Search Results (20,856)

The neonatal heart possesses a unique capacity for reparative healing after myocardial injury, unlike the adult heart. While immune cells, particularly T cells, regulate post-infarction inflammation, their role in age-dependent cardiac repair remains unclear. This study aimed to characterize the temporal activation of T cell subsets and their contribution to immune homeostasis and myocardial repair. Myocardial infarction was induced in mice of different ages, and T cell subsets (CD4+ T cells, CD8+ T cells, and CD4+Foxp3+ T [T-reg] cells) were analyzed using flow cytometry and RNA sequencing. Neonatal hearts exhibited CD4+ T cells, CD8+ T cells, and T-reg cells that gradually increased until seven days post-injury. Transcriptome analysis identified Rcn3 as a neonatal-specific, injury-responsive gene in T-reg cells, with minimal induction in adult and aged hearts, promoting a reparative microenvironment and exerting anti-fibrotic effects via the PI3K/Akt pathway. Under endoplasmic reticulum stress, Rcn3 activated unfolded protein response genes, and Rcn3-conditioned media reduced fibrosis-associated gene expression in adult cardiac fibroblasts. In a conditional knockout mouse model (Lck-cre; Rcn3^fl/fl), Rcn3 deletion in T cells led to impaired cardiac function recovery and increased fibrosis post-injury. These findings suggest that neonatal T-reg cells play a crucial role in cardiac repair, with Rcn3 as a potential therapeutic target for enhancing immune-mediated cardiac repair and limiting pathological remodeling in the adult heart. Full article

Background/Objectives: Branched-chain fatty acids (BCFAs) exhibit a range of biological activities; however, their limited natural abundance and high cost have constrained in vivo research. Lanolin represents a promising source for enriching BCFAs. Nevertheless, the in vivo application, safety, and dose-effect relationship of BCFAs derived from lanolin (BCFAs-DFL) remain unassessed. Methods: In this study, the acute toxicity in C57BL/6J mice was first evaluated for 7 days by a single oral administration of 5000 mg/kg BW of BCFAs-DFL. Subsequently, 40 mice were divided into four groups (control group, low dose of 100 mg/kg BW, medium dose of 300 mg/kg BW, and high dose of 600 mg/kg BW) and were continuously administered by gavage for 28 days to study the effects of BCFAs-DFL on the growth, blood biochemistry, intestinal morphology, and intestinal flora of the mice. Results: In the acute toxicity test, BCFAs-DFL exhibited no lethality or abnormalities in mice, indicating its non-toxic nature. Throughout the 28-day trial, mice in the medium- and high-dose groups experienced a notable decrease in average daily feed intake (p < 0.05), yet their weight gain remained unaffected (p > 0.05). Hemoglobin and hematocrit levels declined in the high-dose group (p < 0.05). Conversely, serum aspartate aminotransferase and total bilirubin levels escalated in the medium- and high-dose groups, while triglycerides and urea nitrogen levels decreased (p < 0.05). The serum’s total antioxidant capacity and immunoglobulin levels (IgA, IgG) rose in proportion to the dosage (p < 0.05). BCFAs-DFL notably enhanced the villus height of the jejunum and ileum in mice (p < 0.05). Gut microbiota analysis indicated no significant impact on overall α and β diversity. Conclusions: The 28-day intervention revealed that BCFAs-DFL can modulate feeding behavior, TG, T-AOC, and immunoglobulin levels in mice. Additionally, it promotes the development of intestinal villi. Based on various indicators, a dosage of 100 mg/kg BW effectively induces beneficial metabolic regulation, such as the reduction of triglycerides, without causing a burden on liver metabolism. This dosage may represent a more suitable application for potential use. Full article

