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Invasive infections caused by Aspergillus flavus are more common in tropical and subtropical countries. The emergence of azole resistance in A. flavus complicates the management of aspergillosis, as azoles are the first-line and empirical therapy. The aim of this study was to investigate the molecular mechanisms underlying azole resistance in A. flavus, focusing on the cyp51C gene. We screened 34 molecularly confirmed A. flavus isolates obtained from patients with invasive aspergillosis for cyp51C gene expression by real-time RT-qPCR and for mutations by PCR sequencing. Molecular modeling and docking studies were performed using SWISS-MODEL, SwissDock, and I-TASSER software. Susceptibility testing revealed that 14.71% and 8.82% of isolates were resistant to itraconazole and posaconazole, respectively, with 5.88% exhibiting cross-resistance. The mRNA expression of cyp51C was upregulated (>2.5-fold) in five of the six resistant strains (83.33%). Hyperexpression of cyp51C was significantly more frequent among resistant isolates than among susceptible isolates (Fisher’s exact test, p = 0.014). Sequencing identified ten point mutations, including six synonymous and four non-synonymous substitutions. The non-synonymous mutations M54T and S240A were detected in the protein sequences of both resistant and susceptible isolates. Notably, D254N and I285V were observed exclusively in resistant isolates and in susceptible isolates with itraconazole MICs near the epidemiological threshold. Homology modeling and 3D structure prediction of the mutated Cyp51C protein demonstrated interactions with itraconazole, posaconazole, and voriconazole. Importantly, I-TASSER analysis indicated that the I285V substitution is located near the itraconazole binding site. Simultaneous overexpression of the cyp51A, cyp51B and cyp51C genes was observed in 33.33% of resistant isolates. These findings suggest that multiple target genes and mechanisms may act concurrently to confer azole resistance in A. flavus. Overall, this study supports the hypothesis that azole resistance in A. flavus is multifactorial and highlights the potential value of combining mutation analysis, gene expression profiling, and structural modeling for improved molecular surveillance and antifungal resistance monitoring. Full article

Background: Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disorder with multifactorial etiologies, while fibromyalgia is a chronic centralized pain condition characterized by widespread pain and central sensitization. Although shared mechanisms such as neurogenic inflammation and altered pain processing have been proposed, longitudinal evidence evaluating whether CTS predisposes to subsequent fibromyalgia remains limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults aged ≥ 18 years with ≥2 clinical encounters between 2018 and 2023 were included. Patients with CTS formed the exposure cohort, while individuals without CTS undergoing routine health examinations served as controls. Those with prior fibromyalgia, malignancy, or death before index were excluded. One-to-one propensity score matching was performed to balance demographics, body mass index, psychiatric conditions, socioeconomic factors, healthcare utilization, and comorbidities including mood, anxiety, stress-related, and sleep disorders. The primary outcome was incident fibromyalgia. Sensitivity analyses included alternative matching strategies, extended washout periods, stricter exposure definitions, and active comparator analyses using osteoarthritis. Stratified analyses by age and sex were conducted. Associations were estimated using hazard ratios with 95% confidence intervals. Results: After matching, 217,208 patients were included in each cohort. CTS was associated with a significantly increased risk of fibromyalgia (HR 2.709, 95% CI 2.521–2.911). Consistent findings were observed across sensitivity analyses. Compared with osteoarthritis, CTS remained associated with higher fibromyalgia risk (HR 1.331, 95% CI 1.254–1.411). Stratified analyses demonstrated consistent associations across age groups (18–64 years: HR 2.820, 95% CI 2.595–3.065; ≥65 years: HR 2.717, 95% CI 2.337–3.159) and sexes (male: HR 3.018, 95% CI 2.482–3.672; female: HR 2.655, 95% CI 2.457–2.869). Conclusions: CTS was associated with coded fibromyalgia diagnosis in this large real-world cohort, and this association was observed across multiple sensitivity and stratified analyses. These findings should be interpreted as evidence of an epidemiologic association rather than a causal relationship. CTS may serve as a clinical marker for patients who warrant attention to broader pain-related symptoms, while future studies are needed to clarify temporality and underlying mechanisms. Full article

