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Discrimination, chronic stress, and multimorbidity in cohort of Black and Latina transgender women with HIV: Longitudinal findings from the LITE Plus study.

Black and Latina transgender women with HIV (BLTWH) are exposed to repeated, intersecting discrimination based on race, gender, and serostatus. Minority stress theory conceptualizes discrimination as minority-specific stressors that drive health inequities. Allostatic load theory posits a pathway between discrimination and chronic disease through multisystem physiological dysregulation caused by chronic stress. To test this pathway, a longitudinal cohort of 108 BLTWH, enrolled December 2020 - June 2022 in Boston, New York City, and Washington, DC, were followed for 24 months, with biomarkers measured at baseline, 12, and 24 months. Questionnaires administered every 6 months assessed anticipated discrimination, everyday discrimination, perceived stress, and other psychosocial factors. Multimorbidity was measured via self-reported non-HIV chronic conditions. In mixed-effects mediation models, allostatic load did not mediate relationships between multimorbidity outcomes and anticipated discrimination (β: -0.0004 [95% CI: -0.004, 0.003]) nor everyday discrimination (β: -0.002 [95%CI: -0.009, 0.003]). Perceived stress demonstrated indirect effects on multimorbidity in unadjusted models of anticipated discrimination (β: 0.024, [95% CI: 0.015, 0.081]) and everyday discrimination (β: 0.021 [95%CI: 0.016, 0.077]). Indirect effects remained significant, with attenuated effects (β: 0.020 for anticipated discrimination; β: 0.017 for everyday discrimination) after adjusting for social support, community connection, and resilient coping. Total effects were only significant for the adjusted model of everyday discrimination (β: 0.056 [0.014, 0.099]). Findings suggest discrimination impacted health through specific psychosocial pathways. Alongside efforts to eliminate intersectional discrimination, stress-lowering interventions and increased access to social support and community connection may be effective approaches to reducing multimorbidity in this highly marginalized group.

Humans

Effect of Narrative-Based Palliative Care on Psychological Stress, Quality of Life, and End-of-Life Acceptance in Elderly Terminal Cancer Patients and Their Families.

ObjectiveThis study aimed to preliminarily evaluate the impacts of narrative-based palliative care on psychological stress, end-of-life acceptance, and quality of life in elderly terminally ill cancer patients and their family caregivers.MethodsThis single-center, small-sample randomized controlled study enrolled 50 elderly terminal cancer patients. Patients were randomly assigned to either the observation group or the control group (n = 25 each). The observation group received narrative-based palliative care, while the control group received routine standard care. Family psychological stress was assessed using the Relative Stress Scale (RSS), and patients' perceived stress was evaluated with the Perceived Stress Scale-10 (PSS-10). Caregiver satisfaction was measured using a hospital-developed questionnaire. Patients' quality of life was evaluated using the SF-36, Chinese Version of the Death Attitude Profile (DAP-C), and Pittsburgh Sleep Quality Index (PSQI), respectively.ResultsBaseline characteristics did not differ significantly between the two groups (P > .05). Post-intervention, the observation group demonstrated significantly lower psychological stress among family members and higher caregiver satisfaction (P < .05). Patients in the observation group reported better quality of life, improved sleep, and greater acceptance of death than those in the control group (P < .05).ConclusionAs a small-sample, single-center study, these findings offer preliminary evidence that narrative-based palliative care may reduce psychological stress in elderly terminal cancer patients and caregivers while enhancing patients' quality of life, sleep quality, and acceptance of death. However, the limited sample size, single-site design, and narrow inclusion criteria restrict generalizability. Larger multicenter trials are needed to confirm these results.

Humans

Fyn signaling in the medial prefrontal cortex regulates resistance to stress-induced object recognition impairments in male rats.

