Search Results (20,409)

Growing evidence has revealed that gut dysbiosis is associated with the development of anxio-depressive disorders through mechanisms that involve neuroimmune signaling, neurotransmitter changes, and neuroplasticity in the brain. This study investigated the effects of gingerol-enriched ginger (GEG) on specifically anxiety-related neuroinflammation-, neuroimmunity-, neuroplasticity-, neurotransmission-, and neurotoxicity-associated genes in different brain regions, as well as on alterations linked to colonic microflora-driven dysbiosis, in the spinal nerve ligation (SNL) rat model of neuropathic pain (NP). Twenty-seven male rats were assigned to 3 groups: sham, SNL, and SNL-treated with GEG at 200 mg/kg body weight (SNL+200GEG) via oral gavage for 5 weeks. Anxiety-like behavior was assessed on the elevated plus maze (EPM). mRNA expression was assessed by qRT-PCR using respective primers. Correlation between behavioral parameters and colonic microbiome composition was analyzed using the Spearman rank correlation. The SNL+200GEG group demonstrated decreased anxiety-like behavior in the SNL model. Compared to the SNL group, the SNL+200GEG group had increased mRNA expression of NRF2 (amygdala: left), LXRα (amygdala: both sides), and CX3CR1 (amygdala: both sides, hippocampus: right). GEG modulated neuroplasticity as shown by increased gene expression of PGK1 (amygdala: right, hippocampus: both sides), MEK1 (frontal cortex: both sides), LDHA (frontal cortex: both sides), GPM6A (frontal cortex: both sides, amygdala: right, hippocampus: right, and hypothalamus), and GLUT1 (amygdala: right) as well by decreased gene expression of HIF1α (in all brain regions except for the hypothalamus). GEG modulated neurotransmission via clearance of excessive glutamate release as suggested by increased gene expression of SLC1A3 (frontal cortex: both sides, hippocampus: right) and via augmenting mGluR5 signaling as shown by increased gene expression of GRM5 (hippocampus: both sides, hypothalamus) as well as downregulation of KMO, HAAO, GRIN2B, and GRIN2C influencing downstream serotonergic neurotransmission and NMDA receptor-mediated glutamatergic pathways in different brain regions. GEG further alleviated neurotoxicity through downregulated gene expression of SIRT1, KMO, IDO1, and HAAO in different brain regions. Moreover, the increased relative abundance of Bilophila spp., accompanied by decreased time spent in the EPM open arms, suggests that increased Bilophila abundance increases anxiety-like behavior. GEG supplementation mitigated anxiety-like behavior in male rats with NP, at least in part, by reducing SNL-induced inflammatory sequelae-related mRNA gene expression in different brain regions. In addition, there is a positive correlation between the abundance of Bilophila wadsworthia and the degree of anxiety-like behavior. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a devastating complication arising primarily after invasive dentoalveolar procedures in patients treated with antiresorptive, antiangiogenic, or targeted therapies. Although recognized risk factors are established, the distinctive vulnerability of jawbones compared to long bones is not fully understood. This review comprehensively synthesizes recent advances regarding the embryological, anatomical, and physiological disparities that contribute to region-specific susceptibility to MRONJ. Recent evidence suggests that jawbones diverge significantly from long bones in embryonic origin, ossification pathways, vascular architecture, innervation patterns, and regenerative capacities. These differences affect bone metabolism, healing dynamics, response to pharmacologic agents, and local cellular activities, such as enhanced bisphosphonate uptake and specialized microcirculation. Experimental and clinical evidence reveals that mandibular periosteal cells exhibit superior osteogenic and angiogenic potentials, and the jaws respond differently to metabolic challenges, trauma, and medication-induced insults. Furthermore, site-specific pharmacologic and inflammatory interactions, including altered periosteal microcirculation and leukocyte–endothelial interactions, may explain the development of MRONJ, although rare cases of medication-related osteonecrosis have also been reported in long bones. Emerging research demonstrates that immune dysregulation, particularly M1 macrophage polarization with overexpression of matrix metalloproteinase-13 (MMP-13), plays a crucial role in early MRONJ development. Understanding these mechanisms highlights the critical need for region-specific preventive measures and therapeutic strategies targeting the unique biology of jawbones. This comparative perspective offers new translational insights for designing targeted interventions, developing tissue engineering solutions, and improving patient outcomes. Future research should focus on gene expression profiling and cellular responses across skeletal regions to further delineate MRONJ pathogenesis and advance personalized therapies for affected patients. Full article

