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This study aimed to explore the prognostic and immune-related associations of adiponectin-related genes in melanoma. Single nucleotide polymorphism (SNP) and transcriptomic data from the Integrative Epidemiology Unit Open Genome-Wide Association Study database (IEU openGWAS) and The Cancer Genome Atlas Skin Cutaneous Melanoma cohort (TCGA-SKCM) were integrated to identify adiponectin-related genes. Consensus clustering defined molecular subtypes. Differentially expressed genes (DEGs) were analyzed using functional enrichment, protein-protein interaction (PPI), and immune infiltration (CIBERSORT). In vitro assays assessed transcriptional changes following endogenous albumin (ALB) modulation in melanoma cells. Five adiponectin-associated SNPs were linked to melanoma prognosis. Four molecular subtypes with distinct survival outcomes were identified, with ALB-high Cluster 3 showing the poorest prognosis. A total of 702 DEGs were enriched in immune-related pathways, including IL-17 signaling and antigen presentation. ALB was identified as a PPI hub and positively correlated with memory B cells (R = 0.34, P = 0.012). In vitro, ALB overexpression was associated with increased mRNA levels of IL-6, TNF-α, TGF-β, IL-17A, and RORγt. Tumor-associated ALB expression is associated with adverse prognosis and immune-related transcriptional features in melanoma, suggesting its potential as a prognostic biomarker and marker of transcriptomic heterogeneity. Melanoma is a serious type of skin cancer. Although immune-based treatments can be effective, not all patients benefit equally. In this study, we investigated whether a gene called ALB, which is related to albumin, is linked to differences in the immune features of melanoma tumors. Using large patient datasets and laboratory experiments in melanoma cells, we found that tumors with higher ALB gene expression showed changes in genes involved in immune and inflammatory processes, including those related to T helper 17 (Th17)–associated pathways. Importantly, these findings are based on changes in gene activity (mRNA levels) and do not directly measure immune cell behavior or protein production. Further analysis using single-cell data showed that ALB and these immune-related genes are mainly expressed in different types of cells within the tumor. This suggests that the observed signals likely reflect interactions between multiple cell types, rather than coordinated activity within individual tumor cells. Overall, our results suggest that ALB gene expression is linked to differences in the immune characteristics of melanoma tumors. These findings may help improve our understanding of why tumors behave differently. More research is needed to better understand the underlying mechanisms and their potential clinical importance.

Semantic-to-autobiographical memory priming (autobiographical priming from general information processing) has been shown to prime involuntary autobiographical memory production in the laboratory and everyday life. This form of priming has been shown to be insensitive to depth of processing, with minimal, shallow processing producing as much priming as deep processing. Semantic-to-autobiographical memory priming has also occurred when prime stimuli were presented below the threshold of consciousness awareness. In this study, we hypothesized that semantic-to-autobiographical memory priming will be unaffected by dividing attention, because this form of priming only requires minimal processing to be expressed. We tested this hypothesis by having a divided-attention group monitor digits for odd number sequences while they simultaneously rated words for their familiarity, followed by an involuntary memory task (the vigilance task). The primed involuntary memory production of this group was then compared to a full-attention group, who had performed word familiarity ratings unimpeded, and a control group. The results showed significant priming for both attention groups, but importantly, the divided-attention group did not differ from the full-attention group. We argue that the results support the idea that semantic-to-autobiographical memory priming only requires minimal processing to be observed, and that autobiographical memory activations in this phenomenon are automatic and unconscious.

