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Research background. Peanut allergy poses a significant threat to human health due to the increased risk of long-term morbidity at low doses. Modifying protein structure to affect sensitization is a popular topic. Experimental approach. In this study, the purified peanut allergen Ara h 1 was enzymatically hydrolysed using Flavourzyme, alkaline protease or a combination of both. The binding ability of Ara h 1 to antibodies, gene expression and secretion levels of the proinflammatory factors interleukin-5 and interleukin-6 in Caco-2 cells was measured. Changes in the secondary and tertiary structures before and after treatment with Ara h 1 were analysed by circular dichroism and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Results and conclusions. The results indicated a decrease of the allergenicity and proinflammatory ability of Ara h 1. The evaluation showed that the Flavourzyme and alkaline protease treatments caused particle shortening and aggregation. The fluorescence emission peak increased by 3.4-fold after the combined treatment with both proteases. Additionally, the secondary structure underwent changes and the hydrophobicity also increased 8.95-fold after the combined treatment. Novelty and scientific contribution. These findings partially uncover the mechanism of peanut sensitization and provide an effective theoretical basis for the development of a new method of peanut desensitization.

Abstract Norovirus (NoV) and hepatitis A virus (HAV) pose a considerable health risk worldwide. In recent years, many cases of virus infection caused by virus‐contaminated strawberries have occurred worldwide. This study applied a critical control point system to analyze the main hazards during the production and marketing of strawberries imported into China and explore the key control points in the whole process. To further evaluate the risks in the supply chain, the established quantitative microbial risk assessment (QMRA) was used to determine the probability that residents would be infected with viruses after consuming imported strawberries. It was found that the risk of virus contamination from imported strawberries was low, and the virus contamination mainly results from water resources and personnel. This research helps the regulatory authorities formulate strategies to ensure the long‐term microbial safety of imported strawberries. In addition, the methods may prove useful in evaluating the risks of other agricultural produce.

The rapid and accurate detection of peanuts and soybeans allergen is important to the food safety. In this study, Cu-TCPP nanosheet, a kind of ultra-thin metal-organic framework (MOF) was synthesized and applied in loop-mediated isothermal amplification (named Cu-TCPP@LAMP), which can inhibit the non-specific amplification by absorbing and precise temperature releasing of single primer. As thus, Cu-TCPP@LAMP can achieve high sensitivity and specific amplification of the target gene. As a result, peanut and soybean allergens genes contained in food were successfully detected with a favorable detection sensitivity (5 ng/μL for peanuts and 10 ng/μL for soybeans) and reliable repeatability (The coefficient of variation was 3.38% for peanuts and 3.33% for soybeans). Moreover, the established method was utilized for detection of several commercial products, and had a high consistency with the standard method. Apart from food allergens, this novel assay can be widely used in other areas, such as pathogen detection, tumor nucleic acid detection and so on.

Listeria monocytogenes is recognized as one of the primary pathogens responsible for foodborne illnesses. The ability of L. monocytogenes to form biofilms notably increases its resistance to antibiotics such as ampicillin and tetracycline, making it exceedingly difficult to eradicate. Residual bacteria within the processing environment can contaminate food products, thereby posing a significant risk to public health. In this study, we used crystal violet staining to assess the biofilm-forming capacity of seven L. monocytogenes strains and identified ATCC 19112 as the strain with the most potent biofilm-forming. Subsequent fluorescence microscopy observations revealed that the biofilm-forming capacity was markedly enhanced after two days of culture. Then, we investigated into the factors contributing to biofilm formation and demonstrated that strains with more robust extracellular polymer secretion and self-agglutination capabilities exhibited a more pronounced ability to form biofilms. No significant correlation was found between surface hydrophobicity and biofilm formation capability. In addition, we found that after biofilm formation, the adhesion and invasion of cells were enhanced and drug resistance increased. Therefore, we hypothesized that the formation of biofilm makes L. monocytogenes more virulent and more difficult to remove by antibiotics. Lastly, utilizing RT-PCR, we detected the expression levels of genes associated with biofilm formation, including those involved in quorum sensing (QS), flagellar synthesis, and extracellular polymer production. These genes were significantly upregulated after biofilm formation. These findings underscore the critical relationship between extracellular polymers, self-agglutination abilities, and biofilm formation. In conclusion, the establishment of biofilms not only enhances L. monocytogenes’ capacity for cell invasion and adhesion but also significantly increases its resistance to drugs, presenting a substantial threat to food safety.

