Search Results (74,812)

This study investigated the role of trpc3 in osmoregulation under salt stress in grass carp (Ctenopharyngodon idella). Tissue expression analysis showed trpc3 was highest in the brain, followed by gills, skin, and muscle. In gills and kidney, its expression increased with salinity. RNA interference using synthesized trpc3-dsRNA (2 μg/g) significantly reduced its expression. Under early salt stress, serum osmolality, Na⁺, Ca²⁺, and renal NKA activity were comparable between the interference and non-interference groups. However, gill CaN, NKA, and Ca²⁺-ATPase, as well as renal CaN and Ca²⁺-ATPase activities were significantly lower in the interference group. During late salt stress, the interference group exhibited significantly higher serum osmolality, Na⁺ concentration, and renal NKA activity than the non-interference group. Serum Ca²⁺ concentration remained unchanged between groups. Conversely, gill CaN, NKA, and Ca²⁺-ATPase, as well as renal CaN and Ca²⁺-ATPase activities were significantly lower in the interference group. Gene expression analysis revealed that early plcxd1 was higher, while trpc3, calm1a, aqp3a, nka beta 1b subunit, IL-1β, hsp70, and gill nkcc1 variant X1 were lower in the interference group. Late-stage expression showed nka beta 1b subunit (gills/kidney) and renal trpc3, nkcc1 variant X1 were higher; gill trpc3, plcxd1, aqp3a, nkcc1 variant X1, IL-1β and renal plcxd1, aqp3a, nkcc1 variant X1, hsp70 were comparable; and gill calm1a, hsp70 and renal calm1a, IL-1β remained lower in the interference group. In summary, grass carp trpc3 may mediate Ca²⁺ influx to regulate ion transport in the gills and kidney, playing a key role in restoring osmotic homeostasis. Full article

Background: To assess associations between possible dysfunction of autonomic cardiovascular modulation and hemispheric localization, seizure frequency, disease duration, and antiseizure medication (ASM) in temporal lobe epilepsy (TLE). Methods: In this prospective observational study, cardiovascular autonomic modulation was monitored in 31 patients with TLE (12 patients with right TLE, 19 patients with left TLE). From 5 min time series of R–R intervals (RRI) and blood pressure (BP) recordings, we calculated autonomic parameters of sympathetic, parasympathetic, and total autonomic cardiovascular modulation. Data were compared to those of 30 healthy volunteers. Subgroup analyses were performed according to (1) disease localization (right vs. left hemispheric TLE), (2) seizure frequency (< vs. >1/month) and disease duration (< vs. >10 years), (3) number of ASMs, and (4) participants’ age (< vs. >30 years). Results: Between right TLE patients, left TLE patients, and controls, there were no significant differences in the assessed bio-signals. Parameters of sympathetic and total autonomic modulation were slightly lower in right TLE patients than in controls. Additionally, reduced vagal modulation was observed in right TLE patients taking three ASMs or not taking any ASMs at all (applicable to one patient) compared to healthy controls. In general, TLE patients with <1 seizure/month showed lower parameters of sympathetic modulation than healthy controls, with differences reaching statistical significance in left TLE patients. In contrast, parameters reflecting vagal tone showed insignificantly, yet consistently, lower values in left TLE patients with increasing seizure frequency. Alterations in autonomic cardiovascular modulation observed across age-matched subgroups were comparable. Conclusions: A trend towards lower values of sympathetic modulation in patients with right TLE supports previous findings suggesting right hemispheric mediation of sympathetic regulation. A decrease in parasympathetic modulation with increasing seizure frequency underscores the importance of sufficient seizure control in order to prevent autonomic complications. In contrast, the absence of significant associations between disease duration and autonomic alterations suggests that epilepsy exerts an early and clinically relevant effect on the autonomic nervous system. Due to comparable alterations in autonomic modulation in a patient without antiseizure medication and in patients undergoing polytherapy, ASM side effects may not account solely for the observed autonomic dysregulation of our TLE patients. Full article