The extracellular matrix (ECM) is a dynamic, tissue-specific network that integrates biochemical and mechanical cues to regulate cell behavior and organ homeostasis. Increasing evidence indicates that dysregulated ECM remodeling is an upstream driver of chronic human diseases rather than a passive consequence of injury. This review summarizes principles of ECM organization, mechanotransduction, and pathological remodeling and highlights translational opportunities for ECM-targeted therapies, biomaterial platforms, and precision diagnostics. We conducted a narrative synthesis of foundational and recent literature covering ECM composition and turnover, stiffness-dependent signaling, and disease-associated remodeling across fibrosis/cardiovascular disease, cancer, and metabolic disorders, together with advances in ECM-based biomaterials, drug delivery, and ECMderived biomarkers and imaging. Across organs, a self-reinforcing cycle of altered matrix composition, excessive crosslinking, and stiffness-dependent mechanotransduction (including integrin–FAK and YAP/TAZ pathways) sustains fibroinflammation, myofibroblast persistence, and progressive tissue dysfunction. In tumors, aligned and crosslinked ECM promotes invasion, immune evasion, and therapy resistance while also shaping perfusion and drug penetration. Translational strategies increasingly focus on modulating ECM synthesis and crosslinking, normalizing rather than ablating matrix architecture, and targeting ECM–cell signaling axes in combination with anti-fibrotic, cytotoxic, or immunotherapeutic regimens. ECM biology provides a unifying framework linking pathogenesis, therapy, and precision diagnostics across chronic diseases. Clinical translation will benefit from standardized quantitative measures of matrix remodeling, mechanism-based biomarkers of ECM turnover, and integrative imaging–omics approaches for patient stratification and treatment monitoring. Full article

Aiming at the wind-blown snow disasters plaguing tunnel portals along the China-Tajikistan Highway Phase II Project, this study optimizes the protective parameters of wind deflectors through numerical simulation to improve the disaster prevention efficiency of tunnel portals in alpine mountainous areas. Three core control parameters of wind deflectors, namely horizontal distance from the tunnel portal (L), plate inclination angle (β), and top installation height (h), were selected as the research objects. Single-factor numerical simulation scenarios were designed for each parameter, and an L9(3³) orthogonal test was further adopted to formulate 9 groups of multi-parameter combination scenarios, with the snow phase volume fraction at 35 m on the leeward side of the tunnel portal set as the core evaluation index. A computational fluid dynamics (CFD) model was established to systematically investigate the influence laws of each parameter on the wind field structure and snow drift deposition characteristics at tunnel portals and clarify the flow field response rules under different parameter configurations. Single-factor simulation results show that the wind deflector exerts distinct regulatory effects on the wind-snow flow field with different parameter settings: when L = 6 m, the disturbance zone of the wind deflector precisely covers the main wind flow development area in front of the tunnel portal, which effectively lifts the main incoming flow path, compresses the recirculation zone (length reduced from 45.8 m to 22.3 m), and reduces the settlement of snow particles, achieving the optimal comprehensive prevention effect; when β = 60°, the leeward wind speed at the tunnel portal is significantly increased to 10–12 m/s (from below 10 m/s), which effectively promotes the transport of snow particles and mitigates the accumulation risk, being the optimal inclination angle; when h = 2 m, the wind speed on both the windward and leeward sides of the tunnel portal is significantly improved, and the snow accumulation risk at the portal reaches the minimum. Orthogonal test results further quantify the influence degree of each parameter on the snow prevention effect, revealing that the horizontal distance from the tunnel portal is the most significant influencing factor. The optimal parameter combination of the wind deflector is determined as L = 6 m, β = 60°, and h = 2 m. Under this optimal combination, the snow phase volume fraction at 35 m on the leeward side of the tunnel portal is 0.0505, a 12.3% reduction compared with the non-deflector condition; the high-concentration snow accumulation zone is shifted 25 m leeward, and the high-value snow phase volume fraction area (>0.06) disappears completely, which can effectively alleviate the adverse impact of wind-blown snow disasters on the normal operation of tunnel portals. The research results reveal the regulation mechanism of wind deflector parameters on the wind-snow flow field at alpine tunnel portals and determine the optimal protective parameter combination, which can provide important theoretical reference and technical support for the prevention and control of wind-blown snow disasters at tunnel portals in similar alpine mountainous areas. Full article