The Jiaduoling area is located in the northern segment of the Southwest Sanjiang Metallogenic Belt, a region characterized by complex geological structures and abundant mineral resources. This study systematically identifies the spatial correlation between subsurface magnetic bodies and tectonic structures by utilizing 1:50,000 high-precision aeromagnetic data. Advanced processing techniques—including upward continuation, vertical derivatives, total gradient modulus, and Euler deconvolution—were integrated to refine the structural framework and clarify the mechanisms of fault-controlled mineralization. The results indicate that the aeromagnetic anomaly pattern is predominantly governed by NW-trending faults. Specifically, the deep-seated major fault F₁ (with a calculated depth exceeding 3 km) served as the primary migration channel for ore-forming fluids, while secondary faults created localized ore-hosting spaces. Physical property analysis reveals a significant magnetic contrast, where Mesozoic intermediate-acid magmatic rocks act as the essential source for mineralization, providing both material and thermal energy for the formation of porphyrite-type iron deposits. Based on these findings, a three-dimensional “aeromagnetic anomaly-structural framework-mineralization” correlation model was established. Finally, two high-potential metallogenic prospective zones (P1 and P2) were delineated, providing precise geophysical evidence and strategic guidance for regional mineral exploration and the targeting of concealed ore bodies. Full article

This study investigates the low-latitude ionospheric response over the Eastern Hemisphere during two successive geomagnetic storms on 12–13 November 2025. BDS-GEO observations from 20 GNSS stations, CODE GIM data, Swarm satellite observations, and simulations from the TIEGCM and HWM14 models were integrated to investigate regional ionospheric disturbances, single-station responses, and Equatorial Ionization Anomaly (EIA) evolution. During the first storm, with SYM-H reaching −254 nT, EIA intensification and poleward expansion beyond ±20° magnetic latitude were observed, with VTEC approaching 100 TECU at stations over Australia and rTEC exceeding 80% over Australia and the adjacent Pacific Ocean. Swarm observations showed TEC decreases within the EIA crest region and TEC increases in the surrounding areas. In contrast, the second storm, with SYM-H reaching −154 nT, produced disturbances with lower amplitudes, mainly characterized by localized positive TEC anomalies near the magnetic equator within 100°E–180°E, together with negative TEC anomalies in the surrounding low-latitude regions. The first storm was associated with southward IMF Bz reaching −54 nT and electrodynamic uplift related to PPEF, which contributed to the superfountain effect, whereas the second storm was influenced by residual disturbed neutral winds, reduced O/N₂ ratios at low latitudes, and the preconditioned ionospheric state inherited from the first storm. These results demonstrate that successive geomagnetic storms can produce different ionospheric responses in terms of intensity, spatial morphology, and driving mechanisms, highlighting the event dependence and regional variability of low-latitude ionospheric storm responses. BDS-GEO observations offer distinct advantages for monitoring localized ionospheric disturbances over the Eastern Hemisphere. Full article

Accurate wind-power forecasting is essential for grid scheduling when renewable generation becomes highly variable. This study developed WindPower-SAFusion, an Informer-inspired forecasting model designed for long wind-power sequences. The framework is built around three complementary designs. First, ProbSparse self-attention is used to lower the attention cost from $O\left(L^2\right)$ to $O\left(L\log L\right)$ while retaining informative temporal dependencies. Second, convolutional distillation is embedded in the encoder to summarize local fluctuations and form multi-scale representations. Third, historical theoretical power and wind speed are fused in a recursive forecasting scheme for multi-step prediction. The model is evaluated using measured data from the Daliang Wind Farm in Guazhou, Gansu Province, China. Experiments conducted using 1-day, 3-day, and 7-day horizons show that WindPower-SAFusion obtained lower errors and higher explanatory ability than the selected statistical and deep learning baselines. The ablation results further confirm the contributions of sparse attention, convolutional feed-forward extraction, and sequence distillation. These findings indicate that the proposed framework can provide an effective data-driven tool for wind-farm dispatching and power-management applications. Full article

