搜索结果：component

Diabetes mellitus (DM) is increasingly prevalent and associated with complications worldwide, negatively impacting the health-related quality of life (HRQoL) of affected people. To analyze the factors associated with HRQoL components in people with diabetes registered in primary healthcare. A cross-sectional study was conducted among people aged 18 years or older with type-2 DM registered in Family Health Strategy units. The dependent variable of the study was HRQoL and its components, as assessed by the Medical Outcomes Study 36-item Short Form Health Survey (SF-36). An ordinal hierarchical multivariate regression was used to estimate odds ratios (ORs) with a 95% confidence level. Findings indicate that the physical functioning component was the most affected (median <50 points). Factors associated with overall HRQoL in people with DM included: Stress (OR: 2.22), anxiety (OR: 1.77), insomnia (OR: 1.80), and depression (OR: 2.22). The physical functioning component was also associated with female gender (OR: 1.86) and lower educational level (OR: 1.71). Other factors influenced the remaining HRQoL components, such as polypharmacy and the presence of comorbidities (respiratory and genitourinary diseases). These data are important for rethinking health prevention strategies in primary care, taking into account the factors that influence different HRQoL components in people with DM.

Although compulsive buying-shopping disorder (CBSD) has over 100 years of clinical history, its nosology remains a topic of debate. In 2021, M&#xfc;ller and colleagues published a set of diagnostic criteria for the disorder based on a Delphi consensus study. The present study evaluated these criteria among 51 participants who reported a lived experience of CBSD and examined whether their experiences aligned with the components model of addiction. Participants were interviewed using a semistructured interview. Transcripts were analyzed using directed content analysis. Most participants reported a persistent and excessive pattern of buying/shopping, diminished control over buying/shopping, buying/shopping for mood modification, experiencing clinically significant distress and impairment, and continuation despite negative consequences. We recommend these symptoms be considered essential features of CBSD, along with ruling out other explanations for the buying/shopping behavior. Intrusive thoughts and preoccupation with buying/shopping, tolerance, and withdrawal were less common, and we recommend these be considered additional, but not required, features of CBSD. Given these findings and evidence that tolerance and withdrawal are not necessary or sufficient components of addiction, we recommend that CBSD be considered a behavioral addiction. Future research should use these empirically informed criteria to develop and validate a structured diagnostic interview to be used in field studies to formally recognize CBSD as a mental disorder. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

As Artificial intelligence (AI) is increasingly integrated into surgical practice, particularly in robotic surgery, the clinical intraoperative implementation remains limited. Continued progress will require not only technical advances but also a clear understanding of which functions surgeons find valuable in practice. This study aimed to assess surgeons' perceptions, knowledge, attitudes, and current use of AI-driven intraoperative assistance. We conducted a structured, web-based survey of 53 surgeons across 5 continents, assessing demographics, attitudes, knowledge, current use, and perceived usefulness of five AI-based intraoperative guidance components, using video footage from robotic upper gastrointestinal surgeries. Participants were stratified by surgical experience level. Ordinal and categorical data were analyzed using non-parametric tests, and paired comparisons, with statistical significance set at p&#x2009;<&#x2009;0.05. Perceived knowledge of AI tools for surgery was rated as average or lower by 83.0% of respondents, and 79.2% reported never using such tools intraoperatively. Confidence in relying on clinically validated AI tools was reported by 75.5%, and 86.8% agreed that intraoperative AI assistance could positively impact surgical performance. Anatomy recognition and risk detection received the highest usefulness scores (4.57&#x2009;&#xb1;&#x2009;0.54 and 4.45&#x2009;&#xb1;&#x2009;0.72, respectively), followed by vision-language model assistance (3.94&#x2009;&#xb1;&#x2009;0.97), while step recognition (3.36&#x2009;&#xb1;&#x2009;1.11) and decision-making guidance (3.51&#x2009;&#xb1;&#x2009;1.15) were rated lowest; overall usefulness differed significantly across the five components (p&#x2009;<&#x2009;0.001). This study clarifies how surgeons expect intraoperative AI to be implemented. Despite high perceived usefulness across multiple surgical AI functions, especially for anatomical guidance, adoption in routine practice remains limited, highlighting a gap between positive perceptions and clinical implementation.

