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Comparative assessment of post-transport disease susceptibility in Asian seabass (Lates calcarifer): Associations with oxidative stress, immune responses, gut microbiota, and tissue pathology.

Stress is a crucial factor that affects aquaculture systems, particularly during transportation, which often leads to deteriorated fish health and reduced survival rates. This study aimed to investigate the comparative differences in physiological changes, oxidative stress parameters, and immune responses between clinically healthy and diseased Asian seabass (Lates calcarifer) following commercial transportation. The study compared the health status of fish after transportation, categorized into healthy (Healthy) and diseased (Disease) groups. Assessments were conducted on oxidative stress parameters, immune responses, gut microbiota composition, and tissue pathology. The results showed that diseased fish exhibited significantly higher oxidative stress levels (P&#xa0;<&#xa0;0.05), as indicated by an increase in malondialdehyde (MDA) levels and altered antioxidant and redox-related markers, including superoxide dismutase (SOD), nitric oxide (NO), catalase (CAT), glutathione (GSH), glutathione reductase (GR), and glutathione peroxidase (GPx), measured across multiple target tissues (head kidney, gills, liver, intestine, and brain), compared with healthy fish. Furthermore, the expression of immune-related genes was significantly downregulated in diseased fish after transportation, indicating immune suppression. In contrast, healthy fish maintained a more balanced immune response, which may partially mitigate the adverse effects of transport-induced stress. Gut microbiota analysis revealed that diseased fish had a significant reduction in beneficial bacteria such as Cetobacterium somerae and Bacillus spp., accompanied by a significant (P&#xa0;<&#xa0;0.05) increase in opportunistic pathogens including Aeromonas spp., Photobacterium spp., and Vibrio spp. Histopathological examination showed severe damage in the gills, liver, and intestines of diseased fish (P&#xa0;<&#xa0;0.05), while only minor tissue alterations were observed in healthy fish. Overall, the findings indicate that post-transport diseased Asian seabass exhibit marked oxidative stress, impaired antioxidant defense, altered immune responses, gut microbial dysbiosis, and multi-organ tissue damage compared with clinically healthy post-transport fish. These results suggest that deterioration of transport conditions may contribute to post-transport morbidity and disease susceptibility.

Animals

Divergent responses of the gill, hepatopancreas, and eyestalk to acute alkalinity stress in Penaeus vannamei: Osmoregulatory compromise, metabolic trade-off, and endocrine disruption.

The expansion of aquaculture into inland saline-alkali waters is constrained by high carbonate alkalinity (CA), a severe environmental stressor for crustaceans. However, the systemic molecular mechanisms underlying its lethal toxicity remain poorly understood. In this study, we employed a comparative transcriptomic approach to investigate the tissue-specific responses of Pacific white shrimp, Penaeus vannamei, under acute lethal stress (48&#xa0;h-LC50). We focused on three functionally distinct organs: the gill, hepatopancreas, and eyestalk. The results revealed a systemic but highly tissue-specific transcriptomic response. The gill, as the primary interface, exhibited severe structural impairment and critical failure of osmoregulation, highlighted by the significant downregulation of delta-1-pyrroline-5-carboxylate synthetase (P5CS). In contrast, the hepatopancreas initiates a profound metabolic trade-off, sacrificing growth-related pathways to bolster a robust antioxidant defense system, as evidenced by the activation of sulfur metabolism and high protein turnover. The eyestalk displayed a striking disconnect between hyperactivated stress signaling pathways (e.g., mTOR/FoxO) and the collapse of its protein secretory machinery, marked by the suppression of the ER translocon component Sec61. Collectively, our findings suggest that lethal alkalinity toxicity in P. vannamei results from systemic collapse driven by a complex interplay of osmoregulatory failure, metabolic trade-offs, and endocrine disruption. This study provides a comprehensive molecular snapshot of an organism at its physiological limit, offering novel insights into the adaptive strategies and ultimate tolerance boundaries of crustaceans in extreme environments.

Animals

The hidden threat from food-derived carbon dots: Formation, biodistribution, and potential health risks.

