Graphitic Carbon Nitride Enters the Scene: A Promising Versatile Tool for Biomedical Applications.

Graphitic carbon nitride (g-C3N4), since the pioneering work on visible-light photocatalytic water splitting in 2009, has emerged as a highly promising advanced material for environmental and energetic applications, including photocatalytic degradation of pollutants, photocatalytic hydrogen generation, and carbon dioxide reduction. Due to its distinctive two-dimensional structure, excellent chemical stability, and distinctive optical and electrical properties, g-C3N4 has garnered a considerable amount of interest in the field of biomedicine in recent years. This review focuses on the fundamental properties of g-C3N4, highlighting the synthesis and modification strategies associated with the interfacial structures of g-C3N4-based materials, including heterojunction, band gap engineering, doping, and nanocomposite hybridization. Furthermore, the biomedical applications of these materials in various domains, including biosensors, antimicrobial applications, and photocatalytic degradation of medical pollutants, are also described with the objective of spotlighting the unique advantages of g-C3N4. A summary of the challenges faced and future prospects for the advancement of g-C3N4-based materials is presented, and it is hoped that this review will inspire readers to seek further new applications for this material in biomedical and other fields.

Multi-Omics Analysis Reveals the Role of Changes in Platelet Activation Pathways in the Survival Outcome of Patients with Esophageal Squamous Cell Carcinoma.

Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy. Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987). Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.

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.

Thrombophilic gene polymorphisms and recurrent pregnancy loss: a systematic review and meta-analysis.

PURPOSE: Recurrent pregnancy loss (RPL) is affecting 1-4% of women who conceive approximately, and no cause could be found in more than 50% of women suffering from RPL. Inherited thrombophilias have got increasing attention in women with unexplained RPL, so we aim to explore the relationship among these most common thrombophilic polymorphisms and RPL through a literature review and meta-analysis. METHODS: Observational studies from PubMed, Embase, Cochrane, and Web of Science from 1997 to 7 April 2022 were searched. For each genetic variant, a fixed or random-effect model was used according to the heterogeneity test to calculate pooled ORs and 95% CIs for both dominant and recessive genetic models. Egger's line regression test was used to assess publication bias. The quality of the included articles was assessed by the Newcastle Ottawa scale. RESULTS: A total of 124 articles comprising 17,278 RPL patients and 16,021 controls were included. Results showed that hyperhomocysteinemia (MTHFR) C677T (dominant model: OR, 1.43; 95% CI, 1.25-1.64; recessive model: OR, 1.60; 95% CI, 1.36-1.87), MTHFR A1298C (dominant model: OR, 1.66; 95% CI, 1.26-2.18; recessive model: OR, 1.79; 95% CI, 1.42-2.26), PAI-1 4G/5G (dominant model: OR, 1.67; 95% CI, 1.36-2.06; recessive model: OR, 1.80; 95% CI, 1.39-2.32), angiotensin-converting enzyme I/D (OR, 1.23; 95% CI, 1.00-1.53), Factor XIII V34L (OR, 1.38; 95% CI, 1.02-1.87), and ß-fibrinogen-455G/A (OR, 1.60; 95% CI, 1.02-2.51) were significantly associated with RPL. CONCLUSION: This study provides potentially useful clinical markers to evaluate the risk of RPL or to help unexplained RPL patients identify possible causes, which may allow for targeted treatment.

MSAACNN for intense noise suppression in DAS-VSP records.

Distributed optical fiber sensor (DAS) is an emerging acquisition technique and has begun to be widely applied in seismic exploration owing to its advantages in acquisition and deployment. Nonetheless, DAS record has a low signal-to-noise ratio (SNR) due to the intense background noise. How to suppress the DAS background noise and increase the SNR of the DAS records has gradually become one of the hot issues in the field of seismic data processing. To solve the challenging tasks in intense DAS noise suppression, a multiscale sparse asymmetric attention convolutional neural network (MSAACNN) is proposed. The network uses dilated convolutions to expand the receptive field and map more feature information. Moreover, asymmetric convolutions are introduced to form an asymmetric unit, aiming to strengthen the feature extraction ability and realize the interaction between feature information of different scales. Finally, a pyramid attention module is used to enhance the primary features and improve the network denoising performance. The experimental results show that MSAACNN can effectively suppress the complex background noise in DAS records, compared with the traditional denoising methods and typical convolutional neural network (CNN) architecture. Additionally, the recovered signal components in the processing results are clear and complete, with significantly improved SNR.

