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Neuroimaging anxious children and adolescents before and after cognitive behavioral therapy: a systematic review.

OBJECTIVE: This systematic review investigates brain changes in youths with anxiety disorders following cognitive behavioral therapy (CBT) and neural markers that predict CBT responses. METHODS: We conducted a systematic search using the electronic databases PubMed, Web of Science, and ProQuest. The inclusion deadline was set to October 27, 2025. We included fifteen peer-reviewed neuroimaging studies that examined the effects of CBT in youths under 19 years old with a primary clinical diagnosis of an anxiety disorder based on DSM-5 criteria. RESULTS: Although the existing literature is marked by substantial diversity in methods and outcomes, task-related neural response in the anterior cingulate cortex (ACC, 2/8, 25.0%), insula (1/8, 12.5%) increased from pre to post CBT and these changes were further correlated with clinical symptom improvements. Moreover, CBT outcomes were predicted by pre-treatment activity or connectivity in the ACC and amygdala (3/13, 23.0%). A smaller proportion of studies (2/13, 15.3%) found that activity or connectivity in the insula, precuneus/cuneus, postcentral gyrus, and activity or structure in the nucleus accumbens (NAcc) predicted response to CBT. The low consistency of these findings was driven by methodological variability, low reliability of the neural markers, and relatively small sample sizes. CONCLUSIONS: This review highlights promises of neural predictors and outcomes to enhance anxiety disorder treatments in children and adolescents, facilitating future personalized and effective CBT. Beyond this initial promise, the field is hindered by methodological inconsistencies and limited replications. While longitudinal and personalized approaches are important next steps, the central challenge remains: identifying neural markers that are both reliable and robust.

Adolescent

Littoral and wetland vegetation decrease carbon emissions from dry inland waters.

Lakes are recognized as active components of the inland water carbon (C) cycle, as organic matter is processed by microbial respiration, inducing large carbon dioxide (CO2) and methane (CH4) emissions. In the context of long-lasting drought periods, large uncertainties remain about: (1) the influence of wet-dry cycle on CO2 and CH4 fluxes in littoral zones and lacustrine wetlands; and (2) the contribution of emergent vegetation to C fluxes in dry inland waters. At the water-land interface of two shallow lakes, this study focuses on CO2 and CH4 fluxes from vegetated and bare dry inland waters in relation to hydrological fluctuations. Three seasonal campaigns were conducted to measure daytime CO2 and CH4 fluxes in pelagic, littoral and wetland surface waters, as well as in temporarily air-exposed sediments, using floating and static chambers, respectively. Our results reveal that wet-dry cycle in the littoral zone and wetlands strongly influence gaseous C fluxes through contrasting patterns, especially in late summer, when the biological processes are most active (primary production and respiration). In air-exposed littoral zones, organic-poor sandy sediments presented the lowest CO2 and CH4 emissions, whereas in air-exposed lacustrine wetlands, water-saturated sediments accumulated high amounts of plant-derived organic matter, promoting intense microbial activity and the highest C emissions. However, amphiphytes and helophytes vegetation in exposed littoral zones and wetlands reversed the direction of C fluxes, inducing the highest CO2 uptake due to high photosynthesis rates. This study underlines the relevance of considering vegetation in dry inland waters, particularly in lacustrine littoral zones and wetlands, to obtain comprehensive lake C budgets, especially under climate change scenarios.

Wetlands

Lower-limb electromyographic responses across four recumbent cycling configurations in healthy young men.

