Serotonin, also known as 5-HT, is a classical neurotransmitter produced both in the nervous system and in non-nervous system. Its involvement in various fundamental physiological processes and pathogenic conditions is significant, as it binds to a diverse array of functionally distinct receptors. Apart from binding to 5-HT receptors and activating downstream signaling cascades, recent studies have revealed a novel posttranslational modification named serotonylation, where serotonin is re-taken up by serotonin transporter and is covalently attached to target proteins ranging from histone proteins to nonhistone proteins. Transglutaminases (TGMs), especially TGM2, catalyze serotonylation through the transfer of serotonin to the glutamine residues of target proteins. This review aims to investigate recent progresses in understanding the involvement of serotonylation in physiological and pathological processes. In addition, this review emphasizes how to target serotonylation as a therapeutic strategy for disease management.

Metastatic castration-resistant prostate cancer (mCRPC) after treatment with docetaxel and androgen receptor signaling inhibitors (ARSIs) has limited treatment options. Although enzalutamide has shown activity after abiraterone and docetaxel, robust evidence from randomized phase III trials is lacking. Deutenzalutamide, a novel derivative with slower metabolism and improved pharmacokinetics, may offer enhanced safety and efficacy. This phase III, double-blind trial conducted at 36 centers in China enrolled patients whose disease progressed on or who were intolerant to abiraterone and docetaxel, or who were ineligible for docetaxel. Patients were randomized (2:1) to receive deutenzalutamide 80 mg once daily or placebo until progression or unacceptable toxicity; the primary endpoint was radiographic progression-free survival (rPFS). Of 417 patients (276 deutenzalutamide; 141 placebo), all had previously received abiraterone, and 68% had also received docetaxel. Deutenzalutamide significantly improved rPFS (HR, 0.58; P = 0.0001), reducing the risk of progression by 42%. Although the initial OS analysis was not significant (HR, 0.95), sensitivity analyses adjusting for subsequent therapies showed significant OS benefits (HR, 0.65-0.73). Treatment-related grade 3 or higher adverse events occurred in 22.3% of patients treated with deutenzalutamide, compared with 15.0% with placebo. The most common treatment-related adverse event was anemia, reported at any grade in 21.2% versus 17.9%, with grade 3/4 anemia in 6.6% versus 2.9%, respectively. Notably, no seizures or falls were reported. In summary, deutenzalutamide significantly prolonged rPFS and, after adjustment, showed a potential OS benefit with a favorable safety profile, supporting its promise as a new treatment option for mCRPC. Clinical trial registration: NCT03851640.

Background: Transplant glomerulopathy (TG) has heterogeneous graft outcomes, but no simple bedside rule is established for post-biopsy risk stratification. We tested whether biopsy-time estimated glomerular filtration rate (eGFR) and proteinuria yield a practical rule and whether pathology and immunology improve risk ranking. Methods: We included 344 adults with kidney-only transplants and indication-biopsy-proven TG at Charité, followed through 2025. Data-derived cutpoints were rounded to eGFR ≤30 mL/min/1.73 m2 and 24-h urine protein >400 mg/day. The primary outcome was death-censored graft failure. The complete cutpoint-selection workflow was repeated in 2000 bootstrap samples. The fixed rule was applied unchanged to an independent 25-patient cohort. In a common subset, performance was benchmarked against reconstructed abbreviated iBox. Findings: Among 320 patients with both markers, 217 experienced graft failure and 150 met both thresholds. Five-year graft-failure risk was 81.2% versus 41.3% (adjusted hazard ratio 3.37, 95% CI 2.41–4.72). Five-year AUC was 0.715 for the rule and 0.738 for the continuous-marker model (ΔAUC −0.023, 95% CI −0.072 to 0.020; p=0.339). Adding histologic, immunologic, or TG-category domains left the 5-year AUC virtually unchanged (ΔAUC, 0.001–0.011; all likelihood-ratio P≥.27). Optimism-corrected rule AUC was 0.704, and the adverse stratum remained worst in 92.5% of full-workflow bootstrap samples. In a common 237-patient subset, AUCs were 0.727 for the rule, 0.744 for continuous markers, and 0.746 for abbreviated iBox; neither comparison with iBox was statistically significant. The fixed rule also separated risk in the independent cohort. Interpretation: The 30/400 rule converts two routine measurements into transparent TG-specific risk strata. It identifies high-risk patients, retains most continuous-model discrimination, and provides a concise framework for risk communication and cohort stratification. Multicentre validation is warranted.