A Lignin Silver Nanoparticles/Polyvinyl Alcohol/Sodium Alginate Hybrid Hydrogel with Potent Mechanical Properties and Antibacterial Activity.

Antibacterial hydrogels have attracted significant attention due to their diverse applications, efficient antimicrobial properties, and adaptability to various environments and requirements. However, their relatively fragile structure, coupled with the potential for environmental toxicity when exposed to their surroundings for extended periods, may significantly limit their practical application potential. In this work, a composite hydrogel was synthesized with outstanding mechanical features and antibacterial capability. The hydrogel was developed through the combination of the eco-friendly and enduring antibacterial agent, lignin silver nanoparticles (Lig-Ag NPs), with polyvinyl alcohol (PVA) and sodium alginate (SA), in varying proportions. The successful synthesis of the hydrogel and the dispersed distribution of Lig-Ag NPs within the hydrogel were confirmed by various analytical techniques, including field emission scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), mercury intrusion porosimetry (MIP), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The formation of multiple hydrogen bonds between Lig-Ag NPs and the composites contributed to a more stable and dense network structure of the hydrogel, consequently enhancing its mechanical properties. Rheological tests revealed that the hydrogel exhibited an elastic response and demonstrated outstanding self-recovery properties. Significantly, the antibacterial hydrogel demonstrated effectiveness against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), achieving a <5% survival of bacteria within 12 h. This study presented a green and straightforward synthetic strategy for the application of antibacterial composite hydrogels in various fields.

LncRNA HAGLROS: A Vital Oncogenic Propellant in Various Human Cancers.

HAGLR Opposite Strand lncRNA (HAGLROS) is a long non-coding RNA (lncRNA) located on the long arm of human chromosome 2 at locus 2q31.1. Emerging evidence highlights HAGLROS as a pivotal player in human cancers, characterized by its significant upregulation across multiple malignancies where it functions as an oncogenic driver. Its aberrant expression is closely linked to the initiation and progression of 13 distinct cancer types, notably correlating with adverse clinical outcomes and reduced overall survival rates in 9 of these cancer types. Mechanistically, HAGLROS is under the regulatory influence of the transcription factor STAT3, exerts competitive binding to 9 miRNAs, activates 5 signaling pathways pivotal for cancer cell proliferation and metastasis, as well as intricately modulates gene expression profiles. Given its multifaceted roles, HAGLROS emerges as a promising candidate for cancer diagnostics and prognostics. Moreover, its potential as a therapeutic target holds considerable promise for novel treatment strategies in oncology. This review synthesizes current research on HAGLROS, covering its expression patterns, biological roles, and clinical significance in cancer. By shedding light on these aspects, this review aims to contribute new perspectives that advance our understanding of cancer biology, enhance diagnostic accuracy, refine prognostic assessments, and pave the way for targeted therapeutic interventions.

2'-Hydroxycinnamaldehyde Alleviates Intestinal Inflammation by Attenuating Intestinal Mucosal Barrier Damage Via Directly Inhibiting STAT3.

BACKGROUND: The currently available clinical therapeutic drugs for ulcerative colitis (UC) are considered inadequate owing to certain limitations. There have been reports on the anti-inflammatory effects of 2'-hydroxycinnamaldehyde (HCA). However, whether HCA can improve UC is still unclear. Here, we aimed to investigate the pharmacological effects of HCA on UC and its underlying molecular mechanisms. METHODS: The pharmacological effects of HCA were comprehensively investigated in 2 experimental setups: mice with dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-treated fetal human colon (FHC) cells. Furthermore, the interaction between HCA and signal transducer and activator of transcription 3 (STAT3) was investigated using molecular docking. The FHC cells with STAT3 knockdown or overexpression and mice with intestinal epithelium-specific STAT3 deletion (STAT3ΔIEC) were used to evaluate whether STAT3 mediated the pharmacological effects of HCA. RESULTS: 2'-Hydroxycinnamaldehyde attenuated dysregulated expression of inflammatory cytokines in a dose-dependent manner while increasing the expression of tight junction proteins, reducing the apoptosis of intestinal epithelial cells, and effectively alleviating inflammation both in vivo and in vitro. 2'-Hydroxycinnamaldehyde bound directly to STAT3 and inhibited its activation. The modulation of STAT3 activation levels due to STAT3 knockdown or overexpression influenced the mitigating effects of HCA on colitis. Further analysis indicated that the remission effect of HCA was not observed in STAT3ΔIEC mice, indicating that STAT3 mediated the anti-inflammatory effects of HCA. CONCLUSIONS: We present a novel finding that HCA reduces colitis severity by attenuating intestinal mucosal barrier damage via STAT3. This discovery holds promise as a potential new strategy to alleviate UC.