Genome-wide association studies on patients with depression have identified FYN and FYB, an FYN-binding protein, as being linked to depression. We have reported that experimental manipulations in gene expression in the medial prefrontal cortex (mPFC) alter stress-induced object recognition impairments in animals. Therefore, we examined the impact of alterations in FYN and FYB expression in the mPFC of adult male rats on resistance to stress-induced impairments in object recognition. Animals with virus-mediated knockdown or overexpression of Fyn in the mPFC were subjected to either a brief 20-min restraint with 20 intermittent tail shocks, which does not induce object recognition impairment, or a prolonged 60-min restraint with 60 intermittent tail shocks, which does. In an object recognition task, control rats maintained intact object recognition following a brief stress, whereas rats with Fyn knockdown or overexpression in the mPFC showed impaired object recognition. Prolonged stress impaired object recognition in both control rats and rats with Fyn knockdown or overexpression. Additionally, rats with Fyn knockdown in the mPFC exhibited fewer c-Fos-positive cells in the mPFC in response to brief stress, accompanied by a trend toward increased c-Fos in the amygdala compared with control rats. Fyn knockdown also reduced Fyb expression in the mPFC. Furthermore, Fyb knockdown in the mPFC impaired object recognition following brief stress, suggesting that the observed effects are consistent with involvement of a coupled Fyn-Fyb signaling axis rather than Fyn alone. These findings suggest that altered Fyn-related signaling in the mPFC may underlie the resistance to stress-induced object recognition impairments.

Animals

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

Genome-wide identification of the HSP70 superfamily in tropical sea cucumber Stichopus monotuberculatus and their expression analysis under low-salinity stress.

Heat shock proteins (HSPs) are a group of evolutionarily conserved molecular chaperones that serve as indispensable core regulators in preserving cellular homeostasis and orchestrating organismal stress responses. The tropical sea cucumber Stichopus monotuberculatus, a high-value aquaculture species, is sensitive to fluctuations in environmental salinity-a challenge that has emerged as a critical bottleneck limiting its large-scale commercial cultivation. However, no systematic investigation has been conducted to characterize the HSP70 superfamily in S. monotuberculatus and elucidate its functional roles in salinity adaptation. In the present study, we performed a comprehensive genome-wide scan and identified 19 HSP70 superfamily genes in the S. monotuberculatus genome, with the HSP70IV subfamily showing remarkable gene expansion, containing 8 distinct copies. Phylogenetic analysis, conserved motif identification, and gene structure characterization demonstrated high evolutionary conservation within each HSP subfamily. These genes were unevenly distributed across the chromosomes of S. monotuberculatus, and prediction of cis-acting elements revealed that their upstream regulatory regions were enriched with numerous functional elements associated with stress response and immune regulation. Salinity stress experiments revealed that under severe low-salinity conditions (18&#x2030;), the expression levels of SmHSPA14L and multiple HSP70IV subfamily members were significantly elevated, while SmHYOU1D was significantly downregulated; in contrast, only subtle changes were detected in the expression of most HSP70 genes under moderate low-salinity stress (24&#x2030;). These findings strongly suggest that HSP70 genes, particularly the expanded HSP70IV subfamily, may act as key modulators in the low-salinity stress response. This work provides valuable insight into the molecular mechanisms underlying salinity adaptation in tropical sea cucumbers.

Animals

Affective reactivity to a remote computer-based Trier Social Stress Test during a planned quit attempt: associations with short-term cigarette smoking lapse risk.

BACKGROUND: The Trier Social Stress Test (TSST) elicits affective responses and has been linked to smoking behavior. However, its remote use during a planned quit attempt-when stress reactivity may influence early lapse-remains understudied. OBJECTIVE: To quantify affective reactivity to a remotely administered TSST on a planned quit date following overnight abstinence and evaluate associations with cigarette use and lapse within 48 h. METHODS: This secondary analysis used data from a randomized controlled trial of adult smokers completing a remotely administered TSST following overnight nicotine abstinence. Urge, anxiety, and stress were assessed using visual analog scales and summarized using area under the curve (AUC) metrics. Smoking outcomes included cigarette count and lapse within 48 h. Associations were estimated using generalized estimating equations. RESULTS: In adjusted models, anxiety reactivity-but not urge or stress-was associated with cigarette count and lapse. Greater anxiety exposure (AUCtot) and change above baseline (AUCab) were associated with higher cigarette count (IRR=1.0004, 95%CI:1.0002-1.001, p=.002; IRR=1.01, 95%CI: 1.002-1.01, p=.002) and increased odds of lapse (OR=1.001, 95%CI: 1.0001-1.002, p=.03; OR=1.02, 95%CI: 1.001-1.03, p=.03). Effect sizes were small. CONCLUSIONS: Anxiety reactivity under nicotine deprivation was associated with increased cigarette use and lapse 48 h post quit attempt, suggesting individual differences in stress-evoked anxiety may serve as a behavioral marker for early lapse. Remote TSST administration appears feasible for eliciting affective responses on a quit date.

