Physiological, cytological and multi-omics analysis revealed the molecular response of Fritillaria cirrhosa to Cd toxicity in Qinghai-Tibet Plateau.

Fritillaria cirrhosa, an endangered plant endemic to plateau regions, faces escalating cadmium (Cd) stress due to pollution in the Qinghai-Tibet Plateau. This study employed physiological, cytological, and multi-omics techniques to investigate the toxic effects of Cd stress and detoxification mechanisms of F. cirrhosa. The results demonstrated that Cd caused severe damage to cell membranes and organelles, leading to significant oxidative damage and reducing photosynthesis, alkaloid and nucleoside contents, and biomass. Cd application increased cell wall thickness by 167.89% in leaves and 445.78% in bulbs, leading to weight percentage of Cd increases of 76.00% and 257.14%, respectively. PER, CESA, PME, and SUS, genes responsible for cell wall thickening, were significantly upregulated. Additionally, the levels of metabolites participating in the scavenging of reactive oxygen species, including oxidized glutathione, D-proline, L-citrulline, and putrescine, were significantly increased under Cd stress. Combined multi-omics analyses revealed that glutathione metabolism and cell wall biosynthesis pathways jointly constituted the detoxification mechanism of F. cirrhosa in response to Cd stress. This study provides a theoretical basis for further screening of new cultivars for Cd tolerance and developing appropriate cultivation strategies to alleviate Cd toxicity.

Carbapenem-Resistant Pseudomonas aeruginosa Infection and Mixed Infections Are Risk Factors for Poor Outcome After Lung Transplant.

OBJECTIVES: In this study, we analyzed the effects of carbapenem-resistant Pseudomonas aeruginosa infection and mixed infection on the perioperative prognosis of lung transplant recipients and studied statistics on antibiotic resistance in P aeruginosa. MATERIALS AND METHODS: This was a retrospective casecontrol study. We collected data on lung transplant recipients with combined lower respiratory tract P aeruginosa infection within 48 hours after lung transplant at the China-Japan Friendship Hospital from August 2018 to April 2022. We grouped recipients according to P aeruginosa resistance to carbapenem antibiotics and summarized the clinical characteristics of carbapenem-resistant P aeruginosa infection. We analyzed the effects of carbapenemresistant P aeruginosa infection and mixed infections on all-cause mortality 30 days after lung transplant by Cox regression. We used the Kaplan-Meier method to plot survival curves. RESULTS: Patients in the carbapenem-resistant P aeruginosa group had a higher all-cause mortality rate than those in the carbapenem-sensitive P aeruginosa group at both 7 days (6 patients [22.3%] vs 2 patients [4.5%]; P = .022) and 30 days (12 patients [44.4%] vs 7 patients [15.9%]; P = .003) after lung transplant. In multivariate analysis, both carbapenemresistant P aeruginosa infection and P aeruginosa combined with bacterial infection were independent risk factors for death 30 days after transplant in lung transplant recipients (P < .05). In subgroup analysis, carbapenem-resistant P aeruginosa combined with bacterial infection increased the risk of death 30 days after transplant in lung transplant recipients compared with carbapenem-sensitive P aeruginosa combined with bacterial infection (12 patients [60%] vs 6 patients [19.4%]; P < .001). CONCLUSIONS: Combined lower respiratory tract carbapenem-resistant P aeruginosa infection and P aeruginosa combined with bacterial infection early after lung transplant increased the risk of 30-day mortality after lung transplant.

Association between the lung microbiome and perioperative prognosis in lung transplant recipients.

