IL-37 protects against airway remodeling by reversing bronchial epithelial-mesenchymal transition via IL-24 signaling pathway in chronic asthma.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of tissue fibrosis, and increased IL-24 levels have been observed in the nasal secretions and sputum of asthmatic patients. However, the role of IL-24 in asthmatic airway remodeling, especially in EMT, remains largely unknown. We aimed to explore the effect and mechanism of IL-24 on EMT and to verify whether IL-37 could alleviate IL-24-induced EMT in chronic asthma. METHODS: BEAS-2B cells were exposed to IL-24, and cell migration was assessed by wound healing and Transwell assays. The expression of EMT-related biomarkers (E-cadherin, vimentin, and α-SMA) was evaluated after the cells were stimulated with IL-24 with or without IL-37. A murine asthma model was established by intranasal administration of house dust mite (HDM) extracts for 5 weeks, and the effects of IL-24 and IL-37 on EMT and airway remodeling were investigated by intranasal administration of si-IL-24 and rhIL-37. RESULTS: We observed that IL-24 significantly enhanced the migration of BEAS-2B cells in vitro. IL-24 promoted the expression of the EMT biomarkers vimentin and α-SMA via the STAT3 and ERK1/2 pathways. In addition, we found that IL-37 partially reversed IL-24-induced EMT in BEAS-2B cells by blocking the ERK1/2 and STAT3 pathways. Similarly, the in vivo results showed that IL-24 was overexpressed in the airway epithelium of an HDM-induced chronic asthma model, and IL-24 silencing or IL-37 treatment could reverse EMT biomarker expression. CONCLUSIONS: Overall, these findings indicated that IL-37 mitigated HDM-induced airway remodeling by inhibiting IL-24-mediated EMT via the ERK1/2 and STAT3 pathways, thereby providing experimental evidence for IL-24 as a novel therapeutic target and IL-37 as a promising agent for treating severe asthma.

Microbial Contamination Characteristics on Touch Surfaces in Outpatient Self-Service Facilities.

BACKGROUND: With the development of science and technology, self-service facilities have been widely used in hospitals. This study aimed to assess the microbial contamination characteristics on touch surfaces in outpatient, self-service facilities from Monday to Friday. METHODS: Touch surfaces in outpatient facilities were swabbed and surveyed for total microbial growth before and after work every morning. Selected bacteria were identified to screen for pathogenic organisms. RESULTS: There were 360 samples collected, 87 samples (24.2%) were culture-positive. Staphylococcus species were the main microbial contamination. The three most common bacteria were S. hominis, S. epidermidis and S. hemolyticus. After work, more microbial contamination was found on Monday (p = 0.029). There was no difference in sample positive rates between self-service facilities and manual service area. Although, the antibiotic resistance patterns of different staphylococcus species were different, the overall drug resistance rate is low. Only one S. aureus was methicillin-Sensitive S. aureus. CONCLUSIONS: The self-service facilities' touch surfaces microbial contamination were similar to manual service area, but the more used, the more microbial contamination was found. Hospitals should enhance cleaning times of self-service facilities to keep them clean, especially on Mondays.

IL-37 alleviates house dust mite-induced chronic allergic asthma by targeting TSLP through the NF-κB and ERK1/2 signaling pathways.

Interleukin (IL)-37 has been described as a negative regulator of immune responses and is critical for asthma pathogenesis, but the mechanisms behind the protective role of IL-37 against allergic asthma are less well understood. We show here that IL-37 administered intranasally inhibited house dust mite (HDM)-induced chronic airway eosinophilic inflammation, goblet cell hyperplasia, peribronchial collagen deposition and airway hyperresponsiveness (AHR) to methacholine. In contrast to a weakened Th2 response in the lung that was characterized by the downregulation of Th2-associated cytokines and chemokines in IL-37-treated mice, IL-37 has no effect on relevant markers of systemic Th2 immune including serum immunoglobulins expression and in vitro production of Th2-associated cytokines by splenocytes on HDM recall. We demonstrated that the production of thymic stromal lymphopoietin (TSLP) in the lung tissue was associated with IL-37. Importantly, compared with IL-37 alone, TSLP coadministration with IL-37 restored HDM-induced airway inflammation and structural alterations, increased AHR to methacholine and promoted Th2-associated cytokine production. We further found that IL-37 inhibited the induction of TSLP expression by the main antigen of house dust mite, Der p1, by suppressing NF-κB and extracellular signal regulated kinase 1/2 (ERK1/2) activation in human bronchial epithelial (16-HBE) cells in vitro. These data highlight the importance of TSLP in IL-37-mediated protective role in asthma. IL-37 might represent a useful innovative and alternative therapy to control TSLP production in the airway.