Humans

Phenotypic, physiological and transcriptomic analysis of graded salt stress responses in Pyrus betulifolia Bunge and functional characterization of the hub gene PbSTY46.

Pyrus betulifolia Bunge is a salt&#x2011;tolerant rootstock for pear, but its salt&#x2011;tolerance mechanisms remain largely unknown. In this study, P. betulifolia seedlings were subjected to graded NaCl stress at concentrations of 0 (CK), 50 (T1), 100 (T2), and 200 (T3) mM. We integrated phenotypic observation, physiological assessment, transcriptomic profiling, and functional gene validation to systematically elucidate its salt tolerance mechanisms. Salt stress inhibited seedling growth and root traits in a concentration-dependent manner, and T3 caused the most severe damage. Osmotic solutes responded differentially: soluble sugars peaked under T2, while proline peaked under T3. Antioxidant enzymes showed tissue-specific biphasic responses and declined after prolonged T3 stress. Meanwhile, chlorophyll and photosynthesis decreased, whereas anthocyanin increased, indicating a metabolic shift from photosynthesis to photoprotection. Transcriptome analysis revealed distinct responses depending on stress intensity: mild stress induced membrane lipid remodeling, moderate stress activated circadian rhythm and hormone signaling, and severe stress enhanced phenylpropanoid biosynthesis and thiamine metabolism. Gene Set Enrichment Analysis (GSEA) further highlighted progressive enrichment of phenylpropanoid biosynthesis, heme binding, and oxidoreductase activity. Weighted Gene Co&#x2011;expression Network Analysis (WGCNA) identified a blue module significantly positively correlated with root traits, from which the hub gene PbSTY46 was identified. Functional validation via overexpression, loss&#x2011;of&#x2011;function mutants, and pharmacological interventions (MeJA/DIECA) confirmed that PbSTY46 acts through JA signaling to enhance antioxidant enzyme activities and thereby confer salt tolerance. Collectively, P. betulifolia adopts a "survival&#x2011;first" strategy that coordinates growth arrest, osmotic homeostasis, and ROS scavenging. These findings establish PbSTY46 as a key regulator that links JA signaling to antioxidant defense. Thus, PbSTY46 represents a promising candidate for marker&#x2011;assisted breeding of salt&#x2011;tolerant pear cultivars.

Salt Stress

Comparative transcriptomic analysis of the gills and hepatopancreas of freshwater-cultured Litopenaeus vannamei under chronic nitrite stress.

To investigate the differences in molecular responses between the gills and hepatopancreas of freshwater-cultured Litopenaeus vannamei under chronic nitrite stress, a 30-day chronic stress experiment was conducted with a control group and a stress group. Transcriptomic analysis of the gills and hepatopancreas was performed using Illumina sequencing; differentially expressed genes (DEGs) were identified, and GO, KEGG, GSEA, PPI, and RT-qPCR validation were carried out. The results showed that 196 DEGs (161 up-regulated and 35 down-regulated) were identified in the gills, and 287 DEGs (199 up-regulated and 88 down-regulated) in the hepatopancreas, with only 18 DEGs shared between the two tissues. DEGs in the gills were enriched in oxidoreductase activity, glycerophospholipid metabolism, and tyrosine metabolism; DEGs in the hepatopancreas were enriched in lipid transporter activity, phagosome, ECM-receptor interaction, and riboflavin metabolism. GSEA revealed significant suppression of the mTOR pathway in the gills and the Polycomb complex pathway in the hepatopancreas. PPI network analysis identified hub genes P5CS and eEF2 in the gills, and PER, TUBB1, SHMT, and TUBB4B in the hepatopancreas. RT-qPCR validation was consistent with the RNA-seq results (R2&#xa0;=&#xa0;0.764). This study indicates that, under chronic nitrite stress, the gill response is centered on redox regulation and inhibition of growth metabolism, whereas the hepatopancreas response primarily involves lipid transport, cytoskeletal remodeling, and phagosome activation. The two tissues synergistically adapt through fundamental biosynthetic and motor protein pathways. This research provides molecular evidence for deciphering the nitrite tolerance mechanisms in freshwater-cultured shrimp.

