Impact of Operator Experience on Left Atrial Appendage Occlusion Outcomes.

BACKGROUND: The relationship between long-term outcomes and operator experience for left atrial appendage occlusion (LAAO) is still unknown. OBJECTIVES: This study sought to explore the association between operator LAAO experience and one-year clinical outcomes. METHODS: The RECORD study (Registry to Evaluate Chinese Real-World Clinical Outcomes in Patients With AF Using the WATCHMAN Left Atrial Appendage Closure Technology; NCT03917563) was a multicenter, prospective registry that included patients with the WATCHMAN LAAO device (Boston Scientific) in China from April 1, 2019, to October 31, 2020. The current analyses included patients with solely LAAO from the registry; those who had concomitant LAAO and ablation/other procedures were excluded. The primary outcome was a composite endpoint of death, stroke, systemic embolism, and Bleeding Academic Research Consortium (BARC)-defined type 3 or 5 bleeding at 1 year. RESULTS: A total of 1,547 LAAO patients and 111 operators were included. The mean ± SD CHA2DS2-VASc and HAS-BLED scores of patients were 4.0 ± 1.8 and 2.5 ± 1.1, respectively. The mean ± SD age of operators was 47.0 ± 7.2 years, 15 (13.5%) were female, and 52 (46.8%) were electrophysiologists. Utilizing maximally selected log-rank statistics, the thresholds to categorize an experienced operator were performing ≥32 LAAOs annually or ≥134 LAAOs in total. Performing ≥32 LAAOs annually is the better criterion than ≥134 LAAOs in total (absolute net reclassification index: 25.79%; P < 0.001). Compared with the ≥32 LAAO annually group, the <32 group was associated with a 1.8-fold (HRadjusted: 1.79; 95% CI: 1.16-2.78; P = 0.009) increase in the risk of the primary endpoint, and such risk in the <32 group can be reduced by ∼12% after performing each additional 5 cases (HRadjusted per 5 cases: 0.88; 95% CI: 0.78-0.99; P = 0.033). CONCLUSIONS: Performing ≥32 LAAOs annually could be a threshold to categorize an experienced operator. Before reaching this threshold, the risk of death, stroke, systemic embolism, and BARC-defined type 3 or 5 bleeding decreased by 12% after every 5 cases performed.

Autophagy defects at weaning impair complement-dependent synaptic pruning and induce behavior deficits.

Autophagy is crucial for synaptic plasticity and the architecture of dendritic spines. However, the role of autophagy in schizophrenia (SCZ) and the mechanisms through which it affects synaptic function remain unclear. In this study, we identified 995 single nucleotide polymorphisms (SNPs) across 19 autophagy-related genes that are associated with SCZ. Gene Set Enrichment Analysis (GSEA) of data from the Gene Expression Omnibus public database revealed defective autophagy in patients with SCZ. Using a maternal immune activation (MIA) rat model, we observed that autophagy was downregulated during the weaning period, and early-life activation of autophagy with rapamycin restored abnormal behaviors and electrophysiological deficits in adult rats. Additionally, inhibition of autophagy with 3-Methyladenine (3-MA) during the weaning period resulted in aberrant behaviors, abnormal electrophysiology, increased spine density, and reduced microglia-mediated synaptic pruning. Furthermore, 3-MA treatment significantly decreased the expression and synaptosomal content of complement, impaired the recognition of C3b and CR3, indicating that autophagy deficiency disrupts complement-mediated synaptic pruning. Our findings provide evidence for a significant association between SCZ and defective autophagy, highlighting a previously underappreciated role of autophagy in regulating the synaptic and behavioral deficits induced by MIA.

CD57+ T Cell Transmigration Through Vascular Endothelial Cells is Enhanced by Tumor Necrosis Factor: A Novel Model of Cardiovascular Risk in People with HIV.

