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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

A systematic review of macaque brain stimulation: Trends and future directions.

Neurostimulation techniques can powerfully modulate neural circuit activity and provide causal insights into the relationship between brain function and behavior. Macaque monkeys have long been a key animal model for brain stimulation studies. While stimulating the macaque brain with one or a few electrodes has already taught us much about brain function and dysfunction, recent technological advances promise a future with more precise stimulation using many more electrodes. However, such possibilities also increase the number of choices an experimenter has when designing their study. We can learn from a rich past, but a comprehensive overview of which brain regions have been studied and with what stimulation parameters is lacking. Here, we present a PRISMA-compliant systematic review of 734 macaque brain stimulation studies using electrical and/or optogenetic stimulation. We find a striking bias in which brain areas have traditionally been stimulated: a mere 10 brain regions account for half of all studies, with the remainder of studies investigating approximately 150 other areas. Across studies, stimulation frequency robustly predicted direct behavioral effects independent of brain region, while amplitude did not. Future studies could more systematically explore less studied regions through lower stimulation frequencies (e.g., 20-50 Hz) alongside established ranges (∼200 Hz). Tools such as fMRI or optical imaging can capture neural circuit engagement evoked by these frequencies, even when behavioral effects are absent or remain subtle. Our synthesis offers a guide towards the next steps in high-channel-count, high-precision stimulation approaches.

Animals

Sex-dependent protective effects of microglial tumor necrosis factor on post-stroke inflammation and myelin injury.

Tumor necrosis factor (TNF) is rapidly induced after ischemic stroke, but its proposed cell-specific and sex-dependent functions during post-stroke inflammation remain insufficiently understood. Here, we investigated the role of microglia-derived TNF in the acute and subacute response to permanent middle cerebral artery occlusion (pMCAO). Tnf expression was transiently upregulated after stroke, becoming significant at 4 h, peaking at 12-24 h, and returning to baseline by 5 days. In situ hybridization confirmed strong Tnf expression in the infarct and peri-infarct regions. Whole-brain transcriptomic profiling showed that global TNF deficiency reshaped the early post-ischemic response, shifting it from microglia-associated phagocytic and wound-healing pathways toward an interferon-related inflammatory signature. To define the specific contribution of microglial TNF, we used inducible Cx3cr1CreER:Tnffl/fl mice. Microglial TNF deletion had no effect on infarct volume in males at 24 h or 5 days after pMCAO, but significantly increased infarct size in females at both time points. In both sexes, brain TNF levels peaked at 24 h and were significantly reduced in Cx3cr1CreER:Tnffl/fl mice, confirming microglia as a major source of early post-ischemic TNF. However, downstream consequences diverged by sex. At 5 days, male Cx3cr1CreER:Tnffl/fl mice showed reduced microglial reactivity and 18 kDa translocator protein (TSPO) signal, with no change in T-cell infiltration, and exhibited increased density of mature oligodendrocytes. In contrast, female Cx3cr1CreER:Tnffl/fl mice displayed enhanced microglial reactivity, increased TSPO binding, higher peri-infarct T-cell infiltration, and reduced oligodendrocyte density and myelin integrity. Together, these findings identify microglial TNF as a sex-dependent regulator of post-stroke inflammation and myelin injury.

Animals

Transcriptomic insights into the molecular mechanism of antifouling agent-induced settlement inhibition in the Pacific oyster Crassostrea gigas.

Marine biofouling remains a persistent challenge to maritime industries and marine ecosystems worldwide. In this study, we systematically evaluated the acute toxicity, settlement inhibitory efficacy, and underlying molecular mechanisms of an N-oleyl-1,3-propanediamine-based antifouling agent using pediveliger larvae of the Pacific oyster Crassostrea gigas. The 96 h-LC50 of the agent was determined to be 0.81 mg/L, and exposure to 1.68 mg/L achieved complete larval settlement inhibition without inducing significant acute toxicity. Transcriptomic analysis identified 791 differentially expressed genes, dominated by downregulated genes associated with ribosomal function, translation, cell adhesion, and cytoskeletal organization. The agent exerts its inhibitory effect primarily through the global suppression of protein synthesis, disruption of cell-substrate adhesion and cytoskeletal integrity, and induction of proteotoxic stress responses. These findings reveal a multi-pathway molecular mechanism underlying antifouling agent-induced settlement inhibition in oyster larvae and provide key molecular biomarkers to support the development of eco-friendly antifouling technologies.

