The widespread application of silver nanoparticles (AgNPs) raises increasing concerns over their male reproductive toxicity, yet a systematic, single-cell-resolved mechanistic understanding remains lacking. Here, we employed single-cell transcriptomics, metabolomics and functional experiments to explore AgNPs-triggered cellular remodeling of testes. Pubertal rats were orally exposed to AgNPs for 35 consecutive days. The particles traversed the blood-testis barrier (BTB), accumulated within the gonad, and ultimately impaired fertility. Metabolomics revealed that AgNPs altered metabolic milieu and reprogramed lipid metabolism. Then, high-resolution single-cell transcriptomic profiling identified ten distinct testicular cell populations, with spermatogenic cells and Sertoli cells exhibiting heightened susceptibility to AgNPs. Pseudotime trajectory analysis further revealed a selective reduction in undifferentiated spermatogonial stem cells. Functional and molecular pathway explorations were further conducted using C18-4, GC-2, and TM4 cell lines, as well as human primary Sertoli cells. Integrated analysis of in vitro and sequencing data reciprocally demonstrated the cell-type-specific toxicity: suppressed proliferation and elevated apoptosis in spermatogonia; intensified oxidative stress and apoptosis in spermatocytes; impaired spermatid differentiation; and disrupted growth factor synthesis and BTB integrity in Sertoli cells. Mechanically, these toxic effects were driven by AgNPs-induced mitochondrial dysfunction, glutathione metabolism dysregulation, and activation of the PINK1/Parkin-mediated mitophagy pathway, thereby disturbing Sertoli cell homeostasis and ultimately impaired the nutritional support and microenvironmental maintenance essential for spermatogenesis. These findings provide a comprehensive understanding of AgNPs-induced testicular toxicity, delineate cellular vulnerabilities and molecular mechanisms, and promise potential therapeutic countermeasures against nanoparticle-induced male infertility.

BACKGROUND:Premature ejaculation is a prevalent sexual dysfunction, yet the variable patient response to first-line dapoxetine treatment poses a major clinical challenge, highlighting the unmet need for biomarkers to guide diagnosis and therapy. AIM:This study aimed to investigate the distinct plasma metabolic profile of primary premature ejaculation (PPE) patients, and to develop machine learning-based diagnostic and therapeutic response prediction models. METHODS:A multicenter cohort comprising 69 patients with PPE and 51 healthy control (HC) subjects was enrolled. Plasma samples underwent untargeted metabolomic analysis. Differentially expressed metabolites were identified, and pathway enrichment analyses were conducted using Small Molecule Pathway Database and Kyoto Encyclopedia of Genes and Genomes. Three machine learning algorithms-Support Vector Machine, Random Forest, and Least Absolute Shrinkage and Selection Operator regression-were employed to screen biomarkers. Subsequently, targeted metabolomics analysis was used to quantify neurotransmitter levels. OUTCOMES:The primary outcomes included the Premature Ejaculation Diagnostic Tool, the intravaginal ejaculation latency time, and the Clinical Global Impression of Change scale score after a 4-week observation period of on-demand dapoxetine treatment. RESULTS:Multivariate analysis revealed clear separations in metabolic profiles between the PPE and HC groups, and between dapoxetine treatment (DT)-Response and DT-No response groups. Pathway analysis indicated significant enrichment in amino acid metabolism pathways for PPE-related differentially expressed metabolites (DEMs). Additionally, DT-Response-related DEMs were associated with D-Amino acid metabolism and Arginine biosynthesis. Machine learning identified a panel of 4 consensus metabolites for diagnosing PPE, achieving an area under the curve (AUC) of 0.995 in the train cohort and 0.917 in the test cohort. For predicting DT response, three metabolites were selected, forming a model with an AUC of 0.905 (train) and 0.811 (test). It is important to note that these promising initial results require further validation in larger, independent cohorts to confirm their generalizability. Furthermore, targeted metabolomics analysis confirmed significant dysregulation of multiple neurotransmitters in the PPE group. CLINICAL IMPLICATIONS:The machine learning-based models we established show robust performance in diagnostic and dapoxetine treatment response prediction. STRENGTHS & LIMITATIONS:The establishment of the machine learning-based diagnostic and predictive models represents a key strength, though their clinical translation requires further validation in larger cohorts. CONCLUSION:This study delineates distinct metabolic profiles in PPE, establishes robust machine learning-based models for diagnosis and DT-Response prediction, and reveals the involvement of neurotransmitter dysregulation in its pathophysiology.