Listeria monocytogenes (L. monocytogenes) is a food-borne pathogenic bacteria that frequently contaminates animal-derived food and low-temperature preserved food. Listeriosis caused by its infection has a high mortality rate and poses a serious threat to human health. Therefore, it is crucial to establish a sensitive, rapid and easy-to-operate technique. In this study, a Recombinase Aided Amplification (RAA) assisted CRISPR/Cas12a (RAA-CRISPR/Cas12a) fluorescence platform was established for highly sensitive nucleic acid detection of L. monocytogenes. The established RAA-CRISPR/Cas12a showed high sensitivity and high specificity, with the sensitivity of 350 CFU/mL and 5.4 × 10−3 ng/μL for pure bacterial solution and genomic DNA, and good specificity for 5 strains of Listeria spp. and 14 strains of other common pathogenic bacteria. L. monocytogenes could be detected at an initial concentration of 2.3 CFU/25g within 2 h of enriching the beef in the food matrix, and this method could be applied to food samples that were easily contaminated with L. monocytogenes The results of RAA-CRISPR/Cas12a could be observed in 5 min, while the amplification was completed in 20–30 min. The speed and sensitivity of RAA-CRISPR/Cas12a were significantly higher than that of the national standard method. In conclusion, the RAA-CRISPR/Cas12a system established in this study has new application potential in the diagnosis of food-borne pathogens.

Little information was so far available about allergenic mechanism of the roasted peanut allergens during initial stages of allergy. The purpose of this study was to determine the influence of roasting (150 °C, 20 min) on biochemical and biological properties of Ara h 3, a major peanut allergen. Allergenicity of roasted peanut emulsion to mice, differences in uptakes between Ara h 3 purified from raw peanuts (named as Ara h 3-Raw) and that purified from roasted peanuts (named as Ara h 3-Roasted) by bone marrow-derived dendritic cells (BMDCs) and the implication of cell surface receptors involving in uptake, and changes in glycosylation and structure of Ara h 3 after roasting were analyzed in this study. This study suggested that roasting increased allergenicity of peanut to BALB/c mice. Maillard reaction and structural changes of Ara h 3 induced by roasting significantly altered the uptake of Ara h 3-Roasted by BMDCs, and modified Ara h 3 fate in processes involved in immunogenicity and hyper allergenicity, indicating that food processing pattern can change food allergenicity.

Abstract Background Peste des petits ruminants (PPR) is a serious disease that affects goats, sheep and other small ruminants. As one of the earliest and most serious countries, PPR has seriously threatened India's animal husbandry economy. Results In this study, the spatiotemporal characteristics of the PPR in India outbreaks were analyzed. Between 2010 and 2018, the epidemic in India broke out all over the country in a cluster distribution. Epidemic clusters in northern and southern India are at higher risk, and the outbreak time of PPR has significant seasonality. The results of the analysis of the development and transmission of PPR under the natural infection conditions showed that the PPR outbreak in India reached a peak within 15 days. Finally, the quantitative risk analysis results based on scenario tree show showed that the average probability of infecting PPRV in live sheep exported from India was 1.45 × 10–4. Conclusions This study analyzed the prevalence of PPR in India. The analysis of transmission dynamics on the development of the epidemic provides a reference for the prevention and control of the epidemic. At the same time, it provides risk analysis and suggestions on trade measures for the trading countries of India.

Homochiral metal-organic frameworks (MOFs) have attracted considerable attention in many fields of research, such as chiral catalysis and chiral chromatography. However, only few homochiral MOFs can be effectively used in capillary electrochromatography (CEC) and their performances are far from adequate. In this study, we successfully synthesized achiral nanocrystalline MIL-53. A facile post-synthetic modification strategy was then implemented to functionalize the product, yielding a homochiral MOF: l-His-NH-MIL-53. This MOF was then employed as a chiral coating in open-tubular CEC mode (OT-CEC), and, as such, it exhibited high enantioselectivities for several racemic drugs. The homochiral MOF and the fabricated capillary coating were systematically characterized using transmission electron microscopy, scanning electron microscopy (with energy-dispersive X-ray spectrometry), Fourier-transform infrared spectroscopy, X-ray diffractometry, thermogravimetric analysis, circular dichroism spectroscopy, Brunauer-Emmett-Teller surface area measurements, and X-ray photoelectron spectroscopy. This study is expected to provide a new strategy for the design and establishment of MOF-based chiral OT-CEC systems.

With the advancement of semiconductor technology, chip cooling has become a major obstacle to enhancing the capabilities of power electronic systems. Traditional electronic packaging materials are no longer able to meet the heat dissipation requirements of high-performance chips. High thermal conductivity (TC), low coefficient of thermal expansion (CTE), good mechanical properties, and a rich foundation in microfabrication techniques are the fundamental requirements for the next generation of electronic packaging materials. Currently, metal matrix composites (MMCs) composed of high TC matrix metals and reinforcing phase materials have become the mainstream direction for the development and application of high-performance packaging materials. Silicon carbide (SiC) is the optimal choice for the reinforcing phase due to its high TC, low CTE, and high hardness. This paper reviews the research status of SiC-reinforced aluminum (Al) and copper (Cu) electronic packaging materials, along with the factors influencing their thermo-mechanical properties and improvement measures. Finally, the current research status and limitations of conventional manufacturing methods for SiC-reinforced MMCs are summarized, and an outlook on the future development trends of electronic packaging materials is provided.

