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Parkinson’s disease (PD) is a disease that involves brain damage and is associated with neuroinflammation, mitochondrial damage, and cell aging. However, the pathogenic mechanism of PD is still unknown. Sequencing data and proteomic data can describe the fluctuation of molecular abundance in diseases at the mRNA level and protein level, respectively. In order to explore new targets in the pathogenesis of PD, the study analyzed molecular changes from the database by combining transcriptomic and proteomic analysis. Differentially expressed genes and differentially abundant proteins were summarized and analyzed. Enrichment and cluster analysis emphasized the importance of neurotransmitter release, mitochondrial damage, and vesicle transport. The molecular network revealed a subnetwork of 9 molecules related to SCNA and TH and revealed hub gene with differential expression at both mRNA and protein levels. It found that ACHE and CADPS could be used as new targets in PD, emphasizing that impaired nerve signal transmission and vesicle transport affect the pathogenesis of PD. Our research emphasized that the joint analysis and verification of transcriptomics and proteomics were devoted to understanding the comprehensive views and mechanism of pathogenesis in PD.

Excessive cholesterol in the liver is harmful for our health and may cause many diseases, such as fatty liver disease. Many studies in human and animal models have reported that royal jelly (RJ) can be used to treat atherosclerosis. However, the real mechanisms behind this action is unclear. In this study, we investigated the efficacy of RJ on gene expression of squalene epoxidase (SE) a major enzyme involved in cholesterol biosynthesis in HepG2 cells. We found that the expression of SE was decreased in response to RJ treatment. We also found that the origin of the RJ affected its strength. To find out the active fraction of RJ in cholesterol suppression, we separated RJ into two parts based on the molecular weights using ultrafiltration membrane. We found that the fraction10kDa from RJ had comparable effect on SE expression, especially its water-soluble part. Taken together, we think RJ suppresses cholesterol by decreasing SE gene expression in liver. The active fraction of RJ in this action is10kDa in water-soluble form.

An [MS4Cux]x−2 cluster unit (M = W, Mo, x = 1, 2,…6) is a kind of heterothiometallic unit of versatile connectivities and geometries for building metal–organic frameworks (MOFs) of intriguing structures and properties. We here report two MOFs based on the [WS4Cux]x−2 unit and a MOF based on the [MoS4Cux]x−2 unit with 9,10-di(pyridin-4-yl)anthracene (dpa). 1 contains penta-nuclear [WS4Cu4]2+ units, which act as tetrahedral nodes and are linked by dpa ligands into a 5-fold interpenetrated diamondoid network. 2 contains an unprecedented [WS4Cu6]4+·I−·[WS4Cu6]4+ unit where two hepta-nuclear [WS4Cu6]4+ units are bridged by an I− ion, which acts as a 7-connector node, leading to a 3D network with the rare hxg-d topology. 3 is built from penta-nuclear [MoS4Cu4]2+ units and dpa ligands and is isostructural to 1. The structural difference between 1 and 2 should come from the isomerization of the [WS4Cux]x−2 unit in the synthesis processes, and we found that temperature was much more important than other factors, such as solvent, the halide anion of the CuI salt and the ratio of [NH4]2WS4 to CuI salt, for the isomerization of the [WS4Cux]x−2 unit in the formation of 1 and 2.

Three coordination polymers (CPs) were synthesized by using CdII, fluorescent 9,10-di(4-pyridyl)anthracene (dpa), and cyclohexane-1,4-dicarboxylic acid (H2cda), and they are [Cd2(dpa)2(cda)Cl2]n (1), [Cd(dpa)2(cda)]n (2) and [Cd(dpa)(cda)(H2O)]n (3). Both 1 and 2 are fluorescent and contain nonporous layers. 3 is an isomer of 2 and contains a porous diamondoid network. Fluorescent mixed matrix membranes were prepared by dispersing the particles of 1 or 2 within the matrix of polymethyl methacrylate, and showed high sensitivity and selectivity for detecting Cr2O72- in water. Both stability and recyclability of the MMMs were remarkably higher than those of the CP powders.