Brain arteriovenous malformations (BAVMs) are increasingly recognized as dynamic vascular diseases driven by endothelial genetic alterations and dysregulated signaling pathways, rather than as static structural anomalies. Accumulating evidence from both hereditary and sporadic forms of BAVMs has established endothelial signaling dysfunction as a central pathogenic mechanism underlying aberrant angiogenesis, progressive lesion remodeling, and vascular instability that predisposes to hemorrhage. These insights have fundamentally shifted the conceptual framework of BAVMs toward a pathway-driven disease model. Despite this progress, direct access to biologically informative molecular material from living AVM lesions remains limited, posing a major barrier to detailed mechanistic interrogation and the translation of molecular insights into clinical decision-making. Historically, molecular characterization of AVMs has relied almost exclusively on surgically resected tissue, restricting analyses to selected patient populations and frequently reflecting late-stage disease biology. Such approaches provide limited insight into disease initiation, temporal evolution, or treatment-induced molecular changes. Recent advances in minimally invasive biopsy strategies, particularly those leveraging endovascular access, have begun to overcome these limitations by enabling molecular interrogation of AVMs in vivo. In this mini review, we summarize emerging approaches for molecular profiling of AVMs, with a primary focus on BAVMs, while also drawing on relevant studies in extracranial and other arteriovenous malformations that share common endovascular access routes, technical principles, and translational implications.

The World Health Organization has identified ST23 carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) as a critical public health threat. Through China's national surveillance system (BRICS), we identified and characterized ST23 CR-hvKP bloodstream isolates from 2019-2023. Among 1069 CRKP bloodstream isolates, four ST23-K1 strains (0.37%) were detected across two hospitals, including a nosocomial transmission pair (differing by only 2 core SNPs). Clinical outcomes revealed that three of the four patients achieved recovery following appropriate antibiotic therapy, with one mortality case attributed to underlying comorbidities. All four ST23 isolates demonstrated resistance to multiple antibiotics, indicating a pattern of multidrug resistance. Genomic analysis uncovered diverse resistance mechanisms: the nosocomial transmission pair possessed conjugative IncFIIK2 NDM-1 plasmids, while the others harbored conjugative IncFIIK34 KPC-2 plasmids, which exhibited reduced carbapenem resistance attributed to the downregulation of blaKPC-2 expression. Conjugation assays revealed high transferability (10-5 for IncFIIK2 NDM-1; 10-4 for IncFIIK34 KPC-2). Whole-plasmid comparative genomics analysis suggested that the IncFIIK2 NDM-1 plasmids shared > 99% identity with historical IncFIIK2 plasmid backbones from Chinese K. pneumoniae isolates (2014-2022), suggesting local evolution. Notably, only 4.4% (26/590) of global IncFIIK2 plasmids carried blaNDM-1 and all IncFIIK2 NDM-1 plasmids maintain conjugative potential. All strains harbored conserved virulence plasmids and maintained hypervirulence, as indicated by a mouse infection model, with the exception of one strain that exhibited cps mutations. This study reports the first genomic evidence of a high-frequency conjugative IncFIIK2 NDM-1 plasmid in a hospital-transmitted ST23 CR-hvKP clone, highlighting the need for plasmid-focused surveillance to control this potential threat.

