Search PubMedSearch

SEARCH · Search PubMed

Results for “Progression-Free Survival”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

217 records · Page 9Linked to original sources

Infra-low-frequency neurofeedback alters EEG network efficiency: exploratory evidence from healthy volunteers.

Infra-Low-Frequency Neurofeedback (ILF-NFB) combines classic frequency-band (FB) and infra-low-frequency (ILF) EEG components in implicit training protocols and is increasingly applied in clinical contexts. Yet, the neurophysiological mechanisms underlying ILF-NFB remain to be further elucidated. In this randomized, sham-controlled and double-blind study, we explored the online impact of a one-session ILF-NFB application on EEG correlates in healthy participants (39 analyzed datasets). Continuous 31-channel EEG was recorded during verum and sham feedback in a double-blind, randomized crossover design. In this exploratory analysis approach, functional connectivity was estimated using the debiased weighted phase-lag index (dwPLI) and analyzed with graph-theoretical measures. The results revealed higher global efficiency during verum compared to sham in the Beta1 band (12-15 Hz), reaching significance in the primary comparison but not surviving Bonferroni correction across the five tested bands; block-wise follow-ups showed a significant verum-sham difference in the first half of the neurofeedback session and a directionally consistent pattern in the second half. The Condition × Block interaction was not significant. No consistent differences were observed in other frequency bands, nor for betweenness centrality. While preliminary, these exploratory results point to possible network-level effects during ILF-NFB and motivate further confirmatory work in extended training protocols and clinical populations.

Humans

Innovations in microbial physical mutagenesis for food fermentation: An overview from traditional to emerging technologies.

Microbial strains serve as an important factor affecting fermentation efficiency and product quality. To obtain superior strains, mutation breeding is a classic strategy. Compared to chemical mutagenesis, physical mutagenesis directly induces genomic changes, providing notable advantages such as the elimination of chemical residues and environmental sustainability, hence rendering it a favored method for enhancing food-grade microorganisms. Conventional physical mutagenesis mostly depends on UV, rays, high pressure, or space radiation. As physical technologies advance, emerging methods such as ion implantation, plasma, microwave, ultrasound, and pulsed light are widely utilized for genetic modification. Mutagenesis technologies are progressively transitioning from single-effect to multi-effect synergy. Recent evaluations indicate that emerging technologies can enhance microbial mutation efficiency at the application level relative to established technologies. Nonetheless, the systematic clarification and comparative analysis at the mechanistic level remain inadequate, hindering intuitive comprehension of the qualities and distinctions across techniques. Furthermore, physical mutagenesis encounters several significant obstacles, such as cellular damage, limited rates of advantageous mutations, and laborious screening processes. This review carefully elucidates the mechanisms and properties of physical mutagenesis technology and delineates the distinctions among approaches through comparative analysis. Simultaneously, solutions for optimizing mutagenesis are presented to tackle the principal challenges mentioned above. This review aims to offer a theoretical foundation and practical guidance for the enhanced application of physical mutagenesis technologies in microbial breeding.

Mutagenesis

Glycerophospholipid remodeling under osmotic stress in grass carp gills.

Salinity fluctuations represent a pervasive environmental challenge for freshwater fishes, yet the cellular and metabolic programs governing early osmoregulatory responses remain understudied. Here, we investigated the time-dependent gill responses of juvenile grass carp (Ctenopharyngodon idella) subjected to an acute, sublethal salinity increase 9 parts per thousand (ppt). Histological and biochemical analyses revealed progressive gill lesions accompanied by elevated lactate dehydrogenase (LDH) activity and lipid peroxidation, indicating rapid tissue injury under osmotic stress. Integrative metabolomic and transcriptomic profiling uncovered pronounced temporal reprogramming, consistently highlighting glycerophospholipid metabolism as a central axis of response. In particular, phosphatidylcholine (PC) species exhibited dynamic remodeling, coupled with transcriptional enrichment of lipid turnover, membrane transport, and innate immune pathways. Network-based integration identified a PC-centered remodeling module characterized by accelerated PC headgroup turnover, disruption of the PLA2-LPCAT2 lyso-PC reacylation cycle, and enhanced ABC transporter-associated lipid and sterol export, reflected by cholesteryl sulfate accumulation and a shifted n-6 polyunsaturated fatty acid-derived oxylipin signature. Functional assays further demonstrated that PC and linoleic acid (LA) supplementation improved cell viability and alleviated oxidative stress and pro-inflammatory signaling in grass carp cells under salinity challenge. Collectively, these findings reveal phospholipid-centered membrane remodeling as an early, integrative mechanism linking osmotic stress to gill injury and immune activation in freshwater fish, providing insights into potential strategies of environmental stress adaptation.

