Exploring the interplay between core and mood symptoms in schizophrenia: A network analysis.

BACKGROUND: Schizophrenia is a complex neuropsychiatric disorder characterized by positive symptoms, negative symptoms, cognitive deficits, and co-occurring mood symptoms. Network analysis offers a novel approach to investigate the intricate relationships between these symptom dimensions, potentially informing personalized treatment strategies. METHODS: A cross-sectional study was conducted from November 2019 to October 2021, involving 1285 inpatients with schizophrenia in Liaoning Province, China. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA-14), and Montreal Cognitive Assessment (MoCA). Network analysis was conducted to investigate the network structure, central symptoms, and bridge symptoms. RESULTS: The network analysis uncovered profound interconnectivity between core symptoms and the anxiety-depression community. Central symptoms, such as psychic anxiety, poor rapport, delusions, and attention, were identified as potential therapeutic targets. Bridge symptoms, including insomnia, depressed mood, anxiety-somatic, conceptual disorganization, and stereotyped thinking, emerged as key nodes facilitating interactions between symptom communities. The stability and reliability of the networks were confirmed through bootstrapping procedures. DISCUSSION: The findings highlight the complex interplay between schizophrenia symptoms, emphasizing the importance of targeting affective symptoms and cognitive impairment in treatment. The identification of central and bridge symptoms suggests potential pathways for personalized interventions aimed at disrupting self-reinforcing symptom cycles. The study underscores the need for a transdiagnostic, personalized approach to schizophrenia treatment.

Helical hollow channel waveguide in YAG fabricated by femtosecond laser enhanced wet etching.

Three-dimensional optical waveguides with hollow channels have many advantages, such as strong mode confinement and excellent dispersion control ability. Femtosecond laser enhanced wet etching is widely used to fabricate hollow channel waveguides in transparent dielectric materials. We propose a method for fabricating hollow channel waveguides in YAG using femtosecond laser enhanced wet etching with a simpler fabrication process and shorter etching time compared with the previous work. After 90 h of etching, a series of helical hollow channel waveguides with a length of 5 mm and a radius of 32 µm were successfully fabricated. At a pitch of 3 µm, the waveguide exhibited a loss (including coupling loss and transmission loss) as low as 0.68 dB at 1030 nm. The helical hollow channel waveguide also exhibited exceptional isotropic light confinement capability and remarkable supercontinuum-generating properties. Moreover, helical hollow channel waveguides with a radius of 2 µm were successfully fabricated. According to simulations, waveguides of such size can effectively control dispersion. Our work presents, to our knowledge, a novel approach to fabricating hollow channel waveguides with arbitrary lengths using femtosecond laser-enhanced wet etching.

[Research progress on risk prediction of cardiac arrest].

Cardiac arrest (CA) is a serious cardiac event, which has a high incidence and low survival rate at home and abroad. In order to predict the risk of CA in advance, a large number of studies have been conducted by relevant researchers. This paper mainly summarizes the characteristics and research status of the existing analysis and prediction of CA from three aspects: the risk prediction factors of CA, the evaluation index of risk prediction of CA and the early warning scoring system of CA. We hope it can help medical staff to understand the current progress in this field, and provide new ways and methods for predicting the risk of CA.

Integration of Network Pharmacology and Experimental Validation to Explore Jixueteng - Yinyanghuo Herb Pair Alleviate Cisplatin-Induced Myelosuppression.