Despite their high specific capacity, O3-type layered oxides face challenges of structural instability and sluggish kinetics as cathode materials for sodium-ion batteries (SIBs). Herein, we report a targeted synergistic strategy involving dual-element (Cu2+/Ti4+) doping at the transition metal (TM) sites and Ca2+ introduction into the Na sites of O3-type NaNi1/3Fe1/3Mn1/3O2 (NFM) to address their inherent defects. This multi-site modification effectively stabilizes the crystal structure, alleviates the phase transition amplitude, suppresses irreversible oxygen loss even at high voltage (up to 4.2 V vs. Na+/Na), and enhances Na+ migration by reducing the migration barrier and interfacial impedance. As a result, the optimized cathode (CCT) delivers a high reversible capacity of 125.3 mAh g-1 with 76.9% capacity retention after 300 cycles (vs. 64.1% for NFM). Even at a high current density of 2000 mA g-1 (∼13 C), the CCT cathode cycled at 4.2 V delivers a remarkable capacity of 94.3 mAh g-1, demonstrating excellent rate capability. The CCT//HC full-cell demonstrates excellent performance, achieving a high initial capacity (123.5 mAh g-1) and outstanding cycling stability (76.2% capacity retention) over 300 cycles. This work underscores the efficacy of multi-site synergistic doping strategy in designing high-performance layered oxide cathodes for practical SIBs.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a poor prognosis, characterized by early metastasis and high mortality rates. Cryptotanshinone (CTS), a diterpenoid quinone, has been extensively studied for its diverse pharmacological effects, particularly its anti-tumor properties, however, its therapeutic potential and mechanisms in the treatment of ESCC remain unclear. This study aimed to examine the impact of CTS on the polarization of TAMs and its subsequent role in inhibiting the metastasis of ESCC, both as a monotherapy and in combination with cisplatin. THP-1 cells were differentiated into M0, M2, and TAM-like macrophages using PMA, IL-4, and ESCC cell-conditioned medium. CTS's effects on macrophage polarization were analyzed via flow cytometry, RT-qPCR, Western blot, and ELISA. The impact of macrophage-conditioned media on ESCC cell migration and invasion was assessed through wound healing and transwell assays. Molecular mechanisms were confirmed using molecular docking, the cellular thermal shift assay (CETSA), and drug affinity responsive target stabilization assay (DARTS). An in vivo footpad xenograft model in nude mice, co-inoculated with KYSE150 cells and TAMs, tested the anti-metastatic effects of CTS with cisplatin. Within the tumor microenvironment of ESCC, TAMs are polarized into a pro-metastatic M2 phenotype. Our findings indicate that CTS disrupts this process by directly targeting the WNT2 protein, thereby interfering with the WNT2/STAT3/SOX4 signaling feedback loop. This disruption leads to a reduction in M2 polarization and a decrease in the secretion of pro-tumorigenic factors from TAMs. As a result, CTS attenuates the pro-tumorigenic effects of TAMs on ESCC cells and, when used in conjunction with cisplatin, synergistically inhibits ESCC metastasis. This study demonstrates that CTS reverses the M2 polarization of TAMs by inhibiting the WNT2/STAT3/SOX4 feedback loop, thereby suppressing ESCC metastasis. These findings underscore the potential of CTS as a therapeutic agent that mitigates the pro-tumoral tumor microenvironment and enhances the efficacy of conventional chemotherapy such as cisplatin.

Type 1 diabetes is caused by immune-mediated destruction of beta cells. Interestingly, individuals with long-standing type 1 diabetes have residual beta cells, suggesting regenerative mechanisms may help beta cell survival. Islet-resident macrophages have an important role in diabetes, and can adopt a tissue-regenerating phenotype that may support beta cells. However, the roles of macrophages in beta cell survival, function, and proliferation remain poorly defined. This study aimed to elucidate how macrophage subtypes influence beta cell survival, function, and proliferation. Mouse and human islets were isolated from the pancreas and co-cultured in vitro with macrophages. To investigate whether macrophages enhance beta cell survival and function, apoptosis was measured using flow cytometry, and insulin secretion was assessed via glucose-stimulated insulin secretion assays. We also examined whether macrophages increased beta cell proliferation in the presence of harmine, a DYRK1A inhibitor. Finally, we evaluated the effect of islet co-culture on macrophage phenotype by flow cytometry and cytokine secretion analysis. We found that regenerative, but not pro-inflammatory, macrophages enhanced beta cell survival and function through mechanisms that did not require direct cell contact. Direct contact between macrophages and islets promoted a macrophage regenerative phenotype characterized by increased CD206 expression and secretion of anti-inflammatory factors. Additionally, regenerative macrophages promoted beta cell proliferation in the presence of harmine. Our findings demonstrate that regenerative macrophages support pancreatic beta cell survival, function, and proliferation. Harnessing the regenerative properties of macrophages could offer a novel strategy to promote beta cell survival and function.

