his is the data of our clinical trial of the traditional Chinese exercise Liu-zi-jue for the respiratory symptoms and physical and mental health evaluation of patients with mild COVID-19, including the basic information of the patients and the original data of the score
The intracellular pathogen Legionella pneumophila hijacks the endoplasmic reticulum (ER)-derived vesicles to create an organelle designated Legionella-containing vacuole (LCV) required for bacterial replication. Maturation of the LCV involved acquisition of Rab1, which is mediated by the bacterial effector protein SidM/DrrA. SidM/DrrA is a bifunctional enzyme having the activity of both Rab1-specific GDP dissociation inhibitor (GDI) displacement factor (GDF) and guanine nucleotide exchange factor (GEF). LidA, another Rab1-interacting bacterial effector protein, was reported to promote SidM/DrrA-mediated recruitment of Rab1 to the LCV as well. Here we report the crystal structures of LidA complexes with GDP- and GTP-bound Rab1 respectively. Structural comparison revealed that GDP-Rab1 bound by LidA exhibits an active and nearly identical conformation with that of GTP-Rab1, suggesting that LidA can disrupt the switch function of Rab1 and render it persistently active. As with GTP, LidA maintains GDP-Rab1 in the active conformation through interaction with its two conserved switch regions. Consistent with the structural observations, biochemical assays showed that LidA binds to GDP- and GTP-Rab1 equally well with an affinity approximately 7.5 nM. We propose that the tight interaction with Rab1 allows LidA to facilitate SidM/DrrA-catalyzed release of Rab1 from GDIs. Taken together, our results support a unique mechanism by which a bacterial effector protein regulates Rab1 recycling.
Herein, we report the discovery of a series of new P300/CBP-associated factor (PCAF) bromodomain (BRD) inhibitors, which were obtained through a hit discovery process and subsequent structure-based optimization and structure–activity relationship analyses toward a retrieved hit compound (12). Among these inhibitors, (R,R)-36n is the most potent one with an IC50 of 7 nM in homogeneous time-resolved fluorescence assay and a KD of 78 nM in isothermal titration calorimetry assay. This compound also exhibited activity against GCN5 and FALZ, but weak or no activity against other 29 BRD proteins and 422 kinases, indicating considerable selectivity. X-ray cocrystal structure analysis revealed the molecular interaction mode and the precise stereochemistry required for bioactivity. Cellular activity, preliminary RNA-seq analysis, and pharmacokinetic properties were also examined for this compound. Collectively, this study provides a versatile tool molecule to explore molecular mechanisms of PCAF BRD regulation and also offers a new lead compound for drug discovery targeting PCAF.
CD4+T cell epitopes plays a key role in anti-tuberculosis (TB) immunity, CD4+T cell epitopes suitable for the domestic population are lacking. Therefore, we predicted and identified novel CD4+T cell epitopes.The bioinformatics software, namely, DNAStar (DNASTAR of the United States), SYFPEITHI (INTERFACTORS INSTITUT Für ZELL Biologie of Germany), RANKPEP, and NetMHC IIpan (National Cancer Institute, United States of America), were used to comprehensively predict the CD4+T cell immune epitope of Mycobacterium TB, and the predicted epitope polypeptide was synthesized by the standard Fmoc scheme. The proliferation of PBMC and CD4+T cells stimulated by peptides was preliminarily detected by the CCK8 method. Then, the candidate polypeptides screened out by the CCK8 method were verified again by the BrdU assay, and flow cytometry was performed to analyze further the extent of their stimulation on the proliferation of CD4+T cells. The changes in the secreted cytokines IFN-γ, TNF-α, IL-2, and IL-10 before and after the candidate polypeptide stimulation of CD4+T lymphocytes were detected by ELISA. The preliminary humoral immunity test was conducted by indirect ELISA to evaluate the serological diagnostic value of the CD4+T cell epitope polypeptide.In this study, 5 novel candidate CD4+T cell epitope polypeptides with the amino acid sequences of LQGQWRGAAGTAAQA, PVTLAETGSTLLYPL, AAAWGGSGSEAYQGV, QFVYAGAMSGLLDPS, and KAALTRTASNMNAAA and others that have not been reported in the research were predicted. For convenience, the 5 candidates were successively named as P39, P50, P40, P185, and P62. P39, P62, and the mixed peptide P39+P62 could effectively induce the proliferation of CD4+T cells and increase the secretion of IFN-γ, TNF-α, and IL-2 from the CD4+T cells, while reducing the content of IL-10. The serological test showed that the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of P39 were 75%, 67.71%, and 0.844, respectively. The sensitivity, specificity, and AUC of P62 were 91.66%, 46.87%, and 0.649, respectively. The sensitivity of the mixed peptide P39+P62 was 95.83%, the specificity was 97.91%, and the AUC was 0.793.The P39 and P62 polypeptides were predicted and identified as potential CD4+T cell immune epitope polypeptides of M. TB. The polypeptide had better diagnosis effect, which provided potential candidate epitope polypeptides for the development of TB-specific diagnosis reagents and novel TB epitope vaccines.
To evaluate the prevalence of avian influenza virus in various environment and the influence factors for subtype H7 prevalence in live poultry markets.We collected environmental samples from various environments across 11 cities of Zhejiang province between October 2014 and March 2015. Cage surface swabs, chopping board surface swabs, feces, water for cleaning, drinking water and swabs of other surfaces were collected. A total of 6 457 samples were collected, including 4 487 samples from poultry markets, 820 samples from poultry farms, 715 samples from backyard poultry pens, 118 samples from poultry processing factories, 118 samples from wild bird habitats and 86 samples from other sites. The chi-squared test was used to compare virus prevalence among sample types, sites types, and poultry markets types. Binary logistic regression was used to analyze factors on H7 subtype prevalence in poultry markets.Of 6 457 samples, 32.54% (2 101) samples were positive for avian influenza, with 3.67% (237) positive for H5 subtype, 12.02%(776) positive for H7 subtype, 11.77%(760) positive for H9 subtype. Of 237 live poultry markets, 33.8% (80) were positive for H7 subtype. The prevalence of influenza A in poultry processing factories was the highest at 43.72% (101/231) (χ(2)=737.80, P<0.001). Poultry markets were contaminated most seriously by subtype H5/H7/H9 with the prevalence of 27.55% (1 236/4 487) (χ(2)=436.37, P<0.001). Compared with markets with 1 type of poultry, OR was 4.58 (95%CI: 1.63-12.87) for markets with ≥2 types of poultry.Live poultry markets and poultry processing factories were contaminated most seriously by avian influenza. The types of poultry might be the factor which influenced the subtype H7 prevalence in poultry markets.
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