Jixueteng, the vine of the bush Spatholobus suberectus Dunn., is widely used to treat irregular menstruation and arthralgia. Yinyanghuo, the aboveground part of the plant Epimedium brevicornum Maxim., has the function of warming the kidney to invigorate yang. This research aimed to investigate the effects and mechanisms of the Jixueteng and Yinyanghuo herbal pair (JYHP) on cisplatin-induced myelosuppression in a mice model. Firstly, ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) screened 15 effective compounds of JYHP decoction. Network pharmacology enriched 10 genes which may play a role by inhibiting the apoptosis of bone marrow (BM) cells. Then, a myelosuppression C57BL/6 mice model was induced by intraperitoneal (i.p.) injection of cis-Diaminodichloroplatinum (cisplatin, CDDP) and followed by the intragastric (i.g.) administration of JYHP decoction. The efficacy was evaluated by blood cell count, reticulocyte count, and histopathological analysis of bone marrow and spleen. Through the vivo experiments, we found the timing of JYHP administration affected the effect of drug administration, JYHP had a better therapeutical effect rather than a preventive effect. JYHP obviously recovered the hematopoietic function of bone marrow from the peripheral blood cell test and pathological staining. Flow cytometry data showed JYHP decreased the apoptosis rate of BM cells and the western blotting showed JYHP downregulated the cleaved Caspase-3/Caspase-3 ratios through RAS/MEK/ERK pathway. In conclusion, JYHP alleviated CDDP-induced myelosuppression by inhibiting the apoptosis of BM cells through RAS/MEK/ERK pathway and the optimal timing of JYHP administration was after CDDP administration.

Cognitive function and cardiovascular health in the elderly: network analysis based on hypertension, diabetes, cerebrovascular disease, and coronary heart disease.

Introduction: Cognitive decline in the elderly population is a growing concern, and vascular factors, such as hypertension, diabetes, cerebrovascular disease, and coronary heart disease, have been associated with cognitive impairments. This study aims to provide deeper insights into the structure of cognitive function networks under these different vascular factors and explore their potential associations with specific cognitive domains. Methods: Cognitive function was assessed using a modified Chinese version of the mini-mental state examination (MMSE) scale, and intensity centrality and side weights were estimated by network modeling. The network structure of cognitive function was compared across subgroups by including vascular factors as subgroup variables while controlling for comorbidities and confounders. Results: The results revealed that cerebrovascular disease and coronary heart disease had a more significant impact on cognitive function. Cerebrovascular disease was associated with weaker centrality in memory and spatial orientation, and a sparser cognitive network structure. Coronary heart disease was associated with weaker centrality in memory, repetition, executive function, recall, attention, and calculation, as well as a sparser cognitive network structure. The NCT analyses further highlighted significant differences between the cerebrovascular disease and coronary heart disease groups compared to controls in terms of overall network structure and connection strength. Conclusion: Our findings suggest that specific cognitive domains may be more vulnerable to impairments in patients with cerebrovascular disease and coronary heart disease. These insights could be used to improve the accuracy and sensitivity of cognitive screening in these patient populations, inform personalized cognitive intervention strategies, and provide a better understanding of the potential mechanisms underlying cognitive decline in patients with vascular diseases.

Environmental Microplastic Exposure Changes Gut Microbiota in Chickens.

As novel environmental contaminants, MPs exist widely in the environment and accumulate in organisms, which has become a global ecological problem. MP perturbations of organismal physiology and behavior have been extensively recorded in aquatic animals, but the potential effects of MPs on poultry are not well characterized. Here, we explored the adverse effects of MP exposure on the growth performance and gut microbiota of chickens. Results showed that the growth performance of chickens decreased significantly during MP exposure. Additionally, Firmicutes, Bacteroidota, and Proteobacteria were found to be dominant in the gut microbiota of MP-exposed chickens, regardless of health status. Although the types of dominant bacteria did not change, the abundances of some bacteria and the structure of the gut microbiota changed significantly. Compared with the controls, the alpha diversity of gut microbiota in chickens exposed to MPs showed a significant decrease. The results of comparative analyses of bacteria between groups showed that the levels of 1 phyla (Proteobacteria) and 18 genera dramatically decreased, whereas the levels of 1 phyla (Cyanobacteria) and 12 genera dramatically increased, during MP exposure. In summary, this study provides evidence that exposure to MPs has a significant impact on the growth performance and gut microbial composition and structure of chickens, leading to a gut microbial imbalance. This may raise widespread public concern about the health threat caused by MP contamination, which is relevant to the maintenance of environmental quality and protection of poultry health.

Identification and Functional Evaluation of Alternative Splice Variants of Dax1 in Mouse Embryonic Stem Cells.