To break the selectivity-activity trade-off in nitrate reduction, we report a self-adaptive W single-atom-anchored CoOOH matrix that constructs Co-W heteroatomic interfaces (referred to as W-CoOOH) created via a spontaneous etching-reconstruction process. Operando analysis demonstrates that a reversible electron relay between the Co-W heteroatomic interfaces, which stabilizes the Co-W dual active sites during nitrate reduction reaction (NITRR). This adaptive electronic structure enables exceptional performance, including a Faradaic efficiency (FE) over 90% in a wide potential range (0 to -0.8 V vs. reversible hydrogen electrode (RHE) and a high NH3 yield rate of 0.64 g h-1 at 10 A using a 5 × 5 cm2 membrane electrode assembly (MEA). Mechanistic investigations, combining in situ spectroscopy and theoretical calculations, support a local Co-W interfacial bifunctional pathway in which Co sites preferentially adsorb/activate NO3 --derived intermediates, while W-associated interfacial sites facilitate H2O dissociation and increase the local availability of hydrogen species for subsequent hydrogenation steps. This dual-site cooperation is further accompanied by interfacial electronic modulation, which together contributes to the superior NITRR performance of W-CoOOH.

IgG4-related disease is a rare, immune-mediated, multisystem fibroinflammatory condition. It is characterized by elevated serum IgG4 concentrations and tissue infiltration of IgG4-positive plasma cells with distinctive histopathological features, including storiform fibrosis and obliterative phlebitis. Gastroenterological involvement is diverse and represents a critical diagnostic consideration, encompassing the pancreas, bile ducts, liver, esophagus, stomach, and intestine. In this review, we summarize the current understanding of genetic susceptibility and environmental risk factors underlying this disease, and systematically describe the clinical presentations, histopathological characteristics, imaging findings, and serological profiles of each major gastroenterological manifestation. We further review evidence-based treatment regimens ranging from glucocorticoids and conventional immunosuppressants to emerging biologic therapies, discuss organ-specific therapeutic responses, and identify predictors of disease relapse along with long-term surveillance strategies. From a gastroenterologist's perspective, this review aims to provide a practical and integrated framework to facilitate early recognition, accurate differentiation from mimicking conditions such as pancreaticobiliary malignancies, and optimized long-term management of this complex yet treatable disease.

There is a high prevalence of poor sleep quality and low energy availability (EA) in athletes during phases of intensive training, which poses significant risks for overreaching, improper recovery, and compromised training adaptations. To mitigate these risks, there is a need to explore the relationship between EA and sleep quality. To determine the interrelationships between EA and sleep quality, we assessed EA and sleep quality (sleep durationhrs, sleep debthrs, percent and hours of: slow-wave sleep (SWShrs/%), and rapid-eye movement (REMhrs/%)). The participants included 26 elite male (n&#x2009;=&#x2009;10; 83.8&#x2009;&#xb1;&#x2009;8.6&#x2009;kg; BMI: 24.1&#x2009;&#xb1;&#x2009;1.9&#x2009;kg/m2) and female (n&#x2009;=&#x2009;16; 68.0&#x2009;&#xb1;&#x2009;5.6&#x2009;kg; BMI: 22.5&#x2009;&#xb1;&#x2009;1.6&#x2009;kg/m2) collegiate swimmers (aged 18-22&#x2009;years). The descriptive data collected included age, weight, height, training data, and body composition measures. Using a wearable device and a dietary recording cell phone application, the collection of EA was matched to sleep data over a two-week period of heavy training. Pearson correlations were utilized to determine relationships between variables. When effects of sex were observed, linear regression analyses were utilized to control for sex-differences. Among all swimmers, 69% exhibited sub-optimal EA (<45&#x2009;kcal/kg FFM/d). Male swimmers exhibited greater EA and SWS versus females (p&#x2009;<&#x2009;0.05). EA was positively correlated with REMhrs (R&#x2009;=&#x2009;0.64; p=&#x2009;0.001) but not related to sleep debthrs. Regression analyses revealed that when controlling for sex, EA positively predicted SWShrs (R2&#x2009;=&#x2009;0.448; F&#x2009;=&#x2009;9.35, p&#x2009;<&#x2009;0.001), where higher EA predicted longer SWS durations. Controlling for sleep durationhrs, EA positively predicted REMhrs (R2&#x2009;=&#x2009;0.425; F&#x2009;=&#x2009;8.509, p&#x2009;<&#x2009;0.002) and negatively predicted sleep debthrs (R2&#x2009;=&#x2009;0.261; F&#x2009;=&#x2009;4.055, p&#x2009;<&#x2009;0.031), such that higher EA was predictive of longer durations of REM, and fewer hours of sleep debt. There was a trend toward a correlation between EA and sleep durationhrs in all swimmers (R&#x2009;=&#x2009;0.33; p&#x2009;=&#x2009;0.06). Higher EA was significantly associated with greater REM and SWS durations, and with lower sleep debt in elite male and female college swimmers. Although cause and effect were not established, these findings provide preliminary evidence that adequate EA may support better sleep quality in elite collegiate swimmers. If this is confirmed, our results may suggest that athletes should get adequate sleep and consume adequate calories to support energy expenditure needs and optimize training and recovery. Future research should explore the underlying mechanisms and whether low EA causally impacts sleep quality.

