QSAR aided design of potent c-Met inhibitors using molecular docking, molecular dynamics simulation and binding free energy calculation.

Mesenchymal-epithelial transition factor (c-Met) is a tyrosine kinase receptor. Under certain disease conditions, the cellular transformation process may be over-activated, resulting in carcinogenesis. Therefore, molecularly targeted therapy targeting the receptor tyrosine kinase c-Met is achieved by inhibiting c-Met activity and thus effectively suppressing cancer propagation. In this paper, 41 compounds were selected from the reported literature as a dataset to build stable Topomer CoMFA and HQSAR models. The feasibility of the constructed models was evaluated by internal and external validation techniques. Based on the Topomer CoMFA model basis the fragments with higher contribution values were screened and the combination yielded 19 compounds with higher than template molecules. Through molecular docking, the ligand complexes formed hydrogen and hydrophobic bonds with strong stable structures. The ligand-protein complexes with better scoring results were selected for MD simulations, and Y14 exhibited a stable and favourable binding pocket. In addition, ADMET results showed that the ligand-complexes have potential medicinal effects on c-Met inhibition. This study provides a reference for molecularly targeted therapy targeting receptor tyrosine-kinetic c-Met.

Bacillus coagulans restores pathogen-induced intestinal dysfunction via acetate-FFAR2-NF-[Formula: see text]B-MLCK-MLC axis in Apostichopus japonicus.

Skin ulceration syndrome (SUS) is currently the main disease threatening Apostichopus japonicus aquaculture due to its higher mortality rate and infectivity, which is caused by Vibrio splendidus. Our previous studies have demonstrated that SUS is accompanied by intestinal microbiota (IM) dysbiosis, alteration of short-chain fatty acids (SCFAs) content and the damage to the intestinal barrier. However, the mediating effect of IM on intestine dysfunction is largely unknown. Herein, we conducted comprehensive intestinal microbiota transplantation (IMT) to explore the link between IM and SUS development. Furthermore, we isolated and identified a Bacillus coagulans strain with an ability to produce acetic acid from both healthy individual and SUS individual with IM from healthy donors. We found that dysbiotic IM and intestinal barrier function in SUS recipients A. japonicus could be restored by IM from healthy donors. The B. coagulans strain could restore IM community and intestinal barrier function. Consistently, acetate supply also restores intestinal homeostasis of SUS-diseased and V. splendidus-infected A. japonicus. Mechanically, acetate was found to specifically bind to its receptor-free fatty acid receptor 2 (FFAR2) to mediate IM structure community and intestinal barrier function. Knockdown of FFAR2 by transfection of specific FFAR2 siRNA could hamper acetate-mediated intestinal homeostasis in vivo. Furthermore, we confirmed that acetate/FFAR2 could inhibit V. splendidus-activated NF-κB-MLCK-MLC signaling pathway to restore intestinal epithelium integrity and upregulated the expression of ZO-1 and Occludin. Our findings provide the first evidence that B. coagulans restores pathogen-induced intestinal barrier dysfunction via acetate/FFAR2-NF-κB-MLCK-MLC axis, which provides new insights into the control and prevention of SUS outbreak from an ecological perspective.IMPORTANCESkin ulceration syndrome (SUS) as a main disease in Apostichopus japonicus aquaculture has severely restricted the developmental A. japonicus aquaculture industry. Intestinal microbiota (IM) has been studied extensively due to its immunomodulatory properties. Short-chain fatty acids (SCFAs) as an essential signal molecule for microbial regulation of host health also have attracted wide attention. Therefore, it is beneficial to explore the link between IM and SUS for prevention and control of SUS. In the study, the contribution of IM to SUS development has been examined. Additionally, our research further validated the restoration of SCFAs on intestinal barrier dysfunction caused by SUS via isolating SCFAs-producing bacteria. Notably, this restoration might be achieved by inhibition of NF-κB-MLCK-MLC signal pathway, which could be activated by V. splendidus. These findings may have important implications for exploration of the role of IM in SUS occurrence and provide insight into the SUS treatment.

