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PubMed2026

PPRC1 is a prognostic biomarker and key regulator of mitochondrial oxidative phosphorylation in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) remains an incurable haematological malignancy, underscoring the need for novel prognostic biomarkers and therapeutic targets. This study aimed to investigate the clinical and biological significance of peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1) in MM. METHODS: Expression and clinical data were obtained from public databases and an independent local cohort. Kaplan-Meier and Cox regression analyses were performed to evaluate prognostic value. Differential expression analysis, pathway enrichment analysis and single-cell RNA-seq data analysis were used to explore biological functions. PPRC1 was silenced in MM cell lines using siRNA to assess its effects on cell survival and oxidative phosphorylation. RESULTS: PPRC1 was significantly upregulated in MM and was associated with advanced disease stage and poor overall survival. Multivariate Cox analysis identified PPRC1 as an independent prognostic factor. A nomogram incorporating PPRC1 and revised-ISS improved survival prediction. Functional analyses revealed that PPRC1 was positively correlated with oxidative phosphorylation and oncogenic signalling pathways. A potential connection between PPRC1 expression and immune cell infiltration was observed. PPRC1 knockdown inhibited cell proliferation, induced cell cycle arrest and apoptosis and impaired oxidative phosphorylation in MM. CONCLUSIONS: PPRC1 acts as a prognostic biomarker and metabolic regulator in MM by sustaining mitochondrial oxidative phosphorylation. These findings highlight PPRC1 as a potential therapeutic target in MM.

Humans↗

PubMed2026

Biomimetic mesoporous silica nanosphere ameliorate experimental autoimmune uveitis by delivering sCD83.

Autoimmune uveitis (AU) is an autoimmune disease that may lead to blindness, but there are currently no precise targeted therapies for its prevention and treatment. Dendritic cell (DC) is key cell involved in the pathogenesis of AU, and specific regulation of their state can help improve AU. In this work, mesoporous silica nanospheres were loaded with the immunomodulator soluble CD83 (sCD83) and subsequently camouflaged with dendritic cell (DC) membranes to fabricate the nanocarrier DCM@MSN/sCD83 for treating experimental autoimmune uveitis (EAU). Research results show that DCM@MSN/sCD83 effectively alleviated the symptoms of uveitis in EAU, reduced the proportion of CD4+CD25-T cell/CD4+CD25+T cell and the percentage of DC in the eyes and cervical lymph nodes. It also decreased the expression of STING in Müller cell. Furthermore, the efficacy of DCM@MSN/sCD83 was found to be primarily targeting DC, and promoted the expression of IL-10 and TGF-β1 in DC by activating the phosphorylated HIF/STAT3 pathway, to induce the production of CD4+CD25+ T. This effect is superior to nanomedicine loaded with dexamethasone. Moreover，DCM enabled the nanocarriers to efficiently cross the blood-eye barrier and reach cervical lymph nodes, thereby regulating peripheral immunity. This research indicate that cell membrane-modified nanoparticles targeting homologous cells can effectively improve treatment efficiency and duration, which is potential therapy strategy for uveitis.

Animals↗

PubMed2025

The effect of penile tourniquet and continuous artificial erection on penile erectile tissues: An experimental study.