Animals

Single-cell transcriptomics reveals heterogeneous stress responses and Mg2+-mediated survival mechanisms in Lactobacillus delbrueckii subsp. bulgaricus during freeze-drying and storage.

Maintaining the viability of lactic acid bacteria during dehydration and subsequent storage remains a significant challenge. Here, we employed single-cell RNA sequencing to reveal the heterogeneous stress responses of Lactobacillus delbrueckii subsp. bulgaricus, identifying seven distinct transcriptional clusters across the liquid culture, freeze-drying, and storage phases. The dominant clusters in the freeze-drying and storage were not completely consistent, showing significant functional differentiation. Genomic stability may be important for survival during freeze-drying and storage, while intracellular energy homeostasis appears important for viability during storage. The magnesium transporter mgtB was highly expressed in clusters tolerant to freeze-drying and storage, suggesting a critical role for Mg2+ homeostasis. Further experimental validation confirmed that Mg2+ treatment significantly bolstered stress resistance, increasing immediate post-freeze-drying survival by over 2-fold (up to 92.90%) and post-storage survival by over 5-fold (up to 5.98%). Proteomic data indicated that Mg2+ supplementation correlated with the maintenance of several biological functions potentially relevant to bacterial survival during freeze-drying and storage, including DNA repair, translation, and central carbon metabolism. These findings provide a map of microbial stress resistance through population heterogeneity and offer a potential strategy that may be adapted for enhancing the stability of other industrial lactic acid bacteria products.

Freeze Drying

Extended Long-Term Effects of Cognitive and Aerobic Training on Cognitive Function in Patients With Stress-Related Exhaustion Disorder: A 4.5-Year Follow-Up of a Randomized Controlled Trial.

Stress-related conditions like clinical burnout and exhaustion disorder (ED) are associated with enduring cognitive problems. We have previously demonstrated that the addition of computerised cognitive training (CCT) and aerobic training (AT) to a multimodal rehabilitation programme (MMR) yielded greater improvements in cognitive function compared to MMR alone in patients with ED. These effects were maintained at the 1-year follow-up for CCT, but not for AT. Building on these findings, the present study examined the extended long-term effects of CCT and AT on cognitive function, psychological health, and work ability, 4.5&#xa0;years after the interventions. Participants were recruited from a stress-rehabilitation clinic and 56 of the initial 132 participants returned for the 4.5-year follow-up. Assessments were conducted before (T1), immediately after (T2), 1-year after (T3) and 4.5-years after (T4) the interventions. Mixed model analyses assessed changes in the intervention groups relative to the control group from T1 to T4, with follow-up comparisons examining within-group stability of outcomes between T3 to T4. The primary outcome was cognitive performance on a global cognitive score. Secondary outcomes included domain-specific cognitive functioning, self-reported cognitive function, psychological health (burnout, depression, anxiety, and fatigue), and work ability. The analysis revealed sustained long-term effects on the global cognitive score, a trained updating task and episodic memory in the CCT group, with stable performance between one- and 4.5-year follow-up. The addition of AT did not yield any extended long-term effects on cognitive performance. Both groups showed extended long-term improvements in self-reported memory problems, although findings were mixed. Extended long-term improvements were observed on burnout for both groups, with additional effects on anxiety and work ability in the AT group. Notably, these effects were not present at the 1-year follow-up and are more plausibly explained by selective attrition rather than a delayed intervention effect. In conclusion, the result indicates that cognitive interventions such as CCT can have lasting positive effects on cognitive function in patients with ED, whereas the long-term psychological effects should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073772.

Adult

Cognitive behavioural therapy-based interventions on stress outcomes in pregnant women: A systematic review and meta-analysis.