RATIONALE: Studies have confirmed that the lung microbiome of lung transplant recipients is altered and serves as a prognostic indicator for long-term mortality. Other studies reported that the lung microbiome affects host immunity and the transcriptome. However, the lung microbiome composition at the early post-transplant period following lung transplantation is unclear, and the relationship of the lung microbiome with pulmonary immunity and the host transcriptome is also not well understood. OBJECTIVES: We hypothesize that changes in the lung microbiome composition in the early post-transplant period may have a predictive value for perioperative outcomes following lung transplantation and that the lung microbiome is correlated with pulmonary immunity and the host transcriptome. Thus, this prospective study aimed at observing the lung microbiome composition in the early post-transplant period and the impact of the lung microbiome on pulmonary cytokines and the host transcriptome. Our findings will help us gain a comprehensive understanding of the distribution and significance of the lung microbiome in the early post-transplant period. METHODS: An observational study was conducted to identify the lung microbiome and the host transcriptome characteristics using next-generation sequencing. Luminex was employed for quantifying alveolar cytokines. Spearman's correlation analysis was utilized to assess the impact of the lung microbiome on pulmonary immunity and differentially expressed genes in patients who died perioperatively after lung transplantation. RESULTS: Patients with poor perioperative outcomes showed an increase in Mycoplasma and Arcobacter, a decrease of Gemella, and increased interleukin (IL)-10, IL-1ß, and tumor necrosis factor (TNF)-α concentration. The lung microbiome correlates with lung immunity in lung transplant recipients. In the death group, the function of differentially expressed genes is associated with cell apoptosis, and promoting TNF production is upregulated. The lung microbiome is related to differentially expressed genes between the two groups. CONCLUSIONS: The lung microbiome and cytokines can be considered as potential biomarkers for early prognosis in lung transplant recipients. The lung microbiome is associated with both lung immunity and differentially expressed genes in lung transplant recipients.

GLUT1-mediated microglial proinflammatory activation contributes to the development of stress-induced spatial learning and memory dysfunction in mice.

BACKGROUND: Stress is a recognized risk factor for cognitive decline, which triggers neuroinflammation involving microglial activation. However, the specific mechanism for microglial activation under stress and affects learning and memory remains unclear. METHODS: The chronic stress mouse model was utilized to explore the relationship between microglial activation and spatial memory impairment. The effect of hippocampal hyperglycemia on microglial activation was evaluated through hippocampal glucose-infusion and the incubation of BV2 cells with high glucose. The gain-and loss-of-function experiments were conducted to investigate the role of GLUT1 in microglial proinflammatory activation. An adeno-associated virus (AAV) was employed to specifically knockdown of GLUT1 in hippocampal microglia to assess its impact on stressed-mice. RESULTS: Herein, we found that chronic stress induced remarkable hippocampal microglial proinflammatory activation and neuroinflammation, which were involved in the development of stress-related spatial learning and memory impairment. Mechanistically, elevated hippocampal glucose level post-stress was revealed to be a key regulator of proinflammatory microglial activation via specifically increasing the expression of microglial GLUT1. GLUT1 overexpression promoted microglial proinflammatory phenotype while inhibiting GLUT1 function mitigated this effect under high glucose. Furthermore, specific downregulation of hippocampal microglial GLUT1 in stressed-mice relieved microglial proinflammatory activation, neuroinflammation, and spatial learning and memory injury. Finally, the NF-κB signaling pathway was demonstrated to be involved in the regulatory effect of GLUT1 on microglia. CONCLUSIONS: We demonstrate that elevated glucose and GLUT1 expression induce microglia proinflammatory activation, contributing to stress-associated spatial memory dysfunction. These findings highlight significant interplay between metabolism and inflammation, presenting a possible therapeutic target for stress-related cognitive disorders.

Additive interaction between birth asphyxia and febrile seizures on autism spectrum disorder: a population-based study.

