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PubMed2026

Prevalence of Slowly Expanding Lesions in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Chronic active lesions (CALs) reflect chronic inflammation in multiple sclerosis (MS). Slowly expanding lesions (SELs) are CALs identified on conventional MRI by linear, concentric expansion over time, while paramagnetic rim lesions (PRLs) are CALs characterized by a paramagnetic rim on susceptibility-sensitive MRI. However, the prevalence of SELs and their overlap with PRLs remain unclear. The aims of this study were to (1) estimate the proportion of SELs among all T2 lesions and the proportion of patients with at least 1 SEL and (2) assess the proportion of SELs overlapping with PRLs. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase on February 1, 2026, for studies evaluating SELs in MS. At least 2 authors independently assessed study eligibility. Primary outcomes were the pooled proportion of SELs among T2 lesions and the proportion of patients with at least 1 SEL. We estimated mean per-patient volumes of SELs and total T2 lesions and the proportion of SELs overlapping with PRLs. Random-effects generalized linear mixed-effects models and inverse-variance methods were used, with between-study heterogeneity assessed using τ2 and I2 and robustness using sensitivity analyses. Univariable meta-regression explored heterogeneity. PROSPERO: CRD42024603778. RESULTS: Of 5,980 records, 20 studies comprising 4,786 patients with MS were included (mean age: 43.6 ± 6.3 years; 63.7% female). Sample sizes varied by outcome. SELs accounted for 14% (95% CI 10-21) of all T2 lesions, and 78% (67-85) of patients had at least 1 SEL. After sensitivity analysis, per-patient mean volumes were 1.42 mL (0.79-2.06) for SELs and 10.6 mL (8.53-12.67) for total T2 lesions. In total, 11% (6-20) of SELs overlapped with PRLs. In subgroup analyses, proportions of SELs were similar in relapsing-remitting and progressive MS (15%), but the proportion of patients with at least 1 SEL was higher in progressive MS. Between-study heterogeneity was high across analyses with no significant sources identified. DISCUSSION: Although SELs represent a minority of T2 lesions, most patients have at least 1 SEL and a subset overlaps with PRLs, suggesting a partial correspondence between these 2 imaging markers of chronic inflammatory activity. Limitations include possible publication bias, high unexplained heterogeneity, differences in SEL identification methods, and differences in MRI time point number/timing.

Humans↗

PubMed2026

Performance of AI-Based Screening Tools for Obstructive Sleep Apnea Across Apnea-Hypopnea Index Thresholds: Systematic Review and Meta-Analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent but remains substantially underdiagnosed. Polysomnography (PSG) is the reference standard, but its cost and limited availability constrain large-scale case identification. AI-based screening tools may support risk stratification and referral prioritization, but their diagnostic accuracy across apnea-hypopnea index (AHI) thresholds remains uncertain. OBJECTIVE: This review aimed to systematically evaluate the diagnostic accuracy of AI-based OSA screening tools at AHI thresholds of ≥5, ≥15, and ≥30 events/hour, with emphasis on models using non-PSG-derived inputs. METHODS: PubMed, Embase, Scopus, and Web of Science were searched for studies published from January 1, 2016, to May 3, 2026. Eligible studies included adults evaluated for suspected OSA or recruited from population-based cohorts, assessed AI-based models intended or interpretable for OSA screening, risk prediction, or screening-oriented severity classification, used PSG as the reference standard, and reported sufficient data to construct or reconstruct 2×2 contingency tables. Diagnostic accuracy was synthesized separately by AHI threshold and input source using bivariate random-effects models, with 95% CIs and prediction intervals (PIs). Risk of bias and certainty of evidence were assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation), respectively. RESULTS: A total of 60 studies were included, of which 47 contributed data to the meta-analysis. At AHI thresholds of ≥5, ≥15, and ≥30 events/hour, pooled sensitivities were 0.94 (95% CI 0.92-0.96; 95% PI 0.71-0.99), 0.87 (95% CI 0.84-0.89; 95% PI 0.66-0.96), and 0.83 (95% CI 0.79-0.87; 95% PI 0.61-0.94), respectively; the corresponding specificities were 0.77 (95% CI 0.69-0.84; 95% PI 0.30-0.96), 0.81 (95% CI 0.75-0.85; 95% PI 0.39-0.96), and 0.91 (95% CI 0.87-0.94; 95% PI 0.55-0.99), respectively. The corresponding areas under the summary receiver operating characteristic curves were 0.943, 0.907, and 0.920. For non-PSG-derived tools, sensitivities were 0.92, 0.85, and 0.81, and specificities were 0.70, 0.74, and 0.85 at the 3 thresholds, respectively. For PSG-derived models, sensitivities were 0.96, 0.90, and 0.85, and specificities were 0.82, 0.88, and 0.96, respectively. Exploratory subgroup analyses suggested performance variation across selected study and model characteristics, including region, algorithmic framework, data source, and validation method. CONCLUSIONS: AI-based tools showed generally favorable screening performance for OSA across clinically relevant AHI thresholds, although wide PIs suggest variable performance across future comparable populations and settings. By synthesizing diagnostic accuracy across 3 AHI thresholds and distinguishing non-PSG-derived from PSG-derived models, this review extends previous broad or modality-specific reviews and offers a clinically interpretable, pathway-specific basis for linking model performance to intended use. The findings may clarify potential roles for non-PSG-derived tools in front-end screening and referral prioritization and for PSG-derived models in reduced-channel assessment and sleep-laboratory workflow support. Given substantial heterogeneity, limited external validation, and low or very low certainty of evidence, prospective validation is needed before routine implementation.