Animals

The HOXA gene cluster: a critical regulator in bone-related disorders.

BACKGROUND: Skeletal homeostasis relies on the dynamic balance between bone formation and bone resorption. The disruption of this balance acts as the central pathological mechanism of multiple metabolic bone diseases including osteoporosis, and is closely correlated with the progression of various other bone-related disorders. As pivotal transcription factors regulating embryonic development and cell fate, the homeobox A (HOXA) gene family plays an essential role in skeletal physiological and pathological processes. METHODS: This review systematically summarizes recent research advances of the HOXA gene family in bone-related diseases, concludes the evolutionarily conserved regulatory patterns of HOXA members, and clarifies the molecular mechanisms by which HOXA genes mediate bone metabolic disorders and the occurrence as well as development of bone diseases. RESULTS: Accumulating evidence demonstrates that HOXA family members present complex functions and strong heterogeneity in bone-related diseases. They participate in the pathogenesis of bone diseases via three evolutionarily conserved regulatory manners: determining regional patterning, modulating signaling pathways, and integrating epigenetic and non-coding RNA (ncRNA) regulatory networks. CONCLUSION: Further exploring the underlying mechanisms of the HOXA family in bone-related diseases provides novel insights into the pathogenesis of bone disorders. Meanwhile, it also supplies solid theoretical basis and potential therapeutic targets for the development of novel HOXA-targeted therapeutic strategies against bone diseases.

Humans

Comparative analyses of olfactory receptor repertoires in Schizothorax fish based on the chromosome-level genomes: Implications for regulatory roles of dietary differentiation and ploidy variation.

The olfactory receptor (OR) genes constitute the molecular basis of fish olfaction, mediating survival behaviors and environmental adaptation while coevolving with habitat-driven evolution. Schizothorax, a cyprinid genus endemic to the Qinghai-Tibetan Plateau, exhibits remarkable dietary divergence and ploidy variation in response to plateau environmental changes, which presumably facilitates the adaptive evolution of OR genes. However, the evolutionary patterns of OR genes associated with trophic divergence and ploidy variation in this genus remain unclear. In this study, three species were selected: the herbivorous diploid S. macropogon, the carnivorous diploid S. lantsangensis, and the herbivorous tetraploid S. curvilabiatus. S. macropogon possessed 142 OR genes (92.25% functional), primarily located on chromosomes 14 and 24, with the fewest sequence clusters. Such compact gene repertoire and highly overlapping chromosomal clusters indicated specialization for a herbivorous olfactory niche. S. lantsangensis contained 127 OR genes (93.70% functional), concentrated on chromosomes 4 and 5, with fewer sequence clusters and a scattered distribution, reflecting evolution of OR genes under carnivorous feeding habits. The herbivorous tetraploid S. curvilabiatus exhibited striking features: 316 OR genes (94.30% functional), the most subfamilies, unique ε and κ OR subfamilies, and species-specific motifs. These characteristics revealed that ploidy, rather than herbivory, dominated OR gene evolution. In conclusion, dietary differentiation and ploidy variation together drove olfactory adaptive evolution in Schizothorax, providing new insights into vertebrate OR gene ecological adaptation.

Animals

Efficacy of afoxolaner (NexGard®) for the treatment of myiasis caused by the zoonotic tumbu fly, Cordylobia anthropophaga, in domestic dogs under field conditions.

