A novel major locus (Qgi.245.ahau-4B.3) controlling seed dormancy, and its candidate genes (TaF-box-B1 and TaF-box-B2), were identified by integrating association and linkage mapping with expression and sequence variation analyses. Moderate seed dormancy is essential for reducing pre-harvest sprouting (PHS) and ensuring uniform germination in cereal crops. In this study, seed dormancy was evaluated in 245 wheat varieties with diverse genetic backgrounds across seven environments, and genotypes were obtained using the Wheat 90 K SNP array. A genome-wide association study (GWAS) identified 55 loci associated with seed dormancy, including a novel major locus (Qgi.245.ahau-4B.3) on chromosome 4B. This locus was validated by integrating molecular marker development, re-GWAS, linkage mapping, and expression analysis. Two candidate F-box protein-encoding genes underlying this locus were identified: TraesCS4B03G0269800 (TaF-box-B1) and TraesCS4B03G0270500 (TaF-box-B2). The expression levels of TaF-box-B1 and TaF-box-B2 were significantly lower in the moderate dormancy wheat variety Annong 1124 (AN1124) than in weak dormancy variety Annong 8455 (AN8455). Sequence and haplotype analyses showed that variations in TaF-box-B1 and TaF-box-B2 were completely linked, forming two haplotypes: TaF-box-Hap1 for strong dormancy and TaF-box-Hap2 for weak dormancy. Frequency analysis further revealed that the favorable haplotype TaF-box-Hap1 was predominantly distributed in the Middle and Lower Yangtze River winter wheat region, characterized by relatively high rainfall and humidity. These findings establish a robust foundation for molecular marker-assisted breeding of wheat varieties with enhanced climate resilience and stable PHS resistance, thereby contributing substantively to global food security.
Burn injuries affect millions globally, with increasing survival rates due to advances in acute care. However, long-term cardiovascular outcomes including major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and mortality in burn survivors remain under-investigated. We conducted a retrospective propensity score-matched cohort study using the TriNetX US Collaborative Network. Individuals aged 18 years or older who had an emergency department visit or hospitalization with a diagnosis of burn injuries occurring between January 1, 2014, and January 1, 2019, were identified and matched 1:1 to nonburn controls who were selected based on similar demographics, comorbidities, and medications. The primary outcomes were the hazard ratios (HRs) and absolute risk differences (ARDs) of MACE, VTE, and mortality occurring between 3 months and 5 years after the index date. Secondary cardiovascular and thromboembolic endpoints included the HRs and ARDs of coronary artery disease (CAD), cerebrovascular disease (CVD), pulmonary embolism (PE), and deep vein thrombosis (DVT). A total of 71,426 propensity score-matched pairs of burn survivors and nonburn controls were included. Burn survivors had significantly elevated risks of MACE (HR 1.95, 95% confidence intervals [CI] 1.84-2.07; ARD 0.9%), VTE (HR 1.99, 95% CI 1.80-2.19; ARD 0.4%), and all-cause mortality (HR 2.29, 95% CI 2.10-2.49; ARD 0.7%) compared with controls. Increased risks were also observed for CAD (HR 1.85, 95% CI 1.72-1.98; ARD 0.5%), CVD (HR 2.05, 95% CI 1.88-2.24; ARD 0.5%), PE (HR 2.09, 95% CI 1.77-2.47; ARD 0.1%), and DVT (HR 1.96, 95% CI 1.69-2.27; ARD 0.1%). We demonstrate that burn injury is associated with sustained long-term cardiovascular and thromboembolic risks up to 5 years after injury. These findings establish burn injury as a chronic condition, requiring routine cardiovascular screening and targeted prevention in long-term care.
