Search PubMedSearch

SEARCH · Search PubMed

Results for “voluntary activation”

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

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

639 records · Page 8Linked to original sources

Cerebellar iTBS enhances gait adaptation by modulating cortical sensorimotor network dynamics: a randomized controlled trial.

Gait adaptation enables individuals to maintain locomotor stability under persistent perturbations. Although the cerebellum is critical for sensory prediction error-based (SPE) adaptation, how cerebellar neuromodulation reshapes cortical sensorimotor networks to enhance gait adaptation remains unclear. This study investigated the behavioral effects and underlying cortical neurodynamic mechanisms of cerebellar intermittent theta-burst stimulation (iTBS) on gait adaptation. Thirty-two healthy adults received either active or sham cerebellar iTBS. Participants performed a split-belt treadmill adaptation task before and after intervention. Cortical responsiveness was evaluated using TMS-evoked EEG over primary motor cortex (M1), while resting-state EEG was analyzed to assess spectral power and directional functional connectivity. Compared to sham, cerebellar iTBS significantly enhanced gait adaptation, evidenced by a faster adaptation rate (p = 0.035) and enhanced Early Adaptation SLS (p = 0.011), without altering initial perturbation responses or post-adaptation outcomes. The iTBS increased TMS-evoked α (p = 0.031) and γ (p = 0.022) power in M1, while the α power was correlated with faster adaptation (r = 0.526, p = 0.002). Furthermore, iTBS strengthened PPC-to-M1 directed connectivity in the β (p = 0.025) and γ (p = 0.013) bands. Enhanced parieto-motor directionality were positively associated with adaptation rate (β: r = 0.515, p = 0.003; γ: r = 0.463, p = 0.009). These findings suggest that cerebellar iTBS facilitates gait adaptation by modulating cortical responsiveness and directional sensorimotor network connectivity, providing multi-level neurodynamic evidence for the cerebello-cortical modulation during gait adaptation and offering a strong physiological rationale for targeted neuromodulation in gait rehabilitation strategies.

Humans

Assessing the Frequency of VEXAS-Related Canonical UBA1 Mutations in Myelodysplastic Syndrome Patients.

OBJECTIVES: Somatic mutations in the UBA1 gene cause VEXAS syndrome, which presents with inflammatory and hematological symptoms. Case studies show a strong overlap between VEXAS and myelodysplastic syndrome (MDS). Recognizing VEXAS is important for differential diagnosis in patients with both inflammation and MDS, as accurate identification guides treatment. The study focuses on determining how often canonical UBA1 mutations linked to VEXAS occur in MDS patients. METHODS: Patients diagnosed with MDS were enrolled in the study, and genomic DNA was isolated from bone marrow FFPE samples. Molecular analysis was performed using a specifically designed ARMS-PCR approach. Additionally, protein-protein interaction (PPI) studies combined with bioinformatic analyses were carried out to explore potential links between UBA1 and pyroptosis. RESULTS: Among the 149 MDS patients analyzed, none exhibited high-Variant Allele Frequency (VAF) the canonical UBA1 point mutations linked to VEXAS syndrome. PPI analysis revealed a possible association between UBA1 and the NLRP3 inflammasome component. CONCLUSIONS: Expanding the sample size and using targeted NGS or ddPCR would improve mutation detection sensitivity and could reveal UBA1 canonical and non-canonical variants and more accurately estimate the frequency of VEXAS-related mutations in the MDS population.

Humans

Latent profile analysis of pregnant exercise adherence and the relationship with demographic and socio-psychological factors: a multicentre cross-sectional study.