This article aims to analyze the effects of enzyme treatment concentration, temperature, and time on peanut protein so as to obtain an optimal enzymatic hydrolysis condition for flavorzyme (Fla) and alkaline protease (Alk). The results were as follows: enzymatic hydrolysis temperature 60 °C and 55 °C, enzyme concentration 10% and 4%, enzymatic hydrolysis time 80 min and 60 min, and double enzyme hydrolysis ratio 2% Fla + 5% Alk, respectively. The BALB/c mice were sensitized with gavage of peanut protein before and after enzyme treatment to evaluate the effects of different enzyme treatments on peanut allergenicity. Compared with the mice sensitized with raw peanuts, the weight growth rate of the mice sensitized with enzyme treatment peanut increased but not as much as the control, the degranulation degree of mast cell and basophils decreased, the inflammatory infiltration and congestion in jejunum and lung tissue decreased, the expression of proinflammatory factors and thymic stromal lymphopoietin (TSLP) gene decreased, and the secretion of specific antibodies (IgE, and IgG) decreased, and the binding ability of peanut protein with peanut-specific IgE antibodies decreased as well. The results above indicate that the allergenicity of peanut protein decreases after enzyme treatment and the dual enzyme (Fla + Alk) treatment can be much more efficient.

Japan is advancing into a super-aged society at an unprecedented speed, and the proportion of the elderly population will continue to rise. The number of older adults needing nursing care will also increase with the aging population. We used a cross-sectional dataset of older Japanese adults to examine their future preferences for care facilities and their relationship with individual characteristics, household structure, and economic status. We further focused on a subgroup of those who lived alone and were experiencing poverty and examined their care needs through their choice of care facilities. We found the following results from multinomial logit and probit regressions. First, compared with living alone, older adults who live with their spouses or other members prefer to live in their own houses. Second, older adults experiencing poverty preferred to choose facilities geared towards low-income groups, while wealthy older adults preferred to choose fee-based nursing homes/nursing homes with diverse services and high costs. Third, single older adults in poverty were less likely to choose to live in facilities. Covariates such as sex, age, and health status also mattered in their choices. Therefore, tailoring the formal care services to the preferences and actual needs of older adults is imperative.

Bluetongue disease (BT) is a viral disease that can be introduced through imported animals and animal products, affecting local animal husbandry. In this study, the spatial and temporal patterns of BT outbreaks (outbreak: a BT infection in cattle, sheep, or goats on a farm, involving at least one infected animal) in France were analyzed and the risk of introducing bluetongue virus (BTV) into countries through trade was assessed. A spatiotemporal analysis of BT reported during the study period (2015–2018) showed that there were clustered outbreaks of BT in France in 2016 and 2017, with outbreaks concentrated from August to December. The outbreak moved eastward from the center of mainland France to surrounding countries. A semi-quantitative risk analysis framework was established by combining the likelihood assessment and consequence analysis of introducing BTV into trading countries through trade. Exemplified by China, the research showed that in the analysis of the likelihood of BTV from France being introduced into trading countries through live cattle trade, China imports a large number of live cattle, bringing high risks. The likelihood of introducing bovine semen into trading countries was similar to that of live cattle, but the harm caused by the trade in live cattle was higher than that caused by the trade in bovine semen. This risk analysis framework can provide a reference for other countries to quickly assess the risk of bluetongue transmission in import and export trade.

Abstract A recently developed synthetic retinoid abrogates proliferation and induces apoptosis of drug‐resistant malignant‐cancer‐stem‐cell‐like cells. However, the underlying mechanisms of how the synthetic retinoid induces cancer‐stem‐cell‐like cell tumor‐repopulating cell (TRC) apoptosis are elusive. Here, it is shown that although the retinoid and conventional anticancer drugs cisplatin, all‐trans retinoic acid, and tazarotene all inhibit cytoskeletal tension and decondense chromatin prior to inducing TRC apoptosis, half‐maximal inhibitory concentration of the retinoid is 20‐fold lower than those anticancer drugs. The synthetic retinoid induces retinoic acid receptor gamma (RARγ) translocation from the nucleus to the cytoplasm, leading to reduced RARγ binding to Cdc42 promoter and Cdc42 downregulation, which decreases filamentous‐actin (F‐actin) and inhibits cytoskeletal tension. Elevating F‐actin or upregulating histone 3 lysine 9 trimethylation decreases retinoid‐induced DNA damage and apoptosis of TRCs. The combinatorial treatment with a chromatin decondensation molecule and the retinoid inhibits tumor metastasis in mice more effectively than the synthetic retinoid alone. These findings suggest a strategy of lowering cell tension and decondensing chromatin to enhance DNA damage to abrogate metastasis of cancer‐stem‐cell‐like cells with high efficacy.