Animals

Positive Margin Rate Following Transoral Surgery in T2-T3 Laryngeal Carcinoma - a Systematic Review and Meta-Analysis.

BACKGROUND: Transoral endoscopic surgery, using either conventional laser techniques or supported by robotic assistance, represents an established treatment modality for selected patients with T2-T3 laryngeal carcinoma. The goal is complete tumor removal, as positive resection margins have been associated with worse oncological outcomes. This systematic review and meta-analysis aimed to determine the positive margin rate following transoral endoscopic surgery for T2-T3 laryngeal carcinoma and to evaluate its impact on oncologic outcomes. METHODS: A systematic search of Medline, Embase, Web of Science, Cochrane CENTRAL, and Google Scholar was performed from inception through March 2025, identifying studies reporting on surgical margin status after transoral resection of T2 and/or T3 laryngeal carcinoma. A random-effects meta-analysis of proportions was used to estimate a pooled positive margin rate. The oncologic impact of margin status is presented descriptively owing to data heterogeneity. RESULTS: Thirty-nine studies comprising 3,281 patients with T2-T3 laryngeal carcinoma met the inclusion criteria. The positive margin rate was 22.0% (95% CI 17.6 - 27.3, I2 = 83.8%) for the total T2-T3 cohort, with stratified rates of 22.4% for T2 and 30.8% for T3 tumors. Among the eight studies assessing the impact of positive margins in T2-T3 stages, three found a significant association with worse oncological outcomes. Conclusion A 22% positive margin rate was identified in T2-T3 laryngeal cancer treated with transoral endoscopic resection. However, the impact of margin status on oncological outcomes remains uncertain, largely due to challenges in sampling and histopathological assessment.

Humans

Measuring Coping Strategies in Daily Life: A Systematic Review of Experience Sampling Methodology and Daily Diary Studies.

Advances in daily diary methods and experience sampling method (ESM) have improved the study of coping strategies in daily life and their role in shaping health and well-being. In this review, we examine study designs, measurement approaches, and analytical practices used to investigate coping in natural contexts. We performed a systematic review of studies published before 5 December 2025 that used daily diary or ESM to measure coping strategies over multiple days or moments. Studies were examined with regard to sampling schemes, assessment frequency and duration, measurement of coping strategies, incorporation of stressor appraisals, and analytic techniques used to model coping processes. Fifty-five studies met the inclusion criteria. Results indicated that 80% employed end-of-day diary designs, generally lasting 1-3 weeks, whereas higher-frequency ESM protocols were less common and ranged 2-14 days. Coping strategies were often assessed using abbreviated or single-item measures, frequently adapted from established questionnaires. Many studies incorporated appraisals such as perceived stressor intensity or controllability, enabling tests of coping flexibility. Multilevel modelling was the dominant analytic approach, allowing researchers to distinguish within-person dynamics from between-person differences. However, analyses were predominantly concurrent, and temporally ordered models remained comparatively rare. Overall, the literature demonstrates substantial progress in capturing coping in everyday contexts, yet heterogeneity in measurement and limited use of temporal modelling constrain cumulative knowledge about the temporal links between coping and psychological and physiological health outcomes. Future research would benefit from greater alignment between theoretical assumptions, assessment strategies, and analytic methods.

Humans

Boosting domestic wastewater treatment with quorum signal-augmented heterotrophic nitrification-aerobic denitrification bacterial-algal aerobic granular sludge.