Recumbent cycling provides an adjustable configuration in which backrest angle and crank-axis height can alter lower-limb loading. Backrest angle changes the orientation of the active musculature relative to gravity, whereas crank-axis height modifies the foot-pedal interface and the ankle lever arm. Whether such positioning is associated with differences in lower-limb electromyographic (EMG) activation across both factors together has not been examined. Using a randomized crossover design, fifty-nine healthy young men cycled at 100&#xa0;W and 50&#xa0;rpm under four conditions combining two backrest angles (30&#xb0;, 75&#xb0;) and two crank-axis heights (Rh, high, 77&#xa0;cm; Rl, low, 45&#xa0;cm). Surface EMG from the rectus femoris (RF), biceps femoris (BF), and gastrocnemius medialis (GAS) was analyzed for root mean square (RMS) amplitude, absolute onset sequence, and relative recruitment timing (%Sequence, derived using Telescan software and referenced to RF). RMS amplitude did not differ across conditions for any muscle (all p&#xa0;&#x2265;&#xa0;0.356), and absolute onset sequence showed no condition effect (all p&#xa0;&#x2265;&#xa0;0.197). For GAS %Sequence, the Greenhouse-Geisser-corrected omnibus test was significant (F(1.32, 76.56)&#xa0;=&#xa0;28.45, p&#xa0;<&#xa0;0.001), driven by a within-30&#xb0; contrast in which %Sequence was lower under Rl than Rh (paired t(58)&#xa0;=&#xa0;10.39, Holm-adjusted p&#xa0;<&#xa0;0.0001; mean difference 22.0 percentage points, 95&#xa0;% CI [17.8, 26.3]; dz&#xa0;=&#xa0;1.35). Because %Sequence is referenced to RF, this exploratory shift should be interpreted cautiously. Lower-limb activation may be constrained by the closed-chain nature of pedaling, whereas distal recruitment timing may be sensitive to crank-axis height and the foot-pedal interface.

Humans

Thoracic paravertebral block with different doses of liposomal bupivacaine versus ropivacaine for postoperative analgesia in single-port thoracoscopic lung surgery: a randomized clinical trial.

OBJECTIVE: To evaluate the analgesic efficacy of thoracic paravertebral block (TPVB) with different doses of liposomal bupivacaine (LB) or ropivacaine in patients undergoing single-port thoracoscopic lung surgery. METHODS: A total of 105 patients scheduled for video-assisted single-port thoracoscopic lung surgery were randomized in a 1:1:1 ratio into three groups: low-dose LB group (group LL), high-dose LB group (group HL), or ropivacaine group (group R). All received ultrasound-guided TPVB at the T5/6 level preoperatively. The primary outcome was the area under the curve (AUC) of NRS of pain at activity (AUC-aNRS) from 1 to 72&#x2009;h postoperatively. Secondary outcomes included the AUC of NRS of pain at rest (AUC-rNRS) from 1 to 72&#x2009;h postoperatively, NRS of pain at rest and at activity at 1, 6, 24, 48, and 72&#x2009;h postoperatively, and the cumulative opioid consumption at 24, 48, and 72&#x2009;h postoperatively. Additionally, postoperative recovery and adverse events were assessed. RESULTS: AUC-aNRS differed significantly among groups (p = 0.0092), with high-dose LB lower than low-dose LB (p = 0.0071), but not versus ropivacaine. No significant difference was found in AUC-rNRS (p&#x2009;>&#x2009;0.05). The group-by-time interactions for NRS of pain at rest and at activity were not significant (p&#x2009;>&#x2009;0.05). Cumulative opioid consumption at 24, 48, and 72&#x202f;h was lower in group HL versus group LL (all p < 0.017), but not versus ropivacaine. Postoperative recovery and adverse events showed no differences (p&#x2009;>&#x2009;0.05). CONCLUSION: LB combined with TPVB is not superior to ropivacaine for postoperative analgesia in single-port thoracoscopic lung resection.

Humans

Changes in hemoglobin levels and cardiometabolic health in adults with metabolic syndrome - a secondary outcome analysis of a six-month randomized controlled trial.