Embryonic diapause, a state of developmental arrest in silkworm (Bombyx mori) eggs, poses a challenge for year-round sericulture. While physical stimuli like corona discharge can effectively terminate diapause, the underlying molecular mechanisms, particularly the initial events, remain poorly understood. This study employed an integrated transcriptomic and proteomic approach to analyze silkworm eggs within 48 h after corona treatment. Our time-series analysis revealed that the Hippo and Wnt signaling pathways were specifically activated as early as 1 h post-treatment, preceding the previously reported FoxO pathway response. We identified two temporally distinct gene clusters within the Hippo pathway, including immediate–early genes (e.g., Dachs_17/25/29, Ft_10) and late-phase effector genes, coordinating the exit from cell cycle arrest. Concurrently, the Wnt pathway was rapidly initiated, marked by the sustained upregulation of key regulators Notum and Pontin52, suggesting its role in unlocking the cell cycle. We propose a synergistic model wherein corona discharge triggers the concurrent, early activation of Hippo and Wnt signaling, which collectively reprogram the cell cycle and reinstate the developmental trajectory by promoting proliferation and suppressing apoptosis. These findings provide crucial insights into the initial molecular events of diapause termination, identifying Hippo and Wnt pathways as master regulators in transducing the physical corona stimulus into a developmental signal. Full article

During liquid drainage from intermediate vessels in various industrial processes such as continuous steel casting, aircraft fuel supply, and chemical separation, free-surface vortices commonly occur. The formation and evolution of these vortices not only entrain surface slag and gas, but also lead to deterioration of downstream product quality and abnormal equipment operation. The vortex evolution process exhibits notable three-dimensional unsteadiness, multi-scale turbulence, and dynamic gas–liquid interfacial changes, accompanied by strong coupling effects between temperature gradients and flow field structures. Traditional macroscopic numerical models show clear limitations in accurately capturing these complex physical mechanisms. To address these challenges, this study developed a mesoscopic numerical model for gas-liquid two-phase vortex flow based on the lattice Boltzmann method. The model systematically reveals the dynamic behavior during vortex evolution and the multi-field coupling mechanism with the temperature field while providing an in-depth analysis of how initial perturbation velocity regulates vortex intensity and stability. The results indicate that vortex evolution begins near the bottom drain outlet, with the tangential velocity distribution conforming to the theoretical Rankine vortex model. The vortex core velocity during the critical penetration stage is significantly higher than that during the initial depression stage. An increase in the initial perturbation velocity not only enhances vortex intensity and induces low-frequency oscillations of the vortex core but also markedly promotes the global convective heat transfer process. With regard to the temperature field, an increase in fluid temperature reduces the viscosity coefficient, thereby weakening viscous dissipation effects, which accelerates vortex development and prolongs drainage time. Meanwhile, the vortex structure—through the induction of Taylor vortices and a spiral pumping effect—drives shear mixing and radial thermal diffusion between fluid regions at different temperatures, leading to dynamic reconstruction and homogenization of the temperature field. The outcomes of this study not only provide a solid theoretical foundation for understanding the generation, evolution, and heat transfer mechanisms of vortices under industrial thermal conditions, but also offer clear engineering guidance for practical production-enabling optimized operational parameters to suppress vortices and enhance drainage efficiency. Full article

Developing high-quality regional integration requires a good-quality water environment. In this study, the impact of formal and informal environmental regulation (FIER) on water environment governance performance (WEP) is examined using a fixed-effects model and spatial Durbin model with a panel data sample of 281 cities from 2011 to 2022. It is found that (i) there is an inverted U-shaped relationship between FIER and WEP, which is first promoted and then inhibited and remains significant after endogeneity exploration and multiple robustness tests; (ii) the pressure of economic growth has weakened this elationship, while the digital economy has strengthened it; and (iii) further analysis reveals that there is an inverted U-shaped relationship between the local and spillover effects of FIER on WEP. Therefore, WEP can be improved by dynamically adjusting the intensity of FIER, optimizing the appraisal orientation of local governments, and accelerating the integration of digital economy and environmental governance Full article