Treatment options for metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. While glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors improve cardiovascular outcomes, comparative effectiveness on liver-related outcomes remains unclear. This study compared the effectiveness of GLP-1 RAs versus SGLT-2 inhibitors on major adverse liver outcomes (MALO), liver cirrhosis and all-cause mortality in people with MASLD and type 2 diabetes. This active comparator, new-user cohort study used claims data from Germany (2005-2024), including 45 256 people with MASLD and type 2 diabetes. New users of GLP-1 RAs (n = 9993) and SGLT-2 inhibitors (n = 35 263) were weighted using matching weights. The primary outcome was MALO, while secondary outcomes comprised individual MALO components (decompensation events, liver transplantation, hepatocellular carcinoma (HCC)), liver cirrhosis and all-cause mortality. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated with weighted Cox proportional hazard models. Over a median 4.3-year follow-up, new users of GLP-1 RAs had a lower hazard of MALO (HR 0.91, 95% CI 0.78-1.07). This association appeared stronger using an on-treatment approach (HR 0.78, 95% CI 0.58-1.03) and when restricting to hospital diagnoses in primary position (HR 0.77, 95% CI 0.56-1.07). Benefits were also observed for liver cirrhosis (HR 0.88), decompensation events (HR 0.91), HCC (HR 0.76), but not all-cause mortality (HR 1.04). GLP-1 RAs were associated with a potentially lower hazard for incident MALO and liver cirrhosis compared with SGLT-2 inhibitors in people with MASLD and type 2 diabetes, suggesting a possible therapeutic advantage for liver-specific outcomes in this population.
The superior labial artery mucosal (SLAM) flap is a versatile, pedicled axial flap ideally suited for mucosal lining in lower lip reconstruction. This article details the surgical anatomy and technique of the SLAM flap, highlighting its role as a standalone liner or mucosal adjunct to microvascular free tissue transfer in major composite reconstructions. Clinical success relies on preserving the submucosal venous plexus, with the axial blood supply from the superior labial artery providing resilience against prior radiation therapy. By providing pliable, homologous mucosa, the SLAM flap effectively restores oral competence and defines the vermilion border. The SLAM flap is a highly reliable option for internal lining in complex lower lip defects.
The adverse health effects of fine particulate matter (PM2.5) depend strongly on its chemical composition, yet the specific organic components responsible for its toxicity remain insufficiently elucidated. To identify potential toxic constituents in PM2.5, we collected sixty-two PM2.5 samples from Chongqing, a typical basin city in China, and characterized their chemical composition and toxicity by coupling nontargeted analysis (NTA) with metabolomics. The results revealed 382 organic compounds, with significant seasonal variations, such as polycyclic aromatic hydrocarbons (PAHs) and their derivatives. Exposure of BEAS-2B human lung epithelial cells to PM2.5 extracts induced significant perturbations in energy, nucleotide, and redox metabolism, with winter samples exhibiting greater toxicity compared to summer samples. A total of 59 pollutants were significantly correlated with extensive metabolic alterations, especially heteroatom-containing and aromatic chemicals. Fifteen pollutants, including typical PAHs and emerging derivatives (e.g., dinaphtho[2,1-b:1',2'-d]furan, 2-methylnaphthalene, and 11H-benzo[a]fluoren-11-one), were prioritized by sparse partial least-squares regression as candidate contributors. We further validated these associations by testing the metabolic disruption effects of individual chemicals and quantifying their contributions to the overall PM mixture effects. Notably, 7H-benz[de]anthracen-7-one and pyrene jointly accounted for 80% of the PM-associated decrease in 2-Thiocytidine, a metabolite involved in nucleotide metabolism. This study offers new insights into the chemical-specific toxicity of PM2.5 and highlights the role of PAHs in cellular metabolic disruption by NTA-Metabolomics pairing and experimental validation.
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This study compared the incidence of intraoperative significant vessel injury between robotic-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) during major pulmonary resection. This retrospective study included 1215 patients who underwent major pulmonary resection via a minimally invasive approach between October 2012 and August 2025 at our institution: 903 underwent VATS (413 uniport, 490 multiport) and 312 underwent RATS. Propensity scores were calculated using preoperative variables, and stabilized inverse probability of treatment weighting (IPTW) was applied. The primary outcome was intraoperative significant vessel injury, defined as bleeding that required additional hemostatic intervention, such as sealant application, clipping, or suturing, after initial compression. Weighted logistic regression was used to assess the association between surgical approach and significant vessel injury. Secondary perioperative outcomes were also compared. After IPTW adjustment, baseline characteristics were well balanced. RATS was associated with a significantly lower risk of intraoperative significant vessel injury than VATS (adjusted odds ratio [OR]: 0.21, 95% confidence interval [CI], 0.08-0.54, P = 0.001). In an exploratory three-group analysis, RATS showed a lower risk than multiport VATS (OR: 0.15, 95% CI: 0.06-0.40, P < 0.001) and a borderline lower risk than uniport VATS (OR: 0.35, 95% CI: 0.12-1.00, P = 0.050). RATS was also associated with more favorable perioperative outcomes. RATS was associated with a lower risk of intraoperative significant vessel injury than VATS and with favorable short-term perioperative outcomes during major pulmonary resection.