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and manifests as progressive memory loss and cognitive dysfunction. Neuroinflammation plays an important role in the development of Alzheimer’s disease and anti-inflammatory drugs reduce the risk of the disease. However, the immune microenvironment in the brains of patients with Alzheimer’s disease remains unclear, and the mechanisms by which anti-inflammatory drugs improve Alzheimer’s disease have not been clearly elucidated. This study aimed to provide an overview of the immune cell composition in the entorhinal cortex of patients with Alzheimer’s disease based on the transcriptomes and signature genes of different immune cells and to explore potential therapeutic targets based on the relevance of drug targets. Transcriptomics data from the entorhinal cortex tissue, derived from GSE118553, were used to support our study. We compared the immune-related differentially expressed genes (irDEGs) between patients and controls by using the limma R package. The difference in immune cell composition between patients and controls was detected via the xCell algorithm based on the marker genes in immune cells. The correlation between marker genes and immune cells and the interaction between genes and drug targets were evaluated to explore potential therapeutic target genes and drugs. There were 81 irDEGs between patients and controls that participated in several immune-related pathways. xCell analysis showed that most lymphocyte scores decreased in Alzheimer’s disease, including CD4+ Tc, CD4+ Te, Th1, natural killer (NK), natural killer T (NKT), pro-B cells, eosinophils, and regulatory T cells, except for Th2 cells. In contrast, most myeloid cell scores increased in patients, except in dendritic cells. They included basophils, mast cells, plasma cells, and macrophages. Correlation analysis suggested that 37 genes were associated with these cells involved in innate immunity, of which eight genes were drug targets. Taken together, these results delineate the profile of the immune components of the entorhinal cortex in Alzheimer’s diseases, providing a new perspective on the development and treatment of Alzheimer’s disease.

Heavy metal pollution is a major threat to agricultural produce and it can pose potential ecological risks which subsequently impacts on human health. Strawberries are an economically important produce of China. The intrinsic link of heavy metal pollution risk in the soil-strawberry ecosystem is of concern. In this study, the pollution index of heavy metal pollutants in farmlands of different provinces were evaluated, and the results showed significantly high levels of cadmium. In addition, Nemerow integrated pollution index analysis showed that low-pollution farmlands only accounted for 14.07% of the total arable land area. Then, the transfer factors were used to calculate the migration of heavy metals from the soil into strawberries. The results showed that cadmium and nickel were relatively high in strawberries from the Guangxi province. Similar results were found for mercury in Jiangxi Province. The pollution index of single food pollution also showed that mercury in strawberries from Jiangxi Province was at a moderate pollution level. The comprehensive pollution index indicated that heavy metal pollution in strawberries in Central China may be severe. In addition, spatial clustering analysis showed that cadmium, chromium, lead, arsenic and zinc in strawberries had significant hotspot clustering in central, south and southwest China. Finally, our studies also suggested that the risk of carcinogenic and non-carcinogenic diseases was higher in the (2, 4] years age group than in other age groups. People in Yunnan Province were also found to have a higher non-carcinogenic risk than those in other provinces and cities in China. This study provides a comprehensive view of the potential risks of heavy metal contamination in strawberries, which could provide assistance in the design of regulatory and risk management programs for chemical pollutants in strawberries, thus ensuring the safety of consumption of these edible fruits.

Abstract Background Recurrent hepatocellular carcinoma (HCC) shows strong resistance to sorafenib, and the tumor-repopulating cells (TRCs) with cancer stem cell-like properties are considered a driver for its high recurrent rate and drug resistance. Methods Suppression of TRCs may thus be an effective therapeutic strategy for treating this fatal disease. We evaluated the pharmacology and mechanism of sulfarotene, a new type of synthetic retinoid, on the cancer stem cell-like properties of HCC TRCs, and assessed its preclinical efficacy in models of HCC patient-derived xenografts (PDXs). Results Sulfarotene selectively inhibited the growth of HCC TRCs in vitro and significantly deterred TRC-mediated tumor formation and lung metastasis in vivo without apparent toxicity, with an IC50 superior to that of acyclic retinoid and sorafenib, to which the recurrent HCC exhibits significant resistance at advanced stage. Sulfarotene promoted the expression and activation of RARα, which down-regulated SOS2, a key signal mediator associated with RAS activation and signal transduction involved in multiple downstream pathways. Moreover, sulfarotene selectively inhibited tumorigenesis of HCC PDXs with high expression for SOS2. Conclusions Our study identified sulfarotene as a selective inhibitor for the TRCs of HCC, which targets a novel RARα-SOS2-RAS signal nexus, shedding light on a new, promising strategy of target therapy for advanced liver cancer.

