Changes in emotion regulation strategies during the pandemic: prospective pathways to adolescent depressive symptoms.

BACKGROUND: Emotion regulation (ER) is considered central in adolescent psychopathology, and ER strategies may change during challenging times, such as a global pandemic. Despite this, there remains a limited understanding of individual differences in ER mechanisms and their associations with psychopathology. This study examined whether and how cognitive reappraisal, expressive suppression, and self-compassion changed over COVID-19 and how these changes uniquely predicted adolescents' depressive symptoms. METHODS: A total of 2,411 adolescents (58.6% females; Mage = 18.51, SD = 0.80) completed the Emotional Regulation Questionnaire, the Self-compassion Scale, and the Symptom Checklist-90 before COVID-19 (in 2019) and during COVID-19 (in 2020). The predictive associations between each ER strategy and depressive symptoms were tested with latent change score models. RESULTS: Adolescents' use of expressive suppression and self-compassion strategies both increased during COVID-19. More increases in expressive suppression predicted more depressive symptoms, whereas more increases in self-compassion predicted fewer depressive symptoms. Although, on average, cognitive reappraisal did not change, it did show significant variations within the sample - increases (vs. decreases) in cognitive appraisal predicted fewer depressive symptoms. CONCLUSIONS: The study indicates how adolescents' ER strategies changed during the unprecedented global pandemic. It underscores protective roles of increased cognitive reappraisal and self-compassion, as well as the adverse consequence of heightened expressive suppression on adolescents' depressive symptoms. Findings offer insights for targeted interventions aimed at addressing specific ER strategies.

The association between human papillomavirus and bladder cancer: Evidence from meta-analysis and two-sample mendelian randomization.

INTRODUCTION: Bladder cancer (BCa) is the 10th most common type of cancer worldwide, and human papillomavirus (HPV) is the most common sexually transmitted infection. However, the relationship between HPV infection and the risk of BCa is still controversial and inconclusive. METHODS: This systematic review and meta-analysis were conducted following the PRISMA 2020 reporting guideline. This study searched four bibliographic databases with no language limitation. The databases included PubMed (Medline), EMBASE, Cochrane Library, and Web of Science. Studies evaluating the interaction between HPV infection and the risk of BCa from inception through May 21, 2022, were identified and used in this study. This study estimated the overall and type-specific HPV prevalence and 95% confidence intervals (95% CI) using Random Effects models and Fixed Effects models. In addition, this study also calculated the pooled odds ratio and pooled risk ratio with 95% CI to assess the effect of HPV infection on the risk and prognosis of bladder cancer. Two-sample mendelian randomization (MR) study using genetic variants associated with HPV E7 protein as instrumental variables were also conducted. RESULTS: This study retrieved 80 articles from the four bibliographic databases. Of the total, 27 were case-control studies, and 53 were cross-sectional studies. The results showed that the prevalence of HPV was 16% (95% CI: 11%-21%) among the BCa patients, most of which were HPV-16 (5.99% [95% CI: 3.03%-9.69%]) and HPV-18 (3.68% [95% CI: 1.72%-6.16%]) subtypes. However, the study found that the prevalence varied by region, detection method, BCa histological type, and sample source. A significantly increased risk of BCa was shown for the positivity of overall HPV (odds ratio [OR], 3.35 [95% CI: 1.75-6.43]), which was also influenced by study region, detection method, histological type, and sample source. In addition, the study found that HPV infection was significantly associated with the progression of BCa (RR, 1.73 [95% CI: 1.39-2.15]). The two-sample MR analysis found that both HPV 16 and 18 E7 protein exposure increased the risk of BCa (HPV 16 E7 protein: IVW OR per unit increase in protein level = 1.0004 [95% CI: 1.0002-1.0006]; p = 0.0011; HPV 18 E7 protein: IVW OR per unit increase in protein level = 1.0003 [95% CI: 1.0001-1.0005]; p = 0.0089). CONCLUSION: In conclusion, HPV may play a role in bladder carcinogenesis and contribute to a worse prognosis for patients with BCa. Therefore, it is necessary for people, especially men, to get vaccinated for HPV vaccination to prevent bladder cancer.

A critical review on graphene oxide membrane for industrial wastewater treatment.