A simple, accurate and sensitive method of high performance liquid chromatography (HPLC) with diode array detector was established to identify Xinfeng capsules and systematically evaluated its quality, based on chromatographic fingerprint integrated with the similarity analysis, hierarchical cluster analysis and the quantitative analysis of multi-components by single marker (QAMS). In this study, 18 peaks were selected as the common peaks to evaluate the similarities among different batches (S1–S10) of Xinfeng capsules samples, which were manufactured in the First Affiliated Hospital of Anhui University of Chinese Medicine with a three-year span. Compared to control fingerprint, the similarities values for 10 batches of samples were more than 0.90. Moreover, by analyzing the reference of astragalus, the chromatogram of astragalus was developed, and 10 common peaks of astragalus were identified. More importantly, simultaneous quantification of three markers in Xinfeng capsule, including Calycosin-7-glucoside, calycosin and Formononetinaldehyde was performed, the three constituents showed good regression (R > 0.999) within linear ranges, and their recoveries were within the range of 97.6–101.5%. The validation results showed that the developed method was specific, accurate, precise and robust. This study demonstrated that the developed method offers an efficient, reliable and practical approach for systematic quality evaluation of Xinfeng capsule.

Background and purpose This study aims to explore the mechanism underlying the up-regulation of major histocompatibility complex (MHC) proteins in glomerular endothelial cells in 5/6 nephrectomy mice. Experimental approach C57/BL6 mice were randomly allocated to sham-operated (2K) and 5/6 nephrectomy (5/6Nx) groups. Mouse splenic lymphocytes, from either syngeneic or allogeneic background, were injected into 5/6Nx mice after total body irradiation. Human glomerular endothelial cells (HGECs) were cultured for experiments in vitro. Western blots, PCR, immunohistochemical and fluorescent staining were used, along with assays of tissue cytokines, lymphocyte migration and renal function. Key results Four weeks after nephrectomy, expression of both mRNA and protein of MHC II, CD80, and CD86 were increased in 5/6Nx glomerular endothelial cells. After total body irradiation, 5/6Nx mice injected with lymphocytes from Balb/c mice, but not those from C57/BL6 mice, exhibited increased creatinine levels, indicating that allograft lymphocyte transfer impaired renal function. In HGECs, the protein levels of MHC and MHC Class II transactivator (CIITA) were increased by stimulation with TNF-α or IFN-γ, which promoted human lymphocytes movement. These increases were reduced by JNK inhibitors. In the 5/6Nx mice, JNK inhibition down-regulated MHC II protein in glomerular endothelial cells, suggesting that JNK signalling participates in the regulation of MHC II protein. Conclusion and implications Chronic inflammation in mice subjected to nephrectomy induces the up-regulation of MHC molecules in glomerular endothelial cells. This up-regulation is reduced by inhibition of JNK signalling.

Cancer cells are defective in DNA repair, so they experience increased DNA strand breaks, genome instability, gene mutagenesis, and tumorigenicity; however, multiple classic DNA repair genes and pathways are strongly activated in malignant tumor cells to compensate for the DNA repair deficiency and gain an apoptosis resistance. The mechanisms underlying this phenomenon in cancer are unclear. We speculate that a key DNA repair gene or signaling pathway in cancer has not yet been recognized. Here, we show that the lipogenic liver X receptor (LXR)-sterol response element binding factor-1 (SREBF1) axis controls the transcription of a key DNA repair gene polynucleotide kinase/phosphatase (PNKP), thereby governing cancer cell DNA repair and apoptosis. Notably, the PNKP levels were significantly reduced in 95% of human pancreatic cancer (PC) patients, particularly deep reduction for sixfold in all of the advanced-stage PC cases. PNKP is also deficient in three other types of cancer that we examined. In addition, the expression of LXRs and SREBF1 was significantly reduced in the tumor tissues from human PC patients compared with the adjacent normal tissues. The newly identified LXR-SREBF1-PNKP signaling pathway is deficient in PC, and the defect in the pathway contributes to the DNA repair deficiency in the cancer. Strikingly, further diminution of the vulnerable LXR-SREBF1-PNKP signaling pathway using a small molecule triptonide, a new LXR antagonist identified in this investigation, at a concentration of 8 nM robustly activated tumor-suppressor p53 and readily elevated cancer cell DNA strand breaks over an apoptotic threshold, and selectively induced PC cell apoptosis, resulting in almost complete elimination of tumors in xenograft mice without obvious complications. Our findings provide new insight into DNA repair and apoptosis in cancer, and offer a new platform for developing novel anticancer therapeutics.