Ganoderma tsugae is a typical white-rot fungus capable of decaying both coniferous and broad-leaved trees and is also used in traditional Chinese medicine for its immunomodulatory and anticancer properties. To elucidate the molecular basis of its broad substrate adaptability, we performed integrated genomic and transcriptomic analyses of two G. tsugae strains (collected from Xingjiang on Betula and Jilin on Larix). The high-quality genomes of G. tsugae Wu 2022 from Xinjiang (40.8 Mb, 12,496 genes) and G. tsugae Cui 14110 from Jilin (45.6 Mb, 13,450 genes) were obtained. There are enriched gene families related to carbohydrate-active enzymes (CAZymes) in two G. tsugae strains. Notably, specific CAZyme families implicated in hemicellulose (GH16), chitin metabolism (GH18), and ester bond cleavage (CE10) were prominently expanded. Transcriptome analyses under the induction of Betula and Larix sawdust revealed a core adaptive response. A total of 5558 genes were differentially expressed, including 2094 up-regulated and 3464 down-regulated genes. Most differentially expressed genes (DEGs) were annotated as “catalytic activity”, “metabolic processes” and specific functions such as nutrient transport (“MFS transporter”), and lipid metabolism (“3-oxoacyl-[acyl-carrier protein] reductase”). In addition, a conserved suite of the eleven shared DEGs were annotated as “Heat shock protein 9/12”, “alcohol dehydrogenase”, and “Cytochrome p450” related to secondary metabolites biosynthesis, transport, and catabolism. Based on the annotation results, the wood degradation mechanism of G. tsugae can be described as synthesizing and secreting degradation enzyme system to obtain energy, using protective enzyme systems to ensure its own health, and employing a transport enzyme system to recycle metabolic capacity. This progress ensures the environmental adaptability and high degradation efficiency of G. tsugae during wood degradation. Full article

Safe overwintering is a challenging issue in rearing management that is inevitably faced by beekeepers in high-latitude regions. Under the combined influence of multiple factors, the overwintering loss rate of Western honey bees has risen continuously, and investigating the molecular mechanisms related to safe overwintering has become key. The Hunchun bee, an Apis mellifera ecotype in Jilin Province, China, exhibits strong overwintering ability during an overwintering period of more than five months. To investigate the molecular mechanisms of its cold resistance, we conducted a comparative transcriptomic analysis between the summer breeding period (July) and different overwintering intervals (November, December, January, and February), and then systematically identified key genes and signaling pathways related to cold resistance. The results showed that the highest number of differentially expressed genes (DEGs) was found between December and July. Compared with July, the upregulated genes in Hunchun bee in December were significantly enriched in several pathways, such as ion transport and neuroactive ligand–receptor interactions, and the downregulated genes were significantly enriched in pathways related to fatty acid metabolism, glutathione metabolism, and the peroxisome. Notably, a total of 378 shared DEGs were obtained from the four comparison groups, and several candidate cold-resistant gene families, such as AFPs, HSPs, C₂H₂-ZFPs, STKs, and LRRCs, were identified among the shared DEGs of the winter season. Additionally, 749 shared DEGs related to protein modification and metabolic process regulation were identified between the four successive overwintering intervals. Four shared genes, including sensory neuron membrane protein 1 (SNMP1), were revealed by pairwise comparison of the four intervals. The above results collectively indicate that the Hunchun bee attenuates winter-induced stress responses during the overwintering process by maintaining osmotic pressure balance, reducing fatty acid metabolism, increasing antioxidant capacity, and synthesizing cold-resistant macromolecular proteins. It was also found that chemical signal perception may serve a role in maintaining the stability of the overwintering bee colony. The key genes and pathways related to cold resistance identified in this study not only provide a basis for explaining the overwintering molecular mechanism for Apis mellifera of Hunchun bee but also offer key data to improve overwintering management strategies for Western honey bees. Full article