People with human immunodeficiency virus (PWH), despite achieving viral suppression through antiretroviral therapy, face increased risk and earlier onset of atherosclerotic cardiovascular diseases than the general population. CD57+ T cells can be readily recovered from atherosclerotic plaques and likely contribute to disease by targeting endothelial cells (ECs); however, the specific mechanisms facilitating the infiltration of these cells into plaques remain elusive. Here, we report the development of a novel assay to quantify T cell adhesion to and transmigration through a primary human vascular EC monolayer and show that CD57+ T cells preferentially adhere to and transmigrate through the monolayer. Moreover, activating the ECs with tumor necrosis factor (TNF) significantly increased the transmigration of CD57+ T cells, supporting the role of TNF in promoting the vascular homing of CD57+ T cells. This model will allow for elucidating the mechanisms of and testing interventions to prevent CD57+ T cell infiltration into plaques.

Propensity-matched study on locally advanced esophageal cancer: surgery versus post-operative radiotherapy.

BACKGROUND: This study aims to delineate the long-term outcomes and recurrence patterns of locally advanced thoracic esophageal squamous cell carcinoma (TESCC) patients managed with or without postoperative radiotherapy (PORT). METHODS: A retrospective cohort from two academic centers, encompassing patients who initially underwent esophagectomy and were pathologically staged T3-4, was analyzed. Survival outcomes were constructed using Kaplan-Meier method, with survival significance was evaluated using the log-rank test. Propensity score matching (PSM) was utilized to balance potential selection bias. RESULTS: Among the 506 patients, 251 underwent surgery alone and 255 received radiotherapy following radical surgery. With a median follow-up of 49.1 months, PORT significantly improved 5-year overall survival (53.8% vs. 25.3%; p < 0.001) and 5-year disease-free survival rates (45.3% vs. 8.5%; p < 0.001) compared to surgery alone. These differences in survival outcomes persisted even after PSM (p < 0.001 for both). Treatment failure was significantly less frequent in the PORT group (46.7%) compared to the surgery-only group (90.0%; p < 0.001), with corresponding reductions in locoregional recurrence (9.4% vs. 54.1%; p < 0.001). This underscores the significant association between PORT and disease control. CONCLUSION: The absence of neoadjuvant chemoradiotherapy highlights the importance of PORT in improving survival and reducing recurrence in advanced T3-4 TESCC patients. This study underscores the importance of PORT as a salvage treatment for locally advanced TESCC patients without neoadjuvant chemoradiotherapy.

Morphological and Phylogenetic Analyses Reveal Three Novel Species of Sanguinoderma (Ganodermataceae, Basidiomycota) from Yunnan Province, China.

Sanguinoderma (Ganodermataceae) is recognized as a valuable medicinal resource in Taiwan, China. Additionally, it serves as a traditional folk medicine for treating neurotic epilepsy in Malaysia. This study involved the collection of six specimens of Sanguinoderma from Yunnan Province, China. Employing multigene phylogenetic analysis of DNA sequences, including internal transcribed spacer (ITS), nuclear large subunit (LSU), RNA polymerase II second largest subunit (rpb2), translation elongation factor 1-alpha (tef1-α), mitochondrial small subunit (mtSSU), nuclear small subunit (nSSU) and morphological examinations, three new species, viz. Sanguinoderma concentricum, S. dehongense and S. ovisporum, are introduced. Sanguinoderma concentricum is characterized by a central stipe basidiomata, an orbicular to suborbicular pileus, a grayish-yellow surface with alternating concentric zones and wavy margin-like petals and regular pileipellis cells (4-8 × 17-28 µm). Sanguinoderma dehongense is characterized by a long stipe and flabelliform basidiomata, a dark-grayish yellow-to-dark-yellow pileus surface, irregular pileipellis cells and wavy margin and ellipsoid basidia (8-11 × 9-13 µm). Sanguinoderma ovisporum is characterized by a reniform basidiomata, a heterogeneous context and ovoid basidiospores (7.5-8.6 × 5.5-7.2 µm). A detailed description and illustrations of these new species are provided, as well as a morphological comparison with similar taxa.

Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment response and white matter density deficits.

Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

From docking to dynamics: Unveiling the potential non-peptide and non-covalent inhibitors of Mpro from natural products.

MOTIVATION: This study aims to investigate non-covalent and non-peptide inhibitors of Mpro, a crucial protein target, by employing a comprehensive approach that integrates molecular docking, molecular dynamics simulations, and top-hits activity predictions. The focus is on elucidating the non-covalent and non-peptide binding modes of potential inhibitors with Mpro. METHODS: We employed a semi-flexible molecular docking methodology, binding score and ADME screening, which are based on structure, to screen compounds from CMNPD and HERB in silico. These methodologies allowed us to find potential candidates depending on their binding values and interactions with the binding site of main protease. To further evaluate the stability of these interactions, we conducted molecular dynamics simulations and calculated binding energies. Ultimately, a top-hits activity prediction method was employed to prioritize compounds based on their predicted inhibitory potential. RESULTS: Through a combination of binding energy calculations and activity predictions, we identified six potential inhibitor molecules exhibiting promising activity against Mpro. These compounds demonstrated favorable binding interactions and stability profiles, making them attractive candidates for further experimental validation and drug development efforts targeting Mpro.

Npc1 deficiency impairs microglia function via TREM2-mTOR signaling in Niemann-Pick disease type C.

Niemann-Pick disease Type C (NPC) is a neurodegenerative disease mainly caused by the mutation in NPC1 gene, leading to massive accumulation of unesterified cholesterol in the late endosome/lysosome of cells. Impaired phenotype of microglia is a hallmark in Npc1 mutant mice (Npc1-/- mice). However, the mechanism of Npc1 in regulating microglial function is still unclear. Here, we showed that the reactive microglia in the neonatal Npc1-/- mice indicated by the increased lysosome protein CD68 and phagocytic activity were associated with disrupted TREM2-mTOR signaling in microglia. Furthermore, in Npc1-deficient BV2 cells, genetic deletion of Trem2 partially restored microglial function, probably via restored mTOR signaling. Taken together, our findings indicated that loss of Npc1 in microglia caused changes of their morphologies and the impairment of lysosomal function, which were linked to the TREM2-mTOR signaling pathway.

First-line treatment with KN046, chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma: an open-label, dose escalation, and dose expansion phase Ib trial.

There is growing evidence to suggest that radiotherapy might enhance the efficacy of immunotherapy. This study aimed to assess the possibility of KN046, a bispecific antibody targeting PD-L1 and CTLA-4, combined with chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma (ESCC). In this open-label, phase Ib trial, patients with advanced ESCC were administered chemotherapy with palliative radiotherapy, and KN046 in the predefined escalation dosages of 1, 3, or 5 mg/kg (every 3 weeks during chemotherapy cycles and every 2 weeks during KN046 maintenance). The chemotherapy regimen constituted cisplatin (75 mg/m2 i.v., d1) and paclitaxel (135-175 mg/m2 ivgtt., d1). Radiotherapy specifics, including site, timing, dose, and fragmentation pattern, were at the investigator's discretion. The primary outcome was dose-limiting toxicity (DLT). From May 2019 to April 2021, 25 patients were enrolled across the dosage groups: 3 in 1 mg/kg, 12 in 3 mg/kg, and 10 in 5 mg/kg. No DLT was observed during the dose escalation. The objective response rate was 41.7% (95%CI 22.1-63.4), while the disease control rate was 87.5% (95%CI 67.6-97.3). At a median follow-up of 11.8 months, the median progression-free survival was 7.8 months (95%CI 5.2-9.7) and median overall survival was 15.9 months (95%CI 8.4-NE). Serious adverse events were reported in 48.0% of patients, predominantly leukopenia (16%), immune-mediated enterocolitis (12%), immune-mediated pneumonitis (8%), and neutropenia (8%). Combining KN046 with chemotherapy and palliative radiotherapy might be feasible, showing a favorable safety profile and notable efficacy in advanced ESCC patients.

EEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytes.

Radiation-induced heart disease (RIHD) is a severe delayed complication of thoracic irradiation (IR). Endonuclease/exonuclease/phosphatase family domain-containing 1 ( EEPD1) plays an important role in DNA damage repair, but its role in RIHD is less known. In this study, EEPD1 global knockout mice, C57BL/6J mice, and C57BL/6J mice overexpressing EEPD1 are treated with radiation at a total dose of 20 Gy or 0 Gy. After 9 weeks, echocardiography is used to assess cardiac hypertrophy and apoptosis. The results show that EEPD1 deletion exacerbates radiation-induced cardiac hypertrophy and apoptosis, while EEPD1 overexpression has the opposite effect. Further mechanistic investigations reveal that EEPD1 interacts with FOXO3A and destabilizes it by catalyzing its deubiquitination. Inhibition of FOXO3A ameliorates cardiac hypertrophy and apoptosis after EEPD1 knockdown. Thus, EEPD1 protects against radiation-induced cardiac hypertrophy and apoptosis via destabilization of FOXO3A, which may offer new insight into therapeutic strategies for RIHD.

Identification of Autophagy-Related Biomarkers and Diagnostic Model in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. Its accurate pathogenic mechanisms are incompletely clarified, and effective therapeutic treatments are still inadequate. Autophagy is closely associated with AD and plays multiple roles in eliminating harmful aggregated proteins and maintaining cell homeostasis. This study identified 1191 differentially expressed genes (DEGs) based on the GSE5281 dataset from the GEO database, intersected them with 325 autophagy-related genes from GeneCards, and screened 26 differentially expressed autophagy-related genes (DEAGs). Subsequently, GO and KEGG enrichment analysis was performed and indicated that these DEAGs were primarily involved in autophagy-lysosomal biological process. Further, eight hub genes were determined by PPI construction, and experimental validation was performed by qRT-PCR on a SH-SY5Y cell model. Finally, three hub genes (TFEB, TOMM20, GABARAPL1) were confirmed to have potential application for biomarkers. A multigenic prediction model with good predictability (AUC = 0.871) was constructed in GSE5281 and validated in the GSE132903 dataset. Hub gene-targeted miRNAs closely associated with AD were also retrieved through the miRDB and HDMM database, predicting potential therapeutic agents for AD. This study provides new insights into autophagy-related genes in brain tissues of AD patients and offers more candidate biomarkers for AD mechanistic research as well as clinical diagnosis.

Radiation-Induced Endothelial Ferroptosis Accelerates Atherosclerosis via the DDHD2-Mediated Nrf2/GPX4 Pathway.

This study sought to explore potential roles of endothelial ferroptosis in radiation-associated atherosclerosis (RAA) and molecular mechanisms behind this phenomenon. Here, an in vivo RAA mouse model was used and treated with ferroptosis inhibitors. We found that the RAA group had a higher plaque burden and a reduction in endothelial cells with increased lipid peroxidation compared to the control group, while ameliorated by liproxstatin-1. In vitro experiments further confirmed that radiation induced the occurrence of ferroptosis in human artery endothelial cells (HAECs). Then, proteomics analysis of HAECs identified domain-containing protein 2 (DDHD2) as a co-differentially expressed protein, which was enriched in the lipid metabolism pathway. In addition, the level of lipid peroxidation was elevated in DDHD2-knockdown HAECs. Mechanistically, a significant decrease in the protein and mRNA expression of glutathione peroxidase 4 (GPX4) was observed in HAECs following DDHD2 knockdown. Co-immunoprecipitation assays indicated a potential interaction between DDHD2 and nuclear factor erythroid 2-related factor 2 (Nrf2). The downregulation of Nrf2 protein was also detected in DDHD2-knockdown HAECs. In conclusion, our findings suggest that radiation-induced endothelial ferroptosis accelerates atherosclerosis, and DDHD2 is a potential regulatory protein in radiation-induced endothelial ferroptosis through the Nrf2/GPX4 pathway.