Conforming to the global commitment of combating viral hepatitis by 2030, India launched the National Viral Hepatitis Control Program (NVHCP) in 2018. NVHCP is a comprehensive strategy that uses a cascade of care approach to tackle all forms of viral hepatitis. This study was conceptualized to assess the implementation status of NVHCP and to understand the key stakeholders' perspective on prevention, screening, diagnosis, and treatment of viral hepatitis in Uttarakhand. The study commenced in July 2021 and was conducted over a year in six districts of Uttarakhand. The program was evaluated using a sequential explanatory mixed-method approach with a pragmatic stance, incorporating a quantitative component of record-based analysis and a qualitative component of key informant interviews (KIIs) with program managers, physicians, and laboratory technicians. NVHCP integrated effectively with the preexisting healthcare infrastructure and programs to provide primary and secondary levels of prevention. The program picked up pace initially by identifying the service delivery points, training the nominated personnel, and supplying logistics for screening and treatment. However, the developments were halted by the COVID-19 pandemic, which ensued shortly after the first NVHCP budget allocation. From 2019-20 to 2020-21, the pandemic resulted in a 73% decline in hepatitis B virus (HBV) screening and a 76% decline in hepatitis C virus (HCV) screening. The biggest missing link in the cascade of care for HCV was the nonavailability of PCR-based diagnostic viral load testing at treatment centers. A lack of a dedicated data management portal, an inefficient supply chain, and a lack of nomination of pharmacists and peer support were some of the gaps that could be addressed to accelerate the elimination process.

Robotic-assisted total knee arthroplasty (RA-TKA) is increasingly used to improve implant positioning, soft-tissue balance, and procedural reproducibility. Yet, little is known about how different components of the operation independently contribute to the overall learning curve. This study aimed to characterize the learning curve of MAKO-assisted TKA by separately evaluating these components and assessing their differential impact on operative workflow. A retrospective observational study included 92 consecutive patients who underwent image-based RA-TKA (MAKO, Stryker) for primary knee osteoarthritis. All procedures were performed by a single experienced arthroplasty surgeon with no prior robotic or computer-assisted surgery background. Cumulative sum (CUSUM) analysis with piecewise linear regression was applied to total surgical time, pin placement time, and composite robotic workflow time to identify inflection points and define learning curve phases. Piecewise regression of the CUSUM plot for total surgical time revealed two breakpoints at cases 11 and 51, defining three phases of the learning curve: (1) initial learning (cases 1-11), (2) competence (cases 12-51), and (3) optimized performance (cases 52-90). Mean surgical time was 68.9&#x2009;&#xb1;&#x2009;20.1&#xa0;min, stabilizing around 65&#xa0;min after 50 cases. Along with total surgical time, the initial learning phase ended around cases 10-11 for both robotic workflow and pin placement. However, subsequent performance patterns differed: pin placement reached optimized performance by case 52 (mean 8.4&#x2009;&#xb1;&#x2009;4.3&#xa0;min), whereas robotic workflow time improved more gradually, without clear stabilization until the end of the series (mean 37.8&#x2009;&#xb1;&#x2009;10.8&#xa0;min). RA-TKA with the MAKO system follows a structured learning curve with early achievement of proficiency after 11 cases. Total surgical time and pin placement reached optimized performance by mid-series, whereas robotic workflow tasks required a longer consolidation period, likely influenced by patient-specific anatomical variability. These findings support RA-TKA as a safe and effective tool, offering rapid surgeon adaptation. IV.