Dax1 (Nr0b1; Dosage-sensitive sex reversal-adrenal hypoplasia congenital on the X-chromosome gene-1) is an important component of the transcription factor network that governs pluripotency in mouse embryonic stem cells (ESCs). Functional evaluation of alternative splice variants of pluripotent transcription factors has shed additional insight on the maintenance of ESC pluripotency and self-renewal. Dax1 splice variants have not been identified and characterized in mouse ESCs. We identified 18 new transcripts of Dax1 with putative protein-coding properties and compared their protein structures with known Dax1 protein (Dax1-472). The expression pattern analysis showed that the novel isoforms were cotranscribed with Dax1-472 in mouse ESCs, but they had transcriptional heterogeneity among single cells and the subcellular localization of the encoded proteins differed. Cell function experiments indicated that Dax1-404 repressed Gata6 transcription and functionally replaced Dax1-472, while Dax1-38 and Dax1-225 partially antagonized Dax1-472 transcriptional repression. This study provided a comprehensive characterization of the Dax1 splice variants in mouse ESCs and suggested complex effects of Dax1 variants in a self-renewal regulatory network.

Parallel Genome-Wide CRISPR Screens to Identify State-Dependent Self-Renewal Regulators of Mouse Embryonic Stem Cells.

The pluripotency of embryonic stem cells (ESCs) is more accurately viewed as a continuous developmental process rather than a fixed state. However, the factors that play general or state-specific roles in regulating self-renewal in different pluripotency states remain poorly defined. In this study, parallel genome-wide CRISPR/Cas9 knockout (KO) screens were applied in ESCs cultured in the serum plus LIF (SL) and in the 2i plus LIF (2iL) conditions. The candidate genes were classified into seven groups based on their positive or negative effects on self-renewal, and whether this effect was general or state-specific for ESCs under SL and 2iL culture conditions. We characterized the expression and function of genes in these seven groups. The loss of function of novel pluripotent candidate genes Usp28, Zfp598, and Zfp296 was further evaluated in mouse ESCs. Consistent with our screen, the knockout of Usp28 promotes the proliferation of SL-ESCs and 2iL-ESCs, whereas Zfp598 is indispensable for the self-renewal of ESCs under both culture conditions. The cell phenotypes of Zfp296 KO ESCs under SL and 2iL culture conditions were different. Our work provided a valuable resource for dissecting the molecular regulation of ESC self-renewal in different pluripotency states.

A multi-omics integrative analysis based on CRISPR screens re-defines the pluripotency regulatory network in ESCs.

A comprehensive and precise definition of the pluripotency gene regulatory network (PGRN) is crucial for clarifying the regulatory mechanisms in embryonic stem cells (ESCs). Here, after a CRISPR/Cas9-based functional genomics screen and integrative analysis with other functional genomes, transcriptomes, proteomes and epigenome data, an expanded pluripotency-associated gene set is obtained, and a new PGRN with nine sub-classes is constructed. By integrating the DNA binding, epigenetic modification, chromatin conformation, and RNA expression profiles, the PGRN is resolved to six functionally independent transcriptional modules (CORE, MYC, PAF, PRC, PCGF and TBX). Spatiotemporal transcriptomics reveal activated CORE/MYC/PAF module activity and repressed PRC/PCGF/TBX module activity in both mouse ESCs (mESCs) and pluripotent cells of early embryos. Moreover, this module activity pattern is found to be shared by human ESCs (hESCs) and cancers. Thus, our results provide novel insights into elucidating the molecular basis of ESC pluripotency.

Identification and functional comparison of novel alternatively spliced isoforms of human YAP.