Humans↗

PubMed2026

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↗

PubMed2026

Endoscopic Ultrasound-Guided Franseen Fine-Needle Biopsy for Solid Pancreatic Lesions: A Systematic Review and Meta-Analysis.

INTRODUCTION: Accurate tissue acquisition (TA) of solid pancreatic lesions is essential for guiding treatment with endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) being the preferred method. Among FNB designs, the three-pronged Franseen-tip needle demonstrates strong diagnostic performance, though direct head-to-head comparisons with other FNB designs remain limited. METHODOLOGY: This meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420251123856). Eligible studies enrolled patients with solid pancreatic lesions who underwent EUS-guided FNB, directly compared the Franseen-tip with other FNB needles. Six databases were systematically searched through July 2025, and study selection, data extraction, and risk of bias assessment (QUADAS-2 tool) were performed independently by two reviewers. Pooled estimates were generated using random-effects and bivariate hierarchical models. RESULTS: Sixteen studies (2,010 Franseen vs. 2,811 comparator) were included. Bivariate analysis showed that sensitivity and specificity of the Franseen needle were comparable to newer-generation comparator needles (sensitivity 91.3% vs. 94.0%; specificity 99.99% vs. 99.15%), whereas older-generation needles demonstrated lower sensitivity (80.8%) and inferior discriminatory performance (Negative Likelihood Ratio [LR⁻] 0.19 vs. 0.09). Diagnostic accuracy was higher with the Franseen needle (RR 1.07, 95% CI 1.01-1.14; I2 = 69%). Sample adequacy was similar overall (RR 1.04, 95% CI 0.95-1.14) but superior to older-generation needles (RR 1.19, 95% CI 1.02-1.41) and in lesions > 30 mm (RR 1.14, 95% CI 1.02-1.28, I2 = 81.2%). The Franseen needle achieved nominally strong diagnostic performance (DOR 116.6), although small-study effects were observed. Primary procedural outcomes were comparable between Franseen and comparator needles, including technical success (RR 1.00, 95% CI 0.98-1.02) and histological core procurement (RR 1.04, 95% CI 0.92-1.17). The Franseen needle had fewer low-cellularity samples (RR 0.56, 95% CI 0.45-0.69) and lower specimen bloodiness (RR 0.48, 95% CI 0.25-0.90) but a slightly higher overall adverse event rate (RR 1.29, 95% CI 1.06-1.57). CONCLUSION: The Franseen needle provides superior diagnostic accuracy and sample adequacy compared to older-generation FNB needles with comparable performance to newer-generation designs. It reduces low-cellularity samples and specimen bloodiness, although adverse events are slightly increased, with other primary procedural outcomes remaining comparable. TRIAL REGISTRATION: PROSPERO (Registration No. CRD420251123856).