BACKGROUND: Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder that can significantly impact an individual's ability to socially integrate and adapt. It's crucial to identify key factors associated with ASD. Recent studies link both birth asphyxia (BA) and febrile seizures (FS) separately to higher ASD prevalence. However, investigations into the interplay of BA and FS and its relationship with ASD are yet to be conducted. The present study mainly focuses on exploring the interactive effect between BA and FS in the context of ASD. METHODS: Utilizing a multi-stage stratified cluster sampling, we initially recruited 84,934 Shanghai children aged 3-12 years old from June 2014 to June 2015, ultimately including 74,251 post-exclusion criteria. A logistic regression model was conducted to estimate the interaction effect after controlling for pertinent covariates. The attributable proportion (AP), the relative excess risk due to interaction (RERI), the synergy index (SI), and multiplicative-scale interaction were computed to determine the interaction effect. RESULTS: Among a total of 74,251 children, 192 (0.26%) were diagnosed with ASD. The adjusted odds ratio for ASD in children with BA alone was 3.82 (95% confidence interval [CI] 2.42-6.02), for FS alone 3.06 (95%CI 1.48-6.31), and for comorbid BA and FS 21.18 (95%CI 9.10-49.30), versus children without BA or FS. The additive interaction between BA and FS showed statistical significance (P < 0.001), whereas the multiplicative interaction was statistically insignificant (P > 0.05). LIMITATIONS: This study can only demonstrate the relationship between the interaction of BA and FS with ASD but cannot prove causation. Animal brain experimentation is necessary to unravel its neural mechanisms. A larger sample size, ongoing monitoring, and detailed FS classification are needed for confirming BA-FS interaction in ASD. CONCLUSION: In this extensive cross-sectional study, both BA and FS were significantly linked to ASD. The coexistence of these factors was associated with an additive increase in ASD prevalence, surpassing the cumulative risk of each individual factor.

Hippocampal Lactate-Infusion Enhances Spatial Memory Correlated with Monocarboxylate Transporter 2 and Lactylation.

Lactate has emerged as a key player in regulating neural functions and cognitive processes. Beyond its function as an energy substrate and signal molecule, recent research has revealed lactate to serve as an epigenetic regulator in the brain. However, the molecular mechanisms by which lactate regulates spatial memory and its role in the prevention of cognitive disorders remain unclear. Herein, we injected L-lactate (10 µmol/kg/d for 6 d) into the mouse's hippocampus, followed by the Morris water maze (MWM) test and molecular analyses. Improved spatial memory performances were observed in mice injected with lactate. Besides, lactate upregulated the expression of synaptic proteins post-synaptic density 95 (PSD95), synaptophysin (SYP), and growth associated protein 43 (GAP43) in hippocampal tissues and HT22 cells, suggesting a potential role in synaptic transmission and memory formation. The facilitative role of monocarboxylate transporter 2 (MCT2), a neuron-specific lactate transporter, in this process was confirmed, as MCT2 antagonists attenuated the lactate-induced upregulation of synaptic proteins. Moreover, lactate induced protein lactylation, a post-translational modification, which could be suppressed by MCT2 inhibition. RNA sequencing of lactated-injected hippocampal tissues revealed a comprehensive gene expression profile influenced by lactate, with significant changes in genes associated with transcriptional progress. These data demonstrate that hippocampal lactate injection enhances spatial memory in mice, potentially through the upregulation of synaptic proteins and induction of protein lactylation, with MCT2 playing a crucial role in these processes. Our findings shed light on the multi-faceted role of lactate in neural function and memory regulation, opening new avenues for therapeutic interventions targeting cognitive disorders.

A Modified Tridecapeptide Probe for Imaging Cell Junction.

Cell junctions, which are typically associated with dynamic cytoskeletons, are essential for a wide range of cellular activities, including cell migration, cell communication, barrier function and signal transduction. Observing cell junctions in real-time can help us understand the mechanisms by which they regulate these cellular activities. This study examined the binding capacity of a modified tridecapeptide from Connexin 43 (Cx43) to the cell junction protein zonula occludens-1 (ZO-1). The goal was to create a fluorescent peptide that can label cell junctions. A cell-penetrating peptide was linked to the modified tridecapeptide. The heterotrimeric peptide molecule was then synthesized. The binding of the modified tridecapeptide was tested using pulldown and immunoprecipitation assays. The ability of the peptide to label cell junctions was assessed by adding it to fixed or live Caco-2 cells. The testing assays revealed that the Cx43-derived peptide can bind to ZO-1. Additionally, the peptide was able to label cell junctions of fixed cells, although no obvious cell junction labeling was observed clearly in live cells, probably due to the inadequate affinity. These findings suggest that labeling cell junctions using a peptide-based strategy is feasible. Further efforts to improve its affinity are warranted in the future.