Bladder cancer (BC) is an aggressive and treatment-resistant malignancy with a high recurrence rate. Current first-line therapies only provide limited relief due to chemoresistance and toxicity. Natural products are emerging as promising chemotherapeutic agents due to their multi-target mechanisms and excellent safety profile. In this study, we evaluated the anti-BC effects of echinocystic acid (EA), a pentacyclic triterpenoid, on BC cells and investigated the underlying mechanism. We found that EA effectively inhibited proliferation, triggered G1-phase cell cycle arrest, and simultaneously suppressed cellular invasion and migration capabilities in vitro. Although EA did not obviously induce apoptosis in BC cells at the doses that were effective in suppressing their growth, it successfully triggered ferroptosis within these cells. Moreover, EA suppressed xenograft tumor growth of BC cells in vivo and demonstrated a favorable safety profile. Mechanistically, EA interacted with AKT1, reducing its phosphorylation and thereby inhibiting the AKT1/GSK3β/β-Catenin signaling pathway. Furthermore, EA exhibited synergistic effects with gemcitabine in inhibiting BC cells in vitro and in vivo. Overall, our results suggest that EA may exert its anti-BC effects, at least in part, by inhibiting the AKT1/GSK3β/β-Catenin signaling pathway. When combined with the clinically approved anti-tumor drug gemcitabine, EA may produce a synergistic anti-BC effect. Most importantly, this study identifies EA as a novel inducer of ferroptosis in BC and underscores its potential for clinical application.

In this study, we report that KIF26B is upregulated in bladder cancer and acts as an independent prognostic factor. Knockdown of kif26b blocks the proliferation, metastasis, and cisplatin resistance of bladder cancer cells. Mechanistically, TCF4 potently stimulates kif26b transcription by directly binding to its promoter. KIF26B activates the Wnt/β-catenin signaling pathway through association with TRAF2 and thus promotes the formation of the TCF4/β-catenin complex. KIF26B promotes the protein stability of TRAF2 by facilitating the OTUB2-mediated de-ubiquitination of TRAF2. Importantly, KIF26B promotes the nuclear translocation of TRAF2 through enhancing its association with IPO11, a process that is dependent on the C-terminal domain of β-catenin. Additionally, phosphorylation of tyrosine 78 in TRAF2 is essential for its binding to KIF26B in response to Wnt3a signaling. Furthermore, a KIF26B/TRAF2/PD-L1 axis is identified in bladder cancer, and combined therapy of anti-B7-H3 antibody with kif26b knockdown yields superior anti-tumor effects.

Histone lactylation modification and RNA m6A modification play important roles in cisplatin resistance of bladder cancer (BCa). Hypoxia drives cisplatin resistance in BCa by analyzing the TCGA-BLCA cohort, where hypoxia signatures predicted poor overall survival. In vitro, hypoxia elevated lactate production via LDHA, inducing H3K18la catalyzed by KAT2B, which activated RBM15 transcription. RBM15 stabilized IGFBP3 mRNA via m6A modification depending on its SPOC domain, increasing IGFBP3 protein. Nuclear translocation of IGFBP3 complexed with p-EGFR/p-DNA-PKcs, enhancing DNA repair and reducing cisplatin-induced damage. Clinically, BCa tissues exhibited elevated LDHA/H3K18la/RBM15/IGFBP3, further amplifying post-cisplatin chemotherapy. Targeting this axis with LDHA inhibitor (stiripentol) and EGFR inhibitor (gefitinib) synergistically reversed cisplatin resistance in vitro and in vivo. This study unveils the “hypoxia–H3K18la–RBM15–IGFBP3” axis as a central driver of cisplatin resistance and proposes dual metabolic–epigenetic inhibition as a therapeutic strategy for refractory BCa.