BACKGROUND: Pregnancy physical activity (PA) and exercise benefits both mothers and babies, but requires sustained adherence. Many pregnant women fail to meet recommended levels. The reasons for low adherence comprised fluctuating physiological and environmental factors. This study aims to identify discrete profiles of pregnant women based on exercise adherence and to examine differences in demographic and socio-psychological factors across these profiles. METHODS: A survey was conducted among 1,255 pregnant women in three hospitals in Shenzhen, Dongguan, and Shunde, China, using the Exercise Adherence Rating Scale (EARS), the Pregnancy Exercise Self-Efficacy Scale (P-ESES), and the Pregnancy Physical Activity Social Support Scale (P-PASSS). In the analysis, EARS items were scored higher, indicating a healthier state (e.g., sufficient time and energy). Latent profile analysis (LPA) was employed to classify adherence profiles, and multinomial logistic regression was used to examine differences in demographic, self-efficacy, and social support across four groups. RESULTS: Four profiles of exercise adherence were identified: (1) Profile 1 (16.97%), characterized by deficits in time and energy, (2) Profile 2 (15.22%), a group with sufficient time resources but the lowest self-efficacy, (3) Profile 3 (43.98%), characterized by high adherence despite moderate barriers, and (4) Profile 4 (23.83%), a group with optimal exercise adherence, confidence, and resources. Women with higher P-ESES (OR: 1.14-1.38) and P-PASSS (OR: 1.04-1.06) scores were more likely to be in Profiles 3 and 4. Additionally, women's partners who never or occasionally exercise were significantly more likely to be categorized into Profile 1 (OR = 0.18 for Profile 4 vs. Profile 1). Furthermore, the first trimester emerged as a significant risk period for lower exercise adherence, whereas overweight/obesity was independently associated with higher odds of membership in Profile 4. CONCLUSION: The study identified four distinct profiles of exercise adherence among pregnant women. 32.19% of participants were in the two lower exercise-adherence groups. Pregnant women in Profile 1 were characterized by challenges related to a lack of time and knowledge. Participants in Profile 2 showed the lowest exercise self-efficacy and social support among the four profiles. Furthermore, women in early pregnancy were more likely to have lower adherence profiles. Hence, targeted interventions addressing these specific groups are warranted to improve exercise adherence during pregnancy.

Humans

Copper-Containing Surface Engineering for Soft-Tissue Biomedical Devices: Structure-Function Relationships and Ion Release-Driven Biological Performance, A Systematic Review.

Copper and copper-based materials have gained increasing attention for the functional modification of implantable medical devices intended for prolonged soft-tissue contact, including vascular stents, catheters, and intrauterine devices. Owing to their broad-spectrum antimicrobial activity, redox reactivity, and involvement in angiogenesis and cellular signaling, copper-based systems offer significant potential for multifunctional surface engineering. However, achieving a balance between antibacterial efficacy, corrosion behavior, controlled ion release, and cytocompatibility remains a critical challenge. This PRISMA-compliant systematic review analyzes copper-containing materials and surface modification strategies for soft-tissue biomedical applications. A structured search of Scopus, Web of Science, and PubMed (2015-2025) identified 65 eligible studies. The review encompasses bulk copper-containing alloys, electrochemical and chemical surface modification techniques, physical vapor deposition approaches, and advanced hybrid systems integrating copper with polymers, hydrogels, or metal-phenolic networks. Across the reviewed literature, antibacterial performance was strongly dependent on copper concentration, microstructural distribution, and spatiotemporal ion release profiles. Moderate, well-controlled copper incorporation frequently improved antibacterial efficacy while maintaining acceptable hemocompatibility and cytocompatibility, particularly in vascular and blood-contacting devices. In contrast, excessive copper loading often accelerated corrosion and induced adverse cellular responses. Emerging multifunctional architectures demonstrated improved regulation of biological interactions, enabling simultaneous antibacterial, antithrombotic, and proendothelial effects. Overall, copper-based surface technologies represent a versatile platform for soft-tissue implant modification. Future translational progress will require precise control of copper release kinetics and comprehensive long-term in vivo validation to ensure safety and sustained therapeutic performance. From the authors' perspective, the most promising future direction involves multifunctional copper-based hybrid coatings capable of dynamically regulating ion release, host tissue integration, and antibacterial performance simultaneously. Strategies integrating hierarchical architectures, stimulus-responsive release systems, and clinically scalable fabrication methods are expected to play a key role in translating copper-containing surfaces from experimental concepts toward commercially viable soft-tissue biomedical devices.