ABSTRACT Clear cell renal cell carcinoma (ccRCC) exhibits notable genetic and epigenetic heterogeneity. Although H4K20me3 is markedly enriched in ccRCC samples, the precise functional role of this histone modification in ccRCC pathogenesis remains elusive. The expression and prognostic value of KMT5C, the catalytic enzyme responsible for H4K20me3, were investigated using public databases and clinical specimens from our institute. Functional experiments were conducted to elucidate the role of KMT5C in ccRCC progression. Mechanistically, comprehensive molecular approaches, including peptide pull‐down, shotgun proteomics, co‐immunoprecipitation, microscale thermophoresis, RNA‐seq, ChIP‐qPCR, and RIP‐qPCR, were employed to dissect the signaling pathway. The levels of H4K20me3 and KMT5C were significantly elevated in ccRCC. And elevated level of KMT5C was associated with the poor prognosis. Functional experiments demonstrated the oncogenic role of KMT5C in ccRCC proliferation and migration. Mechanistically, we identified EWSR1, an RNA/DNA‐binding protein, as a direct interaction partner of H4K20me3. Downregulation of EWSR1 significantly inhibited cell proliferation and migration of ccRCC cells. Transcriptomic analysis combined with ChIP and RIP experiments revealed that KMT5C and EWSR1 co‐regulate the expression of ACADM. Specifically, KMT5C‐mediated H4K20me3 directly suppressed ACADM transcription, whereas EWSR1 further reduced ACADM mRNA stability by modulating its m 6 A modification level. Importantly, the combination of A‐196 (KMT5C inhibitor) and sunitinib effectively inhibited tumor growth in a xenograft model, demonstrating significant therapeutic potential. Our study revealed that KMT5C‐mediated H4K20me3 promotes ccRCC progression by suppressing ACADM transcription and destabilizing its mRNA through recruitment of EWSR1. Targeting KMT5C with A‐196 in combination with sunitinib represents a promising therapeutic strategy for ccRCC.

Renal artery aneurysm and renal vein aneurysm are rare vascular lesions, and their coexistence within the same kidney poses considerable diagnostic and surgical challenges. We report a 51-year-old woman presenting with recurrent left flank and back pain. Computed tomography angiography demonstrated a 2.1-cm upper-pole renal artery aneurysm arising from a terminal intrarenal arterial branch and a 3.0-cm renal vein aneurysm arising from a large intrarenal venous tributary in the mid-pole renal sinus. Nephrectomy had been recommended at another institution because of the anatomical complexity, but the patient strongly wished to preserve the affected kidney. She underwent single-port retroperitoneoscopic excision of both aneurysms, with closure of the terminal arterial stump, primary closure of the venous wall defect, and renorrhaphy. The operative time was 95 min, warm ischemia time was 20 min, and estimated blood loss was 30 mL. Histopathological examination confirmed the diagnoses. At 4 months after surgery, color Doppler ultrasonography demonstrated preserved main left renal arterial flow and intrarenal arterial perfusion without Doppler evidence of hemodynamically significant main renal artery stenosis. Dedicated renal venous Doppler assessment and differential renal function testing were not performed. This case demonstrates that single-port retroperitoneoscopic kidney-sparing excision can be performed in selected patients with concomitant intrarenal arterial and venous aneurysms.

