performance of DRE in different PSA stratifications, and its association with tumor location and Gleason score (GS) were statistically analyzed. Results: Among patients with suspected cancer, the diagnostic accuracy of DRE was 63.45%. Compared with central zone or transition zone tumors, the recall rate of peripheral zone PCa with DRE-positive results was higher (65.50% vs. 34.55%). DRE-positive results were significantly correlated with GS ≥7 PCa (P<0.001), and the average GS of DRE-positive PCa patients was significantly higher than that of DRE-negative (7.92 vs. 7.11, P<0.001). Conclusions: DRE may help physicians further judge the necessity of biopsy in patients with elevated PSA, and preliminarily estimate the location and invasiveness of the tumor. However, it is still necessary to explore the value of DRE in a normal PSA population.

Functional biochar fabricated from red mud and walnut shell for phosphorus wastewater treatment: Role of minerals.

A novel functional biochar (BC) was prepared from industrial waste red mud (RM) and low-cost walnut shell by one facile-step pyrolysis method to adsorb phosphorus (P) in wastewater. The preparation conditions for RM-BC were optimized using Response Surface Methodology. The adsorption characteristics of P were investigated in batch mode experiments, while a variety of techniques were used to characterize RM-BC composites. The impact of key minerals (hematite, quartz, and calcite) in RM on the P removal efficiency of the RM-BC composite was studied. The results showed that RM-BC composite produced at 320 °C for 58 min, with a 1:1 mass ratio of walnut shell and RM, had a maximum P sorption capacity of 15.48 mg g-1, which was more than double that of the raw BC. The removal of P from water was found to be facilitated significantly by hematite, which forms Fe-O-P bonds, undergoes surface precipitation, and exchanges ligands. This research provides evidence for the effectiveness of RM-BC in treating P in water, laying the foundation for future scaling-up trials.

Complement proteins in serum astrocyte-derived exosomes are associated with mild cognitive impairment in type 1 diabetes mellitus patients.

BACKGROUND: The complement system plays a crucial role in cognitive impairment. The aim of this study is to investigate the correlation between the complement proteins levels in serum astrocyte-derived exosomes (ADEs) and mild cognitive impairment (MCI) in type 1 diabetes mellitus (T1DM) patients. METHODS: In this cross-sectional study, the patients with immune-mediated T1DM were enrolled. Healthy subjects matched for age and sex with T1DM patients were selected as controls. The cognitive function was evaluated by a Beijing version of the Montreal Cognitive Assessment (MoCA) questionnaire. The complement proteins including C5b-9, C3b and Factor B in serum ADEs were measured by ELISA kits. RESULTS: This study recruited 55 subjects immune-mediated T1DM patients without dementia, including 31 T1DM patients with MCI, 24 T1DM patients without MCI. 33 healthy subjects were enrolled as controls. The results showed higher complement proteins including C5b-9, C3b and Factor B levels in ADEs from T1DM patients with MCI than those in the controls (P < 0.001, P < 0.001, P = 0.006) and T1DM patients without MCI (P = 0.02, P = 0.02, P = 0.03). The C5b-9 levels in ADEs were independently associated with MCI in T1DM patients(OR: 1.20, 95% CI: 1.00-1.44, P = 0.04). The C5b-9 levels in ADEs were significantly correlated with global cognitive scores (ß = -0.360, P＜0.001) and visuo-executive (ß = -0.132, P＜0.001), language(ß = -0.036, P = 0.026) and delayed recall score (ß = -0.090,P = 0.007). There was no correlation between the C5b-9 levels in ADEs and the fasting glucose, HbA1c, fasting c-peptide and GAD65 antibody in T1DM patients. Furthermore, the C5b-9, C3b and Factor B levels in ADEs exhibited a fair combined diagnostic value for MCI, with an area under the curve of 0.76 (95% CI: 0.63-0.88, P = 0.001). CONCLUSION: The elevated C5b-9 levels in ADEswere significantly associated with theMCI in T1DM patients. The C5b-9 in ADEs may be used as a marker of MCI in T1DM patients.

Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA is a prolonged state before clinical arthritis and RA develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due to the breakdown of immunologic self-tolerance. As early treatment initiation before the onset of polyarthritis may achieve sustained remission, optimize clinical outcomes, and even prevent RA progression, the pre-clinical RA stage is showing the prospect to be the window of opportunity for RA treatment. Growing evidence has shown the role of the gut microbiota in inducing systemic inflammation and polyarthritis via multiple mechanisms, which may involve molecular mimicry, impaired intestinal barrier function, gut microbiota-derived metabolites mediated immune regulation, modulation of the gut microbiota's effect on immune cells, intestinal epithelial cells autophagy, and the interaction between the microbiome and human leukocyte antigen alleles as well as microRNAs. Since gut microbiota alterations in pre-clinical RA have been reported, potential therapies for modifying the gut microbiota in pre-clinical RA, including natural products, antibiotic therapy, fecal microbiota transplantation, probiotics, microRNAs therapy, vitamin D supplementation, autophagy inducer-based treatment, prebiotics, and diet, holds great promise for the successful treatment and even prevention of RA via altering ongoing inflammation. In this review, we summarized current studies that include pathogenesis of gut microbiota in RA progression and promising therapeutic strategies to provide novel ideas for the management of pre-clinical RA and possibly preventing arthritis progression.

Does Moses technology enhance the efficiency and outcomes of regular holmium laser lithotripsy? Results of a pooled analysis of comparative studies.

Holmium laser lithotripsy is currently the optimum standard for surgical treatment of upper urinary calculi. This study aims to evaluate the clinical efficacy and safety of Moses compared with conventional holmium laser lithotripsy for the treatment of patients with upper urinary calculi. We conducted a systematic search using multiple databases (PubMed/Medline, Scopus, Web of Science, and ClinicalTrials.gov) until June 2022. Clinical trials comparing Moses and conventional holmium laser lithotripsy were included. Analysis was performed using RevMan version 5.4.4 software. Four studies with 892 patients were included. There were no significant differences regarding stone-free rate (mean difference [MD] 1.19, 95% CI 0.54, 2.64, p = 0.66), operative time (MD - 9.31, 95% CI - 21.11, 2.48, p = 0.12), fragmentation time (MD - 1.71, 95% CI - 11.81, 8.38, p = 0.74), total energy used (MD 1.23, 95% CI - 0.44, 2.90, p = 0.15), auxiliary procedures (MD 0.38, 95% CI 0.08, 1.90, p = 0.24), and overall complications (odds ratio [OR] 0.70, 95% CI 0.30, 1.66, p = 0.42) between the groups. However, the laser working time (MD - 0.94, 95% CI - 1.20, - 0.67, p < 0.001) of Moses technology was shorter than that of conventional technology. Moses technology has similar outcomes to regular technology in terms of safety and efficacy. Given the higher operating costs of the Moses technology, further study is required to determine whether there are benefits to this new technology.

Cellular landscape of tumour microenvironment in prostate cancer.

Prostate cancer is still a public health priority in men and the impact of this disease will be more pronounced with the ageing of the world's population. Clinical heterogeneity of prostate cancer is reflected in spatial and clonal genomic diversity. Accumulating evidence demonstrates that the malignant behaviour of cancer is not only attributed to cancer cells but also fundamentally affected by stromal activity and controlled by various mechanisms of the tumour microenvironment. Data on prostate cancer in this study was derived from seven GEO datasets and the TCGA database. We analyzed the tumour microenvironment of prostate cancer in terms of clinical process, T stage and Gleason score using EPIC and xCell algorithms. We also analyzed the common immune checkpoints. In this study, we confirmed remarkable tumour tissue remodelling in the development of prostate cancer and further demonstrated the importance of cancer-related fibroblasts in the biochemical recurrence and metastasis for patients with prostate cancer undergoing radical radiotherapy or prostatectomy. In addition, we found that NRP1, CD200, TNFSF18 and CD80 might be the potential targets for prostate cancer.

An autophagy-related gene prognostic index predicting biochemical recurrence, metastasis, and drug resistance for prostate cancer.

Given the dual role of autophagy presenting in tumorigenesis and inhibition, we established an autophagy-related gene prognostic index (ARGPI) with validation to well predict the biochemical recurrence (BCR), metastasis, as well as chemoresistance for patients with prostate cancer (PCa) who underwent radical radiotherapy or prostatectomy. Then, Lasso and COX regression was used to develop the ARGPI. We performed the whole analyses through R packages (version 3.6.3). Secreted phosphoprotein 1 (SPP1), single-minded 2 (SIM2), serine protease inhibitor b5 (SERPINB5), aldehyde dehydrogenase 2 (ALDH2), and acyl-CoA synthetase long-chain 3 (ACSL3) were eventually used to establish the ARGPI score. Patients were divided into two different-risk groups based on the median ARGPI score, high-risk patients with a higher risk of BCR than low-risk patients (hazard ratio [HR]: 5.46, 95% confidence interval [CI]: 3.23-9.24). The risk of metastasis of high-risk patients was higher than low-risk patients (HR: 11.31, 95% CI: 4.89-26.12). In The Cancer Genome Atlas (TCGA) dataset, we observed similar prognostic value of ARGPI in terms of BCR-free survival (HR: 1.79, 95% CI: 1.07-2.99) and metastasis-free survival (HR: 1.80, 95% CI: 1.16-2.78). ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance. Analysis of gene set enrichment analysis (GSEA) indicated that patients in the high-risk group were significantly positively related to interleukin (IL)-18 signaling pathway. Moreover, ARGPI score was significantly related to cancer-related fibroblasts (CAFs; r = 0.36), macrophages (r = 0.28), stromal score (r = 0.38), immune score (r = 0.35), estimate score (r = 0.39), as well as tumor purity (r = -0.39; all P < 0.05). Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene. In conclusion, we found that ARGPI could predict BCR, metastasis, and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.

