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To longevity and beyond: A systems view of aging and stress resilience.

Aging is a dynamic and time-dependent process characterized by progressive functional decline across biological systems. Key hallmarks, including genomic instability, telomere attrition, loss of proteostasis, mitochondrial dysfunction, and immunosenescence, have been widely described, each reflecting distinct yet interconnected mechanistic frameworks. Rather than acting in isolation, these processes arise from complex interactions among cellular stressors, impaired repair mechanisms, and the cumulative burden of maladaptive responses. This system-level perspective explains the inter-individual variability in aging trajectories. Centenarians represent an extreme and informative model of successful aging, in which the balance between damage accumulation and repair is shifted toward the maintenance of physiological function. Their exceptional longevity is supported by coordinated genetic, epigenetic, metabolic, and immunological adaptations that enhance resilience to age-related stressors. Here, we summarize the biological drivers and theoretical frameworks of aging within an integrative context, focusing on mechanisms associated with extended healthspan in centenarians. We also examine the contribution of major animal models, highlighting their complementary roles in elucidating conserved and species-specific aging pathways. Overall, aging outcomes reflect a dynamic equilibrium between damage and repair processes. Understanding how this balance is modulated in long-lived individuals may inform strategies to promote healthy aging and delay the onset of age-related diseases.

Humans

Transpulmonary proteomic gradient analysis in women with pulmonary arterial hypertension associated with systemic sclerosis.

This study investigated proteomic alterations in the pulmonary circulation of patients with pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) by analyzing the transpulmonary protein gradient and comparing the proteomic profiles with systemic sclerosis (SSc) without PAH. Twenty women were included (10 PAH-SSc, 64.6 ± 10.8 years; 10 SSc, 62.8 ± 11.5 years). The transpulmonary gradient was defined as the difference in biomarker concentrations between wedge-position and pulmonary artery blood samples. Peptides were analysed using liquid chromatography-mass spectrometry, and differentially abundant proteins were identified with Proteome Discoverer. Protein-protein interaction networks were generated with STRING and visualized in Cytoscape. A total of 270 proteins were detected, with no significant transpulmonary gradient alterations. However, patients with PAH-SSc showed distinct proteomic profiles compared to SSc. Multivariate analysis identified 48 differentially abundant proteins in pulmonary artery plasma, with 15 overrepresented and 33 downregulated in PAH-SSc. Among these, the downregulation of transforming growth factor-beta-induced protein ig-h3 (TGFβI/ig-h3) points to a potential involvement of the TGF-β-related extracellular matrix remodelling pathway in PAH-SSc. However, further validation in larger and independent cohorts is required before its relevance as a biomarker or therapeutic target can be established. In conclusion, while no transpulmonary proteomic gradient was observed, the proteomic profiles of PAH-SSc and SSc were different. The profile in PAH-SSc was characterized by differences in immune response, lipid metabolism, and hemostatic proteins. SIGNIFICANCE: This study offers the first proteomic characterization of the transpulmonary gradient in PAH-SSc and SSc. Although no differences in the gradient were found, the pulmonary artery plasma proteome of PAH-SSc patients showed a distinct pattern compared to SSc. Several proteins associated with immune function, haemostasis, and cellular processes were altered, which may indicate specific pathophysiological features of PAH-SSc or suggest how lung dysfunction develops in SSc. Targeting dysregulated proteins like TGFβI/ig-h3 or addressing immune-coagulation imbalances may support future research studies. Overall, these findings refine the molecular profile of PAH-SSc and provide a basis for future large-scale studies aimed at clarifying disease mechanisms and identifying clinically relevant molecular signatures.

Humans

Assessing time to symptomatic progression, a patient-relevant efficacy endpoint, in the MARIPOSA study in non-small cell lung cancer.