Phytoremediation is a cost-effective and sustainable method for the remediation of minewaste contaminated with heavy metals such as arsenic (As). However, mine waste soil is often nutrient-limited, especially in nitrogen (N), impairing plant growth and phytoremediation. This study aimed to assess how planting density together with soil amendments, biochar, and an isolated indigenous nitrogen-fixing bacterium (NFB) (Bacillus subtilis) affect the efficacy of phytoremediation by Juncus pauciflorus of an As-contaminated mine waste soil from Bendigo, Victoria. Three plant densities, including 9, 26, and 44 plants/m², were grown in As-contaminated mine waste soil amended with biochar (10% w/w) and B. subtilis (8.1 × 10⁸ CFU/mL) and incubated for 100 days. Plant biomass, plant As uptake, soil As concentration, bacterial abundance (total and NFB using 16S and nifH gene copy numbers, respectively), and total soil N were assessed. Juncus pauciflorus at a higher density (44 plants/m²) promoted the greatest biomass and total As uptake, 70.22 g/m² and 209.53 mg/m², respectively. Plant density significantly influenced the root–shoot partitioning of As. Higher densities increased shoot uptake (BAF_soil→shoot), and TF_root→shoot values remained >1 across all treatments, confirming the active translocation of As to the shoots, suggesting both phytostabilisation and phytoextraction potential by J. pauciflorus. Planting density significantly reduced soil As, ranging from 8000 mg/kg to 9500 mg/kg, compared to the initial concentration (13,032 mg/kg). The abundance of 16S and nifH genes was stable among treatments, ranging from 7 log₁₀ copies/g to 12 log₁₀ copies/g. TN content in soils amended with 44 plants/m² contained the highest TN content at day 33, approximately 7000 mg/kg. This study is the first to report that higher planting density of J. pauciflorus amended with biochar and NFB provides the strongest phytoremediation performance in highly As-contaminated mine soil by enhancing As uptake and accumulation in aboveground biomass. Most importantly, the results show that plant density also regulates the plant’s remediation strategy, shifting J. pauciflorus between phytostabilisation at dense planting and greater phytoextraction at lower density. These findings support the use of native plants in combination with biochar and microbial amendment as a sustainable strategy for remediating As-contaminated mine waste. Full article

Teachers’ language assessment literacy (LAL) encompasses the knowledge and competencies required to design and implement assessment practices that support learning. Although prior research has documented general trends in LAL development, less is known about how individual teachers, particularly student teachers, interpret, appropriate, and negotiate formative assessment (FA) task design within the context of initial teacher education (ITE). Adopting an in-depth qualitative case study approach, this study examines how a single student teacher in a Chinese initial teacher education developed her cognition and classroom practice related to FA tasks across a teaching methodology course and a practicum. Drawing on thematic analysis of semi-structure interviews, lesson plans, classroom observations, stimulated recall interviews, and reflective journals, the study traces developmental changes and the contextual factors shaping the student teacher’s LAL in relation to FA tasks. Findings show that the sustained engagement with FA task design supported more sophisticated understandings of FA, including (1) an increased recognition of the pedagogical necessity of incorporating authentic FA tasks into lesson planning, (2) a growing aspiration to implement FA-oriented instruction that promotes higher-order thinking, (3) an enhanced awareness of the empowering role of FA tasks in fostering students’ self-regulated learning, and (4) a more nuanced understanding of the challenges inherent in implementing FA practices. Meanwhile, the case illustrates how pre-existing assessment conceptions, school culture norms, and limited targeted mentoring can constrain LAL development in relation to FA. By providing a fine-grained account of developmental processes, this study offers insights into how ITE can mediate student teachers’ engagement with FA task design. The findings have implications for teacher education programs in other similar educational contexts, particularly regarding the integration of FA task design into assessment courses and the provision of sustained, context-sensitive support during teaching practicum. Full article

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that relies on the activation of photosensitizers (PS) by specific wavelengths of light to generate reactive oxygen species (ROS), resulting in localized cytotoxicity with relative sparing of healthy tissues. Depending on the PS properties, light dose, and intrinsic cellular features, PDT can elicit multiple cell death pathways, including apoptosis, necrosis, and autophagy. Increasing evidence indicates that PDT is also a potent inducer of ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation (LPO), glutathione (GSH) depletion, and inactivation of glutathione peroxidase 4 (GPX4). PDT-derived ROS promote ferroptosis both indirectly by exhausting antioxidant defenses and directly by peroxidizing PUFAs within membrane phospholipids. At the same time, intense oxidative stress generated by PDT can activate adaptive responses such as mitophagy, a selective autophagic process that removes damaged mitochondria to limit ROS production and preserve redox homeostasis. Ferroptosis and mitophagy are therefore tightly interconnected, functioning as opposing yet complementary regulators of cell fate. PDT emerges as a key upstream modulator of the ferroptosis–mitophagy balance, as spatially and temporally confined oxidative stress can shift cellular responses from adaptive mitochondrial quality control to irreversible ferroptotic injury. Despite growing interest in both PDT and ferroptosis, their mechanistic interplay, particularly in relation to mitophagy, remains underexplored. This narrative review provides an integrated overview of current knowledge on how PDT influences ferroptosis and mitophagy, highlighting the molecular mechanisms that connect these pathways and discussing their implications for improving therapeutic efficacy and overcoming resistance. Full article