As a key effector of the Hippo pathway, yes-associated protein (YAP) is a major regulator of cell proliferation and apoptosis. In this study, 23 hYAP isoforms were identified in HEK293 cells, with 14 isoforms being reported for the first time. These isoforms were classified into hYAP-a and hYAP-b isoforms based on the variation in exon 1. The two groups of isoforms showed distinctly different subcellular localizations. hYAP-a isoforms could activate TEAD- or P73-mediated transcription, affect the proliferation rate, and enhance the cellular chemosensitivity of HEK293 cells. Moreover, different activation abilities and pro-cytotoxic effects were observed among hYAP-a isoforms. However, hYAP-b isoforms were not found to exert any significant biological effects. Our findings add to the knowledge of YAP gene structure and protein-coding capacity and will help in the elucidation of the function and related molecular mechanisms of the Hippo-YAP signaling pathway.

[Anti-pyroptosis effect of Albiziae Cortex-Tribuli Fructus combination on hepatic stellate cell line LX2: based on network pharmacology].

Based on network pharmacology, molecular docking, and in vitro experimental verification, this study aims to explore the effect of Albiziae Cortex-Tribuli Fructus combination on HSC-LX2 pyroptosis. Specifically, the targets of Albiziae Cortex, Tribuli Fructus, and hepatic fibrosis were retrieved from an online database and CNKI, and "drug-component-target" network and "drug-component-target-disease" network were constructed. Protein-protein interaction(PPI) network was established based on STRING. Metascape was employed for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and the mechanism of Albiziae Cortex-Tribuli Fructus combination against liver fibrosis was predicted. Molecular docking was used to verify some of the results of network pharmacology, and in vitro experiment was carried out to further verify the above conclusions. According to the results of network pharmacological analysis, 25 active components and 439 targets of Albiziae Cortex-Tribuli Fructus combination and 152 anti-liver fibrosis targets were screened out, including nucleotide-binding oligomerization domain and leucine-rich-repeat-and pyrin-domain-containing 3(NLRP3) and caspase-1. The key targets were involved in 194 KEGG pathways in which the NOD-like receptor signaling pathway topped. The binding common targets were related to pyroptosis. The results of in vitro experiment showed that the pair-containing serum reduced the proliferation rate of HSC-LX2 and the content of reactive oxygen species(ROS), interleukin-18(IL-18), and interleukin-1ß(IL-1ß)(P<0.05). Western blot and qRT-PCR suggested that the protein and gene expression of NLRP3, caspase-1, α-smooth muscle actin(α-SMA), and gasdermin D(GSDMD) in HSC-LX2 increased after AngⅡ stimulation, and the expression decreased after the intervention of pair-containing serum(P<0.05). In summary, the pair-containing serum can inhibit the classic pathway of pyroptosis, which may be the anti-liver fibrosis mechanism. This is consistent with the predicted results of network pharmacology.

Comparative expression analysis of TEADs and their splice variants in mouse embryonic stem cells.

Transcriptional enhanced associate domain (TEAD) transcription factors play important roles in embryonic stem cell (ESC) renewal and differentiation. Four TEAD transcription factors (Tead1, Tead2, Tead3 and Tead4) and their various splice variants have been discovered in mice, but the expression pattern of them during pluripotency state transition is unclear. Here, we investigated the expression of TEADs and their splice variants in mouse ESCs at different pluripotent/differentiating states and adult mouse tissues. Our results preliminarily revealed the diversity and heterogeneity of TEAD family, which is helpful for understanding their overlapping and distinctive functions. Furthermore, a novel splice variant of Tead1 was identified and named Tead1 isoform 4.

IBD: An Interpretable Backdoor-Detection Method via Multivariate Interactions.

Recent work has shown that deep neural networks are vulnerable to backdoor attacks. In comparison with the success of backdoor-attack methods, existing backdoor-defense methods face a lack of theoretical foundations and interpretable solutions. Most defense methods are based on experience with the characteristics of previous attacks, but fail to defend against new attacks. In this paper, we propose IBD, an interpretable backdoor-detection method via multivariate interactions. Using information theory techniques, IBD reveals how the backdoor works from the perspective of multivariate interactions of features. Based on the interpretable theorem, IBD enables defenders to detect backdoor models and poisoned examples without introducing additional information about the specific attack method. Experiments on widely used datasets and models show that IBD achieves a 78% increase in average in detection accuracy and an order-of-magnitude reduction in time cost compared with existing backdoor-detection methods.