The current clinical therapeutic drugs for ulcerative colitis (UC) remain inadequate owing to certain adverse events. Administration of 2ʹ-hydroxycinnamaldehyde (HCA) significantly reduces colitis severity via direct inhibition of STAT3 to attenuate intestinal mucosal barrier damage. Hence, HCA may be a potential new strategy in UC.

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.

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.

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.

The catalytic hydrodeoxygenation of bio-oil for upgradation from lignocellulosic biomass.

The increasing depletion of oil resources and the environmental problems caused by using much fossil energy in the rapid development of society. The bio-oil becomes a promising alternative energy source to fossil. However, bio-oil cannot be directly utilized, owing to its high proportion of oxygenated compounds with low calorific value and poor thermal stability. Catalytic hydrodeoxygenation (HDO) is one of the most effective methods for refining oxygenated compounds from bio-oil. HDO catalysts play a crucial role in the HDO reaction. This review emphasizes the description of the main processing of HDO and various catalytic systems for bio-oil, including noble/non-noble metal catalysts, porous organic polymer catalysts, and polar solvents. A discussion based on recent studies and evaluations of different catalytic materials and mechanisms is considered. Finally, the challenges and future opportunities for the development of catalytic hydrodeoxygenation for bio-oil upgradation are looked forward.

Effect of Dietary Patterns on Inflammatory Bowel Disease: A Machine Learning Bibliometric and Visualization Analysis.

AIMS: This study aimed to analyze the related research on the influence of dietary patterns on IBD carried out over the past 30 years to obtain the context of the research field and to provide a scientific basis and guidance for the prevention and treatment of IBD. METHODS: The literature on the effects of dietary patterns on inflammatory bowel disease published over the past three decades was retrieved from the Web of Science Core Collection (WoSCC) database. CiteSpace, VOSviewer, the R software (version 4.3.0) bibliometrix package, the OALM platform, and other tools were used for the analyses. RESULTS: The growth of scientific papers related to this topic can be divided into two stages: before and after 2006. Overall, the growth of the relevant literature was in line with Price's literature growth curve. Subrata Ghosh and Antonio Gasbarrini are the authors with the highest academic influence in the field, and Lee D.'s research results are widely recognized by researchers in this field. Among the 72 countries involved in the study, the United States contributed the most, while China developed rapidly with regard to research being carried out in this area. From a regional perspective, countries and institutions in North America, Europe, and East Asia have made the most significant contributions to this field and have the closest cooperation. Among the 1074 articles included in the study, the most influential ones tended to consider the mechanism of the effect of dietary patterns on IBD from the perspective of the microbiome. Multiple tools were used for keyword analysis and mutual verification. The results showed that NF-κB, the Mediterranean diet, fatty acids, fecal microbiota, etc., are the focus and trends of current research. CONCLUSIONS: A Mediterranean-like dietary pattern may be a good dietary habit for IBD patients. Carbohydrates, fatty acids, and inulin-type fructans are closely related to IBD. Fatty acid, gut microbiota, NF-κB, oxidative stress, and endoplasmic reticulum stress are the hot topics in the study of the effects of dietary patterns on IBD and will be emerging research trends.

A Novel Predictive Model of Pathological Lymph Node Metastasis Constructed with Preoperative Independent Predictors in Patients with Renal Cell Carcinoma.