Abstract Background Foot-and-mouth disease (FMD) is a highly contagious disease of livestock worldwide. Russia is a big agricultural country with a wide geographical area where FMD outbreaks have become an obstacle for the development of the animal and animal products trade. In this study, we aimed to assess the export risk of FMD from Russia. Results After simulation by Monte Carlo, the results showed that the probability of cattle infected with FMD in the surveillance zone (Surrounding the areas where no epidemic disease has occurred within the prescribed time limit, the construction of buffer areas is called surveillance zone.) of Russia was 1.29 × 10− 6. The probability that at least one FMD positive case was exported from Russia per year in the surveillance zone was 6 %. The predicted number of positive cattle of the 39,530 - 50,576 exported from Russia per year was 0.06. A key node in the impact model was the probability of occurrence of FMD outbreaks in the Russian surveillance zone. By semi-quantitative model calculation, the risk probability of FMD defense system defects was 1.84 × 10− 5, indicating that there was a potential risk in the prevention and control measures of FMD in Russia. The spatial time scan model found that the most likely FMD cluster (P

Nucleic acid amplification is a sensitive and powerful tool for allergen detection. However, it is limited due to the relatively cumbersome methods required to extract nucleic acids from single plant seed allergen (e.g. peanut and soybean). In view of this, an approach of extracting nucleic acid with untreated glass-fiber paper (paper-based microfluidics) was applied for nucleic acid capture and purification from plant seed allergen and commercial products. After cut by hollow cylindrical cutter, a certain size the paper chip it used to absorb DNA. And this paper-based microfluidics with DNA was directly applied for amplification by loop-mediated isothermal amplification (LAMP). To evaluate the adsorption performance of paper chip to DNA, CTAB and SDS method were used as comparisons. From amplification results, the established technique has good specificity, high repeatability (C.V. values are 4.41% and 6.17% for peanut and soybean) and favorable sensitivity (7.39 ng/μL or peanut and 6.6 ng/μL for soybean), and successfully used for commercial products (2 kinds of candy and 2 kinds of cakes containing peanut, and 2 kinds of drinks, candy and 2 kinds of biscuits containing soybean). This speed and flexible detection method makes it suit for applications in point-of-care (POC) detection at different scenario, such as custom house and import port.

Abstract The development of photo-controlled adhesives can overcome the problems associated with daily lives and industrial applications. Adhesion is a multidiscipline field of engineering, physics, and chemistry. The solid-to-liquid transformation of light-controlled adhesives can be used for direct bonding onto diverse surfaces. Here, a photoresponsive azobenzene compound is developed for photo-controlled adhesion. The azobenzene compound 4, 4'-hexyl diacrylate-3-methylazobenzene (M1) exhibits photoinduced solid-to-liquid transition due to trans–cis photoisomerization. The prepolymer coating based on the azobenzene compound M1 is prepared on an adhesive surface. After UV irradiation, the solid coating was quickly transformed into liquid for adhesion. This photo-controlled adhesive has strong adhesion to different surfaces.

Alzheimer’s disease (AD) is the most common type of dementia and is a serious disruption to normal life. Monoamine oxidase-B (MAO-B) is an important target for the treatment of AD. In this study, machine learning approaches were applied to investigate the identification model of MAO-B inhibitors. The results showed that the identification model for MAO-B inhibitors with K-nearest neighbor(KNN) algorithm had a prediction accuracy of 94.1% and 88.0% for the 10-fold cross-validation test and the independent test set, respectively. Secondly, a quantitative activity prediction model for MAO-B was investigated with the Topomer CoMFA model. Two separate cutting mode approaches were used to predict the activity of MAO-B inhibitors. The results showed that the cut model with q2 = 0.612 (cross-validated correlation coefficient) and r2 = 0.824 (non-cross-validated correlation coefficient) were determined for the training and test sets, respectively. In addition, molecular docking was employed to analyze the interaction between MAO-B and inhibitors. Finally, based on our proposed prediction model, 1-(4-hydroxyphenyl)-3-(2,4,6-trimethoxyphenyl)propan-1-one (LB) was predicted as a potential MAO-B inhibitor and was validated by a multi-spectroscopic approach including fluorescence spectra and ultraviolet spectrophotometry.