Total flavonoids from sea buckthorn ameliorates lipopolysaccharide/cigarette smoke-induced airway inflammation.

The total flavonoids from sea buckthorn (TFSB) exhibit a potent anti-inflammatory activity; however, the effect of TFSB on respiratory inflammatory disease is not fully known. The present study evaluated the potential of TFSB to prevent airway inflammation and the underlying mechanism. The results showed that TFSB remarkably inhibited lipopolysaccharide/cigarette smoke extract (LPS/CSE)-induced expression of IL-1ß, IL-6, CXCL1, and MUC5AC at both mRNA and protein levels in HBE16 bronchial epithelial cells. TFSB also decreased the production of PGE2 through inhibition the expression of COX2 in LPS/CSE-stimulated HBE16 cells. Furthermore, bronchoalveolar fluid and histological analyses revealed that LPS/cigarette smoke exposure-induced elevated cell numbers of neutrophils and macrophages in bronchoalveolar fluid, inflammatory cell infiltration, and airway remodeling were remarkably attenuated by TFSB in mice. Immunohistochemical results also confirmed that TFSB decreased the expression of IL-1ß, IL-6, COX2, CXCL1, and MUC5AC in LPS/CS-exposed mice. Mechanistically, TFSB blocked LPS/CSE-induced activation of ERK, Akt, and PKCα. Molecular docking further confirmed that the main components in TFSB including quercetin and isorhamnetin showed potent binding affinities to MAPK1 and PIK3CG, two upstream kinases of ERK and Akt, respectively. In summary, TFSB exerts a potent protective effect against LPS/CS-induced airway inflammation through inhibition of ERK, PI3K/Akt, and PKCα pathways, suggesting that TFSB may be a novel therapeutic agent for respiratory diseases.

Elevated Blood Urea Nitrogen-to-Serum Albumin Ratio as a Factor That Negatively Affects the Mortality of Patients with Hospital-Acquired Pneumonia.

This study aimed to evaluate the factors that affect 30-day mortality of patients with HAP. The data used in this study were collected from all HAP occurred in our hospital between January 2014 and December 2017. A total of 1158 cases were included. 150 (13.0%) of whom died within 30 days. This reported mortality identified by the univariate Cox regression analysis is found to have been affected by the following factors: age greater than 70 years, presence of diabetes mellitus and chronic obstructive pulmonary disease, gastric tube intubation, administration of proton-pump inhibitor, blood albumin level less than 30 g/l, elevated neutrophil-to-lymphocyte ratio, antibiotics therapy in the preceding 90 days, intensive care unit (ICU) admission, blood lymphocyte count less than 0.8 × 109/L, elevated blood urea nitrogen/albumin (BUN/ALB) level, and presence of multidrug-resistant (MDR) pathogens. In the second multivariate analysis, administration of proton-pump inhibitor, administration of antibiotics in the preceding 90 days, ICU admission, blood lymphocyte count less than 0.8 × 109/L, elevated BUN/ALB level, and presence of MDR pathogens were still associated with 30-day mortality. The area under the receiver operating characteristic curves in the BUN/ALB predicting 30-day mortality due to HAP was 0.685. A high BUN/ALB was significantly associated with a worse survival than a low BUN/ALB (P < 0.001). Therefore, an elevated BUN/ALB level is a risk factor for mortality on patients with HAP.