Food-derived carbon dots (CDs) are a new class of carbon-based nanoparticles generated during the thermal processing of food matrices. These nanomaterials have been extensively studied for their unique fluorescence, good biocompatibility, and tunable surface chemistry in food detection, intelligent packaging, and biomedical applications. However, their nanoscale size and high surface activity have raised safety concerns regarding biological interactions, in vivo biodistribution, and potential long-term health hazards. Although CDs have traditionally been regarded as low-toxicity materials due to their favorable biocompatibility, the potential hidden risks of CDs have not received sufficient attention. CDs exhibit dose-dependent toxicity, not only accumulating in various tissues and organs but also potentially inducing oxidative stress and interfering with cellular metabolic functions. Therefore, this review summarizes the advances in sources, synthetic strategies, and core properties of CDs, with a special focus on in vivo biological interactions, fates, and potential safety challenges. In addition, it is proposed that the standardized detection and risk assessment system should be established to further explore the long-term health effects of CDs under real dietary exposure, thereby ensuring their safety and sustainable application.

Carbon Quantum Dots

Integrative multi-omics reveals a fibroblast-centered, ZFHX3-prioritized regulatory framework linking sick sinus syndrome and atrial fibrillation.

OBJECTIVE: To define shared genetic and multi-scale mechanisms underlying comorbidity between sick sinus syndrome (SSS) and atrial fibrillation (AF). METHODS: We integrated genome-wide association study (GWAS) summary statistics for SSS and AF with Genotype-Tissue Expression (GTEx) expression and splicing quantitative trait loci (eQTL/sQTL), atrial single-cell and spatial transcriptomics, and epigenomics. We identified trait-relevant tissues and pathways, prioritized shared cell types, quantified genome-wide and local genetic sharing, detected joint loci by cross-trait meta-analysis, and linked loci to regulatory programs via colocalization and cell-prioritized co-expression networks. RESULTS: Both traits showed strongest enrichment in cardiac tissue, especially Heart Atrial Appendage. Fibroblasts from the left atrial appendage were consistently prioritized as the key shared cell population. SSS and AF displayed significant positive genome-wide genetic correlation, with multiple locally shared regions, including six major loci. Cross-trait meta-analysis identified eight joint-phenotype SNPs implicating four susceptibility genes. ZFHX3 was the leading tissue-cell-gene candidate, acting as a hub in fibroblast co-expression modules and colocalizing with cardiac regulatory signals. CONCLUSION: Shared liability for SSS and AF is highly tissue- and cell-specific, converging on regulatory networks in atrial appendage fibroblasts, with ZFHX3 serving as a central mechanistic and biomarker node.

Humans

Improved donor-site biomechanics and functional recovery with xenogeneic acellular dermal matrix after ALT flap harvest: A prospective randomized controlled study.

BACKGROUND: Donor-site management after anterolateral thigh (ALT) flap harvest is a significant yet underaddressed concern in reconstructive surgery for oral cancer. While xenogeneic acellular dermal matrix (Xeno-ADM) is common in soft-tissue repair, its efficacy for fascia lata reconstruction at the ALT donor site remains insufficiently characterized. This study aimed to assess the efficacy of xeno-ADM in fascia lata repair, focusing on compartment pressure, inflammatory and muscle injury biomarkers, and functional recovery. METHODS: In this prospective, randomized, single-blind trial, 200 patients undergoing ALT flap reconstruction were allocated to Xeno-ADM repair (n&#x202f;=&#x202f;100) or primary closure (n&#x202f;=&#x202f;100). Primary endpoints included compartment pressure, inflammatory markers in drainage fluid, serum muscle injury biomarkers, and functional outcomes. RESULTS: The xeno-ADM group showed significantly lower compartment pressures throughout postoperative days (POD) 1-5. Inflammatory markers in drainage fluid (CRP on POD 3 and 5) and serum muscle injury biomarkers (creatine kinase on POD 1 and 5) were significantly lower in xeno-ADM group. Functional outcomes were superior in the Xeno-ADM group, with faster gait recovery, lower pain scores at POD 7, and better lower-limb function at the 1- and 6-month follow-ups. Drainage duration did not differ between groups. Stratified analyses revealed that the benefits of xeno-ADM were more pronounced in patients with defect width >3&#x202f;cm or a body mass index &#x2265;24&#x202f;kg/m2. CONCLUSION: Xeno-ADM provides a safe and effective approach for fascia lata repair, reducing biomechanical and inflammatory burdens while enhancing functional recovery. These findings support a transition from simple structural closure toward functional donor-site reconstruction.

