Search Results (19,974)

Verticillium wilt (VW), caused by the soil-borne phytopathogen Verticillium dahliae, is a devastating vascular disease that severely threatens global cotton production and causes substantial economic losses. Jasmonic acid (JA) signaling plays a crucial role in plant innate immunity; however, the molecular mechanisms governing JA biosynthesis during cotton defense responses to V. dahliae infection remain largely elusive. In this study, we identified that GhAOS1 (allene oxide synthase 1), a key rate-limiting enzyme-encoding gene in the JA biosynthetic pathway, was rapidly and significantly induced by V. dahliae infection and exclusively localized in chloroplasts. Functional analysis in GhAOS1-silenced cotton and overexpressing Arabidopsis plants demonstrated that GhAOS1 positively regulates resistance to V. dahliae. Transcriptome analysis of GhAOS1-silenced cotton plants showed that DEGs are significantly enriched in phenylpropanoid biosynthesis, flavonoid biosynthesis, and α-linolenic acid metabolism pathways. Consistent with these findings, silencing GhAOS1 significantly reduced endogenous JA levels and suppressed the expression of defense-related genes and JA biosynthetic genes in cotton. Furthermore, we identified that the transcription factor GhWRKY70 directly binds to the W-box cis-acting element in the GhAOS1 promoter through Y1H, LUC, and EMSA, which activated GhAOS1 transcription. Silencing GhWRKY70 in cotton significantly enhanced plant susceptibility to V. dahliae and suppressed the expression of JA signaling pathway-related genes. Collectively, our results elucidate that GhWRKY70 positively regulates cotton resistance to VW by activating GhAOS1-mediated JA biosynthesis, revealing a novel GhWRKY70-GhAOS1 regulatory module that integrates JA signaling to coordinate cotton immune responses against V. dahliae. This study provides new insights into the molecular mechanism of JA-mediated defense and offers potential targets for molecular breeding of VW-resistant cotton. Full article

Background/Objectives: Remnant cholesterol (remnant-C), derived from triglyceride-rich lipoproteins, is an important risk factor for cardiometabolic diseases. Given the metabolic link between dyslipidemia and skeletal muscle dysfunction, we aimed to evaluate the association between remnant-C and two key components of sarcopenia—low muscle mass and myosteatosis (ectopic fat deposition in skeletal muscle). Methods: This cross-sectional study included 11,570 patients who underwent abdominal computed tomography (CT) for health check-ups. Remnant-C was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. We conducted multivariable logistic and linear analyses to assess the association between remnant-C and low muscle mass, defined as appendicular skeletal muscle mass divided by body mass index. Additional analysis examined the relationship between remnant-C and myosteatosis, defined using the NAMA (normal attenuation muscle area) divided by TAMA (total abdominal muscle area) index, a novel index derived from muscle quality mapping of abdominal CT scans. Results: Low muscle mass was observed in 244 males (3.9%) and 74 females (1.4%). Myosteatosis affected 950 males (15.0%) and 800 females (15.3%). There was an increasing prevalence of both low muscle mass and myosteatosis across remnant-C quartiles. The multivariate-adjusted odds ratios (ORs) for low muscle mass in the highest remnant-C quartile compared with the lowest quartile were 2.17 (95% confidence interval [CI] 1.45–3.26) for males and 1.37 (95% CI 0.68–2.76) for females. The corresponding ORs for myosteatosis were 1.37 (95% CI 1.11–1.69) for males and 1.24 (95% CI 0.96–1.59) for females. Conclusions: Elevated remnant-C level is associated with low muscle mass and myosteatosis, especially in male patients. Individuals with higher remnant-C levels may warrant comprehensive evaluation for skeletal muscle health. Full article