[Name standardization and variety arrangement of Chinese national "Qi medicinal herbs" based on VFP].

"Qi medicinal herbs" in China refers to a kind of regional national folk herbs related to the treatment of five labors and seven injuries,the last word of which is "Qi". Our study is to sort out and standardize the name and basic confused varieties through the establishment of " Qi medicinal herbs" VFP information database. " Qi medicinal herbs" variety sorting model of " literature research-variety survey-data mining-spatial distribution" was developed by means of literature analysis which the names and varieties of " Qi medicinal herbs" in the literature were summarized and sorted out. The relationship between the distribution of " Qi medicinal herbs" resources and the use of ethnic groups were visualized by Cytoscape 2. 8. 0 software. The information database of " Qi medicinal herbs" involved in 230 kinds of medicinal materials which including 211 species of plants( including varieties) from 66 families. Medicinal materials standard in China have 9 kinds of " Qi medicinal herbs". Among them,there are 31 kinds of " Qi medicinal herbs" with the confusion of " the different names of the same" and " the different substance of the same names". The most used ethnic groups are Tujia,Qiang and Miao. The main efficacy is clearing heat and detoxification,dispelling wind and removing dampness,etc.,and the main treatment is for injury,rheumatic arthralgia and so on. Names and varieties of " Qi medicinal herbs" among Chinese ethnic groups and folk are standardized and sorted out,which is served to promotethe " Qi medicinal herbs" reasonable protection and utilization of resources,and provide effective reference for exploring the information technology and geographical distribution of ethnic medicine and standardizing clinical medication.

Evolution and Function of the Populus SABATH Family Reveal That a Single Amino Acid Change Results in a Substrate Switch.

Evolutionary mechanisms of substrate specificities of enzyme families remain poorly understood. Plant SABATH methyltransferases catalyze methylation of the carboxyl group of various low molecular weight metabolites. Investigation of the functional diversification of the SABATH family in plants could shed light on the evolution of substrate specificities in this enzyme family. Previous studies identified 28 SABATH genes from the Populus trichocarpa genome. In this study, we re-annotated the Populus SABATH gene family, and performed molecular evolution, gene expression and biochemical analyses of this large gene family. Twenty-eight Populus SABATH genes were divided into three classes with distinct divergences in their gene structure, expression responses to abiotic stressors and enzymatic properties of encoded proteins. Populus class I SABATH proteins converted IAA to methyl-IAA, class II SABATH proteins converted benzoic acid (BA) and salicylic acid (SA) to methyl-BA and methyl-SA, while class III SABATH proteins converted farnesoic acid (FA) to methyl-FA. For Populus class II SABATH proteins, both forward and reverse mutagenesis studies showed that a single amino acid switch between PtSABATH4 and PtSABATH24 resulted in substrate switch. Our findings provide new insights into the evolution of substrate specificities of enzyme families.

Divergence in Enzymatic Activities in the Soybean GST Supergene Family Provides New Insight into the Evolutionary Dynamics of Whole-Genome Duplicates.

Whole-genome duplication (WGD), or polyploidy, is a major force in plant genome evolution. A duplicate of all genes is present in the genome immediately following a WGD event. However, the evolutionary mechanisms responsible for the loss of, or retention and subsequent functional divergence of polyploidy-derived duplicates remain largely unknown. In this study we reconstructed the evolutionary history of the glutathione S-transferase (GST) gene family from the soybean genome, and identified 72 GST duplicated gene pairs formed by a recent Glycine-specific WGD event occurring approximately 13 Ma. We found that 72% of duplicated GST gene pairs experienced gene losses or pseudogenization, whereas 28% of GST gene pairs have been retained in the soybean genome. The GST pseudogenes were under relaxed selective constraints, whereas functional GSTs were subject to strong purifying selection. Plant GST genes play important roles in stress tolerance and detoxification metabolism. By examining the gene expression responses to abiotic stresses and enzymatic properties of the ancestral and current proteins, we found that polyploidy-derived GST duplicates show the divergence in enzymatic activities. Through site-directed mutagenesis of ancestral proteins, this study revealed that nonsynonymous substitutions of key amino acid sites play an important role in the divergence of enzymatic functions of polyploidy-derived GST duplicates. These findings provide new insights into the evolutionary and functional dynamics of polyploidy-derived duplicate genes.