Introduction: Renal cell carcinoma (RCC) is one of the most common urinary tumors. The risk of metastasis for patients with RCC is about 1/3, among which 30−40% have lymph node metastasis, and the existence of lymph node metastasis will greatly reduce the survival rate of patients. However, the necessity of lymph node dissection is still controversial at present. Therefore, a new predictive model is urgently needed to judge the risk of lymph node metastasis and guide clinical decision making before operation. Method: We retrospectively collected the data of 189 patients who underwent retroperitoneal lymph node dissection or enlarged lymph node resection due to suspected lymph node metastasis or enlarged lymph nodes found during an operation in Tongji Hospital from January 2016 to October 2021. Univariate and multivariate logistic regression and least absolute shrinkage and selection operator (lasso) regression analyses were used to identify preoperative predictors of pathological lymph node positivity. A nomogram was established to predict the probability of lymph node metastasis in patients with RCC before surgery according to the above independent predictors, and its efficacy was evaluated with a calibration curve and a DCA analysis. Result: Among the 189 patients, 54 (28.60%) were pN1 patients, and 135 (71.40%) were pN0 patients. Three independent impact factors were, finally, identified, which were the following: age (OR = 0.3769, 95% CI = 0.1864−0.7622, p < 0.01), lymph node size according to pre-operative imaging (10−20 mm: OR = 15.0040, 95% CI = 1.5666−143.7000, p < 0.05; >20 mm: OR = 4.4013, 95% CI = 1.4892−7.3134, p < 0.01) and clinical T stage (cT1−2 vs. cT3−4) (OR = 3.1641, 95% CI = 1.0336−9.6860, p < 0.05). The calibration curve and DCA (Decision Curve Analysis) showed the nomogram of this predictive model had good fitting. Conclusions: Low age, large lymph node size in pre-operative imaging and high clinical T stage can be used as independent predictive factors of pathological lymph node metastasis in patients with RCC. Our predictive nomogram using these factors exhibited excellent discrimination and calibration.

Pan-cancer analysis reveals the prognostic and immunologic roles of cereblon and its significance for PROTAC design.

Background: Cereblon (CRBN) has emerged as a vital E3 ubiquitin ligase for Proteolysis-targeting chimera (PROTAC) design. However, few studies focus on the physiological mechanism of CRBN, and more studies are needed to explore the influence of CRBN on tumorigenesis. This pan-cancer analysis aims to explore the prognostic and immunologic roles of CRBN, and provide new insight for CRBN into cancer treatment and PROTAC design. Methods: The TCGA database, TIMER 2.0 database, and TISIDB database were used to analyze the role of CRBN in pan-cancer. Multiple bioinformatic methods (ssGSEA, Kaplan-Meier, univariate cox regression, ESTIMATE, CIBERSORT) were applied to investigate the CRBN expression status, gene activity, prognostic values, and its correlation with immune scores, immune infiltration, immune-related functions, HALLMARKs functions, and response to immunotherapy in pan-cancer. Results: In most cancer types, the expression and activity of CRBN in tumor groups were lower compared with normal groups. Upregulated CRBN expression may indicate a better prognosis for cancer patients. The Immune score, stromal score, and tumor purity varied greatly among different cancer types. GSEA analysis showed that high CRBN expression was correlated with the downregulation of tumor-promoting signaling pathways. The level of CRBN was associated with Tumor mutation burden (TMB), Microsatellite instability (MSI), objective response rate (ORR), and immune cell infiltration in a few cancer types. Conclusion: Pan-cancer analysis reveals the potential role of CRBN as a prognostic biomarker and versatile immunologic roles in different cancer types. Upregulated expression of CRBN may be beneficial to CRBN-related immunotherapy and PROTAC design.

The effect of different timing of blood transfusion on oncological outcomes of patients undergoing radical cystectomy for bladder cancer: a systematic review and meta-analysis.