Design of vilazodone-donepezil chimeric derivatives as acetylcholinesterase inhibitors by QSAR, molecular docking and molecular dynamics simulations.

Alzheimer's disease (AD) is a disease that affects the cognitive abilities of older adults, and it is one of the biggest global medical challenges of the 21st century. Acetylcholinesterase (AChE) can increase acetylcholine concentrations and improve cognitive function in patients, and is a potential target to develop small molecule inhibitors for the treatment of Alzheimer's disease (AD). In this study, 29 vilazodone-donepezil chimeric derivatives are systematically studied using 3D-QSAR modeling, and a robust and reliable Topomer CoMFA model was obtained with: q2 = 0.720, r2 = 0.991, F = 287.234, N = 6, and SEE = 0.098. Based on the established model and combined with the ZINC20 database, 33 new compounds with ideal inhibitory activity are successfully designed. Molecular docking and ADMET property prediction also show that these newly designed compounds have a good binding ability to the target protein and can meet the medicinal conditions. Subsequently, four new compounds with good comprehensive ability are selected for molecular dynamics simulation, and the simulation results confirm that the newly designed compounds have a certain degree of reliability and stability. This study provides guidance for vilazodone-donepezil chimeric derivatives as a potential AChE inhibitor and has certain theoretical value.

Hydrogen sulfide donors across time: From origins to cutting-edge applications.

This review aims to analyze the developmental trajectory of hydrogen sulfide (H2S) donors over the past three decades and explore the historical background, research hotspots, and emerging trends in related fields from a temporal perspective. A total of 5092 literature articles on H2S donors were retrieved from the Web of Science Core Collection (WoSCC), encompassing 1303 journals, 20638 authors, 10992 institutions, and 459 countries and regions. Utilizing CiteSpace as a bibliometric tool, historical features, evolving active topics, and emerging trends in the field of H2S donors were identified. Over the past 30 years, the field of H2S donors has remained in a prominent stage. This article discusses both inorganic and organic types of H2S donors, including NaHS and Na2S, GYY4137, AP39, and AP123, as well as briefly outlines research and applications of H2S donors in nanotechnology, advanced materials, composite materials, nanostructures, and optical properties. Mechanistically, the review outlines how H2S donors regulate cellular signal transduction, anti-inflammatory responses, neuroprotection, and other pathways within the organism by modulating protein S-sulfhydration, antioxidant effects, and interactions with metal proteins. In terms of applications, the review summarizes the extensive use of H2S donors in biomedical research, encompassing cardiovascular, neurological, anti-inflammatory, and anti-cancer characteristics, as well as their potential applications in the treatment of metabolic diseases. Finally, challenges and limitations faced by H2S donor research are discussed, and potential future research directions are proposed.

[Cloning and expression analysis of wpHSP90 gene from Whitmania pigra at different temperatures].

HSP90 is a widely distributed molecular chaperone that participates in a variety of cellular processes and plays an important role in the meiosis of germ cells. However, its role in the gonadal development of hermaphroditic Whitmania pigra is not yet clear. To explore the effect of HSP90 on the germ cell development of Wh. Pigra, this study cloned the wpHSP90 gene, performed bioinformatics analysis, and measured its expression levels. The results showed that the cloned wpHSP90 was 2 592 bp in length, with an open reading frame(ORF) of 2 373 bp, encoding 790 amino acids. Prediction analysis revealed 85 phosphorylation modification sites on serine, threonine, and tyrosine residues of the wpHSP90 protein. Structural domain prediction and multiple sequence alignment results showed that wpHSP90 contained two conserved domains of HSP90 and exhibited the highest homology with Helobdella robusta, with a sequence similarity of 80.72%. RT-qPCR results showed that the relative expression level of wpHSP90 in the gonads of 5-month-old Wh. pigra was positively correlated with temperature within the range of 12 ℃ to 28 ℃. The expression level in the female gonads was significantly higher than in the male gonads and correlated with the trend of germ cell development in the ovaries and testes. In conclusion, wpHSP90 may be involved in regulating the development of germ cells, particularly oocytes, in Wh. pigra. This study provides a reference for further research on the gonadal development mechanism in Wh. pigra.