Cordylobia anthropophaga is a major cause of furuncular myiasis in dogs and humans in sub-Saharan Africa, yet evidence for pharmacological control remains limited. Current management relies mainly on mechanical larval removal, and no controlled studies have assessed the efficacy of modern antiparasitic agents. This study evaluated the curative and preventive efficacy of a single dose of afoxolaner (NexGard&#xae;) in dogs with naturally acquired C. anthropophaga infestation under field conditions and explored a possible indirect protective effect in puppies after maternal treatment. A randomized, blinded, negative-controlled field study was conducted in Samburu County, Kenya, and included 104 naturally infested dogs allocated to a treated group (n&#x202f;=&#x202f;53) or an untreated control group (n&#x202f;=&#x202f;51). Clinical evaluations were performed on Days 0, 15 (&#xb1;2), 30 (&#xb1;2), and 45 (&#xb1;2). Efficacy was assessed based on the presence of active nodules and clinical scores. Additional observational data were collected from puppies born to or nursing from treated bitches. Compared to the control group, parasiticide efficacy was 94% on Day 15 and 100% on Day 30. The number of parasite-free dogs reached 86.3% on Day 15, 100% on Day 30, and 95.3% on Day 45. Treated dogs showed a significant clinical improvement from the first post-treatment assessment, whereas infestation persisted in controls (nodules: OR = 0.003, 95% CI 0.001-0.017; skin lesions: OR = 0.010, 95% CI 0.002-0.051; lymph node: OR = 0.013, 95% CI 0.002-0.074; body condition: OR = 0.073, 95% CI 0.027-0.195; all p&#x202f;<&#x202f;.001), with large effect sizes at the final visit for all outcomes (r&#x202f;=&#x202f;0.521-0.793). No C. anthropophaga infestations were detected in examined puppies from treated dams, including puppies exposed during pregnancy or lactation, up to 4 weeks after birth and up to 11 weeks of age, respectively. Afoxolaner appears effective to control canine cordylobiosis and may offer indirect protection to puppies, warranting further investigation.

Animals

ChIP-seq profiling identifies diapause-regulated H3K27me3 targets in the fat body of Culex pipiens.

Culex pipiens, a principal vector of significant arboviruses, survives winter through diapause, a hormonally controlled inactive phase that enhances endurance under severe cold circumstances. Recent data suggests that epigenetic processes, namely histone post-translational modifications (hPTMs), play a crucial role in regulating seasonal dormancy. Prior studies from our laboratory indicated a decrease in the methylation of Histone 3 (H3K27me3) in diapausing fat body tissue, associated with elevated expression of the histone demethylase UTX. Nonetheless, the precise genomic areas impacted by these chromatin alterations remained unidentified. We used chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) to delineate the genome-wide distribution of H3K27me3 across fat body chromatin in diapausing (D) and non-diapausing (ND) female Cx. pipiens. Notably, the higher signal at transcription start sites (TSSs) reflects localized redistribution rather than a global decrease, as diapausing fat bodies retain less H3K27me3 overall but concentrate it at promoters. To investigate the functional significance of these chromatin alterations, we confirmed a number of target loci via ChIP-qPCR and assessed gene expression with qRT-PCR. We identified many critical genes that were markedly increased in diapausing mosquitoes, exhibiting an inverse relation to H3K27me3 enrichment. Our data demonstrates different H3K27me3 chromatin landscapes between diapausing and non-diapausing Cx. pipiens, corroborating a hypothesis of selective, locus-specific repression in the non-diapause state and its targeted removal during diapause to permit activation of dormancy-associated genes. These results suggest that chromatin remodeling is a core driver of the diapause switch.

Animals

Retrograde intrarenal surgery with flexible and navigable suction access sheaths vs mini-percutaneous nephrolithotomy for large upper urinary tract stones: a&#xa0;systematic review and meta-analysis.

OBJECTIVE: To conduct a meta-analysis comparing the efficacy and perioperative outcomes of contemporary flexible and navigable suction access sheath-assisted retrograde intrarenal surgery (FANS-RIRS) against percutaneous nephrolithotomy (PCNL) for the management of large upper urinary tract stones, as despite technological advances in RIRS such as high-powered lasers and FANS that have substantially enhanced its performance, current guidelines continue to recommend&#x2009;PCNL as first-line treatment for renal stones >2cm. METHODS: MEDLINE, Embase, and the Cochrane Library were searched for studies performing direct comparisons of FANS-RIRS against PCNL in adult patients until September 2025. Primary outcomes included stone-free rates (SFRs) and need for ancillary procedures. Secondary outcomes included operative time, length of postoperative hospitalisation, and postoperative complications. RESULTS: A total of 10 studies (three randomised control trials, seven retrospective cohort studies) comprising 2347 patients were included; preoperative stone sizes were predominantly 2-3&#x2009;cm. All PCNL procedures in the studies included were performed as mini-PCNL. The SFRs for FANS-RIRS were comparable with mini-PCNL across all stone sizes (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.70-1.17) and stones &#x2265;2&#x2009;cm (OR 0.80, 95% CI 0.60-1.08), with low heterogeneity. Ancillary procedures rates were similar (OR 1.22, 95% CI 0.61-2.44). FANS-RIRS was associated with significantly fewer overall complications, specifically smaller haemoglobin decline, need for transfusion, and shorter hospital stay. However, mini-PCNL demonstrated shorter operative times for stones &#x2265;2&#x2009;cm. Urosepsis rates were low and similar between both groups. Limitations include predominance of Asian studies, variability of practice, and inclusion of non-randomised studies. CONCLUSIONS: Contemporary FANS-RIRS achieves SFRs comparable to mini-PCNL even for 2-3&#x2009;cm stones, while offering superior safety profiles and shorter hospitalisation; this supports FANS-RIRS as a viable primary treatment in selected patients.

