Search Results (638)

The scientific evidence regarding the use of plant-derived extracts to alleviate exercise-induced muscle damage in horses remains limited. Mulberry leaf flavonoids (MLFs) are the primary bioactive constituents of a traditional medicinal plant and are potent antioxidants. The aim of this study was to investigate the protective effects of MLFs against exercise-induced muscle damage. In this study, twelve Mongolian horses were used in a 3 × 3 Latin square design to investigate the protective effects of MLFs. Our results showed that high-intensity exercise negatively impacted the immune status, metabolic state, myofibrillar structure, and antioxidant capacity of the horses. Conversely, MLFs significantly reduced blood levels of white blood cells (WBC), monocytes (MON), aspartate aminotransferase (AST), creatine kinase (CK), and malondialdehyde (MDA) across various exercise distances and during recovery. Simultaneously, MLFs increased serum glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC). Mechanistically, transcriptomic analysis revealed that dietary MLFs upregulated genes associated with myofibrillar structural proteins (MYOZ2, MYOM3), the antioxidant defense system (GPX3, SOD3), and skeletal muscle satellite cell proliferation and differentiation (MYOD1, MRF6). Furthermore, quantitative proteomics indicated the enrichment of the PI3K-Akt and TGF-β signaling pathways, as well as ECM–receptor interactions, suggesting their potential involvement in regulating protein metabolism and facilitating myofibrillar restoration. Overall, MLFs effectively alleviated inflammation, metabolic disorder, and exercise-induced muscle damage. Under the tested conditions, a daily dosage of 10 g MLFs provided superior protective effects. Full article

To enhance nitrogen removal in low-carbon sewage through heterotrophic and sulfur autotrophic denitrification, a corncob-sulfur circulating packed-bed reactor (CS-CPBR) and a PHBV-sulfur circulating packed-bed reactor (PS-CPBR) were constructed. The results showed that the total nitrogen (TN) and NO₃⁻-N removal efficiencies of both reactors improved with increasing hydraulic retention time(HRT) and NaHCO₃ dosage. With a HRT of 2 h, a NaHCO₃ dosage of 0.4 g/L, and an influent NO₃⁻-N concentration of 30 mg/L, the TN removal efficiencies were 87.9% and 94.0%, respectively. The PS-CPBR exhibited a higher nitrogen removal rate and efficiency. Mechanistic studies indicated that the lower bioavailability of corncob restricted microbial activity in the CS-CPBR, leading to the difference in denitrification efficiency between the two reactors. Metagenomic analysis revealed that, relative to the CS-CPBR, the PS-CPBR significantly enriched denitrifying bacterial genera such as Sinirhodobacter, Rhodobacter, and Brachymonas. The PS-CPBR also harbored higher abundances of denitrification genes (nirS, norC, nosZ), thereby strengthening the complete denitrification pathway. This study provides experimental data to guide carbon source selection and process control for solid carbon-sulfur denitrification in advanced nitrogen removal. Full article

Carbonic anhydrases (CAs) efficiently catalyze CO₂ reversible hydration, critical for carbon capture and sequestration (CCS), but naturally low yield limits industrial use. Yarrowia lipolytica, an unconventional yeast, is an ideal heterologous expression host with robust adaptability, post-translational modification capacity, and versatile genetic tools. In this study, 10 α-, β-, and γ-class CAs were successfully expressed in Y. lipolytica, and two top-performing candidates were identified: Methanosarcina mazei γ-CA (MmaCA) and Sulfurihydrogenibium azorense α-CA (SazCA). Their production was further optimized via promoter and gene dosage adjustment, cultural condition optimization and auxiliary protein co-expression. The optimized intracellular MmaCA activity reached 960 U/mL (64.42-fold improvement), and the extracellular SazCA activity peaked at 925 U/mL (70.08-fold enhancement). CO₂ mineralization experiments confirmed both recombinant CAs significantly accelerated CaCO₃ precipitation, demonstrating a promising CCS application potential. To our knowledge, this is the first systematic investigation of CA heterologously expressed in Y. lipolytica, providing a novel strategy for the highly efficient production of CAs to enable their application in industry. Full article