With the rapid integration of AI into higher education, teachers' psychological responses are critical for technology adoption. This study examines AI self-efficacy and AI anxiety among university teachers in a Chinese university. It investigates the relationship between these two constructs and explores differences based on gender, age and academic major. A quantitative survey was administered to 350 teachers selected through stratified random sampling based on major. Results showed that both AI self-efficacy and AI anxiety were significantly above the neutral midpoint (M = 4.48, SD = 0.76; M = 4.35, SD = 0.85). AI self-efficacy was strongly and negatively associated with AI anxiety (r = - 0.59, p <0.01) and remained a significant negative predictor after controlling for gender, age, and major (β = - 0.112, p = .026). Female teachers reported higher anxiety and lower self-efficacy than male teachers, whereas computer science teachers reported the highest self-efficacy and the lowest anxiety. These findings suggest that university teachers may feel simultaneously capable of using AI and apprehensive about its broader implications. The study provides evidence from Chinese higher education and highlights the value of differentiated institutional support that addresses both teachers' confidence in using AI and their professional concerns.
Evidence regarding the outcomes of intravenous thrombolysis (IVT) in patients taking direct oral anticoagulants (DOACs) within 1 day before acute ischemic stroke remains limited. In this study, we aimed to evaluate the bleeding risk after IVT in patients with and without recent DOAC exposure. This retrospective cohort study analyzed TriNetX global network data (January 2010-September 2024) in adults aged ≥ 20 years receiving IVT for acute ischemic stroke. Groups with DOAC and no anticoagulant (no-OAC) exposure within 1 day before stroke were compared. The primary outcome was intracranial hemorrhage (ICH) within 2 days after IVT. Secondary outcomes included major bleeding, blood transfusion within 2 days, and 30-day and 90-day mortality rates. Subgroup analyses examined individual DOACs (apixaban, rivaroxaban, edoxaban, and dabigatran). Propensity score matching controlled for confounders with risk differences (RDs) and odds ratios (ORs) to estimate outcome events. Among 64,667 patients (mean age 65.1 ± 16.1 years; 50.1% women), 1183 (1.8%) received DOACs, and 63,462 (98.1%) received no anticoagulants. After propensity score matching, the DOAC cohort had lower risks of ICH (RD, - 2.88% [95% CI, - 4.28% to - 1.48%]; OR, 0.36 [95% CI, 0.21-0.60]) and major bleeding (RD, - 2.54% [95% CI, - 4.53% to - 0.55%]; OR, 0.66 [95% CI, 0.47-0.91]) than the no-OAC cohort. Mortality rates were similar at 30 (OR, 0.87 [95% CI, 0.69-1.08]) and 90 (OR, 1.04 [95% CI, 0.85-1.26]) days. In subgroup analyses, apixaban showed lower ICH and mortality risks than no-OAC. DOAC exposure within 1 day before stroke does not result in higher bleeding or mortality risk in patients receiving IVT for acute ischemic stroke.