Humans↗

PubMed2026

A STORM-based protocol for nanoscale imaging and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber.

Stochastic Optical Reconstruction Microscopy (STORM) enables nanoscale mapping of molecular components beyond the diffraction limit; however, its reproducible implementation in hydrophobic polymer matrices remains challenging because fluorescence-labeling specificity, fluorophore photoswitching, three-dimensional localization, chromatic registration, and quantitative image analysis must be carefully controlled. This protocol presents a standardized experimental workflow for dual-color labeling, astigmatism-based three-dimensional STORM acquisition, and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber (NR). The workflow covers sample pretreatment, Cy5 NHS ester labeling of protein-associated primary amines, DiI labeling of phospholipid-rich domains, STORM imaging-buffer preparation, three-dimensional single-molecule localization, dual-channel registration, generation of standardized xy projections, aggregate-size analysis, and projected lateral spatial correlation assessment. Reproducibility is supported by defined acquisition and localization criteria, three independent sample preparations with at least five fields of view analyzed per condition, and unlabeled, single-color, dye-only matrix, and processing-associated Cy5 controls. Mean lateral localization precisions of 11.8 ± 2.3 nm for Cy5 and 13.5 ± 2.9 nm for DiI were obtained, while two-dimensional Fourier ring correlation analysis of the xy projections yielded effective lateral image resolutions of approximately 25 and 28 nm, respectively. Image-based particle segmentation and localization-coordinate-based density-based spatial clustering of applications with noise (DBSCAN) were applied to standardized xy projections as complementary quantitative approaches. Application of the protocol to untreated, centrifuged, and protease-treated NR samples demonstrated treatment-associated changes in the detected abundance and projected size distributions of protein- and phospholipid-associated aggregates, together with a non-monotonic change in their projected lateral spatial correlation. These observations describe alterations in nanoscale organization but do not, by themselves, establish stable protein-phospholipid complex formation. Unlike previous studies that primarily demonstrated the feasibility of STORM imaging in rubber materials, the principal contribution of this work is an end-to-end, step-by-step protocol incorporating defined controls, three-dimensional localization, image-quality metrics, chromatic-registration procedures, and complementary quantitative-analysis pipelines for non-expert users. The workflow may be adaptable to other hydrophobic polymers and soft-material systems after appropriate optimization and validation.

Rubber↗

PubMed2026

Protein profiling and GC-MS product analysis provide insights into lignite solubilization and bioconversion by Lysinibacillus sphaericus strain SH19.

Lignite biosolubilization offers a mild route for valorizing low-rank coal, although the microbial processes that accompany solubilization remain incompletely defined. Here, an endogenous isolate designated Lysinibacillus sphaericus strain SH19 was evaluated using nitric-acid-pretreated Shengli lignite. Under the selected working conditions (4 M nitric-acid pretreatment, initial pH 8, 40°C, and 16 days), the apparent solubilization rate reached 66.81%. Changes in A450, residual solid mass, culture pH, and extracellular protein concentration showed that chemical pretreatment and bacterial culture were both associated with the release of soluble lignite-derived material. SDS-PAGE and two-dimensional electrophoresis revealed treatment-associated differences in extracellular and intracellular protein patterns. LC-MS/MS analysis of excised protein spots yielded 85 candidate protein assignments; the revised supplementary table reports PEAKS scores, sequence coverage, peak area, and unique-peptide counts and highlights the limited support for several entries. GC-MS analysis produced 33 tentative library assignments in the solubilized fraction, but siloxane- and silyl-related signals were treated as possible analytical background, and no pathway was inferred from these assignments alone. Together, the data identify strain SH19 as a promising lignite-biosolubilizing isolate and provide candidate proteins and product signals for future validation. The proposed process model remains exploratory because direct enzyme assays, inhibitor experiments, carbon-balance measurements, transcriptomic or genetic validation, complete GC-MS blank subtraction, and authentic-standard confirmation were not available.