Copy number variations (CNVs) are a major source of structural genomic diversity that influences adaptation, reproduction, and production traits in livestock. The Black Bengal goat, an economically important Indian breed known for its high fecundity, superior skin quality, and resilience to humid tropical climates, was studied to uncover its structural genomic landscape. We performed whole-genome CNV analysis using high-depth (10×) sequencing data from eight individuals. A total of 31,816 copy number variants (CNVs) were identified, predominantly duplications, with an average length of approximately 45 kb. These CNVs were combined into 8910 copy number variation regions (CNVRs) covering approximately 0.15 Gb (about 5.3% of the autosomal genome). CNVR hotspots were mainly located on chromosome 1. Gene annotation showed that regions overlapping with CNVs and CNVRs contained more than 1987 protein-coding genes involved in pathways related to immunity, reproduction, metabolism, and extracellular matrix (ECM) organization. The presence of CNVs involving genes such as GDF9 and BMPR1B on chromosomes 7 & 6, respectively, is important because it indicates that the breed has a high reproductive capacity due to dosage-sensitive duplications. Changes in the extracellular matrix and increased dermal strength have been linked to duplications of genes such as COL6A1, LAMC2, LAMB3, FMN1, and CLDN1. This helps explain the superior hide quality of the breed. This research offers a comprehensive map of CNVs and CNVRs within the genome of the Black Bengal goat. It demonstrates how these duplications lead to structural changes that enhance both reproductive performance and skin resilience. These findings provide a valuable genomic resource for future marker-assisted selection, comparative genomics, and conservation breeding programs aimed at preserving indigenous goat populations. Full article

Background: Chromosome 7 gain (chr7 gain) is a highly prevalent early event in glioblastoma (GBM). Because chr7 gain usually involves broad chromosomal amplification, its biological impact is unlikely to be fully explained by canonical loci such as EGFR and MET. The contribution of less-characterized, dosage-sensitive genes on chromosome 7 remains insufficiently defined. This study aimed to identify additional chr7 candidates associated with malignant phenotypes in GBM. Methods: Transcriptomic, copy-number, and clinical data from TCGA-GBM and TCGA-LGG were analyzed to characterize chr7-gain-associated alterations and prioritize candidate genes. Refined GBM and histologic GBM cohorts based on the WHO 2021 framework were used for candidate selection. RPA3-associated pathway features were examined using ssGSEA, PROGENy, WGCNA, and protein–protein interaction analysis, with external validation in the CGGA-693 cohort. Single-cell RNA-seq analysis compared chr7-gain and chr7-normal-copy tumor subclusters. Functional relevance was evaluated by siRNA-mediated knockdown in U87 and U118 cells. Results: Chr7 gain was enriched in high-grade IDH-wildtype gliomas and was associated with cell-cycle- and DNA repair-related programs. RPA3 was prioritized as a dosage-sensitive chromosome 7 candidate based on its upregulation in chr7-gain tumors, association with poor prognosis, and concordance with replication- and repair-related signatures. In vitro, RPA3 knockdown impaired cell growth, proliferation, colony formation, and migration. Single-cell analysis suggested greater transcriptomic and network-level relevance of RPA3 in chr7-gain tumor cells. Conclusions: RPA3 is a dosage-sensitive chromosome 7 candidate associated with aggressive and replication-/repair-related phenotypes in GBM. Increased RPA3 expression may contribute to the selective advantage associated with chr7 gain, which supports further investigation as potential therapeutic target. Full article

