Mapping Brain Synergy Dysfunction in Schizophrenia: Understanding Individual Differences and Underlying Molecular Mechanisms.

To elucidate the brain-wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information-resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time-series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally-specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole-brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ. Factor 1 exhibits a significant positive correlation with Positive and Negative Syndrome Scale (PANSS) positive scores, while factor 3 demonstrates significant negative correlations with PANSS negative and general scores. By integrating the neuroimaging data with normative gene expression information, this study identifies that each of these three factors corresponded to a subset of the SCZ risk gene set. Finally, by combining data from NeuroSynth and open molecular imaging sources, along with a spatially heterogeneous mean-field model, this study delineates three SCZ synergy factors corresponding to distinct symptom profiles and implicating unique cognitive, neurodynamic, and neurobiological mechanisms.

Deciphering the neural mechanisms of miR-134 in major depressive disorder with population-based and person-specific imaging transcriptomic techniques.

MiR-134 has emerged as a potential molecular biomarker for the detection and management of major depressive disorder (MDD). Nevertheless, the specific effects of miR-134 as a regulatory element on brain function and its implications for the clinical presentation of MDD are not yet fully understood. In order to investigate the potential neural mechanisms that contribute to the relationship between miR-134 and MDD, we employed a parallel two-stage cross-scale multi-omics approach. This involved utilizing the anterior cingulate cortex (ACC) functional connectivity as a means to connect microscopic molecular structures with macroscopic brain function in two separate cohorts: the MDD-I dataset (56 MDD patients and 51 healthy controls) and the MDD-II dataset (57 MDD patients and 52 healthy controls). We found a stable ACC functional dysconnectivity pattern of MDD and established the hierarchical cross-scale association from molecular organizations of miR-134 target genes to macroscopic brain functional dysconnectivity and associated behavior, as revealed by population-based analysis. Additionally, our person-specific imaging transcriptomic study revealed that individual exosomal miR-134 expression levels impact on individual clinical symptoms of MDD by modulating ACC-related functional dysconnectivity. Together, our findings provide compelling evidence of the correlation between miR-134 and depression across multi scales within the gene-brain-behavior context.

Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex.

Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.

Pb exposure causes non-linear accumulation of Pb in D. melanogaster controlled by metallothionein B and exerts ecological effects.

Pb pollution can harm human health and the ecosystem. Therefore, it is worthwhile to study the metabolic processes of heavy metals in individual bodies and their influence on ecological systems. In this work, we analyzed the genetic responses and physiological changes of D. melanogaster which took diets exposed to different doses of Pb using transcriptomic analysis, ICP-MS, and various other physiological methods. We found that the Pb accumulated in D. melanogaster in a nonlinear pattern with the increase of Pb content in food. Metallothioneins (Mtns), especially the MtnB directly affects the accumulation and excretion of metal Pb in D. melanogaster, and causes the nonlinear accumulation. Metal regulatory transcription factor-1 (MTF-1) is involved in the regulation of Pb-induced high expressions of Mtns. Furthermore, an interaction between the metal metabolism pathway and xenobiotic response pathway leads to the cross-tolerances of Pb-exposed D. melanogaster to insecticides and other toxins. The oxidative stress induced by Pb toxicity may be the bridge between them. Our findings provide a physiological and molecular genetic basis for further study of the accumulation and metabolism of Pb in D. melanogaster.

Hierarchical fluctuation shapes a dynamic flow linked to states of consciousness.

Consciousness arises from the spatiotemporal neural dynamics, however, its relationship with neural flexibility and regional specialization remains elusive. We identified a consciousness-related signature marked by shifting spontaneous fluctuations along a unimodal-transmodal cortical axis. This simple signature is sensitive to altered states of consciousness in single individuals, exhibiting abnormal elevation under psychedelics and in psychosis. The hierarchical dynamic reflects brain state changes in global integration and connectome diversity under task-free conditions. Quasi-periodic pattern detection revealed that hierarchical heterogeneity as spatiotemporally propagating waves linking to arousal. A similar pattern can be observed in macaque electrocorticography. Furthermore, the spatial distribution of principal cortical gradient preferentially recapitulated the genetic transcription levels of the histaminergic system and that of the functional connectome mapping of the tuberomammillary nucleus, which promotes wakefulness. Combining behavioral, neuroimaging, electrophysiological, and transcriptomic evidence, we propose that global consciousness is supported by efficient hierarchical processing constrained along a low-dimensional macroscale gradient.