Background and Clinical Significanc: Neuropathic corneal pain is a debilitating condition characterized by ocular pain disproportionate to clinical signs, often resulting from peripheral and central sensitization of the corneal somatosensory pathway. Emerging evidence suggests that chronic involuntary muscle contraction in blepharospasm may lead to irritation of trigeminal afferents and corneal neurogenic inflammation, potentially predisposing patients to neuropathic corneal pain. Given its debilitating nature, early recognition can prevent the progression of neuropathic sequelae. This study examines the potential role of blepharospasm as a predisposing factor contributing to neuropathic corneal pain. Case Presentation: This retrospective case series describes three cases (median age: 50 years) of neuropathic corneal pain in association with blepharospasm and their clinical course following multimodal treatment over a median follow-up period of one year. Ocular surface was evaluated using slit-lamp biomicroscopy, while corneal nerve structure and morphology were assessed with in vivo confocal microscopy. All the three subjects presented with minimal ocular surface staining but disproportionate ocular pain characterized by burning sensation and photophobia. Proparacaine challenge testing was performed to determine the subtype of neuropathic corneal pain. Pain symptoms and quality of life were evaluated using the Ocular Pain Assessment Survey and Ocular Surface Disease Index questionnaires. In vivo confocal microscopy demonstrated characteristic corneal nerve abnormalities including reduced corneal nerve density, increased nerve tortuosity, and the presence of microneuromas. Treatment included oral Pregabalin or Gabapentin, topical lubricants, Cyclosporine 0.05% (1 case), and 20% autologous serum eye drops (1 case). Two of the three cases received four to five injections of botulinum toxin for blepharospasm, whereas one had undergone a single injection prior to review. All patients also received weekly periorbital quantum molecular resonance electrotherapy for two months. Improvements were observed across multiple domains of the Ocular Pain Assessment Survey and Ocular Surface Disease Index evaluation, including ocular pain, photophobia, non-ocular pain, and quality-of-life measures following multimodal treatment. The co-existence of blepharospasm and neuropathic corneal pain observed in our cases supports a possible association between chronic periocular muscle hyperactivity and corneal nociceptor sensitization. Proposed mechanisms include chronic trigeminal nerve irritation, neurogenic inflammation, and sensitization mediated by pro-inflammatory neuropeptides. Multimodal treatment targeting both motor hyperactivity and neuropathic pain pathways appeared to provide symptomatic relief, including the use of quantum molecular resonance electrotherapy, which might modulate pain pathways, block nociceptor neurotransmission, and accelerate corneal nerve regeneration. Given the complexity of the neural pathways responsible for ocular discomfort, further studies are required to elucidate the relationship between neuropathic corneal pain and blepharospasm in larger cohorts, as well as refine existing therapeutic approaches, including evaluating the therapeutic role of electrotherapy. Conclusions: Blepharospasm may represent a potential predisposing factor of neuropathic corneal pain. Early recognition and concurrent treatment of blepharospasm and neuropathic corneal pain can effectively relieve symptoms and improve quality of life. Adopting a multimodal treatment approach is therefore recommended. Full article

This study characterized the basic structure of partridge tea leaves polysaccharides and comparatively analyzed the in vitro lipid-lowering activity of total partridge tea polysaccharide (PTPS) and its two purified homogeneous fractions, namely PTPS-I (13,560 Da) and PTPS-III (30,935 Da). In terms of structural composition, PTPS-I and PTPS-III share identical monosaccharide types but differ significantly in monosaccharide proportions, glycosidic linkages and backbone structures. In vitro experiments demonstrated that PTPS, PTPS-I, and PTPS-III could effectively reduce intracellular lipid levels and oxidative stress in free fatty acids (FFA)-injured L02 cells and alleviate the decline of mitochondrial membrane potential in damaged hepatocytes. At the high concentration of 400 μg/mL, PTPS-III showed a superior effect in reducing triglyceride (TG) content compared with the other two samples, with the value reaching 0.31 ± 0.024 mmol/mg prot. Additionally, 400 μg/mL PTPS markedly decreased total cholesterol (TCHO) content and enhanced superoxide dismutase (SOD) activity, which were 0.55 ± 0.039 mmol/mg prot and 29.92 ± 0.22 μmol/mg prot, respectively. PTPS-I of 400 μg/mL significantly reduced malondialdehyde (MDA) content to 1.31 ± 0.288 μmol/mg prot and inhibited the decline of mitochondrial membrane potential (MMP) by 9.67%. The three polysaccharide fractions could elevate the mRNA expression of Nrf2, NQO1 and HO-1 in the Nrf2/HO-1 signaling pathway and the gene expression of PPARα, CPT-1 and ACOX1 in the lipid metabolism pathway, and ultimately regulate lipid accumulation in L02 cells. This study validated the in vitro antilipid activities of partridge tea leaves polysaccharide and provided fundamental data for research on its bioactivity and functional components. Further in vivo assays and mechanism exploration will be conducted to evaluate its potential application in fatty liver intervention product development. Full article