An important way to promote the environmental industry's goal of carbon reduction is to promote the recycling of resources. Membrane separation technology has unique advantages in resource recovery and advanced treatment of industrial wastewater. However, the great promise of traditional organic membrane is hampered by challenges associated with organic solvent tolerance, lack of oxidation resistance, and serious membrane fouling control. Moreover, the high concentrations of organic matter and inorganic salts in the membrane filtration concentrate also hinder the wider application of the membrane separation technology. The emerging cost-effective graphene oxide (GO)-based membrane with excellent resistance to organic solvents and oxidants, more hydrophilicity, lower membrane fouling, better separation performance has been expected to contribute more in industrial wastewater treatment. Herein, we provide comprehensive insights into the preparation and characteristic of GO membranes, as well as current research status and problems related to its future application in industrial wastewater treatment. Finally, concluding remarks and future perspectives have been deduced and recommended for the GO membrane separation technology application for industrial wastewater treatment, which leads to realizing sustainable wastewater recycling and a nearly "zero discharge" water treatment process.

SPT: Single Pedestrian Tracking Framework with Re-Identification-Based Learning Using the Siamese Model.

Pedestrian tracking is a challenging task in the area of visual object tracking research and it is a vital component of various vision-based applications such as surveillance systems, human-following robots, and autonomous vehicles. In this paper, we proposed a single pedestrian tracking (SPT) framework for identifying each instance of a person across all video frames through a tracking-by-detection paradigm that combines deep learning and metric learning-based approaches. The SPT framework comprises three main modules: detection, re-identification, and tracking. Our contribution is a significant improvement in the results by designing two compact metric learning-based models using Siamese architecture in the pedestrian re-identification module and combining one of the most robust re-identification models for data associated with the pedestrian detector in the tracking module. We carried out several analyses to evaluate the performance of our SPT framework for single pedestrian tracking in the videos. The results of the re-identification module validate that our two proposed re-identification models surpass existing state-of-the-art models with increased accuracies of 79.2% and 83.9% on the large dataset and 92% and 96% on the small dataset. Moreover, the proposed SPT tracker, along with six state-of-the-art (SOTA) tracking models, has been tested on various indoor and outdoor video sequences. A qualitative analysis considering six major environmental factors verifies the effectiveness of our SPT tracker under illumination changes, appearance variations due to pose changes, changes in target position, and partial occlusions. In addition, quantitative analysis based on experimental results also demonstrates that our proposed SPT tracker outperforms the GOTURN, CSRT, KCF, and SiamFC trackers with a success rate of 79.7% while beating the DiamSiamRPN, SiamFC, CSRT, GOTURN, and SiamMask trackers with an average of 18 tracking frames per second.

The Prognosis-Predictive and Immunoregulatory Role of SUMOylation Related Genes: Potential Novel Targets in Prostate Cancer Treatment.

SUMOylation is an important part of post-translational protein modifications and regulates thousands of proteins in a dynamic manner. The dysregulation of SUMOylation is detected in many cancers. However, the comprehensive role of SUMOylation in prostate cancer (PCa) remains unclear. Using 174 SUMOylation-related genes (SRGs) from the MigDSB database and the transcript data of PCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we constructed a SUMOylation-related risk score and correlated it with prognosis, tumor mutation burden (TMB), tumor microenvironment (TME) infiltration, and response to chemotherapy and immunotherapy. Moreover, we validated two vital SRGs by RT-qPCR, western blotting, and immunohistochemistry. Two vital SRGs (DNMT3B and NUP210) were finally selected. The risk score based on these genes exhibited excellent predictive efficacy in predicting the biochemical recurrence (BCR) of PCa. A nomogram involving the risk score and T stage was established to further explore the clinical value of the risk score. We found the high-score group was correlated with worse prognosis, higher TMB, a more suppressive immune microenvironment, and a better response to Docetaxel but worse to PD-1/CTLA-4 blockade. Meanwhile, we validated the significantly higher expression level of NUP210 in PCa at mRNA and protein levels. This study elucidated the comprehensive role of SUMOylation-related genes in PCa. Importantly, we highlighted the role of an important SRG, NUP210, in PCa, which might be a promising target in PCa treatment. A better understanding of SUMOylation and utilizing the SUMOylation risk score could aid in precision medicine and improve the prognosis of PCa.

Circulating soluble receptor for advanced glycation end products and other factors in type 2 diabetes patients with colorectal cancer.