Treatment of allergic rhinitis with CpG oligodeoxynucleotides alleviates the lower airway outcomes of combined allergic rhinitis and asthma syndrome via a mechanism that possibly involves in TSLP.

PURPOSE: Thymic stromal lymphopoietin (TSLP) is a critical regulator of immune responses associated with Th2 cytokine-mediated inflammation. Intranasal administration of oligodeoxynucleotides with CpG motifs (CpG-ODNs) might improve lower airway outcomes of combined allergic rhinitis and asthma syndrome (CARAS), but the inherent mechanisms of CpG-ODNs are not well defined. This study investigated whether CpG-ODNs treated to upper airway could reduce lower airway TSLP expression as well as whether this reduction could contribute to the alleviation of lower allergic inflammation and airway hyper-reactivity (AHR) in CARAS mice. MATERIALS AND METHODS: Ovalbumin (OVA)-sensitized BALB/c mice were intranasal OVA exposure three times a week for 3 weeks. CpG-ODNs or an anti-TSLP mAb was administered to a subset of these mice 1 hour after intranasal OVA challenge, followed by 5 days of OVA aerosol challenge. The resulting immunological variables, nasal symptoms, and nasal mucosa and lung tissues pathology were evaluated. TSLP production in the lung tissues and bronchoalveolar lavage fluid (BALF) were determined by RT-PCR, western blotting or enzyme-linked immunosorbent assay. RESULTS: The CARAS mice exhibited overexpression of TSLP in the lung tissues and BALF, and also demonstrated significant increases in BALF and splenocyte Th2-associated cytokine production, serum OVA-specific IgE, nose and lung pathologies, and AHR. Intranasal administration of CpG-ODNs restored TSLP in the lower airway, and it significantly reduced the following parameters: Th2-type cytokine production levels; the percentage of eosinophils in the BALF; IL-4 and IL-5 concentrations in the supernatants of cultured splenic lymphocytes; serum OVA-specific IgE; peribronchial inflammation score in the lungs; and nose pathology and nasal symptoms. Similar results were obtained when the CARAS mice were treated with an anti-TSLP mAb to block intranasal TSLP activity. CONCLUSIONS: Treatment with intranasal CpG-ODNs improves lower airway immunological variable outcomes in the CARAS model via a mechanism that possibly involves in suppressing pulmonary TSLP-triggered allergic inflammation.

Functional divergence of the glutathione S-transferase supergene family in Physcomitrella patens reveals complex patterns of large gene family evolution in land plants.

Plant glutathione S-transferases (GSTs) are multifunctional proteins encoded by a large gene family that play major roles in the detoxification of xenobiotics and oxidative stress metabolism. To date, studies on the GST gene family have focused mainly on vascular plants (particularly agricultural plants). In contrast, little information is available on the molecular characteristics of this large gene family in nonvascular plants. In addition, the evolutionary patterns of this family in land plants remain unclear. In this study, we identified 37 GST genes from the whole genome of the moss Physcomitrella patens, a nonvascular representative of early land plants. The 37 P. patens GSTs were divided into 10 classes, including two new classes (hemerythrin and iota). However, no tau GSTs were identified, which represent the largest class among vascular plants. P. patens GST gene family members showed extensive functional divergence in their gene structures, gene expression responses to abiotic stressors, enzymatic characteristics, and the subcellular locations of the encoded proteins. A joint phylogenetic analysis of GSTs from P. patens and other higher vascular plants showed that different class GSTs had distinct duplication patterns during the evolution of land plants. By examining multiple characteristics, this study revealed complex patterns of evolutionary divergence among the GST gene family in land plants.

Functional divergence and catalytic properties of dehydroascorbate reductase family proteins from Populus tomentosa.