Highly sensitive frequency upconversion detection from 1 to 3 THz with OH1 crystal.

The wide applications of terahertz (THz) wave technology in the ∼1-3 THz range has resulted in a surge in the demand for the performance improvement of THz wave detection technique. In this study, a frequency tunable, highly sensitive frequency upconversion detection based on a 2-(3-(4-hydroxystyryl)-5,5-dime-thylcyclohex-2-enylidene) malononitrile (OH1) crystal at room temperature is demonstrated. Moreover, to effectively increase the signal-to-noise ratio in the low frequency range, a beam isolation enhancer is proposed and its effect is verified. The minimum detectable THz pulse energy reaches about 100 aJ at 1.9 THz. The frequency tuning ranging from 1 to 3 THz. Sensitivity comparison with a 4-dimethylamino-N-methyl-4-stilbazolium tosylate (DAST) crystal system shows that OH1 is a more suitable nonlinear crystal in the 1-2.4 THz range.

Different degrees of nodes behind obsessive-compulsive symptoms of schizophrenia.

Obsessive-compulsive symptoms are frequently observed in various psychiatric disorders, including obsessive-compulsive disorder, schizophrenia, depression, and anxiety. However, the underlying anatomical basis of these symptoms remains unclear. In this study, we aimed to investigate the mechanism of schizophrenia with obsessive-compulsive symptoms by using diffusion tensor imaging (DTI)-based structural brain connectivity analysis to assess the network differences between patients with obsessive-compulsive disorder (OCD), patients with schizophrenia showing obsessive-compulsive symptoms (SCH), schizophrenia patients with obsessive-compulsive symptoms due to clozapine (LDP), and healthy controls (CN). We included 21 patients with OCD, 20 patients with SCH, 12 patients with LDP, and 25 CN. All subjects underwent MRI scanning, and structural brain connections were estimated using diffusion tensor imaging for further analysis of brain connectivity. The topology and efficiency of the network and the characteristics of various brain regions were investigated. We assessed baseline YALE-BROWN OBSESSIVE COMPULSIVE SCALE (Y-BOCS), Positive and Negative Syndrome Scale (PANSS), and 24-item Hamilton Depression Scale (HAMD-24) scores. Our results showed significant differences among the SCH, OCD, and CN groups (p < 0.05) in the MRI-measured degree of the following nodes: the superior orbitofrontal gyrus (25Frontal_Med_Orb_L), lingual gyrus (47Lingual_L), postcentral gyrus (58Postcentral_R), and inferior temporal gyrus (90Temporal_Inf_R). Additionally, we found significant differences in the degree of the brain regions 02Precentral_R, 47Lingual_L, 58Postcentral_R, and 90Temporal_Inf_R between the CN, OCD, SCH, and LDP groups (p < 0.05). These findings suggest that alterations in the degree of nodes might be the mechanism behind obsessive-compulsive symptoms in schizophrenia.

Comparative analysis for immune response of coelomic fluid from coelom and polian vesicle in Apostichopus japonicus to Vibrio splendidus infection.