Humans

Hippocampal teneurin-4 knockdown promotes depression-like behavioral phenotypes by disrupting oligodendrocyte differentiation in mice.

Depression is one of the most prevalent mental disorders worldwide. The limited clinical efficacy of current antidepressants highlights identifying new therapeutic targets. Emerging evidence suggests that dysfunction of oligodendrocyte lineage cells contributes to the pathophysiology of depression. Teneurin-4 (Tenm4), a transmembrane protein that promotes oligodendrocyte differentiation and myelination, has been implicated in psychiatric disorders in genome-wide association studies; however, its causal role remains unclear. To determine whether Tenm4 contributes to depressive-like behavioral phenotypes, we examined Tenm4 protein expression in mice exposed to repeated forced swimming stress and generated hippocampal Tenm4 knockdown (Tenm4KD) mice. Chronic stress reduced Tenm4 expression levels in the hippocampus. Mice with hippocampus-specific Tenm4KD exhibited depressive-like behaviors, accompanied by reduced hippocampal myelin basic protein. Importantly, administration of clemastine, a myelin formation promoter, inhibited the reduction of myelin and attenuated depression-like behavioral phenotypes. Immunohistochemical analysis showed that Tenm4KD significantly decreased the number of mature oligodendrocyte cells and increased in the number of oligodendrocyte precursor cells, without changes in the total number of oligodendrocyte lineage cells. This study provides the first evidence that hippocampal Tenm4 deficiency induces depression-like behavior phenotypes through impaired oligodendrocyte differentiation and promoting demyelination. Our results identify Tenm4 as a molecular regulator of stress-induced behavioral phenotypes and suggest that it might represent a potential therapeutic target for mood disorders associated with demyelination.

Animals

Age-dependent reorganization of behavioral and striatal function in Cntnap2 knockout mice.

Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and the presence of restricted and repetitive behaviors. While ASD has a neurodevelopmental origin, it remains a lifelong condition, yet little is known about how its behavioral and neural features evolve across adulthood. Here, we investigated behavioral, synaptic, and structural alterations across the transition from early to mature adulthood in Cntnap2 knockout mice, a widely used model of ASD. Using a longitudinal behavioral approach combined with electrophysiological recordings and morphological analysis, we show that KO mice exhibit increased stereotyped and repetitive behaviors and reduced exploratory activity at both ages. However, detailed analysis of behavioral patterns revealed age-dependent differences, with early adult KO mice displaying increased behavioral persistence that later evolved into distinct patterns of behavioral sequences. These behavioral changes were associated with alterations in inhibitory synaptic transmission in the dorsolateral striatum (DLS), including changes in spontaneous inhibitory postsynaptic current (sIPSC) frequency and temporal structure. In parallel, mature adult KO mice showed structural remodeling of spiny projection neurons, characterized by increased distal dendritic arborization and age-dependent organization of dendritic spines. Together, our findings demonstrate that ASD-related alterations are not static but evolve across adulthood, revealing a multi-level reorganization of behavioral, synaptic, and structural features. These results highlight the importance of considering adulthood stages in ASD and provide new insights into the dynamic nature of the condition.

Animals

Effects of rumen fluid transplantation on longissimus dorsi muscle development in Xizang sheep: An association analysis based on transcriptomic and serum metabolomic profiles.