Abnormal expression of kinesins has been observed in several types of cancer. The present study provided the first evidence that KIF26B could induce RNA m5C modification in bladder cancer (BCa). Detailly, KIF26B interacted with NSUN2 and recruited ubiquitinase STUB1 to promote K63-linked ubiquitination of NSUN2 at K511 site. K63-linked ubiquitination enabled NSUN2 to bind to KPNA1 and translocate into nucleus where it drove RNA m5C modification. Furthermore, KIF26B induced liquid-liquid phase separation (LLPS) of YBX1 and upregulated IL-6 expression through NSUN2/m5C/YBX1 axis. Secreted IL-6 then activated STAT3 signaling to promote transcription of kif26b through direct binding between STAT3 and kif26b promoter. IL-6 also recruited DLAT to acetylate NSUN2 at K229 site and increased association affinity between NSUN2 and KIF26B. Together, these established a KIF26B/NSUN2/m5C/IL-6 positive feedback loop, suggesting that targeting KIF26B may be a promising therapeutic strategy for BCa.

Circular RNA (circRNA), a class of non-coding RNAs characterized by its covalently closed circular structure, exhibits high stability and resistance to degradation. Over recent years, circRNAs have emerged as key regulators in various biological processes, which influence tumorigenesis and progression through mechanisms such as regulating gene transcription, competitively binding to miRNA, interacting with proteins, and encoding peptides, making it a potential novel tumor biomarker or therapeutic target. Prostate cancer is increasingly becoming the most common cancer among men in many countries and regions worldwide. However, the specific molecular mechanism of malignant progression of prostate cancer is still not fully determined. In this review, we summarize the regulatory roles and molecular mechanisms of circRNA in prostate cancer, focusing on biological functions such as cell cycle, cell proliferation, apoptosis, ferroptosis, migration, invasion, metastasis, drug or radiotherapy resistance, and immune microenvironment. We provide advanced insights on the role, functions and potential clinical applications of circRNA in prostate cancer.

This paper investigates the adaptive fixed-time stabilization problem for a class of strict-feedback stochastic nonlinear systems with unknown parameter vectors and unbounded but estimable nonlinear boundary functions. By employing distributed Lyapunov functions for state-space partitioning and distinct error transformations, this paper ensures system states converge to zero in a fixed-time regardless of initial conditions and stochastic disturbances. This paper introduces a distributed controller design that uniquely combines adaptive backstepping with the adding one power integrator method, restricting tracking errors to a positive invariant set to avoid the inherent singularity risks in traditional backstepping-based stochastic control. Unlike existing fixed-time control approaches for stochastic systems, which are typically limited to bounded uncertainties or rely on fuzzy logic with high computational overhead, this paper promotes a method handles fully unknown and unbounded nonlinear boundaries by means of adaptive estimation, thereby completely eliminating the redundant terms inherent in fuzzy approximations and enhancing 30–40

Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, with challenges in diagnosis and treatment due to tumor heterogeneity. This study identifies palmitoylation-related signature genes as potential diagnostic and therapeutic targets. Integrating GEO datasets, six differentially expressed genes (DEGs) linked to palmitoylation were identified. Machine learning algorithms (LASSO, RF, SVM) selected three core genes: TRPM4, LAMB3, and APOE. A diagnostic model based on these genes achieved an AUC of 0.929, demonstrating robust accuracy in distinguishing PCa from normal tissues. Functional analysis revealed roles in lipid metabolism and immune modulation, with ssGSEA highlighting correlations between key genes and immune cell infiltration. Experimental validation showed that LAMB3 overexpression suppressed PCa cell proliferation, migration, and invasion, while knockdown enhanced these processes. Molecular docking identified diethylstilbestrol as a potential therapeutic agent targeting LAMB3 and APOE. These findings emphasize the clinical relevance of palmitoylation-related genes in PCa diagnosis and therapy, offering novel biomarkers and insights for personalized treatment strategies.