The polyphagous pest Oxycetonia jucunda Faldermann can cause substantial damage to a range of economically important crops, with the adult beetles feeding directly on floral tissues and young leaves. RT-qPCR is widely used to analyze gene expression, for which the selection of stable reference genes is essential for enabling an accurate normalization of expression. However, no systematic evaluations of suitable reference genes for RT-qPCR analysis using different tissues of O. jucunda have been conducted. To assess their applicability as reliable normalization controls, we used five computational methods to examine the stability of seven potential reference genes (GAPDH, EF1α, RPS3, RPS18, RPL18, RPS31, and UBC5A) across six adult tissues, with three biological replicates per tissue. The findings revealed RPS3 and RPS31 to be the most stably expressed. This pair of reference genes was further validated by normalizing the expression of the odorant-binding protein 3 (OBP3) target gene. Our findings will provide important foundational data for the accurate analysis of functional gene expression in O. jucunda. Full article

To systematically investigate how the olfactory system of Bombus terrestris adapts to its social division of labor and reproductive strategies, this study integrated the micromorphology of antennal sensilla and the expression profiles of olfactory receptor (OR) genes from the heads of its three castes (workers, drones, and queens) for a multi-level analysis. Scanning electron microscopy (SEM) revealed that drones possess significantly longer chaetic sensilla (Sch), sensilla trichodea (Str A/B), and sensilla basiconica (Sba A), as well as larger-diameter sensilla coeloconica (Sco) compared to workers and queens, indicating structural and functional specialization for sensitive detection of single key signals (e.g., queen pheromones). In contrast, workers and queens exhibited a more complete composition of sensilla types and a higher sensilla distribution density, suggesting the construction of a perceptual system capable of processing multiple chemical signals simultaneously. RNA-seq combined with qRT-PCR confirmed the significant upregulation of seven OR genes (e.g., BterOR3, BterOR4) in drones, while workers showed upregulation of BterOR3/5/7 accompanied by enrichment of P450 detoxification pathways. Phylogenetic analysis suggested that BterOR5 serves as a conserved co-receptor, and some OR genes may originate from recent duplication events. In summary, distinct differences were observed in the morphological structure and molecular expression of the olfactory system among B. terrestris castes. Drones exhibited structural and gene expression features consistent with specialization in queen pheromone detection, while workers and queens demonstrated sensilla diversity and olfactory receptor expression patterns indicative of a broader response capacity to diverse chemical signals. These findings support the view that the olfactory system has undergone multi-level adaptive evolution driven by social division of labor and reproductive roles. Full article

The goal of this study was to elucidate the genetic and molecular regulatory mechanisms underlying agronomic traits in elite alfalfa (Medicago sativa L.). Through the analysis of 44 varieties and lines, we measured 19 yield-related traits and performed transcriptome sequencing to investigate the factors driving yield variation. The results indicated extensive variation in agronomic traits among the tested accessions, with the coefficients of variation (CVs) ranging from 7.85% to 42.66%, suggesting substantial potential for genetic improvement. Correlation analysis revealed that seed yield was significantly and positively correlated with the number of reproductive branches and inflorescences at maturity, whereas early vegetative growth was negatively correlated with 100-seed weight. The 44 accessions were categorized into three clusters: Cluster II (the largest group) exhibited balanced traits; Cluster I showed vigorous early growth but low pod yield; and Cluster III was characterized by the highest pod and branch numbers. Principal Component Analysis (PCA) explained 65.88% of the total variation (first six components), identifying GNS31 and GNS43 as the superior and inferior genotypes, respectively. Furthermore, transcriptome profiling detected the highest number of differentially expressed genes (10,089 DEGs) in pod tissues, with 66% being upregulated. Functional enrichment analyses (GO and KEGG) highlighted that varietal differences were primarily enriched in secondary metabolism, lipid metabolism, and plant hormone signal transduction pathways. Notably, within the auxin pathway, the SAUR and GH3 families displayed significant tissue-specific expression in pods. Full article