Copper

Increasing gut short-chain fatty acids protects intestinal barrier function but does not spare muscle glycogen or impact aerobic performance.

Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is needed. This study aimed to determine whether increasing colonic SCFA availability impacts intestinal barrier function, substrate metabolism, muscle glycogen and aerobic performance in healthy adults. Using a randomized, double-blind, crossover design 12 active men (age 18-30&#xa0;years;40.0&#xa0;&#xb1;&#xa0;7.1&#xa0;mL/kg/min) performed prescribed exercise and consumed a provided diet supplemented with acetylated and butyrylated high-amylose maize starch engineered to deliver SCFA to the colon (HAMS-A/B) or low-amylose maize starch (LAMS) for 7 days, separated by a 2 week washout. Indirect calorimetry, stable isotopes and blood, muscle and urine biomarkers were measured on intervention day 8 while participants completed 90&#xa0;min of steady-state cycle ergometry (ExSS; 60 &#xb1; 5%) followed by a 5&#xa0;km treadmill time trial. HAMS-A/B, relative to LAMS, increased faecal and serum SCFA. Multiple markers of intestinal barrier damage and permeability were lower, and the respiratory exchange ratio during ExSS was higher (0.02 [95% confidence interval (CI): 0.01, 0.03], Ptreatment&#xa0;<&#xa0;0.001) following HAMS-A/B versus LAMS. However no between-treatment difference in glucose turnover, muscle glycogen depletion (14&#xa0;&#xb5;mol/kg/g dry wt. [95% CI: -116, 143], Pinteractio n&#xa0;=&#xa0;0.613) or TT performance (5&#xa0;s [95%CI: -44, 54], Ptreatment&#xa0;=&#xa0;0.816) was observed. Increasing colonic and circulating SCFA modestly altered substrate oxidation and preserved intestinal barrier function during endurance exercise. However effects were not sufficient to spare muscle glycogen or increase aerobic endurance performance, leaving the practical relevance unclear and underscoring challenges inherent in translating promising preclinical findings to humans. KEY POINTS: Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is lacking. A gut microbiota-targeted dietary supplementation strategy was used to deliver SCFA to the colon and successfully increased colonic and systemic SCFA concentrations in healthy, physically active adults before and during an endurance exercise bout and aerobic performance test. Increasing colonic and systemic SCFA availability preserved intestinal barrier function but did not impact glucose turnover, alter protein expression in muscle or spare muscle glycogen during endurance exercise. Increasing colonic and systemic SCFA availability did not impact aerobic endurance performance.

Humans

In vitro evaluation of sacituzumab govitecan in non-small cell lung cancer with actionable genomic alterations.

PURPOSE: The TROP2-directed antibody-drug conjugate sacituzumab govitecan (SG) has shown substantial therapeutic benefit in several malignancies; however, preclinical evidence supporting its activity in non-small cell lung cancer (NSCLC) is rare. MATERIALS AND METHODS: We evaluated 16 NSCLC cell lines harboring actionable genomic alterations for TROP2 expression and treated them with SG or its unconjugated payload, SN-38, for 3 days to determine cytotoxic effects. Apoptosis and DNA damage signaling were assessed using flow cytometry and western blot. SG internalization and lysosomal trafficking were visualized by confocal microscopy. RESULTS: SG had greater cytotoxic potency than SN-38, across all NSCLC cell lines, independent of genomic subtype or TROP2 expression level. Cell lines that were sensitive to SN-38 showed enhanced vulnerability to SG (P < 0.0001). Higher SLFN11 expression, a recognized determinant of SN-38 responsiveness, correlated with lower SG IC50 values. Both SG and SN-38 triggered apoptotic and DNA damage responses within 6-48 h, with SG inducing stronger activation of these pathways than SN-38. SG was efficiently taken up in CUTO17 and SNU-3173 adenocarcinoma cells, with more than 60% of the conjugate internalized within 3 h and subsequently localized to lysosomes. CONCLUSION: Our study provides in vitro evidence supporting the potential activity of SG in NSCLC with actionable genomic alterations. The efficacy of SG closely paralleled intrinsic sensitivity to the SN-38 payload, suggesting that DNA-damage responses, rather than oncogenic drivers, predominantly contribute to SG activity.