Bacillaceae↗

PubMed2026

Transcriptomic analysis reveals the molecular mechanisms underlying the inhibition of Mytilus edulis attachment by biofouling control agents.

This study combined acute toxicity assays, phenotypic quantification, and transcriptomic profiling to systematically investigate the inhibitory effects and molecular regulatory mechanisms of a novel alkylamine-based antifouling agent on survival, byssus secretion, and attachment behavior of juvenile Mytilus edulis. The 96 h-LC50 of the agent to juvenile M. edulis was 8.84 mg/L, and 10 mg/L of the agent completely inhibited mussel attachment within 24 h, significantly reducing byssal thread number, length, and diameter while increasing detachment frequency, resulting in irreversible attachment failure. Transcriptomic analysis identified 2746 differentially expressed genes, which were mainly enriched in pathways including signal transduction, immune defense, stress response, cytoskeleton organization, and protein binding. KEGG and GSEA enrichment revealed that the antifouling agent activated the MAPK stress signaling pathway, disturbed transcriptional regulation, and impaired intracellular homeostasis and cytoskeletal stability, thereby synergistically suppressing the expression of key byssal protein genes including mfp-1 and mfp-3 and ultimately blocking byssus synthesis and adhesion. This study clarifies the multi-pathway molecular mechanism underlying antifouling agent-induced attachment inhibition in M. edulis, and provides core molecular targets and theoretical support for developing efficient, specific antifouling activity, and potentially applicable marine antifouling technologies.

Animals↗

PubMed2026

Mapping Wastewater Pathogens and Their Associated Environmental and Public Health Risk Factors: A Systematic Review and Meta-Analysis.

BACKGROUND: Wastewater-based epidemiology (WBE) has emerged as a critical tool for public health surveillance, yet its application across diverse pathogens and geographical settings remains inconsistent. This systematic review synthesizes global evidence on wastewater surveillance to identify associated risk factors. METHODS: Following PRISMA 2020 guidelines (PROSPERO: CRD420261297382), a systematic search was conducted across PubMed, Scopus, Google Scholar, and Web of Science for studies published between 2000 and 2025. RESULTS: Thirty-nine peer-reviewed studies were included. The evidence base is geographically skewed toward the European Region (48.7%) and the Americas (23.1%), with significant underrepresentation in LMICs. Viruses were the primary biological target (89.7%), followed by bacteria (7.7%) and parasites (2.6%). A proportion meta-analysis of 31 eligible studies demonstrated a pooled wastewater pathogen detection prevalence of 62% (95% CI: 47.5-74.6%), with the European Region yielding the highest regional estimate (73%) and the African Region the lowest (8.3%). Conventional PCR and sequencing methods showed higher pooled detection rates (92.4% and 90.1%, respectively) than RT-qPCR (47.9%). CONCLUSION: WBE provides a robust early-warning system indicating a need for broader pathogen diversity, incorporating bacterial and parasitic surveillance and expansion into rural and resource-limited regions.

Contamination↗

PubMed2026

Conduction System Pacing Versus Right Ventricular Pacing in Patients With Atrioventricular Block and Anticipated High Pacing Burden.