Background: Pancreatic adenocarcinoma (PAAD), often referred to as the “king of cancers,” remains poorly understood in terms of the regulatory mechanisms involving brown adipocytes (BAs). Methods: Bioinformatics approaches were employed to explore the role of BAs in PAAD progression, utilizing transcriptomic data from public databases. Prognostic genes were identified through differential expression analysis, univariate Cox regression, and machine learning. A risk model categorizing patients into high- and low-risk groups was developed, accompanied by a nomogram. Functional analysis, immune microenvironment profiling, somatic mutation analysis, and drug sensitivity testing were performed, with further validation via gene localization, immunohistochemistry, and clinical sample analysis. Results: Six prognostic genes (SERPINB5, CALU, TFRC, LY6D, SFRP1, and GBP2) were identified, with the model and nomogram exhibiting robust predictive performance. Notable differences between the high- and low-risk groups were found in immune pathways, cell infiltration, tumor mutational burden, and drug sensitivity (e.g., axitinib). Conclusions: SERPINB5, SFRP1, and TFRC were highly expressed in PAAD samples, providing new insights into potential therapeutic strategies in PAAD treatment. Full article

Epstein-Barr virus (EBV) infection shows the strongest causative association with multiple sclerosis (MS), but its contribution to disease progression and the mechanisms allowing for viral persistence in the MS brain are still elusive. Studies in post-mortem MS brain tissue indicate an ongoing yet ineffective antiviral immune reaction in advanced stages of the disease. EBV has evolved strategies to evade immune recognition and clearance by the host immune system during both the latency and lytic phase of its life cycle. Recent evidence demonstrates that cells expressing EBV latent membrane protein (LMP) 2A exploit the PD-1/PDL1 inhibitory immune checkpoint to escape immune surveillance and maintain a persistent latent infection in the MS brain. This study investigated whether the virus also utilizes this inhibitory mechanism during other phases of the viral life cycle. By using multiple immunostainings on highly inflamed MS brain tissues containing meningeal tertiary lymphoid structures (TLSs), we analyzed PD-L1 expression on EBV-infected cells expressing EBNA2, five EBV lytic gene products, BZLF1, BHRF1, BMRF1, BALF2, and gp350/220, as well as on follicular dendritic cells within the TLSs. This is the first study describing in secondary progressive MS brain tissue the expression and the cellular and tissue distribution of PD-L1 on EBV-infected cells being in different stages of the viral life cycle, and confirms the meningeal TLSs as immune-permissive habitats favoring the maintenance of an intracerebral EBV reservoir. Full article

Serotonin reuptake inhibitors (SSRIs) are commonly prescribed to pregnant women experiencing depression. Such drugs, however, might adversely affect placenta and fetal brain development. Parietal trophoblast giant cells (pTGCs) in the mouse placenta are postulated to internalize maternal serotonin (5-HT) via transport through SERT, encoded by Slc6a4, and to provide the initial source of 5-HT to the emerging brain via the placental–brain axis. Genetic deletion of Slc6a4 in pTGCs has been hypothesized to impact placental and fetal brain development. A transgenic mouse line with high-affinity SERT, encoded by Slc6a4, was selectively deleted by pairing mice with Cre recombinase linked to Prl2c2, with LoxP sites flanking the Slc6a4 gene. PRL2C2 is solely expressed by pTGCs and other giant cells of the placenta. To compare placental and fetal brain development in selective Slc6a4 KO and WT mice, 5-HT content in the placenta and fetal brains of conceptuses was measured. No significant differences in 5-HT content were evident between knockout (KO) and wild-type (WT) placentas or fetal brains. However, there were significantly fewer pTGCs in KO placentas compared to WT (p ≤ 0.05). Sexually dimorphic differences in gene expression were evident in the placenta and fetal brain between KO and WT counterparts, with female conceptuses showing the most dramatic responses, including decrease in Prl7a2, Prl5a1, Prl3a1, Slc28a3, and Ceacam 15 in female placental samples. These findings suggest that ablation of Slc6a4 in pTGC disrupts the placenta–brain axis in a sex-dependent manner. The results might have important clinical ramifications for pregnant women being treated with SSRIs. Full article

