Search Results (91,787)

Background/Objectives: Streptococcus parasuis is an under-recognized member of the Streptococcus suis complex that can be misidentified by routine diagnostic methods. Human clinical isolates remain sparsely characterized. This study investigated the antimicrobial phenotype, genomic features, population position, and larval pathogenicity of a human pleural-fluid isolate. Methods: Strain HUGSPH was recovered during the care of a patient with pneumonia. Hybrid whole-genome sequencing (WGS), average nucleotide identity analysis, multilocus sequence typing (MLST), core-genome phylogenetics, comparative pan-genomics, and an exploratory host-origin association analysis were performed. Minimum inhibitory concentrations (MICs) were determined using the VITEK 2 Compact system with an AST-ST03 card, and virulence was evaluated in Galleria mellonella larvae. Results: Genome-based analysis confirmed HUGSPH as S. parasuis and assigned it to the novel sequence type (ST) 181. The isolate clustered within a predominantly human-origin phylogenetic clade. Because species-specific clinical breakpoints are unavailable, the MICs were interpreted provisionally using explicitly stated surrogate Clinical and Laboratory Standards Institute (CLSI) criteria; erythromycin, clindamycin, and levofloxacin were categorized as resistant under those criteria. Several predicted antimicrobial-resistance-associated genes were detected. In a restricted comparison of seven human-origin and nine swine-origin genomes, eight genes were present in all included human-origin isolates and absent from all included swine-origin isolates, whereas metQ, metP, and metN showed the reciprocal pattern. HUGSPH caused dose-dependent larval mortality, reaching 100% at 10⁷ colony-forming units (CFU) by 96 h. Conclusions: HUGSPH expands the genomic record of human clinical S. parasuis and highlights the diagnostic and surveillance relevance of antimicrobial resistance in this species. The susceptibility categories, source-associated genes, and larval phenotype require validation by reference susceptibility testing, broader phylogenetically balanced collections, comparative strains, and mammalian models. Full article

Background: Obesity is a complex, chronic disease with metabolic complications. Many patients respond suboptimally to conventional interventions like the hypocaloric Mediterranean diet (MD), highlighting the need to investigate alternative supervised nutritional strategies in patients with an insufficient response to conventional dietary treatment. Objectives: This study aimed to evaluate the KETOCOMP (Food-Based KETOgenic Nutritional Protocol for Patients with COMPlicated Obesity), a medically and dietitian-supervised, food-based sequential ketogenic nutritional protocol consisting of a ketogenic phase followed by controlled carbohydrate reintroduction, for improving anthropometric and body composition in patients with complicated obesity who were non-responsive to conventional dietary treatment. Methods: In this longitudinal, observational study, adult patients with obesity/overweight and metabolic comorbidities, previously non-responsive to a hypocaloric MD, were identified. Patients followed a 4-week food-based ketogenic diet (approx. 1200 kcal/day, <20 g carbohydrate, CHO) followed by a 4-week low-carbohydrate reintroduction phase (approx. 1300 kcal/day, up to 100 g CHO). Anthropometric and body composition parameters were assessed at baseline (T0), after the MD (T1), after the ketogenic phase (T2), and after the low-carbohydrate phase (T3). Intra-subject comparisons were performed. Results: Across the entire observed nutritional pathway (T0–T3), body weight (BW), body mass index (BMI), and fat mass (FM) decreased by 7.7%, 9.45%, and 23.1%, respectively. Using T1 as the relevant baseline for the second-line KETOCOMP sequence, mean BW and FM decreased by 7.79 kg and 6.29 kg, respectively, from T1 to T3; during the ketogenic phase alone (T1–T2), BW decreased by 6.10 kg and FM by 4.80 kg. Body Cell Mass (BCM) and Phase Angle (PhA) showed no statistically significant changes during the ketogenic and carbohydrate-reintroduction phases, whereas Fat-Free Mass (FFM) decreased significantly. Significant reductions in waist and hip circumferences (WC, HC) were also observed. No serious adverse events were documented among included participants; however, discontinuation rates could not be assessed because completion through T2 formed part of cohort selection. Conclusions: The KETOCOMP protocol may represent a clinically applicable second-line nutritional strategy for patients with obesity and metabolic complications who respond suboptimally to conventional dietary treatment. The observed reductions in body weight and fat mass, together with the absence of significant changes in BCM and PhA, suggest a favorable short-term change in body composition. However, larger prospective controlled studies incorporating standardized clinical and biochemical safety monitoring and direct assessment of skeletal muscle are required to confirm these findings and evaluate longer-term outcomes. Full article