An integrative database and its application for plant synthetic biology research.

Plant synthetic biology research requires diverse bioparts that facilitate the redesign and construction of new-to-nature biological devices or systems in plants. Limited by few well-characterized bioparts for plant chassis, the development of plant synthetic biology lags behind that of its microbial counterpart. Here, we constructed a web-based Plant Synthetic BioDatabase (PSBD), which currently categorizes 1677 catalytic bioparts and 384 regulatory elements and provides information on 309 species and 850 chemicals. Online bioinformatics tools including local BLAST, chem similarity, phylogenetic analysis, and visual strength are provided to assist with the rational design of genetic circuits for manipulation of gene expression in planta. We demonstrated the utility of the PSBD by functionally characterizing taxadiene synthase 2 and its quantitative regulation in tobacco leaves. More powerful synthetic devices were then assembled to amplify the transcriptional signals, enabling enhanced expression of flavivirus non-structure 1 proteins in plants. The PSBD is expected to be an integrative and user-centered platform that provides a one-stop service for diverse applications in plant synthetic biology research.

AMYGNN: A Graph Convolutional Neural Network-Based Approach for Predicting Amyloid Formation from Polypeptides.

There has been an increasing interest in the use of amyloids for constructing various functional materials. The design of amyloid-associated functional materials requires the identification of the core peptide sequences as the fundamental building block. The existing computational methods are limited in terms of delineating polypeptides, the typical non-Euclidean structural data, and they fail to capture the dynamic interactions between amino acids due to ignoring the contextual information from surrounding amino acids. Here, we first propose the use of a state-of-the-art graph convolutional neural network for predicting the trends of amyloid formation from specific peptide sequences (AMYGNN) by abstracting each polypeptide as a graph, in which the constituting amino acids are viewed as nodes and edges characterizing the connections between pairs of amino acids are established when they meet a given distance threshold (Cα-Cα ≤ 5 Å). Our model achieves high performance with accuracy (0.9208), G-mean (0.9203), MCC (0.8417), and F1 (0.9235) in determining the characteristic peptide sequences to form amyloid. 32 of 534 crucial amino acid properties that greatly contribute to the formation of amyloids are ascertained, and the ß-folding-like graph structure of a polypeptide is believed to be essential for the formation of amyloid. Our model enables the mapping of polypeptides with underlying interactions between amino acids and provides a quick and precise predictive framework for directing the construction of amyloid-associated functional materials.

Myeloid-derived suppressor cells from tumour-bearing mice induce the population expansion of CD19hiFcγRIIbhi regulatory B cells via PD-L1.

Myeloid-derived suppressor cells (MDSCs) increase in number and gain immunosuppressive functions in tumours and many other pathological conditions. MDSCs are characterized by their strong T-cell immunosuppressive capacity. The effects that MDSCs may have on B cells, especially within the tumour microenvironment, are less well understood. Here, we report that either monocytic MDSCs or polymorphonuclear MDSCs can promote increases in interleukin (IL)-10-expressing CD19hiFcγRIIbhi regulatory B cells in vitro and in vivo. Splenic transitional-1, -2, and -3 cells and marginal zone B cells, but not follicular B cells, differentiate into IL-10-expressing CD19hiFcγRIIbhi regulatory B cells. The adoptive transfer of CD19hiFcγRIIbhi regulatory B cells via tail vein injection can promote subcutaneous 3LL tumour growth in mice. The expression of programmed death-ligand 1 on MDSCs was found to be strongly associated with CD19hiFcγRIIbhi regulatory B cell population expansion. Furthermore, the frequency of circulating CD19+FcγRIIhi regulatory B cells was significantly increased in advanced-stage lung cancer patients. Our results unveil a critical role of MDSCs in regulatory B-cell differentiation and population expansion in lung cancer patients.

Combined multi-omics approach to analyze the flavor characteristics and formation mechanism of gabaron green tea.