Identification of senescence-related molecular subtypes and key genes for prostate cancer.

We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 (SFRP4), DNA topoisomerase II alpha (TOP2A), pleiotrophin (PTN), family with sequence similarity 107 member A (FAM107A), C-X-C motif chemokine ligand 14 (CXCL14), prostate androgen-regulated mucin-like protein 1 (PARM1), leucine zipper protein 2 (LUZP2), cluster of differentiation 38 (CD38), cartilage oligomeric matrix protein (COMP), vestigial-like family member 3 (VGLL3), apolipoprotein E (APOE), and aldehyde dehydrogenase 2 family member (ALDH2), were eventually used to subtype PCa patients from The Cancer Genome Atlas (TCGA) database and GSE116918, and the molecular subtypes showed good correlations with clinical features. In terms of the tumor immune environment (TME) analysis, compared with cluster 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells scored lower in cluster 2 in TCGA database. There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence (BCR)-free survival for PCa patients undergoing RP. For the GSE116918 database, cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores than cluster 1; in addition, patients with high levels of CAFs, stromal scores, immune scores, and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR. Based on the median of differentially expressed checkpoints, high expression of CD96, hepatitis A virus cellular receptor 2 (HAVCR2), and neuropilin 1 (NRP1) in GSE116918 and high expression of CD160 and tumor necrosis factor (ligand) superfamily member 18 (TNFSF18) in TCGA database were associated with a significantly higher risk of BCR than their counterparts. In conclusion, we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.

Prognostic Utility of the Modified Glasgow Prognostic Score in Urothelial Carcinoma: Outcomes from a Pooled Analysis.

Background: Many studies explored the prognostic value of the modified Glasgow Prognostic Score (mGPS) in urothelial carcinoma (UC), but the results are controversial. This study aimed to quantify the relationship between pretreatment mGPS and survival in patients with UC. Methods: A systematic literature search was conducted using Embase, PubMed, and Web of Science to identify eligible studies published before August 2022. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the association between pretreatment mGPS and the prognosis of UC. Results: Thirteen eligible studies involving 12,524 patients were included. A high mGPS was significantly associated with poor overall survival (mGPS 1/0: HR = 1.33, 95% CI 1.12−1.58, p = 0.001; mGPS 2/0: HR = 2.02, 95% CI 1.43−2.84, p < 0.0001), progression-free survival (mGPS 1/0: HR = 1.26, 95% CI 1.03−1.53, p = 0.021; mGPS 2/0: HR = 1.76, 95% CI 1.12−2.77, p = 0.013), recurrence-free survival (mGPS 1/0: HR = 1.36, 95% CI 1.18−1.56, p < 0.0001; mGPS 2/0: HR = 1.70, 95% CI 1.44−2.000, p < 0.0001), and cancer-specific survival (mGPS 2/0: HR = 1.81, 95% CI 1.30−2.52, p < 0.0001). A subgroup analysis of OS also yielded similar results. Conclusions: Evidence suggests that high pretreatment mGPS in UC is closely related to poor survival. Pre-treatment mGPS is a powerful independent prognostic factor in patients with UC.

Spindle and kinetochore-associated complex subunit 3 could serve as a prognostic biomarker for prostate cancer.

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore that is required for proper chromosomal segregation and cell division. However, little is known regarding the probable mechanism of SKA3, particularly in terms of prostate cancer (PCA) progression. Multiple databases, including TCGA and GTEx, were utilized to examine the expression of SKA3 in PCA patients and to shed light on the clinical significance and potential mechanism of SKA3 in the onset and progression of PCA. The biological function of SKA3 was evaluated in vitro using RT-qPCR and the CCK8 assay. For statistical analysis, the R 3.6.3 software and its associated packages were utilized. SKA3 was shown to be considerably elevated in PCA patients and was linked to a shorter progress free interval (PFI). Furthermore, we discovered that SKA3 mRNA expression was higher in PCA cells than in normal cells, and inhibition of SKA3 could clearly reduce PCA cell proliferation using the CCK8 assay. Finally, SKA3 could be used as a predictive biomarker in PCA patients.

