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Tumor immunotherapy has garnered considerable attention, emerging as a new standard of care in cancer treatment. The conventional targets, such as VEGF and EGFR, have been extended to others including BRAF and PD-1/PD-L1, which have shown significant potential in recent cancer treatments. This review aims to succinctly overview the impact and mechanisms of therapies that modulate PD-1/PD-L1 expression by targeting VEGF, EGFR, LAG-3, CTLA-4 and BRAF. We investigated how modulation of PD-1/PD-L1 expression impacts growth factor signaling, shedding light on the interplay between immunomodulatory pathways and growth factor networks within the tumor microenvironment. By elucidating these interactions, we aim to provide insights into novel potential synergistic therapeutic strategies for cancer immunotherapy.

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Purpose: Accumulating evidence indicates that oxidative stress and inflammation are the pathological basis of allergic diseases. Inhibition of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome could ameliorate allergic rhinitis (AR). Here, we explored the effects and mechanisms that underlie NLRP3 inhibition on oxidative stress and inflammation in AR. Methods: Ovalbumin (OVA)-induced AR murine model was established using wild-type (WT) and NLRP3-deficient mice. HNEpCs were stimulated with interleukin (IL)-13 with MCC950 pretreatment or PTEN-induced putative kinase 1 (PINK1) siRNA. The indicators of oxidative stress, inflammation, apoptosis, and mitophagy were determined both in vivo and in vitro. Results: NLRP3 knockout (KO) reduced the frequency of nasal rubbing and sneezing, the infiltration of eosinophils, the number of mast cells, and the accumulation of goblet cells in AR mice after OVA stimulation. The NLRP3 KO AR mice exhibited the increased concentrations of OVA-specific immunoglobulin E (OVA-sIgE), IL-1ß, IL-4, IL-13, IL-6, TNF-α, and the upregulated level of IFN-γ. NLRP3 KO significantly inhibited oxidative stress, and also markedly decreased apoptosis in the nasal mucosa of AR mice. Moreover, evaluated protein expressions of PINK1, enzyme 3 (E3) ubiquitin ligase PRKN (Parkin), and LC3 II, decreased expression of TOM20, as well as the increased colocalization of LC3 with mitochondria were observed in NLRP3 KO AR mice. In vitro, IL-13 exposure increased the levels of NLRP3 and IL-1ß. Inhibition of NLRP3 using MCC950 enhanced PINK1/Parkin-mediated mitophagy but attenuated inflammation, oxidative stress, and apoptosis. However, PINK1 knockdown abrogated mitophagy and also reversed the protective effects of MCC950 on inflammation, oxidative stress, and apoptosis in HNEpCs stimulated with IL-13. Conclusion: Inhibition of NLRP3 inflammasome exerts the protective effects on AR by facilitating mitophagy regulated by PINK1/Parkin signaling pathway.

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Bluetongue disease is an infectious disease transmitted by Culicoides as vectors, mainly infecting ruminants. Because ruminants play an important role in animal husbandry in China, the outbreak of bluetongue disease can cause serious economic losses. Maxent model was applied to predict the distribution of bluetongue in China based on the data derived from domestic and foreign academic literature databases including CNKI, Wanfang Database, PubMed, Web of Science and Google Scholar. The results showed that annual mean temperature (BIO1), precipitation in driest month (BIO14), sheep density (SD) and altitude (Elev) were the relevant variables of bioclimatic suitable zones for bluetongue disease. Precipitation in wettest month (BIO13), BIO1, BIO14, Elev were the main variables affecting the habitat of the bluetongue vector Culicoides. The most suitable climate for bluetongue infection occurs in southern China, central China and parts of Xinjiang. The suitable living areas of Culicoides are mainly located in southern, central and eastern China, and the overlap of the two suitable areas is high. The study suggested that southern, central, and eastern China are high-risk areas for bluetongue due to the significant overlap of suitable habitats for both the disease and its vector. Implementing effective surveillance and targeted control strategies in these regions is crucial for mitigating the impact of bluetongue disease.

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With the rapid development of electronic technology and large-scale integrated circuit devices, it is very important to develop thermal management materials with high thermal conductivity. Silicon carbide whisker-reinforced copper matrix (Cu/SiCw) composites are considered to be one of the best candidates for future electronic device radiators. However, at present, most of these materials are produced by high-temperature and high-pressure processes, which are expensive and prone to interfacial reactions. To explore the plating solution system suitable for SiCw and Cu composite electroplating, we tried two different Cu-based plating solutions, namely a Systek UVF 100 plating solution of the copper sulfate (CuSO4) system and a Through Silicon Via (TSV) plating solution of the copper methanesulfonate (Cu(CH3SO3)2) system. In this paper, Cu/SiCw composites were prepared by composite electrodeposition. The morphology of the coating under two different plating liquid systems was compared, and the mechanism of formation of the different morphologies was analyzed. The results show that when the concentration of SiCw in the bath is 1.2 g/L, the surface of the Cu/SiCw composite coating prepared by the CuSO4 bath has more whiskers with irregular distribution and the coating is very smooth, but there are pores at the junction of the whiskers and Cu. There are a large number of irregularly distributed whiskers on the surface of the Cu/SiCw composite coating prepared with the copper methanesulfonate (Cu(CH3SO3)2) system. The surface of the composite is flat, and Cu grows along the whisker structure. The whisker and Cu form a good combination, and there is no pore in the cross-section of the coating. The observation at the cross-section also reveals some characteristics of the toughening mechanism of SiCw, including crack deflection, bridging and whisker pull-out. The existence of these mechanisms indicates that SiCw plays a toughening role in the composites. A suitable plating solution system was selected for the preparation of high-performance Cu/SiCw thermal management materials with the composite electrodeposition process.