Gabaron green tea (GAGT) has unique flavor and health benefits through the special anaerobic treatment. However, how this composite processing affects the aroma formation of GAGT and the regulatory mechanism was rarely reported. This study used nontargeted metabolomics and molecular sensory science to overlay screen differential metabolites and key aroma contributors. The potential regulatory mechanism of anaerobic treatment on the aroma formation of GAGT was investigated by transcriptomics and correlation analyses. Five volatiles: benzeneacetaldehyde, nonanal, geraniol, linalool, and linalool oxide III, were screened as target metabolites. Through the transcriptional-level differential genes screening and analysis, some CsERF transcription factors in the ethylene signaling pathway were proposed might participate the response to the anaerobic treatment. They might regulate the expression of related genes in the metabolic pathway of the target metabolites thus affecting the GAGT flavor. The findings of this study provide novel information on the flavor and its formation of GAGT.

Structural effects of inosine substitution in telomeric DNA quadruplex.

The telomeric DNA, a distal region of eukaryotic chromosome containing guanine-rich repetitive sequence of (TTAGGG)n, has been shown to adopt higher-order structures, specifically G-quadruplexes (G4s). Previous studies have demonstrated the implication of G4 in tumor inhibition through chromosome maintenance and manipulation of oncogene expression featuring their G-rich promoter regions. Besides higher order structures, several regulatory roles are attributed to DNA epigenetic markers. In this work, we investigated how the structural dynamics of a G-quadruplex, formed by the telomeric sequence, is affected by inosine, a prevalent modified nucleotide. We used the standard (TTAGGG)n telomere repeats with guanosine mutated to inosine at each G position. Sequences (GGG)4, (IGG)4, (GIG)4, (GGI)4, (IGI)4, (IIG)4, (GII)4, and (III)4, bridged by TTA linker, are studied using biophysical experiments and molecular modeling. The effects of metal cations in quadruplex folding were explored in both Na+ and K+ containing buffers using CD and UV-melting studies. Our results show that antiparallel quadruplex topology forms with the native sequence (GGG)4 and the terminal modified DNAs (IGG)4 and (GGI)4 in both Na+ and K+ containing buffers. Specifically, quadruplex hybrid was observed for (GGG)4 in K+ buffer. Among the other modified sequences, (GIG)4, (IGI)4 and (GII)4 show parallel features, while (IIG)4 and (III)4 show no detectable conformation in the presence of either Na+ or K+. Our studies indicate that terminal lesions (IGG)4 and (GGI)4 may induce certain unknown conformations. The folding dynamics become undetectable in the presence of more than one inosine substitution except (IGI)4 in both buffer ions. In addition, both UV melting and CD melting studies implied that in most cases the K+ cation confers more thermodynamic stability compared to Na+. Collectively, our conformational studies revealed the diverse structural polymorphisms of G4 with position dependent G-to-I mutations in different ion conditions.

Comprehensive analysis of clinicopathological profiles in adenosquamous carcinoma of the lung.

OBJECTIVES: Adenosquamous carcinoma (ASC), an uncommon subtype within non-small cell lung cancer (NSCLC), manifests distinctive traits of aggressiveness, embodying a fusion of both adenocarcinoma (AC) and squamous cell carcinoma (SCC) components. The clinicopathological characteristics of distinct subtypes of ASC remain unclear. METHODS: This retrospective study included 226 patients diagnosed with lung ASC who consecutively underwent surgical resection at Shanghai Pulmonary Hospital, Tongji University, between January 2015 and March 2021. Data regarding the clinical features and pathological features were collected. RESULTS: Out of this study cohort, 125 patients exhibited AC-predominant ASC, while 81 had SCC-predominant ASC. No significant differences were observed between the two subgroups in terms of age, gender, smoking history, primary site, and T, N classification. AC-Predominant ASC displayed a higher susceptibility to genetic alterations compared to SCC-Predominant ASC (P=0.02). Additionally, we showed that irrespective of the predominant pathological subtype in ASC, when lymph node metastasis occurred, the lymph node biopsies were more likely to exhibit AC, and a chi-square test confirmed that the primary predominant pathological subtype was not associated with the lymph node metastasis subtype. CONCLUSIONS: In conclusion, we describe an overview of ASC in the Chinese population, and upon stratifying into predominant pathological subgroups, we observed a higher frequency of driver gene mutations in AC-predominant ASC. We found that the AC component in ASC has a higher propensity for lymph node metastasis. These findings may suggest the predominant role of the AC component within the context of ASC.