The aerobic bacterial-algal granular sludge (ABGS) enhanced with heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria, as a novel symbiotic technology, exhibits fluctuating treatment efficiency and unstable performance primarily due to the unstable symbiotic relationship. This study proposes an innovative approach to strengthening the bacteria-algae symbiosis by introducing exogenous signaling molecules. Concurrently, high-throughput, correlation analysis of environmental factors and metagenomic sequencing techniques are employed to elucidate the enhancement mechanisms of the signaling molecules. The results demonstrate that signaling molecule enhancement boosted total nitrogen (TN) removal efficiency by 24.51 % in the bacteria-algae symbiotic system (X1). Scanning electron microscopy (SEM) characterization revealed that the addition of signaling molecules resulted in more compact aerobic granular sludge (AGS) and markedly improved stability. High-throughput sequencing showed signaling molecules enriched denitrifying bacteria (Hydrogenophaga, Pseudoxanthomonas, Thauera, Zoogloea) and organic-degrading Desulfomicrobium, optimizing microbial diversity and enhancing nitrogen/organic removal. Correlation analysis of environmental factors indicate that the addition of C8-HSL facilitates the enrichment and functional activation of specific genera. Metagenomic analysis revealed that signaling molecules enhanced the system's denitrification performance by modulating gene expression and associated metabolic pathways. Quantitative polymerase chain reaction (qPCR) analysis further confirmed that the signaling molecules upregulated the expression of the napA, nirK, and nirS genes. An increased abundance of the napA gene facilitated aerobic denitrification (NO₃⁻-N→NO₂⁻-N), while upregulated abundance of the nirK and nirS genes accelerated nitrite reduction (NO₂⁻-N→N₂). This study aims to provide theoretical and practical foundations for implementing advanced bacteria-algae symbiotic technologies.

Denitrification

In situ product monitoring in heterogeneous reaction of gaseous trimethylamine on Fe2O3/Fe(NO3)3: Effect of environmental factor and particle property.

Gas-particle reactions represent an important atmospheric heterogeneous transformation process for organic amines (OAs). Environmental factors and particle properties may impact the gas-particle reaction products. Although the products from gas-particle reactions can be monitored by various in situ techniques, related data remain scarce. Here, the interfacial and gaseous products from the reaction of trimethylamine on Fe2O3/Fe(NO3)3 particles under light irradiation with mixed NO2, O2, SO2 and H2O were monitored using in-situ diffuse reflectance Fourier transform infrared spectroscopy and proton transfer reaction time-of-flight mass spectrometry. Dark reaction of gaseous trimethylamine on Fe2O3/Fe(NO3)3 generated two interfacial products types: N-containing ones (CH3NCH2, CH3NO2, (CH3)2NCHO, and CH3N(OH)CHO) and N-free ones (alcohols, aldehydes and acids), both accumulating with reaction progression. Light irradiation and O2 oxidation enhanced formation of these products, while NO2 promoted the production of CH3NO2 and (CH3)2NCHO. H2O and SO2 occupied the active sites of particles to inhibit the formation of all products. Compared to Fe(NO3)3, Fe2O3 showed absolute dominance in contribution to the formation of products. Considering the smaller particle size of Fe2O3 and excess Fe(NO3)3, the physical mixing of them reduced the generation of interfacial products. Furthermore, gaseous products of CH3OH, HCHO, CH3CHO, HCOOH and CH3COOH detection clarified the N-free interfacial products. The presence of Fe(NO3)3 inhibited the formation of HCOOH and favored the formation of CH3CHO in the gas phase. By combining product information with thermodynamic calculations, the heterogeneous reaction pathways of trimethylamine were tentatively proposed. These findings provide a guiding significance for the migration of OAs in real atmospheric environment.

Methylamines

Psychotherapy training in psychiatry: a systematic review and narrative synthesis on the supervision experiences of early-career psychiatrists.