Humans

How the microbiome shapes epigenetic trained memory in neuroinflammation: Implications for neurodegenerative diseases.

Neurodegenerative diseases are increasingly recognized as disorders involving immune dysregulation. However, the mechanisms underlying this dysfunction remain poorly characterized. Trained immunity has recently emerged as a potential contributor to immune dysregulation, particularly in neuroinflammation and neurodegenerative diseases, where trained immunity is the epigenetic reprogramming of innate immune responses following an initial inflammatory stimulus, which increases responses to subsequent exposures. In parallel, although the brain has traditionally been viewed as an immune-privileged organ, growing evidence indicates that peripheral immune activity exerts significant influence on neuroinflammation in the brain. A major driver of peripheral immunity is the microbiome. Therefore, this perspective aims to present a conceptual framework for a relationship between the microbiome, trained immunity, and neurodegenerative diseases. We first summarize evidence of trained immunity in the brain and its role in neurodegeneration. Next, we highlight the role of the microbiome in peripheral immune modulation and in trained immunity. Finally, we propose potential mechanisms through which the microbiome may induce or modulate trained immunity in the brain. These include: 1) immunogenic microbial metabolites that cross the blood-brain barrier and alter host cell epigenetics; 2) migration of peripherally trained myeloid cells into the brain; 3) viral infection-induced trained immunity that may predispose to neurodegeneration. Together, this perspective suggests that microbiome-induced trained immunity offers a novel mechanism linking peripheral immune regulation with neuroinflammation and neurodegeneration with implications for therapeutic targeting of epigenetic modification as a molecular prevention strategy for progression of neurodegeneration.

Humans

Elucidating the evolution of meat quality, water distribution, microstructure, and protein structure during sous-vide and micro-pressure cooking.

This study investigated the evolution of eating quality (colour, texture and volatile flavour compounds), water status, microstructure and protein structure of pork meat under different cooking methods. The methods analysed included traditional cooking (TC: 10, 20, 30 and 40&#xa0;min, 100&#xa0;&#xb0;C), sous-vide cooking (SV: 1, 2, 3 and 4&#xa0;h, 60&#xa0;&#xb0;C) and micro-pressure cooking (MC: 10, 20, 30 and 40&#xa0;min, 120&#xa0;&#xb0;C). Across the three cooking processes, as cooking time increased, cooking loss, lightness, yellowness, P23, &#x3b2;-sheet, random coil and surface hydrophobicity of the meat samples increased. By contrast, redness, P22, hydrogen proton density, esters content, &#x3b1;-helix, &#x3b2;-turn and sulfhydryl group content decreased. Moreover, the Warner-Bratzler shear force (WBSF), adhesiveness, hardness, springiness, gumminess, chewiness, alcohols, aldehydes, ketones and fluorescence intensity of the meat samples, initially increased and then decreased as cooking progressed. SV resulted in higher water-holding capacity (WHC), improved redness and increased alcohol and ester levels, whereas MC produced softer meat and greater water mobility. Furthermore, MC enhanced the degree of microstructural damage and protein structural unfolding in the meat. MC requires less time to achieve textures and flavours similar to those obtained using the TC and SV methods. Thus, MC is an efficient cooking method for the catering industry to obtain desired meat quality rapidly.

Cooking

Low-salinity stress alters growth, histology, physiology, and transcriptomic profiles of the gills and antennal glands in Macrobrachium rosenbergii.