Dedekind’s problem counts monotone Boolean functions, equivalently downsets of a Boolean lattice. We recast this enumeration as a finite layer-ratio reconstruction problem for the Whitney numbers of the ranked ideal lattice. An exact adjacent-layer double count expresses each layer ratio through local averages of the number of addable elements and the number of removable elements. Reversible fixed-layer Markov chains estimate these averages and hence estimate the Dedekind number $M\left(n\right)$. Backtests at $M\left(8\right)$ and $M\left(9\right)$ calibrate seed-level variability under the fixed protocol and measure the observed Monte Carlo budget scaling. The resulting estimate probes the Whitney-number sequence of the ideal lattice. Although these rows have previously been described empirically as unimodal, the high-precision $n=9$ estimate has a shallow two-shoulder feature around the central rank, contrary to that empirical description; the $n=11$ and $n=13$ center-window estimates show a higher-contrast analogous pattern. The protocol estimate for $M\left(10\right)$ is $\widehat{M}\left(10\right)=(8.9360\pm 0.0010)\times {10}^{78}$, where the displayed uncertainty is the budget-based forecast scale from the cross-n scaling law under the production budget. It is an empirical variability scale associated with the stated Monte Carlo protocol and production budget, estimated from seed-level variation. Full article

The larch bud gall midge (Dasineura rozhkovi Mamaev et Nikolskij) is one of the main pests infesting larches. Its activity causes developmental defects and a noticeable decrease in population growth in adult Siberian larches (Larix sibirica Ledeb.). Due to its complex life cycle and active presence in areas of human habitation, this insect is difficult to exterminate using common methods. D. rozhkovi has not been studied before with the use of sequencing technologies, which means there is no information on the mechanisms occurring in its body at the molecular level. Here, we present for the first time a de novo assembly and analysis of the D. rozhkovi transcriptome. We found a pronounced sexual dimorphism in differential gene expression in D. rozhkovi imagoes and performed a phylogenetic analysis using earlier-published genome assemblies of the insects belonging to several large clades. The resulting phylogenetic tree includes D. rozhkovi and eight other gall midge species and shows the closest relationship between D. rozhkovi and the Hessian fly (Mayetiola destructor Say). We believe that the obtained results can be further used for developing measures to control this pest. Full article

Traditional cheeses represent complex microbial ecosystems and valuable reservoirs of autochthonous lactic acid bacteria (LAB) with functional potential. This study characterized the biodiversity of non-starter LAB (NSLAB) isolated from traditional Serbian raw-milk household cheeses and selected promising autochthonous lactobacilli through a stepwise approach combining a safety assessment, technological characterization, probiotic evaluation and an in vitro interaction with Caco-2 intestinal epithelial cells. From 56 presumptive LAB isolates, RAPD-PCR differentiated 37 distinct genotypes, all of which were taxonomically identified by 16S rRNA gene sequencing. In line with the specific focus of this study on autochthonous lactobacilli, all seven isolates taxonomically assigned to this genus were selected for further characterization. Safety assessment showed that two strains (28.6%) formed biofilms and were excluded, whereas the remaining five isolates complied with EFSA antibiotic susceptibility criteria. These candidates exhibited strain-dependent degradation of αs1- and β-casein fractions and moderate milk acidification. Four strains survived simulated gastrointestinal transit, showed antagonistic activity against foodborne pathogens and adhered to Caco-2 cells without inducing cytotoxicity. Lactiplantibacillus plantarum ZI237 showed the broadest autophagy-related transcriptional response and NQO1 induction. Limosilactibacillus fermentum KT upregulated MUC2, MUC5, NQO1 and HBD-1 but reduced Occludin protein abundance, indicating a mixed epithelial response. Both strains reduced p62 protein levels, supporting modulation of autophagy-related pathways. Overall, Lpb. plantarum ZI237 emerged as the most promising candidate, whereas Lm. fermentum KT requires further evaluation before application in functional dairy products. Full article