Adventitious shoot regeneration in woody species is regulated by interactions between plant growth regulators, endogenous hormone metabolism, and environmental cues such as light quality. Here, we investigated the effects of thidiazuron (TDZ) and the cytokinin oxidase/dehydrogenase (CKX) inhibitors INCYDE and phenyladenine (PA), in combination with different light spectra, on morphogenesis in Melia volkensii leaf explants. TDZ induced the highest frequencies of callus formation and adventitious shoot regeneration, particularly under white light. INCYDE promoted localized regeneration responses, including activation of dormant meristematic regions in secondary leaf axils, whereas PA showed limited regeneration efficiency. Light quality significantly influenced morphogenesis, with white and blue light favoring organized shoot development, while red and far-red light suppressed shoot regeneration and promoted callus formation. Cytokinin profiling revealed treatment-dependent shifts in endogenous cytokinin composition, most notably in isopentenyladenine (iP)-type cytokinins, which is consistent with altered cytokinin degradation dynamics. Cis-zeatin-type cytokinins were abundant across treatments, likely reflecting regulation associated with in vitro culture conditions. These findings indicate that cytokinin metabolism and light quality jointly influence organogenic competence in Melia volkensii Gürke, providing a physiological basis for optimizing regeneration strategies in woody plants. This study provides the first integrated analysis of cytokinin-modulating compounds and light spectra on adventitious shoot regeneration in Melia volkensii. The findings establish a physiological basis for improving regeneration protocols in recalcitrant woody species and support future biotechnological applications, including genetic improvement and advanced propagation strategies. Full article

The MYB transcription factor family plays crucial roles in plant growth, development, and responses to biotic and abiotic stresses. Seashore paspalum (Paspalum vaginatum) is a halophytic grass species with remarkable salt tolerance, yet its MYB gene family has not been systematically characterized. In this study, we conducted a genome-wide identification of MYB genes in seashore paspalum using a Hidden Markov Model (HMM)-based approach, resulting in the identification of 157 PvMYB genes. Phylogenetic and conserved motif analyses revealed distinct subfamily groupings and evolutionary relationships within the PvMYB family. Promoter analysis indicated that PvMYB genes contain multiple cis-acting elements responsive to light, hormones, and abiotic stresses, suggesting their potential regulatory roles under salt stress. Collinearity and duplication analyses demonstrated that gene duplication events contributed to the expansion of the PvMYB family. Moreover, protein interaction network prediction suggested that PvMYB73 may interact with key regulatory proteins such as BZIP8 and DREB1F involved in salt stress signaling. Transcriptome and reverse transcription quantitative PCR (RT-qPCR) analyses showed that PvMYB90, PvMYB123, and PvMYB150 were upregulated in leaves and roots under salinity stress, while PvMYB85 and PvMYB90 were experimentally validated to localize in the nucleus and function in salt tolerance regulation. Collectively, this study provides the first comprehensive characterization of the MYB gene family in seashore paspalum and offers valuable insights into the molecular mechanisms underlying salt tolerance in halophytic grasses. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. MASLD spans a spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and is linked to progressive fibrosis and ultimately hepatocellular carcinoma (HCC). Growing evidence implicates cellular senescence (CS) and lipid droplets (LDs) as key drivers of disease progression, although their interaction remains poorly characterized. This review provides an integrative and stage-dependent synthesis of current mechanistic insights into how bidirectional crosstalk between CS and LD regulation shapes the transition from steatosis to MASH. Senescent hepatocytes display altered lipid metabolism, including upregulation of receptors such as cluster of differentiation (CD) 36, enhancing lipid uptake to meet increased energy demands. Initially, elevated free fatty acid influx can activate peroxisome-proliferator-activated receptor alpha (PPARα), promoting fatty acid oxidation (FAO) as a compensatory response. Over time, persistent CS under steatotic conditions leads to mitochondrial dysfunction and suppression of fatty acid oxidation (FAO), while the senescence-associated secretory phenotype (SASP), largely driven by nuclear factor—kappa B (NF-κB) signaling, promotes chronic hepatic inflammation. By framing LDs as active modulators of senescence-associated signaling rather than passive lipid stores, this review highlights how disruption of senescence–lipid feedback loops may represent a disease-modifying opportunity in MASLD progression. Full article