Morchella is a nutritious and artificially cultivable rare ascomycete, and its growth and development regulation mechanisms are a current research hotspot. High-temperature stress severely limits the annual yield of Morchella, and this challenge is intensifying with global warming. However, previous studies have lacked systematic screening for heat-tolerant Morchella strains, and their molecular response mechanisms to heat stress remain unclear. In this study, we conducted a comprehensive analysis of phenotypic characteristics, physiological metabolism, and transcriptomics on 19 Morchella strains under normal (25 °C) and high-temperature (30 °C) conditions. The heat-tolerant strain HLM exhibited superior performance in mycelial growth, morphology, and field cultivation. It maintained cell homeostasis under heat stress through mild osmotic regulation (elevated levels of proline, soluble sugars, and proteins), a robust antioxidant system (increased activities of CAT, POD, and SOD), and reduced malondialdehyde accumulation. Transcriptomic analysis identified a novel regulatory model of “stress perception—metabolic preparation—terminal detoxification” in the heat-tolerant strain HLM under heat stress. The rapid upregulation of the SMPD1 gene may mediate ceramide signal generation, promoting G6PDH expression to drive carbon flow into the pentose phosphate pathway, thereby increasing NADPH output. As the detoxification terminal, AKR4C uses this reducing power to eliminate toxic carbonyl end products like malondialdehyde, completing the defense loop. These findings offer new insights into the heat-tolerance mechanisms of large ascomycetes, provide a theoretical foundation for stress-resistant Morchella breeding and cultivation in high-temperature areas, and serve as valuable resources for exploring heat-tolerance mechanisms and molecular breeding in other edible fungi. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex and highly polygenic genetic architecture, in which immune-mediated mechanisms play a central role. Here, we integrated single-cell cis-expression quantitative trait loci from 14 immune cell types with AD GWAS summary statistics using a two-sample Mendelian Randomization (MR) framework to resolve cell-specific genetically mediated transcriptional effects. We identified 303 significant cell-specific gene–trait associations with limited overlaps across cell types. A multi-step prioritization strategy refined these findings to 35 genes across all 14 cell types. A comparison with whole blood cis-eQTLs revealed a limited concordance, suggesting an attenuation of cell-specific regulatory effects in bulk transcriptomic approaches. Intersecting single-cell and bulk evidence identified 22 high-confidence genes with a relatively independent mechanism of action. Integrative annotation implicated several immune-relevant and druggable genes, including IL2RA, with distinct cell-specific effects. Our findings demonstrate diverse mechanisms of risk genes for AD at the single-cell level that act across immune cell states and pathways, with implications for therapeutic interventions. Full article

Background: Broodiness is a major limiting factor for reproductive efficiency in indigenous avian breeds, a phenomenon underpinned physiologically by granulosa cell (GC) apoptosis and subsequent follicular atresia. While Serine Protease 23 (PRSS23) has been implicated in mammalian ovarian remodeling, its specific regulatory function in avian follicular dynamics remains elusive. Methods: Utilizing the Wuding chicken—an indigenous breed distinguished by robust environmental adaptability but compromised by high broodiness frequency—as a biological model, this study dissected the molecular mechanism of PRSS23-mediated follicular regression. We cloned the complete coding sequence of the Wuding chicken PRSS23 gene, characterized its spatiotemporal expression profile, and interrogated its function in primary GCs via gain- and loss-of-function assays. Results: RT-qPCR analysis revealed that PRSS23 is differentially expressed across the hypothalamic–pituitary–ovarian (HPO) axis, with ovarian expression being significantly upregulated during the broody period compared to the laying period. Mechanistically, PRSS23 overexpression significantly downregulated the expression of follicle-stimulating hormone receptor (FSHR) and key steroidogenic enzymes (STAR, CYP19A1, HSD3β1), thereby suppressing the expression of genes governing the biosynthesis potential of progesterone and estradiol. Concurrently, PRSS23 overexpression was associated with transcriptional repression of components of the PI3K/AKT/mTOR signaling cascade; this transcriptional regulation further induced cell cycle arrest at the G0/G1 phase, and activated the mitochondrial apoptotic pathway characterized by BAX upregulation and BCL2 downregulation. Conversely, siRNA-mediated knockdown of PRSS23 alleviated these inhibitory effects, promoting GC proliferation and survival. Conclusions: These findings establish PRSS23 as a pivotal pro-atretic factor in Wuding chickens, driving ovarian atrophy through the dual transcriptional-level inhibition of steroidogenesis and survival signaling pathways. This study identifies a potential molecular target for marker-assisted selection programs aimed at attenuating broodiness while preserving the superior meat quality traits of indigenous poultry. Full article