BACKGROUND: Supervision is a fundamental component of psychotherapy training, transforming theoretical knowledge into clinical skills through real-world practice. Psychotherapy training practices vary widely between countries, training programs, and over time, including supervision. Our systematic review aimed to investigate and describe the experiences of psychotherapy supervision through early-career psychiatrists' (ECPs) views. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and PubPsych for survey-based studies on ECPs' experiences of psychotherapy supervision during or after their psychiatry training and reported our findings according to the PRISMA guidelines. Of 32,877 articles screened, 29 articles were included. Each article underwent quality assessment, and results were synthesized narratively. RESULTS: Included articles published between 2000 and 2025, were from Europe (N = 16, 55.1%), the Americas (N = 5, 17.2%), Western Pacific (N = 4, 13.7%), South-East Asia (N = 2, 7%), Eastern Mediterranean (N = 1, 3.5%), and Africa (N = 1, 3.5%), with a total of 4691 participants. Supervision access rates ranged from 26.2% in Nigeria to 85.5% in Russia, with significant variation across countries and psychotherapy modalities. Most ECPs received 50-100 total hours of supervision, frequently delivered in weekly sessions. While formats, individual, group, or mixed, varied by country and training scheme, supervision was generally provided by a psychiatrist-psychotherapist. Common learning techniques included oral consultations and case discussions, followed by audio recordings or transcripts. The need to self-fund psychotherapy supervision costs was identified as a prominent barrier. CONCLUSIONS: Psychotherapy supervision is inconsistent globally, with barriers including supervisor availability and cost. There is a large implementation gap between recommendations and evaluated practice. Digital tools and competency-based frameworks may improve access and quality.

Humans

Efficacy of smartphone- and bibliotherapy-delivered multicomponent lifestyle medicine interventions for probable depression: A three-arm randomized controlled trial.

BACKGROUND: This study examined the efficacy of smartphone- (AG) and bibliotherapy-delivered (BG) lifestyle medicine (LM) interventions compared with a waitlist control group (WLG) in reducing depressive symptoms. METHODS: A total of 122 adults with probable depression were randomized to AG (n&#xa0;=&#xa0;41), BG (n&#xa0;=&#xa0;40), or WLG (n&#xa0;=&#xa0;41). AG and BG received the same core 8-week multicomponent LM intervention via a smartphone application or booklets, respectively. The core content included lifestyle psychoeducation, physical activity, diet and nutrition, stress and sleep management, goal-setting, and motivational techniques. Outcomes were assessed at baseline and immediate post-intervention (Week 9) in all groups, with 1-month (Week 13) and 3-month (Week 21) follow-ups conducted in the intervention groups only. RESULTS: At Week 9, AG (d&#xa0;=&#xa0;0.89) and BG (d&#xa0;=&#xa0;0.64) showed significantly greater reductions in depressive symptoms than WLG, with within-group improvements maintained at 1- and 3-month follow-ups (ps&#xa0;<.001, d&#xa0;=&#xa0;0.77-0.96). Clinically significant improvement was achieved by 78% of AG and 55% of BG participants, both significantly higher than WLG (19.5%; ps&#xa0;<.001). Compared with WLG, both interventions yielded greater improvements in overall lifestyle and physical activity (d&#xa0;=&#xa0;0.59-0.91) at Week 9. The AG showed additional benefits for perceived stress, health responsibility, nutrition, spiritual growth, and stress management (d&#xa0;=&#xa0;0.58-0.73), whereas BG uniquely improved insomnia symptoms (d&#xa0;=&#xa0;0.83). CONCLUSION: Smartphone- and bibliotherapy-delivered LM interventions are efficacious for managing probable depression. Further RCTs comparing them with established treatments are warranted.

Humans

Effect of transcutaneous auricular vagus nerve stimulation on postoperative pain in patients undergoing thoracoscopic partial lung resection: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Postoperative pain after thoracic surgery remains common and challenging. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique with potential analgesic effects. This study aimed to evaluate the efficacy and safety of taVNS for postoperative pain management in patients undergoing thoracoscopic partial lung resection. METHODS: Adults undergoing thoracoscopic partial lung resection were randomized to active or sham taVNS. The primary outcome was cough pain intensity at 48h post-surgery, assessed by Numeric Rating Scale (NRS). Secondary outcomes included cough pain at 24h and 72h, resting pain, moderate-to-severe pain incidence,&#xa0;opioid consumption, quality of recovery, postoperative pulmonary complications , chest tube duration, hospital stay, postoperative nausea/vomiting, and adverse events. RESULTS: Among 119 analyzed patients (active n&#x2009;=&#x2009;60, sham n&#x2009;=&#x2009;59), active taVNS reduced cough pain scores at 24h, 48h, and 72h postoperatively, as well as resting pain (p < 0.05). It also lowered the incidence of moderate-to-severe cough pain at 24h and 48h, reduced cumulative postoperative opioid use at 24h and 72h, and decreased rescue analgesia on postoperative day 3 (p < 0.05). Active taVNS was associated with a lower incidence of postoperative pneumothorax (p < 0.05). No serious adverse events occurred. CONCLUSION: Perioperative taVNS was associated with a modest analgesic benefit and reduced postoperative opioid requirements after thoracoscopic partial lung resection. The observed reduction in postoperative pneumothorax requires cautious interpretation, and further multicenter trials are needed to determine its clinical utility.