BACKGROUND: Lower hemoglobin (Hb) levels within the normal range have been associated with favorable metabolic traits in cross-sectional studies. This study investigated whether changes in Hb levels correlated with changes in physiological and cardiometabolic parameters during a six-month behavioral intervention in individuals with metabolic syndrome. METHODS: The&#xa0;six-month randomized controlled trial aimed to reduce sedentary behavior in adults with metabolic syndrome (n&#x2009;=&#x2009;64). Key measurements included fasting blood samples, insulin sensitivity during a hyperinsulinemic-euglycemic clamp, insulin-stimulated liver glucose uptake, liver fat content (LFC), indirect calorimetry, cardiorespiratory fitness, and cardiac function. Correlations&#xa0;between changes in these variables and changes in Hb levels at baseline, three, and six months were examined. RESULTS: Cross-sectionally, higher Hb levels correlated with&#xa0;lower insulin sensitivity (r=-0.35, p&#x2009;=&#x2009;0.005), higher resting O2 consumption (r&#x2009;=&#x2009;0.41, p&#x2009;<&#x2009;0.001), higher resting energy expenditure (r&#x2009;=&#x2009;0.49, p&#x2009;<&#x2009;0.001), higher LFC (r&#x2009;=&#x2009;0.40, p&#x2009;=&#x2009;0.011), and greater&#xa0;left ventricular wall thickness (r&#x2009;=&#x2009;0.42, p&#x2009;=&#x2009;0.001). The intervention did not significantly impact Hb levels, and changes in Hb levels did not correlate with most cardiometabolic changes. However, reduced Hb levels correlated with reduced fasting blood glucose (r&#x2009;=&#x2009;0.29, p&#x2009;=&#x2009;0.032), improved insulin sensitivity (r = -0.26, p&#x2009;=&#x2009;0.045), and increased cardiorespiratory fitness (r = -0.29, p&#x2009;=&#x2009;0.033). CONCLUSIONS: Changes in Hb levels did not consistently correlate with changes in cardiometabolic markers during&#xa0;the intervention. However, reductions in Hb levels may relate to improved insulin sensitivity and fitness. Along&#xa0;cross-sectional correlations, this may be clinically relevant for individuals with metabolic syndrome. Further studies are merited to clarify&#xa0;the role of Hb levels in this high-risk group.

Humans

Influence of microplastics on microalgal performance during wastewater polishing.

Microplastics (MPs) are emerging contaminants that are increasingly accumulating in aquatic ecosystems due to excessive anthropogenic activity and insufficient mitigation strategies, posing serious environmental and public health risks. Their impact on wastewater (WW) treatment processes remains poorly understood. This study evaluated the effects of five MPs commonly found in WW - polypropylene, polystyrene, polyamide, low-density polyethylene, and high-density polyethylene - on the physiology and bioremediation performance of the microalga Chlorella vulgaris in synthetic WW (SWW). Metabolic responses were assessed via esterase activity and intracellular reactive oxygen species (ROS), while nitrogen (N), phosphorus (P), and glucose removal were monitored to evaluate bioremediation efficiency. MPs inhibited esterase activity and elevated ROS levels, indicating oxidative stress. Nevertheless, C. vulgaris maintained a high bioremediation capacity (> 75 % N, > 60 % P, and > 70 % for glucose). Environmental conditions modulated microalga response to MPs exposure. Under N-limited conditions, C. vulgaris exhibited enhanced nutrient uptake and biomass production, but a 12 h/12 h light/dark photoperiod reduced N removal but stimulated glucose consumption via heterotrophic metabolism. In contrast, C-limited conditions exacerbated oxidative stress and compromised nutrient removal, resulting in residual concentrations exceeding legal limits. These findings highlight that environmental factors can either mitigate or exacerbate the physiological stress induced by MPs, ultimately affecting WW polishing. This work provides a comprehensive insight into the cellular and metabolic effects of MPs on microalgae and supports C. vulgaris as a resilient and sustainable approach for nutrient and carbon removal in MP-contaminated WW systems.

Microalgae

Hypertension in a Randomized Trial of Dolutegravir- Versus Efavirenz-Based Antiretroviral Therapy in Pregnant and Postpartum Women with HIV.

INTRODUCTION: We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS: Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or &#x2265;2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (&#x2265;160-179 and/or &#x2265;100-109 mmHg), and severe (&#x2265;180 and/or &#x2265;110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or &#x2265;2 blood pressures &#x2265; 140 and/or &#x2265;90 mmHg at &#x2265;20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS: Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS: Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

Humans

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

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

Animals

Neurocorrelates of nocturnal enuresis in pre-adolescent children.