Closed loop stimulation reduces the incidence of atrial high-rate episodes compared with conventional rate-adaptive pacing in patients with sinus node dysfunctions.

AIMS: Subclinical atrial fibrillation (AF) is associated with increased risk of progression to clinical AF, stroke, and cardiovascular death. We hypothesized that in pacemaker patients requiring dual-chamber rate-adaptive (DDDR) pacing, closed loop stimulation (CLS) integrated into the circulatory control system through intra-cardiac impedance monitoring would reduce the occurrence of atrial high-rate episodes (AHREs) compared with conventional DDDR pacing. METHODS AND RESULTS: Patients with sinus node dysfunctions (SNDs) and an implanted pacemaker or defibrillator were randomly allocated to dual-chamber CLS (n = 612) or accelerometer-based DDDR pacing (n = 598) and followed for 3 years. The primary endpoint was time to the composite endpoint of the first AHRE lasting ≥6 min, stroke, or transient ischaemic attack (TIA). All AHREs were independently adjudicated using intra-cardiac electrograms. The incidence of the primary endpoint was lower in the CLS arm (50.6%) than in the DDDR arm (55.7%), primarily due to the reduction in AHREs lasting between 6 h and 7 days. Unadjusted site-stratified hazard ratio (HR) for CLS vs. DDDR was 0.84 [95% confidence interval (CI), 0.72-0.99; P = 0.035]. After adjusting for CHA2DS2-VASc score, the HR remained 0.84 (95% CI, 0.71-0.99; P = 0.033). In subgroup analyses of AHRE incidence, the incremental benefit of CLS was greatest in patients without atrioventricular block (HR, 0.77; P = 0.008) and in patients without AF history (HR, 0.73; P = 0.009). The contribution of stroke/TIA to the primary endpoint (1.3%) was low and not statistically different between study arms. CONCLUSION: Dual-chamber CLS in patients with SND is associated with a significantly lower AHRE incidence than conventional DDDR pacing.

Single-nucleus chromatin landscape dataset of mouse brain development and aging.

The development and aging of the brain constitute a lifelong dynamic process, marked by structural and functional changes that entail highly coordinated cellular differentiation and epigenetic regulatory mechanisms. Chromatin accessibility serves as the foundational basis for genetic activity. However, the holistic and dynamic chromatin landscape that spans various brain regions throughout development and ageing remains predominantly unexplored. In this study, we employed single-nucleus ATAC-seq to generate comprehensive chromatin accessibility maps, incorporating data from 69,178 cells obtained from four distinct brain regions - namely, the olfactory bulb (OB), cerebellum (CB), prefrontal cortex (PFC), and hippocampus (HP) - across key developmental time points at 7 P, 3 M, 12 M, and 18 M. We delineated the distribution of cell types across different age stages and brain regions, providing insight into chromatin accessible regions and key transcription factors specific to different cell types. Our data contribute to understanding the epigenetic basis of the formation of different brain regions, providing a dynamic landscape and comprehensive resource for revealing gene regulatory programs during brain development and aging.

A broken network of susceptibility genes in the monocytes of Crohn's disease patients.

Genome-wide association studies have identified over 200 genetic loci associated with inflammatory bowel disease; however, the mechanism of such a large amount of susceptibility genes remains uncertain. In this study, we integrated bioinformatics analysis and two independent single-cell transcriptome datasets to investigate the expression network of 232 susceptibility genes in Crohn's disease (CD) patients and healthy controls. The study revealed that most of the susceptibility genes are specifically and strictly expressed in the monocytes of the human intestinal tract. The susceptibility genes established a network within the monocytes of health control. The robustness of a gene network may prevent disease onset that is influenced by the genetic and environmental alteration in the expression of susceptibility genes. In contrast, we showed a sparse network in pediatric/adult CD patients, suggesting the broken network contributed to the CD etiology. The network status of susceptibility genes at the single-cell level of monocytes provided novel insight into the etiology.