The current detection method of carbendazim suffers from the disadvantages of complicated preprocessing and long cycle time. In order to solve the problem of rapid quantitative screening of finite contaminants, this article proposed a qualitative method based on characteristic peaks and a semi-quantitative method based on threshold to detect carbendazim in apple, and finally the method is evaluated by a validation system based on binary output. The results showed that the detection limit for carbendazim was 0.5 mg/kg, and the detection probability was 100% when the concentration was no less than 1 mg/kg. The semi-quantitative analysis method had a false positive rate of 0% and 5% at 0.5 mg/kg and 2.5 mg/kg, respectively. The results of method evaluation showed that when the added concentration was greater than 2.5 mg/kg, the qualitative detection method was consistent with the reference method. When the concentration was no less than 5 mg/kg, the semi-quantitative method is consistent between different labs. The semi-quantitative method proposed in this study can achieve the screening of finite contaminants in blind samples and simplify the test validation process through the detection probability model, which can meet the needs of rapid on-site detection and has a good application prospect.

Abstract Background Blood transfusion, a common basic supporting therapy, can lead to acute hemolytic transfusion reaction (AHTR). AHTR poses a great risk to patients through kidney function damage in a short time. Previous reports found that heme from destroyed red blood cells impaired kidney function, and NLR family pyrin domain containing 3 (NLRP3) inflammasome was augmented in case of kidney injury. However, the detailed mechanism regarding whether NLRP3 inflammasome is involved in kidney function injury in AHTR is not fully understood yet. Methods Hemolysis models were established by vein injection with human blood plasma or mouse heme from destroyed red blood cells. The injured renal tubular epithelial cells (RTECs) were evaluated by tubular damage markers staining in hemolysis models and in primary RTECs in vitro. The activation of NLRP3 inflammasome in RTECs by hemes was investigated by Western blot, ELISA, scanning electron microscopy, immunofluorescent staining, flow cytometry, and hemolysis models. NLRP3 gene knockout mice were employed to confirm these observations in vitro and in vivo. The binding between a novel inhibitor (66PR) and NLRP3 was affirmed by molecule docking and co‐immunoprecipitation. The rescue of 66PR on kidney function impairment was explored in murine hemolysis models. Results We found that heme could activate NLRP3 inflammasome in RTECs to induce kidney function injury. NLRP3 gene knockout could prevent the damage of RTECs caused by hemes and recover kidney function in AHTR. Moreover, NLRP3 inflammasome chemical inhibitor, 66PR, could bind to NLRP3 protein and inhibit inflammasome activation in RTECs, which consequently relieved the injury of RTECs caused by hemes, and alleviated kidney function damage in the AHTR model. Conclusions Hemes could activate NLRP3 inflammasome in RTECs, and a novel NLRP3 inflammasome inhibitor named 66PR relieved kidney function damage in AHTR. Our findings provided a new possible strategy to treat kidney function failure in AHTR.

Peste des Petits Ruminants (PPR) is an acute and highly contagious transboundary disease caused by the PPR virus (PPRV). The virus infects goats, sheep and some wild relatives of small domestic ruminants, such as antelopes. PPR is listed by the World Organization for Animal Health as an animal disease that must be reported promptly. In this paper, PPR outbreak data combined with WorldClim database meteorological data were used to build a PPR prediction model. Using feature selection methods, eight sets of features were selected: bio3, bio10, bio15, bio18, prec7, prec8, prec12, and alt for modeling. Then different machine learning algorithms were used to build models, among which the random forest (RF) algorithm was found to have the best modeling effect. The ACC value of prediction accuracy for the model on the training set can reach 99.10%, while the ACC on the test sets was 99.10%. Therefore, RF algorithms and eight features were finally selected to build the model in order to build the online prediction system. In addition, we adopt single-factor modeling and correlation analysis of modeling variables to explore the impact of each variable on modeling results. It was found that bio18 (the warmest quarterly precipitation), prec7 (the precipitation in July), and prec8 (the precipitation in August) contributed significantly to the model, and the outbreak of the epidemic may have an important relationship with precipitation. Eventually, we used the final qualitative prediction model to establish a global online prediction system for the PPR epidemic.

Abstract Background African swine fever (ASF) is a devastating infectious disease of pigs. ASF poses a potential threat to the world pig industry, due to the lack of vaccines and treatments. In this study, the Geographic Information System (GIS) spatial analysis was applied to analyze the distribution, dispersion of the epidemic and clustering of ASF in Poland. Results The results show that the center of the epidemic moved gradually towards the southwest, and the distribution of the epidemic changed from south-north to east-west. Through space-time scan statistical analysis, the 3 clusters major of wild boar cases involve longer time spans and larger radii, while the other five with higher relative risks involved in domestic pigs. And then, a quantitative model was constructed to analyse the risk of releasing African swine fever virus (ASFV) from Poland by the legal export of pork and pork products. The Latin hypercube sampling results show that the probability is relatively low (the average value is 4.577 × 10− 7). Conclusions All the identification of the spatio-temporal patterns of the epidemic and the risk analysis model would give a further understanding of the dynamics of disease transmission and help to design corresponding measures to minimize the catastrophic consequences of potential ASFV introduction.