Dehydroascorbate reductase (DHAR) is a key enzyme in the ascorbate-glutathione cycle that maintains reduced pools of ascorbic acid and serves as an important antioxidant. In this study, to investigate functional divergence of plant DHAR family and catalytic characteristics of the glutathione binding site (G-site) residues of DHAR proteins, we cloned three DHAR genes (PtoDHAR1/2/3) from Populus tomentosa and predicted the G-site residues. PtoDHAR1 protein was localized in chloroplast, while PtoDHAR2/3 proteins showed cytosolic localizations. Three DHAR proteins showed different enzymatic activities, apparent kinetic characteristics, optimum T m and pH profiles, indicating their functional divergence. Cys20, Lys8, Pro61, Asp72 and Ser73 of PtoDHAR2 were predicted as G-site residues based on their N-terminal amino acid sequence identity and the available crystal structures of glutathione S-transferases. The biochemical functions of these residues are examined in this study through site-directed mutagenesis. The aforementioned five residues are critical components of active sites that contribute to the enzyme's catalytic activity. Cys20, Pro61 and Asp72 of PtoDHAR2 are also responsible for maintaining proper protein structure. This study provides new insights into the functional divergence of the plant DHAR family and biochemical properties of the G-site residues in plant DHAR proteins.

[Effects of chloride ion channel and its blockers on myocardial ischemia reperfusion arrhythmias in rabbits].

OBJECTIVE: To explore the impact of chloride ion channel and its blockers 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS), cyanato-stilbene-2, 2'-disulfonic acid (SITS) and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB) on arrhythmias caused by myocardial ischemia reperfusion. METHODS: A total of 40 rabbits were divided into control, ischemia reperfusion, DIDS low-dose, DIDS high-dose, SITS low-dose, SITS high-dose, NPPB low-dose and NPPB high-dose groups. Myocardial ischemia reperfusion model was established by ligation of anterior descending coronary artery. And standard limb lead II of electrocardiogram (ECG) was continuously monitored during the experimental process. Then comparisons of heart rate, ECG P wave, R wave, T wave, ST segment changes and arrhythmias score were made between the above groups. RESULTS: During 30-minute ischemia, compared with the control group, all other groups showed significantly decreased heart rate ((199.8 ± 4.0) - (253.6 ± 2.1) vs (267.0 ± 3.4), all P < 0.01), elevated ECG P wave ((0.216 ± 0.019) - (0.356 ± 0.024) vs (0.186 ± 0.019), all P < 0.01), R wave ((0.564 ± 0.017) - (1.138 ± 0.048) vs (0.506 ± 0.018), all P < 0.01), T wave ((0.542 ± 0.013) - (0.856 ± 0.045) vs (0.278 ± 0.015), all P < 0.01) and ST segment ((0.326 ± 0.027) - (0.668 ± 0.054) vs (0.024 ± 0.023), all P < 0.01) and increased arrhythmia score ((1.4 ± 0.5) - (4.6 ± 0.5) vs (0.4 ± 0.5), all P < 0.01). Compared with the ischemia reperfusion group, the above indices significantly improved in the intervention groups (heart rate: (214.8 ± 3.4) - (246.8 ± 4.0) vs (199.8 ± 4.0), all P < 0.01; P wave: (0.216 ± 0.019) - (0.316 ± 0.011) vs (0.356 ± 0.024), all P < 0.01; R wave: (0.564 ± 0.017) - (0.980 ± 0.035) vs (1.138 ± 0.048), all P < 0.01; T wave: (0.542 ± 0.013) - (0.792 ± 0.026) vs (0.856 ± 0.045), all P < 0.01; ST segment: (0.326 ± 0.027) - (0.596 ± 0.018) vs (0.668 ± 0.054), all P < 0.01; arrhythmia score: (1.4 ± 0.5) - (3.8 ± 0.4) vs (4.6 ± 0.5), all P < 0.01). Among which, the DIDS group was the best, followed by the SITS group and then the NPPB group. And the high-dose subgroups were better than those of the low-dose subgroups. During 60-minute reperfusion, the decreased heart rate upswing significantly in each group and the elevated P wave, R wave, T wave and ST segment fell back gradually. The DIDS group showed the most obvious amplitude change, followed by the SITS group and then the NPPB group. And the high-dose subgroups were better than those of the low-dose subgroups. The arrhythmia score during reperfusion showed the same trend. CONCLUSION: Chloride ion channel is involved in the generation of myocardial ischemia reperfusion arrhythmia.Early application of chloride ion channel blockers DIDS, SITS and NPPB may improve the ECG manifestations and reduce the degree of reperfusion arrhythmia.