INTRODUCTION: In the phase 3 randomized MARIPOSA study, amivantamab and lazertinib combination therapy demonstrated improved progression-free survival (PFS) and overall survival (OS) versus osimertinib in participants with previously untreated, epidermal growth factor receptor-mutated advanced non-small cell lung cancer. Time to symptomatic progression (TTSP) was introduced to assess clinical worsening and complement endpoints that investigate radiographic disease progression and patient-reported outcomes. TTSP provides an easily interpretable measure of disease-specific symptom worsening to further support patient experience. METHODS: In MARIPOSA, TTSP was quantitatively assessed as a secondary efficacy endpoint and defined as the time from randomization until participants experience disease-specific symptom worsening requiring a clinical intervention or treatment change, or death. To evaluate the impact of amivantamab and lazertinib on TTSP considering its established OS benefit against osimertinib, an exploratory analysis censoring death events was performed. RESULTS: At the final protocol-specified OS analysis (median follow up: 37.8 months), median TTSP was 43.6 months with amivantamab and lazertinib versus 29.3 months with osimertinib (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.57-0.83; p&#x202f;<&#x202f;0.0001). Amivantamab and lazertinib reduced deaths following a TTSP event compared to osimertinib. A strong correlation between TTSP and PFS or OS was observed. CONCLUSIONS: Amivantamab and lazertinib significantly delayed TTSP versus osimertinib. TTSP offers a clinician-validated measurement of disease-specific symptom worsening, capturing symptoms perceived by patients that prompt clinical action. TTSP is highly correlated with PFS and OS, providing complementary insights alongside traditional endpoints. TTSP enhances understanding of treatment benefit and supports informed clinical decision-making by integrating patient experience.

Humans

School-based sexual violence prevention: A systematic review.

PURPOSE: Sexual violence profoundly affects the health and development of children, adolescents, and young adults, representing a persistent challenge to public policy. This systematic review examined the effectiveness of school-based interventions aimed at prevention. METHODS: Eighteen randomized controlled trials published between 2012 and 2024 were retrieved from four major databases. The programs were implemented in primary, secondary, and higher education settings and targeted children, adolescents, and young adults. RESULTS: The results revealed improvements in knowledge and attitude, particularly regarding consent and awareness, whereas evidence supporting behavioral changes was less frequent and often limited. Methodological limitations, such as short follow-up periods and participant attrition, restricted the assessment of long-term outcomes. CONCLUSIONS: This review highlights the importance of multicomponent, participatory, and culturally sensitive approaches, along with the integration of digital tools and continuous evaluation systems, to strengthen the role of schools as safe and transformative spaces in the prevention of sexual violence. IMPLICATIONS AND CONTRIBUTIONS: This systematic review suggests that school-based interventions hold significant potential for the prevention of sexual violence. It identifies promising strategies and reinforces the importance of culturally sensitive, sustained, evidence-based approaches to ensure learning environments that are safe, protective, and promotive of gender equity.

Humans

Effects of Photobiomodulation Therapy in Lateral Luxation of Anterior Permanent Teeth: A Randomized, Double-Blind Clinical Trial.

