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Background This study evaluated the utility of serum NR1 and NR2 concentrations in identifying individuals with first-episode schizophrenia (FES) and clinical high risk (CHR) as well as their correlations with clinical symptoms and cognitive domains. Methods This cross-sectional study compared peripheral blood NR1 and NR2 concentrations among the FES, CHR, and healthy control (HC) groups and examined their association with cognitive function. Serum concentrations of NR1 and NR2 subunits were measured using ELISA, and cognitive function was assessed using the MATRICS Consensus Cognitive Battery. Concentrations were compared among groups using the analysis of covariance or non-parametric tests and ROC curve analysis, and correlation was determined using the Pearson or Spearman method. Results A total of 41 FES cases, 34 CHR cases, and 41 HC were included in the study. Serum NR1 concentrations significantly varied among the three groups (Z = 16.19, P  < 0.001) and were significantly different between the FES group and the CHR (Z = -4.04, P  < 0.001) and HC groups (Z = -2.49, P  = 0.01). Additionally, serum NR2 concentration was significantly different between the CHR and HC groups (F = 5.37, P  = 0.02). In the FES group, serum NR1 concentration was negatively correlated with speed of processing ( r  = -0.41, P  = 0.02), whereas serum NR2 concentration was negatively correlated with verbal learning ( r  = -0.40, P  = 0.02). In the CHR group, serum NR1 concentration was positively correlated with the total MCCB score ( r  = 0.40, P  = 0.04). ROC curve analysis showed that NR2 level was better for discriminating FES (AUC: 69%; sensitivity: 56%; specificity: 85%; optimal cutoff value: 32.80 ng/mL) and CHR (AUC: 74%; sensitivity: 62%; specificity: 85%; optimal cutoff value: 32.77 ng/mL). Conclusions Serum NR1 and NR2 concentrations show potential for early identification of individuals with psychosis, but further validation is needed, and they are also correlated with cognition. Furthermore, serum NR2 concentration is more stable and serves as a promising objective biomarker for quantitative assessment.

Working memory deficits are linked to irregularities in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in schizophrenia, effective intervention strategies are lacking. We evaluated the differential efficacy and underlying neuromechanisms of targeting transcranial direct current stimulation (tDCS) at the DLPFC and the PPC with concurrent cognitive performance for working memory in schizophrenia. In a randomized and double-blind clinical trial, sixty clinically stable schizophrenic patients with below-average working memory were randomly assigned to active DLPFC, active PPC, and sham tDCS groups. Two sessions of tDCS during N-back task were delivered daily for five days. The primary outcome was changes in spatial span test scores from baseline to week 1. The secondary outcomes included changes in scores of color delay-estimation task, other cognitive tasks, and mismatch negativity (biomarker of N-methyl-d-aspartate receptor functioning). Compared with the active DLPFC group, the active PPC group demonstrated significantly greater improvement in spatial span test scores ( p  = 0.008, d  = 0.94) and an augmentation in color delay-estimation task capacity at week 1; the latter sustained to week 2. Compared with the sham tDCS group, the active PPC group did not show a significant improvement in spatial span test scores at week 1 and 2; however, significant enhancement was observed in their color delay-estimation task capacity at week 2. Additionally, mismatch negativity amplitude was enhanced, and changes in theta band measures were positively correlated with working memory improvement in the active PPC group, while no such correlations were observed in the active DLPFC group or the sham tDCS group. Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia, meriting further investigation. The improvement in working memory appears to be linked to enhanced N-methyl-d-aspartate receptor functioning.

Attenuated positive symptoms syndrome (APSS) is a risk state preceding psychosis, and its early identification is key to early intervention. Previous studies have suggested that disturbances in the frontal–striatal–thalamic (FST) circuit may play a role in the neuropathology of APSS. However, the evidence regarding white matter structure remains fragmented. This study aimed to systematically investigate white matter (WM) alterations within the FST circuits in individuals with APSS. Diffusion magnetic resonance imaging (dMRI) and T1-weighted images were acquired from 43 individuals with APSS and 50 healthy controls (HCs). The dMRI data were preprocessed using FMRIB Software Library software. The Brainnetome Atlas was utilized to extract regions of interest (ROIs) in the frontal lobe, striatum, and thalamus. Bidirectional probabilistic tractography was performed to construct the FST circuit. The connection probability (CP) and diffusion index values were compared between the APSS and HC groups using the two-sample t test. Compared to HCs, individuals with APSS exhibited significantly lower CP values in right orbital gyrus_area 13- right nucleus accumbens (OrG_A13-NAC) fiber tract; higher mean diffusivity values in the left OrG_A13-NAC and left ventral caudate–left caudal temporal thalamus (vCa-cTtha) fiber tracts; higher radial diffusivity values in the right OrG_A13-NAC fiber tract; and higher axial diffusivity values in multiple frontal lobe ROI–striatum ROI and striatum ROI–thalamus ROI fiber tracts. Overall, individuals with APSS demonstrated white matter microstructural abnormalities, especially in the OrG_A13-NAC fiber tracts. These alterations may contribute to our understanding on the neuropathology of APSS.