BACKGROUND: Stress symptoms were the most common psychological problem in pregnancy. Cognitive behavioural therapy-based interventions are effective for antenatal depression and anxiety symptoms; but there are fewer studies for stress symptoms. OBJECTIVE: The review aims to (1) examine the effectiveness of cognitive behavioural therapy-based interventions in reducing stress outcomes (pregnancy-specific stress symptoms, generic symptoms, and objective stress) in pregnant women, and (2) identify significant moderators affecting the effectiveness of the intervention. DESIGN: Systematic review, meta-analysis, and meta-regression analysis of randomised controlled trials. METHODS: We conducted a three-step search (12 databases, 4 clinical registries, and citation searches) in English and Chinese up to July 24, 2025, by two independent reviewers. Meta-analysis, subgroup, and meta-regression analyses were performed using the R software. Quality assessment and certainty of the evidence were assessed with the Cochrane risk-of-bias tool version 2 and Grading of Recommendations, Assessment, Development, and Evaluation criteria. Publication bias was assessed using funnel plots and Egger's test. RESULTS: We included 20 randomised controlled trials involving a total of 6966 pregnant women from nine countries. Random-effects meta-analyses found that interventions significantly alleviated pregnancy-specific stress symptoms (Hedges' g&#xa0;=&#xa0;-0.84, 95% Confidence Interval, CI -1.42, -0.26, p&#xa0;<&#xa0;.01, I2&#xa0;=&#xa0;92.3%), reduced generic stress symptoms (g&#xa0;=&#xa0;-0.64, 95% CI -1.09, -0.20, p&#xa0;<&#xa0;.01, I2&#xa0;=&#xa0;87.4%) with median and large effect sizes at post-intervention. No effect was found in lowering cortisol levels (g&#xa0;=&#xa0;-0.99, 95% CI -2.58, -0.60, p&#xa0;=&#xa0;.12, I2&#xa0;=&#xa0;84%) at post-intervention. Subgroup and meta-regression analyses indicated that region, age of participants, use of intention-to-treat, missing data management analyses, frequency, modalities, and approaches of interventions, use of different comparators, and attrition rate were significant factors affecting the effectiveness of interventions. Subgroup analyses suggested that the intensity of intervention should be more than once per week using a blended mode among Asian populations. Multivariate meta-regression analyses indicated that both younger age (&#x3b2;&#xa0;=&#xa0;0.13, p&#xa0;=&#xa0;.02) and a lower attrition rate (&#x3b2;&#xa0;=&#xa0;0.03, p&#xa0;=&#xa0;.03) significantly improved the effectiveness of interventions. The overall certainty of the evidence was rated as either very low or low. CONCLUSIONS: Cognitive behavioural therapy-based interventions can supplement antenatal care to alleviate pregnancy-specific stress symptoms and generic stress symptoms, particularly in young Asian women. However, the evidence has some uncertainties. These findings should be interpreted with caution due to substantial heterogeneity. Well-designed trials on a large-scale with long-term follow-ups were needed. REGISTRATION: PROSPERO registration ID: CRD420251115913.

Humans

Temporal proteomic analysis reveals a three-phase adaptation strategy in Phytophthora cinnamomi during salinity stress.