Highlights: This meta-analysis and systematic review aim to analyze the association between BT and oncological outcomes of patients undergoing RC for bladder cancer, and tries to find out whether the timing of blood transfusion could also have an effect on this relationship. A total of 20 retrospective studies from online databases and other sources are identified and enrolled in this study. The results show that BT administration during RC operation or perioperative period is significantly associated with worse oncological outcomes including ACM, CSM and DR. Background: Bladder cancer is one of the most common urological malignancies. Radical cystectomy (RC) remains the main treatment for localized muscle-invasive bladder cancer (MIBC) or high-grade non-muscle-invasive bladder cancer (NMIBC). In the process of RC, the administration of blood transfusion (BT) is sometimes needed, however, it may cause transfusion-related complications or lead to worse oncological outcomes. This meta-analysis and systematic review aims to give a comprehensive insight into the association between BT and oncological outcomes of patients undergoing RC, and tries to find out whether the timing of blood transfusion could also have an impact on this association. Methods: This systematic review and meta-analysis were carried out according to the PRISMA 2020 reporting guideline. We have searched four bibliographic databases including PubMed (Medline), EMBASE, Cochrane Library, and Web of Science with no language limitation. Studies investigating the association between BT and oncological outcomes of patients undergoing RC are identified and included in this research from inception through March 20, 2023. This research calculates the pooled hazard ratios (pHR) and 95% confidence intervals (95% CI) of all-cause mortality (ACM), cancer-specific mortality (CSM) and disease recurrence (DR) using Random Effects models or Fixed Effects models. Subgroup analyses stratified by parameters such as timing of transfusion are also conducted. This meta-analysis was registered with PROSPERO, CRD42022381656. Results: A total of 20 retrospective studies from online databases and other sources are identified and enrolled in this study. Results show that blood transfusion significantly increased the risks for ACM (HR = 1.33, 95% CI: 1.23-1.44), CSM (HR = 1.25, 95% CI: 1.15 - 1.35) and DR (HR = 1.26, 95% CI: 1.15 - 1.38). However, when stratified by the timing of BT, we find that only intraoperative and perioperative transfusion significantly increased in risks for worse prognosis, while postoperative transfusion raised none of the risks of ACM (HR = 1.26, 95% CI: 0.92-1.73), CSM (HR = 1.08, 95% CI: 0.93-1.26) nor DR (HR = 1.08, 95% CI: 0.90-1.29) significantly. Conclusion: BT administration during RC operation or perioperative period is significantly associated with worse oncological outcomes including ACM, CSM and DR. Clinicians should consider carefully when deciding to administrate BT to patients undergoing RC and carry out according to current guidelines.

Hyperthermia intravesical chemotherapy acts as a promising alternative to bacillus Calmette-Guérin instillation in non-muscle-invasive bladder cancer: a network meta-analysis.

Introduction: With the shortage of bacillus Calmette-Guérin (BCG) vaccine, it is important to find an alternative to BCG instillation, which is the most commonly used adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC) patients after transurethral resection of bladder tumor treatment (TURBt) to delay tumor recurrence. Hyperthermia intravesical chemotherapy (HIVEC) with mitomycin C (MMC) is a potential treatment choice. We aim to compare HIVEC with BCG instillation for the preventive efficacy of bladder tumor recurrence and progression. Methods: A network meta-analysis (NMA) was taken with MMC instillation and TURBt as the attached comparators. Randomized controlled trials (RCTs) with NIMBC patients after TURBt were included. Articles with pure BCG unresponsive patients and combined therapies were excluded. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023390363). Results: It was found that HIVEC had a non-significant 22% relative reduction in bladder tumor recurrence compared with BCG instillation [HIVEC vs. BCG: HR 0.78, 95% credible interval (CrI) 0.55-1.08] and a nonsignificant higher risk of bladder tumor progression (BCG vs. HIVEC: HR 0.77, 95% CrI 0.22-3.03). Discussion: HIVEC is a potential alternative to BCG, and it is expected to be the standard therapy for NMIBC patients after TURBt during the global shortage of BCG. Systematic Review Registration: PROSPERO identifier, CRD42023390363.

Integrated bioinformatic analysis and cell line experiments reveal the significant role of the novel immune checkpoint TIGIT in kidney renal clear cell carcinoma.