The survival of complex multicellular organisms depends on continuous inter-organ communication networks that coordinate organism-wide responses across physiological conditions and stress states, including adaptation to environmental challenges, infection, and injury. Rather than operating as isolated units, organ systems are integrated through interconnected signaling networks that transmit biological information across tissues. Building on prior work examining individual physiological pathways, this review introduces a unified systems-level framework that integrates inter-organ communication into a coherent model of organism-wide regulation. This review proposes a systems-level framework in which homeostasis is maintained through eight principal communication systems: neural, endocrine, immune-inflammatory, vascular, lymphatic, metabolic, microbiome–gut, and mechanical-structural. Epithelial barriers function as dynamic signaling interfaces within multiple systems, while extracellular vesicles act as cross-system mediators of information transfer rather than as independent communication networks. These systems operate across distinct temporal scales to coordinate host defense, metabolic adaptation, vascular regulation, and tissue repair. The framework further introduces a temporal hierarchy of signaling dynamics that links communication systems to phase-specific responses during physiological stress. Within this integrated network, glucocorticoid receptor α (GRα) is proposed to function as a systems-level regulator of inter-organ communication, supported by converging mechanistic, experimental, and clinical evidence, with variability in the strength of evidence across domains. In contrast to prior reviews, which addressed GRα function within individual systems, this work conceptualizes GRα as a central rheostat coordinating cross-system signaling and temporal transitions in homeostatic correction. Evidence was identified through hypothesis-driven searches using the Consensus AI platform and verified through manual review of primary biomedical literature. GRα, a ligand-activated transcription factor expressed in most nucleated cells, enables hormonal stress signals to coordinate gene-expression programs across tissues, modulating neuroendocrine responses, endothelial function, inflammatory signaling, metabolic regulation, microbiome–host interactions, and tissue remodeling. Systemic responses to stress progress through three phases of homeostatic correction—Priming, Modulatory, and Restorative—within which GRα supports integrated organism-wide adaptation. This integrative framework provides a mechanistic basis for understanding the emergence and temporal evolution of biological responses in health and critical illness. Full article

A common hypoxic scenario in tumors involves unresolved acute hypoxia that eventually leads to sustained (chronic) hypoxia. This shift drives a characteristic “HIF switch”, where the key hypoxia-responsive factors change from HIF-1α to HIF-2α over time, and importantly, this switch is closely linked to stemness regulation. However, the mechanisms underlying this switch and its impact on stemness regulation are not yet fully understood. Here, we developed a mechanistic network model integrating the HIF-1/HIF-2 signaling axis with the stemness regulators OCT4 and SOX2. We found the duration and intensity of hypoxia jointly shape the dynamics of HIF-1α and HIF-2α, ultimately regulating OCT4-mediated stemness. Under physioxia, HIF-2α–mTORC2 positive feedback supports the gradual accumulation of HIF-2α toward a modest steady level and low OCT4 expression, corresponding to a primed state. Under prolonged mild hypoxia, the concurrent induction of HIF-1α, albeit at low levels, and accelerated accumulation of HIF-2α elevate OCT4 to intermediate levels, promoting stem-like traits. Under moderate hypoxia, PHD-2-mediated negative feedback triggers pulsatile HIF-1α dynamics, driving a shift toward HIF-2α dominance. Ultimately, cooperative HIF-1α/HIF-2α signaling induces REDD1 and suppresses mTORC1-dependent protein synthesis, pushing OCT4 into a high-expression state associated with differentiation. This work presents a unified framework for understanding how the HIF signaling hierarchy coordinates metabolic and transcriptional programs to direct cell fate across varying hypoxic landscapes. Full article

Semaglutide represents a unique therapeutic option for patients with type 2 diabetes mellitus (T2DM), being the first and currently only glucagon-like peptide-1 receptor agonist (GLP-1RA) available in both subcutaneous and oral formulations. This study aimed to compare the effectiveness of oral versus subcutaneous (sc) semaglutide on metabolic parameters and cardiovascular risk factors in T2DM patients. This is a retrospective real-world study including adult patients with T2DM taking oral or sc semaglutide followed at the ASUGI Diabetes Center. We analyzed data from 434 patients (median age 70 years, diabetes duration 13 years), treated with oral (n = 232) or sc (n = 202) semaglutide. The oral formulation had a higher discontinuation rate. Among these patients, 130 patients in the oral group and 145 in the sc group had an 18-month follow-up. When comparing these groups, patients taking sc semaglutide had a significantly higher baseline BMI. However, multivariate linear regression models suggested that both formulations were comparably effective in reducing HbA1c and BMI, with baseline values being the primary predictors of response. To address BMI imbalances, propensity score matching was performed, identifying 55 matched pairs. Both oral and sc semaglutide reduced HbA1c and BMI and there were no significant differences in the median change in HbA1c and BMI between groups. Interestingly, oral semaglutide was associated with a significantly greater reduction in diastolic blood pressure compared to the sc formulation. Furthermore, concomitant therapy with SGLT2 inhibitors significantly enhanced the reduction in total and LDL cholesterol. Oral and subcutaneous semaglutide show comparable effectiveness in lowering HbA1c and BMI in a real-world setting. Full article