Rangeland degradation is a major ecological problem in Central Asia, where extensive pasture systems support biodiversity, livestock production, and rural livelihoods. This study presents a systematic review of research on ecological monitoring of rangeland degradation in the region, focusing on satellite-based methods and field observations. Publications from 1990 to 2026 were screened using a structured review process, and 44 studies were included in the final analysis. The reviewed studies show that satellite-based methods are used more frequently because they allow monitoring over large areas, while field studies usually provide more detailed ecological information but cover smaller territories. A major contribution of this review is the combined analysis of regional patterns and monitoring methodologies used across Central Asia. The review analyzes monitoring practices across Central Asia and discusses the advantages and limitations of existing approaches. The review shows that the most reliable assessments are produced when satellite observations are supported by field data on vegetation, biomass, and soil condition. The reviewed studies report different degradation patterns depending on ecological conditions, observation periods, and research methods. In most cases, degradation is associated with both climatic factors and human activities. At the same time, such integrated approaches are still not widely applied, and research remains concentrated in a few countries, especially Kazakhstan and Kyrgyzstan. Considerable gaps persist in Uzbekistan, Tajikistan, and Turkmenistan. Overall, the reviewed literature shows the importance of developing more unified monitoring approaches that integrate satellite observations with field-based ecological data in different parts of Central Asia.
Activating mutations in the RAS-MAPK pathway account for ~20% of cases of pediatric hypertrophic cardiomyopathy (HCM) and are associated with poor outcomes. Mavacamten is approved for obstructive HCM; however, patients with RAS-associated HCM have not been included in the clinical trials so far. We aimed to characterize the functional and energetic disturbances in an in vitro RAS-HCM model and evaluate the therapeutic effects of mavacamten. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying a CRISPR-induced BRAF (p.Thr599Arg) mutation and their isogenic control were studied. Cell size, contractility, and transcriptomics were assessed, while energetics were determined using MitoStress assays, live ATP imaging, and NAD(P)H/FAD autofluorescence. BRAF-mutant hiPSC-CMs showed hypertrophy, hypercontractility, increased mitochondrial cofactor pools, and enhanced maximal respiratory capacity. Despite this, they developed ATP deficiency in response to rapid pacing, suggesting mitochondrial inefficiencies or an overwhelming ATP demand. Mavacamten normalized mitochondrial respiration and excessive ATP consumption, partially restoring energetic balance and highlighting hypercontractility as a major burden in RAS-HCM. BRAF-mutant cardiomyocytes recapitulate the characteristics of HCM in vitro. Mavacamten mitigates dysfunctions and restores energetic balance under stress conditions, indicating it holds potential as a therapeutic option for RASopathy-associated HCM. BRAF-mutant hiPSC-CMs exhibit hypertrophy, hypercontractility, and energetic imbalance under stress, reproducing pathological characteristics of RAS-HCM. Mitochondrial stress tests showed a higher basal respiration and maximal respiratory capacity, indicating that mitochondrial dysfunction is not the main cause of this imbalance. Mavacamten normalized basal mitochondrial respiration and ATP utilization under stress, indicating that hypercontractility represents a major energetic burden. The beneficial effects of mavacamten on BRAF-mutant hiPSC-CMs suggest therapeutic potential for treating RASopathy-associated HCM.
Hepatic inflammation and immunosurveillance play major roles in the progression of liver cancer. A common trigger for hepatic inflammation is oxidative stress, which stems from mitochondrial dysfunction. Here, we demonstrate that deletion of the mitochondrial stress integrator OMA1 increases hepatic primary tumor incidence and impairs survival in mice. Persistent activation of the KEAP1-Nrf2 oxidative stress pathway in the absence of OMA1 promotes early liver injury, which progresses into chronic hepatic inflammation and fibrosis during aging. Exhausted CD8+ and CD4+ T cells gradually accumulate in Oma1KO livers, facilitating hepatic tumor progression. Adoptive transfer and bone marrow-transplant experiments indicate that hepatic immunogenicity increases in the absence of parenchymal OMA1. Furthermore, hepatocyte-specific Oma1 deletion is sufficient to trigger NRF2 signaling, hepatocyte death, and immune exhaustion, suggesting that immunosurveillance during liver aging relies on the hepatic expression of OMA1. Given the therapeutic interest of OMA1 in several pathologies, these data are crucial to guide the generation of safe OMA1-targeted therapies.