A cellular senescence-related gene prognostic index for biochemical recurrence and drug resistance in patients with prostate cancer.

In this study, we aimed to establish a novel cellular senescence-related gene prognostic index (CSG PI) to predict biochemical recurrence (BCR) and drug resistance in patients with prostate cancer (PCa) undergoing radical radiotherapy or prostatectomy. We performed all analyses using R version 3.6.3 and its suitable packages. Cytoscape 3.8.2 was used to establish a network of transcription factors and competing endogenous RNAs. Three cellular senescence-related genes were used to establish the CSGPI. We observed that CSGPI was an independent risk factor for BCR in PCa patients (HR: 2.62; 95% CI: 1.55-4.44), consistent with the results of external validation (HR: 1.88; 95% CI: 1.12-3.14). The CSGPI had a moderate diagnostic effect on drug resistance (AUC: 0.812, 95% CI: 0.586-1.000). The lncRNA PART1 was significantly associated with BCR (HR: 0.46; 95% CI: 0.27-0.77), and might modulate the mRNA expression of definitive genes through interactions with 57 miRNAs. Gene set enrichment analysis indicated that CSGPI was closely related to ECM receptor interaction, focal adhesion, TGF beta signaling pathway, pathway in cancer, regulation of actin cytoskeleton, and so on. Immune checkpoint analysis showed that PDCD1LG2 and CD96 were significantly higher in the BCR group compared to non-BCR group, and patients with higher expression of CD96 were more prone to BCR than their counterparts (HR: 1.79; 95% CI: 1.06-3.03). In addition, the CSGPI score was significantly associated with the mRNA expression of HAVCR2, CD96, and CD47. Analysis of mismatch repair and methyltransferase genes showed that DNMT3B was more highly expressed in the BCR group and that patients with higher expression of DNMT3B experienced a higher risk of BCR (HR: 2.08; 95% CI: 1.23-3.52). We observed that M1 macrophage, CD8+ T cells, stromal score, immune score, and ESTIMATE score were higher in the BCR group. In contrast, tumor purity was less scored in the BCR group. Spearman analysis revealed a positive relationship between CSGPI and M1 macrophages, CD4+ T cells, dendritic cells, stromal score, immune score, and ESTIMATE score. In conclusion, we found that the CSGPI might serve as a biomarker to predict BCR and drug resistance in PCa patients. Moreover, CD96 and DNMT3B might be potential treatment targets, and immune evasion might contribute to the BCR process of PCa.

CD93 orchestrates the tumor microenvironment and predicts the molecular subtype and therapy response of bladder cancer.

BACKGROUND: CD93 is newly reported to normalize vasculature and attenuate pancreatic cancer therapy response, but its role in bladder cancer (BLCA) is unknown. METHOD: The immunologic role of CD93 is analyzed across TCGA pan-cancers. The correlation between CD93 and BLCA clinical and tumor microenvironment features, predicted immunotherapy pathways, molecular subtypes, therapeutic signatures and mutation status was evaluated in TCGA-BLCA and other two BLCA cohorts. The impact of CD93 on immunotherapy response was validated by five real-world cohorts, and chemotherapy response was assessed with IC50. CD93-based risk model was constructed with LASSO regression and validated by seven independent cohorts. RESULT: CD93 is positively correlated with immunomodulators, tumor-infiltrating lymphocytes (TILs) and immune checkpoints across pan-cancers. In BLCA, CD93 leads to higher T cell inflamed score and expression of immune checkpoints. However, CD93 is indicative of more aggressive clinical features, worse survival, more tumor-associated macrophages and regulatory T cells recruitment, less recognition and killing of cancer cells by T cells, lower predicted chemotherapy and immunotherapy response, which is further validated by immunotherapy cohorts (IMvigor210: 16.11% vs 29.53%; GSE176307: 15.56% vs 20.93%). Notably, CD93 correlates with enriched neuroendocrine subtype and epithelial-mesenchymal transition differentiation, while CD93-low group has enriched luminal subtype. Pathways including hypoxia and Wnt-ß-catenin are enriched along with CD93 expression, and more frequent FGFR3 mutation is also observed. Lastly, the CD93-based risk model, validated by seven independent cohorts, is powerful in distinguishing the survival probability of BLCA (3-year AUC 0.808). CONCLUSION: CD93 plays a critical role in tumor immune regulation. CD93 expression indicates more aggressive clinicopathological status and molecular subtypes of BLCA and worse therapy response, which implies that combing anti-CD93 therapy with immunotherapy (or chemotherapy) may be potentially beneficial for BLCA in clinical practice.