Primula nutans Georgi, a medicinal herb used in Mongolian and Tibetan medicine for treating respiratory ailments, is a natural agent with antiobesity potential. We investigated the antiobesity and insulin-sensitizing effects of P. nutans Georgi extract (PGE) using in vitro and in vivo models. In 3T3-L1 preadipocytes, PGE inhibited adipocyte differentiation and lipid accumulation without cytotoxicity, accompanied by the reduced expression of adipogenic transcription factors (PPARG, C/EBPA, and adiponectin) and lipogenic genes (FASN, SCD1, and ACC), particularly during the early stages of adipogenesis. Similar effects were observed in primary stromal vascular cells derived from mouse inguinal white adipose tissue. PGE upregulated C/EBP homologous protein and C/EBPB and was associated with altered cell cycle progression, increased G2/M phase distribution, and the potential disruption of mitotic clonal expansion during early adipogenesis. In HFD-induced obese mice, intraperitoneal administration of PGE (10 or 30 mg/kg) significantly reduced body weight gain, white adipose tissue mass, and hepatic steatosis, independent of food intake. PGE downregulated lipogenic and proinflammatory gene expression in adipose and hepatic tissues and increased AMPK phosphorylation in white adipose tissue. PGE improved glucose tolerance and was associated with enhanced insulin sensitivity, as evidenced by reduced areas under the curve in the glucose tolerance and insulin tolerance tests and increased circulating adiponectin levels. Feature-based molecular networking identified 61 compounds from PGE. Network pharmacology analysis revealed several antiobesity targets, including PPARG and AKT1. Molecular docking analyses suggested favorable binding affinities between major compounds and metabolic regulators. Collectively, these findings suggest that PGE may suppress adipogenesis and improve metabolic parameters in obese mice, supporting its potential as a natural candidate for obesity and related metabolic disorders. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a globally prevalent hepatic disorder, characterized by hepatic lipid accumulation and extrahepatic complications, notably intestinal barrier injury, which further exacerbates MASLD progression. The “gut–liver axis” has been identified as a critical contributor to MASLD development, with insulin-like growth factor 1 (IGF-1) serving as a pivotal coupling factor of this axis. However, the specific role and molecular mechanism by which IGF-1 modulates intestinal barrier function in the context of MASLD remains unclear. Methods: This study analyzed the correlations between the GH/IGF-1 axis and intestinal barrier function in MASLD rats, and explored the effects of IGF-1 intervention both in vivo and in vitro. Results: Our results showed that MASLD rats exhibited intestinal barrier impairment, characterized by elevated serum Diamine oxidase (DAO) and D-Lactate (D-LAC) levels, villus damage, and downregulation of tight junction proteins and Mucin (MUC2). These changes were accompanied by suppression of the GH/IGF-1 axis. Correlation analysis uncovered a negative association between IGF-1 levels and markers of barrier dysfunction. IGF-1 intervention effectively repaired the intestinal barrier structure of MASLD rats and significantly upregulated the expressions of IGF-1R, PI3K, and AKT. In vitro, IGF-1 treatment improved transepithelial electrical resistance (TEER), enhanced barrier-related gene expression, promoted cell proliferation, and inhibited apoptosis. Conclusions: These findings suggested that GH/IGF-1 axis suppression, intestinal barrier dysfunction, and IGF-1R/PI3K/AKT signaling were interconnected within the gut–liver axis in MASLD. IGF-1 may contribute to barrier regulation through associated signaling changes, highlighting the GH/IGF-1 axis as a potential complementary target. Full article