Inflammatory immune activation is increasingly recognized as an important pathogenic component in antiphospholipid syndrome (APS). However, the clinical relevance of circulating cytokine alterations and their integrative immune patterns in APS remain incompletely understood. Serum samples were obtained from 250 patients with APS and 81 healthy controls (HCs). Concentrations of 12 cytokines were measured using a multiplex bead-based immunoassay. Principal component analysis followed by K-means clustering was applied to identify cytokine-based subgroups among APS patients. Clinical manifestations and laboratory parameters were compared among clusters. Compared with HCs, patients with APS showed significantly elevated levels of IL-6, IL-8, IL-12p70, and IFN-&#x3b3;, together with reduced levels of IL-5 and TNF-&#x3b1; (all P&#x2009;<&#x2009;0.05). Unsupervised clustering based on cytokine profiles identified four distinct immune phenotypes among APS patients, characterized by low-inflammatory, pan-inflammatory, selectively enriched inflammatory (TNF-&#x3b1;/IL-5-abundant), and T-cell-priming (IL-12p70, IL-2, and IL-4). In particular, the pan-inflammatory cluster was associated with higher adjusted Global Antiphospholipid Syndrome Score (aGAPSS), greater anticardiolipin antibody positivity, and more pronounced hematologic abnormalities, whereas the T-cell-priming cluster was abundant for primary APS and exhibited relatively lower systemic inflammatory burden. APS is characterized by heterogeneous cytokine profiles reflecting distinct immune activation patterns. Cytokine-based clustering identifies clinically relevant inflammatory subgroups, supporting the potential value of immune stratification for improved risk assessment in APS. Key Points &#x2022; Patients with APS exhibit a distinct circulating cytokine signature characterized by elevated IL-6, IL-8, IL-12p70, and IFN-&#x3b3; with reduced IL-5 and TNF-&#x3b1;, underscoring the thrombo-inflammatory nature of the disease. &#x2022; Unsupervised clustering of cytokine profiles identifies four immunologically distinct APS subgroups (low-inflammatory, pan-inflammatory, TNF-&#x3b1;/IL-5-abundant, and T-cell-priming), each associated with different clinical and laboratory features. &#x2022; The pan-inflammatory cluster is linked to higher antiphospholipid antibody burden and greater hematologic abnormalities, whereas the T-cell-priming cluster is enriched for primary APS and exhibits a lower systemic inflammatory burden.

Slope-reducing high tibial osteotomy (SRO-HTO) surgically corrects elevated posterior tibial slope (PTS) and is often performed in the setting of failed anterior cruciate ligament (ACL) reconstruction. Lateral supratubercle angle (LSTA) quantifies the supratubercle component of elevated PTS, but the infratubercle component of elevated PTS has not been quantified. The purpose of this study was to describe and establish mean values for lateral infratubercle angle (LITA) within non-ACL tear, primary ACL tear, and ACL graft tear cohorts. It was hypothesized that LITA would differ between non-ACL tear and ACL graft tear cohorts, would positively correlate with PTS elevation, and, when used with LSTA, would localize the deformity leading to PTS elevation. Cross-sectional study; Level of evidence, 3. Patients seen for a knee complaint were categorized into non-ACL tear, primary ACL tear, or ACL graft tear cohorts. PTS, LSTA, and LITA were measured on full-length lateral (FLL) tibia radiographs. Descriptive statistics were calculated for each measurement and cohort, and comparisons were performed using a 1-way analysis of variance with a Bonferroni correction (P < .01 indicating statistical significance). The non-ACL tear cohort's mean LITA value served as the cutoff. Pearson's correlation determined the relationship between elevated PTS with LITA and LSTA. P < .05 indicated statistical significance. A total of 300 patients were included, 100 per cohort. The mean LITA in the non-ACL tear, primary ACL tear, and ACL graft tear cohorts were 89&#xb0;&#xb1; 4.6&#xb0;, 90.7&#xb0;&#xb1; 5.8&#xb0;, and 92&#xb0;&#xb1; 5&#xb0;, respectively. Significant differences existed in LITA between the non-ACL tear and ACL graft tear cohorts (P < .001). Within the ACL graft tear cohort, 74.4% (64/86) of patients with elevated medial or lateral PTS (PTS-M/L) had elevated LITA, regardless of LSTA elevation status. Significant positive correlations existed between PTS-M/L and LITA in the non-ACL tear (P = .011/P = .004), primary ACL tear (P = .002/P = .029), and ACL graft tear cohorts (P < .001/P < .001/P < .001). LITA is a novel measurement, with distinct anatomic landmarks, that quantifies infratubercle deformity and can be easily incorporated into FLL radiographic assessment. Elevated LITA was present in most patients with elevated PTS in both the primary ACL tear and ACL graft tear cohorts, indicating a contribution from infratubercle deformity. We recommend utilizing LITA and LSTA with PTS to quantify region-specific proximal sagittal deformity. Future studies should determine whether this quantification can help surgeons select the SRO-HTO technique and influence outcomes.