Di(2-ethylhexyl) phthalate (DEHP) is a widely used industrial plasticizer, raising global concerns due to its potential endocrine-disrupting effects and environmental persistence. Human exposure to DEHP primarily occurs through the ingestion of contaminated food and water, inhalation of airborne particles, and dermal contact with products containing DEHP. Understanding the toxicological mechanisms of DEHP is essential for evaluating its health risks and developing effective strategies to mitigate its adverse effects. In this study, we conducted long-term exposure experiments to DEHP using both an animal model and in vitro system to investigate the complex interplay among DNA methylation, hyperactivation of macroautophagy/autophagy, mitochondrial dysfunction, and lipid accumulation induced by DEHP. The results revealed that DEHP exposure induced the degradation of DNMT1 (DNA methyltransferase 1) by enhancing its interaction with the autophagy-related protein SQSTM1 (sequestosome 1). DNMT1 degradation resulted in decreased methylation of the promoter regions of genes associated with autophagosome formation, subsequently increasing their expression. The resulting demethylation excessively activated autophagy, contributing to mitochondrial dysfunction and lipid accumulation in the liver. This study uncovered a previously unrecognized interplay among hyperactivation of autophagy, mitochondrial dysfunction, and lipid accumulation in the context of DEHP exposure. These findings enhanced our understanding of DEHP's toxicity and underscored concerns about the long-term health effects of environmental pollutants, particularly regarding metabolic diseases.

Mycoplasma pneumonia (MP), as a global infectious disease in sheep, seriously affects the production performance of sheep and economic benefits of sheep industry. However, current research on sheep resistance to MP remains limited. To address this gap and explore the potential epigenetic regulation of sheep MP resistant, this study employed high-throughput sequencing techniques (ATAC-Seq and CUT&Tag) to analyze epigenetic modifications in lung tissue from healthy and MP-affected sheep and reveal differential epigenetic landscapes associated with disease resistance. Integrating transcriptome analysis related to MP and genome-wide association studies (GWAS), FOXF1 was identified as a candidate gene for MP-resistance in sheep. We established a Mycoplasma ovipneumoniae (MO)-infected sheep alveolar epithelial cell model and regulated FOXF1 expression in cells through interference and overexpression techniques to study MO's adhesion and damage. The results showed that activation promoters or enhancer elements in FOXF1 introns of healthy lungs may enhance its transcription. FOXF1 overexpression reduced MO-mediated adhesion damage to cells, while knock-down increased it. Our work has enriched the gene pool for anti-pneumonia and studied the role of the FOXF1 gene in MO-infected cells, accumulating reliable genetic resources for sheep MP disease resistant breeding.

Organic luminescent radicals with efficient doublet emission can directly transfer electrons and energy to oxygen, enabling fluorescence-guided photodynamic therapy. However, their water insolubility and unclear oxygen interaction mechanisms limit their application. To address these challenges, we synthesized an amphiphilic organic radical (TTM-2PyPh) that forms self-assembled water-soluble nanoparticles (TTM-2PyPh_SA@NPs) with deep-red emission, serving as Type-I/II photosensitizers. Quantum chemistry calculations confirm an efficient electron transfer process between the radicals and oxygen. These nanoparticles self-assemble in vivo, target tumors, and produce reactive oxygen species more effectively than core-shell nanoparticles (TTM-2Py_CS@NPs), chlorin e6, and methylene blue. Additionally, TTM-2PyPh_SA@NPs demonstrate superior tumor eradication in vivo. This work advances the development of novel water-soluble radical-based photosensitizers for enhanced photodynamic therapy.