Salinity is a major abiotic constraint in freshwater aquaculture of the giant freshwater prawn Macrobrachium rosenbergii, yet the coordinated roles of the gills and antennal glands, the two primary osmoregulatory organs in decapod crustaceans, under low-salinity stress remain poorly characterized. Here, we integrated histological, physiological, and transcriptomic analyses to characterize the adaptive responses of M. rosenbergii to acute (96&#xa0;h) and chronic (8&#xa0;weeks) exposure to salinity 5. Chronic low-salinity stress significantly impaired growth performance and decreased the survival rate. Acute stress induced thinning of the gill filaments, partial disorganization of pillar cells, and dilation of the intermicrovillar space in the antennal glands, whereas chronic stress caused gill vacuolization, cuticle thinning, and adaptive folding of antennal gland microvilli. In parallel, acute exposure significantly decreased hemolymph sodium and potassium ion concentrations but increased magnesium ion concentration, whereas chronic exposure increased hemolymph sodium and potassium ion concentrations, upregulated gill Na+/K+-ATPase activity, and enhanced hepatopancreatic antioxidant capacity. Transcriptomic analyses revealed distinct tissue-specific responses. Under acute stress, the gills preferentially activated pathways associated with cytoskeletal remodeling, motor proteins, and tight junctions, whereas chronic acclimation shifted the transcriptional response toward the renin-angiotensin system and glutathione metabolism. In the antennal glands, acute stress rapidly activated the renin secretion pathway, whereas chronic exposure promoted membrane remodeling by enriching pathways related to lipid and glycan metabolism. These findings reveal tissue-specific functional differentiation and synergistic coordination between the gills and antennal glands that underpin M. rosenbergii's adaptive response to low-salinity stress.

Animals

GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.

BACKGROUND: GPR3(G-protein-coupled receptor 3), an orphan G-protein-coupled receptor (GPCR) with constitutive Gs activity, is expressed in the brain, liver, ovary, and other tissues, regulating cell proliferation, differentiation, and apoptosis across the nervous, reproductive, immune, and metabolic systems. This review synthesizes evidence on its integrated signaling and physiological functions to address the lack of a comprehensive multisystem pathophysiology overview. METHODS: A systematic literature search was conducted on PubMed and Web of Science, using keywords such as "GPR3", "GPCR", "neurodegeneration", "metabolism", "immune", "reproduction", "agonist", "inhibitor", and "therapeutic target". This search identified GPR3's roles in neurodegenerative diseases, immune inflammation, reproduction, and energy metabolism. The analysis focused on signaling pathways, ligand regulation, and therapeutic potential. RESULTS: The research indicates that GPR3 is involved in neuronal survival, synaptic plasticity, and microglial activity via the cAMP/PKA, PI3K/Akt, and &#x3b2; - arrestin pathways. It promotes amyloid - &#x3b2; formation in Alzheimer's disease (AD), yet provides neuroprotection in Parkinson's disease (PD) models. It may contribute to anxiety/depression - like states, maintain oocyte meiotic arrest in the ovary, and activate thermogenic genes in adipose tissue. GPR3 modulates immune responses. Using oleic acid (OA) and diphenyleneiodonium (DPI) as activators, and AF64394 and cannabidiol (CBD) as antagonists, it shows potential in disease models. CONCLUSION: GPR3 acts as a central molecular hub integrating neural, metabolic, immune, and reproductive signaling, highlighting its potential as a therapeutic target for chronic multisystem disorders. However, its dual roles in certain pathologies and translation challenges necessitate further research.

Humans

Acetylcholine signaling regulates osmotic stress adaptation in the phytopathogen Dickeya solani.

Plants impose strong selective pressures that shape both the composition and functional potential of plant microbiomes. The adaptation of plant-associated bacteria to their hosts relies on an extensive repertoire of signal transduction systems that sense plant-derived molecules and dynamically adjust bacterial physiology and metabolism within the holobiont. These signals include key plant signaling compounds that regulate processes essential for plant-microbe interactions. Among them, acetylcholine is emerging as an important signaling molecule in both plants and bacteria. Here, we demonstrate that acetylcholine regulates the expression of the osmotic stress response betIBA gene cluster in the important phytopathogen Dickeya solani, where it plays an important role in osmoprotection. We show that the TetR-family transcriptional regulator associated with this pathway, BetIDs, recognizes acetylcholine as well as choline and trimethylamine. These three ligands differentially induce betIBA transcription in a manner that correlates with their binding affinities. Ligand binding does not affect BetIDs binding to the bet promoter or its oligomeric state. Instead, it induces pronounced changes in the secondary structure of BetIDs, with the magnitude of these conformational changes being ligand-dependent. We further show that quorum sensing modulates osmotic stress tolerance in D. solani by regulating the expression of the Bet pathway. The Bet system is required for the full virulence of D. solani, particularly in chemically complex plant tissues. Phylogenetic analyses reveal that the BetIBA system is widely distributed among plant-associated Pseudomonadota, collectively supporting its importance for bacterial survival and adaptation in plant-related environments.