Observational studies have consistently reported associations between serum uric acid (SUA) and post-stroke epilepsy (PSE) in acute ischemic stroke (AIS), including a recently published large cohort study identifying a U-shaped relationship. However, whether these associations reflect causality and whether SUA provides incremental predictive value beyond established clinical factors remains unknown. we conducted a two-sample Mendelian randomization (MR) analysis to test whether lifelong genetically predicted serum urate shares a genetic causal architecture with general epilepsy susceptibility, using 299 independent genetic instruments. In parallel, we performed a prespecified secondary analysis of a multicenter AIS cohort (n&#x2009;=&#x2009;21,459) using multivariable logistic regression with restricted cubic splines (RCS) to characterize the observational SUA-PSE relationship. Formal sex interaction testing (Wald tests) and sex-stratified spline analyses were performed. Predictive utility was evaluated through discrimination (AUC), calibration, decision curve analysis (DCA), and internal validation with 1000 bootstrap resamples. The two analytical components address related but distinct biological questions: observational analysis tests the admission-SUA-to-1-year-PSE pathway, while MR tests whether lifelong genetically predicted urate shares a causal architecture with general epilepsy susceptibility. MR analysis found no evidence supporting a shared lifelong genetic causal architecture between serum urate and general epilepsy susceptibility across all four methods (IVW: OR&#x2009;=&#x2009;1.043, 95% CI 0.926-1.174, p&#x2009;=&#x2009;0.487; MR-Egger p&#x2009;=&#x2009;0.582; weighted median p&#x2009;=&#x2009;0.589; weighted mode p&#x2009;=&#x2009;0.996), with no pleiotropy (Egger intercept p&#x2009;=&#x2009;0.865) or heterogeneity (Cochran Q p&#x2009;=&#x2009;0.206). In the observational cohort (n&#x2009;=&#x2009;21,459; 936 PSE events (4.36%)), RCS analyses confirmed a significant nonlinear SUA-PSE association (P for nonlinearity <&#x2009;0.001). Importantly, a formal sex-by-SUA interaction revealed strikingly divergent patterns (overall p&#x2009;<&#x2009;0.001; nonlinear component p&#x2009;=&#x2009;0.0002): Women in the highest SUA tertile had markedly elevated PSE risk (adjusted OR&#x2009;=&#x2009;2.33, 95% CI 1.71-3.19), a finding confirmed with sex-specific tertile cut-points (OR&#x2009;=&#x2009;1.50, p&#x2009;=&#x2009;0.005). The apparent protective association in men using overall tertiles (OR&#x2009;=&#x2009;0.36, 95% CI 0.28-0.46) was attenuated and non-significant with sex-specific cut-points (OR&#x2009;=&#x2009;0.84, p&#x2009;=&#x2009;0.16), indicating sensitivity to stratification method. Adding SUA to a base clinical model produced a modest but statistically significant increment in discrimination (AUC: 0.8498 to 0.8607, &#x394;AUC&#x2009;=&#x2009;0.011, DeLong p&#x2009;=&#x2009;0.001) with consistent positive net benefit on DCA. Genetically predicted lifelong SUA does not share a causal genetic architecture with general epilepsy susceptibility; this null does not exclude acute post-stroke, context-specific mechanisms, which operate on biological timescales outside the scope of Mendelian randomization. The sex-dependent observational association (female high-SUA OR&#x2009;=&#x2009;1.50 with sex-specific tertiles; sex &#xd7; SUA continuous interaction p&#x2009;=&#x2009;3.99&#x2009;&#xd7;&#x2009;10-9) generates the hypothesis that sex-stratified SUA monitoring merits prospective investigation, pending external validation.