B-cell lymphoma 6 (BCL6) is an attractive drug target for diffuse large B-cell lymphoma (DLBCL). This study aimed to create a lipid nanoparticle (LNP)-based peptide-proteolysis-targeting chimera (PROTAC), specifically BCL6-PROTAC, to develop effective strategies for treating DLBCL via targeted degradation of the BCL6 protein. Molecular docking, SPR and cellular thermal shift assays revealed that F1324 (Ac-LWYTDIRMSWRVP-OH) is a high-affinity BCL6-binding peptide. PROTAC LNPs were synthesized by modifying F1324 and pomalidomide aptamers onto LNPs via a covalent chemical reaction in a certain proportion. The LNPs were characterized using dynamic light scattering and transmission electron microscopy. The ligand ratio (F1324:pomalidomide) used to verify the optimal BCL6 degradation was 1:5, as determined using western blotting. In vitro and in vivo studies revealed that BCL6-PROTAC significantly inhibited the proliferation of DLBCL cells. Target-specific uptake was used to evaluate the accumulation of BCL6-PROTAC in vivo. Toxicity in normal tissues was detected using H&E staining and serum indices. Overall, we developed a PROTAC that exhibited persistent and excellent BCL6 degradation ability in DLBCL, with an excellent safety profile. Thus, our BCL6 degrader provides a complementary approach to existing clinical&#x2011;stage candidates.

Metal cluster-based metal-organic frameworks (MOFs) offer many classical MOF materials because of their better directionality and selectivity of coordination geometry. However, unlike the numerous substitutable organic ligands and metal ions in MOFs, precisely controlling the inorganic bridging species in the metal cluster remains a significant challenge. Here, we use a prefabricated fluoride-bridged lanthanide cluster as a precursor to unambiguously introduce fluoride bridges into a well-known UiO-66-type MOF with an fcu topology. This blueprint provides eight isoreticular coordination networks with bridging F- through organic ligand alterations of different lengths and functional groups. The characterization of the content and position of bridging F- proves the complete substitution of O-bridge with F-bridge. More importantly, the rapid and moderate reaction process allows for the synthesis of ten-gram scale at room temperature within 5 s. Compared with prototypical UiO-66, the bridging F- in the representative structure can promote C2H2 adsorption and conduct efficient C2H2/CO2 separation.

Stage III non-small cell lung cancer (NSCLC) presents marked heterogeneity under evolving therapeutic paradigms. Real-world evidence on current treatment practices and outcomes remains limited. The MOOREA study aimed to evaluate real-world molecular testing, treatment patterns, and clinical outcomes of treatment-na&#xef;ve Chinese patients with stage III NSCLC. MOOREA is a prospective, multicenter Chinese study enrolling patients with untreated stage III NSCLC (16 July 2019 to 28 February 2022) from 28 hospitals. Patients were consecutively enrolled. The primary endpoint was treatment pattern of cohort 1 (C1; unresectable stage III NSCLC), and the secondary endpoints included molecular testing pattern, progression-free survival (PFS), overall survival (OS) of C1, and treatment pattern of cohort 2 (C2; resectable stage III NSCLC). In total, 486 patients were analyzed (C1: 379; C2: 107). Molecular testing rates were: EGFR (20.0%), ALK (15.0%), and PD-L1 (13.0%). Of the 45.6% (173/379) of individuals in C1 who received chemoradiotherapy (CRT), 53.8% (93/173) underwent consolidation therapy, including 37.6% (35/93) who received immunotherapy (IO). In C2, lobectomy was the main surgical approach (85.8%, 91/106), whereas pneumonectomy was performed on 14.2% of patients (15/106). Adjuvant treatment was planned for 71.4% (75/105) of the patients in C2. For C1, the median follow-up was 27.5 months, with PFS and OS of 12.6 (95% CI: 11.0-14.0) and 33.3 months (95% CI: 29.6-not estimable), respectively. Subgroup analysis showed better OS and PFS for patients receiving CRT with IO consolidation versus CRT only, especially for those who underwent more than six IO consolidation cycles (24-month OS: 79.3% versus 66.4%; PFS: 49.6% versus 24.2%). MOOREA reveals the real-world management of stage III NSCLC in 20 provinces/cities in mainland China and Hong Kong SAR. Patients with unresectable tumors derived significant benefit from radiotherapy and consolidation after CRT. Substantial disparity persists between actual practice and guideline recommendations, necessitating efforts to enhance adherence to guideline-based care. NCT04023812.