A pavement crack synthesis method based on conditional generative adversarial networks.

A Generative Adversarial Network (GAN) based asphalt pavement crack image generation method was proposed to improve the dataset size of the road images. Five open-source road crack datasets were leveraged to construct an image dataset, which contained two labels - transverse cracks and longitudinal cracks. The constructed dataset was used to facilitate crack detection and classification research by providing a diverse collection of labeled crack images derived from multiple public sources. The network structure of fully connected, convolutional and attention mechanisms based on the Conditional Generative Adversarial Network (CGAN) was used in this project. The purpose of this study was to train a generative model on selected categories of input pavement crack images and generate realistic crack images of those categories. We aim to tune the parameters of the GAN and optimize hyperparameters to improve the realism possibility of generated images. It also explored the generated images with different sizes and evaluated the performance of networks with different architectures. In particular, we analyzed the structural characteristics of conditional GAN. Results demonstrated that the Self-Attention Generative Adversarial Networks (SAGAN) model, which combines self-attention mechanisms with CGAN, can effectively address challenges related to limited crack image data and the inability to selectively generate images from specific categories. By conditioning the generator on category information, the SAGAN model was able to generate high-quality images while focusing on the target categories. Overall, the self-attention and conditional aspects of the SAGAN framework helped improve the generation of realistic pavement crack images.

Application of Four-Dimensional Pelvic Floor Ultrasound in the Diagnosis of Postpartum Pelvic Floor Dysfunction and Evaluation of Curative Effect.

Objective: To explore the application of four-dimensional pelvic floor ultrasound in the diagnosis of postpartum pelvic floor dysfunction (PFD) and evaluation of curative effect. Methods: A total of 100 patients with postpartum PFD undergoing vaginal delivery in the hospital were enrolled as the research objects between January 2020 and January 2023. A total of 100 postpartum women with good pelvic floor muscle function during the same period were enrolled as a control group. Both groups underwent four-dimensional pelvic floor ultrasound detection. The bladder neck descent (BND), retrovesical angle (RVA), urethral tilt angle (UTA), urethral rotation angle (ROT), levator ani thickness under rest state (LATr), levator ani thickness under Valsalva state (LATs), levator ani hiatus area under rest state (LHAr) and levator ani hiatus area under Valsalva state (LHAs) in both groups were compared. The patients in the study group were given Kegel training for pelvic floor muscle rehabilitation exercise and bio-feedback electrical stimulation. According to the clinical curative effect, patients in the study group were divided into a recovery group (n=87) and a non-recovery group (n=13). The value of four-dimensional pelvic floor ultrasound in the diagnosis of PFD and evaluation of curative effect was analyzed. Results: In the observation group, BND, RVA, UTA, ROT, LHAr, and LHAs were higher, while LATr and LATs were lower compared to the control group. (P < .05). The results of ROC curves analysis showed that the AUC of BND combined with RVA, UTA, ROT, LATr, LATs, LHAr, and LHAs in the diagnosis of PFD was 0.818, greater than that of the single index (0.728, 0.705, 0.680, 0.715, 0.677, 0.696, 0.719, 0.654; P < .05). BND, RVA, UTA, ROT, LHAr, and LHAs in the non-recovery group were higher than those in the recovery group, while LATr and LATs were lower than those in the recovery group (P < .05). The results of ROC curves analysis showed that the Area Under the Curve (AUC）of BND combined with RVA, UTA, ROT, LATr, LATs, LHAr, and LHAs for predicting the curative effect were 0.804, greater than that of a single index (0.725, 0.653, 0.651, 0.744, 0.733, 0.720, 0.661, 0.718; P < .05). Conclusion: Four-dimensional pelvic floor ultrasound can be applied to intuitively evaluate the structure and function of postpartum pelvic floor tissues, which can provide a reliable basis for the diagnosis of postpartum PFD and evaluation of curative effect.