Background: Ventral hernias are a common complication following abdominal surgery, occurring in up to 20% of patients after midline laparotomy and as many as 43% of those who undergo orthotopic liver transplantation (OLT). These hernias pose unique challenges due to chronic immunosuppression, impaired wound healing, and the anatomic disruption caused by subcostal and “Mercedes-Benz” incisions. As survival after OLT continues to improve, the need for durable, infection-resistant abdominal wall reconstruction has become increasingly important. Methods: We performed a single-institution retrospective review of all OLT patients undergoing abdominal wall reconstruction by the senior author between June 2014 and April 2026. Our approach emphasizes component separation to reestablish myofascial continuity, biologic onlay reinforcement with human acellular dermal matrix (HADM), and multipoint fixation in a progressive tension pattern. Results: Forty patients (43 encounters) were included. Mean age was 55.7 ± 10.2 years, mean BMI was 31.2 ± 4.9 kg/m², and 60.0% were obese. The majority presented with recurrent hernias (67.4%), and 41.9% had prior mesh in situ. Component separation was performed in all cases, and intraoperative Botox in 18.6%. HADM was used in 83.7% of encounters. At a mean follow-up of 34.0 months, there was 1 hernia recurrence (2.3%). The surgical site occurrence rate was 14.0%, with seroma as the most common complication (9.3%). There were no 30-day mortalities. Conclusions: By integrating biologic and mechanical principles, this reconstructive strategy provides a durable solution for abdominal wall repair in liver transplant recipients. A 2.3% recurrence rate and 14.0% surgical site occurrence rate compare favorably to published benchmarks in the transplant population. Full article

Background: Cytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available. Objectives: This scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-organ toxicity, to characterize their mechanisms of action and organ targets, and to identify evidence gaps and agents with translational potential. Methods: The review was designed and reported in accordance with the PRISMA-ScR checklist. A structured electronic search was conducted across PubMed/MEDLINE, Scopus, Cochrane Library and Embase, and Web of Science from database inception to 15 July 2025. Eligible studies were restricted to full-text, peer-reviewed, English-language research involving in vivo mammalian models administered cytarabine as the principal toxin, with at least one pharmacological co-intervention and at least one quantitative or histopathological organ-injury outcome. Results: From 5701 retrieved records, 36 eligible in vivo mammalian studies (spanning 1964–2024) were identified. Included studies addressed neurotoxicity (n = 6), gastrointestinal mucositis (n = 9), ocular toxicity (n = 3), hepatotoxicity (n = 3), bone marrow suppression (n = 4), chemotherapy-induced alopecia (n = 5), and reproductive and developmental toxicity (n = 4). Five recurring mechanistic strategies were identified across the heterogeneous agents tested: redox buffering (N-acetylcysteine, α-lipoic acid, rutin, swertiamarin, α-tocopherol), mitochondrial preservation (betanin, thymoquinone, vitamin D, sodium zinc dihydrolipoylhistidinate [DHLHZn]), tissue-microenvironment reprogramming (apraglutide, BADGE, plerixafor, short-chain fatty acids, β-glucan), molecular antagonism (deoxycytidine, dCMP), and immunomodulation (lienal peptide, IL-1β, AHCC). Conclusions: This scoping review provides the first systematic cartography of pharmacological mitigation strategies for cytarabine-induced multi-organ toxicity. Five mechanistic pathways converge across eight organ systems, with apraglutide and N-acetylcysteine representing the most clinically translatable candidates. Plerixafor and PPARγ blockade by BADGE constitute high-priority candidates for bone marrow niche protection, while the deoxycytidine antagonism principle warrants formal pharmacokinetic evaluation. The complete absence of cardiotoxicity mitigation data defines the most critical gap for future research. Full article

Neutrophil extracellular traps (NETs) are web-like structures composed of decondensed DNA, histones, and proteins released by activated neutrophils. Originally identified as an innate defense mechanism against pathogens, NETs have since been implicated in cancer progression and immune evasion. Within the tumor microenvironment (TME), NETs suppress anti-tumor immunity through multiple mechanisms, including the physical exclusion of CD8⁺ cytotoxic T lymphocytes from the tumor interior and upregulation of exhaustion markers via checkpoint ligands. This review synthesizes current preclinical and clinical evidence on the interplay between NETs and CD8⁺ T cells across multiple malignancies, including non-small cell lung cancer, pancreatic ductal adenocarcinoma, cholangiocarcinoma, colorectal cancer, bladder cancer, hepatocellular carcinoma, skin cancer, and penile cancer. Cancer-specific mechanisms of NET-mediated immune suppression are discussed, including IL-8, IL-17, CXCL6, and TGF-β-driven NETosis pathways. Clinical data consistently demonstrate that elevated NET levels correlate with reduced CD8⁺ T cell infiltration, T cell dysfunction, and worse patient outcomes. Emerging therapeutic strategies targeting this axis are reviewed, including DNase I-mediated NET degradation, Peptidyl arginine deiminase 4 (PAD4) inhibition, CXCR2 blockade, and combination approaches with immune checkpoint inhibitors. These interventions have shown promise in restoring CD8⁺ T cell cytotoxicity and overcoming immunotherapy resistance in preclinical models. Collectively, the evidence supports the NET-CD8⁺ T cell axis as a promising prognostic and therapeutic target warranting further clinical investigation. Full article