INTRODUCTION: Nocturnal enuresis (NE) is a common neurodevelopmental condition, yet its underlying neural mechanisms remain unclear. This study leverages the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to identify structural and functional brain correlates associated with active symptoms and the resolution of bedwetting. METHODS: Using cross-sectional data from 3472 participants aged 9-10 years, children were categorized into three groups: active nocturnal enuresis (ANE, n = 225), history of nocturnal enuresis (HNE, n = 1171), and healthy control groups (CG, n = 2076). Multimodal neuroimaging protocol evaluated macrostructural properties via structural MRI (sMRI), microstructural white matter integrity via diffusion MRI (dMRI), and functional connectivity via resting-state fMRI (fMRI). Group differences were evaluated using linear models within an ANCOVA framework, adjusting for intracranial volume and handedness with False Discovery Rate (FDR) correction. RESULTS: Compared to controls, the ANE group exhibited a significant volume deficit in the right caudate, decreased sulcal depth in the left insula, and lower internal correlation within the Cingulo-Opercular Network (CON). Conversely, the dry HNE group demonstrated significant structural adaptations, including bilaterally larger putamen volumes and increased right caudate volume compared to the ANE group. The HNE group also showed increased microstructural density (decreased mean diffusivity) in the bilateral hippocampus and an increased cortical surface area in the left insula. Both NE groups demonstrated persistently reduced functional coupling within the CON. CONCLUSIONS: Nocturnal enuresis appears to be associated with a potential complex central signaling deficits. Reduced internal correlation within the CON across both active and former bedwetters indicates a potential for impairment in processing internal homeostatic bladder signals during sleep.

Humans

Integrated physiological and transcriptomic analyses reveal coordinated gill responses to heat stress in pikeperch (Sander lucioperca).

Climate change-driven warming of aquatic environments has made thermal stress an increasingly important factor influencing fish physiological homeostasis. Given their central roles in respiration and osmoregulation, gills are particularly responsive to variations in ambient temperature. Histological examination, physiological measurements, and transcriptome profiling were integrated to investigate the mechanisms associated with heat stress-induced gill injury in pikeperch (Sander lucioperca). Histological analysis revealed that exposure to 29&#xa0;&#xb0;C directly caused structural damage to the gills of pikeperch. Oxidative status was evaluated by measuring malondialdehyde (MDA) levels and the activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). MDA accumulation was significantly enhanced under heat stress, while antioxidant enzyme activities (SOD, POD, and CAT) displayed a transient increase followed by a subsequent decline. Transcriptome profiling showed marked enrichment of the protein processing in endoplasmic reticulum pathway after heat stress, suggesting activation of endoplasmic reticulum (ER) stress in pikeperch gills. With increasing stress duration, the unfolded protein response (UPR) appeared unable to re-establish ER homeostasis, shifting ire1 and atf6 toward a pro-apoptotic state. Protein-protein interaction (PPI) analysis further highlighted hub genes potentially involved in heat stress-induced ER stress and apoptosis. TUNEL staining and western blotting collectively confirmed that heat stress triggered apoptosis in pikeperch gill tissue. Overall, this study provides new insights into the physiological and molecular responses of pikeperch gills to heat stress and enhances our understanding of thermal stress adaptation in cold-water aquaculture species under climate change.

Animals

Low-salinity stress alters growth, histology, physiology, and transcriptomic profiles of the gills and antennal glands in Macrobrachium rosenbergii.

Salinity is a major abiotic constraint in freshwater aquaculture of the giant freshwater prawn Macrobrachium rosenbergii, yet the coordinated roles of the gills and antennal glands, the two primary osmoregulatory organs in decapod crustaceans, under low-salinity stress remain poorly characterized. Here, we integrated histological, physiological, and transcriptomic analyses to characterize the adaptive responses of M. rosenbergii to acute (96&#xa0;h) and chronic (8&#xa0;weeks) exposure to salinity 5. Chronic low-salinity stress significantly impaired growth performance and decreased the survival rate. Acute stress induced thinning of the gill filaments, partial disorganization of pillar cells, and dilation of the intermicrovillar space in the antennal glands, whereas chronic stress caused gill vacuolization, cuticle thinning, and adaptive folding of antennal gland microvilli. In parallel, acute exposure significantly decreased hemolymph sodium and potassium ion concentrations but increased magnesium ion concentration, whereas chronic exposure increased hemolymph sodium and potassium ion concentrations, upregulated gill Na+/K+-ATPase activity, and enhanced hepatopancreatic antioxidant capacity. Transcriptomic analyses revealed distinct tissue-specific responses. Under acute stress, the gills preferentially activated pathways associated with cytoskeletal remodeling, motor proteins, and tight junctions, whereas chronic acclimation shifted the transcriptional response toward the renin-angiotensin system and glutathione metabolism. In the antennal glands, acute stress rapidly activated the renin secretion pathway, whereas chronic exposure promoted membrane remodeling by enriching pathways related to lipid and glycan metabolism. These findings reveal tissue-specific functional differentiation and synergistic coordination between the gills and antennal glands that underpin M. rosenbergii's adaptive response to low-salinity stress.