INTRODUCTION: Penile tourniquet (PT) is known to cause ischemic injury, which worsens with prolonged application. Artificial erection (AE), formed by intracorporal saline injection mostly under PT, has been practiced for decades to evaluate penile curvature, yet its effect on erectile tissues has never been investigated. In this study, we examined a modified approach, continuous artificial erection (CAE), and investigated its effects on erectile tissues. OBJECTIVE: This study aims to investigate the histopathological and immunohistochemical effects of CAE on penile erectile tissues. STUDY DESIGN: Thirty-five rats were randomized into five groups. Four experiment groups received 20 or 40 min of isolated PT (20T and 40T) or PT with CAE (20T&E and 40T&E). CAE was achieved through continuous intracavernosal saline injection. Penectomy was performed three weeks post-procedure in the experiment groups and directly in the control group. Erectile tissue samples were evaluated using light microscopy for histopathological parameters including inflammation, neovascularization and fibrosis, and by immunohistochemistry. Endothelial function was assessed by eNOS and e-selectin staining, while ICAM-1 staining was used to assess chronic inflammation. RESULTS: 40T showed the highest levels of inflammation, fibrosis, and endothelial dysfunction. 20T had significantly less inflammation than 40T, with a non-significant increase in fibrosis and alteration of endothelial markers. 40T&E displayed the second-highest fibrosis rate (adjusted p > 0.05), while 20T&E showed complete absence of fibrosis. Both 40T&E and 20T&E preserved strong eNOS and e-selectin expression, identical to controls. ICAM-1 expression in 20T&E was also consistent with the control group. The most significant difference in erectile tissue damage was noted between 40T and 20T&E. CONCLUSION: This is the first study to evaluate the effects of AE on erectile tissues. Findings of this experimental model support that, CAE does not increase the tissue damage that is already caused by PT, but rather reduces it, likely through the washout of blood elements contributing to reperfusion injury. CAE possibly provides a protective effect on erectile tissues by preserving endothelial function, reducing inflammation and fibrosis, especially under 20 minutes of duration. These findings may support that AE maneuvers such as "artificial erection test" and CAE are potentially safe, while further studies are needed to assess the detailed effects of CAE.

Male↗

PubMed2026

Source- and Solubility-specific Choline, Gut Microbiota, and Dyslipidemia Risk: Trimethylamine N-oxide-associated and Non-trimethylamine N-oxide-Associated Patterns in a Prospective Cohort Study.

BACKGROUND: Dietary choline, a major precursor of the gut microbial metabolite trimethylamine N-oxide (TMAO), is implicated in dyslipidemia risk; however, source- and form-specific associations and interactions with gut microbiota remain unclear. OBJECTIVES: The aim of this study was to examine longitudinal associations of source- and form-specific dietary choline with plasma TMAO and dyslipidemia and to identify gut microbiota interactions. METHODS: Using data from the China Health and Nutrition Survey (2018-2023), dietary intake was assessed via 3 consecutive 24-h recalls in this prospective cohort study. Two-level generalized linear mixed-effects models were applied in 4828 adults (mean age: 55.9 ± 12.6 y, 56.6% females) to assess choline-dyslipidemia associations. Choline-TMAO and TMAO-dyslipidemia analyses were conducted in 1091 participants free of dyslipidemia at baseline. Among 7169 adults with gut microbiome data, Least Absolute Selection and Shrinkage Operator and logistic regression identified lipid-associated gut genera; TMAO relationships were examined in a subset of 693 participants. RESULTS: Higher intakes of total [Q4 compared with Q1: odds ratio (OR) = 1.261; 95% confidence interval (CI): 1.007, 1.580], red meat-derived (OR: 1.753; 95% CI: 1.196, 2.568), and lipid-soluble choline (OR: 1.304; 95% CI: 1.047, 1.624) were associated with higher risk of elevated low-density lipoprotein cholesterol (LDL cholesterol), whereas vegetable-derived choline was inversely associated. Egg-derived and lipid-soluble choline were positively associated with plasma TMAO, which was prospectively associated with 5-y incident dyslipidemia (Q4 compared with Q1-OR: 1.620; 95% CI: 1.047, 2.509), elevated LDL cholesterol (Q3 compared with Q1-OR: 2.478; 95% CI: 1.187, 5.174), and hypertriglyceridemia (Q4 compared with Q1-OR: 1.829; 95% CI: 1.028, 3.225). Three TMAO-associated genera were identified: Lachnospiraceae and Phascolarctobacterium as pro-risk taxa and Turicibacter as protective. The adverse LDLcholesterol association of egg-derived choline was observed exclusively in Phascolarctobacterium-enriched individuals. CONCLUSIONS: Dietary choline source and solubility differentially associated with dyslipidemia risk through TMAO-associated and non-TMAO-associated patterns, with gut microbiota as key modulators.