Background: T cell immunoglobulin and ITIM domain (TIGIT) is a widely concerned immune checkpoint, which plays an essential role in immunosuppression and immune evasion. However, the role of TIGIT in normal organ tissues and renal clear cell carcinoma is unclear. We aim to identify the critical role of TIGIT in renal clear cell carcinoma and find potential targeted TIGIT drugs. Materials and methods: Data retrieved from the GTEX database and TCGA database was used to investigate the expression of TIGIT in normal whole-body tissues and abnormal pan-cancer, then the transcriptome atlas of patients with kidney renal clear cell carcinoma (KIRC) in the TCGA database were applied to distinguish the TIGIT related features, including differential expression status, prognostic value, immune infiltration, co-expression, and drug response of sunitinib an anti-PD1/CTLA4 immunotherapy in KIRC. Furthermore, we constructed a gene-drug network to discover a potential drug targeting TIGIT and verified it by performing molecular docking. Finally, we conducted real-time polymerase chain reaction (PCR) and assays for Transwell migration and CCK-8 to explore the potential roles of TIGIT. Results: TIGIT showed a moderate expression in normal kidney tissues and was confirmed as an essential prognostic factor that was significantly higher expressed in KIRC tissues, and high expression of TIGIT is associated with poor OS, PFS, and DSS in KIRC. Also, the expression of TIGIT was closely associated with the pathological characteristics of the tumor, high expression of TIGIT in KIRC was observed with several critical functions or pathways such as apoptosis, BCR signaling, TCR signaling et al. Moreover, the expression of TIGIT showed a strong positive correlation with infiltration of CD8+ T cells and Tregs and a positive correlation with the drug sensitivity of sunitinib simultaneously. Further Tide ips score analysis and submap analysis reveal that patients with high TIGIT expression significantly show a better response to anti-PD1 immunotherapy. Following this, we discovered Selumetinib and PD0325901 as potential drugs targeting TIGIT and verified the interaction between these two drugs and TIGIT protein by molecular docking. Finally, we verified the essential role of TIGIT in the proliferation and migration functions by using KIRC cell lines. Conclusions: TIGIT plays an essential role in tumorigenesis and progression in KIRC. High expression of TIGIT results in poor survival of KIRC and high drug sensitivity to sunitinib. Besides, Selumetinib and PD0325901 may be potential drugs targeting TIGIT, and combined therapy of anti-TIGIT and other treatments show great potential in treating KIRC.

A Four-Cell-Senescence-Regulator-Gene Prognostic Index Verified by Genome-Wide CRISPR Can Depict the Tumor Microenvironment and Guide Clinical Treatment of Bladder Cancer.

Bladder cancer (BCa) is the 10th most commonly diagnosed cancer worldwide, and cellular senescence is defined as a state of permanent cell cycle arrest and considered to play important roles in the development and progression of tumor. However, the comprehensive effect of senescence in BCa has not ever been systematically evaluated. Using the genome-wide CRISPR screening data acquired from DepMap (Cancer Dependency Map), senescence genes from the CellAge database, and gene expression data from The Cancer Genome Atlas (TCGA), we screened out 12 senescence genes which might play critical roles in BCa. A four-cell-senescence-regulator-gene prognostic index was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression model. The transcriptomic data and clinical information of BCa patients were downloaded from TCGA and Gene Expression Omnibus (GEO). We randomly divided the patients in TCGA cohort into training and testing cohorts and calculated the risk score according to the expression of the four senescence genes. The validity of this risk score was validated in the testing cohort (TCGA) and validation cohort (GSE13507). The Kaplan-Meier curves revealed a significant difference in the survival outcome between the high- and low-risk score groups. A nomogram including the risk score and other clinical factors (age, gender, stage, and grade) was established with better predictive capacity of OS in 1, 3, and 5 years. Besides, we found that patients in the high-risk group had higher tumor mutation burden (TMB); lower immune, stroma, and ESTIMATE scores; higher tumor purity; aberrant immune functions; and lower expression of immune checkpoints. We also performed gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to investigate the interaction between risk score and hallmark pathways and found that a high risk score was connected with activation of senescence-related pathways. Furthermore, we found that a high risk score was related to better response to immunotherapy and chemotherapy. In conclusion, we identified a four-cell-senescence-regulator-gene prognostic index in BCa and investigated its relationship with TMB, the immune landscape of tumor microenvironment (TME), and response to immunotherapy and chemotherapy, and we also established a nomogram to predict the prognosis of patients with BCa.