The complete chloroplast genome of Salix lindleyana (salicaceae), a plateau plant species.

Salix lindleyana Wallich ex Andersson 1851 is a species of genus Salix which mainly grows on mountains above 3000 m at sea level in Qinghai-Tibetan Plateau (including the Himalayas and Hengduan Mountains). To determine its phylogenetic position within Salix, we reconstructed S. lindleyana complete chloroplast (cp) genome sequence by de novo assembly using whole-genome sequencing data. The completed chloroplast genome was 155,304 bp, with a total GC content of 36.7%. It had a very typical tetrad structure, including a large single-copy (LSC) region of 84,539 bp, a small single-copy (SSC) region of 16,161 bp, and two inverted repeats (IR) regions of 27,302 bp. A total of 132 functional genes were distributed in the chloroplast genome, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis showed that S. lindleyana was clustered with Salix dasyclados Wimmer 1849 and Salix variegata Franchet 1887. The complete chloroplast genome of S. lindleyana provides potential genetic resources for further phylogenetic studies.

Discovery of specific catalytic activity toward IAA/FA by LaSABATHs based on genome-wide phylogenetic and enzymatic analysis of SABATH gene family from Larix kaempferi.

The SABATH methyltransferases catalyze methylation of small-molecule metabolites, which participate in plant growth, development and defense response. Given lack of genome-wide studies on gymnosperms SABATH family, the formation and functional differentiation mechanism of the Larix kaempferi SABATH gene family was systematically and exhaustively explored by analyzing gene sequence characteristics, phylogenetic relationship, expression pattern, and enzyme activities. Phylogenetic analysis showed that 247 SABATH genes from 14 land plants were divided into 4 clades, and lineage-specific gene duplication events were important factors that contributed to the evolution of the SABATH gene family in gymnosperms and angiosperms. Substrate specificity analysis of 18 Larix SABATH proteins showed that LaSABATHs could catalyze O-methylation of indole-3-acetic acid (IAA) and farnesic acid (FA), N-methylation of theobromine, and S-methylation of thiobenzoic acid. Furthermore, only LaSABATH2 and LaSABATH29 could catalyze O-methylation of FA, and only LaSABATH30 could catalyze O-methylation of IAA. Homology modeling and molecular docking studies showed the hydrogen bond formed between the His188 of LaSABATH30 and IAA and the noticeable hydrophobic IAA-binding pocket may be helpful for IAA methylation. In this study, identification of proteins with significant specific catalytic activity toward FA and IAA provided high-quality candidate genes for forest genetics and breeding.

Down-expression of Foxj1 on airway epithelium with impaired cilia architecture in non-cystic fibrosis bronchiectasis implies disease severity.

