The C-terminal self-binding helical peptide of human estrogen-related receptor γ can be druggably targeted by a novel class of rationally designed peptidic antagonists.

Orphan nuclear estrogen-related receptor γ (ERRγ) has been recognized as a potential therapeutic target for cancer, inflammation and metabolic disorder. The ERRγ contains a regulatory AF2 helical tail linked C-terminally to its ligand-binding domain (LBD), which is a self-binding peptide (SBP) and serves as molecular switch to dynamically regulate the receptor alternation between active and inactive states by binding to and unbinding from the AF2-binding site on ERRγ LBD surface, respectively. Traditional ERRγ modulators are all small-molecule chemical ligands that can be classified into agonists and inverse agonists in terms of their action mechanism; the agonists stabilize the AF2 in ABS site with an agonist conformation, while the inverse agonists lock the AF2 out of the site to largely abolish ERRγ transcriptional activity. Here, a class of ERRγ peptidic antagonists was described to compete with native AF2 for the ABS site, thus blocking the active state of AF2 binding to ERRγ LBD domain. Self-inhibitory peptide was derived from the SBP-covering AF2 region and we expected it can rebind potently to the ABS site by reducing its intrinsic disorder and entropy cost upon the rebinding. Hydrocarbon stapling was employed to do so, which employed an all-hydrocarbon bridge across the [i, i + 4]-anchor residue pair in the N-terminal, middle or C-terminal region of the self-inhibitory peptide. As might be expected, it is revealed that the stapled peptides are good binders of ERRγ LBD domain and can effectively compete with the native AF2 helical tail for ERRγ ABS site, which exhibit a basically similar binding mode with AF2 to the site and form diverse noncovalent interactions with the site, thus conferring stability and specificity to the domain-peptide complexes.

Synthesis of novel polyethyleneimine-capped silver nanoclusters exhibiting ultraviolet-A fluorescence and their application in multiple sensing.

Cupric ions (Cu2+), pyrophosphate (PPi), and alkaline phosphatase (ALP) are involved in a variety of biochemical processes such as DNA replication, cellular metabolism and play an important role in human growth and development. It is of great significance to establish a method for the sensitive detection of Cu2+, PPi and ALP. In this work, polyethyleneimine-capped silver nanoclusters (PEI-AgNCs) were successfully synthesized by a one-pot method using hydrazine sulfate as reductant, exhibiting a unique strong fluorescence emission in the near-ultraviolet region at ∼339 nm. Since the fluorescence of PEI-AgNCs can be quenched by Cu2+ through inner filtering effect (IFE), then recovered by competitive binding of pyrophosphate and Cu2+, and later weakened again by catalytic hydrolysis of alkaline phosphatase, a sensitive and selective strategy based on the changes of fluorescence "ON" or "OFF" was established to detect Cu2+, PPi and ALP. The LODs of these three analytes were 36 nM, 0.2 µM, and 0.14 U L-1 at a S/N ratio of 3, respectively. A series of logic gate circuits for sensing cupric ions, pyrophosphate, and alkaline phosphatase were successfully constructed. The established methods have the potential for biosensing and environmental analysis and the specific UV-A fluorescence property of PEI-AgNCs may be helpful in photonic and optical areas.

Integrated gold nanorods-based dual-signal platform for accurate total antioxidant capacity assessment in food samples.

Accurate assessment of Total Antioxidant Capacity (TAC) in food is crucial for evaluating nutritional quality and potential health benefits. This study aims to enhance the sensitivity and reliability of TAC detection through a dual-signal method, combining colorimetric and photothermal signals. Gold nanorods (AuNRs) were utilized to establish a dual-signal method duo to the colorimetric and photothermal properties. Fenton reaction can etch the AuNRs from the tips, as a result, a blue shift in the longitudinal LSPR absorption peak was obtained, leading to significant changes in color and photothermal effects, facilitating discrimination through both visual observation and thermometer measurements. In the presence of antioxidants, the Fenton reaction was suppressed or inhibited, protecting the AuNRs from etching. The colorimetric and photothermal signals were therefore positively correlated with TAC levels, enabling dual-signal detection of TAC. The linear range of AA was 4-100 µM in both colorimetry and photothermal modes, with detection limits of 1.60 µM and 1.38 µM, respectively. This dual-signal approach achieves low detection limits, enhancing precision and sensitivity. The method thus has the potential to act as a promising candidate for TAC detection in food samples, contributing to improved food quality and safety assessment.