Background/Objectives: Healthy longevity depends on not only lifespan but also the maintenance of physiological, metabolic, physical, and cognitive functions throughout aging. Identifying early determinants of health is crucial for preventing age-related decline. This narrative review aims to synthesize current evidence on how diet and specific nutrients relate to these early risk factors and indicators of healthy longevity. Methods: A review was performed to identify the links between dietary factors, energy balance, and gut microbiota composition and normal body weight; blood cholesterol, pressure, and glucose; healthy sleep; an active lifestyle; and normal physical function and cognitive performance. Particular attention was given to Mediterranean and other plant-based dietary models as sources of key nutrients. Evidence from observational studies, randomized controlled trials, and meta-analyses was considered. Results: Across all markers, dietary quality and nutrient adequacy emerged as consistent determinants of health outcomes. Key nutrients were associated with favorable cardiometabolic, cognitive, and musculoskeletal functions, such as omega-3 fatty acids, fiber, vitamins D and B, minerals like magnesium and potassium, and polyphenols. Common nutrition gaps included insufficient intake of fiber, unsaturated fats, and micronutrients, which was often linked to a shift toward less plant-based diets. Gut microbiota diversity may mediate several of these associations, influencing metabolism, inflammation, sleep quality, and cognitive performance, although inter-individual variability and causal pathways remain incompletely understood. Conclusions: An integrated dietary approach emphasizing the consumption of whole and plant-rich foods, with moderate amounts of animal foods, supports multiple early markers, risk factors, and indicators of healthy longevity. The modulation of the gut microbiota through plant-based diets and fermented foods represents a promising strategy for maintaining health across aging trajectories. Full article

Typical saline lacustrine mixed sedimentary strata are developed in the Middle Permian Lucaogou Formation (P₂l) in the Jimsar Sag, with frequent interbedding of mudstone, dolomitic mudstone, and argillaceous dolomite. The widespread development of dolomite is a key factor controlling the quality of shale oil reservoirs. To reveal the formation mechanism of dolomite in mixed sedimentary rocks and its constraint on lithological assemblages, this study focuses on comparing the differences in mineralogy, geochemistry, and sedimentary environment of the three types of lithologies based on systematic tests such as thin-section observation, X-ray diffraction, major and trace element analysis, organic petrology, and biomarker analysis. The results indicate that dolomite formation in the study area is not controlled by a single factor, but instead results from the combined control of hydrothermal activity, microbial metabolism, and paleoclimatic fluctuations. Hydrothermal activity provided a source of Mg²⁺, and together with evaporation driven by an arid climate, elevated the Mg/Ca ratio of the lake water, establishing the hydrochemical basis favorable for dolomite development. Metabolic activities of lower aquatic organisms, such as bacteria and algae, promoted the formation of a sustained alkaline environment, creating favorable conditions for dolomite precipitation. Against a background of a relatively arid climate, the alternation of extreme arid and extreme precipitation events caused frequent fluctuations in lake water saturation, potentially providing ideal dynamic conditions for rapid and abundant dolomite formation. This combined control governed dolomite development and produced the interbedded lithological succession in the P₂l mixed sedimentary strata. This study integrates the dominant controlling factors and synergistic mechanisms of dolomite development in mixed sedimentary strata of continental saline lacustrine basins, which helps predict the occurrence and distribution of high-quality reservoir lithologies within such strata and has important implications for the optimization of “sweet spots” in shale oil exploration. Full article

To maintain homeostatic conditions and optimal function during stressors, mitochondria initiate retrograde signaling. The mitochondrial integrated stress response (ISR) and unfolded protein response (UPR^mt) are critical quality control mechanisms activated during instances of mitochondrial perturbations. Restoration of mitochondrial homeostasis is orchestrated by three transcription factors, ATF4, CHOP, and ATF5, which upregulate protective genes to counteract stress. As the health and function of skeletal muscle are heavily dependent on a highly adaptive mitochondrial network, defining how mitochondrial health is maintained across various conditions is essential. Although several studies demonstrate the importance of these responses following instances of stress, the signaling mechanisms required to initiate such pathways remain poorly characterized in skeletal muscle. This review examines how the mitochondrial ISR/UPR^mt and related transcription factors respond to organellar stress by emphasizing the molecular events that occur during exercise, aging and muscle disuse. By consolidating the literature, this work aims to highlight the current understanding of mitochondrial stress response signaling within skeletal muscle and thus emphasize areas for future research and potential therapeutic strategies during divergent metabolic conditions. Full article