Avian influenza is a serious zoonotic infectious disease with huge negative impacts on local poultry farming, human health and social stability. Therefore, the design of new compounds against avian influenza has been the focus in this field. In this study, computational methods were applied to investigate the compounds with neuraminidase inhibitory activity. First, 2D-SAR model was built to recognize neuraminidase inhibitors (NAIs). As a result, the accuracy of 10 cross-validation and independent tests is 96.84% and 98.97%, respectively. Then, the Topomer CoMFA model was constructed to predict the inhibitory activity and analyses molecular fields. Two models were obtained by changing the cutting methods. The second model is employed to predict the activity (q2 = 0.784 and r2 = 0.982). Molecular docking was also used to further analyze the binding sites between NAIs and neuraminidase from human and avian virus. As a result, it is found that same binding Total Score has some differences, but the binding sites are basically the same. At last, some potential NAIs were screened and some optimal opinions were taken. It is expected that our study can assist to study and develop new types of NAIs. Keywords: Avian influenza, Neuraminidase, 2D-SAR, Topomer CoMFA, Molecular docking

Abstract Background Cronobacter species are associated with severe foodborne infections in neonates and infants, with particular pathovars associated with specific clinical presentations. However, before 2008 the genus was regarded as a single species named Enterobacter sakazakii which was subdivided into 8 phenotypes. This study re-analyzed, using multi-locus sequence typing (MLST) and whole genome sequence with single nucleotide polymorphism analysis (WGS-SNP), 52 strains which had been identified as Enterobacter sakazakii as according to the convention at the time of isolation. These strains had been isolated from dairy product imports into China from 9 countries between 2005 and 6. Bioinformatic analysis was then used to analyze the relatedness and global dissemination of these strains. Result FusA allele sequencing revealed that 49/52 strains were Cronobacter sakazakii, while the remaining 3 strains were Escherichia coli, Enterobacter cloacae, and Franconibacter helveticus. The C. sakazakii strains comprised of 8 sequence types (STs) which included the neonatal pathovars ST1, ST4 and ST12. The predominant sequence type was ST13 (65.3%, 32/49) which had been isolated from dairy products imported from 6 countries. WGS-SNP analysis of the 32 C. sakazakii ST13 strains revealed 5 clusters and 5 unique strains which did not correlate with the country of product origin. Conclusion The mis-identification of E. coli, E. cloacae and F. helveticus as Cronobacter spp. reinforces the need to apply reliable methods to reduce the incidence of false positive and false negative results which may be of clinical significance. The WGS-SNP analysis demonstrated that indistinguishable Cronobacter strains within a sequence type can be unrelated, and may originate from multiple sources. The use of WGS-SNP analysis to distinguishing of strains within a sequence type has important relevance for tracing the source of outbreaks due to Cronobacter spp.

Foot-and-mouth disease (FMD) is a highly contagious disease of livestock and seriously affects the development of animal husbandry. It is necessary to defend the spread of FMD. To explore the distribution characteristics and transmission of FMD between 2010 and 2017 in China, Global Moran's I test and Getis-Ord Gi index were used to analyze the spatial cluster. A space-time permutation scan statistic was applied to analyze the spatio-temporal pattern. GIS-based method was employed to create a map representing the distribution pattern, directional trend, and hotspots for each outbreak. The number of cases was defined as the number of animals with FMD for the above analysis. We also constructed a phylogenetic tree to compare the homology and variation of FMD virus (FMDV) to provide a clue for the potential development of an effective vaccine. The results indicated that the FMD outbreaks in China had obvious time patterns and clusters in space and space-time, with the outbreaks concentrated in the first half of each year. The outbreaks of FMD decreased each year from 2010 with an obvious downward trend of hotspots. Spatial analysis revealed that the distribution of FMD outbreaks in 2010, 2015, and 2017 exhibited a clustered pattern. Space-time scanning revealed that the spatio-temporal clusters were centered in Guangdong, Tibet and the junction of Wuhan, Jiangxi, Anhui. Comparison of the spatial analysis and space-time analysis of FMD outbreaks revealed that Guangdong was the same cluster of the two in 2010. In addition, the directional trend analysis indicated that the FMD transmission was oriented northwest-southeast. The findings demonstrated that FMDV in China can be divided into three pedigrees and the homology of these strains is very high while comparing the first FMDV strain with the others. The data provide a basis for the effective monitoring and prevention of FMD, and for the development of an FMD vaccine in China.

