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.

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.

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.

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.

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.

Fuzzy kernel evidence Random Forest for identifying pseudouridine sites.

Pseudouridine is an RNA modification that is widely distributed in both prokaryotes and eukaryotes, and plays a critical role in numerous biological activities. Despite its importance, the precise identification of pseudouridine sites through experimental approaches poses significant challenges, requiring substantial time and resources.Therefore, there is a growing need for computational techniques that can reliably and quickly identify pseudouridine sites from vast amounts of RNA sequencing data. In this study, we propose fuzzy kernel evidence Random Forest (FKeERF) to identify pseudouridine sites. This method is called PseU-FKeERF, which demonstrates high accuracy in identifying pseudouridine sites from RNA sequencing data. The PseU-FKeERF model selected four RNA feature coding schemes with relatively good performance for feature combination, and then input them into the newly proposed FKeERF method for category prediction. FKeERF not only uses fuzzy logic to expand the original feature space, but also combines kernel methods that are easy to interpret in general for category prediction. Both cross-validation tests and independent tests on benchmark datasets have shown that PseU-FKeERF has better predictive performance than several state-of-the-art methods. This new method not only improves the accuracy of pseudouridine site identification, but also provides a certain reference for disease control and related drug development in the future.

De Novo Design and Facile Synthesis of Highly Crystalline 2D Conductive Metal-Organic Frameworks: A "Rotor-Stator" Strategy.

Two-dimensional conductive metal-organic frameworks (2D c-MOFs), which feature high electrical conductivity and large charge carrier mobility, hold great promise in electronics and optoelectronics. Nevertheless, the limited solubility of commonly used planar ligands inevitably brings challenges in synthesis and purification and causes laborious coordination conditions for screening. Moreover, most reported 2D c-MOFs are polycrystalline powders with relatively low crystallinity and irregular morphology, hindering the unveiling of the detailed structure-function relationship. Herein, we developed a "rotor-stator" molecular design strategy to construct 2D c-MOFs using a delicately designed nonplanar biscarbazole ligand (8OH-DCB). Benefiting from the special "rotor-stator" structure of the ligand, crystals of Cu-DCB-MOF were successfully prepared, allowing for the precise determination of their crystal structure. Interestingly, the crystals of Cu-DCB-MOF can be obtained in various organic solvents, indicating excellent solvent compatibility. The versatility of the "rotor-stator" molecular design strategy was further demonstrated by another two new ligands with a "rotor-stator" structure, and afford corresponding 2D c-MOF crystals (Cu-DCBT-MOF and Cu-DCBBT-MOF). The current work presents a facile approach toward the rational design and direct construction of highly crystalline 2D c-MOFs using nonplanar ligands.

Long-term efficacy of left bundle branch pacing and biventricular pacing in patients with heart failure complicated with left bundle branch block.

Background: Left bundle branch pacing (LBBP) can physiologically correct complete left bundle branch block (CLBBB), and has become the best alternative to biventricular pacing (BiVP). Objective: To compare the efficacy of LBBP and BiVP in patients with heart failure (HF) complicated with CLBBB. Methods: This was a single-center retrospective study. Patients with HF complicated with CLBBB who underwent successful cardiac resynchronization therapy (CRT) in Wuhan Asian Heart Hospital from June 2018 to June 2023 were enrolled and divided into LBBP group and BiVP group according to the pacing method. The primary endpoints were the absolute increase of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and echocardiographic response rate. Secondary endpoints were all-cause mortality, heart failure hospitalization (HFH), NT-proBNP, paced QRS duration, pacing threshold, and procedural duration. Results: A total of 120 patients were enrolled in this study, including 60 patients in LBBP group and 60 patients in BiVP group. The median follow-up time was 37 ± 19 months. Compared with BiVP group, LBBP group had a more significant increase in absolute LVEF (ΔLVEF) (14.8 ± 9.9% vs. 10.7 ± 9.0%, P = 0.02), a more significant reduction in LVEDD (56.9 ± 10.9 mm vs. 61.1 ± 10.8 mm, P = 0.03), and a higher echocardiographic super response rate (65% vs. 45%, P = 0.02). There were no significant differences in all-cause mortality (1.7% vs. 10.0%, P = 0.11) and HFH (6.7% vs. 13.3%, P = 0.22). In terms of paced QRS duration (128.7 ± 14.1 ms vs. 137.5 ± 16.5 ms, P = 0.002), pacing threshold (0.72 ± 0.21 V/0.4 ms vs. 1.39 ± 0.51 V/0.4 ms, P < 0.001), procedural duration (134.1 ± 32.2 min vs. 147.7 ± 39.4 min, P = 0.04), the LBBP group was superior to the BiVP group. Conclusion: In nonischemic cardiomyopathy (NICM) patients with HF combined with CLBBB and LVEF ≤ 35%, LBBP is better than BiVP.