The polian vesicle and coelom of sea cucumber Apostichopus japonicus were full of coelomic fluid in which many types of coelomocytes with different functions were suspended. Our previous work has indicated the differences of coelomocytes between two sites mainly in subtype proportion, non-specific immune enzymes activities and several immune-related genes expression levels in healthy A. japonicus. However, the functional similarities and differences of coelomic fluid in two sites including the coelom and polian vesicle after pathogenic infection still remain unclear. Here, we investigated the changes of the total coelomocyte density (TCD) and differential coelomocyte density (DCD) after pathogen infection by Vibrio splendidus in coelom and polian vesicle. After infected by V. splendidus, the TCD in the coelom and polian vesicle rapidly declined at 12 h, and then the TCD in the coelom showed a stably ascending trend, while the TCD in the polian vesicle reached a peak at 24 h post infection (hpi), and then showed a continuously decline trend from 24 hpi to 72 hpi followed by a slow elevation until recovering the normal level from 72 hpi to 96 hpi. Then the activities of acidic phosphatase (ACP), alkaline phosphatase (AKP), catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate the response of cell-free coelomic fluid to V. splendidus infection. The activities of ACP, AKP and CAT showed similar trends in the coelom and polian vesicle. The SOD activity significantly increased in the polian vesicle, whereas it exhibited a decreasing trend in the coelom. Finally, the expression profiles of nine immune-related genes including Aj-MyD88, Aj-IRAK4, Aj-i-Lys, Aj-Rel, Aj-p50, Aj-DMBT1, Aj-CDC, Aj-Rrp15 and Aj-Fibrinogen C were detected after V. splendidus challenge. The results suggested all the detected genes were significantly up-regulated both in the coelom and polian vesicle, and the expression levels of these genes in two sites shared similar trends except Aj-MyD88 and Aj-DMBT1. This research provides a new insight into the differentially immune roles of coelomic fluid and coelomocytes in polian vesicle and coelom response to bacterial infections and supplements comprehensive resources for better understanding the innate immune response of A. japonicus.

Output characteristics of 3-8 µm mid-infrared source based on BaGa4Se7 crystal.

An optical parametric oscillator based on B a G a 4 S e 7 crystal is constructed for use as a 3-8 µm mid-infrared source. The output characteristics of the light source, including wavelength tuning, beam quality, and energy stability, are studied, which are usually concerned differently in spectral analysis, imaging, and laser processing. When the light source operates far from the threshold, the mid-infrared output is poor in beam quality and good in energy stability, and the contradiction should be addressed in practice. The results provide guidance on the selection of operating parameters and performance optimization for the application of the B a G a 4 S e 7 based mid-infrared source in various settings.

Autoantibodies against eukaryotic translation elongation factor 1 delta in two patients with autoimmune cerebellar ataxia.

Background: Autoantibodies are useful biomarkers for the early detection and diagnosis of autoimmune cerebellar ataxia (ACA). Objective: To identify novel autoantibody candidates in ACA patients. Methods: Patients with cerebellar ataxia of unknown cause were recruited from July 2018 to February 2023. Anti-neural autoantibodies in patient samples were detected by tissue-based indirect immunofluorescence assay (TBA) on rat cerebellum sections. TBA-positive samples were further screened for well-established anti-neural autoantibodies using commercial kits. Tissue-immunoprecipitation (TIP) and subsequent mass spectrometric (MS) analysis were used to explore the target antigens of autoantibodies in samples that were TBA-positive but negative for known autoantibodies. The specific binding between autoantibodies and the identified target antigen was confirmed by neutralization experiments, recombinant cell-based indirect immunofluorescence assay (CBA), and western blotting experiments. Results: The eukaryotic translation elongation factor 1 delta (EEF1D) protein was identified as a target antigen of autoantibodies in samples from a 43-year-old female ACA patient, while the specific binding of autoantibodies and EEF1D was confirmed by subsequent experiments. A second anti-EEF1D autoantibody-positive ACA patient, a 59-year-old female, was detected in simultaneous screening. The main clinical manifestations in each of the two patients were cerebellar syndrome, such as unsteady walking and limb ataxia. Both patients received immunotherapy, including corticosteroids, intravenous immunoglobulin, and mycophenolate mofetil. Their outcomes provided evidence to support the effectiveness of immunotherapy, but the cerebellar atrophy that occurred before treatment may be irreversible. Conclusion: In the current study, we identified anti-EEF1D autoantibody as a novel autoantibody candidate in ACA. Its pathological roles and diagnostic value need to be further verified in larger-scale studies.