Background/Objectives: Emerging evidence has suggested that choline is an effective treatment for at least some of the neurobehavioral deficits associated with Fetal Alcohol Spectrum Disorders (FASD). However, the mechanism of how choline works to ameliorate ethanol’s teratogenic effects, and whether it acts directly on the fetus or indirectly by altering the uterine environment, remains unknown. Previous work from our lab demonstrated that 4 BXD mouse strains that show high levels of ethanol-induced cell death on embryonic day 9.5 (E9.5) have differential responses to choline supplementation. This differential response in mouse strains highlights a need to further understand the role of genetics in choline metabolism. Because the liver is the central organ for choline metabolism, and the embryonic liver of mice is not functional this early in gestation, we focused on choline metabolism in the liver of the dam. Methods: Using a bioinformatics approach, the goals were to assess whether (1) genetic differences in liver choline metabolism in the dam could affect ethanol-induced cell death in a genotype-specific manner and (2) any of these candidate genes in the liver of the dam could be linked to differential response to choline amongst the strains. By performing a literature review, haplotype analysis among the 4 BXD strains, and liver protein expression analysis among 3 strains, we show that there are genetic differences in choline metabolic genes that are consistent with the hypothesis that maternal choline metabolism could mediate differential sensitivity. Results: While we identified two genes as promising candidates for the variable responses to choline supplementation among the four previously identified BXD strains choline/ethanolamine phosphotransferase 1 (cept1) and choline transporter gene solute carrier family 44 member 1 (slc44a1), the wealth of data on slc44a1 makes it the stronger candidate and suggests that it should be further explored. Conclusions: Genetic differences in maternal choline metabolism are present and may underlie variable therapeutic responses to choline, warranting a hypothesis that requires further investigation across animal models and human populations. Full article

Leaf abscission is a cell separation process that occurs throughout the entire plant life cycle, leading to the detachment of tissues or organs. The application of chemical defoliants to induce cotton leaf abscission not only saves the energy required for maintaining life processes but also facilitates mechanical harvesting. However, the molecular mechanisms underlying cotton leaf abscission remain poorly understood. In this study, multiple comparative analyses of gene expression differences were conducted between two cotton cultivars with different sensitivities to chemical defoliant Thidiazuron (TDZ) after TDZ application, resulting in 1,505,720,260 clean reads together with the average 92.77% of Q30 base percentage and 43.13% of GC content. A total of 35,739 differentially expressed genes (DEGs) were identified and these DEGs were mainly enriched in pathways of zeatin biosynthesis, secondary metabolite biosynthesis, and hormone metabolic processes. Integration of temporal expression pattern analysis and weighted gene co-expression network analysis (WGCNA) revealed that plant hormone signal transduction and MAPK signaling pathways might play important roles in TDZ-induced leaf abscission. Among them, a sucrose non-fermenting 1 (SNF1)-related protein kinase 2 gene (SnRK2, GH_A11G1981 and GH_D11G2017) in the abscisic acid (ABA) signaling pathway might be a potential key regulatory factor in defoliant induced leaf abscission. These findings provide novel insights into understanding the molecular mechanisms of chemical defoliant-induced leaf abscission in cotton and lay a foundation for future breeding programs and practical applications in cotton production. Full article

Lion-head goose is a large-sized breed native to Guangdong Province, China, exhibits remarkable capacity for fatty liver production under overfeeding conditions and is highly valued by local farmers and consumers. However, the molecular mechanisms driving fatty liver development in this breed are still unknown. In this study, we evaluated liver weight differences between normally fed and overfed Lion-head geese and further examined sex-specific differences following overfeeding. Overfeeding significantly increased liver weight more than 340%, and males possess a stronger capacity for lipid deposition under the same feeding regimen compared with females. RNA-Seq analysis identified 1476 differentially expressed genes (DEGs) shared by both sexes, which were mainly enriched in lipid and energy metabolism, oxidative stress, and mitochondrial pathways. In addition, 627 male-specific and 420 female-specific DEGs revealed sex-dependent differences, with males showing stronger transcriptional regulation and females exhibiting enhanced antioxidant and detoxification responses. Weighted gene co-expression network analysis (WGCNA) revealed 320 co-hub genes enriched in lipid and energy metabolism in overfeeding-induced fatty liver, along with 9 co-hub genes related to sex differences. Alternative splicing (AS) analysis detected 131 differentially spliced genes (DSGs). Integration of both approaches identified 7 overlapping genes, HYCC2 (Hyccin PI4KA lipid kinase complex subunit 2), AGL (Amylo-Alpha-1,6-Glucosidase and 4-Alpha-Glucanotransferase), CCDC62 (Coiled-coil domain containing 62), IGSF5 (Immunoglobulin superfamily member 5), MGARP (Mitochondria-localized glutamic acid-rich protein), CD80 (Cluster of Differentiation 80), and FPGS (Folylpolyglutamate synthase), as potential key regulators. These findings provide new insights into transcriptional and post-transcriptional regulation of overfeeding-induced fatty liver in geese. Full article