BACKGROUND: Among the traumatic dental injuries (TDIs), lateral luxation may present poor prognosis due to frequent root resorption and consequent tooth loss. Photobiomodulation therapy (PBMT) modulates cellular activities (proliferation, differentiation, growth factor secretion) and may improve outcomes. OBJECTIVE: This randomized, double-blind, placebo-controlled trial evaluated PBMT (660 vs. 808&#x2009;nm) for post-operative pain and pulp sensitivity recovery in lateral luxation of permanent anterior teeth. METHODS: Initially, 41 patients were included, with a total of 63 teeth traumatized by lateral luxation and were allocated to G1 (n&#x2009;=&#x2009;21): Splinting&#x2009;+&#x2009;sham PBM (placebo), G2 (n&#x2009;=&#x2009;21): Splinting&#x2009;+&#x2009;808&#x2009;nm infrared PBM and G3 (n&#x2009;=&#x2009;21): Splinting&#x2009;+&#x2009;660&#x2009;nm red PBM. Four weekly sessions (3&#x2009;J/point, 3 points) were administered. Pain (by numeric rating scale) and pulp sensitivity (by cold test) were assessed weekly. Pain was analyzed using the Kruskal-Wallis test, followed by multiple comparisons using Dunn's method with Bonferroni correction, and pulp sensitivity by a logistic regression model (p&#x2009;<&#x2009;0.05). RESULTS: Three participants (total of 5 teeth) were excluded due to loss to follow-up. Fifty-eight teeth were analyzed (G1&#x2009;=&#x2009;21, G2&#x2009;=&#x2009;17, G3&#x2009;=&#x2009;20). Pain: All groups showed a significant reduction in pain over time (p&#x2009;<&#x2009;0.001). Both G2 and G3 demonstrated a significantly greater reduction in pain compared to G1 (p&#x2009;<&#x2009;0.001 and p&#x2009;=&#x2009;0.026, respectively). No significant difference in pain reduction was observed between G2 and G3. Pulp sensitivity: G2 showed a significant improvement over time (p&#x2009;<&#x2009;0.001), despite starting from a more unfavorable baseline. In contrast, no significant change in pulp sensitivity was observed for G1 or G3 between the initial and final assessments. CONCLUSION: Within the limitations of this clinical study, all intervention groups were effective in reducing pain in lateral luxation of permanent anterior teeth, with superior results for laser groups compared to the placebo. However, only the 808&#x2009;nm laser irradiation protocol demonstrated a significant improvement in pulp sensitivity, suggesting it may offer a more complete therapeutic response.

Humans

Proteomic serum profiles before and after lipoprotein apheresis in patients with peripheral artery disease with ulceration.

INTRODUCTION: The efficacy of lipoprotein apheresis (LA) in peripheral arterial disease (PAD) has been primarily attributed to its anti-atherosclerotic effects through the adsorption of lipoproteins. However, the other potential effects of LA remain unknown. We evaluated changes in serum profiles before and after LA using a comprehensive analysis to explore the underlying mechanism. METHODS: Ten patients with leg ulcers were included from the LETS-PAD study, in which patients with lipoprotein-controlled PAD underwent LA. Serum samples collected at baseline and 1&#x2009;month after LA were analyzed for proteomic changes. RESULTS: Six patients exhibited ulcer epithelialization and skin perfusion pressure improvement. Proteomic analysis identified 2033 proteins. Fifty-five proteins showed significant differences. B-cell lymphoma protein-2 associated X (BAX) and C-X-C motif chemokine 10 (CXCL10) were downregulated. CONCLUSION: Serum BAX and CXCL10 levels significantly decreased after LA, which may be involved in the ulcer epithelialization mechanism of LA, which potentially acts through angiogenesis promotion.

Humans

Paramedian supracerebellar transtentorial approach for Ya&#x15f;argil T2 tentorial incisura meningiomas.