Island coastal aquifers, though spatially limited, sustain key ecosystem functions linked to locally critical provisioning, maintenance and cultural ecosystem services. These functions are largely dependent on the presence of highly adapted biological communities, whose microbial components remain poorly understood. Here, we describe bacterial communities across groundwater-dependent ecosystems on Lanzarote (Canary Islands, Spain), spanning habitats with contrasting environmental conditions and degrees of human influence, using 16&#xa0;S rRNA gene amplicon sequencing. We then infer the processes shaping community variation by integrating diversity partitioning, indicator species analysis, and machine-learning classification. Bacterial taxonomic diversity varied significantly among habitats, with community composition primarily structured by turnover, consistent with environmental filtering. In contrast, predicted human-associated and potentially pathogenic taxa showed patterns dominated by nestedness, indicating localized enrichment linked to anthropogenic inputs. Caves, enclosed marine bays, and hypersaline systems hosted the most compositionally distinct microbial communities, whereas wells and anchialine pools showed greater overlap in community composition. Together, our results suggest that groundwater microbial communities are influenced by the interplay between environmental filtering and anthropogenic inputs, and that coastal aquifers can act simultaneously as reservoirs of natural biodiversity and sinks of human-associated bacteria. These findings highlight the need for integrative monitoring and conservation strategies that incorporate both hydrological and biological components to safeguard groundwater-dependent ecosystems on oceanic islands.

This commentary discusses the scoping review by da Silva et al. on care bundles to prevent infiltration in short peripheral intravenous catheters in hospitalized children. While the review addresses an important paediatric patient safety issue, its conclusions should be interpreted cautiously. The evidence base comprised only four heterogeneous studies, mainly quality improvement or pre-post designs, which is sufficient for mapping bundle elements but not for determining which components are truly effective. Recurrent elements such as site assessment, securement, review of catheter need, and timely removal may indicate a preventive core. Further prospective multicenter studies are needed to define components.

To investigate the complement-modulating mechanisms of Ginkgo biloba extract (EGb 761) in dry age-related macular degeneration (dry AMD) through an integrative approach combining bioinformatics, molecular docking, and molecular dynamics (MD) simulations. Bioinformatics analysis was used to identify dry AMD-related targets, followed by molecular docking and 100-ns MD simulations to evaluate the binding stability and free energy of EGb 761 components with complement proteins C3 and C5. Quercetin and ginkgolide B showed the strongest and most stable interactions with complement proteins C3 and C5. Persistent hydrogen bond networks were observed in the C3/ginkgolide B and C3- and C5-quercetin complexes. MM-Poisson-Boltzmann surface area analysis indicated that van der Waals and electrostatic interactions were the main contributors to binding, and key residues (C3: ASP1435, GLU1433, LYS1001, LYS1436; C5: ASP1457, GLU837, GLU932) were identified as critical hotspots. These results suggest that the major active components of G. biloba extract may act as natural complement modulators, stabilizing interactions with C3 and C5 to mitigate inflammation and oxidative injury in dry AMD. Because the blood-retinal barrier limits the efficacy of systemic drugs for retinal diseases, nanomaterial-based ocular delivery systems are gaining attention. However, identifying suitable bioactive compounds for nanocarrier encapsulation remains challenging. EGb 761, a standardized and clinically validated G. biloba extract with proven safety and efficacy in ophthalmology, represents a promising candidate. This study provides a mechanistic basis for its potential in dry AMD and offers insights for developing natural complement-targeting therapeutics.

The environmental transformation of engineered CeO2 nanoparticles is strongly mediated by natural organic matter (NOM); however, the interplay between NOM and light in regulating their fate remains unclear. Here, we systematically investigated the dissolution behavior of CeO2 in the presence of NOM under dark and illuminated conditions. Results revealed that NOM-induced Ce3+ release was significant in the dark but suppressed under visible light, which is a striking phenomenon validated in both aqueous and soil systems. Spectroscopic and microscopic analyses reveal that in the dark, the carbonyl-rich aliphatic components of NOM preferentially coordinate with Ce(III) at the oxygen vacancy sites of CeO2, promoting continuous ligand-driven Ce3+ release. Under visible light, however, the dominant interfacial redox pathway shifted. We found that the photoactivation of quinone chromophores within macromolecular NOM diverts interfacial electron transfer away from surface Ce(IV) reduction toward dissolved O2, initiating a cascade of reactive oxygen species (ROS) formation that degrades NOM and stabilizes the CeO2 surface against dissolution. In contrast to previously reported light-enhanced dissolution of metal oxides by NOM, this work reveals that the effect of NOM photochemistry is fundamentally governed by the intrinsic dissolution pathway of the oxide and thus provides a conceptual basis for predicting when illumination will enhance or suppress metal release in natural environments.