Cotton, as a globally significant economic crop, is intricately regulated in its growth and development by the key genes for SA (Salicylic acid) biosynthesis. In the present study, a systematic analysis of genes related to SA biosynthesis was conducted across four cotton species, leading to the identification of 70 genes. Specifically, the tetraploid species Gossypium hirsutum and G. barbadense were found to harbor 22 and 23 genes, respectively, representing a substantial expansion compared to the 12 and 13 genes identified in the diploid progenitors G. arboreum and G. raimondii. Comprehensive characterization of chromosomal localization, phylogeny, domain architecture, and promoter cis-elements revealed a uniform distribution of key genes involved in SA biosynthesis across A/D sub-genomes of tetraploids with extensive interspecific collinearity; whole-genome and segmental duplication act as the dominant drivers for the expansion of this gene family, while partial gene loss following polyploidization results in non-doubled gene copy numbers in tetraploids relative to diploids, which reflects the evolutionary selection for genomic dosage balance. The key genes for SA biosynthesis demonstrate a high degree of conservation in protein sequences, protein structures, and conserved motifs, which constitute the structural basis for the stable maintenance of their core functions in the SA biosynthesis pathway during plant evolution. This is closely related to their core function in the salicylic acid (SA) synthesis pathway and serves as the structural basis for the stable maintenance of gene functions during evolution. Analysis of cis-elements revealed that the expression of key genes involved in SA biosynthesis is governed by a complex interplay of phytohormones, stress signals, and transcription factors. Yeast one-hybrid (Y1H) assays confirmed the interaction between the GhPAL and GhICS gene and predicted candidate transcription factors, specifically the binding of GhWRKY21 to GhICS2-1 promoter and GhMYB12 to GhPAL1-2 promoter, thus elucidating their stage-specific regulatory mechanisms in cotton fiber development and reflecting their evolution. This study provides a fundamental basis for investigating the role of the SA signaling pathway in cotton development and offers support for cotton molecular breeding. Full article

Ovarian cancer (OC) remains the deadliest gynecological malignancy, with aged tumor microenvironments linked to poorer outcomes. Our prior work identified reduced levels of free fatty acids (FFAs) within tumor-surrounding adipose tissue of aged OC xenograft rats compared to younger counterparts. In this study, we investigated the therapeutic potential of one such FFA, punicic acid (PunA). We evaluated PunA’s effects on OC and normal cell viability and compared its activity with that of its structural isomer, α-eleostearic acid (α-ESA). Both compounds decreased OC cell viability; however, α-ESA was cytotoxic to normal cells, whereas PunA selectively impaired OC cell viability while sparing normal cells. Additionally, PunA enhanced cisplatin efficacy, demonstrating its potential for use in combination therapy to reduce cisplatin dosage and toxicity without compromising antitumor activity. Mechanistically, PunA induced ferroptosis in OC cells while sparing normal cells by differently modulating lipid peroxidation, fatty acid oxidation, and mitochondrial function. Transcriptomic profiling further revealed coordinated gene expression changes associated with oxidative stress and ferroptosis in PunA-treated OC and normal cells. In a preliminary C57BL/6J-ID8 OC mouse model, PunA suppressed tumor growth. Collectively, these findings identify PunA as a promising therapeutic candidate for OC, acting through ferroptosis and mitochondrial dysfunction, and enhancing cisplatin efficacy while sparing normal cells. Full article

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Its main contributors are obesity, insulin resistance, diabetes and metabolic syndrome. Liver pathogenesis exacerbates when oxidative stress, inflammation, lipid accumulation, and attenuated autophagy signals coexist together with the main determinants of the liver disease. These findings may indicate that the suppression of the disease requires multi-targeting compounds to alleviate more than one factor, resulting in improved histopathological outcomes. This review studies natural compounds, given as supplements, with antioxidant and anti-inflammatory properties. The compounds included are vitamins, carotenoids, low-molecular-weight thiol-containing compounds, fatty acids and others that have been investigated for their pleiotropic activity alone or in combination. They act at different pathways and signals, and at gene expression control, modulating oxidative stress and inflammation, such as collagen, TNF-α, NF-κB, Nrf2 and PPARs genes. Their mechanism of action and characteristics may be encouraging treatment options as multi-targeting compounds for NAFLD and other diseases whose pathophysiology is closely related to metabolic syndrome. However, extensive study on their safety, toxicity, mechanisms of action and dosage regimen is needed before their final establishment as potential treatment options. Full article