Modeling for extracavity-pumped terahertz parametric oscillators.

This paper presents a modeling method for extracavity-pumped terahertz parametric oscillators (TPO) based on stimulated polariton scattering, in which the pumping beam is from a different laser, and the Stokes beam oscillates in its cavity. After suitable approximations and assumptions, the average THz wave amplitude in the nonlinear crystal is expressed as a function of the fundamental and Stokes wave amplitudes. Then the rate equation for the Stokes wave is obtained based on the Stokes wave increment within a cavity roundtrip timescale. After solving the Stokes wave rate equation, the Stokes wave temporal evolution is considered as a known parameter, and the properties of the residual fundamental and terahertz waves are obtained by numerically solving the coupled wave equations. This modeling method is applied to an extracavity-pumped TPO based on MgO:LiNbO3 crystal. The simulation results are basically consistent with the experimental results. The main reasons causing the deviations of the simulation results from the experimental results are analyzed. To the best of our knowledge, this is the first time to perform the modeling for extracavity-pumped Q-switched TPOs.

[Effects of shading on photosynthetic physiology and energy metabolism of Asarum forbesii].

Light is the main source for plants to obtain energy.Asarum forbesii is a typical shade medicinal plant, which generally grows in the shady and wet place under the bushes or beside the ditches.It can grow and develop without too much light intensity.This experiment explores the effects of shading on the growth, physiological characteristics and energy metabolism of A.forbesii, which can provide reference and guidance for its artificial planting.In this experiment, A.forbesii was planted under 80%, 60%, 40%, 20% and no shade.During the vigorous growth period, the photosynthetic physiological characteristics such as fluorescence parameters, photosynthetic parameters, photosynthetic pigment content and ultrastructure, as well as the content of mitochondrial electron transport chain(ETC) synthase and nutrients were measured.The results showed that the photosynthetic pigment content, chlorophyll fluorescence parameters and net photosynthesis rate(P_n) decreased with the decrease of shading.Under 20%-40% shading treatment, the plants had damaged ultrastructure, expanded and disintegrated chloroplast, disordered stroma lamella and grana lamella, and increased osmiophi-lic granules and starch granules.The activities of nicotinamide adenine dinucleotide dehydrogenase(NADH), succinate dehydrogenase(SDH), cytochrome C oxidoreductase(CCO) and adenosine triphosphate(ATP) synthasewere positively related to light intensity.With the reduction of shading, the content of total sugar and protein in nutrients increased first and then decreased, and the content was the highest under 60% shade.In conclusion, under 60%-80% shading treatment, the chloroplast and mitochondria had more complete structure, faster energy metabolism, higher light energy-conversion efficiency, better absorption and utilization of light energy and more nutrient synthesis, which was more suitable for the growth and development of A.forbesii.

Low expression of PRDM5 predicts poor prognosis of esophageal squamous cell carcinoma.