Dietary intake and gastrointestinal symptoms are altered in children with Autism Spectrum Disorder: the relative contribution of autism-linked traits.

BACKGROUND: Dietary and gastrointestinal (GI) problems have been frequently reported in autism spectrum disorder (ASD). However, the relative contributions of autism-linked traits to dietary and GI problems in children with ASD are poorly understood. This study firstly compared the dietary intake and GI symptoms between children with ASD and typically developing children (TDC), and then quantified the relative contributions of autism-linked traits to dietary intake, and relative contributions of autism-linked traits and dietary intake to GI symptoms within the ASD group. METHODS: A sample of 121 children with ASD and 121 age-matched TDC were eligible for this study. The dietary intake indicators included food groups intakes, food variety, and diet quality. The autism-linked traits included ASD symptom severity, restricted repetitive behaviors (RRBs), sensory profiles, mealtime behaviors, and their subtypes. Linear mixed-effects models and mixed-effects logistic regression models were used to estimate the relative contributions. RESULTS: Children with ASD had poorer diets with fewer vegetables/fruits, less variety of food, a higher degree of inadequate/unbalanced dietary intake, and more severe constipation/total GI symptoms than age-matched TDC. Within the ASD group, compulsive behavior (a subtype of RRBs) and taste/smell sensitivity were the only traits associated with lower vegetables and fruit consumption, respectively. Self-injurious behavior (a subtype of RRBs) was the only contributing trait to less variety of food. Limited variety (a subtype of mealtime behavior problems) and ASD symptom severity were the primary and secondary contributors to inadequate dietary intake, respectively. ASD symptom severity and limited variety were the primary and secondary contributors to unbalanced dietary intake, respectively. Notably, unbalanced dietary intake was a significant independent factor associated with constipation/total GI symptoms, and autism-linked traits manifested no contributions. CONCLUSIONS: ASD symptom severity and unbalanced diets were the most important contributors to unbalanced dietary intake and GI symptoms, respectively. Our findings highlight that ASD symptom severity and unbalanced diets could provide the largest benefits for the dietary and GI problems of ASD if they were targeted for early detection and optimal treatment.

Exosomal circMACF1 drives PI3K/AKT/mTOR-mediated autophagy suppression in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor. The regulatory functions of circular RNAs (circRNAs) in cancers have been broadly reported. The hsa_circ_0011773 (circMACF1) is reported to be overexpressed in LSCC tissues, while its biological function in LSCC remains unclear. CircMACF1 expression in LSCC tissues and cells was assessed via RT-qPCR. Exosomes extracted from cells were identified by TEM and NTA. Autophagy-related proteins were tested by western blot. Confocal microscope was employed for analyzing LC3 expression. Cell proliferation, migration, and invasion were assessed by CCK-8 assay and transwell assay. The levels of main proteins on PI3K/AKT/mTOR were tested by western blot. We observed that circMACF1 was highly expressed in LSCC tissues and cells. Furthermore, circMACF1 expression was also upregulated in the exosomes derived from LSCC cells. CircMACF1 depletion promoted LC3 expression in cells. Additionally, we proved that circMACF1 knockdown suppressed LSCC cell proliferative, migratory and invasive capabilities via promoting autophagy. Exosomal circMACF1 was found to promote LSCC tumor growth. Then, we proved that circMACF1 could activate PI3K/AKT/mTOR pathway to regulate autophagy. Moreover, MACF1 was positively regulated by circMACF1 and its overexpression notably reversed the effects of circMACF1 depletion in LSCC progression. Exosomal circMACF1 can regulate PI3K/AKT/mTOR-mediated autophagy suppression to facilitate LSCC development.