OBJECTIVE: Tentorial incisura meningiomas, particularly those arising from the middle incisural region (Ya&#x15f;argil T2), are surgically challenging because of their deep location and compression of critical neurovascular structures. These lesions typically have supratentorial or infratentorial extension but can also extend across both compartments. Although approach selection is often guided by the dominant compartment of tumor extension, for lesions with supratentorial-dominant extension, the optimal approach remains controversial, and a standardized strategy has not been established. Authors of this study evaluated the feasibility and outcomes of the paramedian supracerebellar transtentorial (PST) approach for Ya&#x15f;argil T2 tentorial incisura meningiomas with a supratentorial-dominant or combined extension. METHODS: The authors retrospectively reviewed data from consecutive patients with radiographic and intraoperative findings consistent with a Ya&#x15f;argil T2 tentorial incisura lesion treated via the PST approach from September 2005 through December 2025. Patients were placed in a semisitting position whenever feasible and in a semilateral position when semisitting was contraindicated. Collected data included demographics, tumor extension patterns, extent of resection on postoperative MRI, neurological outcomes, histopathology, rate of recurrence, and follow-up. RESULTS: Six patients, 1 male and 5 female, with an overall mean age of 43 years, underwent resection via the PST approach. Four lesions had predominantly supratentorial extension, and 2 had combined supra- and infratentorial growth, with no cases of isolated infratentorial extension. Five patients had been placed in the semisitting position and 1 in a semilateral position because of a cardiac contraindication to the semisitting position. No new permanent neurological deficits were observed. Postoperative MRI showed Simpson grade I resection in all 6 patients. The mean follow-up was 8.6 years. Histopathological analysis revealed 3 WHO grade 1 meningiomas, 1 WHO grade 2 meningioma (clear cell), and 2 solitary fibrous tumors (meningioma mimics). These diagnoses were evaluated according to the 2021 WHO classification. CONCLUSIONS: In this consecutive series, the PST approach was a viable single-corridor strategy for Ya&#x15f;argil T2 tentorial incisura lesions, including supratentorial-dominant tumors, achieving Simpson grade I resection with no permanent neurological deficits. By providing early devascularization at the tentorial attachment and a gravity-assisted, retractorless working corridor with favorable deep venous visualization, the PST approach challenges compartment dominance as the primary determinant of approach selection.

Humans

A Critical Assessment of Evidence-Based Design's Knowledge Base and Inspiration: A Systematic Review.

PurposeThis study examines Evidence-Based Design (EBD) as an epistemological framework for guiding design research and practice, with a particular focus on its reliance on Evidence-Based Medicine (EBM) as a source of methodological inspiration.BackgroundOver the past two decades, EBD has been promoted as a way to strengthen design processes through the systematic use of scientific evidence. Its relationship to EBM, however, remains conceptually ambiguous: EBD draws legitimacy from EBM's hierarchical conception of "best evidence" while at the same time acknowledging the specificities of design practice, which do not easily fit such a model.MethodologyA systematic review was conducted on 31 publications in the design research literature that explicitly address the tension surrounding EBD's conception of "best evidence." The criticisms raised were coded and analyzed by main topics and subtopics.ResultsThe review highlights several reasons why EBM's hierarchical view of "best evidence" is an unsuitable epistemological foundation for EBD. It imposes scientifically inappropriate and practically ineffective methodological standards, devalues important sources of design knowledge, and fails to address central epistemic challenges intrinsic to design processes.ConclusionsBy bringing together critical yet fragmented insights from the literature, this study argues for the development of an updated epistemological framework for EBD. Constructing this framework will require sustained interdisciplinary dialogue between design research and philosophy of science.

Humans

Genome-wide identification and characterization of ABC transporters and their expression in response to saline-alkaline stress and WSSV infection in Fenneropenaeus chinensis.

ATP-binding cassette (ABC) transporters play crucial roles in stress responses across organisms, yet their functions in Fenneropenaeus chinensis remain largely unknown. In this study, we identified 42 FcABC genes (FcABCs) in the F. chinensis genome and analyzed their phylogenetic relationships, gene structures, and chromosomal distributions. Phylogenetic analysis grouped the FcABCs into eight subfamilies (ABCA-ABCH), with conserved motif and domain compositions within each subfamily. Expression analysis showed that several FcABC genes, including FcABCG5, FcABCA1, and FcABCC3, were significantly induced under saline-alkaline stress in gill and hepatopancreas tissues. In contrast, most FcABCs were downregulated after WSSV challenge, though a subset (e.g., FcABCB1, FcABCC1) exhibited early upregulation. Functional validation via RNA interference demonstrated that knockdown of FcABCG5 increased shrimp mortality under saline-alkaline stress. Cis-regulatory element analysis revealed an enrichment of stress- and immune-related elements in FcABC promoters. Protein-protein interaction network predictions indicated potential roles for FcABCs in cholesterol metabolism and organic anion transport. Our findings provide insights into the roles of FcABC genes in stress adaptation and immune defense, offering candidate genes for the breeding of stress-resistant shrimp varieties.