Humans↗

PubMed2026

'Sawa Aqwa' (Stronger Together): A multi-site randomized controlled trial of a brief family systemic intervention for adolescent mental health in Lebanon.

BACKGROUND: There are no evaluated family-based mental health and psychosocial support (MHPSS) interventions for adolescents in Southwest Asia (known as the Middle East), and few whole-family interventions in low- and middle-income countries, despite consistent evidence for the impact of family support on mental health and well-being. This study aims to evaluate the effectiveness of a brief family systemic mental health intervention, deliverable by non-specialists in mental health. METHODS: We conducted an assessor-blind type I hybrid effectiveness-implementation multi-site randomized controlled trial comparing the locally developed family intervention to a waitlist control group for randomly allocated families residing in North Lebanon and Beqa'a governorates. Eligible families presented with medium-to-high risk for child protection concerns (abuse, neglect, child labor, early marriage) and had at least one adolescent aged 12-17 who demonstrated psychological distress. Outcomes at the family, caregiver, and adolescent level were measured pre- and post-intervention, and at 3-month follow-up. RESULTS: Intent-to-treat analyses found a significant between-group effect of the intervention on adolescent-reported family functioning, caregiver mental health, and parenting. No change was found for adolescent psychological distress. Further analyses found effects on adolescent well-being for those who completed the intervention, and that father attendance was associated with better outcomes for adolescent well-being in the intervention group. No other significant moderators were found. At the 3-month follow-up for the intervention condition, family functioning and caregiver well-being significantly dropped from endline. CONCLUSIONS: The study demonstrates mixed results for a non-specialist-delivered family-systemic intervention developed in the context of humanitarian crises in Lebanon. While the intervention did not result in benefits in adolescent-reported symptoms of psychological distress, the intervention group did show greater improvements than the control group on a number of other outcomes, showing the potential impact of working with the wider family system to support adolescents in humanitarian settings.

Humans↗

PubMed2026

Investigation of ACE gene polymorphism and serum ACE activity in relation to alopecia areata among Iraqi patients.

BACKGROUND: Alopecia areata (AA) is a multifactorial disorder with immune dysregulation and genetic susceptibility, affecting 0.5-2% globally. OBJECTIVE: This study investigated angiotensin converting enzyme (ACE) gene insertion /deletion (I/D) polymorphism and serum ACE activity in Iraqi AA patients and their association with inflammatory cytokines (interleukin [IL]-17) and nutritional markers to understand disease progression. METHODS: This case-control study included 50 AA patients (Male and Female) and 35 healthy controls. ACE gene polymorphism (rs1799752) was analyzed using real-time polymerase chain reaction (qPCR) with high-resolution melting (HRM) analysis. Serum IL-17 levels were determined by enzyme-linked immunosorbent assay (ELISA), and biochemical markers were measured using an automated analyzer. RESULTS: ACE gene polymorphism (rs1799752) showed non-significant genotype distribution between patient and control groups (p > 0.05), though a trend toward DD genotype enrichment was observed in patients. Serum ACE levels were significantly higher in patients versus controls (p < 0.0001) with high diagnostic performance. ACE correlated positively with IL-17 (P < 0.0001) and negatively with vitamin D3 and zinc (P < 0.0001). Female patients had significantly higher ACE levels than males (P < 0.01). CONCLUSIONS: ACE emerges as an immunometabolic hub in AA pathogenesis, integrating inflammation with nutritional deficits, suggesting its potential as a biomarker and therapeutic target.

Humans↗

PubMed2026

Practical Saudi Guidelines on management of moderate-to-severe psoriasis: 2026 update.

BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory skin disease that affects approximately 5.3% of the population in the Kingdom of Saudi Arabia (KSA). Thus, we aim to develop updated evidence-based clinical practice guidelines for the management of adults and pediatric patients with moderate-to-severe plaque psoriasis in the KSA. METHODS: These guidelines followed the "Grading of Recommendations, Assessment, Development, and Evaluation" (GRADE) methodology. We conducted a systematic literature review of PubMed, EMBASE, and the Cochrane Library for high-quality evidence published between 2020 and 2026. The panel developed 31 PICO questions that address key treatment considerations for moderate-to-severe psoriasis. RESULTS: We established 27 evidence-based recommendations and 4 good-practice statements addressing key aspects of moderate-to-severe psoriasis management. These guidelines strongly recommend adopting the Psoriasis Area and Severity Index (PASI) 90 as the primary treatment goal over PASI 75. For adult patients, the guidelines recommend biologic therapies, including interleukin (IL)-17 inhibitors, IL-23 inhibitors, IL-12/23 inhibitors, and tumor necrosis factor (TNF)-α inhibitors, for better disease control. For pediatric patients, the guidelines recommend early initiation of biologic therapy, with etanercept, secukinumab, ixekizumab, and adalimumab as preferred options. CONCLUSION: These Saudi national guidelines offer a comprehensive, evidence-based framework for managing moderate-to-severe psoriasis in adults and pediatric patients.

Humans↗

PubMed2026

Impact of a multimodal prehabilitation program on postoperative cognitive dysfunction: a single-center randomized controlled trial.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a frequent complication after cardiac surgery. Exercise-based prehabilitation may enhance functional reserve and reduce vulnerability to perioperative cerebral insults. We hypothesized that multimodal prehabilitation reduces POCD 3 months after cardiac surgery. METHODS: This prespecified substudy of a single-center randomized controlled trial (NCT03466606) included patients aged ≥50 years undergoing elective coronary artery bypass grafting and/or valve surgery. Participants were randomized 1:1 to 4-6 weeks of multimodal prehabilitation (exercise training, nutritional support, and psychological support) or standard preoperative care. Cognitive function was assessed at baseline and 3 months postoperatively using an age- and education-adjusted neuropsychological battery. POCD was defined as performance ≥1.5 standard deviations below normative values in at least 2 cognitive tests, excluding the Mini-Mental State Examination. Logistic regression analyses were performed to evaluate factors associated with POCD. RESULTS: Of 160 participants screened from the parent trial, 134 met eligibility criteria for the substudy and were randomized; 116 completed 3-month follow-up (prehabilitation n = 53; control n = 63). POCD occurred in 29 patients (25%), including 15/53 (28%) in the prehabilitation group and 14/63 (22%) in controls (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.54-3.50, P = 0.52). In multivariable analysis, preoperative cognitive impairment was independently associated with POCD (OR 13.28, 95% CI 4.06-43.41, P < 0.001), whereas prehabilitation was not (OR 1.09, 95% CI 0.35-3.45, P = 0.877). Higher physical activity levels at 3 months were associated with lower odds of POCD (OR 0.97, 95% CI 0.95-1.00, P = 0.047). CONCLUSIONS: In this randomized controlled trial, a 4-6-week multimodal prehabilitation program did not reduce postoperative cognitive dysfunction 3 months after cardiac surgery. Although the intervention did not achieve measurable cognitive protection, the observed association between postoperative physical activity levels and postoperative cognitive dysfunction warrants further investigation.

Humans↗

PubMed2026

Siglec-7 orchestrates mitochondrial dynamics and metabolic reprogramming to restrain human NK cell cytotoxic function.