Antisense oligonucleotides (ASOs) represent a promising therapeutic modality for central nervous system (CNS) disorders, offering highly specific modulation of gene expression. However, their clinical utility is severely limited by their inability to cross the blood-brain barrier (BBB), necessitating effective shuttling strategies. While transferrin receptor (TfR1)-mediated shuttling has shown therapeutic promise, the fundamental mechanisms governing the delivery of antibody-ASO conjugates across the BBB remain poorly understood. This study directly addresses this critical knowledge gap by establishing a mechanistic understanding of how the ASO cargo impacts major cellular interactions during the BrainshuttleTM-mediated transport across the BBB. Using a panel of advanced in vitro assays developed specifically for this purpose, including quantitative transcytosis, detailed imaging-based intracellular trafficking, and binding assays with brain endothelial cells (BECs), the shuttling process was systematically investigated. We demonstrate that ASO conjugation profoundly alters the cellular fate of the BrainshuttleTM. Specifically, conjugation increased the binding to BECs of low-affinity TfR1 shuttles via avidity effects while paradoxically reducing the binding strength of high-affinity shuttles. Functional assays confirmed the biological activity of the delivered ASOs; however, transcytosis of high-to-moderate affinity binders across the BBB model was significantly delayed upon ASO conjugation. Building on these mechanistic insights, we engineered TfR1 BrainshuttlesTM with optimized affinity and explored the shuttling potential of an alternative BBB receptor, CD98hc. These efforts culminated in the development of a novel bispecific BrainshuttleTM targeting both CD98hc and TfR1. This dual-targeting strategy exploits distinct and potentially non-competing trafficking pathways to overcome ASO-induced delays and significantly enhance in vitro transcytosis efficiency. The in vitro findings in this study underscore the necessity of mechanism-driven design to overcome ASO-induced limitations in delivery across the BBB. The bispecific CD98/TfR1 approach presented here provides a promising new strategy for maximizing delivery efficiency and enabling more effective therapeutic outcomes for CNS diseases.
Ticks are major ectoparasites and vectors of pathogens affecting humans, livestock, and wildlife. They harbor diverse microbial communities that may influence tick biology and interactions with microorganisms; however, functional information on tick-associated microbiomes remains limited, particularly in North Africa. In this pilot study, we applied a metaproteomic approach based on high-resolution tandem mass spectrometry to characterize bacterial communities associated with three tick species collected in Algeria: Rhipicephalus sanguineus sensu lato, Hyalomma aegyptium, and Hyalomma dromedarii. Peptide spectra were assigned to taxa using a two-step database search strategy based on NCBInr, and bacterial composition and relative abundance were compared across tick species and sampling locations. A total of 40 bacterial genera belonging to 32 families and four phyla were identified. Microbiome composition differed significantly between tick genera and collection locations, suggesting an influence of species-specific and geographical factors on microbial community structure. Dominant genera included Streptomyces, Bacillus, Clostridium, Escherichia, Flavobacterium, Paenibacillus, and Providencia. Peptides related to Coxiella spp. were frequently detected, consistent with previous reports of Coxiella-like endosymbionts in ticks. This pilot study provides a first metaproteomic characterization of tick-associated communities in Algeria. The results reveal species- and location-associated differences in microbial composition and highlight the potential of metaproteomics for exploring tick-associated microbiomes in North Africa.