Down syndrome (DS), caused by trisomy 21, is the most prevalent genetic condition associated with accelerated aging and near-universal development of early-onset Alzheimer’s disease (AD). Beyond gene-dosage imbalance, trisomy 21 induces widespread transcriptional, metabolic, and proteomic remodeling that establishes a chronic state of proteotoxic and oxidative stress from early development. Increasing evidence identifies DS as a disorder of proteostasis network failure, in which sustained translational pressure, redox disequilibrium, and degradation pathway insufficiency progressively erode cellular resilience. In the DS brain, persistent endoplasmic reticulum stress with PERK-dominant signaling, mitochondrial dysfunction characterized by oxidative phosphorylation deficits and excessive reactive oxygen species production, and impaired antioxidant responses create a highly vulnerable intracellular environment. Concomitantly, degradation systems become compromised: proteasomal catalytic activity declines, ubiquitin-dependent signaling is remodeled, and chronic mTOR hyperactivation suppresses autophagic and mitophagic flux. The coordinated impairment of the ubiquitin–proteasome system and autophagy establish a feed-forward cycle of proteotoxic accumulation and redox amplification. Within this framework, Alzheimer-like neuropathology in DS emerges not solely from amyloid precursor protein triplication but as the late manifestation of decades-long proteostasis exhaustion. Therapeutic strategies aimed at restoring global proteostasis and redox balance may therefore represent a more effective systems-level approach to mitigating neurodegeneration in DS. Full article

Background/Objectives: The growing prevalence of obesity necessitates innovative gut-targeted material strategies to modulate diet-associated metabolic dysfunction. This study investigates a spray-dried konjac glucomannan–montmorillonite (KGM-MMT) hybrid designed to integrate fermentable polysaccharide properties with luminal lipid-adsorptive clay functions within a single micro-engineered formulation. Methods: In HFD-fed mice treated for 42 days with 2% w/w KGM-MMT, cumulative body weight gain was attenuated by 7.6%, with an AUC of 5094 ± 52.95, compared to 5513 ± 81.35 in HFD controls (p < 0.0001). Results: Serum IL-6 concentrations were reduced by 97% (p = 0.0002), while blood glucose decreased by 46% (p < 0.0001); these effects were greater than those observed with MMT (24%, p = 0.0271) and KGM (16%, ns). Gut microbiota profiling demonstrated a significant 6.2-log₂-fold increase in Lactobacillaceae (p = 0.023) and a 2.4-log₂-fold increase in Enterococcaceae (p = 0.015) following KGM-MMT treatment. Functional shifts inferred from 16S rRNA gene-based prediction indicated a 1.9-fold increase in short-chain fatty acid-related pathways and a 5.4-fold increase in bile acid deconjugation pathways. Conclusions: Although the KGM-MMT hybrid did not consistently outperform its individual components across all endpoints, it consolidated complementary KGM- and MMT-associated effects within a single dosage form. These findings support spray-dried KGM-MMT as a gut-targeted biomaterial strategy that integrates multiple luminal and microbiota-associated functions within a single formulation. Future studies should define dose–response relationships, validate microbiota-derived functional predictions using higher-resolution approaches, and assess durability and safety under longer-term exposure. Full article