Exposure to hydrochloric acid (HCl) can provoke severe chronic pulmonary injury. Children are particularly vulnerable due to their smaller airways, higher respiratory rate, and stronger inflammatory response; yet no countermeasures exist for HCl-induced chronic lung injury in the pediatric population. We have previously demonstrated the involvement of HSP90 during HCl-induced lung injury in pre-pubertal (p24) mice, who develop stronger persistent inflammation with higher NLRP3 inflammasome activation, but less pulmonary fibrosis compared to adults. Here, we tested the hypothesis that post-treatment with the second-generation HSP90 inhibitor AT13387 (Onalespib), administered subcutaneously beginning 24 h after HCl instillation, would prevent HCl-induced chronic lung injury and pulmonary fibrosis in young (p24) C57BL/6J mice. Pre-pubertal (p24) C57BL/6J mice received a single intratracheal instillation of 0.1 N HCl and were treated with AT13387 (10 mg/kg, s.c., 3×/week for 30 days) beginning 24 h post-exposure. Bronchoalveolar lavage fluid (BALF) analysis, lung function measurements, histological assessment (Ashcroft fibrosis score), and Western blot analysis of key signaling mediators were performed. Additionally, publicly available single-nucleus RNA sequencing (snRNA-Seq) data from a cohort of 13 infants with bronchopulmonary dysplasia (BPD) and 11 age-matched controls were analyzed to evaluate HSP90 isoform expression in human pediatric lung disease. AT13387 significantly reduced BALF white blood cell concentration without affecting total BALF protein levels. Importantly, AT13387 did not impair normal weight gain or development over the 30-day observation period. AT13387 abrogated HCl-induced expression of TGF-β1, phosphorylation of HSP90, ERK1/2, SMAD2, IκBα, and upregulation of the inflammasome NLRP3. Additionally, AT13387 prevented changes in lung function dynamics and reduced the Ashcroft fibrosis score. Analysis of the human snRNA-Seq BPD dataset revealed a widespread pan-overexpression of all three HSP90 isoforms, i.e., HSP90AA1, HSP90AB1, and HSP90B1. These findings suggest that the HSP90 inhibitor AT13387 exhibits strong antidotal properties against HCl-induced chronic lung injury and pulmonary fibrosis in a pre-clinical pediatric model and identify HSP90 as a conserved therapeutic target in pediatric chronic lung disease. Full article

Doxorubicin (Dox)-induced cardiotoxicity (DIC) is a major clinical challenge in cancer therapy. Camel milk exosomes (CMEs) have been applied in anti-tumor treatments as they have a variety of effects, including on inflammation, oxidative stress, metastasis, and apoptosis. However, their role in DIC treatment remains incompletely understood. This research was designed to evaluate the protection provided by CMEs against DIC. The DIC mice were treated with Dox intraperitoneally and divided into a model group and groups treated with different doses of CMEs. Dox-induced H9c2 cell injury was also established and divided into a model group and groups treated with different concentrations of CMEs. The evaluation parameters in vitro included H9c2 cell viability, reactive oxygen species (ROS), mitochondria, and apoptotic cells. The apoptosis and autophagy markers, as well as the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, were assessed via Western blotting both in vivo and in vitro. In addition, transcriptome sequencing of cardiac tissue was also applied to investigate the related mechanisms. Our results indicate that CMEs significantly attenuated the cell viability reduction, apoptosis, and ROS production in H9c2 cells caused by Dox. CMEs also regulated autophagy, inhibited apoptosis, and inhibited the NF-κB and MAPK pathways. In conclusion, our findings demonstrate that CMEs exert a cardiac protective effect against DIC by inhibiting apoptosis and regulating autophagy via NF-κB and MAPK signaling pathways. Full article