EGR1 Promotes Erastin-induced Ferroptosis Through Activating Nrf2-HMOX1 Signaling Pathway in Breast Cancer Cells.

Purpose: Early growth response 1 (EGR1) is a crucial transcription factor composed of zinc finger structures, inhibitory and activating regulatory regions. We identified the biological effect and molecular mechanisms of EGR1 in breast cancer (BC). Methods: We used qRT-PCR, western blot and immunohistochemistry to examine the expression of EGR1 in BC samples. CCK-8 and colony assay were performed to reveal the effect of EGR1 on the proliferation of BC cells. LDH release assay, MCB assay, MDA assay, C-AM assay and TMRE assay were performed to measure the levels of LDH release, GSH, MDA, LIP and mitochondrial membrane potential. The regulation of EGR1 on the expression of Nrf2 and HMOX1 was investigated through Western blot. Xenograft models were conducted to determine the impact of EGR1 overexpression on BC in vivo. Results: The expression of EGR1 was downregulated in BC tissues compared with the normal tissues, and lower expression of EGR1 associated with poorer clinical outcome in BC patients. Through in vitro experiments, we found that EGR1 downregulation facilitated the proliferation of BC cells, and overexpression of EGR1 inhibited the proliferation of BC cells. In addition, EGR1 knockdown alleviated erastin-induced ferroptosis and overexpression of EGR1 facilitated erastin-induced ferroptosis in BC cells. Moreover, overexpression of EGR1 facilitated the anti-tumor effect caused by erastin in vivo. Mechanistically, the phosphorylation levels of Nrf2 and the expression of HMOX1 were reduced due to the downregulation of EGR1, and increased due to the upregulation of EGR1. Additionally, the finding that EGR1 facilitated erastin-induced ferroptosis was alleviated by the inhibition of Nrf2-HMOX1. Conclusion: The expression of EGR1 is downregulated in BC, which is correlated with poor prognosis of BC patients. EGR1 suppresses the proliferation of BC cells and facilitates erastin-induced ferroptosis by activating Nrf2-HMOX1 signaling pathway in BC cells.

Thermally resistant nuclease in Serratia marcescens hinders PCR reactions and degrades PCR products.

Polymerase chain reaction (PCR) is an important tool for exogenous gene acquisition and recombinants identification. There exist two problems when using Serratia marcescens as a template for PCR amplification: amplified PCR products are rapidly degraded, and the results of PCR amplification are unstable. The aim of the present work was to elucidate the reasons for this. By mixing PCR products amplified from Escherichia coli DH5α with S. marcescens supernatant or pellet, we found that the DNA-degrading substance in S. marcescens is thermally resistant and present both intracellularly and extracellularly. We then determined that it is protein, and most likely S. marcescens nuclease, that degrades PCR products since the addition of SDS and EDTA can effectively inhibit or block the degradation of PCR products. By knocking out the S. marcescens nuclease encoding gene, nucA, we confirmed that the nuclease is responsible for the degradation of PCR products and the instability of PCR amplification. This work is the first to show that the S. marcescens nuclease is temporarily and partially inhibited by high temperatures during PCR and recovers rapidly at room temperature after PCR.

Postoperative intra-abdominal hypertension predicts worse hospital outcomes in children after cardiac surgery: a pilot study†.