Objective: Robot-assisted simple prostatectomy (RASP) is increasingly used as a surgical treatment option for large benign prostatic hyperplasia (BPH) (>80 mL). However, there is no sufficient expert consensus or guidelines to guide clinical practice. We aimed to obtain expert opinions for RASP for large BPH. Methods: A systematic review of the literature was performed in April 2024 using the PubMed, Embase, and Web of Science databases. Search terms were combined to construct the following search strings: (robotic) AND (simple OR benign) AND (prostatectomy). Search results were filtered by language (English only), species (human), and publication type (original article). This study used a two-phase modified Delphi approach. Results: In this expert consensus, some frequently used RASP techniques, including robot-assisted retropubic prostatectomy, robot-assisted transvesical prostatectomy, and robot-assisted urethra-sparing prostatectomy, are described. RASP offers a short learning curve for surgeons with experience in robotic surgery. Severe complications are rare in patients who undergo RASP. Conclusion: RASP technique can be recommended as a safe and effective minimally invasive treatment for symptomatic BPH patients with large prostate glands.

Background:Bladder cancer (BC) represents a common malignancy and is characterized by high heterogeneity and complex biological behaviors, which pose substantial challenges to its effective treatment. Mounting evidence highlights the pivotal roles of ribonucleic acid (RNA) modifications, particularly N6-methyladenosine, alongside others such as 1-methyladenosine, 5-methylcytosine, N4-acetylcytidine, and 7-methylguanosine, in the regulation of the proliferation, migration, drug resistance, and immune evasion of BC cells. Objective:This article comprehensively reviewed the regulatory mechanisms and biological impacts of these RNA modifications in BC, with a focus on the interplay between RNA modifications and immune evasion, as well as their emerging roles in precision medicine. By looking into these underexplored areas, this work provided novel insights into RNA modifications as diagnostic markers, prognostic indicators, and therapeutic targets, paving the way for advancements in BC precision medicine. Conclusion:RNA modifications impact key processes such as proliferation, migration, drug resistance, and immune evasion of BC cells. Targeting RNA modification pathways offers promising strategies for enhancing the efficacy of current treatments for and overcoming drug resistance of BC.

In the present study, a novel mesoporous silica/nitrogen-doped graphene composite modified electrode (MS/ NGR/GCE) is prepared using an in-situ electrochemical method. The large specific surface area, excellent loading and electron transfer capabilities of the mesoporous silica/nitrogen-doped graphene composite make the modified electrode favored for electrochemical sensing. The sensing properties of different electrodes towards tannins are investigated, and the results show that MS/NGR/GCE exhibits much better sensing performance than individual graphene or mesoporous silica modified electrodes. Under optimal conditions, the linear range of MS/ NGR/GCE for determination of tannins is 0.10-5.0 mu mol/L and 5.0-80 mu mol/L, respectively, with a detection limit of 0.050 mu mol/L (S/N = 3). These results demonstrate that this study has opened up a new pathway for constructing high-performance nanocomposite electrochemical sensors.

Piwi-interacting RNAs (piRNAs), while crucial for genomic integrity in germline cells, remain poorly characterized in somatic cancers. This study identifies piR-43452 as a significantly downregulated piRNA in bladder cancer (BCa), with loss of expression correlating clinically with muscle invasion and lymph node metastasis. Through assays in vitro and in vivo, we demonstrate that piR-43452 acts as a potent tumor suppressor, inhibiting BCa cell proliferation, migration, and xenograft growth while promoting apoptosis. Mechanistically, we identified that piR-43452 directly binds the 3'UTR of LRP1 mRNA and recruits the GTSF1/PIWIL4 complex, which enhances target cleavage through GTSF1-dependent conformational activation. This post-transcriptional regulation led to significant LRP1 suppression, subsequently inhibiting proliferation and restoring chemosensitivity. Our findings establish a novel piRNA-guided mechanism for overcoming chemoresistance and suggest that targeting the piR-43452/GTSF1/PIWIL4/LRP1 axis may provide therapeutic benefit in gemcitabine-resistant BCa.

This post-approval commitment study addressed the limited data on the safety and efficacy of apalutamide in Chinese patients with non-metastatic castration-resistant prostate cancer (NM-CRPC). Utilizing a double-blinded, placebo-controlled trial with pre-planned crossover design, 75 patients were randomized (2:1) to receive apalutamide 240 mg daily or placebo while continuing androgen deprivation therapy. Apalutamide significantly reduced the risk of prostate-specific antigen (PSA) progression by 76.7% compared with placebo (hazard ratio [HR] = 0.233, p = 0.0052), with confirmed PSA response rate of 92.0% versus 12.0%. The median metastasis-free survival with apalutamide was 36.8 months, while the median overall survival was not reached. Grade 3 and 4 treatment-emergent adverse events were reported in 43.1% and 4.2% of patients, respectively, with hypertension, pneumonia, and rash being the most frequently reported, and the safety profile was consistent with existing data on apalutamide. Overall, these findings indicate that apalutamide is both efficacious and safe for Chinese patients, providing a valuable treatment option for high-risk NM-CRPC.