BACKGROUND:Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), characterized by persistent pain, is significantly associated with sexual dysfunction, yet the underlying mechanisms remain poorly understood. AIM:This study sought to elucidate the underlying central mechanisms linking autoimmune prostatitis to sexual dysfunction by employing an integrated multi-omics approach in a well-established rodent model. METHODS:An experimental autoimmune prostatitis (EAP) model was induced by injecting a mixture of rat prostate protein and Freund's adjuvant. Comprehensive assessments were conducted, including histopathological evaluation of prostate and penile tissues via H&E and Masson's trichrome staining, quantification of serum cytokines and neurochemicals using ELISA, functional assessment of erectile capability by measuring intracavernous pressure/mean arterial pressure (ICP/MAP) ratio, and detailed mating behavior analysis. Brain tissues from rats were collected for comprehensive transcriptomic profiling and non-targeted metabolomic analyses. OUTCOMES:Primary outcomes included brain transcriptomic and metabolomic alterations, mating behavior parameters, erectile function assessed by ICP/MAP measurement, histological changes in prostate and penile tissues, and serum inflammatory cytokine and neurochemical levels. RESULTS:The EAP model demonstrated significant prostatic inflammation, elevated serum pro-inflammatory cytokines (TNF-α, IL-8, IL-6, IL-1β), impaired erectile function (reduced ICP/MAP ratio), increased penile fibrosis, and disturbed ejaculatory behavior with shorter ejaculation latency. Serum analyses revealed altered neurochemical levels, including reduced 5-HT and elevated norepinephrine and leptin. Transcriptomic analysis identified 557 differentially expressed genes with enrichment in cGMP-PKG, calcium, oxytocin, RAP1, and MAPK signaling pathways. Besides, metabolomic analysis detected 45 differentially abundant metabolites, including key molecules such as N-acetyl-DL-aspartic acid, aspartic acid, threonine, and the nitric oxide pathway intermediate argininosuccinic acid. Integrated pathway analysis highlighted significant alterations in neuroactive ligand-receptor interaction, GABAergic synapse, and glutathione metabolism pathways. Immunofluorescence validation confirmed substantial downregulation of GABAergic proteins (GABRA5, GAD65, VGAT) in the paraventricular nucleus. Furthermore, integrated multi-omics analysis revealed coordinated alterations between gene expression and metabolic profiles. CLINICAL IMPLICATIONS:The identified central GABAergic dysregulation presents a promising therapeutic target for managing CP/CPPS-related sexual dysfunction. STRENGTHS & LIMITATIONS:The novel application of integrated brain multi-omics represents a key strength, while limited translational applicability to humans remains a constraint. CONCLUSION:Autoimmune prostatitis induces significant central genetic and metabolic alterations that contribute to sexual dysfunction, providing new mechanistic insights and potential therapeutic avenues for this challenging condition.

Abstract Solid tumors remain refractory to conventional treatments, yet cell surface proteins, by virtue of their extracellular accessibility and critical roles in tumor signaling, represent an attractive class of targets for precision-targeted therapy. Here, we report that transmembrane protein 132A (TMEM132A) is an essential and previously unrecognized pan-cancer target. TMEM132A interacts directly with EGFR and stabilizes its expression, thereby tethering EGFR at the plasma membrane and sustaining constitutive activation of lipid synthesis. Mechanistically, the TMEM132A-EGFR axis promotes lipogenesis by facilitating SREBP nuclear translocation, which in turn upregulates ACLY and ACSS2 expression to drive acetyl-CoA production and downstream lipid biosynthesis, ultimately disrupting lipid droplet homeostasis. To therapeutically target this axis, we developed a nanobody, LFNanoT132A#3, which effectively blocks the TMEM132A-EGFR interaction, abrogates downstream signaling activation, and potently inhibits proliferation across multiple solid tumor types. Our findings establish TMEM132A#3 as a critical node in membrane-tethered oncogenic signaling and metabolic rewiring, and position LFNanoT132A#3 as a promising therapeutic candidate for precision cancer therapy.

Objective:Varicocele (VC) is a leading cause of male infertility, but its pathophysiological mechanisms remain inadequately defined. This study aimed to characterize metabolic alterations in spermatic vein blood of varicocele patients with/without infertility (VI/VF groups) compared to healthy donors. Methods:We collected spermatic vein blood samples from VC patients and peripheral blood samples from healthy donors. VC patients scheduled for surgery were categorized into VF (without infertility) group or VI (with infertility) group based on fertility status, with healthy donors as the negative control (NC) group. Metabolic profiling of spermatic vein blood from VC patients and peripheral blood from healthy donors was performed using liquid chromatography-mass spectrometry (LC-MS). Semen parameters and ultrasound findings were recorded. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to identify metabolic differences, followed by pathway enrichment analysis. Results:A total of 40 VC patients and 35 healthy donors were included in this study. Semen quality in the VI group was significantly compromised compared to VF and NC groups (P < 0.001). Metabolic profiling revealed profound alterations in varicose spermatic veins of VC groups, including upregulated steroid hormone biosynthesis, disrupted amino acid and energy metabolism, and elevated reactive oxygen species (ROS) production compared to healthy donors. Differences between VI and VF groups were primarily localized to the alanine, aspartate, and glutamate pathway, with γ-aminobutyric acid, succinic acid, and aspartate significantly upregulated in VI groups (P < 0.05). Among renal and adrenal metabolites, only calcitroic acid exhibited differential expression (P < 0.01), while oxidative stress markers, including N-acetylcysteine and acylcarnitines (P < 0.05), showed significant variation. Conclusion:Untargeted metabolomics highlighted D-aspartic acid overexpression as a potential contributor to infertility in VC patients. This study provided only limited support for the retrograde reflux theory of renal and adrenal metabolites, while offering additional evidence consistent with the oxidative stress hypothesis. Oxidative stress-related metabolites may represent potential candidate diagnostic and therapeutic targets for VC-induced infertility.