Humans

Evidence-based insights into medial pedicle reduction mammaplasty: A systematic review and meta-analysis.

BACKGROUND: Breast reduction relieves the physical and psychosocial burden of macromastia. Medial pedicle reduction mammaplasty may enhance vascular reliability, preserve nipple-areola complex (NAC) sensation, and sustain upper pole fullness, even in large-volume reductions. The purpose of this study was to assess the outcomes of medial pedicle breast reduction. METHODS: A search across ScienceDirect, Cochrane, and PubMed was conducted. Included studies reported on perioperative outcomes and complications of medial pedicle breast reduction. Data on demographics, surgical variables, complications, sensory recovery, volumetric changes, and patient satisfaction were extracted. Proportion meta-analysis was performed, and odds ratios were calculated for comparison with inferior pedicle breast reduction. RESULTS: Twenty-five studies comprising 1033 patients met the inclusion criteria. Mean BMI ranged from 27 to 42&#xa0;kg/m2, with mean resection weights between 412 and 3828&#xa0;g. Mean surgical times ranged from 104 to 204&#xa0;min. Pooled complication rates were low: infection 1%, seroma 1%, hematoma 1%, fat necrosis 2%, NAC necrosis 1%, dehiscence 8%, and reintervention 5%. Odds of complications did not differ significantly from inferior pedicle reductions. NAC sensation typically recovered by 6-12 months, with no long-term deficits. Volumetric analyses demonstrated stable breast shape after the first postoperative year, with superior upper pole tissue maintained. Patient satisfaction ranged 75-100%, with higher ratings for scar appearance and overall aesthetics in medial pedicle reductions. CONCLUSION: Medial pedicle breast reduction is a well-established and reproducible technique, preserving NAC sensation, achieving stable long-term shape, and enhancing upper pole fullness. It offers satisfactory aesthetic outcomes compared to other traditional methods, even in large-volume reductions.

Humans

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

Determination of 13 per- and polyfluoroalkyl substances in human plasma samples using LC-MS/MS: application to capillary microsamples.

Per- and polyfluoroalkyl substances (PFAS) are chemicals widely applied in industrial processes and highly persistent in the environment, whose extensive use has been linked to adverse health effects. Venous plasma is the conventional matrix for PFAS assessment in blood, and LC-MS/MS is the most used quantification technique. Despite the relevance of this topic, biomonitoring data on human exposure to PFAS in Brazil remain limited. This study validated an LC-MS/MS method for determination of 13 PFAS in human plasma. Blood samples were collected from volunteers by phlebotomy, followed by protein precipitation with acetonitrile containing 1% formic acid (v/v) and solid-phase extraction. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column. The assay was linear over a calibration range of 0.2-20&#xa0;ng/mL. Intra- and inter-assay precision (CV%) were within the ranges of 2.06-12.0% and 0.25-10.7%, respectively. As for accuracy, results were 89.0-112.9%. Matrix effect ranged from -1.31 to 0.05%. Stability after four freeze/thaw cycles and under autosampler conditions were also confirmed for all analytes. The method was applied to 40 paired venous and capillary plasma samples. Both measures exhibited high correlation (r&#xa0;=&#xa0;0.926). PFOS was the only compound detected at concentrations &#x2265;0.2&#xa0;ng/mL (LLOQ) in all samples, with capillary plasma concentrations of 0.85-13.50&#xa0;ng/mL. In summary, the method showed good validation performance and demonstrated the suitability of capillary plasma samples as an alternative matrix for PFAS quantification.