Actionable genomic alterations

Inhibitory mechanism of phloretin on the AgrA LytTR domain-agr operon complex formation and its application in beef.

Staphylococcus aureus (S. aureus) represents a major foodborne pathogen whose enterotoxin production poses significant challenges to food safety due to its high environmental resistance and limited efficacy of conventional sterilization. Since the expression of enterotoxins is predominantly governed by the agr quorum sensing system, targeting this regulatory pathway has become a strategic choice for virulence control. This study elucidated the mechanism by which phloretin, a potential quorum sensing inhibitor, interferes with the agr system to attenuate virulence. To achieve this, the recombinant AgrA LytTR domain was expressed and purified, and its interaction with phloretin was characterized using thermal shift assays (TSA), electrophoretic mobility shift assays (EMSA), and molecular dynamics (MD) simulations. The results showed that phloretin specifically binds to the AgrA LytTR domain, enhancing its thermal stability and disrupting AgrA LytTR-agr operon binding by reducing the free energy of interaction between them, without causing significant structural rearrangement. Mechanistic analysis indicated that phloretin sterically hinders key &#x3b2;-sheet turn residues (HIS169, ASN201, ARG233), thereby impairing DNA recognition, downregulating RNAIII transcription, and inhibiting agr signaling. In cooked beef, phloretin significantly inhibited the secretion of enterotoxins and &#x3b1;-hemolysin, while delaying lipid oxidation and protein degradation, and maintaining the meat texture. These findings suggested that phloretin is a multifunctional substance with anti-virulence, antioxidant, and preservative properties, demonstrating its potential as a natural food preservative.

Phloretin

Ultra-high-frequency ECG quantifies residual electrical dyssynchrony during left bundle branch area pacing in patients with wide QRS: a paired within-patient study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may restore a more physiological pattern of ventricular activation in patients with conduction delay; however, QRS narrowing alone may incompletely characterize electrical resynchronization. Ultra-high-frequency ECG (UHF-ECG) provides quantitative markers of ventricular activation timing and dyssynchrony. OBJECTIVE: To quantify paired OFF-to-ON changes in conventional ECG and UHF-ECG metrics during LBBAP in patients with baseline wide QRS and to assess the relationship between paced R-wave peak time (RWPT) and residual UHF-ECG dyssynchrony. METHODS: In this prospective single-center paired study, 21 patients with bradycardia and baseline wide QRS underwent standard ECG and UHF-ECG assessment during intrinsic rhythm (pacing OFF) and during LBBAP (pacing ON). Endpoints included QRS duration, signed VED16, absolute VED16 (|VED16|), mean ventricular delay (meanVD), and a clinically interpretable distance-to-normal metric defined as dist&#xa0;=&#xa0;max(|VED16|-20, 0). Paired changes were summarized as medians with bootstrap 95% confidence intervals and tested using the Wilcoxon signed-rank test. Associations between paced RWPT and residual dyssynchrony during pacing were evaluated using Pearson and Spearman correlation coefficients. RESULTS: LBBAP significantly narrowed QRS duration from 136.8 [130.2-153.6] ms during intrinsic rhythm to 116.0 [107.8-125.6] ms during pacing (median &#x394; -21.0&#xa0;ms; 95% CI -33.9 to -18.6; p&#xa0;<&#xa0;0.001). Signed VED16 did not change significantly (median &#x394; 0.4&#xa0;ms; p&#xa0;=&#xa0;1.000), consistent with the mixed conduction-phenotype composition of the cohort. In contrast, severity-oriented UHF-ECG endpoints improved: |VED16| decreased numerically (median &#x394; -5.2&#xa0;ms; p&#xa0;=&#xa0;0.070), whereas dist decreased significantly (median &#x394; -0.7&#xa0;ms; 95% CI -14.4 to 0.0; p&#xa0;=&#xa0;0.015). The proportion of patients within the normal dyssynchrony band (|VED16|&#xa0;&#x2264;&#xa0;20&#xa0;ms) increased from 7/21 (33.3%) to 12/21 (57.1%). Median paced RWPT was 66.6 [58.6-74.6] ms, and shorter RWPT correlated with lower residual |VED16| during pacing (Pearson r&#xa0;=&#xa0;-0.45, p&#xa0;=&#xa0;0.038). CONCLUSIONS: In patients with baseline wide QRS, LBBAP produces marked QRS narrowing, whereas UHF-ECG provides complementary quantification of residual electrical dyssynchrony. Severity-oriented UHF-ECG endpoints, particularly a distance-to-normal metric, may offer an interpretable mechanistic framework beyond conventional ECG alone. Shorter paced RWPT was associated with lower residual dyssynchrony during pacing, supporting physiological coherence between procedural and high-resolution electrocardiographic markers.