Characterization of ultrasound-assisted covalent binding interaction between ß-lactoglobulin and dicaffeoylquinic acid: Great potential for the curcumin delivery.

The low bioavailability and poor gastrointestinal instability of curcumin hampers its application in pharmaceutical and food industries. Thus, it is essential to explore efficient carrier (e.g. a combination of polyphenols and proteins) for food systems. In this study, covalent ß-lactoglobulin (LG)-dicaffeoylquinic acids (DCQAs) complexes were prepared by combining ultrasound and free radical induction methods. Covalent interactions between LG and DCQAs were confirmed by analyzing reactive groups. Variations in secondary or tertiary structure and potential binding sites of covalent complexes were explored using Fourier transform infrared spectroscopy and circular dichroism. Results showed that the ß-sheet content decreased and the unordered content increased significantly (P < 0.05). The embedding rate of curcumin in prepared LG-DCQAs complexes using ultrasound could reach 49 % - 62 %, proving that complexes could embed curcumin effectively. This study highlights the benefit of ultrasound application in fabrication of protein-polyphenol complexes for delivering curcumin.

Predicting the potential distribution range of Batocera horsfieldi under CMIP6 climate change using the MaxEnt model.

Batocera horsfieldi (Hope) (Coleoptera, Cerambycidae, Batocera) is an important wood-boring pest in China, mainly affecting natural forests, economic forests, urban gardens, and green landscapes. In this study, based on the MaxEnt model and ArcGIS, we combined 216 distribution records of B. horsfieldi with 11 selected key environmental variables to predict its potential suitable distribution under current climate data (1970-2000) and 3 climate emission scenarios from the Sixth Phase of the Coupled Model Intercomparison Project (CMIP6). The results showed that monthly mean diurnal temperature ranges (bio2), isothermality (bio3), temperature seasonality (bio4), minimum temperature of the coldest month (bio6), mean temperature of the wettest quarter (bio8), mean temperature of the driest quarter (bio9), annual precipitation (bio12), precipitation of the wettest month (bio13), precipitation of the driest month (bio14), precipitation seasonality (coefficient of variation) (bio15), and altitude were the key environmental variables influencing the potential distribution of B. horsfieldi. In the future scenarios of SSP1-2.6, SSP2-4.5, and SSP5-8.5, the areas of high, moderate, and low suitable distribution areas have varied to different extents. However, under the SSP2-4.5 scenario (2050s), there is an observable increase in the areas of high, moderate, and low suitability. The total area of the suitable area reaches 160.88 × 104 km2 and is also shifting toward higher latitudes and altitudes. This study provides scientific reference for future pest control by predicting B. horsfieldi's potential distribution. A "graded response" detection and early warning system and prevention and control strategies can be formulated based on the potential suitable areas to address this pest challenge effectively.

Fabricating Composite Cell Sheets for Wound Healing: Cell Sheets Based on the Communication Between BMSCs and HFSCs Facilitate Full-Thickness Cutaneous Wound Healing.

BACKGROUND: Insufficient angiogenesis and the lack of skin appendages are critical challenges in cutaneous wound healing. Stem cell-fabricated cell sheets have become a promising strategy, but cell sheets constructed by a single cell type are inadequate to provide a comprehensive proregenerative microenvironment for wound tissue. METHODS: Based on the communication between cells, in this study, bone marrow mesenchymal stem cells (BMSCs) and hair follicle stem cells (HFSCs) were cocultured to fabricate a composite cell sheet (H/M-CS) for the treatment of full-thickness skin wounds in mice. RESULTS: Experiments confirmed that there is cell-cell communication between BMSCs and HFSCs, which enhances the cell proliferation and migration abilities of both cell types. Cell-cell talk also upregulates the gene expression of pro-angiogenic-related cytokines in BMSCs and pro-hair follicle-related cytokines in HFSCs, as well as causing changes in the properties of secreted extracellular matrix components. CONCLUSIONS: Therefore, the composite cell sheet is more conducive for cutaneous wound healing and promoting the regeneration of blood vessels and hair follicles.