This study investigated the effects of letrozole (LE) on reproductive performance, hormones, and plasma metabolites in Turpan Black ewes. Sixty-six multiparous non-pregnant ewes were randomly assigned to a Control group or an LE group (0.2 mg/kg body weight, added to the basal diet) for 180 days, both receiving estrus synchronization. LE significantly increased the twinning rate (p < 0.05), but no significant differences were observed in estrus rate, conception rate, or lambing rate (p > 0.05). Hormone analysis revealed significant changes in Luteinizing Hormone (LH), Progesterone (P₄) (group, time, and interaction effects), Estradiol (E₂), Testosterone (T) (time effect), Gonadotropin-Releasing Hormone (GnRH) (group and interaction effects), and Follicle-Stimulating Hormone (FSH) (primarily time effect). Metabolomic analysis identified 3451 differential metabolites. L-saccharopine and 5-hydroxylysine were downregulated (p < 0.01), and estrone was decreased (p < 0.05). Lysylhistidine was upregulated (p < 0.05), while testosterone and LE showed rising trends without statistical significance (p > 0.05). These metabolites were mainly enriched in amino acid metabolism and lipid metabolism pathways related to reproduction. Significant correlations were also detected between several metabolites and reproductive hormones. LE improves the twinning rate in Turpan Black ewes, likely by modulating key reproductive hormones (LH, P₄, GnRH, FSH, E₂, T) and altering plasma metabolites involved in amino acid and lipid metabolism. These findings provide new insights into the regulatory mechanisms of letrozole on ovine reproduction. Full article

Every year, respiratory syncytial virus (RSV) causes an estimated 33 million lower respiratory tract infections in children under five years of age, driving millions of hospitalizations worldwide and substantial mortality in developing countries. For 28 years, the monoclonal antibody (mAb) palivizumab has been the principal agent for RSV immunoprophylaxis, reducing hospitalization in defined high-risk groups through monthly intramuscular dosing. The recent approval of two second-generation long-acting mAbs, nirsevimab and clesrovimab, and maternal preF vaccine has fundamentally changed the RSV prevention landscape. In contrast to palivizumab, the long-acting mAbs offer single-dose seasonal protection across a broader infant population, enabling universal immunization programmes for the first time. In this review, we conjointly examine nirsevimab and clesrovimab across their mechanisms of action, pharmacokinetics, efficacy, safety and cost-effectiveness, using palivizumab as the reference standard. Cross-trial efficacy comparisons are complicated by differences in study populations and endpoint definitions; however, when these factors are considered, the available evidence suggests that all three agents offer broadly comparable protection against severe RSV disease. All three agents also demonstrate favourable and comparable tolerability profiles. Nirsevimab is now supported by a substantial body of real-world evidence confirming effectiveness in routine immunization programmes that closely align with registrational studies. Clesrovimab, as the newest agent, currently lacks real-world effectiveness, and both long-acting monoclonals require further confirmatory evidence in high-risk groups. Overall, existing data support that both monoclonals have equivalent efficacy and safety profiles as palivizumab, and choice should be based on cost-effectiveness and local availability, with consideration given to optimal integration of infant immunoprophylaxis alongside maternal RSV vaccination programmes. Full article

A common limitation of existing multi-AGV cooperative systems is their reliance on the obstacle-agnostic Manhattan distance as the basis for reward signals. This causes agents to receive misleading feedback, engage in excessive futile exploration, and ultimately achieve poor training quality. To address this, we introduce an A*-distance guidance mechanism for multi-agent reinforcement learning (MARL) path planning, built on the precise path distance computed via the A* algorithm (A*-distance). Within the QMIX framework, we incorporate an A*-distance-based guiding function into the action selection mechanism. This function evaluates candidate actions by quantifying their immediate effect on the A*-distance, providing positive incentives for actions that bring the agent closer to the goal and applying negative penalties for those that lead it farther away. This effectively biases exploration towards actions that genuinely shorten the obstacle-aware path to the goal, suppresses ineffective exploration, and accelerates policy convergence. Experiments in four warehouse environments (simple obstacles, complex obstacles, large-scale, and congested) show that, compared with standard QMIX, the proposed method achieves higher global average reward and faster convergence. The advantage grows as environment scale and obstacle density increase. In the large-scale and congested environments, standard QMIX and the other MARL baselines fail to solve the task, whereas the proposed method still succeeds. It is the only learning-based method to solve these hardest tasks while keeping path length close to that of dedicated search-based solvers. Ablation experiments further show that the A*-distance-guided action selection is the primary contributor to these gains, while the A*-distance reward plays a supporting role. Full article