Prostate cancer (PCa) is a prevalent cancer and a major cause of cancer-related deaths in men worldwide. Growing evidence indicates that Staphylococcal nuclease and Tudor domain containing 1 (SND1) is a multifunctional protein extensively involved in transcriptional regulation, RNA maturation, post-transcriptional modifications, and other processes. However, previous studies have rarely investigated the function of SND1 as an RNA-binding protein in PCa tumorigenesis. The Cancer Genome Atlas and NCBI Gene Expression Omnibus (GEO) databases were used to evaluate SND1 expression levels in PCa. We conducted a series of in vitro and in vivo functional experiments to assess the biological functions of SND1, including cell counting kit-8, colony formation, Transwell and wound-healing assays, and animal experiments in nude mice. Chromatin immunoprecipitation, dual-luciferase reporter assay, and DNA pull-down assay were performed to validate the association between the upstream transcription factor and SND1. Based on mass spectrometry, RNA-seq, and RNA immunoprecipitation (RIP)-seq, we identified the downstream targets of SND1- Sestrin 2 (SESN2), which were validated through qRT-PCR, Western blotting, RIP-qPCR, dual-luciferase reporter assay, and RNA pull-down assay. Finally, a series of functional assays and Western blotting analyses confirmed SESN2 as a downstream target of SND1. Our research identified that SND1 was significantly elevated in PCa, and knocking down SND1 repressed PCa multiplication and migration. Mechanistically, sterol regulatory element binding transcription factor 1 (SREBF1) bound to the promoter of the SND1 gene and activated its transcription, which subsequently formed a complex with metadherin (MTDH). This complex is directly bound to and degraded SESN2 mRNA, and disruption of this interaction with C26-A6 inhibited MTDH-SND1-mediated SESN2 degradation. Notably, SESN2 expression was inhibited in PCa and may exert tumor-suppressive effects by affecting the AMPK/mTOR signaling pathway. Rescue experiments indicated that knocking down SND1 or MTDH significantly inhibited PCa proliferation and migration, and knocking down SESN2 partially reversed this effect. Our study reveals SND1 overexpression in PCa, which is transcriptionally activated by SREBF1. Mechanistically, SND1 interacts with MTDH and promotes SESN2 mRNA degradation, modulating PCa progression through the AMPK/mTOR pathway.

Patulin (PAT) in food is a menace to human health. Hence, a sensitive and precise approach to PAT detection is significant. In this research, an innovative electrochemical assay was developed for sensitively determining PAT by assembling aptamers on a carboxylation hierarchically porous carbon (HPC-COOH) modified glassy carbon electrode. Diverse analytical methods were used to describe electrode morphology, structure, chemical composition, and electrochemistry properties. The HPC-COOH, with a large surface area, played a crucial role as a unique substrate to effectively immobilize aptamers and enhance target PATs' recognition and capture ability. Simultaneously, the excellent electrical conductivity of HPC-COOH was significant for the signal amplification of sensors. Under optimized conditions, the aptasensor enabled efficient PAT detection in a broad concentration range (0.5 to 5.0×106ng/L) with a low detection limit (0.25ng/L). The designed aptasensor showed high sensitivity, selectivity, reproducibility, and stability under optimized conditions. The sensors’ feasibility for practical applications was further demonstrated by analyzing apple juice and haw juice samples.