HDAC2 Inhibits Hippocampal Neurogenesis and Impairs the Cognitive Function in Prenatally Stressed Adult Offspring / HDAC2 Inhibe la Neurogénesis del Hipocampo y Afecta la Función Cognitiva en la Descendencia Adulta Estresada Prenatalmente

SUMMARY: The objective of this study was to investigate the mechanism of prenatal stress on the cognitive function of offspring, and clarify the change of histone deacetylase 2 (HDAC2) expression in hippocampal neurons of offspring. 16 pregnant SD rats were randomly divided into control group and stress group, with eight rats in each group. The stress group received restrained stress from 15 to 21 days of pregnancy, while the control group did not receive any treatment. Anxiety-like behavior and spatial memory, learning and memory ability were detected in open field, elevated plus maze, novel object recognition test, and Barnes maze. Nissl staining was used to detect the function of hippocampal neurons. Western blot was used to detect the expression of HDAC2 protein in hippocampal neurons of adult offspring. Immunofluorescence staining was used to detect the expression of HDAC2 protein and hippocampal neurogenesis. The learning and memory ability of adult offspring was decreased. The prenatal stress damaged the function of hippocampal neurons , the expression of HDAC2 was down-regulated, and the number of neurons was reduced. Maternal prenatal stress can down- regulate the expression of HDAC2 in the hippocampus of offspring, inhibits hippocampal neurogenesis and impairs the cognitive function.

El objetivo de este estudio fue investigar el mecanismo del estrés prenatal en la función cognitiva de la descendencia y aclarar el cambio de la expresión de la histona desacetilasa 2 (HDAC2) en las neuronas del hipocampo de la descendencia. 16 ratas SD preñadas se dividieron aleatoriamente en un grupo de control y un grupo de estrés, con ocho ratas en cada grupo. El grupo de estrés recibió estrés durante 15 a 21 días de pre, preñez, mientras que el grupo de control no recibió ningún tratamiento. El comportamiento similar a la ansiedad y la memoria espacial, el aprendizaje y la capacidad de memoria se detectaron en campo abierto, laberinto en cruz elevado, prueba de reconocimiento de objetos novedosos y laberinto de Barnes. La tinción de Nissl se utilizó para detectar la función de las neuronas del hipocampo. Se utilizó Western blot para detectar la expresión de la proteína HDAC2 en las neuronas del hipocampo de la descendencia adulta. La tinción de inmunofluorescencia se utilizó para detectar la expresión de la proteína HDAC2 y la neurogénesis del hipocampo. La capacidad de aprendizaje y memoria de la descendencia adulta se redujo. El estrés prenatal dañó la función de las neuronas del hipocampo, se reguló negativamente la expresión de HDAC2 y se redujo el número de neuronas. El estrés prenatal materno puede regular a la baja la expresión de HDAC2 en el hipocampo de la descendencia, inhibe la neurogénesis del hipocampo y deteriora la función cognitiva.

KNTC1, regulated by HPV E7, inhibits cervical carcinogenesis partially through Smad2.

Cervical cancer is the second most common malignancy of the female reproductive tract worldwide. Although cervical cancer is caused by human papillomavirus (HPV) infection, its underlying pathogenesis requires further investigation. The present study investigated the role of kinetochore associated protein 1 (KNTC1) in cervical cancer and its association with the key virus oncoprotein, HPV E7. A series of bioinformatic analyses revealed that KNTC1 might be involved in the tumorigenesis of multiple human malignancies, including cervical cancer. Tissue microarray analysis showed that in vivo KNTC1 expression was higher in high-grade squamous intraepithelial lesions (HSILs) than in normal cervix and even higher in cervical cancer. In vitro silencing of KNTC1 increased the proliferation, invasion and migration of cervical cancer cell lines. Although not affecting apoptosis, KNTC1 silencing significantly promoted G1/S phase transition of the cell cycle. High-throughput analysis of mRNA expression showed that KNTC1 could regulate its downstream target protein Smad2 at the transcriptional level. Moreover, as the key oncoprotein of the virus, HPV E7 could inhibit the expression of KNTC1 protein, and decrease Smad2 protein expression with or without the aid of KNTC1. These results indicated that KNTC1 is a novel tumor suppressor that can impede the initiation and progression of cervical carcinoma, providing insight into the molecular mechanism by which HPV induces cervical cancer.