Humans

Comparison of ultrasound-guided two-point block of the rhomboid intercostal vs. thoracic paravertebral for postoperative analgesia in patients undergoing three-port thoracoscopic surgery: a prospective, randomized, non-inferiority study.

BACKGROUND: The anesthetic characteristics of ultrasound-guided two-point rhomboid intercostal block (RIB) have not been fully established. This study compared the analgesic efficacy of ultrasound-guided two-point RIB with that of two-point thoracic paravertebral block (TPVB) for postoperative pain control and recovery in patients undergoing three-port thoracoscopic surgery. METHODS: Seventy patients aged 18-80&#x2009;years scheduled for three-port thoracoscopic pulmonary resection were block-randomized in a 1:1 ratio to receive either TPVB or RIB. Both techniques were performed using 10&#x2009;mL of 0.5% ropivacaine at each injection site. The primary outcome was the numerical rating scale (NRS) pain score at rest 24&#x2009;h after surgery, with a predefined non-inferiority margin of &#x394;&#x2009;=&#x2009;1. Secondary outcomes included NRS at rest and during coughing at 0.5, 2, 4, 12, 18, 24, and 48&#x2009;h postoperatively, as well as the 24h postoperative Quality of Recovery-40 (QoR-40) score. RESULTS: The final analysis included 34 patients in the TPVB group and 34 in the RIB group. The mean difference in resting NRS scores at 24&#x2009;h between the two groups was 0.088 (95% CI, -0.377 to 0.553), confirming the non-inferiority of RIB. However, the need for rescue analgesia was numerically greater in the RIB group than in the TPVB group (p&#x2009;=&#x2009;0.045). The 24-h postoperative QoR-40 scores and cumulative sufentanil consumption within 48&#x2009;h after surgery were comparable between the groups (both p&#x2009;>&#x2009;0.05). CONCLUSION: Ultrasound-guided two-point RIB provided postoperative analgesia that was non-inferior to TPVB in patients undergoing three-port thoracoscopic surgery.

Adolescent

A pragmatic randomized controlled trial of self-directed online writing interventions for posttraumatic stress symptoms in a real-world digital setting.

Background: Public health and other large-scale crises, such as the COVID-19 pandemic, have intensified the global mental health burden, creating unprecedented demand for accessible interventions for posttraumatic stress symptoms (PTSS).Objective: We evaluated the feasibility and effectiveness of two self-directed online writing interventions embedded within China's WeChat ecosystem during the COVID-19 pandemic through a pragmatic randomised controlled trial.Methods: Between December 2021 and August 2022, 1,526 adults were screened for PTSS via a Tencent Medinfo Mini-Program. Eligible participants (n&#x2009;=&#x2009;211) were randomised to Guided Narrative Technique-Writing (GNT-W, n&#x2009;=&#x2009;100) or Expressive Writing (EW, n&#x2009;=&#x2009;111). Both interventions comprised three self-directed daily writing sessions delivered entirely online without human support. Primary outcome was PTSD symptom severity (PTSD Checklist-Short), assessed at baseline, post-intervention, 2-week, and 1-month follow-ups.Results: While initial engagement followed typical digital health patterns (64.5% overall attrition), participants who initiated treatment showed strong adherence (77% completion). Both interventions were associated with significant within-group reductions in PTSS severity (GNT-W: b&#x2009;=&#x2009;-0.43, p&#x2009;=&#x2009;.023, d&#x2009;=&#x2009;-0.43; EW: b&#x2009;=&#x2009;-0.60, p&#x2009;=&#x2009;.001, d&#x2009;=&#x2009;-0.58), with no significant between-group difference (group &#xd7; time: b&#x2009;=&#x2009;0.18, p&#x2009;=&#x2009;.48). GNT-W did not confer additional benefit over EW protocol on PTSS severity.Conclusions: Both self-directed writing interventions were associated with within-group reductions in PTSS; without an inactive control condition, however, these changes cannot be firmly attributed to the interventions. GNT-W showed no advantage over the simpler EW protocol. These findings offer preliminary support for embedding scalable, low-barrier writing interventions in widely used digital platforms.Chinese Clinical Trial Registry: ChiCTR2000034836.