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by core features of social communication deficits and high prevalence of gastrointestinal comorbidities. With its continuously rising global prevalence, current therapeutic modalities remain unable to target and ameliorate the core symptoms of ASD. The microbiota–gut–brain axis (MGBA), a critical pathway mediating crosstalk between the gut microbiota and the brain, has been extensively documented to be deeply involved in the pathological progression of ASD in recent years. However, prior studies have predominantly focused on the unidirectional regulation of the brain by gut microbiota, lacking an integrated account of the bidirectional regulation across immune, metabolic, and endocrine systems. Centered on the immune–metabolic–endocrine interactive network, this review systematically delineates the bidirectional regulatory mechanisms of the MGBA in ASD by integrating recent evidence from microbiota sequencing, animal models, and clinical intervention studies, with the aim of clarifying the bidirectional causal controversy between intestinal microecological disturbance and ASD behavioral abnormalities. This review proposes that in children with ASD, decreased abundance of beneficial intestinal bacteria and disrupted metabolic profiles of short-chain fatty acids synergistically impair intestinal barrier integrity, triggering peripheral chronic inflammation that further drives excessive microglial activation-mediated central neuroinflammation. Subsequently, disturbances in the homeostasis of multiple neurotransmitters including 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), histamine, and dopamine occur via the vagus nerve and hypothalamic–pituitary–adrenal (HPA) axis, ultimately driving ASD behavioral abnormalities. Conversely, chronic stress and behavioral characteristics associated with ASD reshape the intestinal microecology through neuroendocrine pathways, forming a vicious cycle of “microbiota dysbiosis—immune inflammation—HPA axis hyperactivity—further intestinal microecological imbalance”. This review summarizes the therapeutic efficacy and translational bottlenecks of three types of microecological interventions: fecal microbiota transplantation (FMT), probiotics, and ketogenic diet, and analyzes the current limitations in the field, including pronounced population heterogeneity, unclear cross-talk mechanisms among multiple pathways, and the scarcity of large-sample clinical evidence. Collectively, this review preliminarily elucidates the complete multi-system interactive framework of MGBA regulation in ASD, providing theoretical support for mechanistic research and gut-targeted individualized interventions for ASD. Full article

Aspergillus section Nigri is distributed ubiquitously in nature and is reported to be the third most clinically significant species of the Aspergillus genus. In this study, we surveyed Aspergillus section Nigri isolates from Zhongshan Hospital, Fudan University, Shanghai, China, from 2019 to 2023. We determined the species distribution of section Nigri isolates by partial β-tubulin gene sequencing. We characterized the antifungal susceptibility profiles of these isolates to medical azoles (itraconazole, voriconazole, posaconazole, and isavuconazole) using the Sensititre^TM custom-designed broth microdilution system. The cyp51A sequences were compared between azole-resistant and azole-susceptible strains in order to determine the potential antifungal resistance mechanism. A total of 54 Aspergillus section Nigri isolates were obtained. A. tubingensis (50.0%) and A. niger (46.3%) were the most prevalent species. Two isolates of A. welwitschiae were identified. Resistance to Itraconazole, voriconazole, and isavuconazole was found in 26%, 33.3%, and 33.3% of A. tubingensis isolates, respectively. All A. niger and A. welwitschiae isolates were sensitive to these azoles. Three amino acid mutations were found in azole-resistant A. tubingensis isolates, namely Y119F, Y119H, and T321A. Results from this study provide us with an understanding of species distribution and antifungal susceptibility profiles of clinical Aspergillus section Nigri isolates in Eastern China. It highlights the importance of accurate species identification and antifungal susceptibility testing. Our results also suggest that the novel Y119F substitution is potentially a key player in azole resistance. Full article