Osmotic Pressure

Plasticity of hepatic metabolism in Arctic char (Salvelinus alpinus) in response to cyclic hypoxia.

The emergence of cyclic hypoxia puts aquatic organisms' homeostasis under significant strain. Energetic metabolism as well as protein synthesis and folding are particularly altered during hypoxia, while reoxygenation imposes an oxidative challenge. Currently, little is known about how hypoxia-sensitive organisms respond to large oxygen fluctuations. Our previous work on Arctic char revealed that this salmonid, despite being strongly affected by acute hypoxia and reoxygenation (H/R), can successfully reestablish homeostasis, notably through adjustments to hepatic mitochondrial metabolism. However, the mechanisms underlying this acclimation remain poorly understood. We hypothesized that Arctic char remodel their hepatic proteome to optimize energy metabolism, reorganize oxygen-demanding pathways, and maintain cellular homeostasis during repeated H/R cycles. By exposing Arctic char to two or fifteen days of diel cyclic hypoxia, we confirmed this species' limited capacity to respond to acute H/R. Nevertheless, after fifteen cycles, fish adjusted their energetic metabolism through coordinated regulation of carbohydrate and lipid pathways and upregulation of amino acid metabolism. Mitochondrial metabolism was strongly reorganized, particularly at the ubiquinone-Complex III interaction level, alongside adjustments in proline utilization and protein processing. Moreover, protein processing and folding pathways were stimulated in both mitochondria and the endoplasmic reticulum. However, chronic cyclic hypoxia may still promote non-mitochondrial ROS production, DNA replication stress, and impaired immune function. This study highlights how a hypoxia-sensitive fish progressively reorganizes its metabolism and oxygen-demanding pathways to establish a phenotype adapted to chronic cyclic hypoxia, while also revealing the physiological costs associated with this acclimation.

Animals

Cloning of two Hsp70 genes and association analysis between SNP haplotypes and high temperature tolerance trait in red swamp crayfish (Procambarus clarkii).

Aquaculture is suffering the challenge from high temperature climate. Two Hsp70 genes, PcHsp70-1 and PcHsp70-2, as key genes involved in the high temperature tolerance of red swamp crayfish (Procambarus clarkii) were identified and cloned in this study. Their molecular features and expression patterns were characterized, revealing the distinct tissue-specific upregulation expression under high temperature stress (33&#xa0;&#xb0;C). Two SNPs, PcHsp70-1 (SNP258) and PcHsp70-2 (SNP555) were examined to associate with high temperature tolerance in three populations (n&#xa0;=&#xa0;675). The genotypes of PcHsp70-1-SNP258 (GA) and PcHsp70-2-SNP555 (TT) were significantly associated with stronger high temperature tolerance. Notably, individuals carrying the haplotype of Hap I (GG&#xa0;+&#xa0;TT) showed a survival rate exceeding 70% under high temperature stress, whereas, the Hap VIII (AA + CT) showed it at 5.2%. RNA interference of PcHsp70-1 resulted in a significant decrease expression of the gene GSH-Px and its encoding protein (glutathione peroxidase) activity, and damage in intestinal tissue under high temperature stress. The transcriptome result revealed that PcHsp70-1 participates in regulation of the pathways related to cytoskeletal construction, immune response, apoptosis, and antioxidant defense. These findings indicate that PcHsp70 genes are crucial for the cellular stress response under high temperature stress. The developed Kompetitive Allele Specific PCR (KASP) markers provide valuable tools for the marker-assisted selection of high temperature tolerant crayfish varieties, supporting the sustainable development of aquaculture under the challenge of global warming.

Animals

Genome-wide identification of the peanut HD-Zip gene family and AhHDZ15 positively regulating salt and drought stress in heterologously overexpressed Arabidopsis.