This study aimed to investigate the effects of rumen fluid transplantation (RFT) on the growth and development of the longissimus dorsi muscle in female Xizang sheep. After RFT, muscle lightness differed significantly between the two groups, with the LDC group showing significantly higher lightness than the LDT group. In contrast, no significant differences were observed between groups in other muscle phenotypic traits, including drip loss, pH, cooking loss, shear force, redness, and yellowness. Antioxidant-related indices (SOD, GSH-PX, MDA, CAT, and T-AOC) also showed no significant differences between groups. Histological analysis revealed that muscle fiber length, width, and density were significantly greater in the experimental group than in the control group. Transcriptomic analysis identified 515 differentially expressed genes (DEGs), of which 419 were downregulated. KEGG analysis indicated that genes involved in muscle development-related pathways, such as cell adhesion and the PI3K-Akt signaling pathway, were predominantly downregulated. Key serum metabolites (L-kynurenine, IPA, allantoin, and propionylcarnitine) showed highly significant positive correlations with muscle fiber growth indices. In contrast, metabolites such as l-carnitine, acetylcarnitine, and citrulline were negatively correlated with muscle fiber growth, but positively correlated with the expression of muscle structure-related genes (COL11A1 and EFNA5) and with meat lightness. Overall, this study provides new insights into the potential molecular basis by which RFT influences muscle growth and development. However, the mechanisms by which RFT affects muscle development and meat quality-related traits remain unclear and warrant further investigation.

Animals

Clinical characteristics and outcomes of post-stroke seizures following reperfusion therapy: a retrospective single-center study.

BACKGROUND: Post-stroke seizures (PSS) are a recognized complication of ischemic stroke and may adversely affect functional outcomes and survival; however, their characteristics in patients receiving contemporary reperfusion therapy remain incompletely defined. We aimed to describe the clinical characteristics, treatment patterns, and outcomes of patients who developed PSS following reperfusion therapy and to compare early- and late-onset seizure subgroups. METHODS: This single-center retrospective study included adult patients with acute ischemic stroke treated with intravenous thrombolysis (IV-tPA), mechanical thrombectomy (MT), or combined therapy between January 2020 and September 2025. Early seizures were defined as occurring within 7&#xa0;days of stroke onset. Clinical, radiological, and treatment-related variables were analyzed, and functional outcome was assessed using the modified Rankin Scale at 3&#xa0;months. RESULTS: Of 1242 patients who received reperfusion therapy, 53 (4.27&#xa0;%; 95&#xa0;% CI 3.28-5.54) developed PSS. Observed seizure rates were 3.39&#xa0;% in the MT group, 4.06&#xa0;% in the IV-tPA group, and 7.02&#xa0;% in the combined therapy group; these observed rates did not differ significantly across treatment modalities. Early seizures occurred in 23 patients and late seizures in 30. No significant differences were found between early- and late-onset seizure subgroups in demographic characteristics, vascular risk factors, stroke severity, reperfusion success, or clinical outcomes, with the exception of an isolated, exploratory difference in stroke laterality. Three-month mortality among patients with PSS was 45.28&#xa0;% (95&#xa0;% CI 32.66-58.55), and in-hospital mortality was 20.75&#xa0;%. CONCLUSIONS: In this single-center cohort, the incidence of PSS after reperfusion therapy was comparable to previously reported rates, with no marked differences across treatment modalities. The high mortality among patients with PSS likely reflects underlying stroke severity rather than a treatment-specific risk.

Humans

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans

The gonadal matrisome and its correlation with sex change in the ricefield eel Monopterus albus.

The matrisome is a comprehensive list of genes in the genome of an organism, which encodes proteins constituting or interacting with the extracellular matrix (ECM). The gonadal ECM is important for folliculogenesis and spermatogenesis. This study characterized the composition of the matrisome and the expression of matrisome genes in the gonad of ricefield eel, a protogynous sex-changing teleost, during sex change. A total of 838 matrisome genes were identified in the genome of ricefield eel through an in-silico orthology-based approach, of which 482, 443, 429, and 570 matrisome genes were shown to be expressed in the gonads of female (F), early intersexual (EI), mid-intersexual (MI), and late intersexual (LI) fish, respectively. Differentially expressed matrisome genes (DEMGs) were observed across all the sexual stages as well as in each category of ECM components. Analysis of DEMGs in the comparison between EI and F revealed dramatic upregulation of adam8a, mmp9, and s100a11 while downregulation of col4a5, col15a1b, clec3ba, f13a1, and ccl44, which were further confirmed by qPCR analysis. Together, these findings revealed significant changes in the expression of many matrisome genes, particularly three regulator genes, adam8a, mmp9 and f13a1, as female ricefield eels initiate sex change, suggesting that gonadal tissues undergo dramatic remodeling involving the regression of ovarian tissues and the development of testicular tissues to facilitate this process. These data provide valuable resources for further unraveling the roles of matrisome genes in gonadal development of ricefield eel and other vertebrates.