Migration is one of the most feared complications following lip filler. The use of a specific filler with a high degree of elasticity and cohesiveness could be the key to solve the problem if injections are performed in the correct anatomical plane. The purpose of this study was to describe the authors' 5-year experience with a new concept of lip filling, iLips. This reproducible approach combines elasticity and cohesiveness of a 25,5 mg/ml filler injected through superficial micro-tunnels in a virtual space between orbicularis muscle and mucosa creating a tridimensional net that respects lip dynamic also leading to a low risk of filler migration. A total of 4583 consecutive patients who underwent lip filler with iLips technique were enrolled in this prospective study. An objective evaluation on the aesthetic results was obtained by a jury composed of 3 external plastic surgeons using Lip Fullness Merz scale. PROMs were investigated through FACE-Q administration to the patients ("Psychological function", "Satisfaction with outcome" and "Satisfaction with lips" scales). Statistical analysis was performed through Prism10. Complications were reported. t-test with Welch's correction showed an improvement in Lip Fullness Merz score both in upper and lower lip (p<0.05). A similar trend was shown also for "Psychological function", "Satisfaction with outcome" and "Satisfaction with lips" mean values after the procedure. Just 2 cases of major vascular complications were reported. iLips ® seem to be a safe, highly reproducible, effective and satisfying approach for lip augmentation positively impacting also the patient's psychological sphere. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Chronic obstructive pulmonary disease (COPD) represents a major global health burden, largely attributable to tobacco exposure, including emerging patterns such as early initiation and dual use with electronic cigarettes. Early detection through spirometry in primary care remains suboptimal, potentially limiting timely identification of early disease stages, including Pre-COPD and Preserved Ratio Impaired Spirometry (PRISm). This study aimed to assess whether the implementation of a structured, spirometry-based COPD clinic within primary care networks (Aggregazioni Funzionali Territoriali, AFTs) may be associated with improved diagnostic appropriateness, more consistent therapeutic management, and more efficient use of healthcare resources. We conducted a retrospective observational analysis of routinely collected clinical data from approximately 30,000 patients across three AFTs in the Campania Region (Italy), each including about 10,000 individuals. One AFT was equipped with a dedicated respiratory clinic providing in-house spirometry performed by trained personnel, while the other two followed standard care pathways without structured respiratory services. Key variables included spirometry utilization, diagnostic confirmation of COPD, patterns of care, and selected indicators of healthcare use. In the two standard AFTs, COPD diagnoses were not supported by spirometric confirmation in approximately 65% and 70% of cases, respectively. In contrast, the AFT with a dedicated clinic showed a substantially higher use of spirometry (approximately 80% vs. 30-35%), predominantly performed within the primary care setting. This organizational model was associated with improved alignment between diagnosis and objective testing, and with indicators suggestive of better therapeutic adherence and more appropriate use of secondary care services. The integration of structured, spirometry-enabled respiratory services within primary care networks may contribute to more appropriate COPD diagnosis and management. While the availability of spirometry alone is insufficient, organizational models that incorporate trained personnel, standardized procedures, and coordinated care pathways could represent a potentially effective approach to addressing under- and misdiagnosis in COPD.