Antipsychotic drug-induced behavioral abnormalities in common carp: The potential involvement of the gut microbiota-brain axis.

The effects of antipsychotic drugs on aquatic organisms have received widespread attention owing to their widespread use and continued release in aquatic environments. The toxicological effects of antipsychotics on aquatic organisms, particularly fish, are unexplored, and the underlying mechanisms remain unelucidated. This study aimed to use common carp to explore the effects of antipsychotics (olanzapine [OLA] and risperidone [RIS]) on behavior and the potential mechanisms driving these effects. The fish were exposed to OLA (0.1 and 10 µg/L) and RIS (0.03 and 3 µg/L) for 60 days. Behavioral tests and neurological indicators showed that exposure to antipsychotics could cause behavioral abnormalities and neurotoxicity in common carp. Further, 16 S rRNA sequencing revealed gut microbiota alteration and decreased relative abundance of some strains related to SCFA production after OLA and RIS exposure. Subsequently, a pseudo-sterile common carp model was successfully constructed, and transplantation of the gut microbiota from antipsychotic-exposed fish caused behavioral abnormalities and neurotoxicity in pseudo-sterile fish. Further, SCFA supplementation demonstrated that SCFAs ameliorated the behavioral abnormalities and neurological damage caused by antipsychotic exposure. To our knowledge, the present study is the first to investigate the effects of antipsychotics on various complex behaviors (swimming performance and social behavior) in common carp, highlighting the potential health risks associated with antipsychotic drug-induced neurotoxicity in fish. Although these results do not fully elucidate the mechanisms underlying the effects of antipsychotic drugs on fish behavior, they serve as a valuable initial investigation and form the basis for future research.

Redox Synergy: Enhancing Gas Sensing Stability in 2D Conjugated Metal-Organic Frameworks via Balancing Metal Node and Ligand Reactivity.

Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) have emerged as promising candidates in gas sensing, owing to their tunable porous structure and conductivity. Nevertheless, the reported gas sensing mechanisms heavily relied on electron transfer between metal nodes and gas molecules. Normally, the strong interaction between the metal sites and target gas molecule would result poor recovery and thus bad recycling property. Herein, we propose a redox synergy strategy to overcome this issue by balancing the reactivity of metal sites and ligands. A 2D c-MOF, Zn3(HHTQ)2, was prepared for nitrogen dioxide (NO2) sensing, which was constructed from active ligands (hexahydroxyltricycloquinazoline, HHTQ) and inactive transition-metal ions (Zn2+). Substantial characterizations and theoretical calculations demonstrated that by utilizing only the redox interactions between ligands and NO2, not only high sensitivity and selectivity, but also excellent cycling stability in NO2 sensing could be achieved. In contrast, control experiments employing isostructural 2D c-MOFs with Cu/Ni metal nodes exhibited irreversible NO2 sensing. Our current work provides a new design strategy for gas sensing materials, emphasizing harnessing the redox activity of only ligands to enhance the stability of MOF sensing materials.

2D Conjugated Metal-Organic Frameworks Bearing Large Pore Apertures and Multiple Active Sites for High-Performance Aqueous Dual-Ion Batteries.