Cognitive dysfunction is a defining characteristic impairing social functioning in schizophrenia (SZ). N-methyl-D-aspartate receptor (NMDAR) hypofunction may underlie these impairments. This study explored the association between peripheral blood levels of the NMDAR subunits NR1 and NR2 and cognitive improvement in SZ, evaluating their potential as biomarkers for the efficacy of cognitive intervention. This secondary analysis of a randomized controlled trial included 60 clinically stable SZ patients and 30 healthy controls (HCs). Patients received five-day transcranial direct current stimulation (tDCS) during cognitive tasks across three groups: the active dorsolateral prefrontal cortex (DLPFC), the active posterior parietal cortex (PPC), and the sham stimulation group. Cognition was evaluated, and blood samples were collected at baseline, week 1, and week 2. Baseline blood samples were also obtained from HCs. NR1 and NR2 concentrations were quantified using enzyme-linked immunosorbent assay (ELISA). We found that baseline NR1 concentration was significantly lower in the patient group than in HCs, with no NR2 differences observed. Compared to the other two groups, the active PPC group demonstrated significant working memory improvements. In the active PPC group, baseline NR1 and NR2 concentrations were negatively correlated with working memory improvements at week 1. Moreover, changes in NR1 at weeks 1 and 2, and NR2 at week 1, were positively associated with working memory improvements at week 1 in the active PPC group. Peripheral NR1 and NR2 levels may serve as biomarkers for predicting cognitive improvement in SZ, supporting the role of NMDAR dysfunction in SZ-related cognitive deficits.

While individuals with schizophrenia (SZ) exhibit deficits in social cognition, the specific profile of these deficits across multiple domains and their relationship with clinical symptoms warrants further characterization. This study aimed to systematically assess key social-cognitive domains—theory of mind (ToM), emotion recognition, attributional style, and social perception—and examine their associations with psychopathology in SZ. Sixty-eight individuals with SZ and 68 matched healthy controls (HC) completed a comprehensive battery of social-cognitive measures, including the false-belief task (assessing first- and second-order ToM), the Faux Pas task, the emotional recognition task, the attributional style questionnaire, and the social perception scale. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Compared to HC, individuals with SZ showed significant deficits across all social-cognitive measures. Specifically, the SZ group exhibited deficits in emotion recognition for all negative emotions (fear, anger, sadness, disgust) but not for happiness, and in attributional style for positive but not negative events. Correlation analyses identified a statistically significant inverse relationship between attributional stability for negative events (i.e., the tendency to attribute the causes of negative events to factors that are persistent over time) and PANSS general psychopathology scores (τ = −0.25, P < 0.043). Furthermore, no other social-cognitive domains (ToM, emotion recognition, social perception) showed significant correlations with any PANSS symptom dimensions. Network analysis further characterized second-order ToM as the core deficit, exhibiting the highest strength and centrality within the social-cognitive network, with mediation effects most pronounced for sadness and happiness recognition. These findings highlight second-order ToM as a core deficit in individuals with schizophrenia and suggest that a stable attributional style may be associated with a lower overall burden of general psychopathology. These social-cognitive domains may represent promising targets for future cognitive remediation interventions for people living with schizophrenia.

Both the brain-derived neurotrophic factor (BDNF) valine (Val)/methionine (Met) polymorphism and mismatch negativity (MMN) amplitude are reportedly linked to working memory impairments in schizophrenia. However, there is evident scarcity of research aimed at exploring the relationships among the three factors. In this secondary analysis of a randomized, controlled, double-blind trial, we investigated these relationships. The trial assessed the efficacy of transcranial direct current stimulation for enhancing working memory in clinically stable schizophrenia patients, who were randomly divided into three groups: dorsolateral prefrontal cortex stimulation, posterior parietal cortex stimulation, and sham stimulation groups. Transcranial direct current stimulation was administered concurrently with a working memory task over five days. We assessed the BDNF genotype, MMN amplitude, working memory capacity, and interference control subdomains. These assessments were conducted at baseline with 54 patients and followed up post-intervention with 48 patients. Compared to BDNF Met-carriers, Val homozygotes exhibited fewer positive and general symptoms and increased working memory capacity at baseline. A correlation between MMN amplitude and working memory capacity was noted only in BDNF Val homozygotes. The correlations were significantly different in the two BDNF genotype groups. Furthermore, in the intervention group that showed significant improvement in MMN amplitude, BDNF Val homozygotes exhibited greater enhancement in working memory capacity than Met-carriers. This study provides in vivo evidence for the interaction between MMN and BDNF Val/Met polymorphism for working memory capacity. As MMN has been considered a biomarker of N-methyl-D-aspartate receptor (NMDAR) function, these data shed light on the complex interactions between BDNF and NMDAR in terms of working memory in schizophrenia.