Angiotensin II can trigger HSC-LX2 pyroptosis through both classical and non-classical pathways.

BACKGROUND: Current evidence suggests that liver fibrosis is reversible even at late stages. Pyroptosis is reportedly regulated by classical and non-classical pathways and is also involved in the activation of the human hepatic stellate cell line LX2. This study sought to identify regulatory pathways that pyroptosis of HSC during AngII-ROS-induced HSC activation and provides novel insights for anti-fibrosis therapy by targeting HSC. MATERIALS AND METHODS: All experiments were conducted in HSC-LX2. The expressions of α-SMA, NLRP3, Caspases-1, -4, -5, ASC and GSDMD-N were detected in HSC-LX2 cells induced with AngII by Western blot and qRT-PCR. CCK8 was used to detect cell proliferation and activity. 2'-7'dichlorofluorescin diacetate (DCFH-DA) was used to measure ROS generation. An LDH assay kit was used to detect LDH released from damaged cells, and ELISA was used to quantify IL-18 and IL-1ß levels. RESULTS: After AngII stimulation, HSC-LX2 cell viability, ROS, LDH, IL-18, and IL-1ß were increased compared with Control group. At the same time, the protein and mRNA levels of α-SMA, NLRP3, Caspases-1, -4, -5, ASC and GSDMD-N were increased. In addition, after NAC and NSA treatment, LDH, IL-18 and IL-1ß levels and the protein and mRNA expression of α-SMA, Caspases-4 and -5, and GSDMD-N were decreased. CONCLUSION: HSC-LX2 pyroptosis induced by AngII-ROS is mediated by the classical pathway involving NLRP3/Caspase-1 and the non-classical pathway involving Caspases-4 and -5. Our results provide compelling evidence that AngII could activate Caspases-4 and -5 by producing ROS.

Effects of hot and humid environments on thermoregulation and aerobic endurance capacity of Laser sailors.

Objectives: The purpose was to investigate the effects of hot and humid environments on thermoregulation and aerobic endurance capacity and whether high skin temperature serves as a more important thermoregulatory factor affecting aerobic exercise capacity. Methods: A randomized cross-over design was applied to this study, in which nine Laser sailors performed the 6 km rowing test (6 km test) in both a warm (ambient temperature: 23 ± 1.4 °C; relative humidity: 60.5 ± 0.7%; wind speed: 0 km/h; WARM) and hot environment (ambient temperature: 31.8 ± 1.1 °C; relative humidity: 63.5 ± 4.9%; wind speed: 3.5 ± 0.7 km/h; HOT). Results: The time for completing 6 km test of HOT group was significantly longer than that of WARM group (P = 0.0014). Mean power of 3-4 km, 4-5 km and 5-6 km were significant lower in HOT group (P = 0.014, P = 0.02, P = 0.003). Gastrointestinal temperature and skin temperature were significantly higher in HOT group during the 6 km test (P = 0.016, P = 0.04). Heat storage at 5 min and 15 min of HOT group were significantly higher than that of WARM group (P = 0.0036; P = 0.0018). Heart rate and physiological strain index of HOT group were significantly higher than that of WARM group during the 6 km test (P = 0.01, P < 0.01). Conclusion: When skin temperature and core temperature both increased, high skin temperature may be the more important thermoregulatory factor that affected the aerobic endurance performance in hot and humid environments. The high skin temperature narrowed the core to skin temperature gradient and skin to ambient temperature gradient, which may result in greater accumulation of heat storage. The greater heat storage led to the lower muscle power output, which contributed to the reduction of the heat production.

Role of TRPV1 in High Temperature-Induced Mitochondrial Biogenesis in Skeletal Muscle: A Mini Review.