Left bundle branch area pacing (LBBAP) has been reported to improve long-term clinical outcomes in patients requiring permanent pacemaker implantation (PPMI) after transcatheter aortic valve replacement (TAVR). Deep septal pacing (DSP) has emerged as a potential alternative to LBBAP. This study investigated whether short-term and long-term clinical outcomes differ between LBBAP and DSP in post-TAVR patients. Consecutive patients undergoing LBBAP or DSP following TAVR were retrospectively included at our institution. Short-term clinical outcomes (1-year follow-up) were assessed by echocardiographic measures of reverse remodeling and changes in QRS duration and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. For long-term outcomes, the primary composite endpoint was all-cause mortality or heart failure hospitalization (HFH). Secondary endpoints included HFH and improvement in New York Heart Association (NYHA) class (&#x2265;&#x2009;2 grades). A total of 82 patients (39 LBBAP and 43 DSP) were observed for a mean duration of 731.8 days. There was no significant difference between two groups in the risk of primary endpoint (23.1% vs. 23.3%, adjusted hazard ratio [aHR] 0.61; 95% CI: 0.23-1.61, p&#x2009;=&#x2009;0.315) and HFH (17.9% vs. 20.9%, aHR 0.64; 95% CI: 0.22-1.82; p&#x2009;=&#x2009;0.402). However, LBBAP was a robust predictor of NYHA class improvement compared to DSP (53.8% vs. 27.9%, aHR 2.23; 95% CI: 1.03-4.87, p&#x2009;=&#x2009;0.043), especially when left bundle branch (LBB) capture was independently confirmed (aHR 2.74, p&#x2009;=&#x2009;0.006). Both modalities were similarly effective in improving electromechanical and biochemical parameters, including LVEF, LVEDD, QRS duration, and NT-proBNP (all p&#x2009;>&#x2009;0.05). LBBAP and DSP yield comparable risks for the primary composite endpoint and HFH, yet LBBAP provides superior symptomatic relief. Confirmation of left bundle branch capture is advisable to optimize clinical benefits. Liangzhen Qu and Xueting Duan contributed equally to this manuscript.

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Urological cancers exhibit significant sex differences in incidence, treatment response, and prognosis, with males generally showing higher morbidity and mortality. This review systematically summarizes the underlying molecular and clinical mechanisms of these disparities, focusing on sex hormones, chromosome biology, tumor immune microenvironment, and microbiota. Sex hormones modulate key tumor processes including proliferation, apoptosis, non-apoptotic cell death, and DNA repair. Genetic factors such as X chromosome inactivation escape genes and Y chromosome loss also contribute to sex-biased cancer susceptibility. Furthermore, sex-specific differences in the urinary system and gut microbiota influence local immunity and inflammation, thereby affecting tumor progression and therapeutic response. Lifestyle and environmental factors, including smoking, alcohol consumption, and occupational exposures, further exacerbate these disparities. Clinically, sex differences impact the efficacy of immunotherapy and targeted therapies, underscoring the need for sex-informed treatment strategies. Integrating sex as a biological variable in research, clinical practice, and public health policies is essential for advancing precision oncology in urologic cancers.