Right ventricular pacing (RVP) in patients with atrioventricular (AV) block and high anticipated pacing burden is associated with pacing-induced cardiomyopathy (PICM) in approximately 12% to 20% of patients, whereas conduction system pacing (CSP) preserves more physiologic ventricular activation and may mitigate these consequences; the totality of contemporary randomized evidence has not been systematically pooled. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing CSP with RVP in patients with AV block or anticipated high ventricular pacing burden and a minimum 6-month follow-up, with co-primary outcomes of PICM incidence and change in left ventricular ejection fraction (ΔLVEF) and secondary outcomes of heart failure hospitalization (HFH), all-cause mortality, composite clinical endpoint, and paced QRS duration (PROSPERO CRD420261400227); random-effects meta-analysis used DerSimonian-Laird estimation. Five RCTs (LBBP-FAVOUR, CSPACE, Prague CSP, PACE-HF, STAY; N = 806) met inclusion criteria. CSP significantly reduced PICM (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.18 to 0.48; p <0.001; I² = 0%; k = 4), was associated with greater LVEF preservation (pooled mean difference [MD] +4.41%, 95% CI +1.82 to +6.99; p = 0.001; I² = 87%; k = 5), and reduced HFH (HR 0.24, 95% CI 0.12 to 0.48; p <0.001; I² = 0%; k = 5). CSP shortened paced QRS duration (MD -27.5 ms, 95% CI -32.6 to -22.5; p <0.001; k = 5). All-cause mortality was numerically lower with CSP but did not reach significance (HR 0.57, 95% CI 0.29 to 1.12; p = 0.10; k = 4). In a prespecified sensitivity analysis restricting to multicenter trials with N ≥ 150, all findings were concordant with the primary analysis. In conclusion, CSP substantially reduces PICM, preserves LVEF, and reduces HFH compared with RVP in patients with AV block and anticipated high pacing burden, supporting its consideration as the preferred pacing strategy in appropriately selected patients.

Humans↗

PubMed2026

Mechanisms of impact of mental health peer support in high-, middle- and low-income settings: mediation analysis of the UPSIDES randomised controlled trial.

AIMS: While there is growing evidence for the effectiveness of peer support (PS) in improving psychosocial outcomes among individuals with severe mental health conditions, the mechanisms through which these effects occur remain insufficiently understood. This study examines whether social inclusion, hope and empowerment mediate the relationship between PS, personal recovery and health and social functioning. METHODS: Data were collected from 565 adults with severe mental health conditions who participated in the multicentre UPSIDES randomised controlled trial across six sites in Germany, Uganda, Tanzania, India and Israel. Participants in the intervention group received structured PS from trained peer workers over a 6- to 8-month period. Standardised, self-report measures of social inclusion, hope, empowerment and personal recovery, as well as clinician-rated health and social functioning, were administered at baseline, 4 months, end of intervention (8 months) and 12-month follow-up. Cross-lagged panel modelling was used to explore longitudinal associations and mediating pathways. RESULTS: The cross-lagged models showed strong autoregressive effects across all variables, indicating high temporal stability. There were no significant direct effects of PS on recovery or health and social functioning. However, mediation analysis identified significant indirect effects of PS on personal recovery via social inclusion (β = 0.114, 95% confidence interval [CI] [0.049, 0.194], P < 0.05) and hope (β = 0.037, 95% CI [0.001, 0.086], P < 0.05). Similar indirect effects were observed for health and social functioning (via social inclusion: β = -0.035, 95% CI [-0.064, -0.013]; via hope: β = -0.026, 95% CI [-0.052, -0.006]; both P < 0.05). CONCLUSIONS: Findings suggest that PS affects recovery-related outcomes primarily through intermediate mechanisms of enhanced hope and social inclusion. These results support theoretical models positing indirect pathways of change in PS interventions and highlight the value of targeting social and psychological domains when designing and implementing PS in mental health services. Individuals with lower baseline levels of hope and social inclusion may particularly benefit from PS.