Malignant pleural mesothelioma (MPM) remains a rare but highly aggressive malignancy with limited treatment options and poor prognosis. For nearly twenty years, platinum-pemetrexed chemotherapy has persisted as the unchanged standard treatment; although recent progress in immunotherapy has modestly disrupted this therapeutic plateau, survival outcomes remain disappointingly limited. This review aims to provide a comprehensive overview of the epigenetic landscape of MPM, focusing particularly on the oncogenic and therapeutic implications of enhancer of zeste homolog 2 (EZH2), and to discuss its potential as a target for novel therapeutic strategies and combination regimens. Epigenetic dysregulation has emerged as a central driver of mesothelioma pathogenesis. EZH2, the catalytic component of the polycomb repressive complex 2 (PRC2), mediates histone H3K27 trimethylation, silencing tumor suppressor genes and promoting malignant transformation. In addition to its canonical role, EZH2 has non-canonical oncogenic effects that modulate transcription, apoptosis, DNA repair, and immune evasion. High EZH2 expression correlates with BAP1 loss, which enhances chromatin remodeling defects and disease aggressiveness. Preclinical and early clinical data demonstrate that EZH2 inhibitors-including tazemetostat, valemetostat, GSK126, EPZ011989, tulmimetostat, and novel PROTAC-based degraders such as MS1943-can suppress tumor progression, modulate the tumor immune microenvironment, and restore therapeutic sensitivity. Furthermore, combination approaches integrating EZH2 inhibition with chemotherapy or immune checkpoint blockade show synergistic potential in overcoming resistance. EZH2 represents a pivotal epigenetic regulator and a promising therapeutic target in MPM. Further understanding the dual canonical and non-canonical roles of EZH2 in tumor biology will be key to optimizing targeted and combinatorial treatment strategies. Future research should focus on translating EZH2 inhibition into clinical benefit, identifying predictive biomarkers of response, and exploring rational combinations with chemotherapy, targeted drugs, or immunotherapy to improve survival outcomes in mesothelioma patients.

The widespread use of petroleum-derived plastics has led to massive environmental exposure to micro- and nanoplastics (MNPs), generated by the degradation of plastic polymers. Ubiquitous, these contaminants enter the body mainly through the gastrointestinal tract, but also via inhalation or iatrogenic sources, reach the systemic circulation, and accumulate in the brain. Recent data show increasing cerebral concentrations of MNPs, paralleling their environmental rise, as well as their presence in human thrombi and atherosclerotic plaques. Acute ischemic stroke, a leading cause of mortality and disability worldwide, is driven by thrombo-inflammatory mechanisms involving coordinated activation of the endothelium, platelets, and leukocytes. Converging preclinical and clinical evidence suggests that MNPs amplify these processes. They promote intestinal permeability and induce systemic and local inflammation through activation of all cellular components involved in thrombo-inflammation. In addition, MNPs may contribute to the development and destabilization of atherosclerotic plaques and, indirectly, to atrial fibrillation via activation of the thrombo-inflammatory processes. Despite methodological limitations, these findings indicate that MNPs represent an emerging environmental factor that may worsen both the risk and prognosis of acute ischemic stroke. Preventive, detection, and exposure-control strategies are therefore urgently needed to address this major public health challenge. La g&#xe9;n&#xe9;ralisation des plastiques d&#xe9;riv&#xe9;s du p&#xe9;trole a conduit &#xe0; une exposition environnementale massive aux micro- et nanoplastiques (MNP), issus de la d&#xe9;gradation de polym&#xe8;res plastiques. Omnipr&#xe9;sents, ces contaminants p&#xe9;n&#xe8;trent l&#x2019;organisme principalement par voie digestive, mais aussi respiratoire ou iatrog&#xe8;ne, gagnent la circulation syst&#xe9;mique et s&#x2019;accumulent dans le cerveau. Des donn&#xe9;es r&#xe9;centes montrent des concentrations c&#xe9;r&#xe9;brales croissantes de MNP, parall&#xe8;les &#xe0; l&#x2019;augmentation environnementale, et leur pr&#xe9;sence dans les thrombi et les plaques d&#x2019;ath&#xe9;rome humains. L&#x2019;accident vasculaire c&#xe9;r&#xe9;bral isch&#xe9;mique (AVCi), cause majeure de mortalit&#xe9; et de handicap, repose sur des m&#xe9;canismes de thrombo-inflammation impliquant l&#x2019;activation coordonn&#xe9;e de l&#x2019;endoth&#xe9;lium, des plaquettes et des leucocytes. Des donn&#xe9;es pr&#xe9;cliniques et cliniques convergentes sugg&#xe8;rent que les MNP amplifient ces processus. Ils favorisent la perm&#xe9;abilit&#xe9; intestinale, l&#x2019;inflammation syst&#xe9;mique et locale par l&#x2019;activation de tous les types cellulaires impliqu&#xe9;s dans la thrombo-inflammation. En outre, les MNP contribueraient &#xe0; la gen&#xe8;se et &#xe0; l&#x2019;instabilit&#xe9; de l&#x2019;ath&#xe9;rome et, indirectement, &#xe0; la fibrillation auriculaire via l&#x2019;activation de la thrombo-inflammation. Malgr&#xe9; des limites m&#xe9;thodologiques, ces donn&#xe9;es sugg&#xe8;rent que les MNP constituent un facteur environnemental aggravant le risque et le pronostic de l&#x2019;AVCi. Des strat&#xe9;gies de pr&#xe9;vention, de d&#xe9;tection et de contr&#xf4;le apparaissent n&#xe9;cessaires face &#xe0; cet enjeu majeur de sant&#xe9; publique.