Humans

Psychotherapy vs antidepressants in heart failure: Impact of adherence.

BACKGROUND: Depression affects nearly half of patients with heart failure (HF), which is associated with increased morbidity and reduced health-related quality of life (HRQoL). This secondary per-protocol analysis of a previously published randomized trial evaluated the behavioral activation (BA) versus antidepressant medication (MEDS) among patients with depression and HF who adhered to study interventions. METHODS: This analysis is based on a pragmatic randomized comparative-effectiveness trial conducted from 2018 to 2022, with a 1-year follow-up. 416 participants diagnosed with HF and a DSM-5 depressive disorder were randomized to BA or MEDS, and the current analysis examined outcomes according to treatment adherence. OUTCOMES: The primary outcome was depressive symptom severity (PHQ-9) at 6&#xa0;months, and the secondary outcomes were physical and mental HRQoL (SF-12v2-PC and SF-12v2-MC, respectively) and HF-specific HRQoL (Kansas City Cardiomyopathy Questionnaire; KCCQ) overall and clinical scores (KCCQ-OS and KCCQ-CS), at 3, 6, and 12&#xa0;months. High adherence was defined as completion of >75-100% of intervention components. Overall adherence rates were similar between BA and MEDS. At 6&#xa0;months, among patients with >75-100% adherence who followed treatment as directed in both arms, BA was associated with higher Mental HRQoL (SF-12v2-MC: 5.22; 95% CI: 0.72 to 9.72; p&#xa0;=&#xa0;0.023) and higher HF-specific HRQoL (KCCQ-OS: 16.08; 95% CI: 7.20 to 24.97; p&#xa0;<&#xa0;0.001); (KCCQ-CS: 16.04; 95%CI: 7.05 to 25.02; p&#xa0;<&#xa0;0.001) compared to MEDS. There were no significant differences in depressive symptoms or physical HRQoL at 6&#xa0;months. INTERPRETATION: Both BA and MEDS were equally effective treatments for depression in HF. However, among highly adherent patients, BA was associated with greater improvements in mental and HF-specific HRQoL than MEDS. FUNDING/SUPPORT: The study was funded by PCORI Award Number: 2017C2-7716.

Humans

Context-dependent functional diversity of dorsomedial posterior parietal neurons revealed by single-unit fMRI mapping during naturalistic viewing.