Animals

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals

Dissociable neural mechanisms of cognitive enhancement through transcranial stimulation and behavioral training.

BACKGROUND: Transcranial direct current stimulation (tDCS) and adaptive working memory (WM) training are promising cognitive enhancement approaches; however, their neural mechanisms and potential synergies remain poorly understood. OBJECTIVE: We directly compared how tDCS and WM training modulate neural oscillations during WM performance and examined whether combining both interventions produces additive effects. METHODS: We randomized 112 healthy adults into four groups: control (sham tDCS&#xa0;+&#xa0;non-adaptive 1-back), tDCS-only (active tDCS&#xa0;+&#xa0;non-adaptive 1-back), training-only (sham tDCS&#xa0;+&#xa0;adaptive n-back training), or combined (active tDCS&#xa0;+&#xa0;adaptive training). Participants underwent five daily intervention sessions. We recorded high-density EEG during transfer n-back tasks at baseline, post-intervention, and one-week follow-up. RESULTS: All active interventions improved WM performance relative to the control group, with the combined group showing the largest gains (n-back accuracy: +15.6% vs.&#xa0;+&#xa0;10.1% tDCS-only, +9.7% training-only, +0.7% control; all p&#xa0;<&#xa0;0.001). Critically, tDCS selectively increased gamma-band (30-50&#xa0;Hz) power in the frontal and parietal regions (cluster p&#xa0;=&#xa0;0.018, d&#xa0;>&#xa0;1.0), whereas WM training enhanced frontal theta-band (4-8&#xa0;Hz) power and theta-gamma phase-amplitude coupling (both cluster p&#xa0;<&#xa0;0.012, d&#xa0;>&#xa0;0.85). The combined group exhibited both neural signatures. Brain-behavior correlations revealed dissociable relationships: gamma increases predicted n-back accuracy improvements (r&#xa0;=&#xa0;0.61, p&#xa0;<&#xa0;0.001), whereas theta enhancements correlated with operation span gains (r&#xa0;=&#xa0;0.58, p&#xa0;=&#xa0;0.002). CONCLUSIONS: tDCS and WM training enhance cognition through distinct yet complementary neural mechanisms: tDCS via gamma-mediated cortical excitability and WM training via theta-mediated cognitive control. These findings provide neurophysiological evidence for multimodal enhancement strategies that target parallel pathways within WM networks.

Humans

Clustering patterns of behavioral and metabolic risk factors for noncommunicable diseases in Iran: findings from a national STEPS survey.