Phytophthora cinnamomi, a highly invasive hemibiotrophic oomycete, threatens global agriculture, forestry, and native ecosystems. Although drought and temperature effects on P. cinnamomi-host interactions are well studied, current knowledge of abiotic stress responses in P. cinnamomi remains largely centered on infection and phytopathology, with limited molecular insight into the pathogen's direct response to salinity independent of its host. To address this gap, we combined growth assays, time-resolved proteomics, and network analysis to define how P. cinnamomi responds and adapts to salinity exposure. Growth assays showed that NaCl-modified agar enhanced mycelial expansion in a concentration-dependent manner, with 100&#xa0;mM NaCl significantly increasing growth at 48, 72, and 96&#xa0;h compared with controls, while 50&#xa0;mM NaCl remained comparable to control conditions. Temporal proteomic analysis of 100&#xa0;mM NaCl treatment at 0, 1, 6, 12, and 24&#xa0;h post treatment revealed dynamic shifts in protein abundance. Early induction of ROS (Reactive Oxygen Species)-detoxifying enzymes, including glutathione S-transferases and peroxidases, was consistent with ROS-specific staining assays. Network analysis identified modules enriched for redox regulation, ATP generation, ion transport, and translational control, highlighting multi-layered adaptation to elevated NaCl levels. Notably, clusters of conserved hypothetical proteins were strongly upregulated, indicating unexplored stress tolerance components in Phytophthora species. Here, we propose that P. cinnamomi rapidly activates a three-phase strategy involving metabolism readjustments, redox defenses, and cellular structure alterations under salinity conditions. With increasing soil salinization due to climate change, our study provides first mechanistic insights into P. cinnamomi's adaptive plasticity and ecological resilience to abiotic stress. SIGNIFICANCE: This study represents the first temporal proteomic analysis of salinity stress adaptation in Phytophthora cinnamomi, revealing a sophisticated three-phase adaptation strategy. This research fundamentally advances our understanding of how this globally destructive plant pathogen, P. cinnamomi, maintains environmental resilience. Our findings reveal proteome remodelling as a mechanistic framework for understanding stress tolerance in oomycetes, a group of microorganisms responsible for some of the world's most destructive agricultural and forest diseases. Our results show proteins involved in emergency damage control through metabolic recalibration to sustained adaptation. These findings have relevance for predicting pathogen behavior under climate change scenarios, where increasing soil salinity threatens agricultural productivity while simultaneously enhancing pathogen survival and virulence. Understanding how P. cinnamomi responds to prolonged salinity exposure may inform targeted biocontrol strategies and improve predictive models of disease pressure in salt-affected agricultural regions. The temporal analysis framework we present offers a broadly applicable approach for understanding microbial stress adaptation, with implications extending beyond plant pathology to environmental microbiology and biotechnology applications where stress tolerance is paramount.

Phytophthora

Efficacy and safety of pantoprazole for stress-ulcer prophylaxis in critically ill patients: A systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: Stress-related mucosal damage (SRMD) is common in critically ill patients, and pharmacologic prophylaxis remains essential. This study evaluated the efficacy and safety of pantoprazole for stress-ulcer prophylaxis in ICU patients. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted per PRISMA-2020 guidelines. PubMed, Scopus, and CENTRAL were searched for studies comparing pantoprazole with placebo in adult and pediatric ICU patients. The primary outcome was clinically important gastrointestinal (GI) bleeding; secondary outcomes included mortality, ventilator-associated pneumonia (VAP), and Clostridioides difficile infection. RESULTS: Seven RCTs (n&#xa0;&#x2248;&#xa0;9127; pantoprazole&#xa0;=&#xa0;4575; placebo&#xa0;=&#xa0;4552) were included. Pantoprazole significantly reduced clinically important GI bleeding (RR&#xa0;=&#xa0;0.53; 95% CI 0.29-0.94; p&#xa0;=&#xa0;0.03) without affecting overall mortality (RR&#xa0;&#x2248;&#xa0;0.99 [95% CI 0.92-1.05]; p&#xa0;=&#xa0;0.68). Infection rates were similar between groups (VAP: RR&#xa0;=&#xa0;0.99; p&#xa0;=&#xa0;0.78; C. difficile: RR&#xa0;=&#xa0;1.11; p&#xa0;=&#xa0;0.73). Sensitivity analyses confirmed robustness. CONCLUSIONS: Pantoprazole effectively reduces clinically important GI bleeding without increasing infection or overall mortality.

Pantoprazole

Gene expression patterns in the intestines of sea urchins (Strongylocentrotus intermedius) under prolonged high-salinity stress.