A Flexible NO2 Gas Sensor Based on Single-Wall Carbon Nanotube Films Doped with a High Level of Nitrogen.

Carbon nanotubes (CNTs) are considered a promising candidate for the detection of toxic gases because of their high specific surface area and excellent electrical and mechanical properties. However, the detecting performance of CNT-based detectors needs to be improved because covalently bonded CNTs are usually chemically inert. We prepared a nitrogen-doped single-wall CNT (SWCNT) film by means of gas-phase fluorination followed by thermal annealing in NH3. The doped nitrogen content could be changed in the range of 2.9-9.9 at%. The N-doped SWCNT films were directly used to construct flexible and transparent gas sensors, which can work at a low voltage of 0.01 V. It was found that their NO2 detection performance was closely related to their nitrogen content. With an optimum nitrogen content of 9.8 at%, a flexible sensor had a detection limit of 500 ppb at room temperature with good cycling ability and stability during bending.

The similar eye movement dysfunction between major depressive disorder, bipolar depression and bipolar mania.

OBJECTIVE: To find eye movement characteristics in patients with affective disorders. METHOD: The demographic and clinical evaluation data of patients with major depressive disorder (MDD), bipolar disorder (BPD), and healthy control (HC) were collected. EyeLink 1000 eye tracker was used to collect eye movement data. Chi-squared test and independent sample t-test were used for demographics and clinical characteristics. The Mann-Whitney U-test was used to compare the eye movement variables among four groups, and the FDR method was used for multiple comparison correction. Pearson correlation analysis was used to analyse the relationship between clinical symptoms and eye movement variables. RESULTS: Patients with affective disorders showed smaller saccade amplitude under free-viewing task, more fixations and saccades, shorter fixation duration, longer saccade duration under fixation stability and smooth pursuit tasks (all, p < 0.05) when compared to HC, but there was no significant difference in all eye movement variables among patients in the three groups. Also, all eye movement variables under the three paradigms had no significant correlation with clinical scale scores. CONCLUSION: Patients with major depression, bipolar depression and bipolar mania share similar eye movement dysfunction under free-viewing, fixation stability and smooth pursuit tasks.

An environmental energy-enhanced solar steam evaporator derived from MXene-decorated cellulose acetate cigarette filter with ultrahigh solar steam generation efficiency.

Although solar energy is promising for water purification, there is still a room for further improving the solar steam generation efficiency. Herein, an environmental energy-enhanced solar steam evaporator is fabricated by immersing a cellulose acetate fiber-based cigarette filter (CF) in an aqueous solution of polyvinyl alcohol (PVA) followed by freeze-drying and decorating with MXene sheets. The presence of MXene is to absorb solar light and convert solar energy to thermal energy for efficient water evaporation, while the porous PVA network generated inside the pores of the filter during the freeze-drying process accommodates the dispersed MXene sheets and interconnects the CF and MXene. Because of the constructed PVA/MXene network inside the CF porous architecture and the hydrophilic feature of both MXene and PVA, the resultant MXene/PVA modified CF (MPCF) is highly hydrophilic and competent for rapid upward transfer of water. Interestingly, in addition to the normal energy input by the incident solar light, the large-area sidewall of MPCF gains thermal energy from the environment in the forms of heat convection and heat radiation to enhance the solar steam generation efficiency, resulting in an ultrahigh water evaporation rate of 3.38 kg m-2 h-1 with an outstanding evaporation efficiency of 132.9%.

Dynamic reconfiguration of human brain networks across altered states of consciousness.

Consciousness is supported by rich neuronal dynamics to orchestrate behaviors and conscious processing can be disrupted by general anesthetics. Previous studies suggested that dynamic reconfiguration of large-scale functional network is critical for learning and higher-order cognitive function. During altered states of consciousness, how brain functional networks are dynamically changed and reconfigured at the whole-brain level is still unclear. To fill this gap, using multilayer network approach and functional magnetic resonance imaging (fMRI) data of 21 healthy subjects, we investigated the dynamic network reconfiguration in three different states of consciousness: wakefulness, dexmedetomidine-induced sedation, and recovery. Applying time-varying community detection algorithm, we constructed multilayer modularity networks to track and quantify dynamic interactions among brain areas that span time and space. We compared four high-level network features (i.e., switching, promiscuity, integration, and recruitment) derived from multilayer modularity across the three conditions. We found that sedation state is primarily characterized by increased switching rates as well as decreased integration, representing a whole-brain pattern with higher modular dynamics and more fragmented communication; such alteration can be mostly reversed after the recovery of consciousness. Thus, our work can provide additional insights to understand the modular network reconfiguration across different states of consciousness and may provide some clinical implications for disorders of consciousness.

pH and folic acid dual responsive polysaccharide nanospheres used for nuclear targeted cancer chemotherapy.