Humans↗

PubMed2026

Prothrombin complex concentrate (PCC) vs. non-PCC strategies for warfarin reversal in left ventricular assist device recipients: A systematic review and meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) prolong survival in end-stage heart failure, and warfarin thromboprophylaxis is recommended to prevent device thrombosis and thromboembolic complications. When bleeding occurs or emergency surgery is required, rapid anticoagulation reversal is critical. Prothrombin complex concentrate (PCC) provides rapid reversal; however, its risk-benefit profile in LVAD recipients remains unclear. We conducted a systematic review and meta-analysis comparing PCC with non-PCC strategies for warfarin reversal in LVAD recipients. METHODS: MEDLINE, Embase, and Scopus were searched through June 2025 for studies of PCC versus non-PCC strategies for warfarin reversal in LVAD recipients. Two reviewers independently extracted data. Random-effects models were used to pool arm-level estimates and to pool head-to-head comparisons using mean differences or risk ratios (RRs). RESULTS: Eighteen studies involving 779 patients were included. Arm-level pooled estimates for PCC versus non-PCC comparators were 24.0% versus 15.8% for mortality, 16.5% versus 12.1% for thrombotic events, and 3.1 versus 5.7 for FFP units. Arm-level time to INR correction was longer with PCC overall (16.5 versus 13.6 h), driven by one elective cohort, but faster within the ICH subgroup (6.0 versus 13.7 h). In head-to-head comparisons, PCC achieved faster INR correction than non-PCC comparators (mean difference - 7.6 h; p = 0.001) and required fewer FFP units (-2.6 units; p = 0.019), with no significant difference in all-cause mortality (RR 1.14; p = 0.490) or thrombotic events (RR 1.43; p = 0.176). CONCLUSIONS: In head-to-head studies, PCC was associated with faster INR correction and lower FFP requirements than non-PCC strategies, whereas mortality and thrombotic events did not differ significantly. Given the observational evidence, wide confidence intervals, and heterogeneity, equivalent safety cannot be established, and prospective studies are needed to define the relative safety and effectiveness of the two approaches. IMPLICATIONS FOR CLINICAL PRACTICE: PCC-based strategies may be considered for urgent warfarin reversal in LVAD recipients, particularly when rapid INR reduction or avoidance of large-volume plasma transfusion is clinically important. Treatment decisions should account for the indication, bleeding severity, and underlying thrombotic risk. TRIAL REGISTRATION: CRD42024573925.

Humans↗

PubMed2026

Pharmacological and non-pharmacological modulation of striatal dopamine release: a meta-analysis of [11C]raclopride PET studies.

The dopaminergic system has long been a central focus of functional neuroimaging. Positron emission tomography (PET) with the D2/D3 receptor radioligand [11C]raclopride remains the most widely used method for indirectly quantifying striatal dopamine release in vivo. However, no previous meta-analysis has studied the relative magnitude and regional distribution of dopamine release across different interventions or cognitive interventions overall. To address this gap, in this meta-analysis of 92 [11C]raclopride PET studies (n = 1640), we compared the magnitude and regional distribution of dopamine release induced by amphetamine, methylphenidate, ketamine, alcohol, and cognitive challenges with and without reward. Amphetamine induced approximately four-fold greater dopamine release than cognitive challenges (10.9 vs. 2.7%, p < 0.001), and approximately twice that of alcohol (4.8%, p < 0.001), with effects comparable to methylphenidate (11.5%) and slightly greater than ketamine (9.8%). Psychostimulant-induced increase in synaptic dopamine was greater in putamen and ventral striatum than in caudate, whereas alcohol preferentially engaged ventral striatum. Dopamine release did not differ between rewarded and non-rewarded cognitive tasks in the ventral striatum (p > 0.14) or overall striatum (p > 0.10). Methylphenidate-induced increases in synaptic dopamine appeared to attenuate with advancing age, whereas cognitive challenges were associated with greater dopamine release in older individuals. These findings demonstrate that individual pharmacological and cognitive interventions differ markedly in both magnitude and regional pattern of dopamine release. They also suggest that [¹¹C]raclopride PET may have limited sensitivity for distinguishing reward-related from non-reward-related dopamine release. These findings have implications for the design and interpretation of future neuroimaging studies of dopaminergic function in health and disease.

Journal Article↗

PubMed2026

Integrated analysis uncovers exogenous induction and molecular regulation of erinacine A accumulation in Hericium erinaceus.