BACKGROUND: Although a varicella vaccine has been available in China since 1998 in the private sector, varicella outbreaks and breakthrough varicella (BV) still occur. In 2018, four varicella outbreaks with high BV rate sequentially occurred in four schools in Lu'an, sparking local public health authority's concerns on the varicella vaccine. Therefore, we conducted this investigation to evaluate varicella vaccine effectiveness (VE), characterize BV, and detect potential risk factors associated with BV. METHODS: This was a three-stage study. First, a retrospective cohort study was done in each school to estimate the VEs of varicella vaccine during outbreaks. Second, a descriptive epidemiological method was used to describe the characteristics of the four outbreaks and to compare the clinical characteristics between the BV cases and unvaccinated varicella cases. To identify the risk factors associated with BV, we conducted an unmatched case-control study in the third stage of the study. RESULTS: A total of 199 cases were identified among four outbreaks, and the overall attack rate was 14%. Of 1203 students with available vaccination information, 822 (68%) were vaccinated at least once. The overall VEs among four outbreaks ranged from 19% to 69%, whereas the VE against moderate or severe varicella ranged from 74% to 90%. Compared with unvaccinated varicella cases, the moderate or severe varicella (p

Metal–organic frameworks (MOFs) or porous coordination polymers (PCPs) with tunable pore sizes, shapes and functionalities have excellent prospects in many applications, such as carbon capture. Molecular sieving can usually enable very high CO2 adsorption selectivity but has rarely been achieved, because it is difficult to precisely control the pore size in the range of 3–4 A. We report here three MOF isomers built from CdII, terephthalic acid and 3,6-di(pyridin-4-yl)-1,2,4,5-tetrazine with the same stoichiometric ratio, among which 1 and 2 are framework-catenation isomers and 2 and 3 are framework-topological isomers. 1 contains 2-fold interpenetrated networks (topology of pcu) and 1D ultra-micropores and shows highly selective adsorption of CO2 over N2 and CH4, which is mainly ascribed to the molecular sieving effect of the framework. 2 contains a pcu network with 3D interconnected micropores, and 3 contains a kag network with much larger pores of 15 A. Framework isomerization, in this case, was shown to be a feasible way of tuning the pore size of a MOF for selective CO2 adsorption. The effects of hydrothermal reaction conditions and additives on the structures and the formation of the MOF isomers were also studied.

Tetrazole-based molecules have numerous bridging coordination modes which afford great synthetic possibilities for the preparation of porous metal-tetrazolate architectures for many applications, such as carbon capture. We reported here three tetrazole-based MOFs: 1, {[Cu12(ttz)8/3Cl5(H2O)16]11+·11Cl-}n (H3ttz = N2,N4,N6-tris(4-(1H-tetrazol-5-yl)phenyl)-1,3,5-triazine-2,4,6-triamine), contains highly positively charged Cu12 clusters and the largest mesopores (32 A) among the reported MOFs based on a tri-topic tetrazole ligand. 2 and 3 are two MOF isomers built by using CuII and 2-(1H-tetrazol-5-yl)pyrimidine. 3 contains nonporous layers, while 2 contains 1D channels and showed high selectivity for adsorbing CO2, which should be attributed to the high density of free nucleophilic tetrazole N atoms on the pore surfaces. We found that the isomerization between 2 and 3 was caused by the diverse coordination modes of tetrazole-based ligands and can be controlled in synthesis processes.

As the pearl of China’s intangible cultural heritage, there are still many difficulties in the development of opera. This paper takes Meilin opera of Sanming City, Fujian Province, as an example, analyzes the current situation of the inheritance of Meilin opera in the context of “Internet+”, and compares it with the development of similar operas, and finally discusses the new strategies for the protection and development of intangible cultural heritage such as opera from the perspective of communication path and communication mechanism.

Objective: To observe the prognosis of RRDCD after vitrectomy using OCTA.Methods: We gathered information of three groups including RRDCD group, RRD group and normal control group respectiv...