Natural killer (NK) cells are innate lymphocytes that directly eliminate tumor and virus-infected cells by integrating signals from activating and inhibitory receptors, and their effector functions are tightly coupled to cellular metabolism. Given that the inhibitory receptor PD-1 reprograms T cell metabolism to shape functional fate, the bioenergetic consequences of inhibitory receptor engagement on human NK cells remain largely unexplored, particularly for sialic acid-binding immunoglobulin-like lectin (Siglec-7), a glyco-immune checkpoint receptor. Here, we investigated metabolic programs and effector functions associated with Siglec-7 expression and antibody-mediated Siglec-7 ligation in primary NK cells and NK-92MI cells. Siglec-7POS NK cells exhibited selectively impaired CD107a degranulation under glycolytic and oxidative phosphorylation inhibition, whereas Siglec-7NEG cells remained relatively resistant, indicating distinct energetic wiring between these subsets. Engagement of Siglec-7 by an agonistic antibody induced mitochondrial fission with altered Drp1 phosphorylation, transient mitochondrial depolarization, and broadly suppressed mitochondrial respiration, while concurrently enhancing glycolytic capacity, consistent with a dual metabolic shift upon Siglec-7 ligation. In contrast, sustained Siglec-7 expression in NK-92MI-S cells was associated with globally enhanced mitochondrial respiratory capacity, indicating that sustained Siglec-7 expression and short-term treatment with an agonistic anti-Siglec-7 antibody were associated with distinct metabolic profiles in NK cells. Furthermore, Siglec-7POS NK cells showed increased accumulation of autophagic vacuole, reduced proliferation, and heightened apoptotic susceptibility compared with Siglec-7NEG counterparts. Collectively, these findings support an association between Siglec-7 status, mitochondrial homeostasis, and metabolic fitness in NK cells, with Siglec-7NEG cells retaining a metabolically robust, cytotoxic phenotype.

Journal Article↗

PubMed2026

A machine learning-derived and functionally validated circadian rhythm signature predicts clinical outcomes and in silico drug sensitivity in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) displays considerable heterogeneity in clinical outcomes, highlighting the need for reliable prognostic biomarkers. While the aberrant expression of circadian rhythm-related genes has been implicated in cancer pathogenesis, its comprehensive role in CRC progression and predicted therapeutic vulnerabilities remains inadequately characterized. METHODS: Bulk and single-cell RNA-sequencing data were integrated from multiple CRC cohorts. A circadian rhythm signature (CRS) was developed through machine learning algorithms and validated for prognostic value. Comprehensive analyses of tumor microenvironment, genomic alterations, and drug sensitivity were performed. Furthermore, the biological function of the core gene, BHLHE40, was validated in CRC cell lines through CCK-8, EdU, and wound healing assays. RESULTS: Single-cell analysis demonstrated an elevated expression signature of circadian rhythm-related genes in dendritic cells. The optimized CRS, comprising 14 circadian rhythm-related genes, successfully categorized patients into high- and low-risk groups. Patients with a high CRS showed markedly poorer overall survival and computationally inferred immunosuppressive features, including reduced CD8+ T cell infiltration and increased M2 macrophage polarization. Genomic analysis revealed enhanced mutation burden in TP53 and alterations in RTK-RAS/WNT pathways. Notably, in vitro assays confirmed that BHLHE40 is significantly overexpressed in CRC cells. Knockdown of BHLHE40 markedly inhibited tumor cell proliferation and migration. Drug sensitivity profiling identified bexarotene and SMER-3 as potential therapeutic options for high-CRS patients. A nomogram integrating CRS with clinical parameters demonstrated superior predictive accuracy for 1-, 3-, and 5-year survival. CONCLUSIONS: The CRS represents a promising prognostic biomarker that reflects tumor immune status and genomic features, providing valuable insights for personalized treatment strategies in CRC.

Circadian rhythm↗

PubMed2026

Safety profiles of CAR-T cell therapy in systematic autoimmune diseases: a systematic review and analysis.

BACKGROUND: Chimeric antigen receptors (CARs)-T cell therapy is emerging as a potent approach for autoimmune diseases. However, its application in autoimmune conditions remains limited, and safety outcomes observed in malignancies can't reliably serve as a reference. Therefore, it's necessary to summarize the safety profiles in autoimmune diseases to provide evidence for future expanding trials. METHODS: A systematic review was conducted to analyze the CAR-T therapy safety in rheumatic diseases via database searches up to December 2025. Studies reporting safety data were included, while abstracts, reviews, and cases with malignancies were excluded. Factors associated with cytokine release syndrome (CRS) were analyzed using Firth's penalized logistic regression. RESULTS: This study included 38 studies, involving a total of 115 patients with autoimmune disease. Severe adverse events were rare. CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 70.4% and 4.3% of patients, respectively. Most CRS were low-grade. Multivariate analysis identified BCMA-targeted therapy and allogeneic CAR-T products may as independent factors associated with a reduced risk of CRS. Transient hematologic toxicity and hypogammaglobulinemia were frequently reported, with infections occurring in nearly half of the patients. However, prolonged cytopenia and severe infection were infrequent. CONCLUSION: Based on the current available evidence, CAR-T therapy appears to have a generally manageable safety profile in autoimmune diseases, supporting its potential as a promising treatment option for patients with relapsed or refractory autoimmune diseases. However, these findings remain preliminary, and further expanded studies are warranted in the future to provide higher-level evidence.