Osteoporosis and hyperglycemia are increasingly recognized as dual public health concerns in T1DM. However, the precise molecular mechanisms by which exercise ameliorates these conditions, particularly the contribution of mechanosensitive channels such as Piezo1, remain incompletely elucidated. To explore these mechanisms, T1DM mice were subjected to a 6-week treadmill training protocol (15 m/min, 20 min/day, 6 days/week) to evaluate the functions of exercise on diabetic osteoporosis and hyperglycemia. Exercise intervention markedly improved bone quality in T1DM mice, alleviating osteoporotic manifestations, as evidenced by enhanced mechanical strength, restored bone microarchitecture, and normalized histomorphology. Concurrently, exercise significantly reduced hyperglycemia. To clarify the role of Piezo1, mechanical stretch was applied to Piezo1-knockout MC3T3-E1 (Piezo1^−/−) cells in vitro, mimicking the mechanical stimulation induced by exercise. Consistent with the in vivo results, mechanical stimulation facilitated osteogenic differentiation and glucose metabolism through Piezo1-mediated mechanotransduction. Importantly, these beneficial effects were substantially abrogated in Piezo1^−/− cells, highlighting the central role of Piezo1. Collectively, these findings demonstrate that Piezo1-mediated mechanotransduction constitutes a critical factor by which exercise mitigates osteoporosis and hyperglycemia in T1DM mice. This study provides a framework for the development of new therapeutic strategies targeting Piezo1-mediated mechanotransduction for T1DM management. Full article

In recent years, the pivotal role of the gut microbiota and its metabolites in host health and disease has garnered increasing attention. Dietary phosphatidylcholine and choline are metabolized by gut bacteria to generate trimethylamine (TMA). Upon entering the bloodstream, TMA is oxidized by host liver enzymes to trimethylamine N-oxide (TMAO), a known independent risk factor for various systemic diseases, including atherosclerosis, thrombosis, and chronic kidney disease. Within this complex “diet–gut–host” metabolic axis, the microbial choline TMA-lyase (CutC) acts as the key rate-limiting enzyme that catalyzes the cleavage of choline to produce TMA. This review systematically summarizes the discovery history, enzymatic structural characteristics, and catalytic mechanism of CutC, highlighting its potential as a microbial metabolic target for treating associated diseases. By specifically analyzing existing inhibitor strategies and interventions, this article emphasizes the extensive potential of specific targeting of the CutC enzyme in precisely regulating the functions of the microecology. Full article

Geroprotective molecules are currently being actively investigated for the prevention of skin aging. An overview of geroprotectors in dermatology encompasses agents such as antioxidants, ultraviolet (UV) photoprotective agents, chemical peels, and carbon dioxide (CO₂) lasers, each with inherent limitations, including poor tolerability in individuals with sensitive skin. Regarding biostimulators, high-molecular-weight peptides (exceeding 500 kDa) exhibit limited cutaneous bioavailability, underscoring the need for low-molecular-weight geroprotective compounds. One such candidate is dehydroepiandrosterone DHEA, a neurosteroid with anti-aging and anti-stress properties, which also serves as a precursor to sex steroids. Although topical hormone replacement therapy with estrogens and androgens is being utilized, it remains confined to formal hormone replacement regimens and is associated with a significant adverse effect profile. The aim of this review was to analyze the key molecular mechanisms underlying the effects of DHEA on the skin, with particular emphasis on its metabolism and sex- and age-dependent mechanisms of action. Additionally, this review seeks to elucidate the factors contributing to the absence of approved topical DHEA formulations and to outline the potential of DHEA as an anti-aging agent in dermatological applications. DHEA has demonstrated significant skin-improving effects in several studies; its investigation has been predominantly confined to postmenopausal women. Furthermore, the outcome measures employed in these studies lacked specificity. DHEA is not permitted for use in cosmetic products within the European Union due to its hormonal activity. Its use is only allowed as an extemporaneous formulation under the established regulatory frameworks of individual countries. The indications for its use and the appropriate dosage for men and women must be clearly defined based on the results of future clinical studies. Promising research directions include the pharmacogenetic characterization of steroidogenic enzymes and sex hormone receptors, as well as the evaluation of DHEA in both sexes, specifically in premenopausal women and in men presenting with late-onset hypogonadism. Additionally, the biological effects of the primary metabolites of DHEA, androstenedione, and 5-androstenediol, on the cutaneous function remain unexplored, including their potential anti-aging activity mediated through retinoid receptor activation. Full article