The dorsomedial posterior parietal cortex (dmPPC) plays an important role in episodic processing by integrating sensory, cognitive, and motor information across distributed brain systems. However, how individual dmPPC neurons participate in large-scale functional organization during naturalistic experience remains poorly understood. To address this question, we combined single-unit electrophysiology and awake fMRI in five rhesus macaques of both sexes viewing identical naturalistic video stimuli. Using single-unit fMRI mapping, we generated whole-brain neuron-BOLD functional maps by correlating individual neuronal activity with voxel-wise fMRI signals across the brain. We found that neuron-BOLD functional maps exhibited strong context-dependent organization, with neurons recorded during the same video context showing substantially greater similarity than neurons recorded during different video conditions. Compared with neuronal spiking activity or critical fMRI frames alone, neuron-BOLD functional maps more robustly captured contextual structure. Despite this shared large-scale organization, a substantial subset of neighboring neurons recorded simultaneously from the same electrode displayed markedly distinct whole-brain association patterns, revealing substantial local functional heterogeneity within the dmPPC. This local heterogeneity was not readily explained by waveform-based putative cell class or by opposing neuronal firing dynamics. In addition, distributed cortical and medial temporal regions exhibited highly context-dependent neuron-BOLD association patterns during naturalistic viewing. Together, these findings demonstrate that dmPPC neurons participate in dynamic and heterogeneous large-scale functional organization during naturalistic episodic processing. More broadly, this study establishes single-unit fMRI mapping as a framework for linking single-neuron activity to distributed whole-brain dynamics across contextual conditions.Significance Statement Using single-unit fMRI mapping, this study examined how individual dorsomedial posterior parietal cortex (dmPPC) neurons relate to large-scale brain activity during naturalistic video viewing in macaque monkeys. We found that neuron-BOLD functional maps exhibit strong context-dependent organization and capture contextual structure more robustly than neuronal spiking activity or fMRI frames alone. Despite this shared organization, a substantial subset of neighboring dmPPC neurons displayed markedly distinct whole-brain association patterns, revealing local functional heterogeneity that was not readily explained by waveform-based putative cell class or opposing firing dynamics. These findings provide insight into how local neuronal populations participate in distributed brain-wide functional organization during naturalistic episodic processing.

Journal Article

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

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

Humans

Effects of Family-Based Intervention for Childhood Obesity on Parental and Offspring Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Childhood obesity is a global public health issue with strong familial and intergenerational transmission. However, existing syntheses often overlook the active role of parents and fail to assess outcomes beyond the child. This systematic review and meta-analysis specifically investigate the effects of family-based interventions, which position parents as active co-agents of change, on health outcomes for both children with obesity and their parents. METHODS: A systematic review and meta-analysis were conducted. Six databases were searched for randomized controlled trials (RCTs) targeting children with obesity and at least one family member. Primary outcomes were children's BMI z-score and parental BMI; secondary outcomes included other adiposity measures and dietary behaviors. Outcomes for both children and parents were synthesized. Subgroup analyses were conducted based on intervention characteristics. Risk of bias was assessed using RoB 2, and evidence certainty was evaluated using GRADE. RESULTS: Twenty RCTs with 1740 participants were included in the meta-analysis. The interventions demonstrated a significant reduction in children's BMI z-score. Additional benefits were observed for long-term BMI z-score and percentage of total body fat. The most effective interventions commonly integrate health education, behavioral strategies, and motivational support. Subgroup analyses indicated that interventions positioning parents as active co-participants, rather than mere supporters, yielded larger effects. However, no significant effects were found on parental BMI. CONCLUSION: This study demonstrates that family-based interventions can confer significant benefits for children with obesity. Their success hinges on strategically framing parents as active co-agents and integrating motivational strategies.

Humans

Identification of elements determining KIR gene demethylation at the CD56-bright stage of NK cell development.

The variegated expression of the KIR family of class I MHC receptors generates specialized natural killer (NK) cells capable of allele-specific HLA recognition. Understanding the mechanism of KIR gene activation will lead to improved methods for the generation of fully functional NK cells. A central RUNX-binding site in the KIR proximal promoter is required for gene activation. RUNX proteins recruit ten-eleven translocation (TET) proteins that generate 5-hydroxymethylcytosine (5hmC) and drive DNA demethylation. Assessment of 5-methylcytosine (5mC) and 5hmC residues at four stages of NK cell development reveals deposition of 5hmC primarily in a CREB site next to the RUNX site at the CD56Bright stage but not the subsequent CD56Dim stage representing fully mature NK cells. KIR promoter demethylation is delayed relative to other lineage-associated genes, indicating a high threshold for KIR gene demethylation in developing NK cells, and a window of opportunity for RUNX/TET-dependent KIR gene activation in CD56Bright NK cells.