OBJECTIVES: Our goal was to determine the incidence and characteristics of postoperative intra-abdominal hypertension (IAH) in paediatric patients undergoing open-heart surgery. METHODS: This single-centre study included consecutive children (aged <16 years) who underwent open-heart surgery between July 2020 and February 2021. Patients who entered the study were followed until in-hospital death or hospital discharge. The study consisted of 2 parts. Part I was a prospective observational cohort study that was designed to discover the association between exposures and IAH. Postoperative intra-abdominal pressure was measured immediately after admission to the intensive care unit and every 6 h thereafter. Part II was a cross-sectional study to compare the hospital-related adverse outcomes between the IAH and the no-IAH cohorts. RESULTS: Postoperatively, 24.7% (38/154) of the patients exhibited IAH, whereas 3.9% (6/154) developed abdominal compartment syndrome. The majority (29/38, 76.3%) of IAH cases occurred within the first 24 h in the intensive care unit. Multivariable analysis showed that the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score [odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.23-2.83, P = 0.004], right-sided heart lesion (OR = 5.60, 95% CI 2.34-13.43, P < 0.001), redo sternotomy (OR = 4.35, 95% CI 1.64-11.57, P = 0.003), high baseline intra-abdominal pressure (OR = 1.43, 95% CI 1.11-1.83, P = 0.005), prolonged cardiopulmonary bypass duration (OR = 1.01, 95% CI 1.00-1.01, P = 0.005) and deep hypothermic circulatory arrest (OR = 5.14, 95% CI 1.15-22.98, P = 0.032) were independent predictors of IAH occurrence. IAH was associated with greater inotropic support (P < 0.001), more gastrointestinal complications (P = 0.001), sepsis (P = 0.003), multiple organ dysfunction syndrome (P < 0.001) and prolonged intensive care unit stay (z = -4.916, P < 0.001) and hospitalization (z = -4.710, P < 0.001). The occurrence of a composite outcome (P = 0.009) was significantly increased in patients with IAH. CONCLUSIONS: IAH is common in children undergoing cardiac surgery and is associated with worse hospital outcomes. Several factors may be associated with the development of IAH, including basic cardiac physiology and perioperative factors. TRIAL INFORMATION: This study was registered in the Chinese Clinical Trial Registry (Trial number: ChiCTR2000034322)URL site: https://www.chictr.org.cn/hvshowproject.html?id=41363&v=1.4.

Purification of aquaculture wastewater by macrophytes and biofilm systems: Efficient removal of trace antibiotics and enrichment of antibiotic resistance genes.

The purification performance of aquaculture wastewater and the risk of antibiotic resistance genes (ARGs) dissemination in wetlands dominated by macrophytes remain unclear. Here, the purification effects of different macrophytes and biofilm systems on real aquaculture wastewater were investigated, as well as the distribution and abundance of ARGs. Compared to the submerged macrophytes, artificial macrophytes exhibited higher removal rates of TOC (58.80 ± 5.04 %), TN (74.50 ± 2.50 %), and TP (77.33 ± 11.66 %), and achieved approximately 79.92 % removal of accumulated trace antibiotics in the surrounding water. Additionally, the biofilm microbial communities on the surface of artificial macrophytes exhibited higher microbial diversity with fewer antibiotic-resistant bacteria (ARB) enrichment from the surrounding water. The absolute abundance of ARGs (sul1, sul2, and intI1) in the mature biofilm to be one to two orders of magnitude higher than that in the water. Although biofilms could decrease ARGs in the surrounding water by enriching ARB, the intricate network structure of biofilms further facilitated the proliferation of ARB and the dissemination of ARGs in water. Network analysis suggested that Proteobacteria and Firmicutes phyla were dominant and potential carriers of ARGs, contributing 69.00 % and 16.70 %, respectively. Our findings highlight that macrophytes and biofilm systems have great performance on aquaculture wastewater purification, but with high risk of ARGs.

Impact of fatty acid composition on markers of exocrine pancreatic stimulation in dogs.