Background/Objectives: Advanced endometrial cancer (FIGO III–IV) is characterised by poor prognosis and a heterogeneous biological profile, and molecular classification enables treatment personalisation by identifying subtypes with distinct therapeutic targets. We aimed to characterise the molecular and histopathological features of FIGO III–IV cases in a Polish multicentre cohort and to discuss the resulting treatment implications. Methods: This retrospective multicentre study included 915 consecutive patients with endometrial cancer operated on between April 2022 and May 2025 at three oncology centres in south-eastern Poland. Molecular subtyping (POLEmut, p53abn, dMMR/MSI-H, NSMP) was performed using immunohistochemistry (IHC) and next-generation sequencing (NGS). FIGO stage was assigned according to the FIGO 2009 classification. Results: Among 888 patients with a known molecular subtype, FIGO III–IV cases accounted for 15.9% (n = 141). The p53abn subtype predominated (35.5%), followed by dMMR/MSI-H (26.2%), NSMP (24.1%), and POLEmut (5.7%). The proportion of p53abn increased with stage (I–II vs. III–IV, p < 0.001), whereas dMMR/MSI-H remained stable regardless of stage (p = 0.83). POLEmut was absent in FIGO IV (0/16; 95% CI 0.0–19.4%), which should be regarded as an exploratory observation requiring prospective validation. Conclusions: The molecular profile of advanced endometrial cancer may inform treatment strategy; the therapeutic implications presented here are descriptive and hypothesis-generating, as the study did not include survival data. The dMMR/MSI-H subtype identifies patients who may benefit from immunotherapy in accordance with current clinical indications, supporting routine MMR testing regardless of disease stage. Conversely, p53abn tumours point to the need for a more intensive treatment strategy, in line with current guidelines. The absence of POLEmut in FIGO IV is an exploratory observation requiring prospective validation. Treatment de-escalation in POLEmut FIGO IIIC remains subject to further clinical validation and requires individualised assessment after complete staging. Full article

This article examines how Zhu Xi’s Family Rituals organizes ritual objects into a relational material system. Focusing on ritual vessels, attire, documents, offerings, ancestral tablets, and domestic spaces, it analyzes how their prescribed positions, uses, relations, and trajectories structure ritual practice. Rather than treating these objects as passive accessories or isolated symbols, the article argues that their significance emerges from their coordination with bodies, spaces, kinship positions, and sequences of action. Through this coordination, distinctions of kinship, status, obligation, and ritual role become materially perceptible and practically enforceable. The article further argues that the material organization prescribed in Family Rituals was not merely an expression or representation of Confucian ritual order, but one of the mechanisms through which that order was produced, enacted, and reproduced. By reading these heterogeneous objects as an interconnected system, the study shifts attention from the symbolic meaning of individual things to the material relations that made Confucian ethical and ritual order practicable in domestic life. Full article

To explore the regulatory effects and mechanisms of LED green light (peak at 520 nm) combined with different low temperatures on broccoli postharvest storage, the Brassica oleracea var. italica ‘Meiqing’ was harvested and stored under two temperatures and pretreated with supplemental LED green light. Periodic determinations were conducted on physical and chemical indexes, including appearance, texture, nutritional quality, and antioxidant capacity, along with differential gene expression analysis via transcriptome sequencing. Results showed that 0 °C storage outperformed 4 °C overall, and the 1 h green light pretreatment achieved the optimal effect. This treatment significantly delayed curd yellowing, reduced weight loss, maintained high firmness, preserved nutritional components, enhanced the activities of antioxidant enzymes and key enzymes in the AsA-GSH cycle, and alleviated membrane damage by reducing H₂O₂ and MDA levels. Transcriptome analysis revealed that green light pretreatment regulated gene expression in chlorophyll metabolism and antioxidant-related pathways. Overall, 0 °C combined with 1 h of green light pretreatment effectively prolonged the storage period of broccoli and maintained its commercial and nutritional quality, providing a novel technical strategy for postharvest broccoli preservation. Full article