Biological soil crusts (BSCs) are critical ecological components in arid lands. Their formation and stability hinge on the assembly and interactive networks of cyanobacteria-led bacterial communities. Yet, how different functional cyanobacteria shape the underlying microbial structure and assembly rules is poorly understood. Here, we cultivated artificial algal crusts using two representative cyanobacteria: the nitrogen-fixing Leptolyngbya sp. and the non-nitrogen-fixing Microcoleus vaginatus (M. vaginatus CM01). A total of six treatments were established based on the presence or absence of spraying with in situ BSCs leachate: a control group without inoculation of algae or bacteria (soil, S); a treatment group sprayed only with bacterial suspension (soil + bacteria, SB); a treatment group sprayed only with M. vaginatus CM01 (soil + M. vaginatus CM01, SM); a treatment group co-inoculated with both BSCs leachate and M. vaginatus CM01 (soil + M. vaginatus CM01 + bacteria, SMB); a treatment group inoculated only with Leptolyngbya sp. CT01 (soil + Leptolyngbya sp. CT01, SL); and a treatment group co-inoculated with Leptolyngbya sp. CT01 and biocrust leachate (soil + Leptolyngbya sp. CT01 + bacteria, SLB). By integrating 16S rRNA gene sequencing, neutral community modeling (NCM), and structural equation modeling (SEM), we dissected differences in Cyano-BSCs development, bacterial community composition, co-occurrence networks, and assembly mechanisms. Inoculation with M. vaginatus CM01 (SM, SMB) superiorly promoted Cyano-BSCs development: the SM group achieved the highest coverage (23.33%), while the SMB group showed marked increases in organic matter (OM, 4.10 g·kg⁻¹) and chlorophyll a (Chla, 13.40 μg·g⁻¹), alongside a >5-fold rise in bacterial, cyanobacterial, and nitrogen-fixation gene abundances versus controls. The mechanism centers on extracellular polymeric substances (EPS) secreted by M. vaginatus, which homogenized the microenvironment, suppressed stochastic bacterial dispersal (NCM, SM: R² = 0.698), and enhanced deterministic selection. This process forged a highly cooperative network (89.74% positive links, average degree 34.71) that directionally enriched Cyanobacteria (relative abundance 40.40%). The Shannon index of Cyano-BSCs from the group (SMB) reached 7.72 ± 0.09, reflecting high microbial community diversity. SEM confirmed M. vaginatus directly regulated bacterial assembly (path coefficient = 0.59, p < 0.05) and indirectly improved the soil environment (path coefficient = 0.64, p < 0.05), establishing a “cyanobacteria-community-environment” feedback loop. Conversely, the Leptolyngbya sp. groups (SL, SLB), despite enriching nitrogen-fixing bacteria and fungi, exhibited low carbon fixation efficiency (notably 1.26 g·kg⁻¹ OM in SL) and lack of EPS; communities remained stochastic (NCM, SL: R² = 0.751) with no effective regulatory pathway—a pattern mirrored in S and SB groups. Our findings demonstrate that M. vaginatus acts as a core engineer of biological soil Cyano-BSCs formation via an “EPS-mediated habitat filtering—functional group enrichment—cooperative network assembly” cascade, enforcing deterministic community construction. Leptolyngbya sp., with limited niche-constructing ability, fails to exert comparable control. This work provides a targeted framework for the artificial restoration of Cyano-BSCs in arid zones. Full article