Humans↗

PubMed2026

[Complex therapy of chronic bacterial prostatitis using the immunomodulatory drug sodium aminodihydrophthalazinedione].

INTRODUCTION: Chronic bacterial prostatitis (CBP) is characterized by a recurrent course caused by pathogen persistence and impaired local immunity of the prostate. AIM: To assess the effectiveness of the use of sodium aminodihydrophthalazinedione in the complex therapy of chronic bacterial prostatitis. MATERIALS AND METHODS: The prospective comparative study included 60 men aged 21-50 years with CBP (NIH category II). Patients were randomized into two groups of 30: the comparison group received levofloxacin 500 mg/day for 28 days; the main group additionally received rectal sodium aminodihydrophthalazinedione. NIH-CPSI, IPSS, QoL, uroflowmetry, leukocyte and lecithin body counts in prostatic secretion, and bacteriological examination were assessed at baseline and on day 28, and the recurrence rate over 3 months. RESULTS: By day 28, the main group showed a more pronounced decrease in the total NIH-CPSI score (8.1+/-2.1 vs 13.4+/-2.6; p<0.001), restoration of lecithin bodies (+65.1% vs +24.5%; p<0.05), normalization of uroflowmetry, and pathogen eradication in 86.7% vs 66.7% of patients (p<0.05). The 3-month recurrence rate decreased from 26.7 to 10.0% (p<0.05). No adverse events were registered. DISCUSSION: The advantage of combinationtherapy is due to the combination of anti-inflammatory,immunomodulatory,antioxidantandregenerativeeffects of the drug,which is confirmed by the restoration of the secretoryfunction of the prostateepitheliumaccording to the dynamics of lecithingrains. CONCLUSION: The inclusion of sodium aminodihydrophthalazinedione in the combination therapy of CBP increases the clinical and microbiological efficacy of treatment and reduces the recurrence rate.

Humans↗

PubMed2026

Transcriptomic responses to developmental temperature in two field-collected Spodoptera exigua populations from Korea.

The beet armyworm, Spodoptera exigua, is a polyphagous insect whose development and seasonal occurrence are strongly influenced by temperature. However, transcriptomic responses to developmental thermal regimes remain insufficiently characterized in field-collected populations. In this study, we compared two Korean field-collected populations of S. exigua: a Haenam population collected in May and initially maintained at 15 ± 1 °C (HN), and a Jeju population collected in July and initially maintained at 27 ± 1 °C (JJ). F1 larvae from each population were reared under three fluctuating developmental temperature regimes: low (15-21 °C), middle (21-27 °C), and high (27-33 °C), followed by RNA-seq analysis. Differential expression analysis revealed population-associated variation in transcriptomic responses across developmental temperatures. HN exhibited a larger number of differentially expressed genes under the high-temperature regime, suggesting stronger transcriptomic sensitivity to elevated developmental temperature. Functional enrichment analyses identified population-associated differences in pathways related to heat response, oxidative metabolism, cytoskeletal organization, cuticle-associated processes, lipid metabolism, and immune-related functions. In JJ, heat-response and cuticle-related expression patterns were more prominent under warmer developmental conditions, whereas HN showed broader changes in stress- and metabolism-associated pathways under high temperature. Overall, this study provides a comparative transcriptomic analysis of two field-collected S. exigua populations under different developmental temperature regimes and identifies RNA-seq-based molecular response patterns associated with population-specific thermal response profiles.