2D conjugated metal-organic frameworks (2D c-MOFs) with large pore sizes and high surface areas are advantageous for adsorbing iodine species to enhance the electrochemical performance of aqueous dual-ion batteries (ADIBs). However, most of the reported 2D c-MOFs feature microporous structures, with few examples exhibiting mesoporous characteristics. Herein, we developed two mesoporous 2D c-MOFs, namely PA-TAPA-Cu-MOF and PA-PyTTA-Cu-MOF, using newly designed arylimide based multitopic catechol ligands (6OH-PA-TAPA and 8OH-PA-PyTTA). Notably, PA-TAPA-Cu-MOF exhibits the largest pore sizes (3.9 nm) among all reported 2D c-MOFs. Furthermore, we demonstrated that these 2D c-MOFs can serve as promising cathode host materials for polyiodides in ADIBs for the first time. The incorporation of triphenylamine moieties in PA-TAPA-Cu-MOF resulted in a higher specific capacity (423.4 mAh g-1 after 100 cycles at 1.0 A g-1) and superior cycling performance, retaining 96 % capacity over 1000 cycles at 10 A g-1 compared to PA-PyTTA-Cu-MOF. Our comparative analysis revealed that the increased number of N anchoring sites and larger pore size in PA-TAPA-Cu-MOF facilitate efficient anchoring and conversion of I3 -, as supported by spectroscopic electrochemistry and density functional theory calculations.

Right superior frontal gyrus: A potential neuroimaging biomarker for predicting short-term efficacy in schizophrenia.

Antipsychotic drug treatment for schizophrenia (SZ) can alter brain structure and function, but it is unclear if specific regional changes are associated with treatment outcome. Therefore, we examined the effects of antipsychotic drug treatment on regional grey matter (GM) density, white matter (WM) density, and functional connectivity (FC) as well as associations between regional changes and treatment efficacy. SZ patients (n = 163) and health controls (HCs) (n = 131) were examined by structural magnetic resonance imaging (sMRI) at baseline, and a subset of SZ patients (n = 77) were re-examined after 8 weeks of second-generation antipsychotic treatment to assess changes in regional GM and WM density. In addition, 88 SZ patients and 81 HCs were examined by resting-state functional MRI (rs-fMRI) at baseline and the patients were re-examined post-treatment to examine FC changes. The Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were applied to measure psychiatric symptoms and cognitive impairments in SZ. SZ patients were then stratified into response and non-response groups according to PANSS score change (≥50 % decrease or <50 % decrease, respectively). The GM density of the right cingulate gyrus, WM density of the right superior frontal gyrus (SFG) plus 5 other WM tracts were reduced in the response group compared to the non-response group. The FC values between the right anterior cingulate and paracingulate gyrus and left thalamus were reduced in the entire SZ group (n = 88) after treatment, while FC between the right inferior temporal gyrus (ITG) and right medial superior frontal gyrus (SFGmed) was increased in the response group. There were no significant changes in regional FC among the non-response group after treatment and no correlations with symptom or cognition test scores. These findings suggest that the right SFG is a critical target of antipsychotic drugs and that WM density and FC alterations within this region could be used as potential indicators in predicting the treatment outcome of antipsychotics of SZ.

Human umbilical cord blood mesenchymal stem cells mediate microglia activation and improve anxiety-like behavior in MIA-induced offspring of schizophrenic rats.

Current treatments for schizophrenia (SCZ) remain largely ineffective in one-third of patients. Recent studies using stem cell therapy show a close relationship between stem cell immunomodulatory function and neuroinflammation in SCZ. To better investigate the efficacy of stem cell therapy for SCZ, human umbilical cord blood mesenchymal stem cells (hUC-MSC) with powerful immunomodulatory effects were administered to rats via the tail vein (once a week for 5 consecutive weeks starting from the weaning period) using a maternal immune activation (MIA) rodent model. Open field, PPI, Western blotting, Q-PCR, and immunofluorescence were used to assess the biological effects of repeated tail vein injections of hUC-MSC in offspring rats following the MIA model of SCZ. The results indicated that offspring of MIA rats exhibited schizophrenia-like (SCZ-like) anxiety behavior, with observed microglial activation triggering neuroinflammation. Furthermore, levels of IBA1, HMGB1, and PSD95 were significantly up-regulated, while SYP was significantly down-regulated. It is suggested that hUCB-MSCs may act through HMGB1, Iba1, PSD95, and related pathway molecules to alleviate neuroinflammation and repair synaptic damage by regulating the activity state of microglia. Consequently, this could improve the abnormal behavior observed in MIA offspring rats.