Erinacine A, a cyathane-type diterpenoid mainly from Hericium erinaceus mycelia, exhibits prominent neurotrophic and neuroprotective activities, making it a promising candidate for managing neurodegenerative diseases. However, its low abundance and unclear genetic regulatory mechanisms hinder its application as a nutraceutical. This study aimed to decipher its regulatory mechanisms and enhance production. Four exogenous inducers were screened, with salicylic acid (SA) and ergosterol (ERG) significantly increasing erinacine A content by 62.21% and 146.70% at 20 days, respectively. Transcriptome and WGCNA of inducer-treated sample identified darkorange and magenta modules associated with erinacine A biosynthesis, with the eri gene cluster enriched in the darkorange module and eriG and eriF as hub genes. Forward genetic analysis via QTL mapping of the HeD127 dikaryon population revealed significant phenotypic variation in erinacine A content (0.341-13.085 mg/g) and identified two loci (erA-1 and erA-2) explaining 18.63% of phenotypic variation. Integrating these forward and reverse genetic analyses revealed that salicylic acid and ergosterol synergistically regulate core carbon metabolic pathways to augment acetyl-CoA supply for the mevalonate pathway, suppressed competitive metabolism, enhanced diterpene skeleton construction and structural modification. These results deepen our understanding of the genetic and molecular basis governing accumulation of erinacine A, and facilitate its application in neuroprotective pharmaceuticals.

Diterpenes↗

PubMed2026

Peripheral pain threshold, glycaemic status, and LAMP3 genetic variation: A community-based analysis.

Diabetic polyneuropathy is a common complication of diabetes, yet substantial inter-individual variation in peripheral pain perception suggests underlying genetic influences. This population-based study investigated clinical, metabolic, and genetic determinants of pain threshold using intraepidermal electrical stimulation in 906 participants from the Iwaki Health Promotion Project 2017. Genome-wide association analysis identified 12 loci showing suggestive associations, among which a missense variant in LAMP3 (rs482912) was prioritized as a biologically plausible candidate. Phenotype-stratified analyses showed that individuals carrying the CT or CC genotypes had lower PINT indices than those with the TT genotype, indicating reduced pain thresholds. Notably, the CC genotype retained an association with lower pain threshold using intraepidermal electrical stimulation under conditions of metabolic stress, including impaired glucose tolerance, elevated HbA1c, and obesity, whereas this association was attenuated in the presence of hypertension. Single-cell RNA sequencing analysis of human skin revealed that LAMP3-positive mature dendritic cells, enriched in immunoregulatory molecules, exhibited transcriptional enrichment of inflammatory, antigen-presenting, and nociception-related pathways, including NF-κB, JAK-STAT, cytokine signaling, and neuroimmune sensitization cascades. Autopsy-based skin analysis further demonstrated genotype-associated differences in dermal LAMP3-positive cell infiltration and CD8-positive T-cell abundance, while CD4-positive T-cell abundance and intraepidermal nerve fiber density remained unchanged across genotypes. Taken together, these findings suggest a potential association between LAMP3 variation and individual differences in peripheral pain threshold and provide biological context supporting a role for neuroimmune interactions in early sensory modulation under metabolic stress. Given the suggestive genetic evidence and indirect mechanistic data, these observations should be interpreted as exploratory and hypothesis-generating.

Humans↗

PubMed2026

Multi-omics analysis reveals stage-associated differences in gut immunity and microbiota between juvenile and adult common carp (Cyprinus carpio).

In vertebrates, the development of intestinal immunity is closely associated with dynamic changes in the gut microbiota. However, stage-associated differences in intestinal immunity and gut microbial communities remain poorly characterized in teleost fish. In this study, transcriptomic analysis combined with 16S rRNA gene sequencing was employed to characterize intestinal immunity and gut microbial communities in juvenile and adult common carp (Cyprinus carpio). Transcriptomic profiling revealed marked developmental differences in intestinal immune function. Juvenile carp exhibited a predominantly innate immune phenotype, characterized by elevated expression of pro-inflammatory cytokines, antimicrobial peptides, and lysozyme-related genes. This immune profile was accompanied by enhanced mucosal barrier function and a relatively pro-inflammatory intestinal environment. In contrast, adult carp displayed increased expression of genes associated with adaptive immunity, suggesting that adult common carp exhibit relatively stronger adaptive immune characteristics than juvenile fish. Gut microbiota analysis demonstrated significant stage-dependent differences in microbial diversity and community composition. Juvenile fish were enriched with bacterial taxa potentially associated with innate immune activation, whereas adult fish harbored distinct microbial communities linked to intestinal homeostasis and barrier maintenance. Furthermore, correlation analyses identified significant associations between specific microbial taxa and innate immune-related gene expression, suggesting a close association between gut microbiota composition and intestinal immune characteristics in juvenile and adult common carp. Collectively, these findings reveal stage-associated differences in intestinal immunity and gut microbial communities between juvenile and adult common carp, thereby providing insights into intestinal immune characteristics at different developmental stages in teleost fish.