Patients with diabetes mellitus-induced erectile dysfunction (DMED) usually suffer more severe symptoms, and efficacy of the first-line therapy is limited. This study develops an integrated framework combining single-cell RNA sequencing (scRNA-seq) and machine learning (ML) to design nanozymes with specific enzyme-mimicking types for precision treatment of DMED. First, scRNA-seq analysis demonstrated increased reactive oxygen species (ROS) level and downregulated expression level of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in the corpus cavernosum of DMED patients. Second, a nanozyme database is constructed based on the published researches. With this database, two ML models are developed to predict the enzyme-mimicking types of nanozymes, which showed that iron (Fe)-based nanozymes are particularly suitable for addressing reductase deficiencies in DMED. Thus, the Fe-DMOF, an Fe-based single atom nanozyme (SAzyme), is synthesized, simultaneously exhibiting GPx-, CAT- and SOD-like activities. Fe-DMOF can significantly reduce the ROS accumulation and inhibit the ROS-induced histone lactylation modifications, furtherly reversing the inflammatory differentiation of fibroblasts and macrophages in the diabetic corpus cavernosum. These results not only highlight the efficacy of Fe-DMOF in DMED treatment, but also validate the scRNA-seq + ML framework as an effective approach for data-driven SAzyme design for disease-specific treatment.

Immunotherapy has achieved limited efficacy in prostate cancer (PCa), largely due to its profoundly immunosuppressive tumor microenvironment (TME). However, the metabolic mechanisms underpinning this immune resistance remain poorly defined. Here, we identify lactate dehydrogenase A (LDHA)-driven lactate metabolism as a critical regulator of myeloid-derived suppressor cell (MDSC) activation in PCa. Integrated metabolomic, single-cell, and spatial transcriptomic analyses revealed that LDHA is highly expressed in PCa malignant epithelial cells and correlates with increased lactate production and immune exclusion. LDHA-high tumors exhibited enriched infiltration of polymorphonuclear MDSCs (PMN-MDSCs), which were spatially co-localized with LDHA-positive tumor regions. Mechanistically, lactate uptake through monocarboxylate transporter 1 (MCT1) enhanced PMN-MDSC differentiation and upregulated Arg1 and NOS2, reinforcing T cell suppression. Genetic ablation of LDHA in murine models markedly reduced PMN-MDSC infiltration, restored CD8+T cell activity, and inhibited tumor growth. Pharmacological inhibition of LDHA with FX-11 synergized with anti-PD-L1 therapy, producing durable tumor regression. Collectively, these findings define LDHA-driven lactate metabolism as a key metabolic checkpoint in PCa immune evasion and provide a rationale for combining LDHA inhibition with immune checkpoint blockade to overcome immunotherapy resistance.

Male reproductive disorders have emerged as a global issue. Infertility affects 8% to 12% of couples of childbearing age. The sperm concentration and total sperm count of men have shown a significant downward trend over the past four decades, with a decrease of more than 50%. Male reproductive disorders are related to multiple factors. Circular RNA (circRNA) is a type of non-coding RNA with covalently closed circular structures. It is involved in a variety of biological processes, including gene expression regulation, protein function regulation and epigenetic regulation. Studies have shown that there are differences in the expression of circRNA in the testicles and semen between infertile patients and healthy people, suggesting that circRNA is involved in the process of spermatogenesis, and its abnormal expression is associated with male infertility. This review takes the biological functions of circRNA as the starting point and summarizes the research progress of circRNA in male reproductive disorders. CircRNA has the potential to serve as a novel biomarker due to its conservative, special structure and tissue specificity, which provides a new strategy for the clinical diagnosis of male reproductive disorders.