INTRODUCTION: The pathogenesis of non-cystic fibrosis bronchiectasis has not been clearly clarified. This study aimed to investigate the expression of ciliary regulating protein forkhead box protein j1 (Foxj1) on airway epithelium in non-cystic fibrosis bronchiectasis and its association with airway cilia structure disorder and disease severity. METHODS: Lung tissue sections excised from 47 patients with non-cystic fibrosis bronchiectasis were included between January 2018 and June 2021. Specimens from 26 subjects who underwent a lobectomy due to lung nodule were chosen as controls. Clinical information was collected, and pathologic analysis was performed to assess the epithelial structure and expression of ciliary regulating Foxj1. RESULTS: Of the 47 patients with non-cystic fibrosis bronchiectasis, 25 were considered as mild, 12 were moderate whereas the remaining 10 cases were severe according to the bronchiectasis severity index score evaluation. Epithelial hyperplasia, hyperplasia of goblet cells and inflammatory cell infiltration were observed in non-cystic fibrosis bronchiectasis, compared with control subjects. Cilia length in non-cystic fibrosis bronchiectasis patients were shorter than that in the control group, (5.34 ± 0.89) µm versus (7.34 ± 0.71) µm, respectively (P = 0.002). The expression of Foxj1 was (2.69 ± 1.09) × 106 in non-cystic fibrosis bronchiectasis, compared with (6.67 ± 1.15) × 106 in the control group (P = 0.001). Moreover, patients with lower expression of Foxj1 showed shorter airway cilia and worse in disease severity. CONCLUSION: Foxj1 declined in the airway epithelium of patients with non-cystic fibrosis bronchiectasis, positively correlated to cilia length and might imply worse disease severity.

Design and Application of Health Education Apps Based on WeChat for Self-Management among Patients.

Background: We started to design and test health education Apps for self-management among patients to provide a rich source of clinical support and information for patients to increase their ability of self-management. Methods: First, a multidisciplinary research team worked together to design and conduct the research. With their help, we redesigned an apps to incorporate some personalized changes for patients' needs. Second, we chose a questionnaire from the Comprehensive Service Platform for the Elderly self-designed by CHENYu. Finally, a purposive sample of 34 users were tested experiences and satisfaction of users in Jul 2021. Results: This research was successfully conducted in 22 wards among 23159 patients and 40440 chapters about healthy information sent to patients from Mar 2019 to January 2021 by smartphone. The data showed that 91.2% of participants resolved that the evaluation effect of the proposed application was better, in comparison with the paper version as routine verbal instruction. Additionally, 85.3% of participants wanted to continue to receive medical education information after discharge from the hospital. The top four most popular medical education information that they would like to receive included drug administration, disease prevention, nursing, and home care. Moreover, the top four most popular types of user suggestions were one-on-one online Q & A, continue to see every session, accelerate the speed of browsing and page updated, and free Wifi. The user satisfaction of the application was considerably high. Conclusion: The apps was welcomed by patients who wanted to increase their knowledge level of disease and perform self-management better.

Non-synonymous substitution of evolutionarily conserved residue in Tau class glutathione transferases alters structural and catalytic features.

Plant-specific tau glutathione transferases (GSTs) are basically involved in catalysing γ-glutathione (GSH)-dependent conjugation reactions with pesticides and herbicides, which play an important role in the detoxification of pollutants. Given the lack of systematic biochemical and structural information on tau GSTs, the study of their mediated defence mechanisms against toxic compounds has been greatly hindered. Here, we reveal the importance of the Ile residue closely interacting with GSH for the structural stability and catalytic function of GST. Evolutionary conservation analysis indicated that the crucial G-site Ile55 in the SbGSTU6 was converted to Thr53 of SbGSTU7. The comparative biochemical data on SbGSTU6, SbGSTU7 and their mutants showed that the substitution of Ile by Thr caused significant decrease in the affinity and catalytic efficiency of the GSTs. The unfavourable structural flexibility and pKa distribution of the active cavity residues were also demonstrated. Crystallography studies and molecular dynamics simulations showed that the conversion resulted in the hydrogen bond recombination with GSH and conformational rearrangement of GST active cavity, in which the Ile residue was more conducive to the formation of enzyme substrate complexes. The extensive biochemical and structural data not only reveal the critical role of the conserved G-site Ile residue in catalysing GSH-conjugate reactions but also provide valuable resources for the development of GST engineering in analytical and agricultural biotechnology.

Conserved residues in the subunit interface of tau glutathione s-transferase affect catalytic and structural functions.