To explore the active components and potential molecular mechanisms of Xiangsha Liujunzi decoction (XSLJZ) in the treatment of thyroid cancer. Active components and corresponding targets of XSLJZ were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Thyroid cancer-related targets were collected from seven bioinformatics databases, including GeneCards, OMIM, DisGeNET, DrugBank, TCGA, GEO, and TTD. A protein-protein interaction (PPI) network and a multi-level "XSLJZ-medicinal materials-active components-potential targets-thyroid cancer" network were constructed to identify core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by molecular docking to assess binding affinities. In vitro, CCK-8, flow cytometry, colony formation, Transwell, and Western blotting assays were used to evaluate cell proliferation, death, colony formation, migration, and protein expression in 8505C and TPC-1 thyroid cancer cells. In vivo, a subcutaneous xenograft model was established in female BALB/c nude mice (6-8 weeks old, 15-16 g) by injecting 2×106 8505C cells. Mice were randomly divided into model control (vehicle), low-dose XSLJZ (2 mg/kg), and high-dose XSLJZ (4 mg/kg) groups (n=6 per group), receiving daily gavage for 24 days. Tumor volume and body weight were measured every four days. Histopathological changes were observed by HE and immunohistochemical staining. Five major active components of XSLJZ (isoliquiritigenin, naringenin, baicalein, nobiletin, and glycyrrhetinic acid) and 45 core targets for thyroid cancer were identified. XSLJZ and these five components significantly inhibited the proliferation of 8505C and TPC-1 cells without notable toxicity to normal thyroid cells, with isoliquiritigenin showing the most prominent effect. Flow cytometry revealed that XSLJZ (16 mg/mL) induced up to 84.91% death in TPC-1 cells. Molecular docking showed low binding energies between isoliquiritigenin and Akt1, Caspase-3, Caspase-9, and PARP (lowest: －9.9 kcal/mol with PARP). XSLJZ and isoliquiritigenin dose-dependently suppressed colony formation and migration, downregulated RAGE, p-PI3K, and p-Akt, upregulated Bax and mitochondrial cytochrome c, and activated Caspase-3/9-mediated apoptosis and GSDME-dependent pyroptosis via the AGE-RAGE→PI3K/Akt axis. In vivo, both low and high doses of XSLJZ significantly inhibited tumor growth, reduced Akt and Ki-67 expression in tumor tissues (all P<0.05), and showed no obvious toxicity to the heart, liver, or kidneys. XSLJZ inhibits thyroid cancer cell proliferation and induces cell death through multi-component, multi-target synergistic regulation of the AGE-RAGE→PI3K/Akt signaling pathway. 目的: 探究香砂六君子汤（XSLJZ）治疗甲状腺癌的活性成分及潜在分子机制。方法: 利用中药系统药理学数据库与分析平台（TCMSP）筛选XSLJZ的药物有效活性成分及其靶点。运用GeneCards、在线人类孟德尔遗传（OMIM）、DisGENET、DrugBank、癌症基因组图谱（TCGA）、基因表达综合（GEO）数据库及治疗靶点数据库（TTD）等七个生物信息学数据库筛选甲状腺癌相关靶点。通过构建蛋白-蛋白相互作用（PPI）网络和“XSLJZ-药材-活性成分-潜在靶点-甲状腺癌”多层次网络筛选核心靶点，并通过基因本体（GO）功能注释、京都基因和基因组数据库（KEGG）通路进行富集分析，分子对接分析XSLJZ活性成分与靶点的结合能力。体外试验中，通过CCK-8检测细胞活性，流式细胞术检测甲状腺癌细胞死亡情况，克隆形成实验检验甲状腺癌细胞增殖能力，Transwell实验检验甲状腺癌细胞迁移能力，蛋白质印迹法检测目标蛋白表达。取6~8周龄雌性BALB/c裸鼠（体重15~16g）建立皮下移植瘤模型，于裸鼠侧腹部皮下注射2×10⁶/100 µL的8505C细胞悬浮液。一周后，将小鼠随机分为模型对照组（给予赋形剂）、XSLJZ小剂量组（给予XSLJZ 2 mg/kg）和XSLJZ大剂量组（给予XSLJZ 4 mg/kg），均每日一次灌胃，持续24 d，每组6只。每四天测量一次小鼠的体重和肿瘤大小。HE染色和免疫组织化学染色观察组织病理学变化。结果: 筛选出XSLJZ的五种主要活性成分（异甘草素、柚皮素、黄芩素、川陈皮素、甘草次酸）及45个XSLJZ治疗甲状腺癌的核心靶点。CCK-8实验显示，XSLJZ及五种活性成分可显著抑制8505C、TPC-1细胞增殖，对正常甲状腺细胞无明显毒性，以异甘草素抑癌效果最突出。流式细胞术结果显示，XSLJZ及五种活性成分能诱导甲状腺癌细胞死亡，其中16 mg/mL XSLJZ处理后TPC-1细胞死亡率达84.91%;分子对接结果显示异甘草素与Akt1、Caspase-3、Caspase-9及PARP的结合能较低，其中与PARP的结合能低至－9.9 kcal/mol。XSLJZ及异甘草素可呈剂量依赖性抑制甲状腺癌细胞克隆形成与迁移能力，通过阻断AGE-RAGE→PI3K/Akt信号轴下调RAGE、磷酸化PI3K及磷酸化Akt表达，上调促凋亡蛋白Bax与线粒体细胞色素C，同时激活Caspase-3/9介导的凋亡与GSDME依赖的焦亡。体内试验显示，小、大剂量XSLJZ均抑制移植瘤裸鼠的肿瘤生长，下调肿瘤组织Akt和Ki-67表达（均P<0.05），且对小鼠心、肝、肾无明显毒性。结论: XSLJZ通过多成分-多靶点协同调控AGE-RAGE→PI3K/Akt通路抑制甲状腺癌细胞增殖并诱导细胞死亡。.