Blood-brain barrier dysfunction mediated by the EZH2-Claudin-5 axis drives stress-induced TNF-α infiltration and depression-like behaviors.

Growing evidence suggests that neurovascular dysfunction characterized by blood-brain barrier (BBB) breakdown underlies the development of psychiatric disorders, such as major depressive disorder (MDD). Tight junction (TJ) proteins are critical modulators of homeostasis and BBB integrity. TJ protein Claudin-5 is the most dominant BBB component and is downregulated in numerous depression models; however, the underlying mechanisms remain elusive. Here, we demonstrate a molecular basis of BBB breakdown that links stress and depression. We implemented an animal model of depression, chronic unpredictable mild stress (CUMS) in male C57BL/6 mice, and showed that hippocampal BBB breakdown was closely associated with stress vulnerability. Concomitantly, we found that dysregulated Cldn5 level coupled with repression of the histone methylation signature at its promoter contributed to stress-induced BBB dysfunction and depression. Moreover, histone methyltransferase enhancer of zeste homolog 2 (EZH2) knockdown improved Cldn5 expression and alleviated depression-like behaviors by suppressing the tri-methylation of lysine 27 on histone 3 (H3K27me3) in chronically stressed mice. Furthermore, the stress-induced excessive transfer of peripheral cytokine tumor necrosis factor-α (TNF-α) into the hippocampus was prevented by Claudin-5 overexpression and EZH2 knockdown. Interestingly, antidepressant treatment could inhibit H3K27me3 deposition at the Cldn5 promoter, reversing the loss of the encoded protein and BBB damage. Considered together, these findings reveal the importance of the hippocampal EZH2-Claudin-5 axis in regulating neurovascular function and MDD development, providing potential therapeutic targets for this psychiatric illness.

Arsenic induced neurotoxicity in the brain of ducks: The potential involvement of the gut-brain axis.

BACKGROUND: Arsenic is a widely distributed ecotoxic pollutant that has been found to cause neurotoxicity in a variety of species. Gut-brain axis is a two-way information network between the gut microbiome and the brain, which is closely related to organismal health. However, the role of the gut-brain axis in arsenic-induced neurotoxicity remains largely unknown. METHODS: In order to explore whether there is a relationship between brain and gut microbiota of meat ducks, we performed molecular biological detection including RT-qPCR and Western blot, as well as morphological detection including, HE staining and immunohistochemistry. Meanwhile, intestinal contents were analyzed using 16 S ribosomal RNA gene sequencing and analysis RESULTS: In this study, we investigated whether arsenic trioxide (ATO) can activate the gut microbiome-brain axis to induce intestinal and brain injury. The results showed that ATO-exposure disrupted the diversity balance of intestinal microbiota and integrity and injured the intestinal structure. ATO-exposure also reduced the number of glycogen and goblet cells in the duodenum. In addition, exposure to ATO caused intestinal inflammatory injury by activating NF-κB signaling pathway and promoting the expression of its target genes. Meanwhile, the tight junction-related proteins (ZO-1, occludin) of gut and brain were reduced by ATO exposure. Furthermore, results also revealed that ATO-exposure induced brain injury, including neuronal cell vacuolization and reduced numbers of neuronal cells in the cortex and hippocampus. Remarkably, ATO-exposure also disrupted neurotransmitter levels. Additionally, our further molecular mechanism study revealed that ATO-exposure increased the expression of autophagy and apoptosis related mRNA and proteins levels in the brain tissues. CONCLUSION: Altogether, these findings provide a new insight into that ATO-exposure induced intestinal injury and aggravated neurotoxicity via the gut-brain axis.