Animals

Extending the Treatment Window for Intravenous Thrombolysis in Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke within 4.5 hours of onset. However, imaging-based selection may extend the treatment window. This systematic review and meta-analysis evaluated the efficacy and safety of IVT administered beyond 4.5 hours after stroke onset or last known well (LKW) in patients selected based on imaging findings. METHODS: A comprehensive search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials comparing IVT with alteplase or tenecteplase (TNK) administered >4.5 hours after stroke onset/LKW vs standard care. Primary outcomes were 3-month excellent (modified Rankin Scale [mRS] 0-1) functional outcome and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included good (mRS 0-2) functional outcome, recanalization, and 3-month mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis assessed differences between alteplase and TNK. RESULTS: Fourteen studies involving 4,944 patients were included. The mean age was 69.8 years, 58.2% were male, the median National Institutes of Health Stroke Scale score was 9, and 12.3% received preplanned endovascular thrombectomy (EVT). A total of 2,492 patients received IVT in an extended time window (4.5-24 hours). Compared with standard care, extended IVT was associated with higher odds of achieving an excellent functional outcome (OR: 1.43 [95% CI 1.25-1.63]), a good functional outcome (OR: 1.25 [95% CI 1.11-1.40]), and recanalization (OR: 3.28 [95% CI 2.09-5.16]). There was no difference in 3-month mortality (OR: 1.21 [95% CI 0.95-1.53]). However, IVT increased the risk of sICH (OR: 2.51 [95% CI 1.47-4.28]). Sensitivity analysis excluding patients who received EVT showed no impact on the outcomes. TNK exhibited similar efficacy to alteplase but showed potentially lower odds of sICH (OR: 1.96, 95% CI 1.06-3.64) compared with alteplase (OR: 5.29, 95% CI 1.80-15.57); however, the subgroup difference was not significant (p = 0.11). DISCUSSION: Among patients selected based on imaging, 4.5-24 hours after stroke onset/LKW, IVT improves outcomes despite an increased risk of sICH. TNK showed similar efficacy to alteplase, with a possible lower risk of sICH; however, direct comparisons in future trials are needed.

Humans

Comparative transcriptome analysis provides insights into dorso-ventral color pattern formation of Holothuria edulis.

Animal body color patterns are highly diverse and play critical roles in camouflage, intraspecific communication, and environmental adaptation. Holothuria edulis, an important echinoderm inhabiting tropical waters, exhibits a typical dorsoventral dichromatism. This unique body color difference represents a key phenotypic trait for its habitat adaptation; however, the core differential genes regulating this trait remain to be elucidated. In this study, comparative transcriptome sequencing was performed on the dorsal and ventral body wall tissues of H. edulis, leading to the identification of a number of differentially expressed genes (DEGs), followed by GO functional annotation and KEGG pathway enrichment analysis. GO enrichment analysis indicated that the DEGs were significantly enriched in functional categories such as extracellular region, peptidase inhibitor activity, and tetrapyrrole binding. KEGG pathway analysis further revealed significant enrichment of protein digestion and absorption, the TNF signaling pathway, and cholesterol metabolism. Notably, the pigmentation-related gene FMO2 was highly expressed in the dorsal body wall tissue, whereas cyp1a1, ZIC1, Slc7a11, WNT-1, and ADAMTS20 were highly expressed in the ventral body wall tissue. This study identified DEGs and enriched pathways associated with dorsoventral body color differences in H. edulis, providing new insights into the molecular regulatory mechanisms underlying body color pattern formation. From the perspective of aquaculture applications, body color is one of the important traits affecting the quality and market value of sea cucumber products. Elucidating the molecular mechanisms of body color variation can provide a scientific basis for molecular marker-assisted breeding of superior sea cucumber variety.