BACKGROUND: The role of the PRDM5 in esophageal squamous cell carcinoma (ESCC) has not been revealed. This study investigated the relationship between PRDM5 expression and survival outcome in esophageal squamous cell carcinoma and explored the mechanism in tumor development. METHODS: In present study, expression of PRDM5 mRNA in esophageal squamous cell carcinoma patients was conducted using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The expression of PRDM5 was assessed by immunohistochemical staining. Kaplan-Meier curve and Cox regression analysis was performed to analyze the survival outcome and independent predictive factors. qRT-PCR and Methylation-specific PCR were performed to identify the mRNA level of PRDM5 and Methylation rate. Cibersort algorithm to analyze the relationship between PRDM5 expression and immune cell invasion. Western-blot was performed to confirm the expression of esophageal tumor tissues and adjacent tissues. RESULTS: The TCGA database and GEO database show that PRDM5 mRNA level in esophageal squamous cell carcinoma adjacent tissues was higher than that of cancer tissues, and ESCC patients with high expression of PRDM5 mRNA had better overall survival. Tissue microarray showed that the protein level of PRDM5 in the adjacent tissues of patients with ESCC was higher than that in cancer tissues, and the expression level of PRDM5 was significantly correlated with the grade of clinicopathological characteristics (P < 0.001). Patients with high expression of PRDM5 displayed a better OS and DFS. Cox regression analysis showed that PRDM5 was an independent risk factor and prognostic factor for ESCC patients (HR: 2.626, 95%CI: 1.824-3.781; P < 0.001). The protein level of PRDM5 matched with the transcriptional level, whereas the DNA methylation affected the transcriptional level. Cibersort showed that T cells CD4 memory resting, mast cells resting, eosinophils, M2 macrophages and mast cells activated were significantly positively correlated with PRDM5 expression (P < 0.05), while regulatory T cells, monocytes and dendritic cells negatively correlated with PRDM5 expression (P < 0.05). CONCLUSION: PRDM5 can be used as a biomarker to predict the survival of ESCC patients. Furthermore, PRDM5 expression in ESCC cells may affect WNT/ß-catenin signaling pathways, thus further affect the ESCC cell proliferation, migration, and invasion capacity.

[Comparison of internal quality and nutrients between male and female Eupolyphaga sinensis].

According to the Chinese Pharmacopoeia(2020 edition), Eupolyphaga Steleophaga is prepared from female Eupolyphaga sinensis. To explore the quality difference between male and female E. sinensis, the present study determined indexes in the Chinese Pharmacopoeia, anticoagulant activity, and content of primary metabolites, amino acids, and trace elements in male and female E. sinensis before and after sexual maturity. The results showed that the content of ash, water, extract, and aflatoxin of the larvae and female adults of E. sinensis met the Chinese Pharmacopoeia standards, while the content of ash and extract of male adults failed to meet the standards. After sexual maturity, the content of water-soluble proteins, crude fat, and extract of female E. sinensis was higher than that of the other three groups(P<0.05). Although the content of total protein, total amino acid(TAA), essential amino acid(EAA), non-essential amino acid(NEAA), branched-chain amino acid(BCAA), functional amino acid(FAA), and delicious amino acid(DAA) of male adults was higher than that of the other groups(P<0.05), the anticoagulant activity was the weakest(P<0.05). Before sexual maturity, the content of Fe in E. sinensis larvae was significantly higher than that in adults(P<0.05). The content of K and Mg in female larvae was the highest, while the content of Ca was the lowest(P<0.05). The content of Cu in male adults was higher than that in the other three groups(P<0.05). In conclusion, except for male adults, the larvae and female adults of E. sinensis meet the Chinese Pharmacopoeia standards. There is no difference in the internal quality of male and female E. sinensis larvae. It is recommended to collect female adults as much as possible. Male adults are rich in proteins and amino acids with high fibrinolytic activities, which can be developed in the future.

Clinical Significance of Nutrition and Inflammation in Esophageal Cancer Patients with Surgery: A Meta-Analysis.

Many studies have reported that the geriatric nutritional risk index (GNRI) and C-reactive protein to albumin ratio (CAR) may be associated with prognosis of esophageal cancer (EC); however, the results are inconsistent. Therefore, we performed a meta-analysis to evaluate the effect of preoperative GNRI and CAR on the prognosis of EC. PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to analyze the relationship between GNRI/CAR and prognosis. Publication bias was estimated using Begg's funnel plot asymmetry test and Egger's test. A total of 21 studies comprising 5,018 patients were included in the meta-analysis. A decreased GNRI was significantly associated with poorer overall survival (OS) (HR = 1.808, 95% CI: 1.489-2.196, P < 0.001) and cancer-specific survival (CSS) (HR = 1.769, 95% CI: 1.193-2.624, P = 0.005), and an increased CAR was significantly associated with lower OS (HR = 2.179, 95% CI: 1.587-2.992, P < 0.001), CSS (HR = 1.733, 95% CI: 1.333-2.253, P < 0.001), and recurrence-free survival (HR = 2.178, 95% CI: 1.328-3.573, P = 0.002). Thus, preoperative GNRI and CAR may be noninvasive and powerful tools for predicting survival outcomes in patients with EC.