Chronic pancreatitis in dogs is typically managed with a low-fat diet. Human research suggests that consumption of medium-chain triglycerides (MCT) may lessen pancreatic enzyme release compared to consumption of long-chain fatty acids (LCFA). Twelve healthy adult colony dogs were fed a meal of cod and rice with either 3% metabolizable energy (ME) fat (control), high MCT (25% ME MCT oil, 25% ME butter), high saturated LCFA (50% ME butter), or high unsaturated LCFA (50% ME canola oil) in a 4-period by 4-treatment crossover design. Serum concentrations of canine pancreatic lipase immunoreactivity, gastrin, cholesterol, triglycerides, and serum activities of amylase and DGGR lipase (1,2-o-dilauryl-rac-glycero-3-glutaric acid-(69-methylresorufin) ester lipase) were measured at times 0 (fasted), 30, 120 and 180 minutes post-prandially. Following a 3-or 4-day wash-out period, each dog was assigned a new diet and the process was repeated for all treatments. Data were analyzed as a repeated-measures mixed model ANOVA. Post-hoc pairwise comparisons were run using Tukey-Kramer adjusted p-values. Shapiro-Wilk tests were used to evaluate residual normality. All statistical assumptions were sufficiently met. Statistical significance was defined as P<0.05. Of the markers tested, only serum triglyceride concentrations were affected by treatment, with consumption of high MCT resulting in lower triglycerides than both LCFA groups at times 120 and 180 minutes (P<0.0001). As expected, the high MCT group had higher triglycerides compared to the control group (P<0.0001). The type of dietary fat consumed had little acute impact on most markers of exocrine pancreatic stimulation in healthy dogs.

[Source Analysis and Pollution Assessment of Soil Heavy Metals in Typical Geological High Background Area in Southeastern Chongqing].

In order to understand the pollution characteristics of soil heavy metals in typical geological high background areas in southeastern Chongqing, analyze its pollution sources, and put forward risk management and control suggestions, 211 topsoil samples (0-20 cm) were collected in Xinglong Town and Muye Township in the north of Youyang County, Chongqing City, and the contents of eight heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) and the soil pH value in the surface soil were analyzed. Additionally, mathematical statistics, pollution load index (P), potential ecological risk index (RI), correlation analysis, and the positive matrix factorization (PMF) model were used to study the content and spatial distribution characteristics of heavy metals in the topsoil, and pollution assessment and source analysis of heavy metals were carried out. The results showed that the average concentrations of heavy metals in the surface soil all exceeded the soil background value in Chongqing, showing different levels of enrichment. Among them, the proportion of Cd exceeding the screening value in the "soil environmental quality risk control standard for soil contamination of agricultural land" (GB 15618-2018) was as high as 83.41%, the proportion of exceeding the control value was 7.58%, and the potential risk was relatively high. The evaluation results of the pollution load index method showed that the study area was slightly polluted as a whole, and the evaluation results of the potential ecological risk index showed that the overall ecological risk of the study area was relatively high. Among them, the contribution rates of heavy metals Hg, Cd, and As were 50.27%, 28.63%, and 11.70%, respectively. The PMF results showed that there were three main sources of heavy metals in the soil in the study area:natural parent material sources, agricultural sources, and mixed sources of industrial activities and traffic emissions, accounting for 40.49%, 29.12%, and 30.39%, respectively. The quantitative source analysis results of soil heavy metals in the study area have important reference significance for soil heavy metal pollution control in geologically high background areas.

[Source Analysis and Ecological Risk Assessment of Heavy Metals in the Arable Soil at the Geological High Background, Based on the Township Scale].

Due to the extensive development of carbonate rocks in southwest China, heavy metals are naturally occurring elements that have high natural background levels in the environment. Therefore, it is important to conduct ecological risk assessments and identify potential sources of heavy metals in the geological high background area. Based on the township scale, a total of 307 surface soil samples were collected in Qinglong Town, Fengjie County, Chongqing. The concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn and pH were analyzed and determined. The spatial distribution and source of soil heavy metals were discussed using the geostatistical analysis and an absolute principal component score-multiple linear regression (APCS-MLR) model in the studied area. The results showed that the average values of seven heavy metals (As, Cd, Cr, Cu, Hg, Ni, and Zn) in the arable soil exceeded the background values of Chongqing, and the cumulative effect of Cd and As was obvious. The concentrations of Cd significantly exceededthe screening values in The Risk Control Standard for Soil Environmental Quality and Soil Pollution in Agricultural Land (GB 15618-2018), with the over-standard rates of 52.12%. The spatial characteristics of soil heavy metal contents exhibited a pattern of high in the south and low in the north. PCA and APCS-MLR modeling revealed that the contributions of natural sources to Cr, Cu, Ni, and Zn were 86.62%, 64.34%, 76.44%, and 85.46%, respectively. As, Pb, and Hg mainly derived from industrial activities, which accounted for 74.63%, 61.90%, and 73.49%, respectively, and Cd was affected by both natural sources and industrial activities (accounting for 47.74% and 39.56% of the total Cd content, respectively). The evaluation of the soil by the Nemerow comprehensive index (P) showed that Cd pollution was relatively serious, accounting for 27.04% of soil pollution. The potential ecological hazard index showed that Cd and Hg were the main ecological hazard elements, and the distribution range of RI was 51.77 to 2228, indicating mainly mild and moderate risks, and the moderate and above risk areas in the study area were mainly located around the southern industrial source area. Altogether, our results revealed that in the study area, the heavy metal pollution was mainly caused by industrial activities, and the heavy metal pollution caused by geological background was mainly light to moderate. In conclusion, the medium and above risk areas in the study area were mainly caused by mineral and industrial activities, whereas the heavy metal pollution caused by geological background was mainly light to moderate pollution.