Recognition and binding to β-galactose-containing carbohydrates and lipids are crucial for several fundamental biological processes that are mediated primarily by a family of proteins known as galectins (S-type lectins). Galectins in the human placenta regulate critical processes such as maternal–fetal immune tolerance, trophoblast invasion, vascular remodeling and angiogenesis, ensuring proper fetal development and preventing pregnancy complications such as preeclampsia and miscarriage. Gestational diabetes mellitus (GDM) is a widespread complication of pregnancy, affecting approximately 1 in 7 pregnancies, and its incidence is increasing globally, indicating a particularly strong association with the obesity pandemic. Profiles of placental expression and distribution of individual galectins significantly change during the course of GDM. This is accompanied by placental dysfunction, which is especially severe with poor glycemic control. The aim of this review is to present the current state of knowledge on the involvement of abnormal galectin signaling in the pathomechanisms of GDM-associated placental dysfunction. Further research is needed to determine whether changes in placental galectins occur secondary to metabolic abnormalities in GDM or are involved as a primary cause. Galectins present in placental tissue and serum should be validated as potential biomarkers of GDM. Full article

Background/Objectives: Tuberculosis (TB) remains a major global health challenge, and the Bacillus Calmette–Guérin (BCG) vaccine has limited efficacy against adult pulmonary disease. Protein subunit vaccines are a promising alternative but require strong adjuvants to induce cell-mediated immunity. Synthetic agonists targeting toll-like receptor 4 (TLR4) and stimulators of interferon genes (STINGs) have emerged as effective immunostimulants. Therefore, we aimed to evaluate the immunogenicity and protective efficacy of Ag85B-based subunit vaccines formulated with synthetic TLR4 and STING agonists in a BCG-boosted mouse model. Methods: Three synthetic adjuvants—QTP709-1, QTP709-3, and QTP701—were formulated as oil-in-water emulsions containing distinct surfactant and immunostimulant components. The potential of vaccine formulations to activate dendritic cells (DCs) and elicit Ag85B-specific immune responses, including IgG subclass levels, interferon-γ (IFN-γ) enzyme-linked immunosorbent spots, and polyfunctional T-cell responses, was assessed by flow cytometry. Protective efficacy was evaluated based on pulmonary bacterial burden and histopathology following Mycobacterium tuberculosis (M. tb) Erdman challenge. Results: All formulations promoted DC maturation and enhanced antigen-specific immune responses. Each adjuvant elicited strong Ag85B-specific humoral immunity, increased IFN-γ secretion, and polyfunctional CD4⁺ and CD8⁺ T cells co-producing IFN-γ, TNF-α, and interleukin-2. Among them, QTP709-1 was associated with increased levels of chemokine receptor 5-associated chemokines and showed a trend toward reduced lung bacterial burden and histopathological inflammation following M. tb challenge. Conclusions: Synthetic TLR4 and STING agonists were associated with enhanced immunogenicity of TB subunit vaccines and showed evidence of protective potential, with TLR4-based formulations exhibiting more pronounced immunological responses. QTP709-1 exhibited strong immunostimulatory and protective effects, supporting its potential as a candidate adjuvant for next-generation TB vaccines. Full article

Mitochondrial dysfunction lies at the core of numerous cardiac pathologies, yet restoring mitochondrial health remains a therapeutic frontier. In recent years, extracellular vesicles (EVs) have emerged as nature’s delivery nanocarriers, capable of transporting a wide array of biomolecules, including mitochondrial-associated microRNAs (mito-miRs). These miRNAs regulate bioenergetics, redox homeostasis, and apoptotic signaling—making them prime candidates for non-cellular mitochondrial therapy. This review explores the evolving landscape of mitochondrial miRNA encapsulation within EVs, focusing on their potential to restore mitochondrial transcriptional and metabolic programs governing ATP synthesis and redox balance, enhance cellular energy output, and mitigate oxidative stress. We integrate insights from stem cell biology, RNA epigenetics, systems cardiology, and bioengineering, offering a unifying framework for therapeutic applications across ischemic heart disease, heart failure, and chemotherapy-induced cardiomyopathy. An integrative narrative synthesis of recent peer-reviewed literature was performed across major biomedical databases, prioritizing mechanistic studies linking EV-mediated mito-miR delivery to cardiomyocyte mitochondrial function. By harmonizing multi-omic signaling, vesicle engineering, and mitochondrial medicine, this review seeks to guide future research toward targeted, customizable, and scalable bioenergetic interventions—unlocking a next-generation path for cardiovascular regeneration. Full article