Transient receptor potential vanilloid 1 (TRPV1) is a protein that is susceptible to cell environment temperature. High temperatures of 40-45°C can activate the TRPV1 channel. TRPV1 is highly expressed in skeletal muscle and located on the sarcoplasmic reticulum (SR). Therefore, TRPV1 activated by high-temperature stress releases Ca2+ from the SR to the cytoplasm. Cellular Ca2+ accumulation is a key event that enhances TRPV1 activity by directly binding to the N-terminus and C-terminus. Moreover, Ca2+ is the key messenger involved in regulating mitochondrial biogenesis in skeletal muscle. Long-term activation of TRPV1 may promote mitochondrial biogenesis in skeletal muscle through the Ca2+-CaMKII-p38 MAPK-PGC-1α signaling axis. The discovery of the TRPV1 channel highlights the potential mechanism for high-temperature stress improving muscle mitochondrial biogenesis. The appropriate hot stimulus in thermal environments might be beneficial to the muscular mitochondrial adaptation for aerobic capacity. However, the investigation of TRPV1 on mitochondrial biogenesis is at an early stage. Further investigations need to examine the role of TRPV1 in response to mitochondrial biogenesis in skeletal muscle induced by different thermal environments.

Transcriptome analysis reveals potential key immune genes of Hong Kong oyster (Crassostrea hongkongensis) against Vibrio parahaemolyticus infection.

Hong Kong oyster (Crassostrea hongkongensis) is one of the main species of economic shellfish cultivated in the coastal areas of southern China. The cultivation of this shellfish may be adversely impacted by Vibrio parahaemolyticus, a harmful pathogenic bacterium for many mariculture species, as it usually exists on the surface of Hong Kong oysters. Although previous studies have discovered that oysters rely on non-specific immune system to fight pathogen invasion, the genes corresponding to the complex immune system against Vibrio is still not fully elucidated. Therefore, we conducted a transcriptome analysis on the gill from Hong Kong oysters at two time points (i.e., 12 h and 24 h after V. parahaemolyticus or PBS challenge) to identify potential immune genes against V. parahaemolyticus infection. A total of 61779 unigenes with the average length of 1221 bp were obtained, and the annotation information of 39917 unigenes were obtained from Nr, SwissProt, KEGG and COG/KOG. After a pairwise comparison between V. parahaemolyticus or PBS challenge at the two time points, three groups of differentially expressed genes induced by V. parahaemolyticus were captured and analyzed. GO and KEGG analyses showed that multiple immune-related genes played an important role in pathogen infection, including HSP70, PCDP3 and TLR4. Furthermore, genes annotation indicated that LITAF, TNFSF10, Duox2 and big defensin family are also involved in immune regulation. Our study provides a reference for further exploration the molecular mechanism that defenses the pathogen infection regarding the identified immune-related genes in Hong Kong oysters.

Genome-Wide CRISPR Screen Identifies Puf60 as a Novel Stemness Gene of Mouse Embryonic Stem Cells.

The mechanisms underlying self-renewal of embryonic stem cells (ESCs) hold great value in the clinical translation of stem cell biology and regenerative medicine research. To study the mechanisms in ESC self-renewal, screening and identification of key genes maintaining ESC self-renewal were performed by a genome-wide CRISPR-Cas9 knockout virus library. The mouse ESC R1 were infected with CRISPR-Cas9 knockout virus library and cultured for 14 days. The variation of single guide RNA (sgRNA) ratio was analyzed by high-throughput sequencing, followed by bioinformatics analysis to profile the altered genes. Our results showed 1375 genes with increased sgRNA ratio were found to be mainly involved in signal transduction, cell differentiation, and cell apoptosis; 2929 genes with decreased sgRNA ratio were mainly involved in cell cycle regulation, RNA splicing, and biological metabolic processes. We further confirmed our screen specificity by identifying Puf60, U2af2, Wdr75, and Usp16 as novel positive regulators in mESC self-renewal. Meanwhile, further analysis showed the relevance between Puf60 expression and tumor. In conclusion, our study screened key genes maintaining ESC self-renewal and successfully identified Puf60, U2af2, Wdr75, and Usp16 as novel positive regulators in mESC self-renewal, which provided theoretical basis and research clues for a better understanding of ESC self-renewal regulation.