Animals

Beyond species trees: pervasive gene flow limits phylogenomic resolution in the diversification of Juniperus from the Qinghai-Tibet Plateau.

Understanding how lineages diversify despite persistent ancestral polymorphism and recurrent gene flow remains a central challenge in evolutionary biology. Juniperus distributed across the Qinghai-Tibet Plateau provide an ideal system for addressing this question because repeated geological uplift and climatic oscillations have likely promoted cycles of lineage divergence, range shifts, and secondary contact. Here, we combined approximately 1.08 million genome-wide SNPs from 164 individuals representing thirteen Juniperus lineages with phylogenomic datasets comprising 3,381 nuclear single-copy genes and nearly complete plastomes. We detected extensive phylogenomic discordance and cytonuclear incongruence across genomic datasets. Topology weighting, coalescent simulations, quartet-based tests, and analyses of gene flow and reticulation collectively support the interpretation that these patterns were shaped by the combined effects of prolonged incomplete lineage sorting and gene flow during lineage diversification. Ecological niche analyses further provide a spatial and climatic context in which environmentally similar lineages may have had greater opportunities for secondary contact during historical range shifts. Collectively, our results reveal that the evolutionary history of Qinghai-Tibet Plateau Juniperus is characterized by reticulate diversification rather than strictly bifurcating evolution, and demonstrate how genome-wide discordance can provide biological insights into the evolutionary processes underlying lineage diversification.

Gene Flow

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P&#x202f;<&#x202f;0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-&#x3ba;B-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-&#x3ba;B-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals

Protein sorting and proteostasis mechanisms in CFTR-related exocrine pancreas dysfunction: A systematic narrative review.

The pancreas consists of exocrine and endocrine compartments. In the exocrine pancreas, cystic fibrosis transmembrane conductance regulator (CFTR) functions mainly in ductal epithelial cells as a chloride and bicarbonate channel. Its activity depends on proper protein folding, trafficking, and localization to the apical membrane. This systematic narrative review aims to synthesize the available evidence on the role of protein sorting machinery in CFTR channelopathies and its contribution to exocrine pancreatic dysfunction. A thorough search was conducted using PRISMA criteria on PubMed, Wiley Online Library, and Scopus for studies published in English between January 2000 and November 2025. Twenty studies that met the inclusion criteria were included in this review. Pathogenic CFTR variants impair protein folding, endoplasmic reticulum (ER) exit, and endosomal recycling, resulting in reduced apical membrane expression and stability. These defects disrupt the localization of associated transporters and secretory proteins, impair ductal bicarbonate secretion, alter zymogen handling, and promote acinar injury, although these claims are supported mainly by indirect experimental models and therefore require clinical confirmation. CFTR channelopathies in the exocrine pancreas encompass both ion transport defects and broader disruptions of protein sorting machinery. CFTR may contribute to the assembly, stabilization, or localization of selected apical transport complexes, and its loss can secondarily alter epithelial organization. Therapeutic approaches targeting both channel correction and intracellular trafficking may improve pancreatic function and mitigate disease progression.

Humans

A Letter Matters: ADRB2 rs1042713 c.46A Modulates Anti-osteogenic Effect of Epinephrine in Human Mesenchymal Stem Cells.