BACKGROUND: Noncommunicable diseases (NCDs) are the leading cause of mortality in Iran, driven by behavioral and metabolic risk factors that frequently co-occur. OBJECTIVE: To identify patterns of co-occurring behavioral and metabolic NCD risk factors among Iranian adults and characterize their demographic and socioeconomic correlates. METHODS: This cross-sectional study analyzed data from 16,618 adults aged &#x2265;25&#x2009;years who participated in Iran's 2021 nationally representative STEPS survey. Thirteen behavioral and metabolic variables, including physical activity, nutrition score, smoking frequency, alcohol intake, salt intake, body mass index, blood pressure, fasting plasma glucose, and lipid markers, were entered into a K-means clustering analysis. Clusters were characterized by their risk profiles and demographic/socioeconomic attributes. Multinomial logistic regression examined associations between cluster membership and sociodemographic factors. RESULTS: Five distinct behavioral-metabolic clusters emerged. The smokers-drinkers (SD) cluster (3.1%) comprised mostly older, less-educated men with high smoking and alcohol use. The healthy-low-risk (HLR) cluster (40.3%) showed favorable profiles and included younger, more educated individuals. The physically active (PA) cluster (6.6%) was characterized mainly by younger men with markedly high physical activity levels. The dyslipidemic (DLP) cluster (26.0%) exhibited high dyslipidemia and overweight prevalence, while the hypertensive-diabetic (HTD) cluster (24.0%) had the highest obesity, hypertension, and diabetes rates, common among older urban adults. CONCLUSION: Behavioral and metabolic NCD risk factors in Iran formed five distinct co-occurrence patterns. Nearly half of adults belonged to metabolically high-risk clusters, highlighting the need for targeted prevention strategies that combine lifestyle interventions with screening and management of obesity, hypertension, diabetes, and dyslipidemia.

Humans

Lactylation-related immune-metabolic dysregulation defines prognostic and therapeutic stratification in lung adenocarcinoma.

BACKGROUND: Lactylation links lactate metabolism with inflammatory signaling and immune regulation in tumors. However, its cellular distribution and translational value in lung adenocarcinoma (LUAD) remain unclear. METHODS: Single-cell RNA-sequencing datasets GSE189357 and GSE171145 were integrated to characterize lactylation-related activity, intercellular communication, and malignant epithelial cell states in LUAD. Single-cell-derived lactylation-related differentially expressed genes were mapped to TCGA-LUAD and multiple GEO cohorts. Univariate Cox regression and machine learning algorithms were used to construct a lactylation-related prognostic signature (LRPS). The associations of LRPS with prognosis, immunotherapy response, drug sensitivity, genomic alterations, immune infiltration, and inflammation- and metabolism-related pathways were evaluated. KRT7 was further validated using virtual knockout analysis, spatial transcriptomics, and in vitro and in vivo experiments. RESULTS: lactylation-related transcriptional activity showed heterogeneous distribution across LUAD cell populations and was associated with altered cell-cell communication. In malignant epithelial cells, LRTS-high and LRTS-low states exhibited distinct metabolic, inflammatory, and tumor-related pathway activities. LRPS showed stable prognostic performance in TCGA-LUAD and multiple GEO cohorts and remained an independent prognostic factor. Low LRPS was associated with greater potential benefit from immunotherapy, whereas different LRPS groups displayed distinct drug sensitivity, genomic alteration, and immune microenvironment patterns. KRT7 was highly expressed in LUAD and associated with poor prognosis. KRT7 knockdown suppressed LUAD cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. CONCLUSIONS: This study identifies lactylation-related immune-metabolic dysregulation as a clinically relevant feature of LUAD and develops a single-cell-guided LRPS for prognosis and therapeutic stratification. KRT7 emerged as an LRPS-related functional candidate with experimentally supported roles in malignant LUAD phenotypes.

Immunotherapy

Integrated photoelectrocatalytic reduction and oxidation processes to achieve efficient degradation of fluoxetine in pharmaceutical wastewater.

Fluorinated organic compounds have been frequently detected in aquatic environments, with the widespread use of fluorinated drugs. The existing processes of urban sewage treatment plants are difficult to completely remove these pollutants containing the persistent C-F bonds. In this work, an integrated system of UV-activated sulfite and UV-assisted electrochemical oxidation was innovatively constructed for efficient degradation of fluoxetine. For the UV-activated sulfite unit system, when the sulfite dosage was 0.5 mmol/L and the initial pH was about 10, the defluorination efficiency of 5 mg/L fluoxetine wastewater under nitrogen atmosphere was about 98 %. Subsequently, the UV-assisted electrochemical oxidation unit system was employed to treat the reduced wastewater mentioned above. When the sodium chloride dosage was 25 mmol/L, the initial pH was about 5, and the current density was 30 mA/cm2, the total organic carbon (TOC) removal of the wastewater arrived at 65 %. Active species capture experiments and ESR tests confirmed that hydrated electrons, hydroxyl, and chlorine radicals were the main components for the efficient degradation of fluoxetine. According to the analysis of Fukui function and HPLC-MS, the degradation pathway of pollutants was proposed including defluorination and mineralization. Meanwhile, the toxicity of intermediates was predicted using the ECOSAR program. In addition, the verification test of actual wastewater treatment indicated that the defluorination and TOC removal efficiency of fluorouracil by the integrated system were similar to those for fluoxetine. This work provided a new approach for the efficient degradation of fluorinated organic pollutants in pharmaceutical wastewater.