Vesicular stomatitis (VS) is an important viral disease of livestock. The main feature of VS is irregular blisters that occur on the lips, tongue, oral mucosa, hoof crown and nipple. Humans can also be infected with vesicular stomatitis and develop meningitis. This study analyses 2014 American VS outbreaks in order to accurately predict vesicular stomatitis outbreak trends.American VS outbreaks data were collected from OIE. The data for VS keywords were obtained by inputting 24 disease-related keywords into Google Trends. After calculating the Pearson and Spearman correlation coefficients, it was found that there was a relationship between outbreaks and keywords derived from Google Trends. Finally, the predicted model was constructed based on qualitative classification and quantitative regression.For the regression model, the Pearson correlation coefficients between the predicted outbreaks and actual outbreaks are 0.953 and 0.948, respectively. For the qualitative classification model, we constructed five classification predictive models and chose the best classification predictive model as the result. The results showed, SN (sensitivity), SP (specificity) and ACC (prediction accuracy) values of the best classification predictive model are 78.52%,72.5% and 77.14%, respectively.This study applied Google search data to construct a qualitative classification model and a quantitative regression model. The results show that the method is effective and that these two models obtain more accurate forecast.

ObjectiveTo describe and analyze the clinical characteristics, laboratory data, management, and outcome of patients with onconeural antibody-associated disorders (OAAD) and identify predictors for poor outcome.MethodsThis was a retrospective review of all patients with potential OAAD, who were hospitalized in Jinan General Hospital between September 2009 and July 2017. We clarified the diagnosis, collected comprehensive information and categorized patients into three groups: paraneoplastic neurological disorders (PNDs), autoimmune encephalitis (AE), and possible OAAD. Within the three groups, we analyzed a range of clinical and laboratory parameters and used univariate and multivariate regression analysis to identify predictors for poor outcome [modified Rankin Scale (mRS) = 3–6].ResultsFrom 158 patients, we identified 70 who fulfilled the criteria for OAAD, including 44 men (62.9%) and 26 women (37.1%). There were 38 patients (54.3%) in the PNDs group, 14 patients (20%) in the AE group, and 18 patients (25.7%) in the possible OAAD group. After the last follow-up, 14 (36.8%), 9 (64.2%), and 12 (66.7%) had a good outcome (mRS = 0–2). However, 6 (15.8%), 2 (14.3%), and 3 (16.7%) died, respectively. Univariate analysis showed that duration prior to the hospital (p = 0.0224) and urinary incontinence/retention (p = 0.0043) were associated with poor outcome (mRS = 3–6). After multivariate regression analysis, urinary incontinence/retention (p = 0.0388) and an immunocompromised state (p = 0.0247) remained as significant factors for poor outcome.ConclusionUrinary incontinence/retention and an immunocompromised state represent significant predictors of a worse prognosis for patients with OAAD. By contrast, cerebrospinal fluid analysis showed that serum autoantibodies and tumor markers, the function of crucial organs, electrophysiology, and radiological findings were not associated with a poor outcome.

PURPOSE:To evaluate the short-term changes in ocular surface measures and tear inflammatory mediators after femtosecond lenticule extraction (FLEx) and small-incision lenticule extraction (SMILE) procedures. METHODS:Eighteen subjects (18 eyes) underwent FLEx and 23 subjects (23 eyes) underwent SMILE in this single-center and prospective study. Central corneal sensitivity, Schirmer I test (SIT), noninvasive tear breakup time (NI-TBUT), tear meniscus height, corneal fluorescein (FL) staining, and ocular surface disease index (OSDI) were assessed in all patients. Concentrations of interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF), interferon-γ (IFN-γ), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) in collected tears were measured by multiplex antibody microarray. RESULTS:Central corneal sensitivity was reduced in both groups, but the scores in the SMILE group were higher than those in the FLEx group at all time points postoperatively (P

Acquired immune deficiency syndrome (AIDS) is a severe infectious disease that causes a large number of deaths every year. Traditional anti-AIDS drugs directly targeting the HIV-1 encoded enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) usually suffer from drug resistance after a period of treatment and serious side effects. In recent years, the emergence of numerous useful information of protein-protein interactions (PPI) in the HIV life cycle and related inhibitors makes PPI a new way for antiviral drug intervention. In this study, we identified 26 core human proteins involved in PPI between HIV-1 and host, that have great potential for HIV therapy. In addition, 280 chemicals that interact with three HIV drugs targeting human proteins can also interact with these 26 core proteins. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying novel anti-HIV drugs.