Enhancing Light Out-coupling in Perovskite Light-Emitting Diodes through Plasmonic Nanostructures.

Perovskite light-emitting diodes (PeLEDs) have emerged as promising candidates for lighting and display technologies owing to their high photoluminescence quantum efficiency and high carrier mobility. However, the performance of planar PeLEDs is limited by the out-coupling efficiency, predominantly governed by photonic losses at device interfaces. Most notably, the plasmonic loss at the metal electrode interfaces can account for up to 60% of the total loss. Here, we investigate the use of plasmonic nanostructures to improve the light out-coupling in PeLEDs. By integrating these nanostructures with PeLEDs, we have demonstrated an effectively reduced plasmonic loss and enhanced light out-coupling. As a result, the nanostructured PeLEDs exhibit an average 1.5-fold increase in external quantum efficiency and an ∼20-fold improvement in device lifetime. This finding offers a generic approach for enhancing light out-coupling, promising great potential to go beyond existing performance limitations.

Diversity of Distoseptispora (Distoseptisporaceae) taxa on submerged decaying wood from the Red River in Yunnan, China.

The Red River Basin is located in the Indo-Burma biodiversity hotspot and is rich in lignicolous freshwater fungi, but no systematic research has been conducted. A systematic study on the species diversity of lignicolous freshwater fungi in the basin is ongoing. Seven distoseptispora-like specimens were collected from the Red River Basin in Yunnan. Phylogenetic analysis of ITS, LSU, tef1-α, and rpb2 genes and combined morphological data indicate that there are six distinct species of Distoseptispora, including two new species and four known species. Two new species were named D.suae and D.xinpingensis, and the four known species were D.bambusae, D.euseptata, D.obpyriformis and D.pachyconidia. This study provides detailed descriptions and illustrations of these six species and an updated phylogenetic backbone tree of Distoseptispora.

Decreased CNNM2 expression in prefrontal cortex affects sensorimotor gating function, cognition, dendritic spine morphogenesis and risk of schizophrenia.

Genome-wide association studies (GWASs) have reported multiple single nucleotide polymorphisms (SNPs) associated with schizophrenia, yet the underlying molecular mechanisms are largely unknown. In this study, we aimed to identify schizophrenia relevant genes showing alterations in mRNA and protein expression associated with risk SNPs at the 10q24.32-33 GWAS locus. We carried out the quantitative trait loci (QTL) and summary data-based Mendelian randomization (SMR) analyses, using the PsychENCODE dorsolateral prefrontal cortex (DLPFC) expression QTL (eQTL) database, as well as the ROSMAP and Banner DLPFC protein QTL (pQTL) datasets. The gene CNNM2 (encoding a magnesium transporter) at 10q24.32-33 was identified to be a robust schizophrenia risk gene, and was highly expressed in human neurons according to single cell RNA-seq (scRNA-seq) data. We further revealed that reduced Cnnm2 in the mPFC of mice led to impaired cognition and compromised sensorimotor gating function, and decreased Cnnm2 in primary cortical neurons altered dendritic spine morphogenesis, confirming the link between CNNM2 and endophenotypes of schizophrenia. Proteomics analyses showed that reduced Cnnm2 level changed expression of proteins associated with neuronal structure and function. Together, these results identify a robust gene in the pathogenesis of schizophrenia.

Cytomegalovirus Infection Facilitates the Costimulation of CD57+CD28- CD8 T Cells in HIV Infection and Atherosclerosis via the CD2-LFA-3 Axis.