BackgroundThere is no systematic classification of renal vascular injuries conducted for severe post-percutaneous nephrolithotomy (PCNL) bleeding.AimThe aim of the present study was to explore the various types of artery injury and clinical characteristics of patients who underwent transcatheter angioembolization (TAE) after PCNL.MethodsA retrospective analysis was performed on 52 patients who underwent renal arteriography (RA) because of severe bleeding after PCNL between April 2009 and December 2023. Among the patients, 38 underwent TAE due to positive RA results. Clinical data on the TAE patients, such as gender, age, body mass index, TAE interval, hemoglobin (Hb) decrease, operation time, stone size, the number and size of tracts, and clinical bleeding type, were summarized. The types of artery injury in TAE patients and their relationships with clinical characteristics were analyzed.ResultsRetrospective analysis revealed that, among the 38 TAE patients (32 males and 6 females), the mean TAE interval, average Hb decrease, mean tract number, and mean tract size reached 5.00 (6.25) days, 44.50 (24.50) g/L, 1 (0.25), and F20(6), respectively. Among the TAE patients, four kinds of vascular injury were observed, namely, 18 cases of pseudoaneurysm (PA), 12 cases of arteriocaliceal fistula (ACF), 7 cases of arteriovenous fistula (AVF), and 1 case of arterioperirenal fistula (APF). Analysis of the clinical characteristics of the three types of vascular injury (PA, ACF, and AVF) revealed that the number of tracts was the only factor that differed.ConclusionThe RA results indicate that the types of postoperative renal artery injury mainly include PA, ACF, AVF, and APF, and the number of tracts may be related to the type of vascular injury.

BackgroundEmphysematous pyelonephritis (EPN) is a rare but aggressive infectious disease that lacks specificity in its early stages and tends to progress to life-threatening septic shock in a short period of time. Its diagnosis is based on imaging tests, and treatment requires a combination of staging and risk factors.Case presentationWe report a case of emphysematous pyelonephritis in a patient with massive emphysema of the left kidney (the longest diameter up to 51 mm) on CT. After multidisciplinary consultation, the patient underwent CT-guided percutaneous drainage combined with targeted antibiotic therapy, and was discharged from the hospital with improvement of the condition. However, relapse of symptoms occurred after 1 day of discharge from the hospital, prompting readmission. After an additional 7-day course of antibiotic therapy, the patient recovered completely with no recurrence during 1-month follow-up.ConclusionStaged diagnosis and individualized therapeutic measures are key to the prognosis of this disease. Despite advances in therapeutic techniques, the risk of relapse is still high, and a comprehensive assessment of infection control is recommended for discharge from the hospital, with intensive follow-up to improve the prognosis.

BACKGROUND:Although some studies have revealed the close relationship between leptin and premature ejaculation in clinical practice, whether and how leptin participates in the regulation of ejaculatory behaviors are still unknown. OBJECTIVE:To explore the role of leptin on ejaculatory behaviors and its underlying mechanism. MATERIALS AND METHODS:Copulation behavior tests were performed after acute and chronic leptin administration at peripheral and central levels. To compare changes in sympathetic nervous system activity, lumbar sympathetic nervous activity, serum noradrenaline levels, and the distribution of sympathetic fibers in vas deferens and seminal vesicles were analyzed. Construction of virus vector, immunohistochemistry, and optogenetics techniques were used to explore the neural circuit mechanism. The density of dendritic spines in parvocellular region of paraventricular nucleus was measured by Golgi staining. RESULTS:Acute administration of leptin had no effect on ejaculation behavior in male mice. However, both mount latency and ejaculation latency were significantly shortened, even if serum leptin decreased to normal level, after chronic administration of leptin at peripheral or central level. Additionally, sympathetic fibers in vas deferens and seminal vesicles obviously increased, in which arcuate nucleus‒paraventricular nucleus circuit and glutamatergic neurons in paraventricular nucleus played an important role. Dendritic spine density in parvocellular region increased after chronic leptin administration. DISCUSSION AND CONCLUSION:The role of leptin in regulating ejaculation behavior was chronic, not acute, in which leptin chronically modulated sympathetic neuroplasticity via arcuate nucleus‒paraventricular nucleus circuit and glutamatergic neurons in paraventricular nucleus and promoted ejaculatory behaviors. Increased dendritic spine density in parvocellular region of paraventricular nucleus may be involved as well.