Osteoporosis (OP) is a systemic bone disease affecting millions worldwide, characterized by long-term asymptomatic development that manifests in low-energy fractures. Due to their high stability, genetic markers represent a promising strategy for early diagnostics. The ADRB2 rs1042713 polymorphism is one such marker, considered as a potential predictor for OP. Although the anti-osteogenic role of the &#x3b2;2-adrenergic receptor is well-established, debate continues on which allele (G or A) of this polymorphism drives bone deterioration. In this study, we examined the influence of the ADRB2 rs1042713 G/G and A/A variants on osteogenic differentiation in patient-derived mesenchymal stem cells (MSCs) under treatment with the endogenous agonist epinephrine. We show that epinephrine (whose levels are often elevated in comorbid conditions) drastically impairs osteogenic differentiation, specifically at the matrix mineralization stage in MSCs A/A. Epinephrine fails to activate the canonical &#x3b2;2-adrenergic receptor pathway and promotes receptor perinuclear and nuclear localization in MSCs A/A. Crucially, metformin, a common anti-diabetic drug, rescues this anti-osteogenic effect. These results open new perspectives for early diagnostics by identifying epinephrine sensitivity as a critical factor, while also suggesting a potential therapeutic strategy to counteract epinephrine detrimental effect in individuals carrying the ADRB2 rs1042713 A-allele.

Humans

Molecular Determinants and Therapeutic Targeting of Stop Codon Readthrough in Eukaryotic Translation.

Accurate translation termination is essential for proteome integrity and in eukaryotes is primarily governed by the release factors eRF1 and eRF3, which ensure precise recognition of stop codons and efficient release of nascent polypeptides. However, proteome integrity is challenged by mutations that generate premature termination codons (PTCs), leading to truncated, nonfunctional proteins and degradation of the aberrant transcript via nonsense-mediated mRNA decay (NMD). Collectively, these events account for &#x223c;1800 human genetic diseases. Translational readthrough, the process by which near-cognate tRNAs decode stop codons and allow ribosomes to continue elongation beyond the stop codon, represents a possibility to suppress PTCs and restore full-length protein synthesis. Initially discovered in viruses as a mechanism to expand coding capacity, readthrough is now recognized as a regulated feature of eukaryotic gene expression influenced by both cis-acting sequence elements and trans-acting factors. Recent evidence highlights the remarkable context dependence of readthrough, revealing variation across transcripts, tissues, and developmental stages. In this review, we examine the molecular determinants that define stop codon recognition and readthrough efficiency, with particular emphasis on nucleotide context. We further discuss the mechanisms and binding sites of small molecules that promote PTC readthrough, and summarize the clinical development landscape of readthrough-inducing compounds for the treatment of diseases caused by nonsense mutations.

Humans

Does high fructose consumption trigger microglia activation and neuroinflammation? A systematic review.

This systematic review evaluated the effects of fructose intake on neuroinflammatory markers in rodent models. The search terms Fructose AND neuroinflammation OR Neurodegeneration OR chemokines OR interleukins OR microglia OR behaviour OR memory OR cognition were used in Google Scholar, Scopus and Web of Science. Thirteen animal studies investigating fructose-induced neuroinflammation that matched the eligibility criteria were included in the study. Across the studies, 16 inflammatory markers were identified and significantly altered following exposure to fructose. The findings consistently demonstrated elevated expression of pro-inflammatory cytokines, TNF-&#x3b1;, IL-6, and IL-1&#x3b2;, following fructose administration. Fructose consumption also dysregulated MCP-1, fractalkine, and CX3CR1 levels, thereby promoting inflammatory signalling and microglial activation. Furthermore, fructose exposure significantly increased IBA-1 and CD11b, indicating sustained neuroimmune activation. Alterations in important inflammatory pathways involving TLR4, NLRP3, NF-&#x3ba;B, MyD88, iNOS, and cyclooxygenases (COX-1 and COX-2) were also observed. In contrast, expression of the anti-inflammatory regulator peroxisome proliferator-activated receptor gamma (PPAR&#x3b3;) was reduced after fructose treatment. Overall, the findings suggest that chronic fructose consumption induces neuroinflammation through multiple inflammatory and immune-related mechanisms in the brain. These effects appear to be dose- and duration-dependent and may contribute significantly to neurodegeneration and cognitive impairment.

Microglia

Unconfined compressive strength prediction for the ordinary Portland cement-steel slag-silica fume ternary system based on response surface methodology.