Portable smartphone-assisted ratiometric fluorescence sensor for visual detection of glucose.

Fluorescence-based visual assays have sparked tremendous attention in on-site detection due to their obvious color gradient changes and high sensitivity. In this study, a novel emission wavelength shift-based visual sensing platform is constructed to detect glucose based on the oxidation of Rhodamine B (RhB). MnO2 nanosheets (MnO2 NS) with strong oxidizing properties were introduced to oxidize RhB, which resulted in a blue shift in the emission wavelength, and a visual color changed of the fluorescence from orange-red to green. The oxidation reaction could be inhibited via reducing and destroying MnO2 NS by H2O2, which was produced by the oxidizing procedure of glucose in the presence of glucose oxidase (GOx). A series of wavelength shifts and fluorescence color variations appeared with the addition of various amounts of glucose. A ratiometric fluorescence glucose sensor with a lowest recorded concentration of 0.25 µM was developed. Meanwhile, test paper-based assays integrated with the smartphone platform were established for the sensing of glucose by means of the significant fluorescence color changes, offering a reliable, sensitive, and portable on-site assay of glucose.

[Availability of Se-rich Arable Land in High Geological Background Area and Suggestions for Zoning].

In order to promote the results of land quality geochemical surveys to serve the development of characteristic land resources and realize the safe utilization of Se-rich resources in high geological background areas, Wuli Town, Qianjiang District, Chongqing City were taken as the research object to evaluate the Se-rich level and heavy metal content of soil crops and carry out research on Se-rich cultivated area division and the availability method system in the high geological background area, in order to improve the utilization efficiency of Se-rich resources and provide ideas for the safe utilization of Se-rich resources in high geological background areas. The results showed that the soil and crops in the study area were rich in Se and had the potential to develop Se-rich resources, but some samples had the problem of excessive Cd. Soil pH was a key factor affecting the content of Se and Cd in crops, and alkaline conditions were conducive to the safe utilization of Se-rich resources. The areas of Class A-E (A:selenium-enriched arable land, B:crops that were not selenium-enriched but were safe, C:crops that were selenium-enriched but unsafe, D:crops that were not selenium-enriched and unsafe, and E:soil selenium content less than the selenium-enriched threshold and soil heavy metals not exceeding the standard)cultivated land were 0.72, 0.75, 0.28, 0.13, and 0.56 km2, respectively. It is recommended to develop safe and Se-rich resources in the distribution area of Class A cultivated land and to carry out soil acidification conditioning and low-accumulation crops in the distribution area of Class C and D cultivated land; other agronomic measures should be taken to reduce the risk of excessive heavy metals in crops and strengthen the protection of cultivated land in the region to prevent the input of new pollutants.

Investigating and Developing a Practical Domestic-Medication System of Public Health for Chinese Family.