Further research is needed to investigate the association between netosis and clear cell renal cell carcinoma (ccRCC). We developed a prognostic framework for netosis using univariate, Lasso, and multivariate Cox regression analyses. The CIBERSORT algorithm was employed to compute immune infiltration metrics for The Cancer Genome Atlas (TCGA) dataset. These scores, combined with Cox regression analysis and patient survival data, contribute to the establishment of a prognostic model for the tumor microenvironment (TME). A combined prognostic model incorporating netosis and TME was then developed, stratifying patients based on median results. Further evaluation of the variations in the pathways within the model was conducted using Fast Gene Set Enrichment Analysis (FGSEA) and Weighted Correlation Network Analysis (WGCNA). Additionally, single-cell data integration allowed us to examine netosis-related genes in the context of cell communication and tumor development using the CellChat and Monocle packages. Netosis and TME scores exhibited a high degree of predictive power for patient survival, as illustrated by Kaplan-Meier (KM) curves. Gene set enrichment analysis (GSEA) revealed significant disparities in pathways associated with tumor occurrence between netosis and TME scores. A combined prognostic model incorporating both netosis and TME scores showed excellent performance in the validation set and TCGA data. FGSEA and WGCNA revealed significant differences in pathways associated with traditional tumor development and occurrence within distinct groups of the combined model. Furthermore, single-cell data analysis revealed substantial variations in intercellular communication levels among groups of netosis model genes with high and low expression. Pseudotime analysis highlighted increased expression of EREG, LYZ, S100A8, and S100A9. The combined netosis and TME prognostic model demonstrated high accuracy and efficacy, underscoring its potential value in guiding the treatment and prognosis of future ccRCC patients.

Investigating the application of single-port single-channel and single-port multi-channel adrenalectomy in various maximum tumor diameters. Retrospective analysis of clinical data from 218 adrenal tumors treated with single-port retroperitoneoscopic adrenalectomy at Lianyungang Clinical Medical College of Nanjing Medical University from September 2018 to November 2023. All adrenal tumors are benign lesions classified as T1 stage. Tumors were classified into three groups based on their maximum diameter: ≤3 cm (Group A), >3 cm and ≤ 4 cm (Group B), and > 4 cm and ≤ 5 cm (Group C). Based on the surgical approach, patients were divided into single-port single-channel and single-port multi-channel groups. Group A had an average tumor diameter of (2.32 ± 0.45) cm with 46 single-port single-channel and 53 single-port multi-channel cases; Group B had (3.42 ± 0.31) cm with 33 single-port single-channel and 45 single-port multi-channel cases; Group C had (4.60 ± 0.28) cm with 18 single-port single-channel and 23 single-port multi-channel cases. Comparisons were made between single-port single-channel and single-port multi-channel groups in terms of operation time, hospital stay, intraoperative bleeding, postoperative pain score, surgical complications, incision length (total length of all incisions), and the need for additional puncture holes for each tumor size group. All 218 surgeries were successfully completed without conversion to open surgery. In Group A, no significant difference was observed between single-channel and multi-channel groups in terms of operation time and blood loss (P > 0.05), but significant differences were found in hospital stay, pain score, subcutaneous emphysema incidence, and incision length (P < 0.05). In Group B, there was no significant difference between single-channel and multi-channel groups regarding operation time and blood loss (P > 0.05), but significant differences were observed in hospital stay, pain score, subcutaneous emphysema incidence, and incision length (P < 0.05). In Group C, no significant difference was observed between single-channel and multi-channel groups in terms of hospital stay, blood loss, pain score, incision length, vascular injury, and subcutaneous emphysema incidence (P > 0.05), but significant differences were found in operation time and the incidence of additional puncture holes (P < 0.05). Postoperative follow-up ranged from 4 to 22 months, with an average of 11.5 months, and no complications were observed. Single-port single-channel laparoscopy has significant advantages in surgeries for tumors with a maximum diameter ≤ 4 cm, as it can directly reach the target organ, reduce separation operations, cause less damage, and has good cosmetic effects. For adrenal tumor surgeries with a maximum diameter > 4 cm, the multi-channel technique is superior to the single-channel technique in terms of shorter hospital stay and the need for additional punctures.