Browning is the major physiological cause of quality loss in lotus root. This study explored the effects of temperature (4 °C, 25 °C, 35 °C) or ethylene (ET) on quality, especially browning, as well as polyphenol and starch metabolism in lotus root. Low temperature (4 °C) reduced browning and color changes (L*, a*), while retaining water and vitamin C (Vc) content. ET maintained Vc and soluble protein, while high temperature (35 °C) promoted total soluble solids (TSS) and soluble sugar accumulation. ET or 35 °C upregulated polyphenol metabolism-related genes including NnPAL1/4, NnCHS1, NnF3H and NnANR, increased total phenolic and flavonoid content, and enhanced antioxidant capacity. Moreover, 35 °C increased PAL activity, and ET also upregulated NnUGT88B1. Furthermore, 4 °C downregulated NnGBE1-1/2, promoted starch accumulation, while ET upregulated NnSSI, downregulated NnGBE1-1/2, and delayed starch decline. Meanwhile, ET elevated NnETR and NnEBF1-2 and mediated ethylene signaling transduction. In conclusion, 4 °C storage was optimal for delaying browning and starch metabolism of lotus root. Meanwhile, ET treatment or 35 °C were more beneficial to obtain more phenolics and flavonoids. Full article

Tripterygium glycoside (TG) is known to disrupt the oxidative balance in bio-systems, inducing oxidative stress-mediated toxic effects on testicular tissue. This study aimed to explore the therapeutic potential of coumestrol (COU) against these adverse effects. Sixty-four male Sprague–Dawley rats were randomized into control and Tripterygium glycoside (TG) groups for four weeks. Following initial intervention, eight rats per group were sacrificed to verify the establishment of the oligospermia model and hormonal dysfunction. The remaining rats were subdivided into five therapeutic subgroups, TG, TG + L-carnitine, and three COU dosage groups (low, medium, and high) to evaluate potential protective effects. The present study comprehensively analyzed its impacts on testicular histomorphology, circulating testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and redox balance status, as well as a suite of serum biochemical and physiological biomarkers. Our results revealed that TG induced oligospermia in rats, causing significant testicular oxidative stress characterized by excessive accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), alongside depleted superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC). Conversely, COU treatment effectively mitigated these impairments by significantly downregulating ROS and MDA levels while restoring SOD activity and T-AOC. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, and has emerged as a common etiological factor for hepatocellular carcinoma (HCC). MASLD and MASLD-associated HCC lack specific clinical biomarkers. Extracellular vesicles (EVs) and their microRNA (miRNA) cargo have emerged as key mediators of intercellular communication and promising diagnostic tools. This review provides a systematic overview of the stage-specific roles of EV-derived miRNAs across the MASLD spectrum. We focus on how key EV-miRNAs regulate lipid metabolism, inflammatory responses, hepatic stellate cell (HSC) activation, and the remodeling of the tumor microenvironment (TME). This review provides an updated perspective on cross-stage EV-derived miRNA regulatory circuits. In addition, we critically evaluate the potential of EV-derived miRNAs as non-invasive biomarkers and therapeutic targets. By integrating mechanistic insights with clinical relevance, this review provides a comprehensive framework for the early identification, risk stratification, and precision intervention of MASLD-associated HCC. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting the central nervous system and is the most common form of dementia in the elderly. Current diagnostic methods are limited in the early and definitive diagnosis of the disease, necessitating the need for new and more reliable biomarkers. Circular RNAs (circRNAs) are non-coding, single-stranded, and highly stable RNA molecules commonly found in the eukaryotic transcriptome. Recent studies have shown that changes in the expression levels of circRNAs may play a role in AD pathogenesis. Furthermore, these molecules are considered as potential non-invasive biomarkers for early diagnosis of AD. In this study, we comprehensively assessed plasma levels of classical neurodegenerative biomarkers [amyloid-β42/amyloid-β40 (Aβ42/Aβ40) ratio, total Tau (tTau), and phosphorylated Tau (pTau)], as well as glial and inflammatory mediators, TAM receptor family members (Tyro3 and AXL), and the newly identified circular RNA molecule hsa_circ_003077. The findings revealed that the expression levels of TAM receptors were significantly increased, the Aβ42/Aβ40 ratio decreased, and both total Tau and phosphorylated Tau levels were significantly increased in AD patients. In the receiver operating characteristic (ROC) curve analysis performed to determine the diagnostic potential of hsa_circ_003077, the area under the curve (AUC) was 0.90 (95% CI: 0.82–0.97). This high AUC value suggests that hsa_circ_003077 may be a strong and novel biomarker candidate for the non-invasive diagnosis of AD. The data obtained confirmed the diagnostic efficacy of classical AD biomarkers and revealed that hsa_circ_003077 is a promising biomarker for early and accurate detection of the disease. However, in order to assess the transferability of these findings to clinical practice, confirmatory studies with larger sample groups are needed to ensure reproducibility of the results. Full article