This brief describes a fast finite time adaptive control strategy for p-norm stochastic nonlinear systems (SNSs) using adding a power integrator approach. In terms of convergence speed, finite time control (FTC) offers a substantial advantage in the vicinity of the equilibrium point, but it may exhibit notably slower convergence compared to exponential convergence when the initial state is far from the origin. To overcome this problem, the Lyapunov function is skillfully constructed in this study. A method is devised based on this function, which incorporates the characteristic of adding a power integrator technique and the symbolic function to effectively tackle challenges posed by complex system structures. Then, adaptive control is utilized to deal with the mismatched uncertain nonlinear function. Subsequently, a novel fast FTC strategy is proposed for p-norm SNSs with dead-zone via the back-stepping framework, which ensures the transient performance of the closed-loop system. In comparison to existing results, this controller effectively achieves performance control for p-norm SNSs with dead-zone and mismatched uncertainties functions. Finally, the superiority of the scheme is illustrated by comparative simulations. Note to Practitioners-The FTC problem is a prominent subject in the field of control, playing a crucial role in practical applications. This is especially notable in p-norm nonlinear systems, where the dynamic behavior exhibits uncontrollable linearization characteristics near the origin, introducing complexity to control analysis. Another challenging aspect in nonlinear control is the impact from external disturbances. In practical systems, the presence of random disturbances is inevitable and frequently results in system instability. A fundamental technical barrier is the involvement of Brownian motion integral terms in stochastic nonlinear systems, along with It & ocirc; differential, which introduces not only gradients in Lyapunov analysis but also the Hessian of the Lyapunov function. Furthermore, it is observed that mismatched uncertainties and dead-zone phenomena exist in real systems. Designing fast finite-time controllers has become a focal point of controller research. To address these issues, this paper proposes a fast FTC algorithm tailored for a class of p-norm SNSs with mismatched uncertainties. The proposed approach ensures that the system state can converge to the desired region near the origin in an almost fast finite time.

Accurate prediction of solar irradiance is crucial for the effective utilization of solar energy. However, in real-world scenarios, complex irradiance patterns and prevalent incomplete data pose challenges to precise forecasting, resulting in additional uncertainties and instability. To address these issues, this study proposes a novel irradiance forecasting model that integrates a Mask-Transformer data imputation module and a prediction module centered around the typical patterns representation mechanism. The Mask-Transformer leverages a mask modeling mechanism to model the context of missing data, facilitating accurate estimation of missing values and reducing noise and uncertainty in the input data. The typical patterns representation mechanism comprises a series decomposition module and a feature fusion module, providing the module with the capability to mitigate nonlinearity and nonstationarity in solar irradiance data. This enhancement leads to improved short-term forecasting performance while maintaining long-term forecasting capabilities. Experimental results on two datasets demonstrate that the proposed model exhibits sufficient robustness and accuracy, making it effective in scenarios with incomplete data.

R-loops are prevalent three-stranded nucleic acid structures, comprising a DNA-RNA hybrid and a displaced single-stranded DNA, that frequently form during transcription and may be attributed to genomic stability and gene expression regulation. It was recently discovered that RNA modification contributes to maintain the stability of R-loops such as N6-methyladenosine (m6A). Yet, m6A-modified R-loops in regulating gene transcription remains poorly understood. Here, we demonstrated that insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) recognize R-loops in an m6A-dependent way. Consequently, IGF2BPs overexpression leads to increased overall R-loop levels, cell migration inhibition, and cell growth retardation in prostate cancer (PCa) via precluding the binding of DNA methyltransferase 1(DNMT1) to semaphorin 3 F (SEMA3F) promoters. Moreover, the K homology (KH) domains of IGF2BPs are required for their recognition of m6A-containing R-loops and are required for tumor suppressor functions. Overexpression of SEMA3F markedly enhanced docetaxel chemosensitivity in prostate cancer via regulating Hippo pathway. Our findings point to a distinct R-loop resolution pathway mediated by IGF2BPs, emphasizing the functional importance of IGF2BPs as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology. The manuscript summarizes the new role of N6-methyladenosine in epigenetic regulation, we introduce the distinct R-loop resolution mediated by IGF2BP proteins in an m6A-dependent way, which probably lead to the growth retardation and docetaxel chemotherapy resistance in prostate cancer. Moreover, our findings first emphasized the functional importance of IGF2BPs as epigenetic R-loop readers in transcriptional genetic regulation and cancer biology. In addition, our research provides a novel RBM15/IGF2BPs/DNMT1 trans-omics regulation m6A axis, indicating the new crosstalk between RNA m6A methylation and DNA methylation in prostate cancer.