Humans

Transcriptomic insights into the coordinated regulation of signaling, apoptosis, immunity, and metabolism during Sinonovacula constricta larval metamorphosis.

Metamorphosis is a critical ontogenetic transition for marine bivalves, marking the shift from planktonic to benthic lifestyles, where successful transformation dictates survival. The razor clam Sinonovacula constricta is economically important; however, low larval metamorphosis rates remain a major bottleneck in seedling production. To elucidate the mechanisms governing this process, we performed a comparative transcriptome analysis of S. constricta larvae at pre- and post-metamorphosis stages using Illumina sequencing. A total of 3701 differentially expressed genes (DEGs) were identified, including 3254 up-regulated and 447 down-regulated genes. Functional annotation of the respective top 20 significantly up-regulated and down-regulated DEGs indicated their potential pivotal roles in signal transduction (e.g., up-regulated: CAV1, CHRNA2; down-regulated: APP, NOTCH1), cellular proliferation and differentiation (e.g., up-regulated: TUBA, EGF1; down-regulated: KIF23, TTC25), transcriptional and epigenetic regulation (e.g., up-regulated: NFIL3; down-regulated: OVO, HMX1), substance transport (e.g., up-regulated: LRP2, LRP1B; down-regulated: SLC51A, Slc33a1), substance metabolism (e.g., up-regulated: CPK3, CYP26A1; down-regulated: RDMT1, ADAC), immunomodulation (e.g., up-regulated: CPN2, CRISP2), and protein homeostasis (e.g., up-regulated: HSP27, NAS-27). Functional enrichment analysis further revealed that DEGs were significantly enriched in pathways related to signal transduction and developmental regulation (e.g., Ras, TNF), cell death and homeostasis (e.g., apoptosis), immune responses (e.g., Toll-like receptor), energy metabolism (e.g., lipid), cardiovascular related (e.g., Fluid shear stress), cell junction and architecture (e.g., Tight junction), and infectious disease (e.g., measles). These results suggest a synergistic interplay between signaling, apoptosis, immunity, and metabolism during S. constricta metamorphosis. This study advances our understanding of marine bivalve metamorphosis and offers candidate genes for further mechanistic studies.

Animals

Herbicolin A, an antifungal lipopeptide produced by Pantoea agglomerans APC 4211 is a promising biocontrol agent against food spoilage fungi.

Fungal contamination of food with yeast and molds is associated with major economic losses due to spoilage and also poses health risks in the form of mycotoxin production. The strain Pantoea agglomerans APC 4211 isolated from leaves of Ilex aquifolium (holly tree) has broad spectrum antifungal activity against a variety of food spoilage fungi. Genomic analysis of the strain confirmed the presence of biosynthetic gene clusters potentially encoding for the enzymatic machinery required for the production of the antifungal lipopeptide herbicolin A. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the cell-free supernatant (CFS) confirmed the presence of molecular masses corresponding to herbicolin A (1300.8&#xa0;Da), and herbicolin B (1138&#xa0;Da). Purified herbicolin A has desirable properties for biotechnological applications, including potent antifungal activity against a range of spoilage fungi, thermal stability and resistance to proteases. The lipopeptide has low cytotoxicity against epithelial cell lines and has minimum inhibitory concentrations (MICs) lower than those of some commercial antifungal drugs (0.2-2.5&#xa0;mg/L). In a model dairy system (10% skim milk), herbicolin A demonstrated excellent solubility and stability, effectively eliminating Aspergillus niger and Penicillium notatum at a concentration of 5&#xa0;mg/L. Overall, the study determines herbicolin's A spectrum against food spoilage organisms and examines potential applications in food. In conclusion, herbicolin A is a potent, naturally occurring antifungal agent with the potential to be applied as a biopreservative in food systems, providing a safe, clean-label, and efficient compound for synthetic preservatives replacement.

Pantoea