Animals

Culture of infectious human norovirus isolated from live contaminated oysters.

Human noroviruses are a major cause of foodborne outbreaks worldwide. Filter-feeding shellfish, such as oysters, can bioaccumulate these viruses in their digestive tissue when grown in sewage-impacted coastal areas and are often implicated in norovirus foodborne outbreaks. Despite the high sensitivity of current molecular assays, these methods for norovirus detection in shellfish fail to distinguish between infectious and non-infectious particles. Assessing norovirus infectivity in shellfish remains a challenge due to the lack of suitable isolation methods that maintain capsid integrity. In this study, a protocol for isolating infectious norovirus from oyster tissues, based on chloroform-butanol elution and polyethylene glycol concentration (CB-PEG), was optimized for the recovery of human norovirus GI and GII. While CB-PEG method recovered various norovirus GI and GII genotypes, it was less efficient at the genomic level than a protocol based on proteinase K elution (adapted from ISO 15216) and showed genotype-dependent viral recovery rates. By optimizing the flocculation step, we improved the method's compatibility with human intestinal enteroid (HIE) cultures. Using this approach, we successfully quantified infectious norovirus GII.3 titers recovered from artificially-contaminated live oysters. Interestingly, infectious virus was better isolated following a freezing step of the digestive tissues, with titers ranging from 13 to 40 TCID50/mL for positive samples. In conclusion, this study established an optimized methodological approach for the relative quantification of infectious norovirus GII.3 in shellfish, paving the way for future research on viral persistence and inactivation strategies in this foodstuff.

Norovirus

Studies on functional differentiation of xpr1a and xpr1b genes in zebrafish.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is known to be involved in various biological processes, including phosphate homeostasis, cellular signaling, brain and vascular mineralization, whereas its specific contribution to bone development remains incompletely characterized. Due to genome duplication in teleosts, zebrafish Danio rerio possess two paralogous genes of XPR1 namely xpr1a and xpr1b, whose functional divergence remains unclear. The amino acid sequence similarity between zebrafish xpr1a and xpr1b was 83.26%. In situ hybridization demonstrated overlapping localization in the head and spinal cord at 24-48 hpf, while diverged by 72 hpf, with xpr1a becoming restricted to the head while xpr1b persisted in both regions. CRISPR/Cas9 was used to generate xpr1a and xpr1b mutants. The xpr1a mutants are comparatively healthy, viable but with mild growth reduction, whereas the xpr1b mutants display high mortality, reduced body length and severe vertebral deformities. Interestingly, all the double mutants died at the embryonic stage. Moreover, to further investigate the molecular and regulatory mechanisms, we conducted comparative transcriptome analysis on bone and brain tissues from xpr1b+/+ and xpr1b-/- zebrafish. In bone tissue, 6749 DEGs were identified, comprising 3846 upregulated and 2903 downregulated genes. These DEGs were mainly enriched in the MAPK signaling pathway, Wnt signaling pathway, cysteine and methionine metabolism, and ECM-receptor interaction. RT-qPCR validated results showed that seven osteogenesis-related genes (col1a1a, sp7, runx2b, col1a2, col1a1b, alp1 and entpd5), and two phosphate homeostasis related genes (slc20a2 and pdgfba), which are essential for skeletal mineralization and phosphate homeostasis, exhibited significantly downregulated expression in bone tissue of xpr1b mutant zebrafish. These results highlight the pivotal role of xpr1b in regulating skeletal mineralization and phosphate metabolism, thereby elucidating the functional specialization of XPR1 paralogs while providing a theoretical basis for understanding bone developmental mechanism in teleost vertebrates.

Animals

Effects of phenylephrine and norepinephrine with restrictive infusion on oxygenation during one-lung ventilation for lung surgery: a randomized controlled trial.