6-base sequencing

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

Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway.

BACKGROUND: Tranexamic acid (TXA) is widely used for pigmentary disorders, but its anti-ageing potential remains unclear. This study aimed to evaluate whether topical 3% TXA improves early periorbital wrinkles in women with facial melasma and to investigate whether TXA protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. METHODS: Fifty women with melasma were randomized to 3% TXA serum plus moisturizer or moisturizer alone for 8&#x2009;weeks, with follow-up to week 12. Periorbital wrinkles were graded using a modified Fitzpatrick Wrinkle Scale (MFWS). Separately, D-gal-induced senescence in HDFs was assessed via viability, SA-&#x3b2;-gal activity, senescence markers, ROS, antioxidant enzymes, SASP/ECM gene expression, and MAPK activation. GPR30 involvement was examined using antagonist G15, shRNA knockdown, and molecular docking. RESULTS: Topical TXA produced significantly greater MFWS reductions versus moisturizer alone at weeks 4, 8, and 12, with benefit persisting post-treatment. In HDFs, TXA preserved viability, reduced SA-&#x3b2;-gal positivity, attenuated p21/p16, restored Lamin B1, decreased ROS, and rescued antioxidant activities. TXA downregulated IL-6, IL-8, MMP1, and MMP3, and suppressed D-gal-induced ERK, JNK, and p38 phosphorylation. These effects were weakened by G15 or GPR30 knockdown; docking supported a stable TXA-GPR30 interaction. CONCLUSIONS: TXA showed clinical anti-wrinkle activity in melasma patients and protected HDFs from D-gal-induced senescence, partly via GPR30-dependent modulation of oxidative stress, SASP/ECM expression, and MAPK signalling. TXA is a promising candidate for skin ageing intervention.

Humans

Biomonitoring of industrial heavy metal pollution via enzymatic and metabolic responses in desert ants (Cataglyphis savignyi) and beetles (Tentyrum sp) as bioindicators.

The current work seeks to evaluate the effectiveness of Cataglyphis saviginyi and Tentyrum sp as indicators of pollution in the city's main industrial regions by analyzing their enzymatic activity and primary metabolites. Soil samples were collected at each site under investigation to analyze soil characteristics and heavy metal content. C. saviginyi and Tentyrum sp were collected across four consecutive seasons (2023-2024) to investigate enzymatic (GPT, GOT, ALP, ACP, LDH) and metabolic (lipid, protein, carbohydrate) biomarkers. The physicochemical properties of the soil differed substantially between the industrial areas and the control site. Soil heavy metal buildup was highest at industrial sites (1 and 4) compared to the control site, with the order being Zn&#x2009;>&#x2009;Cr&#x2009;>&#x2009;Cd&#x2009;>&#x2009;Cu. Heavy metal pollution indices were determined. Increased industrial activity from metal industries, ceramics, and chemical painting companies defines this area, as seen by the high Cdeg, mCd, PI, and PLI values derived for industrial sites 1 and 4. While C. saviginyi and Tentyrum sp deconcentrated and released Cr, Cd, and Zn into the soil via the biological accumulation factor (BAF), Cu acted as a macro-concentrator. Compared with the control site, industrial environments were shown to increase levels of GPT, GOT, LDH, ACP, protein, and carbohydrates in C. saviginyi. However, lipid and ALP activity was suppressed. at industrial sites, Tentyrum sp carbohydrate content was higher than at control sites, but GPT, GOT, ALP, ACP, LDH, protein, and lipid activities were all suppressed. Consequently, enzymatic and metabolic biomarkers proved to be sensitive indicators for assessing industrial heavy metal pollution in desert ecosystems.