Ideal nanoscale drug delivery system (DDS) should be biocompatible, having targeted recognition and controlled release properties. In this work, monodispersed, doxorubicin (Dox) loaded chitosan (Cts) nanospheres functionalized by mesoporous SiO2 and folic acid (FA) were prepared, briefly named as DCSF NSs. The prepared raspberry-like DCSF NSs had an average size of 440 nm and drug loading efficiency (DLE) of 42.61%. The drug release results confirmed that the release of Dox could be controlled by pH change. Cell apoptosis results indicated that the obtained DCSF NSs could kill 90% of MCF-7 cells in 48 h. Confocal laser scanning microscopy (CLSM) results further revealed that folic acid could mediate the cellular uptake of DCSF NSs. These results demonstrated that the obtained DCSF NSs were pH-responsive, folic acid-triggered nuclear targeted, which can be used as ideal DDS for tumor chemotherapy.

GSH and enzyme responsive nanospheres based on self-assembly of green tea polyphenols and BSA used for target cancer chemotherapy.

Developing safe and effective stimuli-responsive nanocarriers is very important for tumor chemotherapy. In this work, bovine serum albumin (BSA) and green tea polyphenol (TP) were used to prepare glutathione (GSH) and enzyme (trypsin) responsive nanocarriers for doxorubicin (DOX). These nanocarriers were further modified with folate, briefly named as DOX@BSA-TP-FA NSs. The diameter of nanocarriers was about 220 nm. The DOX loading efficiency and loading amount were 86.4% and 23.5 wt%, respectively. The cellular uptake, apoptosis, and GSH and trypsin responsive release properties of these nanocarriers were investigated.

Preparation of anticancer micro-medicine based on quinoline and chitosan with pH responsive release performance.

N-(2-(3-fluorobenzyl)-2H-indazol-5-yl)-2-phenyl-2H-pyrazolo[4,3-c]qui- nolin-4-amine (LZC-2b) with a quinoline structure was synthesized as an anticancer prodrug. The pH sensitive anticancer drugs obtained by a simple hydrothermal method. The interaction of chitosan (Cts) and LZC-2b is used to complete the encapsulation without any cross-linking. The obtained micromedicine (LZC-2b@Cts-MSs) has an average size of ∼980 nm. The drug loading efficiency (DLE) of LZC-2b@Cts-MSs was about 79%. In addition, drug release from LZC-2b@Cts-MSs was pH depended. At pH = 7.4, only 5.1% of loaded LZC-2b was released, while 90.3% of loaded LZC-2b was released at pH = 5.0. Cell culture results indicate that LZC-2b@Cts-MSs can be easily uptaken by KB cells. Cell viability results show that KB cells can be effectively killed by LZC-2b@Cts-MSs. Our strategy of synthesis and preparation of pH responsive LZC-2b@Cts-MSs has promising prospect in chemotherapy of oral cancer.

Preparation of core-shell structured CaCO3 microspheres as rapid and recyclable adsorbent for anionic dyes.

Core-shell structured CaCO3 microspheres (MSs) were prepared by a facile, one-pot method at room temperature. The adsorbent dosage and adsorption time of the obtained CaCO3 MSs were investigated. The results suggest that these CaCO3 MSs can rapidly and efficiently remove 99-100% of anionic dyes within the first 2 min. The obtained CaCO3 MSs have a high Brunauer-Emmett-Teller surface area (211.77 m2 g-1). In addition, the maximum adsorption capacity of the obtained CaCO3 MSs towards Congo red was 99.6 mg g-1. We also found that the core-shell structured CaCO3 MSs have a high recycling capability for removing dyes from water. Our results demonstrate that the prepared core-shell structured CaCO3 MSs can be used as an ideal, rapid, efficient and recyclable adsorbent to remove dyes from aqueous solution.