Animals↗

PubMed2026

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 °C). Two SNPs, PcHsp70-1 (SNP258) and PcHsp70-2 (SNP555) were examined to associate with high temperature tolerance in three populations (n = 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 + 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↗

PubMed2026

Using Organoids to Unlock the Potential of Human Torpor for Spaceflight.

PURPOSE OF REVIEW: This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. RECENT FINDINGS: On future deep space missions such as NASA's planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement - all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. SUMMARY: This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.

Astronaut Health↗

PubMed2026

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‰), 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‰). 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↗

PubMed2026

The composition of the periostracum in the razor clam Sinonovacula constricta and the mantle's response to sulfide.

The razor clam Sinonovacula constricta inhabits sulfide-rich intertidal sediments and exhibits remarkable tolerance to this toxicant, yet the role of its periostracum in sulfide adaptation remains poorly understood. In this study, we investigated the composition and structure of the periostracum proteins, and the response of the mantle to sulfide stress. Scanning electron microscopy and energy-dispersive X-ray spectroscopy revealed that the periostracum is approximately 10 μm thick and contains 1.43 wt% sulfur, and proteomic analysis further confirmed the presence of organic sulfur (Cys/Met-rich proteins), suggesting its involvement in sulfur deposition. Using LC-MS/MS, we identified 77 high-confidence proteins from the periostracum, which were classified into six functional categories: enzymes, framework proteins, immune-related proteins, calcium ion-related proteins, other proteins, and proteins with unknown functions. Phylogenetic analyses of representative proteins revealed bivalve-specific evolutionary patterns, with several proteins exclusively present in Bivalvia, such as Unknown protein 2 and 7, which possess signal peptides and low-complexity domains. For the sulfide exposure experiment, razor clams were subjected to three Na2S concentrations (0, 10, and 100 μM). qPCR analysis showed that, compared with the control group, Chitin-binding protein 3 and Tyrosinase were significantly upregulated in the mantle, peaking in the 100 μM group at 48 h (5677.84-fold and 157.20-fold, respectively), whereas Collagen and Cadherin 3 were generally suppressed. This study represents one of the most comprehensive proteomic profiles of the razor clam periostracum and highlights the mantle's potential role in sulfide tolerance, offering insights for sulfur-tolerant aquaculture breeding and bioremediation applications.

Animals↗

PubMed2026

Identification of CXCL13 as an agonist and CXCL11 as an inverse agonist for the viral G protein-coupled receptor ORF74.

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latent infection in humans, but under conditions of immune suppression, it may reactivate and contribute to severe diseases, including Kaposi's sarcoma (KS) and B-cell malignancies. The KSHV genome encodes a single G protein-coupled receptor (GPCR), open reading frame 74 (ORF74), which shows homology to human chemokine receptors. Since its identification in 1996, ORF74 has subsequently been shown to interact with a broad range of human CXC chemokines, as well as CCL1 and the viral chemokine vCCL2. Compared with many human chemokine receptors, ORF74 displays high basal activity. These properties allow ORF74 to deregulate host cellular pathways through constitutive and chemokine-modulated signaling. In this study, we evaluated several human chemokines that, to our knowledge, had not previously been tested in ORF74-dependent cellular assays. Whereas CXCL9, CXCL14, CXCL16 and CXCL17 did not interact with ORF74, CXCL13 was identified as an additional ORF74 agonist and CXCL11 as an inverse agonist. CXCL13 dose-dependently induced ORF74-mediated Ca2+ release, β-arrestin1/2 recruitment and chemotaxis, and enhanced basal nuclear factor κB (NF-κB) activity in ORF74-expressing cells. In contrast, CXCL11 showed no detectable ORF74 agonist activity in the calcium mobilization or chemotaxis assay, but antagonized CXCL1-induced responses in both readouts. CXCL11 also elicited inverse agonist-like responses in β-arrestin1/2 recruitment assays and reduced basal NF-κB signaling. Our study thus reveals CXCL13 and CXCL11 as two additional chemokine ligands for ORF74, further expanding the pharmacological profile of this viral GPCR.

Humans↗