(1) Background: The main research aim of this paper is to investigate the commonly stocked medicines in Chinese households. Firstly, a large number of questionnaires were collected to uncover the problem: most Chinese families have the habit of stocking their family medicine boxes. However, there is a lack of a standardized, systematic, and scientific list of household medicine stockpiles. As a result, there are major problems in stocking medicines in households: (1) There is little connection between the type and quantity of medicines stocked and real life; (2) The expiration date of medicines leads to misuse and waste of medicines; (3) The existing list of medicines can provide little help. (2) Methods: The preliminary drug stock list was summarized through case studies; the authenticity of the questions and the credibility of the list were verified through interviews; the number of different types of drugs and the relationship between the resident's perception of the importance of drugs and their frequency of use was determined through questionnaires; the authenticity of the list was verified through interviews with senior doctors. (3) Results: We finally composed a scientific and practical list of common household medicines, developed a practical domestic-medication system for Chinese families, and conducted validation studies, which received the approval of senior doctors. (4) Conclusions: (1) Chinese families need to prepare medicines according to the actual composition of the family; (2) Chinese families need a scientific and systematic list of commonly prepared medicines; and (3) in addition to the types of medicines, it is also necessary to consider the number of individual types of medicines to be stocked.

Theaflavin-3,3'-digallate ameliorates learning and memory impairments in mice with premature brain aging induced by D-galactose.

Age-related neurodegenerative diseases accompanied by learning and memory deficits are growing in prevalence due to population aging. Cellular oxidative stress is a common pathomechanism in multiple age-related disorders, and various antioxidants have demonstrated therapeutic efficacy in patients or animal models. Many plants and plant extracts possess potent antioxidant activity, but the compounds responsible are frequently unknown. Identification and evaluation of these phytochemicals is necessary for optimal targeted therapy. A recent study identified theaflavin-3,3'-digallate (TFDG) as the most potent among a large series of phytochemical antioxidants. Here we examined if TFDG can mitigate learning and memory impairments in the D-galactose model of age-related neurodegeneration. Experimental mice were injected subcutaneously with D-galactose (120 mg/kg) for 56 days. In treatment groups, different doses of TFDG were administered daily by gavage starting on day 29 of D-galactose injection. Model mice exhibited poor learning and memory in the novel object recognition and Y-maze tests, reduced brain/body mass ratio, increased brain glutamate concentration and acetylcholinesterase activity, decreased brain acetylcholine concentration, and lower choline acetyltransferase, glutaminase, and glutamine synthetase activities. Activities of antioxidant enzymes glutathione peroxidase and superoxide dismutase were also reduced, while the concentration of malondialdehyde, a lipid peroxidation product, was elevated. Further, antioxidant genes Nrf2, Prx2, Gsh-px1, and Sod1 were downregulated in brain. Each one of these changes was dose-dependently reversed by TFDG. TFDG is an effective antioxidant response inducer and neuroprotectant that can restore normal neurotransmitter metabolism and ameliorate learning and memory dysfunction in the D-galactose model of age-related cognitive decline.

The synergistic effect and mechanisms of flavonoids and polysaccharides from Houttuynia cordata on H1N1-induced pneumonia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (HC, Saururaceae family) is a classical Traditional Chinese Medicine used to treat pneumonia clinically. The total flavonoids (HCF) and polysaccharides (HCP) are key medicinal components of H. cordata involved in its beneficial effect on viral pneumonia. AIM OF THE STUDY: The purpose of the study is to investigate the synergistic or complementary effects of combination of HCF and HCP on viral pneumonia as well as the mechanisms underlying. MATERIALS AND METHODS: HCF or HCP were administrated separately or combined in different proportions on influenza virus H1N1 - infected mice. The survival and lung weight of mice were recorded. The synergistic effect on HCF and HCP combination was calculated by Chou-Talalay method. H&E staining was performed to detect lung histomorphology. Western blot, immunohistochemistry and enzyme linked immunosorbent assay were done to analyze the representative protein expression in lung and intestine tissues. AB - PAS staining on intestine tissue sections was performed to evaluate the histopathology of intestines. Bacterial genomic DNA was extracted and sequenced for gut microbiota analysis. RESULTS: In H1N1 lethally infected mice, the combined administration of HCF and HCP significantly increased the survival rate and prolonged the life span of mice, compared with mono-drug therapy. The viral pneumonia was remarkably improved by HCF and HCP combination reflected by lower lung index, more intact lung morphology, and less inflammatory cells and mediators. Furthermore, the combination of HCF and HCP regulated intestinal microbiota, significantly reduced the proportion of pathogenic Proteobacteria and the secretion of proinflammatory cytokine in gut. The combined HCF and HCP showed synergistic effect on reducing lung and intestine injury. The complementary interaction was also found in HCF and HCP combined therapy, as HCF provided the significant antiviral activity and HCP markedly improved intestinal physical barrier and increased the protein expression involving removal of edema. CONCLUSIONS: Our findings indicated that combination of HCF and HCP from H. cordata synergistically alleviated H1N1-induced viral pneumonia in mice via multimodal regulation of both pulmonary and intestinal homeostasis, which might imply novel therapeutic strategy for treating viral pneumonia.