The high-value recovery of valuable components from spent LiFePO₄ (LFP) batteries is of considerable significance for both resource recycling and environmental conservation. This study systematically investigates the simultaneous sulfuric acid leaching of Li, Fe, and P from spent LFP cathode materials, integrating process optimization with kinetic analysis. The effects of acid concentration, temperature, and stirring speed on the leaching behavior of Li, Fe, and P were evaluated to elucidate the underlying kinetic mechanisms. The results demonstrated that under optimal conditions—namely, a sulfuric acid concentration of 2.0 mol/L, a leaching temperature of 60 °C, and a stirring speed of 300 r/min—the leaching rates of Li, Fe, and P all exceeded 99.5%. Kinetic analysis revealed a diffusion-controlled leaching mechanism well described by the Avrami model, with a selective dissolution sequence of Li > Fe > P. The leaching of Li, Fe, and P exhibited apparent activation energies of 9.56 kJ/mol, 14.83 kJ/mol, and 12.82 kJ/mol, respectively. These findings provide theoretical support for the leaching and resource recovery of Li, Fe, and P from spent LFP cathode materials. Full article

Jujube is an important fruit tree and one of the five major economic forest tree species native to China, possessing high nutritional and medicinal value. It plays a key supporting role in the efficient utilization of marginal land resources—such as mountainous, sandy, saline-alkali, and drought-prone areas—as well as in the revitalization of rural industries. Molecular marker technology, with its advantages of stability, accuracy, and efficiency, has become an important tool in jujube genetic breeding research and is widely applied. This article summarizes molecular markers based on three generations of technological intergenerational systems: the first generation of hybridization-based markers (Restriction Fragment Length Polymorphism, RFLP), the second generation of PCR-based markers (represented by Simple Sequence Repeat, SSR), and the third generation of high-throughput sequencing markers (Single Nucleotide Polymorphism, SNP, Genotyping-by-Sequencing, GBS, etc.). A comprehensive classification system based on technical principles, polymorphism sources, and other dimensions is constructed to clearly explain the driving forces and development trends of molecular marker system evolution in jujube tree research, and to clarify the selection criteria and adaptation strategies of molecular markers. Research has found that the second-generation molecular marker SSR is the fundamental core tool for standardized identification of jujube germplasm resources and genetic analysis of low-budget populations. The third-generation molecular markers represented by SNPs and InDel are high-density maps, Genome-Wide Association Study(GWAS), Genomic selection, and other modern precision breeding core carriers, forming a layered complementary technology system, and are gradually becoming the mainstream of research. This paper summarizes the application progress of molecular markers in the precise identification of jujube germplasm resources, analysis of genetic diversity, determination of genetic relationships, construction of high-density genetic maps, genome-wide association analysis, functional gene mapping, and tracing of domestication and evolution. This article integrates all existing research using the unified scientific framework of “technology defect driven tagging iteration”, analyzes the internal logic of the evolution and replacement of different tagging systems, the inherent limitations of early tagging, the existing problems in current research, and discusses future research directions, aiming to provide a reference for the scientific and efficient application of molecular markers in jujube and to promote the improvement and upgrading of the jujube molecular marker-assisted breeding technology system. Full article

Rural low-carbon planning requires evaluation tools that connect carbon-related performance with the ecological, socioeconomic, and infrastructure conditions of rural settlements, yet carbon inventories and conventional human-settlement assessments do not fully integrate these dimensions. This study developed an exploratory carbon-benefit-oriented sustainability diagnostic and applied it to Qingge Village, Fujian Province. Fuzzy Delphi screening retained 27 indicators across ecological, social, production, and engineering subsystems; Delphi consultation generated expert-based weights; a dimensionless ratio transformation standardized the indicator values; threshold, standardization, and weighting sensitivity analyses evaluated the stability of results across analytical specifications. The primary composite score was 0.413 compared with 0.590 under the target-achievement transformation, and both expert-weighted transformations ranked subsystem contributions as production, ecological, social, and engineering. The ecological and production subsystems performed more strongly against the selected references than the social and engineering subsystems, whereas fully equal global weights placed ecology ahead of production. The principal diagnostic priorities were household energy emissions, green agricultural upgrading, public-transport access, and recorded energy-efficient building coverage. These findings indicate that the diagnostic can organize village-scale low-carbon planning priorities and translate multidimensional performance evidence into a sequenced set of spatial improvement options. This study therefore provides a transparent and practically applicable approach for linking carbon-related indicators with rural human-settlement planning and supporting evidence-informed low-carbon revitalization. Full article