The tau class glutathione S-transferases (GSTs) have important roles in stress tolerance and the detoxification of herbicides in crops and weeds. Structural investigations of a wheat tau GST (TaGSTU4) show two subunit interactions: a hydrogen bond between the Tyr93 and Pro65 from another subunit of the dimer, and two salt bridges between residues Glu78 and side chains of Arg95 and Arg99 in the opposite subunit. By investigating enzyme activities, kinetic parameters and structural characterizations, this study showed the following results: (i) the hydrogen bond interaction between the Tyr93 and Pro65 was not essential for dimerization, but contributed to the enzyme's catalytic activity, thermal stability and affinity towards substrates glutathione and 1-chloro-2, 4-dinitrobenzene; and (ii) two salt bridges mainly contributed to the protein structure stability and catalysis. The results of this study form a structural and functional basis for rational design of more selective and environmentally friendly herbicides.

Blood urea nitrogen to serum albumin ratio independently predicts 30-day mortality and severity in patients with Escherichia coli bacteraemia.

BACKGROUND: Elevated blood urea nitrogen to serum albumin (BUN/ALB) ratio had been identified as an independent risk factor related to mortality in community-acquired and hospital-acquired pneumonia. This study aimed to investigate whether this clinical index can predict the clinical outcomes of E. coli bacteraemia. MATERIAL AND METHODS: Clinical data were collected from patients with E. coli bacteraemia attended at our hospital between January 2012 and December 2018. The endpoints were mortality within 30 days after the diagnosis of E. coli bacteraemia and intensive care (IC) requirement. Cox regression analysis was performed to evaluate the risk factors. RESULTS: A total of 398 patients with E. coli bacteraemia were enrolled in this study and 56 patients died within 30 days after bacteraemia onset. Multivariate Cox regression analysis showed that age greater than 65 years, lymphocyte count<.8×10e9/L, elevated BUN/ALB ratio, increased SOFA score, carbapenem resistance, central venous catheterization before onset of bacteraemia, and infection originating from abdominal cavity were independent risk factors for 30-day mortality (P<.05). The risk factors associated with IC requirement were similar to those for 30-day mortality except central venous catheterization before onset of bacteraemia. The area under the receiver-operating characteristic curve for BUN/ALB ratio predicting 30-day mortality and IC requirement was similar to that for SOFA score, but higher than that for lymphocyte count. The cut-off points of BUN/ALB ratio to predict 30-day mortality and IC requirement were both .3. CONCLUSIONS: BUN/ALB ratio is a simple but independent predictor of 30-day mortality and severity in E. coli bacteraemia. A higher BUN/ALB ratio at the onset of bacteraemia predicts a higher mortality rate and IC requirement.

Deep Learning-Based Available and Common Clinical-Related Feature Variables Robustly Predict Survival in Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Although there are many predictors of death for CAP, there are still some limitations. This study aimed to build a simple and accurate model based on available and common clinical-related feature variables for predicting CAP mortality by adopting machine learning techniques. METHODS: This was a single-center retrospective study. The data used in this study were collected from all patients (≥18 years) with CAP admitted to research hospitals between January 2012 and April 2020. Each patient had 62 clinical-related features, including clinical diagnostic and treatment features. Patients were divided into two endpoints, and by using Tensorflow2.4.1 as the modeling framework, a three-layer fully connected neural network (FCNN) was built as a base model for classification. For a comprehensive comparison, seven classical machine learning methods and their integrated stacking patterns were introduced to model and compare the same training and test data. RESULTS: A total of 3997 patients with CAP were included; 205 (5.12%) died in the hospital. After performing deep learning methods, this study established an ensemble FCNN model based on 12 FCNNs. By comparing with seven classical machine learning methods, the area under the curve of the ensemble FCNN was 0.975 when using deep learning algorithms to classify poor from good prognosis based on available and common clinical-related feature variables. The predicted outcome was poor prognosis if the ControlNet's poor prognosis score was greater than the cutoff value of 0.50. To confirm the scientificity of the ensemble FCNN model, this study analyzed the weight of random forest features and found that mainstream prognostic features still held weight, although the model is perfect after integrating other factors considered less important by previous studies. CONCLUSION: This study used deep learning algorithms to classify prognosis based on available and common clinical-related feature variables in patients with CAP with high accuracy and good generalizability. Every clinical-related feature is important to the model.