A Complete Genome of Nocardia terpenica NC_YFY_NT001 and Pan-Genomic Analysis Based on Different Sources of Nocardia spp. Isolates Reveal Possibly Host-Related Virulence Factors.

Objective: We aimed to identify the possible virulence genes associated with Nocardia NC_YFY_NT001 isolated by ourselves and other Nocardia spp. Methods: The genome of Nocardia terpenica NC_YFY_NT001 was completed by using PacBio and Illumina platforms. A pan-genomic analysis was applied to selected complete Nocardia genomes. Results: Nocardia terpenica NC_YFY_NT001 can cause healthy mice death by tail intravenous injection. The genome of NT001 has one circular chromosome 8,850,000 bp and one circular plasmid 70,000 bp with ~68% GC content. The chromosome and plasmid encode 7914 and 80 proteins, respectively. Furthermore, a pan-genomic analysis showed a total of 45,825 gene clusters, then 304 core, 21,045 shell and 24,476 cloud gene clusters were classified using specific parameters. In addition, we found that catalases were more abundant in human isolates. Furthermore, we also found no significant differences in the MCE proteins between different strains from different sources. The pan-genomic analysis also showed that 67 genes could only be found in humoral isolates. ReX3 and DUF853 domain protein were found in all eight human isolates. The composition of unique genes in humoral isolate genomes indicated that the transcriptional regulators may be important when Nocardia invades the host, which allows them to survive in the new ecological system. Conclusion: In this study, we confirmed that NT001 could cause infected animal death, and identified many possible virulence factors for our future studies. This study also provides new insight for our further study on Nocardia virulence mechanisms.

A new performance analysis method for rolling bearing based on the evidential reasoning rule considering perturbation.

Rolling Bearing is a key component of the transmission of rotating machinery, and it is widely used in industrial fields. Therefore, it is of vital importance to evaluate the performance and reliability of rolling bearing. Aiming at the interference problems faced by rolling bearings during operation, a performance evaluation model based on the evidential reasoning (ER) rule is proposed in this article. Firstly, the time domain and frequency domain characteristic indicators of bearing vibration signals are taken as evaluation indicators, and the evaluation system is constructed. Secondly, various indicator information is unified into a belief structure, and the reliability and the weight of the indicators are fully considered in the ER rule. Thirdly, to simulate the complex working environment of rolling bearings, the perturbation analysis method is adopted. After determining the maximum perturbation error and perturbation coefficient, the performance reliability of the rolling bearing is analysed, and a performance reliability evaluation model considering perturbation is proposed. Finally, based on the whole-life open data set of rolling bearing from the University of Cincinnati, the validity and reliability of the proposed model are verified in performance analysis.

Intestinal microbiota metabolizing Houttuynia cordata polysaccharides in H1N1 induced pneumonia mice contributed to Th17/Treg rebalance in gut-lung axis.

Influenza A virus is intricately linked to dysregulation of gut microbiota and host immunity. Previous study revealed that Houttuynia cordata polysaccharides (HCP) exert the therapeutic effect on influenza A virus inducing lung and intestine damage via regulating pulmonary and intestinal mucosal immunity. However, whether this result was due to the regulation of gut microbiota in the gut-lung axis remains unclear. Here, we firstly found that the elimination of gut microbiota using antibiotic cocktails led to both loss of the protective effect of HCP on intestine and lung injury, and reduction of the efficacy on regulating Th17/Treg balance in gut-lung axis. Fecal microbiota transplantation study confirmed that the gut microbiota fermented with HCP under pathological conditions (H1N1 infection) was responsible for reducing pulmonary and intestinal injury. Moreover, the interaction of HCP and gut microbiota under pathological conditions exhibited not only much more abundant gut microbial diversity, but also higher content of the acetate. Our results demonstrated that the underlying mechanism to ameliorate viral pneumonia in mice involving Th17/Treg rebalance via the gut microbiota and HCP metabolite (acetate) metabolized in pneumonia mice. Our results provided a new insight for macromolecular polysaccharides through targeting intestinal microenvironment reducing distant pulmonary infection.