Clear cell renal cell carcinoma (ccRCC) represents the most common subtype of renal cell carcinoma, accounting for approximately 70% of cases. Notably, the majority of ccRCC tumors are surrounded by a prominent pseudocapsule tissue, highlighting its potential diagnostic, prognostic, and therapeutic relevance. To comprehensively understand the implications of pseudocapsules in ccRCC, we constructed an extensive multi-omics atlas. The cohort included single-cell RNA sequencing, spatial transcriptomics, proteomics, and extracellular matrix (ECM) proteomics, derived from 36 ccRCC cases. These analyses were further augmented with functional assays and animal studies, enabling a multi-dimensional exploration of pseudocapsule biology. Our cohort analysis demonstrated that pseudocapsules are predominantly composed of fibroblasts and a rich diversity of immune cells, a finding corroborated through immunofluorescence (IF) and immunohistochemistry (IHC). The tissue was also characterized by a substantial accumulation of extracellular matrix components. Importantly, pseudocapsule invasion revealed significant alterations in the tumor microenvironment (TME). During tumor invasion, CD8+ T cells and dendritic cells (DCs) within the pseudocapsule exhibited increased activation, accompanied by pronounced exhaustion. Concurrently, tumor-associated fibroblasts underwent functional reprogramming, transitioning from a myofibroblast-like state (myoCAF) to an inflammatory CAF phenotype (iCAF). These iCAFs primarily interacted with T cells and promoted their exhaustion, which was critical to ccRCC progression. Additionally, our investigation identified a loss of chromosome 14q during tumor cell invasion. Notably, the FOS gene on chromosome 14 was significantly downregulated and identified as a key gene. Clinical data from large patient cohorts revealed that low FOS expression was associated with advanced tumor stage, higher histological grade, and poorer overall survival. Functional assays demonstrated that FOS overexpression reduced the invasive potential of ccRCC cell lines in vitro, whereas FOS knockdown enhanced lung metastasis in vivo. Transcriptomic analysis further indicated that FOS is involved in regulating extracellular matrix dynamics and immune-related pathways. These findings provide novel insights into the role of pseudocapsules in ccRCC and highlight critical molecular mechanisms underlying tumor progression. By uncovering key invasion biomarkers and therapeutic targets, this study lays the groundwork for precision medicine approaches in ccRCC management. Xiyi Wei, Yitong Pan, Weiyu Kong, Da Zhong, Zijie Yu, Yang Wang, Longjun Ma, Zhou Yang, Yize Li, Chenxi Tian, Bing Yao, Ninghong Song, Chao Qin. Comprehensive characterization of pseudocapsules in clear cell renal cell carcinoma reveals unique invasion mechanisms: A multi-omics investigation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5247.

BackgroundErectile dysfunction (ED) is a prevalent male sexual disorder, commonly associated with hypertension, though the underlying mechanisms remain poorly understood.ObjectiveThis study aims to explore the role of Fatty acid synthase (Fasn) in hypertension-induced ED and evaluate the therapeutic potential of the Fasn inhibitor C75.Materials and methodsErectile function was assessed by determining the intracavernous pressure/mean arterial pressure (ICP/MAP) ratio, followed by the collection of cavernous tissue for transcriptomic and non-targeted metabolomic analyses. In vitro, a concentration of 10-6 M angiotensin II (Ang II) was applied to rat aortic endothelial cells (RAOECs) to establish a model of hypertension. In vivo, spontaneously hypertensive rats (SHR) were randomly divided into two groups. The SHR+C75 group received intraperitoneal injections of C75 at a dose of 2 mg/kg once a week. After five weeks of treatment, the erectile function of the rats was assessed, and penile tissues were harvested for further analysis. Molecular and protein expression were assessed using Western blotting, qRT-PCR, immunofluorescence staining, and immunohistochemistry.ResultsThe SHR exhibited ED, indicated by reduced maximum ICP/MAP ratios. Histologically, corpus cavernosum tissue of SHR showed elevated fibrosis and endothelial dysfunction. Additionally, increased expression of the NLRP3 inflammasome, Caspase-1, GSDMD, and the pro-inflammatory cytokines IL-1β and IL-18 was observed. Multi-omics analysis revealed significant enrichment in lipid metabolic pathways, with Fasn identified as a hub gene. In vitro, siFasn and C75 enhanced antioxidant markers Nrf2 and HO-1, reduced ROS accumulation, and suppressed NLRP3 and GSDMD levels. In vivo, C75 treatment restored endothelial function and reversed erectile dysfunction, accompanied by decreased oxidative stress and pyroptosis in the penile corpus cavernosum.ConclusionThese findings suggest that Fasn inhibition may offer a promising therapeutic strategy for hypertension-induced ED by alleviating oxidative stress and suppressing NLRP3 inflammasome-dependent endothelial cell pyroptosis via activation of the Nrf2/HO-1 pathway.