Gastric cancer ranks among the most prevalent malignancies globally and remains a major contributor to cancer-related mortality. Its progression is profoundly shaped by the tumor microenvironment (TME), a dynamic milieu comprising extracellular matrix components, soluble mediators, and diverse non-malignant immune populations that collectively influence tumor initiation and evolution. Although immunotherapeutic strategies have recently attracted increasing attention in the management of solid tumors, including gastric carcinoma, the determinants of immune evasion in this context are still not fully delineated. The Farnesoid X receptor (FXR), a key nuclear receptor for bile acids, has recently been implicated in regulating TME composition and immune cell recruitment within gastric tumors. Yet, how bile acid signaling contributes to the bidirectional interactions between malignant and immune cells remains largely undefined. This study aimed to investigate the role of FXR in modulating immune-regulatory networks associated with PD-L1/PD-1 in gastric cancer. RNA-seq analysis of paired gastric mucosa from 39 gastric cancer patients revealed significant molecular differences between intestinal and diffuse tumors. FXR was overexpressed in the intestinal subtype and correlated with poor prognosis. MS/MS analysis demonstrated enrichment of tumor tissues by cholic acid and chenodeoxycholic acid compared to non-neoplastic pairs, supporting the hypothesis of dysregulated bile acid metabolism. In vitro, exposure of gastric cancer cell lines and patient-derived organoids to FXR ligands increased PD-L1 expression through direct binding of FXR-responsive elements in the PD-L1 promoter. Targeting FXR may offer a therapeutic approach to improve the effectiveness of immunotherapies in intestinal gastric cancer.