Metronidazole (MTZ), a widely used antiamoebic and antibacterial drug, has been linked to male reproductive damage. The aim of this study was to investigate Olea europaea L. and Equisetum arvense L. ethanol extracts for the protection against testicular toxicity and male infertility caused by MTZ, and to characterize the underlying mechanisms. Forty-two male rats were divided into six groups. The animals in group 1 served as the controls and received a daily oral dose (1 mL) of the vehicle. The animals in group 2 received metronidazole at doses of 400 mg/kg. Group 3 was treated with E. arvense extract at doses of 100 mg/kg. Group 4 was treated with O. europaea leaf extract at doses of 400 mg/kg. Group 5 was treated with metronidazole and E. arvense extract at doses of 400 and 100 mg/kg, respectively. Group 6 was treated with metronidazole with O. europaea leaf extract at doses of 400 and 400 mg/kg, respectively. The rats were given a daily oral dose of different treatments for 60 days, after which the animals were euthanized to study the histopathological and molecular changes in the testis and the sperm count in the epididymis. The testosterone levels, MDA levels, and GSH contents were also assessed in the rats in all groups. The findings revealed that the MTZ treatment caused a substantial increase in MDA levels and upregulated the NBN gene expression relative to the control. Moreover, the MTZ treatment produced significant reductions in the sperm count and viability, testosterone levels, and GSH content, and downregulated the INSL-3, STAR, HSD-3β, and CYP11A1 gene expression compared to the control. The adverse effects in testicular tissue were significantly reduced in rats given the O. europaea leaves and E. arvense treatment. The findings may show that MTZ can enhance testicular toxicity and infertility, but both plant extracts can prevent these harmful consequences. Full article

The growth and development of aquaculture organisms are significantly influenced by environmental variations shaped by different aquaculture systems. In this study, a 90-day controlled experiment was conducted to compare two pond culture setups for largemouth bass: with water hyacinth co-planted (FM group) and without (M group). As this experiment progressed, the FM group exhibited significantly superior water quality (p < 0.05) compared to the M group across multiple parameters, including total nitrogen (TN), total phosphorus (TP), ammonia nitrogen (NH₃-N), dissolved oxygen (DO) and transparency, among which, the difference in transparency was especially evident (p < 0.001). Subsequently, by 90 days, the fish body weight, condition factor, and gonadosomatic index (GSI) were significantly higher in the FM group than in the M group, with the GSI difference being particularly pronounced (p < 0.001). While the GSI of M group fishes ranged exclusively from 0.01 to 0.02 (M1), the FM group displayed a much-expanded GSI range of 0.01–0.06, with 21.4% at 0.01–0.02 (FM1), 48.1% at 0.02–0.03 (FM2), and 30.5% at 0.03–0.06 (FM3). Accordingly, omics analyses of ovarian tissues were conducted between the control (M1) and the high-performing groups (FM2 and FM3). The analyses identified significant enrichment of the glycerophospholipid metabolic pathway and a marked upregulation of the Mettl3 gene (log2FC = 12.59) in the FM2 and FM3 than the M1 group, and both the pathway and the Mettl3 gene were actively involved in growth, reproductive processes, and oocyte maturation. Given that water transparency was the most markedly improved parameter, our results indicate that it may be a key driver in upregulating ovarian glycerophospholipid metabolism and Mettl3 expression in largemouth bass, thereby promoting better growth and ovarian development. Full article