BACKGROUND: Recent study showed that individuals with type 2 diabetes have a high risk of developing colorectal cancer (CRC), in which Receptor for Advanced Glycation End Products (RAGE) plays a pivotal role. We conducted a cross-sectional study to examine the relationships of circulating sRAGE, CRC and other clinical factors in type2 diabetes patients. METHODS: A total of 150 type 2 diabetes patients aged 50 years and older were enrolled, including 50 patients with CRC and 100 patients without CRC. We measured Serum levels of sRAGE and interleukin-6(IL-6) using an enzyme-linked immunosorbent assay (ELISA). In addition, other clinical parameters were also measured during hospitalization. RESULTS: Type 2 diabetes patients with CRC had higher triglyceride, total cholesterol, IL-6, and circulating sRAGE levels and lower use of medicines than type 2 diabetes patients without CRC. Circulating sRAGE was associated with an increased risk for CRC (OR = 2.289 for each SD increase in sRAGE, 95% CI = 1.037-5.051; P = 0.04) among Type 2 diabetes patients after adjustment for confounders. Furthermore, circulating sRAGE levels among type 2 diabetes patients were positively correlated with triglyceride (r = 0.377, P < 0.001), total cholesterol (r = 0.491, P < 0.001), and low-density lipoprotein cholesterol (LDL-c)(r = 0.330, P < 0.001) levels; the homeostatic model assessment for insulin resistance(HOMA-IR)score (r = 0.194, P = 0.017); and fasting serum insulin (r = 0.167, P = 0.041) and IL-6 (r = 0.311, P < 0.001) concentrations. CONCLUSIONS: Our results suggested that circulating sRAGE is independently risk factor for CRC, and also closely related to inflammation, dyslipidemia in type 2 diabetes patients.

Analysis and Differential Expression of Primo Genes Using RNA-Seq and qRT-PCR Experiments.

Although the existence of the primo vasculature system has been shown in many species, including mice, rats, rabbits and humans, the biological role of this system, including expression of genes and proteins, has not yet been investigated. Especially the transcriptional action by mRNA, which is required for biological action, needs to be studied in primo vasculature biology. Differentially expressed genes in both isolated primo vessels and lymphatic vessels of rabbits were analyzed by RNA sequencing experiments. Primer efficiency and RNA purity of the primo vessels under lipopolysaccharides were confirmed prior to performing real-time qRT-PCR analysis following RNA extraction. We demonstrated that FLT4 was enriched in primo vessels and that several genes, including HSPH1 and EPHB2, were highly expressed in primo vessels compared with lymphatic vessels. Our data show that almost all genes, except HSPA4, were increased or sustained in isolated primo vessels compared with lymphatic vessels (FLT4 2.58 fold, HSPH1 1.83 fold, EPHB2 1.52 fold; whereas HSPA4 decreased 0.50 fold), suggesting primo vessels as a central regulator in diverse physiology. This implies that FLT4, HSPH1, and EPHB2 in high amounts may be involved in the functional activity of primo vessels. Our experimental data show that several genes are highly enriched in primo vessels in the lymphatic vessels of the rabbit.

Hepatitis B virus full-length genomic mutations and quasispecies in hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatitis B virus (HBV) full-length genomic mutations and quasispecies characteristics in hepatocellular carcinoma (HCC) were investigated. METHODS: Hepatitis B virus DNA was extracted from the tumor and non-tumor tissues of 16 HCC patients. Overlapping DNA fragments covering the entire HBV genome were amplified and sequenced. To study HBV sequence at the quasispecies level, the preS region was amplified and clonally sequenced. HBV mutation profiles, quasispecies complexity and diversity, and phylogenetic characteristics were assessed. RESULTS: Fourteen patients had full-length HBV amplification. Hot-spot mutations at HBx aa130-131 and pre-S deletions were detected in 13 (93%) and 6 (43%) patients, respectively. Deletions in the X/preC/C regions were more frequently detected in the tumor than in the non-tumor tissues (P = 0.031). Compared with the non-tumor tissues, the tumor tissues had a lower quasispecies complexity (P = 0.014 and 0.043, at the nucleotide and amino acid levels, respectively) and diversity (P = 0.048 and 0.022, at the nucleotide and amino acid levels, respectively). Phylogenetic analysis showed that HBV sequences derived from tumor and non-tumor tissues were separately clustered, suggesting the occurrence of compartmentalization, which was confirmed by the correlation coefficient testing on both the number and length of branches of viral populations (all P < 0.02). CONCLUSIONS: Hepatitis B virus mutation patterns in HCC tumor tissues and non-tumor tissues were different. HBV quasispecies within the preS region were compartmentalized, and tumor tissues had a lower genome complexity and diversity. Our study suggests HBV evolution is conditioned by the differential host cellular environment in HCC tumors.