Homeodomain-leucine zipper (HD-Zip) transcription factors play important roles in plant growth, development, and abiotic stress responses. However, bioinformatic analyses and functional studies of HD-Zip family in peanut are scarce. In this study, 128 AhHDZ genes were identified and classified into four subfamilies in the phylogenetic analysis. Transcriptomic data and RT-qPCR analysis indicated the expression levels of AhHDZ4 and AhHDZ15 were significantly elevated in response to 12&#x202f;h of salt stress, while AhHDZ4/15/60/69/126 all showed a progressive increase over time in response to drought stress. AhHDZ15 protein was localized in the nucleus. Under salt and drought stress, the germination rates of AhHDZ15-overexpressing in Arabidopsis were significantly higher than wild-type (WT), and root lengths were also significantly longer than WT. In addition, the SOD, CAT, chlorophyll content, and Relative Leaf Water Content (RLWC) value of leaves in AhHDZ15-overexpressing lines were significantly higher than WT, while the MDA content was significantly lower than WT. The above results indicate that heterologous overexpression of AhHDZ15 enhanced salt and drought tolerance in Arabidopsis. Furthermore, AhHDZ15 could bind to the L1-box element of the AhVNI2 promoter, thereby activating AhVNI2 transcription and enhancing the expression of downstream salt stress-responsive genes. These findings implies a potential function of AhHDZ15 in peanut that requires further validation.

Arabidopsis

Post-weaning social isolation increases reward-seeking behavior in mice.

Social isolation is a growing public health concern. Although isolation at any age is harmful, previous studies have shown that isolation during adolescence, correlating with critical periods of brain development, can impair cognitive function and increase the risk for psychiatric illness later in life. In this study, we utilized a mouse model of social isolation (SI) during adolescence (postnatal day 21-35) and compared performance of isolated and group-housed mice on a touchscreen-based continuous performance test (rCPT) and fixed ratio/progressive ratio (FR/PR) tasks in adulthood. SI improved performance in the rCPT and the improvement in performance was consistent across time bins within the 45-minute testing session. There were no effects of SI on reaction times or reward retrieval latencies. A possible confound for performance in the rCPT would be SI-induced changes in reward-seeking or motivation for the strawberry milk reward. We next compared the SI mice to their group-housed littermate controls on both PR and FR schedules of reinforcement and found that SI mice had higher breakpoints on a PR4 schedule and earned significantly more reinforcers on an FR1 schedule of reinforcement compared to their group-housed littermates, suggesting that high performance in the CPT may be due to increased motivation for food rewards. These data indicate that SI during adolescence has significant effects on reward-seeking behavior in adult mice and may provide a useful behavioral model for studying the link between SI and risk for neuropsychiatric disorders.

Animals

Bacteroides cellulosilyticus-derived 2-hydroxyphenylacetic acid rectifies hepatic lipid homeostasis in MASLD by targeting the PPAR&#x3b3;-CD36 axis.

The gut microbiota plays an important role in the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD), but the specific molecular mechanisms involved have not been fully elucidated. In this study, human cohort studies were performed to identify that the relative abundance of Bacteroides cellulosilyticus (B. cellulosilyticus) was significantly decreased in patients with MASLD. Through the integration of metagenomic and metabolomic analyses, it was confirmed that B. cellulosilyticus and its metabolite 2-hydroxyphenylacetic acid (2HPAA) are key factors regulating the occurrence and development of MASLD. Single-cell sequencing and lipidomic analyses revealed that 2HPAA can enter the liver through the enterohepatic circulation to exert regulatory effects. Specifically, 2HPAA inhibits the peroxisome proliferator-activated receptor &#x3b3; (PPAR&#x3b3;) signaling pathway, thereby suppressing the expression of the fatty acid transporter CD36. Meanwhile, 2HPAA regulates lipid metabolism in hepatocytes by significantly enhancing palmitate conversion efficiency and inhibiting CD36 palmitoylation. This dual regulatory effect on CD36 expression and palmitoylation can reduce lipid accumulation in hepatocytes and ultimately alleviate MASLD progression. These findings reveal the mechanism by which B. cellulosilyticus and 2HPAA alleviate MASLD by targeting the PPAR&#x3b3;-CD36 pathway. This work provides a new perspective for the study of gut microbiota-host interactions in regulating liver diseases.

PPAR gamma