The Mediator complex is a central regulator of eukaryotic transcription, functioning as a dynamic molecular interface between gene-specific transcription factors and RNA polymerase II (Pol II). Although its overall architecture and general role in transcription have been extensively reviewed, accumulating genetic, genomic, and clinical evidence indicates that individual Mediator subunits make distinct and non-redundant contributions to human physiology and disease. In this review, we move beyond a generic description of Mediator function and present a subunit-resolved synthesis of Mediator biology with an emphasis on disease pathogenesis. A key feature of this review is a comprehensive table integrating disease associations and molecular functions of individual human Mediator subunits, enabling rapid assessment of functional specialization across the complex. We further discuss chromatin-based mechanisms of Mediator action, including cooperation with cohesin and architectural factors to regulate enhancer-promoter communication and higher-order genome organization. By organizing recent structural, mechanistic, and pathological findings into a unified framework, this review highlights how disruption of specific Mediator subunits contributes to cancer, developmental disorders, and metabolic disease, and outlines emerging opportunities for therapeutic intervention. Full article

This study employs a difference-in-differences (DID) design to evaluate the impact of China’s Environmental Vertical Management Reform (EVMR) on urban concentrations of six major air pollutants. The findings reveal a pronounced efficacy hierarchy: the EVMR significantly reduces PM_2.5, PM₁₀, and SO₂, but its effects on the remaining pollutants are heterogeneous. We find no statistically significant impact on NO₂ or O₃, while CO exhibits a counterintuitive pattern—remaining unaffected in the immediate term but showing a significant lagged increase in the second and third years post-reform. In the year of implementation, the reform reduced PM_2.5, PM₁₀, and SO₂ concentrations by 15.4%, 15.5%, and 9.7%, respectively. While reductions for particulate matter persisted over the following two years, the effect on SO₂ was largely confined to the implementation year. Treatment effects exhibit selective heterogeneity: the SO₂ reduction was significantly stronger in less developed cities, while a far more pronounced amplification emerged for cities located in key national air pollution governance areas. Mediation analysis confirms that strengthened environmental enforcement—measured by increased imposition of penalties—operates as a significant channel for pollution reduction, with the indirect effect notably strongest for SO₂ in the reform year. In conclusion, this study provides comprehensive evidence on the differential impacts of EVMR. Our findings validate the efficacy of this centralized governance model in curbing particulate and sulfur pollution, but also highlight its limitations in addressing secondary pollutants like O₃. More alarmingly, the unintended lagged increase in CO reveals a critical pollution-shifting effect: the very measures that achieve deep SO₂ reduction may inadvertently elevate CO through interconnected engineering pathways. These insights are crucial for designing more targeted, multi-pollutant control policies in China and other transitioning economies. Full article