Antimicrobial resistance and genomic investigation of non-typhoidal Salmonella isolated from outpatients in Shaoxing city, China.

Human non-typhoidal salmonellosis is among the leading cause of morbidity and mortality worldwide, resulting in huge economic losses and threatening the public health systems. To date, epidemiological characteristics of non-typhoidal Salmonella (NTS) implicated in human salmonellosis in China are still obscure. Herein, we investigate the antimicrobial resistance and genomic features of NTS isolated from outpatients in Shaoxing city in 2020. Eighty-seven Salmonella isolates were recovered and tested against 28 different antimicrobial agents, representing 12 categories. The results showed high resistance to cefazolin (86.21%), streptomycin (81.61%), ampicillin (77.01%), ampicillin-sulbactam (74.71%), doxycycline (72.41%), tetracycline (71.26%), and levofloxacin (70.11%). Moreover, 83.91% of isolates were resistant to ≥3 categories, which were considered multi-drug resistant (MDR). Whole-genome sequencing (WGS) combined with bioinformatic analysis was used to predict serovars, MLST types, plasmid replicons, antimicrobial resistance genes, and virulence genes, in addition to the construction of phylogenomic to determine the epidemiological relatedness between isolates. Fifteen serovars and 16 STs were identified, with the dominance of S. I 4, [5], 12:i:- ST34 (25.29%), S. Enteritidis ST11 (22.99%), and S. Typhimurium ST19. Additionally, 50 resistance genes representing ten categories were detected with a high prevalence of aac(6')-Iaa (100%), bla TEM-1B (65.52%), and tet(A) (52.87%), encoding resistance to aminoglycosides, ß-lactams, and tetracyclines, respectively; in addition to chromosomic mutations affecting gyrA gene. Moreover, we showed the detection of 18 different plasmids with the dominance of IncFIB(S) and IncFII(S) (39.08%). Interestingly, all isolates harbor the typical virulence genes implicated in the virulence mechanisms of Salmonella, while one isolate of S. Jangwani contains the cdtB gene encoding typhoid toxin production. Furthermore, the phylogenomic analysis showed that all isolates of the same serovar are very close to each other and clustered together in the same clade. Together, we showed a high incidence of MDR among the studied isolates which is alarming for public health services and is a major threat to the currently available treatments to deal with human salmonellosis; hence, efforts should be gathered to further introduce WGS in routinely monitoring of AMR Salmonella in the medical field in order to enhance the effectiveness of surveillance systems and to limit the spread of MDR clones.

Deep belief rule based photovoltaic power forecasting method with interpretability.

Accurate prediction of photovoltaic (PV) output power is of great significance for reasonable scheduling and development management of power grids. In PV power generation prediction system, there are two problems: the uncertainty of PV power generation and the inexplicability of the prediction result. The belief rule base (BRB) is a rule-based modeling method and can deal with uncertain information. Moreover, the modeling process of BRB has a certain degree of interpretability. However, rule explosion and the inexplicability of the optimized model limit the modeling ability of BRB in complex systems. Thus, a PV output power prediction model is proposed based on a deep belief rule base with interpretability (DBRB-I). In the DBRB-I model, the deep BRB structure is constructed to solve the rule explosion problem, and inefficient rules are simplified by a sensitivity analysis of the rules, which reduces the complexity of the model. Moreover, to ensure that the interpretability of the model is not destroyed, a new optimization method based on the projection covariance matrix adaptation evolution strategy (P-CMA-ES) algorithm is designed. Finally, a case study of the prediction of PV output power is conducted to illustrate the effectiveness of the proposed method.