Analysis of Distributions of HPV Infection in Females with Cervical Lesions in the Western District of Beijing Chaoyang Hospital.

Objective: To analyze the distribution of human papilloma virus (HPV) infection in women with cervical lesions of different grades and analyze the relationship of high-risk HPV and cervical lesions in order to facilitate targeted prevention. Methods: The infection status of HPV subtype was statistically analyzed in patients who underwent colposcopy examination from April 2017 to June 2019. Results: The infection rate of HPV was 81.4% in chronic cervicitis, 82.9% in 1ow-grade squamous intraepithelial lesion (LSIL), 63.7% in HSIL (high-grade squamous intraepithelial lesion), and 50% in cervical squamous cell carcinoma (CSCC). Among the 16 high-risk HPV types, the top six HPV types with the comprehensive infection rates were HPV16 > HPV52 > HPV58 > HPV18 > HPV51 > HPV53 in turn, and the infection rates were 23.3%, 14.8%, 13.3%, 9.8%, 9.2%, and 8.8%, respectively. The infection rates of HPV16 in chronic cervicitis group, LSIL group, and HSIL group were significantly different. There was no significant difference in the injection rates of HPV52, HPV58, and HPV18 among the three groups. HPV infection rates were highest in the 31-40 years old group, followed by the 41-50 years old group. Conclusion: The distribution of different types of HPV varies in different tissue types, which can be used to develop relevant vaccines to achieve better prevention and treatment of cervical cancer.

Preservation Analysis on Spatiotemporal Specific Co-expression Networks Suggests the Immunopathogenesis of Alzheimer's Disease.

The occurrence and development of Alzheimer's disease (AD) is a continuous clinical and pathophysiological process, molecular biological, and brain functional change often appear before clinical symptoms, but the detailed underlying mechanism is still unclear. The expression profiling of postmortem brain tissue from AD patients and controls provides evidence about AD etiopathogenesis. In the current study, we used published AD expression profiling data to construct spatiotemporal specific coexpression networks in AD and analyzed the network preservation features of each brain region in different disease stages to identify the most dramatically changed coexpression modules and obtained AD-related biological pathways, brain regions and circuits, cell types and key genes based on these modules. As result, we constructed 57 spatiotemporal specific networks (19 brain regions by three disease stages) in AD and observed universal expression changes in all 19 brain regions. The eight most dramatically changed coexpression modules were identified in seven brain regions. Genes in these modules are mostly involved in immune response-related pathways and non-neuron cells, and this supports the immune pathology of AD and suggests the role of blood brain barrier (BBB) injuries. Differentially expressed genes (DEGs) meta-analysis and protein-protein interaction (PPI) network analysis suggested potential key genes involved in AD development that might be therapeutic targets. In conclusion, our systematical network analysis on published AD expression profiling data suggests the immunopathogenesis of AD and identifies key brain regions and genes.

Prevalence and Correlates of Anxiety and Depressive Symptoms in Patients With and Without Multi-Drug Resistant Pulmonary Tuberculosis in China.