To investigate the therapeutic effects of Cuscuta chinensis Lam. (CCL) on ovariectomy (OVX)-induced osteoporosis (OP) and elucidate the underlying molecular mechanisms, focusing on the VCP-METTL3 axis. The bioactive components of CCL were identified using liquid chromatography-mass spectrometry. An OVX-induced OP mouse model was established and treated with CCL. Bone microarchitecture was assessed by micro-CT, and bone metabolism markers were measured by ELISA. In vitro, bone marrow-derived mesenchymal stem cells (BMSCs) were used to assess osteogenic differentiation (alkaline phosphatase and alizarin red S staining). N6-methyladenosine (m6A) levels were quantified colorimetrically. Protein expression and interactions were analyzed by Western blot, co-immunoprecipitation, and immunohistochemistry. Protein stability and ubiquitination levels were assessed following cycloheximide (CHX) and MG132 treatments. Potential targets were screened via bioinformatics. CCL alleviated bone loss in OVX mice, improving bone volume/total volume (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), while reducing trabecular separation/spacing (Tb.Sp). It also restored the balance between bone formation and resorption. In BMSCs, CCL enhanced osteogenic differentiation and increased m6A levels by stabilizing METTL3, extending its half-life. Mechanistically, CCL targeted VCP, inhibiting its interaction with METTL3. VCP, in concert with the E3 ligase BARD1, promoted METTL3 ubiquitination and proteasomal degradation. Knockdown of METTL3 attenuated the pro-osteogenic effects of CCL. Conversely, METTL3 overexpression rescued the inhibitory effects of VCP overexpression on osteogenesis. CCL alleviates OP by targeting VCP to inhibit BARD1-mediated METTL3 ubiquitination and degradation, thereby promoting osteogenic differentiation. These findings highlight the VCP/METTL3 axis as a potential therapeutic target for OP.

The Central-marginal hypothesis predicts that populations occurring at the periphery of a species' geographic distribution experience more adverse environmental conditions, resulting in reduced population density, lower fitness, and potential morphological changes. In insects, morphological traits are strongly associated with ecological performance and resource acquisition, making them useful indicators of how populations respond to environmental gradients. Here, we investigated whether populations of the ant Dinoponera quadriceps differ in activity density and morphofunctional traits between the center and edge of the species' geographic distribution along the Espinha&#xe7;o Mountain Range, Brazil. Ants were sampled using pitfall traps in two sites approximately 610&#xa0;km apart. Generalized Linear Mixed Models were used to evaluate differences in activity density and trait variation between sites, and a Principal Component Analysis summarized multivariate body size variation. The activity density of D. quadriceps was -higher in the central population in the full dataset but this difference was not robust to the removal of a single outlier trap. A positive correlation between D. quadriceps activity density and richness of other ant species was observed in the full dataset but also disappeared after outlier exclusion. Individuals from the marginal population exhibited significantly smaller overall body size. Additionally, trait-specific differences emerged, with marginal individuals displaying larger cephalic index, longer femora, and larger eyes. These findings suggest that peripheral environments impose energetic constraints that reduce body size while favoring morphological adjustments that enhance locomotor and sensory efficiency, highlighting the importance of intraspecific functional variation in understanding species responses at geographic range limits.

Giant skull base collision tumors in neurofibromatosis type 2-related schwannomatosis (NF2-SWN) pose a complex surgical challenge in young patients with lifelong tumor burden. Gross total resection is often impossible without severe neurological morbidity, and data on operative timing and durability are limited. We assessed long-term outcomes of planned, selective resection prioritizing neurological preservation. We queried a prospective institutional database for NF2-SWN patients undergoing surgery for giant (&#x2265;&#x2009;4.0&#xa0;cm) intracranial skull base collision tumors (&#x2265;&#x2009;2 neoplasms forming one mass) from January 2009 to December 2025. Surgery targeted symptomatic or high-risk components, accepting residual disease. Outcomes included time to reoperation, overall survival, and functional status. Thirteen patients underwent 31 skull base operations. Mean age at first surgery was 27 years (range 19-42), with mean tumor diameter 5.0&#xa0;cm (range 4.0-7.7&#xa0;cm). Most (69%) had prior surgery and/or radiotherapy. Gross total resection was never achieved. Over mean 9.4-year follow-up, Kaplan-Meier analysis demonstrated reoperation-free survival of 61.5% at 5 years (95% CI, 26.6-83.7%), with a median reoperation-free survival of 6.1 years. The mean interval between reoperations was 4.8 years (median, 3.9 years; IQR, 2.7-5.7; range, 0.8-14.6). Overall survival was 100% at 5 years and 88% at 10 years. At last follow-up, median Karnofsky Performance Status was 70. Planned, selective resection of giant NF2-related skull base collision tumors yielded a median reoperation-free interval of 6.1 years and maintained functional independence in a young, heavily pretreated population, supporting its feasibility as a longitudinal management strategy.