Adsorption and photocatalytic degradation of pharmaceuticals and pesticides by carbon doped-TiO2 coated on zeolites under solar light irradiation.

To evaluate the performance of zeolite-supported carbon-doped TiO(2) composite catalysts toward target pollutants under solar light irradiation, the adsorption and photocatalytic degradation of 18 pharmaceuticals and pesticides with distinguishing features (molecular size and volume, and photolysis) were investigated using mordenite zeolites with SiO(2)/Al(2)O(3) ratios of 18 and 240. Different quantities of carbon-doped TiO(2) were coated on the zeolites, and then the finished composite catalysts were tested in demineralized, surface, and hospital wastewater samples, respectively. The composite photocatalysts were characterized by X-ray diffraction, field emission scanning electron microscopy, and surface area and porosity analyses. Results showed that a dispersed layer of carbon-doped TiO(2) is formed on the zeolite surface; this layer blocks the micropores of zeolites and reduces their surface area. However, these reductions did not significantly affect adsorption onto the zeolites. Our results demonstrated that zeolite-supported carbon-doped TiO(2) systems can effectively degrade 18 pharmaceuticals and pesticides in demineralized water under natural and simulated solar light irradiation. In surface and hospital wastewaters, zeolite-supported carbon-doped TiO(2) systems present excellent anti-interference capability against radical scavengers and competitive organics for pollutants removal, and higher pollutants adsorption on zeolites evidently enhances the removal rate of target pollutants in surface and hospital wastewater samples with a complicated matrix.

Effect of hepatitis B virus reverse transcriptase variations on entecavir treatment response.

BACKGROUND: Entecavir therapy often reduces hepatitis B virus (HBV) DNA to an undetectable level, but HBV DNA remain detectable in some patients. We investigated whether baseline HBV reverse transcriptase (rt) polymorphism and quasispecies complexity and diversity were associated with treatment response. METHODS: Pretreatment HBV DNA levels, HBV rt sequence, serology, and quasispecies complexity and diversity from 305 entecavir-treated patients were determined. These data were tested for their association with year 1 virological outcome, defined by optimal response (undetectable HBV DNA; lower limit of detection, ≤12 IU/mL) or partial response (detectable HBV DNA). RESULTS: Four rt variants were more frequently detected in the 64 partial responders than in the 241 optimal responders (all P < .05). Multivariate analysis revealed that high baseline HBV DNA level (P < .0001; odds ratio [OR], 2.32), HBV e antigen (HBeAg) positivity (P < .001; OR, 3.70), and rt124N (P = .002; OR, 3.06) were associated with a partial entecavir response. Compared with the optimal responders, the partial responders had a lower quasispecies complexity and diversity. CONCLUSIONS: Apart from the known factors (high baseline HBV DNA level and HBeAg positivity), a novel single nucleotide polymorphism (rt124N) and lower quasispecies complexity and diversity were associated with partial entecavir response at year 1.

Simultaneous determination of calycosin-7-O-ß-d-glucoside, calycosin, formononetin, astragaloside IV and schisandrin in rat plasma by LC-MS/MS: application to a pharmacokinetic study after oral administration of Shenqi Wuwei chewable tablets.

A rapid, sensitive and reliable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantification of the five main bioactive components, calycosin, calycosin-7-O-ß-d-glucoside, formononetin, astragaloside IV and schisandrin in rat plasma after oral administration of Shenqi Wuwei chewable tablets. Plasma samples were extracted using solid-phase extraction separated on a CEC18 column and detected by MS with an electrospray ionization interface in multiple-reaction monitoring mode. Calibration curves offered linear ranges of two orders of magnitude with r > 0.995. The method had a lower limit of quantitation of 0.1, 0.02, 0.1, 1 and 0.1 ng/mL for calycosin, calycosin-7-O-ß-d-glucoside, formononetin, astragaloside IV and schisandrin, respectively. Intra- and inter-day precisions (relative standard deviation) for all analytes ranged from 0.97 to 7.63% and from 3.45 to 10.89%, respectively. This method was successfully applied to the pharmacokinetic study of the five compounds in rats after oral administration of Shenqi Wuwei chewable tablets.