China is still among the 30 high-burden tuberculosis (TB) countries in the world and TB remains a public health concern. TB can be a cause of mental illness, with prolonged treatment and several anti-TB drugs leading to extreme mental health problems such as depression and anxiety in TB patients. To investigate the prevalence of anxiety and depressive symptoms among TB patients, and to explore whether drug resistance is a covariate for depressive and anxiety symptoms, a total of 167 pulmonary tuberculosis patients were enrolled in this study, which was conducted from January 1 to September 30, 2020. Data were collected, using a structured questionnaire with a demographic component, the Hospital Anxiety and Depression Scale (HADS), General Health Questionnaire 20 (GHQ-20), the Tuberculosis-related Stigma Scale (TSS) and the Social Support Rating Scale (SSRS). Association between demographics, disease/treatment characteristics, stigma, social support, and anxiety/depression symptoms were investigated either based on Pearson's correlation coefficient or group comparisons based on independent t-test (or Mann-Whitney U-test) Multiple linear stepwise regression analysis was used for determining the predictors of anxiety and depression. The results showed that multi-drug resistance pulmonary tuberculosis patients were associated with anxiety challenges. Multiple linear regression analysis indicated that self-esteem accounted for 33.5 and 38% of the variation in anxiety and depression, respectively. This shows that among tuberculosis patients, self-esteem is the factor that could most explains the depression and anxiety symptoms of patients, suggesting that we may could through improving the environment, society, and family respect and tolerance of tuberculosis patients, thereby improving the mental health of tuberculosis patients.

Transcriptome analysis reveals roles of polian vesicle in sea cucumber Apostichopus japonicus response to Vibrio splendidus infection.

Polian vesicle is originally regarded as a hematopoietic and inflammatory response organ in sea cucumber by the operations of cell depletion and heterogeneous cells injection, respectively. In the present study, to reveal the role and immune mechanisms of polian vesicle in response to pathogen, Vibrio splendidus, we first performed a comparative transcriptome analysis for the cells from polian vesicle wall in V. splendidus-challenged Apostichopus japonicus through RNA high-throughput sequencing technology. Briefly, 465,356,848 clean reads were obtained after cleaning up low-quality reads in total. Approximately 73% of the sequenced reads could be aligned to the reference genome of A. japonicus. The DEGs of CG (control group) vs TG 24 h (24 h post-infection group), CG vs TG 72 h (72 h post-infection group) and TG 24 h vs TG 72 h were 3762, 1391 and 3258, respectively. Gene Ontology (GO) annotation assay revealed that those genes associated with the processes such as cell process, cell, binding and catalytic activity were significantly induced in all three groups post V. splendidus infection. KEGG enrichment analysis suggested the DEGs in TG 24 h were enriched in Toll-like receptor (TLR) signaling pathway, complement and coagulation cascades, antigen processing and presentation and IL-17 signaling pathway compared with that in CG, while the pathways including ribosome biogenesis in eukaryotes, DNA replication, and cell cycle related with cell proliferation were mainly enriched in TG 72 h than that of CG. Furthermore, six important DEGs were chosen and showed the consistent expression patterns with the results of RNA-seq by qPCR. Overall, our analysis towards the current data demonstrates that polian vesicle may play an essential role in the regulation of immune response in A. japonicus and provide new insights into hematopoietic function of polian vesicle in response to pathogen infection.

Autoantibody against the Rab6A/Rab6B in primary autoimmune cerebellar ataxia associated with Sjogren's syndrome: A case report.

In the current study we report a novel autoantibody against Purkinje cells in a patient with primary autoimmune cerebellar ataxia (PACA) associated with Sjogren's syndrome (SS). Tissue-based indirect immunofluorescence assay (TBA) of the patient's serum and cerebrospinal fluid (CSF) revealed IgG antibody to Purkinje cells and the granular layer of the rat cerebellum. Rab6A was identified as autoantigen by mass spectrometry (MS) and Western blotting, and the interactions between Rab6A or its homologous Rab6B and autoantibody in patient serum were verified by recombinant cell-based assay (CBA) and neutralization experiments. This autoantibody may represent a novel biomarker in the diagnosis of PACA.