OBJECTIVE: This study compared&#xa0;the effects of norepinephrine or phenylephrine combined with restrictive infusion on the oxygenation during thoracoscopic one-lung ventilation (OLV). METHODS: Ninety patients were randomly divided into three groups: the norepinephrine group (Group N), the phenylephrine group (Group P), and the control group (Group C). Arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt fraction (Qs/Qt) were measured with patients in lateral positions during two-lung ventilation (TLV) at 10&#x2009;min (T1), and during OLV at 15&#x2009;min (T2) and 45&#x2009;min (T3). Lung tissue samples were analyzed for endothelin and COX-2 levels after surgery. RESULTS: At T3, Group P had significantly higher PaO2 and lower Qs/Qt than Groups N and C (all p&#x2009;<&#x2009;0.05), with no significant differences between Groups N and C (all p&#x2009;>&#x2009;0.05). Compared to T1, Groups N and C showed significantly lower PaO2 and higher Qs/Qt at T2 and T3 (all p&#x2009;<&#x2009;0.05), with no significant differences in PaO2 and Qs/Qt at T3 compared with T2 (all p&#x2009;>&#x2009;0.05). Group P patients had lower PaO2 and higher Qs/Qt at T2 and T3 compared to T1 (all p&#x2009;<&#x2009;0.05), but at T3, PaO2 increased and Qs/Qt decreased compared to T2 (all p&#x2009;<&#x2009;0.05). Lung tissue levels of endothelin and COX-2 were significantly elevated in group P compared to groups N and C (all p&#x2009;<&#x2009;0.05). CONCLUSION: Combining phenylephrine with restrictive infusion during OLV improved oxygenation by increasing PaO2, decreasing Qs/Qt, and raising endothelin and COX-2 levels in lung tissue, thereby enhancing the HPV effect.

Humans

Genome-wide identification and expression profiling of HSD3B and SDR42E1 genes in the Pacific oyster (Crassostrea gigas): potential associations with gonadal development.

Sex steroids are lipid-soluble signaling molecules that regulate sex differentiation, reproductive development and physiological homeostasis in animals. 3&#x3b2;-Hydroxysteroid dehydrogenase/&#x394;5-&#x394;4 isomerase (3&#x3b2;-HSD) is a key steroidogenic enzyme, whereas SDR42E1, an extended short-chain dehydrogenase/reductase, has been implicated in sterol- and steroid-related metabolism. However, the composition, evolutionary relationships and expression patterns of the HSD3B- and SDR42E1-related genes in bivalve gonadal development remain poorly characterized. In this study, five PF01073-containing genes, comprising three CgHsd3b and two CgSdr42e1 genes, were identified in the Pacific oyster Crassostrea gigas. Phylogenetic analysis separated the proteins into HSD3B-related and SDR42E1-related groups, and gene-structure and motif analyses indicated subfamily-level divergence. All five proteins retained the SDR domain but differed in exon-intron structure and motif composition. Each contained the extended-SDR TGxxGxxG motif, whereas exact classical [ST]GxxxGxG and NNAG motifs were absent. Tyr- and Lys-equivalent residues were conserved, while the HSD3B1 Ser-equivalent position contained Thr in two C. gigas proteins and Ser in one. These features support their classification as extended-SDR proteins but do not establish enzymatic activity or substrate specificity. The three CgHsd3b genes were dispersed on one chromosome, whereas CgSdr42e1-1 and CgSdr42e1-2 were adjacent on another chromosome, suggesting a possible local duplication event for the CgSdr42e1 pair. Public RNA-seq data showed distinct tissue- and gonadal-stage expression patterns, with several genes displaying gonad-biased or female-stage-associated expression. Independent RT-qPCR profiling of the representative genes CgHsd3b-3 and CgSdr42e1-1 detected stage-dependent expression, although tissue rankings differed from those in the public RNA-seq datasets. These differences may reflect the use of independent biological samples, tissue composition, normalization procedures, and platform-specific measurements. Because enzymatic assays, metabolite measurements, cellular localization, and functional perturbation were not performed, the results identify candidate genes whose expression is associated with gonadal development rather than demonstrating regulatory roles. This study provides a comparative framework for future functional investigation of sterol- and steroid-related metabolism in bivalves.

Animals