Bacterial stem and root rot (BSRR), caused by Dickeya dadantii, poses a severe threat to global sweetpotato production, yet the genetic architecture underlying resistance remains elusive. To dissect these mechanisms, we conducted a high-resolution genome-wide association study (GWAS) on 135 diverse accessions, integrating two-year field phenotyping with best linear unbiased prediction (BLUP) and 6.8 million single-nucleotide polymorphism (SNP) markers. This approach mapped nine quantitative trait loci (QTLs) exhibiting significant allelic dosage-dependent effects, with the major locus, qBSRR.6.1 was the primary discriminator between resistant and susceptible genotypes. Crucially, transcriptomic profiling within these loci revealed distinct expression patterns: IbTCP5 and IbERF003 (located in qBSRR.5.1 and qBSRR.6.2) were highly expressed in the susceptible cultivar ‘Xinxiang’ but suppressed in the resistant ‘Guangshu87’. Furthermore, BSRR challenge identified IbPUB4, IbKCS5, and IbLig1 as priority candidate genes involved in defense, with expression patterns suggesting roles in ubiquitin-mediated protein turnover, cuticular wax biosynthesis, and DNA repair, respectively. In stark contrast, IbPUB25 was constitutively upregulated in ‘Xinxiang’, potentially acting as a negative regulator of immunity via degradation of target proteins. These findings elucidate the polygenic, dosage-sensitive nature of BSRR resistance and prioritize specific targets for future functional characterization. Pyramiding favorable alleles of positive candidates while silencing potential negative regulators like IbPUB25 offers a promising avenue for developing durable, high-resistance sweetpotato varieties. Full article

The efficient resource utilization of duck manure and agricultural/forestry wastes (AFW) plays a significant role in environmental protection and promoting the sustainable development of the economy and society. This study examined the effects of hydrochar derived from AFW in the anaerobic digestion (AD) process, determining the optimal addition ratio. This research systematically investigated the impact of hydrochar on methane yield, as well as changes of short-chain fatty acids, microbial community dynamics, and metabolic pathways during AD of duck manure. The underlying mechanisms were clarified by metagenomic and metabolomic analyses. This experiment used duck manure as substrate and added hydrochar of four different dosage levels. Laboratory batch tests ran for 32 days at 37 ± 0.5 °C, with three parallel samples for each group. The results indicated that hydrochar additive significantly improved methane yield (p < 0.05), with a maximum increase of 27.13% at an optimal dosage of 10.91 g·L⁻¹. This amendment enhanced the abundance of Firmicutes, Bacteroidota, Chloroflexota, Halobacteriota, and Methanosarcina significantly. Compared to the control group, the abundances of functional genes involved in hydrolysis, acidogenesis, and acetogenesis pathways increased by 28–254% in the optimal treatment group, with methanogenesis-related genes showing a 16–155% enhancement (p < 0.05). Full article

Accurate sex identification in reptiles with genotypic sex determination is essential for breeding management, veterinary care and evolutionary research, yet commonly used methods are often invasive, stressful or unreliable. This study aimed to evaluate a dosage-based quantitative PCR approach for molecular sex determination in caenophidian snakes, using naturally shed epidermal skin as a non-invasive DNA source. Genomic DNA extracted from shed skin was analysed by qPCR targeting conserved Z-linked genes (ADARB2, ARMC4 and TANC2), together with autosomal and reference genes, to assess sex-specific differences in gene copy number. Sixteen caenophidian snake species were examined, including taxa for which molecular sexing data are currently scarce or unavailable. The autosomal control gene showed dosage ratios close to parity between sexes, supporting DNA quality and reference gene reliability; meanwhile, Z-linked markers generally exhibited reduced dosage in females relative to males, consistent with a ZZ/ZW sex determination system. These results demonstrate that dosage-based qPCR applied to shed epidermal skin provides a promising and non-invasive framework for molecular sex determination in caenophidian snakes, without compromising animal welfare. Full article