The effective development of high-salinity aquaculture for the sea urchin Strongylocentrotus intermedius depends on understanding its molecular mechanisms. Therefore, we conducted a 60-day experiment to investigate the effects of prolonged high-salinity stress on the survival, growth, amino acid levels, antioxidant enzyme activity, and gene expression of S. intermedius. The experiment involved the preparation of two groups: one with a salinity of 32 (group S32) and another with 36 (group S36). The results showed that the survival rate of S. intermedius in group S36 was 80%&#xa0;&#xb1;&#xa0;6.7%, while the weight gain rate was only 61.58%&#xa0;&#xb1;&#xa0;1.92%. Both parameters were significantly lower than those in group S32 (P&#xa0;<&#xa0;0.05). In addition, the GSH, Cys, and Glu expression in S. intermedius was significantly higher than that observed in group S32 (P&#xa0;<&#xa0;0.05). The transcriptomic results showed that, when comparing groups S32 and S36, 179 differentially expressed genes were identified. These genes were predominantly enriched in pathways related to metabolism and amino acid biosynthesis. We highlight the genes CGL, EAAT3, AMY, and NADH, which are associated with the energy metabolism, cysteine transport, and amino acid biosynthesis of S. intermedius. We speculated that S. intermedius exposed to high salinity enhances energy metabolism, as well as Cys synthesis and transport, to mitigate oxidative stress. This study provides a theoretical reference for the healthy aquaculture of S. intermedius in high-salinity environments.

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

Elucidation of the immunotoxicity of PEDOT: PSS on RAW264.7 macrophages by oxidative stress, inflammatory response, and NF-&#x3ba;B pathway activation.

Poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) nanoparticles, widely used conductive polymers, pose environmental and health risks due to their nanoscale dispersion. However, the characteristics of PEDOT: PSS in aquatic systems and the underlying mechanisms of its toxicity in animal and cell models remain poorly understood. This study aimed to investigate the toxicological effects of PEDOT: PSS nanoparticles on macrophages, with a focus on RAW 264.7 cells. After an acute exposure to PEDOT: PSS nanoparticles at different concentrations (5, 10, 20 &#x3bc;g/mL), we observed significant impairments in cell viability, proliferation, migration, adhesion, and phagocytosis, as well as morphological alterations. Concurrently, there was a marked upregulation of inflammatory markers, including reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-&#x3b1;), interleukin-6 (IL-6), and interleukin-1 beta (IL-1&#x3b2;), indicating the induction of oxidative stress and inflammation. Mechanistically, PEDOT: PSS nanoparticles activated the nuclear factor kappa B (NF-&#x3ba;B) signaling pathway, a key regulator of inflammatory responses, suggesting that they may mediate inflammatory responses and cell damage via activation of the NF-&#x3ba;B signaling pathway. These findings reveal the toxic mechanism of PEDOT: PSS nanoparticles in macrophages and provide new insights into their biological safety implications.

Animals

Evolutionary expansion of the NF-Y gene family in bivalves and divergent subunit responses to thermal and pathogenic stress in the noble scallop.

Nuclear factor Y (NF-Y) is a conserved eukaryotic transcription factor complex that specifically interacts with the CCAAT motif. Prior research has demonstrated that this gene family participates in various biological processes, encompassing growth, development, and stress responses, across a broad spectrum of organisms. However, research on the role of the NF-Y family in bivalves remains limited. In this study, we comprehensively identified the NF-Y family in 34 bivalve species, and further investigated its expression in the noble scallop Chlamys nobilis. A total of 296 NF-Y genes were identified and classified into three subfamilies, NF-YA, NF-YB, and NF-YC. Phylogenetic analysis revealed that NF-YA and NF-YC have remained relatively conserved, whereas NF-YB has undergone significant expansion. Additionally, while substantial disparities in gene copy numbers exist across species, the motif composition and exon-intron structures within each subfamily demonstrate notable conservation. Tissue expression profiling revealed distinct expression patterns among CnNF-Y genes, with several members exhibiting relatively high transcript abundance in gonadal tissues. Furthermore, qRT-PCR results demonstrated that CnNF-YA2, CnNF-YB6, and CnNF-YC were significantly and continuously upregulated under heat stress. Conversely, several genes, particularly CnNF-YA2, CnNF-YB3, and CnNF-YB4, exhibited dynamic transcriptional responses to Vibrio parahaemolyticus exposure. These findings enhance our understanding of the evolutionary trajectory and functional diversification of the NF-Y gene family in bivalves, laying a theoretical foundation for future research on thermal adaptation, immune regulation, and molecular breeding in scallops.

Animals

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