BACKGROUND This study identified microRNAs (miRNAs) and mRNAs associated with Compound Longmaining (CLMN) treatment of acute myocardial infarction (AMI). Our results provide a theoretical framework to guide AMI treatment and improve myocardial injury. MATERIAL AND METHODS The myocardial tissues of the sham operation group (S), the model group (M), and the CLMN treatment group (T) were obtained. The mRNA and miRNA expression profiles were identified using RNA-sequencing analysis. The sequencing results were verified by quantitative real-time PCR (qRT-PCR). Bioinformatics was used to predict the function of differentially expressed genes (DEGs) and related signal transduction pathways. The target genes of miRNAs were predicted by software analysis, and the relationship between miRNA and mRNA was studied by network analysis. RESULTS RNA-sequencing revealed 22 differentially expressed miRNAs (DEMs) and 76 DEGs in myocardial tissue. Six DEMs and 9 DEGs were randomly selected for qRT-PCR validation, and corroborating results were obtained. The results of Gene ontology (GO) showed that DEGs participated in different biological processes. Through the combined analysis of miRNAs and mRNAs expression, it was confirmed that a single miRNA is involved in the regulation of multiple genes, and also multiple miRNAs can target one gene. CONCLUSIONS The analysis based on the miRNA-mRNA network can not only help to elucidate the potential molecular mechanism of CLMN treatment of AMI, but can also help in identifying novel therapeutic targets.

This study was aimed at exploring the application value of transcranial Doppler (TCD) based on artificial intelligence algorithm in monitoring the neuroendocrine changes in patients with severe head injury in the acute phase; 80 patients with severe brain injury were included in this study as the study subjects, and they were randomly divided into the control group (conventional TCD) and the experimental group (algorithm-optimized TCD), 40 patients in each group. An artificial intelligence neighborhood segmentation algorithm for TCD images was designed to comprehensively evaluate the application value of this algorithm by measuring the TCD image area segmentation error and running time of this algorithm. In addition, the Glasgow coma scale (GCS) and each neuroendocrine hormone level were used to assess the neuroendocrine status of the patients. The results showed that the running time of the artificial intelligence neighborhood segmentation algorithm for TCD was 3.14 ± 1.02 s , which was significantly shorter than 32.23 ± 9.56 s of traditional convolutional neural network (CNN) algorithms ( P < 0.05 ). The false rejection rate (FRR) of TCD image area segmentation of this algorithm was significantly reduced, and the false acceptance rate (FAR) and true acceptance rate (TAR) were significantly increased ( P < 0.05 ). The consistent rate of the GCS score and Doppler ultrasound imaging diagnosis results in the experimental group was 93.8%, which was significantly higher than the 80.3% in the control group ( P < 0.05 ). The consistency rate of Doppler ultrasound imaging diagnosis results of patients in the experimental group with abnormal levels of follicle stimulating hormone (FSH), prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), and thyroid stimulating hormone (TSH) was significantly higher than that of the control group ( P < 0.05 ). In summary, the artificial intelligence neighborhood segmentation algorithm can significantly shorten the processing time of the TCD image and reduce the segmentation error of the image area, which significantly improves the monitoring level of TCD for patients with severe craniocerebral injury and has good clinical application value.

Background. The impact of corticosteroids on severe patients with coronavirus disease 2019 (COVID-19)/ chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate effect of corticosteroid on these subgroup patients.Methods. In this retrospective multicenter study including 5447 confirmed COVID-19 patients from Jan 1, 2020 to Apr 18, 2020, severe patients with COVID-19/HBV co-infection were identified. To minimize the bias of confounding variables on effect of corticosteroid treatment, inverse probability of treatment weighting (IPTW) based on propensity score was employed.Results. The prevalence of HBV co-infection in hospitalization COVID-19 patients was 4.1%. 105 severe patients with COVID-19/HBV co-infection were enrolled (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. Corticosteroid treatment was associated with high D-dimer level, neutrophil count (all PP=0.043). Corticosteroids might delay SARS-CoV-2 viral RNA clearance (OR, 4.963, 95%CI, 2.717-9.065, P P P 1µg/ml) (OR, 10.686, 95%CI, 2.421-47.159, P=0.002) and corticosteroid therapy (OR, 11.236, 95%CI, 1.273-99.154, P=0.029) were independently associated with 28-day mortality. Methylprednisolone dose per day and cumulative dose in non-survivors was significantly higher than in survivors.Conclusions. In severe patients with COVID-19/HBV co-infection, corticosteroid treatment may increase mortality. Therefore, corticosteroid therapy should be prescribed with caution in the subset of patients.