Background: Bile acids participate in several metabolic processes, and disturbances in their circulating profiles are commonly observed in type 2 diabetes. In a cohort of older adults, individuals with diabetes exhibited markedly lower concentrations of metabolites derived from lithocholic acid. These findings prompted further evaluation of the metabolic effects of lithocholic acid. Methods: We assessed the actions of lithocholic acid in a mouse model of diabetes induced by a high-fat diet and streptozotocin. Fasting glucose, insulin levels, lipid parameters, and measures of insulin resistance were evaluated. Gut microbial composition, short-chain fatty acids, fecal enzyme activities, intestinal barrier markers, and bile acid patterns were analyzed. In vitro assays examined the direct effects of lithocholic acid on A. muciniphila and bile acid metabolism. Results: Lithocholic acid supplementation lowered fasting glucose and insulin levels and improved insulin resistance. It shifted the gut microbial community toward a healthier structure, increased the abundance of A. muciniphila, and raised short-chain fatty acid concentrations. Fecal bile salt hydrolase and β-glucuronidase activity declined, and intestinal barrier markers improved. Lithocholic acid enhanced TGR5 expression and reduced FXR signaling in the ileum. In vitro, physiologically relevant concentrations promoted A. muciniphila growth and altered microbial bile acid metabolism. Conclusions: Lithocholic acid influences the interactions among gut microbes, bile acid pathways, and host metabolic regulation. These findings suggest that this compound may have value as a dietary component that supports metabolic health in type 2 diabetes. Full article

Colorectal cancer (CRC) progression and therapy resistance are driven in part by metabolic reprogramming and the persistence of cancer stem-like cells (CSCs). The seven in absentia homolog 2 (SIAH2)/with-no-lysine kinase 1 (WNK1) signaling axis has emerged as a potential regulator of these processes, yet its functional role in CRC metabolism and tumor–stroma crosstalk remains incompletely understood. Integrated analyses of The Cancer Genome Atlas–Colon Adenocarcinoma (TCGA-COAD) and Gene Expression Omnibus (GEO, GSE17538) datasets revealed significant upregulation of SIAH2 and WNK1 in CRC tissues, with strong positive correlations to glycolysis- and hypoxia-associated genes, including PFKP, LDHA, BPGM, ADH1A, ADH1B, and HIF-1α. Single-cell and clinical profiling further demonstrated preferential enrichment of SIAH2 in undifferentiated, stem-like tumor cell populations. Functional studies across multiple CRC cell lines showed that SIAH2 silencing suppressed proliferation, clonogenic growth, tumor sphere formation, and cell-cycle progression, whereas SIAH2 overexpression exerted opposite effects. Seahorse extracellular flux analyses established that SIAH2 promotes glycolytic capacity and metabolic flexibility. At the protein level, SIAH2 regulated glycolytic enzymes and WNK1/hypoxia-inducible factor-1α (HIF-1α) signaling, effects that were amplified by cancer-associated fibroblast (CAF)-derived conditioned medium. CAF exposure enhanced SIAH2 expression, CSC spheroid growth, and resistance to fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy, whereas SIAH2 depletion effectively abrogated these effects. Collectively, these findings identify the SIAH2/WNK1 axis as a central metabolic regulator linking glycolysis, CSC maintenance, and microenvironment-driven therapy resistance in CRC, highlighting its potential as a therapeutic target. Full article