Pu'er tea fermentation relies on complex microbial activities. This study explored aroma formation in ripe Pu'er tea inoculated with a synthetic fungal consortium using a multi-omics approach across six sampling stages. Sensory evaluation, physicochemical analysis, volatile profiling (HS-SPME-GC×GC-TOFMS), non-volatile metabolomics (UHPLC-Q-Exactive/MS), and metagenomic sequencing were integrated. Inoculation was associated with a distinct floral-fruity aroma. Combined ROAV and VIP analyses identified four volatile compounds, namely phenylethyl alcohol, trans-β-ionone, geraniol, and 1-octen-3-ol, as potentially important aroma-active contributors. Among them, phenylethyl alcohol, trans-β-ionone, and geraniol might play a major role in the floral-fruity character, and their accumulation appeared associated with tea moisture content. Nonanal exhibited a high ROAV but a low VIP value. Non-targeted metabolomics revealed 154 significantly altered metabolites, 38 of which were associated with these volatile compounds. Metagenomic analysis indicated substantial shifts in microbial community structure and function, correlated with physicochemical parameters and volatile profiles. Random forest modeling identified Sphingomonas, Rothia, and Bacteroides as potentially involved in aroma formation. These findings provide insights into the metabolic and microbial dynamics underlying floral-fruity aroma development, offering a scientific basis for tailored starter culture design.
This study aimed to develop and evaluate a deep learning-based surgical navigation system capable of recognizing the ureter, uterine artery, and bladder-uterine dissection plane during minimally invasive gynecologic surgery. An artificial intelligence (AI) model was developed at the University of Tokyo Hospital using videos of prior surgeries. Surgical videos of 27 laparoscopic or robot-assisted total hysterectomies were used to create training and validation datasets, with an additional set of cases serving as an independent test set. Key frames were manually annotated to train segmentation models for the ureter and uterine artery. A separate model visualized loose connective tissue fibers (LCTF) to aid in recognizing the bladder-uterine peritoneal dissection plane. Quantitative performance was assessed using standard segmentation metrics, and a qualitative evaluation was conducted by nine gynecologic surgeons using predefined scoring criteria. The segmentation models achieved moderate quantitative performance, with Dice similarity coefficients of approximately 0.51 for the ureter and 0.45 for the uterine artery. In contrast, qualitative evaluation demonstrated favorable clinical interpretability. The mean recognition scores assigned by nine expert surgeons were 4.12 for the ureter and 3.45 for the uterine artery on a five-point scale, indicating that most structures were recognized clearly with only minor misrecognition. For bladder dissection, visualization of connective tissue fibers enabled identification of the correct dissection plane in the majority of evaluated frames; more than 70-80% of connective tissue was recognizable in most frames, and substantial misrecognition was uncommon. This study demonstrates that a deep learning-based system can recognize three key elements of a total hysterectomy: the ureter, the uterine artery, and the bladder-uterine dissection plane. Despite modest quantitative metrics, qualitative assessments indicated strong clinical utility. These findings establish a foundation for an integrated AI-assisted surgical navigation platform to enhance the safety and standardization of minimally invasive gynecologic surgery.
Mental health disorders are highly prevalent worldwide, yet access to timely and effective mental health assessment (and care) remains limited. Artificial intelligence (AI) offers potential solutions, but the literature on its use in psychological assessment contexts has not been comprehensively mapped. This review aimed to systematise existing research, identify gaps, evaluate methodological limitations, and outline future directions. Using a librarian-approved search strategy, 7595 records were retrieved from major databases and screened independently by two coders. Following the eligibility assessment, 320 peer-reviewed articles were included. Studies showed wide variability in sample sizes (1-19,400,000) with no clear temporal trend. Most recruited clinical (21%) or general population (16%) samples from China (24%) or the United States (21%), and focused on depression (54%), anxiety (14%), suicidality (12%) or stress (8%). Supervised (75%) and deep learning (47%) approaches predominated, often with multiple algorithms compared (77% of the studies). Validation commonly relied on cross-validation and convergence with screening instruments, with relatively little use of DSM or ICD diagnostic criteria (71% used neither). Area-Under-the-Receiver-Operating-Characteristics-Curve (AUC) was the most frequently used performance metric, and unsupervised models achieved the highest average AUC. A marginal improvement in performance was evident from 2014 to 2025. Overall, AI shows promise as a psychological assessment tool, but progress is constrained by limited transparency, heavy reliance on self-report data, inconsistent use of validated diagnostic standards, a narrow focus on outcomes, and insufficient demographic and cultural analyses. Future research should prioritise interpretability, ethical and cultural responsiveness, multi-modal data, diverse samples, and clinically meaningful validation.