Background: Periprosthetic joint infections (PJIs), a significant complication of total knee replacement surgery, are influenced by patient, surgeon, and healthcare system factors. Natural disasters can disrupt healthcare services and alter microbiological factors in the hospital environment. The impact of natural disasters on pathogen distribution in periprosthetic joint infection (PJI) is unclear. Therefore, this study investigated the association between the 2023 Kahramanmaraş-centered earthquakes in Türkiye and changes in microbiological patterns of PJI after knee arthroplasty. Methods: This retrospective cohort study included patients who developed PJI following total knee arthroplasty at the study center. The patients were divided into two groups based on the timing of their PJI diagnosis: pre-earthquake and post-earthquake. The demographic characteristics, comorbid diseases, and perioperative characteristics of each patient were recorded, and their microbiological profiles were analyzed. Logistic regression analysis examined the relationships between patient-related factors and causative agents. Results: 56 patients were studied and divided into two groups: 26 patients in the pre-earthquake group and 30 in the post-earthquake group. Furthermore, 79 bacterial isolates were obtained from these patients. Demographic, metabolic, and preoperative characteristics were similar between the two groups. No significant difference was found in the overall distribution of bacterial isolates. However, Gram-negative organisms, primarily Acinetobacter baumannii and Pseudomonas aeruginosa, increased in the isolate distribution after the earthquake. Patient analysis revealed that polymicrobial PJIs were significantly more frequent after the earthquake (56.7% vs. 23.1%; p = 0.011). Diabetes mellitus (DM) and smoking were associated with an increased risk of polymicrobial infection; the association was not statistically significant. Conclusions: In the post-earthquake period, patients who had undergone total knee arthroplasty and developed PJI showed a higher proportion of polymicrobial infections and a numerical increase in Gram-negative pathogens, along with more complex infection patterns compared to the pre-earthquake period. Although both patient groups demonstrated similar characteristics regarding patient-related and surgical factors, the observed changes indicate that the pressure on the healthcare system after a natural disaster can affect a hospital’s microbiological ecology. Identifying these indirect effects is crucial for guiding microbiological surveillance and infection control during post-disaster recovery periods, even for elective patients. Full article

Ambrosia beetle Platypus quercivorus is a vector of Japanese oak wilt. Only females possess 4−12 mycangial pits on the pronotum, which are essential for carrying symbiotic fungi and are thought to be a significant determinant of beetle fitness. However, the factors influencing the pit numbers remain poorly understood. To elucidate the effects of environmental conditions and parental traits on the pit number, we conducted a controlled breeding experiment. Collected P. quercivorus broods were categorized into three groups (large, middle and small) based on their average number of maternal mycangial pits. Excluding the middle groups, male−female pairs from the same group (large or small) were inoculated into Quercus crispula logs and incubated under four temperature regimes: 18, 22, 26, and 30 °C. We analyzed offspring pit number and body weight relative to temperature and parental traits. Both traits increased at lower temperatures likely because accelerated metabolism and developmental rates at higher temperatures, reduces the time and resources available for body growth and pit development. Notably, the traits exhibited distinct inheritance patterns: offspring pit number was significantly influenced by maternal pit number but not by the body weight of either parent. In contrast, offspring body weight was significantly correlated with maternal pit number, paternal body weight, and maternal body weight. Thus, we conclude that temperature plays a critical role in shaping these traits. Parental effects indicate that both mycangium pit number and body weight are heritable in P. quercivorus. However, their distinct inheritance patterns suggest a weak genetic association between the traits, implying that they may evolve largely independently. Full article