Animals

Plasma proteomics reveal SERPINA1 and CD59 as candidate biomarkers for COVID-19 severity stratification and prognosis prediction.

BACKGROUND: COVID-19 has been closely associated with coagulation abnormalities. However, existing biomarkers, including D-dimer and fibrin degradation products (FDP), exhibit limited accuracy in stratifying disease severity and predicting long-term clinical outcomes. OBJECTIVES: This study aimed to use proteomic analysis to identify plasma biomarkers associated with COVID-19 severity and prognosis, and validate their predictive utility for mortality and thromboembolic complications. METHODS: Plasma proteomic profiles were analyzed across three COVID-19 severity classes. Differential expression analysis and functional analysis were performed. Clustering analysis was used to identify proteins correlated with disease severity. Candidate biomarkers were validated in an independent cohort. Predictive performance of the biomarkers for mortality, sepsis and venous thromboembolism was evaluated using bootstrap-corrected ROC analyses and multivariable regression analyses. RESULTS: Proteomic analysis revealed progressive involvement of the coagulation and complement pathway with increasing disease severity. SERPINA1 and CD59 were identified as candidate biomarkers and exhibited significantly higher plasma levels in severe cases. Bootstrap-corrected ROC analyses demonstrated strong predictive performance: SERPINA1 achieved AUCs of 0.775 and 0.924 for 30-day and 12-month mortality, and CD59 achieved AUCs of 0.720 for sepsis; the combined model further improved prediction of 12-month mortality (AUC 0.946) and sepsis (AUC 0.904), outperforming D-dimer and FDP. Multivariable regression confirmed their independent prognostic value. CONCLUSION: This exploratory study identifies SERPINA1 and CD59 as candidate prognostic biomarkers in COVID-19, highlighting the role of coagulation and complement-related pathways in disease severity and warranting further prospective validation.

Humans

The effect of antiretroviral therapy adherence on viral load suppression rate among people living with HIV in Ethiopia: A systematic review and meta-analysis.

BACKGROUND: Antiretroviral therapy (ART) adherence is a key determinant of viral load suppression among people living with HIV (PLHIV). In Ethiopia, evidence on the magnitude of ART adherence and its effect on virological outcomes remains fragmented. This systematic review and meta-analysis aimed to estimate the pooled prevalence of ART adherence and viral load suppression, and to measure the association between adherence and viral suppression among PLHIV in Ethiopia. METHODS: This systematic review and meta-analysis used the PRISMA checklist for systematic reviews and meta-analyses. The review protocol has been registered onPROSPERO:(CRD420251125899). PubMed, ScienceDirect, Scopus, Epistemonikos, and Google Scholar were searched. The quality of included articles has been evaluated with a Newcastle-Ottawa Scale (NOS), adapted for observational studies. A random-effects model using restricted maximum likelihood (REML) with Knapp-Hartung adjustment was used to estimate pooled prevalence and odds ratio. Heterogeneity was assessed using I2, &#x3c4;2, and Cochran's Q test. RESULTS: A total of 39 studies were included in the final analysis. The pooled prevalence of good ART adherence was 79.4% (95% CI: 74.8%-83.4%), while the pooled viral load suppression rate was 77.5% (95% CI: 72.5%-81.8%). The pooled odds ratio showed that good ART adherence was strongly associated with viral load suppression (OR = 6.30, 95% CI: 4.84-8.19). Substantial heterogeneity was observed across studies for both adherence and viral suppression outcomes (I2&#x2009;>&#x2009;90%). CONCLUSIONS: ART adherence and viral load suppression among PLHIV in Ethiopia are relatively high but remain below global targets. Good adherence was significantly associated with virologic suppression, highlighting adherence as a critical modifiable factor for achieving optimal treatment outcomes. Strengthening adherence support interventions is essential to improve virological success and advance progress toward HIV epidemic control.

Humans