CD8 T cells are emerging as important mediators in atherosclerosis and cardiovascular disease (CVD). Immune activation may play a particular role in people with HIV (PWH) who are at an increased risk of CVD, even after controlling for known CVD risk factors. Latent CMV infection is associated with increased CVD risk for both PWH and people without HIV, and human CMV-specific CD4 and CD8 T cells are enriched for an immunosenescent phenotype. We previously showed that CMV coinfection in PWH promotes vascular homing and activation of inflammatory CD4 T cells through the CD2-LFA-3 axis. However, the role of CD2/LFA3 costimulation of CD8 T cells in PWH with CMV has yet to be described. In the present study, we demonstrate that CD2 expression on CX3CR1+CD57+CD28- inflammescent CD8 T cells is increased on cells from CMV-seropositive PWH. In vitro CD2/LFA-3 costimulation enhances TCR-mediated activation of these inflammatory CD8 memory T cells. Finally, we show that LFA-3 is highly expressed in aortas of SIV-infected rhesus macaques and in atherosclerotic plaques of people without HIV. Our findings are consistent with a model in which CMV infection enhances CD2 expression on highly proinflammatory CD8 T cells that can then be stimulated by LFA-3 expressed in the vasculature, even in the absence of CD28 costimulation. This model, in which CMV infection exacerbates toxic cytokine and granzyme production by CD8 T cells within the vasculature, highlights a potential therapeutic target in atherosclerosis development and progression, especially for PWH.

Lactate levels in the brain and blood of schizophrenia patients: A systematic review and meta-analysis.

BACKGROUND: The pathophysiological mechanisms of schizophrenia are still unclear. Converging evidence suggests that energy metabolism abnormalities are involved in schizophrenia, and support its role in the pathophysiology of this disease. Lactate plays an important role in energy metabolism. Many studies have reported changes in the levels of lactate in the brain and serum of schizophrenia patients; however, the results from these studies are not consistent. To overcome this limitation, the goal of the present meta-analysis is to analyze the changes in lactate levels in the brain and blood of schizophrenia patients. METHODS: For this systematic review and meta-analysis, we performed a thorough search of relevant literature in the English language, using the MEDLINE, Cochrane, and Embase databases. RESULTS: In the present meta-analysis, 20 studies were scrutinized, including 13 studies on brain lactate levels, which involved 322 schizophrenia patients and 324 healthy individuals as controls. 7 studies on blood lactate levels, involving 234 schizophrenia patients and 238 healthy individuals, were also included. Brain lactate levels were elevated in schizophrenia patients, both in vivo and in post-mortem studies. Nevertheless, blood lactate levels in schizophrenia patients have revealed no statistically significant difference, as compared with control individuals. CONCLUSIONS: In comparison with healthy individuals, schizophrenia patients had higher lactate levels in the brain, rather than in the blood. These findings suggest independent regulatory mechanisms of lactate levels in the brain and peripheral tissues. Abnormal lactate metabolism in the brain may be an important pathological mechanism in schizophrenia.

Associations between maternal exposure to air pollution during pregnancy and trajectories of infant growth: A birth cohort study.

OBJECTIVE: We examined the relationships between infants' growth trajectories and prenatal exposure to air pollution, which is still under-investigated. METHODS: A birth cohort study was constructed using medical records of pregnant women and infants born between 2015 and 2019 in Foshan, China. Using satellite-based spatial-temporal models, prenatal exposure to air pollutants including particulate matter with an aerodynamic dimension of < 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) was assessed at each woman's residence. Latent class growth modeling was used to identify trajectories of physical (body length and weight) growth and neurodevelopment, which were repeatedly measured within 1 year after birth. Logistic regression models were used to investigate the associations between prenatal exposure to air pollution and the risks of growth disorders, adjusting for an array of potential confounders. RESULTS: We identified two growth trajectories for body length [normal: 3829 (93%); retardation: 288 (7%)], three for weight [normal: 2475 (59.6%); retardation: 390 (9.4%); overgrowth: 1287 (31%)], and two for neurodevelopment [normal: 956 (66.1%); retardation: 491 (33.9%)]. For exposure over whole pregnancy, SO2 was associated with an increased risk of body length retardation (OR for per 1 µg/m3 increment: 1.09, 95%CI: 1.01-1.17); PM2.5 (OR: 1.05, 95%CI: 1.03-1.07), SO2 (OR: 1.15, 95%CI: 1.08-1.22), and NO2 (OR: 1.05, 95%CI: 1.03-1.07) were positively associated with neurodevelopmental retardation. Such associations appeared stronger for exposures over the first and second trimesters. No significant associations were detected for weight growth. CONCLUSIONS: Maternal exposure to air pollution during pregnancy was associated with higher risks of impairments in both physical growth, particularly body length, and neurodevelopment.