A gene prognostic index from cellular senescence predicting metastasis and radioresistance for prostate cancer.

BACKGROUND: Senescent cells have been identified in the aging prostate, and the senescence-associated secretory phenotype might be linked to prostate cancer (PCa). Thus, we established a cellular senescence-related gene prognostic index (CSGPI) to predict metastasis and radioresistance in PCa. METHODS: We used Lasso and Cox regression analysis to establish the CSGPI. Clinical correlation, external validation, functional enrichment analysis, drug and cell line analysis, and tumor immune environment analysis were conducted. All analyses were conducted with R version 3.6.3 and its suitable packages. RESULTS: We used ALCAM and ALDH2 to establish the CSGPI risk score. High-risk patients experienced a higher risk of metastasis than their counterparts (HR: 10.37, 95% CI 4.50-23.93, p < 0.001), consistent with the results in the TCGA database (HR: 1.60, 95% CI 1.03-2.47, p = 0.038). Furthermore, CSGPI had high diagnostic accuracy distinguishing radioresistance from no radioresistance (AUC: 0.938, 95% CI 0.834-1.000). GSEA showed that high-risk patients were highly associated with apoptosis, cell cycle, ribosome, base excision repair, aminoacyl-tRNA biosynthesis, and mismatch repair. For immune checkpoint analysis, we found that PDCD1LG2 and CD226 were expressed at significantly higher levels in patients with metastasis than in those without metastasis. In addition, higher expression of CD226 significantly increased the risk of metastasis (HR: 3.65, 95% CI 1.58-8.42, p = 0.006). We observed that AZD7762, PHA-793887, PI-103, and SNX-2112 might be sensitive to ALDH2 and ALCAM, and PC3 could be the potential cell line used to investigate the interaction among ALDH2, ALCAM, and the above drugs. CONCLUSIONS: We found that CSGPI might serve as an effective biomarker predicting metastasis probability and radioresistance for PCa and proposed that immune evasion was involved in the process of PCa metastasis.

A closed-loop electrokinetic system for recovery of PbO2@Fe composite derived from lead-containing sludge.

Lead-containing sludge produced from lead-acid battery factory will cause environmental hazards if they are not treated properly. A novel process was developed to recycle lead from sludge back into Fe-doped PbO2 electrodes and realize sludge reduction in this study. The effects of Fenton conditioning on Pb removal efficiency in electro-kinetic (EK) treatment process and its mechanism as well as electro-dewatering (ED) performance were investigated. It was found that the oxidation of Fenton can promote desorption and release of Pb from the organic binding state, and improve the removal efficiency of Pb during EK process, as well as enhance sludge ED performance. About 63.8 wt% Pb can be removed from sludge during EK process, achieving sludge reduction of 63.5 wt% by ED treatment. The composite PbO2@Fe electrode recovered from lead-containing sludge showed a high electrocatalytic activity for acid red G (ARG) degradation. The electrode obtained by electrodeposition at 20 mA cm-2 had the largest exchange current density (3.26 × 10-5 A cm-2). In the experiment of dye wastewater electrocatalytic degradation, over 99.5% organic matter was degraded within 80 min.

The Prognostic and Clinicopathological Significance of Systemic Immune-Inflammation Index in Bladder Cancer.

Background: Systemic immune-inflammation index (SII) has recently emerged as a biomarker for the prognosis of a variety of malignant tumors. However, the role of SII in bladder cancer (BC) remains unclear. To this end, we performed a pooled analysis to investigate the prognostic value of preoperative SII in patients with BC. Methods: A comprehensive search of electronic databases (PubMed/Medline, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials) was conducted to determine the eligible studies that were published until January 2022. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association between preoperative SII and the prognosis and clinicopathological characteristics of BC. Results: Ten studies with 7,087 patients were included in this analysis. SII was observed to be correlated with inferior overall survival (HR = 1.22, 95% CI 1.04-1.44, p = 0.013), cancer-specific survival (HR = 1.68, 95% CI 1.14-2.47, p = 0.009), and recurrence-free survival (HR = 1.29, 95% CI 1.03-1.61, p = 0.027). An increased preoperative SII was also associated with poor tumor differentiation, higher tumor stage, presence of lymph node involvement, and tumor size ≥3 cm (all p < 0.05). Conclusions: An elevated preoperative SII is significantly associated with worse survival outcomes and adverse pathological features in patients with BC. Hence, SII may serve as a strong independent prognostic predictor for patients with BC after surgery.