This research was undertaken to address environmental concerns associated with industrial solid waste and to reduce cement consumption in geotechnical engineering. It specifically investigates the feasibility of using steel slag (SS) and silica fume (SF) as partial substitutes for ordinary Portland cement (OPC) in soil stabilization. The effects of SS, SF, OPC, and initial moisture content on the unconfined compressive strength (UCS) of stabilized soil were investigated through single-factor experiments and response surface methodology (RSM). The results show that SS and SF can synergistically enhance the strength of stabilized soil, although their interaction effect was not statistically significant within the investigated ranges. Compared with soil stabilized solely with OPC, the addition of 18 % SS and 10 % SF reduced OPC consumption by 3 % without compromising strength. Microstructural and compositional analyses further revealed that SS mainly supplied calcium- and silica-bearing components, while SF provided highly reactive silica and micro-filling effects, jointly promoting hydration reactions and improving the compactness of the stabilized soil matrix. As a result, more hydration products were formed in the OPC/SS/SF-stabilized soil than in the OPC-stabilized soil, which contributed to pore filling and strength enhancement. This study provides useful guidance for the sustainable utilization of industrial solid waste and the low-carbon development of soil stabilization materials.

Construction Materials

Gut microbiota and metabolic alterations in participants with flatulence identify Faecalibacterium prausnitzii as a key microbial target for clinical intervention.

Flatulence is closely associated with gut dysbiosis, yet the characteristic microbial signatures, metabolic alterations, and actionable intervention targets remain unclear. This limited mechanistic understanding has hindered the development of precise microbiota-based strategies for managing flatulence. Here, we found that participants with flatulence exhibited marked shifts in gut microbial functions and fecal metabolic profiles compared with healthy controls, characterized by enhanced abnormal fermentation, enrichment of oxidative stress-related functions, elevated low-grade inflammatory signatures, and reduced anti-inflammatory and mucosal-protective metabolic features. Faecalibacterium prausnitzii was significantly negatively associated with the high-gas-producing phenotype. In vitro replenishment experiments further validated the role of F. prausnitzii in reducing gas production, promoting butyrate generation, and remodeling butyrate-associated microbial communities. Based on microbial interaction analysis, we identified Bifidobacterium longum CCFM1319 as a candidate strain for targeting F. prausnitzii. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with B. longum CCFM1319 significantly increased intestinal F. prausnitzii abundance and improved flatulence-related symptoms. Collectively, these findings reveal the microbiota and metabolic dysbiosis underlying flatulence, highlight the key regulatory role of F. prausnitzii, and lays the foundation for targeted microbiota-based intervention strategies for flatulence.

Humans

Comparative analysis of gut microbiota in yaks under different feeding management strategies during cold seasons.

Yaks (Bos grunniens) are crucial for the livelihoods of pastoral communities in cold regions, where feed scarcity during the cold season poses challenges to their health and productivity, underscoring the necessity of understanding how dietary management influences the gut microbiota. In this study, 24 yak steers matched for body weight and health status were randomly allocated to four groups: natural grazing or indoor feeding with roughage-to-concentrate ratios of 50:50, 70:30, or 90:10. Fecal samples were collected for 16S rDNA sequencing and subsequent functional prediction of the microbiota. The results showed that Firmicutes and Bacteroidetes were the dominant phyla across all groups, and UCG-005 and Rikenellaceae_RC9_gut_group were the predominant genera. Concentrate supplementation during the cold season significantly enhanced microbial richness and diversity, with the 70:30 ratio exerting the most pronounced beneficial effects on microbiota structure and key taxa enrichment. These findings highlight the critical role of dietary management in shaping the yak gut microbiota during cold seasons and suggest that the 70:30 ratio optimally improves microbial community structure, thereby promoting yak health and productivity under harsh climatic conditions. Future research should explore the long-term implications of such dietary strategies.

Animals