Fluoxetine

Reducing state anxiety with alpha-frequency transcranial alternating current stimulation.

BACKGROUND: Anxiety reactivity to acute stress is a transdiagnostic vulnerability factor. We tested whether a single session of alpha-frequency transcranial alternating current stimulation (tACS) targeting the frontoparietal control network reduces stress-evoked state anxiety in healthy adults. METHODS: In a randomized, blinded, sham-controlled study, 42 participants (mean age 58.9&#xa0;years) completed an acute stress task before and after stimulation. The task was an adapted moving-circles paradigm in which circle collisions triggered a brief aversive event (mild electric shock plus unpleasant noise and a white flash). Active stimulation consisted of 20&#xa0;min of 10-Hz tACS (2.0&#xa0;mA/channel; 30-s ramp up/down) delivered via electrodes at F3, P3, Cz, and T7 (0&#xb0; phase at F3/P3; 180&#xb0; at Cz/T7). Sham stimulation used the same montage and ramp periods but no sustained current. RESULTS: State anxiety showed a significant Time &#xd7; Protocol interaction (F(1,35)&#xa0;=&#xa0;4.22, p&#xa0;=&#xa0;.047): STAI-S decreased after active tACS (&#x394;&#xa0;=&#xa0;-3.16) but increased slightly after sham (&#x394;&#xa0;=&#xa0;+1.17). Perceived stress appraisal (SAAS) did not change. Resting-state alpha power at F3/P3 showed no reliable pre-post effects. During the task, left-frontal relative alpha differed by protocol and showed a trend toward larger increases following active tACS. Electrodermal and pupil indices changed across sessions in both groups, with no differential stimulation effects. CONCLUSIONS: A single alpha-tACS session produced a modest, selective reduction in stress-evoked state anxiety, supporting oscillatory neuromodulation as a scalable approach to dampen anxiety reactivity.

Humans

Continuous theta-burst stimulation over the right DLPFC modulates central executive network connectivity in depression: exploratory analysis of a randomized clinical trial.

Previous studies suggest that transcranial magnetic stimulation exerts antidepressant effects and is associated with alterations in functional connectivity (FC), but the neural correlates remain unclear. This exploratory sham-controlled trial investigated the effect of continuous theta-burst stimulation (cTBS) over the right dorsolateral prefrontal cortex (DLPFC) on FC in major depressive disorder (MDD). Seventy MDD patients were randomized to receive two-week treatment of personalized cTBS or sham stimulation. Resting-state fMRI was performed at baseline and post-treatment. Ultimately, 31 patients in the active cTBS group and 28 patients in the sham group passed imaging quality control and were included in the final analysis. To identify the FC that may have been influenced by cTBS treatment, two complementary FC analyses were conducted: (1) voxel-wise degree centrality (DC) followed by seed-based FC, and (2) an individual FC analysis based on the stimulation targets. Furthermore, correlations between FC changes and clinical symptoms improvement were examined. Both groups exhibited reductions of depression scores, with greater improvement in the active group. Compared to the sham group, active cTBS showed increased DC in the precuneus and elevated FC between the precuneus (within the para-cingulate network) and the right inferior parietal lobule (IPL) and DLPFC. Further stimulation target-based analysis revealed increased FC between stimulation targets and both the precuneus and visual regions following treatment. Our findings reveal neural changes associated with cTBS over the right DLPFC in MDD, notably involving the precuneus and its connectivity with the right IPL/DLPFC, suggesting alterations within the central executive network. TRIAL REGISTRATION: chictr.org.cn; ChiCTR2300068273.

Humans