The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials.

BACKGROUND: Sex is an important factor influencing the immune system, and the distribution of tumors, including their types and subtypes, is characterized by sexual dichotomy. The aim of this study was to investigate whether there is an association between sex and the treatment effect of immune checkpoint inhibitors (ICI). METHODS: Four bibliographic databases were searched. Studies of randomized controlled trials (RCTs) assessing the efficacy of ICI were identified and used, and the primary endpoint was the difference in efficacy of ICI between males and females, presented as overall survival (OS), progression-free survival (PFS) and recurrence-free survival (RFS). The study calculated the pooled HRs and 95% CIs for OS, PFS and RFS for males and females using a random effects model or a fixed effects model, and thereby assessed the effect of sex on the efficacy of ICI treatment. This study is registered with PROSPERO (CRD42022370939). RESULTS: A total of 103 articles, including a total of 63,755 patients with cancer, were retrieved from the bibliographic database, of which approximately 70% were males. In studies with OS as the outcome, the combined hazard ratio (HR) was 0.77 (95% CI 0.74-0.79) for male patients treated with ICI and 0.81 (95% CI 0.78-0.85) for female patients compared to controls, respectively. The difference in efficacy between males and females was significant. CONCLUSIONS: ICI therapy, under suitable conditions for its use, has a positive impact on survival in various types of tumors, and male patients benefit more than females. It may be necessary to develop different tumor immunotherapy strategies for patients of different sexes.

A clinical evaluation of robotic-assisted radical prostatectomy (RARP) in located prostate cancer: A systematic review and network meta-analysis.

Prostate cancer (PCa) is a prevalent malignant tumor affecting the male reproductive system and there are mainly three widely accepted PCa surgery types in current clinical treatment: open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP). Here, we aimed to evaluate the clinical effect of RARP for PCa patients compared with ORP and LRP based on the context of PCa encompass two dimensions: oncological outcomes (biochemical recurrence (BCR) and positive surgical margin (PSM)) and functional outcomes (urinary continence and recovery of erectile function) in this network meta-analysis (NMA). PubMed, Embase and Cochrane databases were systematically searched in January 7, 2024. 4 randomized controlled trials (RCTs) and 72 non-RCTs were included. RARP displayed significant positive effect on lower BCR and better recovery of erectile function but no significant differences existed among three surgery types for PSM and urinary continence.

Knowledge mapping of application of image-guided surgery in prostate cancer: a bibliometric analysis (2013-2023).

BACKGROUND: Image-guided surgery (IGS) refers to surgery navigated by medical imaging technology, helping doctors better clarify tumor boundaries, identify metastatic lymph nodes and preserve surrounding healthy tissue function. Recent studies have provided expectable momentum of the application of IGS in prostate cancer (PCa). The authors aim to comprehensively construct a bibliometric analysis of the application of IGS in PCa. METHOD: The authors searched publications related to application of IGS in PCa from 2013 to 2023 on the web of science core collection (WoSCC) databases. VOSviewer, CiteSpace, and R package 'bibliometrix' were used for bibliometric analysis. RESULTS: Two thousand three eighty-nine articles from 75 countries and 2883 institutions led by the United States were included. The number of publications related to the application of IGS in PCa kept high in the last decade. Johns Hopkins University is the top research institutions. Journal of Nuclear Medicine has the highest popularity as the selection of journal and co-cited journal. Pomper Martin G. had published the most paper. Ali Afshar-Oromieh was co-cited most frequently. The clinical efficacy of PSMA-PET/CT in PCa diagnosis and treatment are main topics in this research field, with emerging focuses on the use of fluorescence imaging guidance technology in PCa. 'PSMA' and 'PET/CT' are the main keywords as long-term research hotspots. CONCLUSION: This study is the first bibliometric analysis of researches on application of IGS in PCa with three recognized bibliometric software, providing an objective description and comprehensive guidance for the future relevant investigations.

Recent breakthroughs in innovative elements, multidimensional enhancements, derived technologies, and novel applications of PROTACs.