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cancer and remains a clinical challenge due to its frequent resistance to therapy and poor prognosis in advanced stages. Apoptosis, a fundamental tumor-suppressive mechanism, exhibits paradoxical roles in cancer, wherein apoptotic tumor cells can also contribute to immunosuppression and tumor progression. However, the spatial dynamics, transcriptional heterogeneity, and prognostic relevance of apoptosis-related gene programs in ccRCC remain poorly defined. We performed an integrative analysis combining single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and summary-based Mendelian randomization (SMR) to dissect apoptosis-related malignant cell states in ccRCC. Cancer cells were stratified based on apoptosis gene signatures and CASP9 expression. Cell–cell communication was assessed using CellChat and spatial interaction networks were constructed using RCTD and mistyR. SMR was employed to link genetically regulated CASP9 expression with renal cancer risk. A CASP9-associated prognostic model was developed using LASSO Cox regression and DeepSurv on TCGA and E-MTAB-1980 cohorts. We identified transcriptionally and spatially distinct apoptosis-high and apoptosis-low malignant cell subpopulations. Apoptosis-high tumor cells, characterized by elevated CASP9 expression, preferentially localized near macrophage-enriched stromal regions and exhibited stronger spatial clustering. Ligand–receptor modeling revealed directional signaling via the SPP1–CD44 axis between CASP9-high cancer cells and macrophages. SMR analysis provided genetic evidence supporting CASP9 as a causal gene for renal cancer. CASP9-high cells demonstrated distinct developmental trajectories and formed multicellular spatial modules with macrophages and cycling cells. A five-gene apoptosis-related signature derived from CASP9-stratified tumor cells robustly predicted patient survival across both training and validation cohorts. Low-risk patients exhibited enriched immune infiltration, increased immune checkpoint expression, and enhanced immune pathway activity. Our study reveals that apoptosis, particularly CASP9-driven programs, defines a spatially organized, immunosuppressive malignant cell state in ccRCC. CASP9 acts as both a genetic driver and spatial regulator of tumor–macrophage interactions, contributing to disease progression. The CASP9-associated risk model demonstrates strong prognostic utility and highlights apoptosis as a promising therapeutic axis in ccRCC.

The incidence of prostate cancer is increasing, and its poor prognosis is associated with metadherin overexpression; however, its molecular mechanisms are unclear. This study used Western blot, quantitative real-time polymerase chain reaction, immunofluorescence, and tumorigenicity assays to investigate metadherin and epithelial-mesenchymal transition in prostate cancer. We found that metadherin was highly expressed in prostate cancer tissues, especially PC-3 cells. Metadherin overexpression promoted t epithelial-mesenchymal transition and tumor growth. Bioinformatics analysis and assays revealed that lymphoid enhancer-binding factor 1 directly activates the metadherin promoter. The epithelial-mesenchymal transition and tumorigenicity were suppressed by the silencing of lymphoid enhancer-binding factor 1; however, these effects were reversed by metadherin overexpression. Vitamin D treatment downregulated metadherin and lymphoid enhancer-binding factor 1, counteracting lymphoid enhancer-binding factor 1-induced metadherin upregulation. Our findings indicate that metadherin enhances epithelial-mesenchymal transition and tumorigenicity through lymphoid enhancer-binding factor 1, with vitamin D modulating this interaction in prostate cancer.