Background: Menstrual migraine (MM), including pure menstrual migraine (PMM) and menstrually related migraine (MRM), is characterized by attacks occurring in close temporal association with menstruation and is often more severe, longer lasting, and less responsive to treatment than non-menstrual migraine. Prostaglandin-mediated inflammation and calcitonin gene-related peptide (CGRP) release play a key role in MM pathophysiology. Phycocyanin (PC) and palmitoylethanolamide (PEA) are nutraceutical compounds with anti-inflammatory, analgesic, and neuroprotective properties that may be beneficial as short-term perimenstrual prophylaxis. Objectives: To evaluate the effectiveness of an oral supplementation combining phycocyanin and palmitoylethanolamide as a short-term prophylaxis for menstrual migraine in a real-world clinical setting, a retrospective observational study without a control group was conducted in five Italian centers between May 2023 and June 2025. Methods: Clinical records of 800 women were reviewed, and 220 patients receiving perimenstrual supplementation with phycocyanin and palmitoylethanolamide were screened. Sixty-one women diagnosed with migraine without aura, according to the International Classification of Headache Disorders, met all inclusion criteria and were analyzed. Phycocyanin and palmitoylethanolamide were taken at a dosage of two capsules daily from five days before to five days after the onset of menstruation for three consecutive months. Outcomes during the perimenstrual window were compared with a three-month period without supplementation. Primary outcomes included migraine severity, frequency, and duration of the attacks; secondary outcomes included analgesic consumption and menstrual migraine-associated symptoms. Results: Among the 61 included patients, phycocyanin and palmitoylethanolamide supplementation was associated with a significant reduction in migraine severity across all monitored perimenstrual days (p < 0.0001). While the overall monthly frequency of migraine attacks did not change, the number of migraine days during the perimenstrual window significantly decreased from the first month of supplementation (p < 0.05). Moreover, migraine duration during the perimenstrual window was significantly reduced at one, two, and three months of phycocyanin and palmitoylethanolamide supplementation compared with baseline. Analgesic use and the number of days with migraine-associated symptoms (nausea, vomiting, photophobia/phonophobia) were also significantly reduced. Treatment was well tolerated. Conclusions: In this real-world retrospective study, perimenstrual supplementation with phycocyanin and palmitoylethanolamide was associated with reduced severity, duration, and perimenstrual frequency of menstrual migraine attacks, along with decreased analgesic use, suggesting a safe and potentially beneficial short-term prophylactic strategy for women with menstrual migraine. Full article

Lactiplantibacillus plantarum LP28 (LP28), isolated from traditional Taiwanese dried tofu, has been demonstrated to have substantial probiotic potential because it increases the production of short-chain fatty acids (SCFAs) and strengthens anti-inflammatory responses. In this study, the safety of LP28 was assessed using both in vitro and in vivo approaches, including whole-genome sequence analysis, the Ames bacterial reverse mutation assay, a chromosomal aberration test, a rodent peripheral blood micronucleus test, a 28-day subacute oral toxicity assay, and an assessment of hemolytic activity. In vitro phenotypic evaluation revealed that LP28 exhibited no hemolytic activity and was susceptible to all the tested antibiotics except kanamycin. In vivo assessments revealed no significant alterations in reticulocyte counts or micronuclei incidence in ICR mice, and SD rats exhibited no subacute toxicity at an oral LP28 dosage of 2000 mg/kg body weight/day for 28 days. Moreover, a whole-genome sequence analysis of LP28 revealed the absence of antimicrobial resistance genes, harmful virulence factors, and genes associated with biogenic amine synthesis. Additionally, the presence of genes involved in stress responses (e.g., acid, bile salt, heat, osmotic, and oxidative stresses) and adhesion-related genes was confirmed. Furthermore, LP28 contains six genes (plnA, plnE, plnF, plnJ, plnK, and plnN) that encode bacteriocin precursor peptides, suggesting the potential for enhanced probiotic effects through the production of antimicrobial plantaricins. These findings highlight the potential of LP28 as a safe and effective probiotic for human consumption. Full article