Proteolysis Targeting Chimera (PROTAC) is an emerging and evolving technology based on targeted protein degradation (TPD). Small molecule PROTACs have shown great efficacy in degrading disease-specific proteins in preclinical and clinical studies, but also showed various limitations. In recent years, new technologies and advances in TPD have provided additional optimized strategies based on conventional PROTACs that can overcome the shortcomings of conventional PROTACs in terms of undruggable targets, bioavailability, tissue-specificity, spatiotemporal control, and degradation scope. In addition, some designs of special targeting chimeras and applications based on multidisciplinary science have shed light on novel therapeutic modalities and drug design. However, each improvement has its own advantages, disadvantages and application conditions. In this review, we summarize the exploration of PROTAC elements, depict a landscape of improvements and derived concepts of PROTACs, and expect to provide perspectives for technological innovations, combinations and applications in future targeting chimera design.

Enhanced cellular therapy: revolutionizing adoptive cellular therapy.

Enhanced cellular therapy has emerged as a novel concept following the basis of cellular therapy. This treatment modality applied drugs or biotechnology to directly enhance or genetically modify cells to enhance the efficacy of adoptive cellular therapy (ACT). Drugs or biotechnology that enhance the killing ability of immune cells include immune checkpoint inhibitors (ICIs) / antibody drugs, small molecule inhibitors, immunomodulatory factors, proteolysis targeting chimera (PROTAC), oncolytic virus (OV), etc. Firstly, overcoming the inhibitory tumor microenvironment (TME) can enhance the efficacy of ACT, which can be achieved by blocking the immune checkpoint. Secondly, cytokines or cytokine receptors can be expressed by genetic engineering or added directly to adoptive cells to enhance the migration and infiltration of adoptive cells to tumor cells. Moreover, multi-antigen chimeric antigen receptors (CARs) can be designed to enhance the specific recognition of tumor cell-related antigens, and OVs can also stimulate antigen release. In addition to inserting suicide genes into adoptive cells, PROTAC technology can be used as a safety switch or degradation agent of immunosuppressive factors to enhance the safety and efficacy of adoptive cells. This article comprehensively summarizes the mechanism, current situation, and clinical application of enhanced cellular therapy, describing potential improvements to adoptive cellular therapy.

A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance.

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.

The role of TERT C228T and KDM6A alterations and TME in NMIBC treated with BCG.

We aimed to investigate the genomic and tumor microenvironmental (TME) profiles in non-muscle invasive bladder cancer (NMIBC) and explore potential predictive markers for Bacillus Calmette-Guérin (BCG) treatment response in high-risk NMIBC patients (according to European Association of Urology (EAU) risk stratification). 40 patients with high-risk NMIBC (cTis-T1N0M0) who underwent en bloc resection followed by BCG instillation were retrospectively enrolled. Surgical samples were subjected to Next Generation Sequencing (NGS) and multiplex immunofluorescence (mIF) assay. Genomic profiling revealed high prevalences of alterations in TERT (55%), KDM6A (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%) and ARID1A (20%). TME analysis showed different proportions of macrophages, NK cells, T cells subsets in tumoral and stromal compartment. Multivariate analysis identified TERT C228T and alteration in KDM6A as two independent factors associated with inferior RFS. The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment.

Four new koumine metabolites in rat liver microsomes.

Four new metabolites M-1 [1,2,18,19-tetradehydro-4-demethyl-3,17-epoxy-7,20(2H,19H)-cyclovobasan], M-2 [1,2,4,21,18,19-hexadehydro-4-demethyl-3,17-epoxy-7,20(2H,19H)-cyclovobasan], M-3 [1,2,18,19-tetradehydro-4-demethyl-4-formaldehyde-3,17-epoxy-7,20(2H,19H)-cyclovobasan], and M-4 [1,2,4,21,18,19-hexadehydro-4-demethyl-4-oxy-3,17-epoxy-7,20(2H,19H)-cyclovobasan] were isolated from the chloroform extract of koumine incubated with phenobarbital-treated rat liver microsomes. The structures of M-1, M-2, M-3, and M-4 were elucidated by spectroscopic methods including ESI-TOF-MS, 1D, and 2D NMR experiments. The metabolic pathway of koumine was proposed. The cytotoxic activities between koumine and its metabolites were also compared in the A549 cell line.