Straggler synchronization is a dominant wall-clock bottleneck in synchronous wireless federated learning (FL). Under non-IID data, however, aggressively sampling only fast clients may significantly slow convergence due to statistical heterogeneity. This paper studies PASS-enabled FL, where a radiating pinching antenna (PA) can be activated at an arbitrary position along a dielectric waveguide to reshape uplink latencies. We consider a joint optimization of PA placement and client participation to minimize a proxy for time-to-accuracy, coupling the exact expected maximum round latency via order statistics with a heterogeneity-aware statistical-efficiency proxy. We derive first-order optimality conditions that reveal an explicit tail-latency premium in the KKT recursion, quantifying how latency gaps are amplified by maximum-order-statistic synchronization. Under a latency-class structure, we obtain a within-class square-root sampling law and establish a two-class phase transition where slow-class participation collapses under an explicit heterogeneity-threshold condition as the per-round sample size grows. For PA placement, we prove a piecewise envelope-derivative characterization and provide an exact breakpoint-and-root candidate-enumeration procedure. Simulation results validate the structural findings and show that PASS enables more eligible participation, yielding higher wall-clock accuracy.

Single-atom catalysts (SACs) enable greener and more economically sustainable chemical production by significantly improving thermocatalysis efficiency and selectivity through maximized atom utilization and highly homogeneous metal coordination environments. Unfortunately, SACs are fundamentally constrained by the stability owing to the severe aggregation of single atoms, especially under the high-temperature thermocatalysis operations, which compromises the overall catalytic performance. Here, we report a synthetic strategy to realize the highly thermal-stable SACs resistance to sintering at harsh conditions through harnessing the inherent metal affinity and fluidity of liquid metal. A stable liquid metal-active metal interaction is formed, profiting from the superior metal affinity of liquid metal. Combined with the fluidity of liquid metal, active metal atoms can move but remain confined to the liquid metal as the metallic single-atom state at high temperatures. This catalyst exhibits outstanding thermal durability for ethane dehydrogenation, sustaining stable operation for over 100 h at 650 °C with an impressive ethylene selectivity of 98%. The strategy of constructing stable metal-metal interactions by utilizing the inherent metal affinity and dynamic fluidity of liquid metal will pave a practical way for the design of highly thermal-stable SACs. Single-atom catalysts promise efficient reactions, but readily aggregate at high temperatures, limiting durability. Confining single metal atoms in liquid metal stabilizes them, enabling long-lasting ethane dehydrogenation at high temperature.

Diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC) are the major histological types of gastric cancer (GC). The molecular mechanism underlying DGC and IGC differences are poorly understood. In this research, we carry out multilevel proteomic analyses, including proteome, phospho-proteome, and transcription factor (TF) activity profiles, of 196 cases covering DGC and IGC in Chinese patients. Integrative proteogenomic analysis reveals ARIDIA mutation associated with opposite prognostic effects between DGC and IGC, via diverse influences on their corresponding proteomes. Systematical comparison and consensus clustering analysis identify three subtypes of DGC and IGC, respectively, based on distinct patterns of the cell cycle, extracellular matrix organization, and immune response-related proteins expression. TF activity-based subtypes demonstrate that the disease progressions of DGC and IGC were regulated by SWI/SNF and NFKB complexes. Furthermore, inferred immune cell infiltration and immune clustering show Th1/Th2 ratio is an indicator for immunotherapeutic effectiveness, which is validated in an independent GC anti-PD1 therapeutic patient group. Our multilevel proteomic analyses enable a more comprehensive understanding of GC and can further advance the precision medicine. The molecular differences between the two major gastric cancer subtypes diffuse-type gastric cancer (DGC) and intestinaltype gastric cancer (IGC) remain to be investigated. Here, integrated analysis of proteome, phospho-proteome and transcription factor activity for DGC and IGC reveals potential subtypes.

No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.