Animals↗

PubMed2026

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

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

Salt Stress↗

PubMed2026

Type, severity, frequency and management of adverse reactions associated with ultrasound contrast agents: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis are aimed at evaluating the incidence of adverse drug reactions (ADRs) following administration of clinically approved ultrasound contrast agents (UCAs) in adults and children, to assess risks in patients with cardiovascular disease and in pregnancy, and to evaluate the effectiveness of emergency management of severe ADRs. MATERIALS AND METHODS: A PRISMA 2020 systematic review was conducted searching PubMed, Scopus, and Embase. Two reviewers independently screened, extracted data, and assessed quality. Incidence estimates were pooled when feasible, stratified by age group, contrast agent, and administration route. RESULTS: Seventy-four studies encompassing > 1 million adults and > 36,000 children were included, contributing multiple analytic cohorts to the quantitative synthesis. Severe acute ADRs were extremely rare (6 and 16 cases per 100,000 in adults and children, respectively) and absent following endocavitary administration in children. Non-severe acute ADRs occurred in 11 and 8 cases per 10,000 adults and children, respectively. Delayed reactions were very rare (< 1 case per million in adults). No significant safety differences emerged between UCA products. The incidence of ADRs in patients with cardiovascular disease was analogous to the general population. No ADRs were reported in pregnant women. Standard emergency management was effective in almost all serious cases, though rare fatalities occurred. CONCLUSION: UCAs show an excellent safety profile in adults and children, with very rare severe ADRs and few non-severe, typically self-limiting reactions. Strict adherence to recommended emergency management protocols mitigates the remaining risks, supporting safe use across a broad range of clinical indications. PROSPERO REGISTRATION: CRD42023432668. KEY POINTS: Question What is the incidence, type, and severity of acute and delayed ADRs associated with clinically approved UCAs across different patient populations? Findings Severe acute adverse reactions are very rare, and non-severe reactions are rare and self-limiting, with no significant safety differences between adults, children, or patients with cardiovascular disease. Clinical relevant UCAs show an excellent safety profile across populations. These findings support their safe clinical use as reliable alternatives to iodine-based and gadolinium-based contrast agents in routine diagnostic imaging.

Contrast Media↗

PubMed2026

The incidence and descriptive factors of calcaneal malunion after surgical fixation of intra-articular calcaneal fractures using the sinus tarsi approach: A retrospective cohort study with binary logistic regression analysis.

BACKGROUND: This study evaluated the incidence of calcaneal malunion after minimally invasive sinus tarsi approach (MIS-STA) in displaced intra-articular calcaneal fractures (I-ACFs) and identified related descriptive factors of calcaneal malunion. METHODS: A retrospective review of 99 displaced I-ACFs treated with MIS-STA was conducted. Demographic data, pre-operative radiographs, and operative details were analyzed. Outcomes included numerical rating scale (NRS) pain scores at rest and during activities of daily living (ADL), Foot and Ankle Ability Measure (FAAM) for ADL and radiographic parameters. Logistic regression was used to identify descriptive factors associated with malunion. RESULTS: Malunion occurred in 33/99 cases (33.3%). The significant descriptive factors were the initial Böhler angle < 0.5 °, time to surgery > 12.5 days, and Sanders type ≥ III. Malunion patients had significantly worse NRS and FAAM scores (p ≤ 0.001). CONCLUSION: Calcaneal malunion after MIS-STA occurred in one-third of cases, with three descriptive factors identified and poorer outcomes observed. LEVEL OF EVIDENCE: III, Comparative retrospective study with binary logistic regression analysis.

Humans↗