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The creation of well-defined surface nanostructures is important for a diverse set of applications such as cell adhesion, superhydrophobic coating, and lithography. In this study, we describe a robust bottom-up method for surface functionalization that involves surface-initiated reversible deactivation radical polymerization (RDRP) and the grafting of block copolymer nanoparticles to material surfaces via aqueous photoinduced polymerization-induced self-assembly (photo-PISA) at room temperature. Using silica nanoparticles as a model substrate, colloidal mesoscale hybrid assemblies with various morphologies were successfully prepared. The morphologies can be easily tuned by changing the lengths of macromolecular chain transfer agents and parameters of the silica nanoparticles. The surface-initiated photo-PISA approach can also be employed for other large-scale substrates such as silicon wafer. Taking advantage of mild reaction conditions of this method (room temperature, aqueous medium, and visible light), enzymatic deoxygenation was introduced to develop oxygen-tolerant surface-initiated photo-PISA that can fabricate well-defined nanostructures on large-scale substrates under open-to-air conditions.

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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.

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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.

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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.

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FMD is an acute contagious disease that poses a significant threat to the health and safety of cloven-hoofed animals in Asia, Europe, and Africa. The impact of FMD exhibits geographical disparities within different regions of China. The present investigation undertook an exhaustive analysis of documented occurrences of bovine FMD in China, spanning the temporal range from 2011 to 2020. The overarching objective was to elucidate the temporal and spatial dynamics underpinning these outbreaks. Acknowledging the pivotal role of global factors in FMD outbreaks, advanced machine learning techniques were harnessed to formulate an optimal prediction model by integrating comprehensive meteorological data pertinent to global FMD. Random Forest algorithm was employed with top three contributing factors including Isothermality(bio3), Annual average temperature(bio1) and Minimum temperature in the coldest month(bio6), all relevant to temperature. By encompassing both local and global factors, our study provides a comprehensive framework for understanding and predicting FMD outbreaks. Furthermore, we conducted a phylogenetic analysis to trace the origin of Foot-and-mouth disease virus (FMDV), pinpointing India as the country posing the greatest potential hazard by leveraging the spatio-temporal attributes of the collected data. Based on this finding, a quantitative risk model was developed for the legal importation of live cattle from India to China. The model estimated an average probability of 0.002254% for FMDV-infected cattle imported from India to China. TA sensitivity analysis identified two critical nodes within the model: he possibility of false negative clinical examination in infected cattle at destination (P5) and he possibility of false negative clinical examination in infected cattle at source(P3). This comprehensive approach offers a thorough evaluation of FMD landscape within China, considering both domestic and global perspectives, thereby augmenting the efficacy of early warning mechanisms.

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Pork is one of the most commonly consumed meats, and its safety has always been a concern. Recently, safety incidents caused by chemical or biological contamination such as drug residues, heavy metals, and pathogenic microorganisms in pork have been reported, and the safety of pork is a cause for concern. Salmonella spp. is one of the important foodborne pathogens that threaten human health. Pork is a high-risk vector food for Salmonella spp. infection. The assessment of the safety risk of Salmonella spp. in pork is conducive to the prevention of related foodborne diseases. In this paper, risk assessment models for Salmonella spp. in meat were developed. The quantitative risk assessment model for Salmonella spp. based on the pork supply chain showed that the annual number of cases of salmonellosis due to pork consumption in China is approximately 27 per 10,000 males and 24 per 10,000 females. Sensitivity analysis showed that the main factors affecting the risk of Salmonella spp. in pork were the display temperature, display time, and Salmonella spp. contamination concentration in pork at the sale.

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Long-term exposure to pesticides is associated with the incidence of cancer. With the exponential increase in the number of new pesticides being synthesized, it becomes more and more important to evaluate the toxicity of pesticides by means of simulated calculations. Based on existing data, machine learning methods can train and model the predictions of the effects of novel pesticides, which have limited available data. Combined with other technologies, this can aid the synthesis of new pesticides with specific active structures, detect pesticide residues, and identify their tolerable exposure levels. This article mainly discusses support vector machines, linear discriminant analysis, decision trees, partial least squares, and algorithms based on feedforward neural networks in machine learning. It is envisaged that this article will provide scientists and users with a better understanding of machine learning and its application prospects in pesticide toxicity assessment.

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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.

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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.

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Melamine is one of the common limited contaminations in dairy products. The traditional detection method has a long period and complicated pretreatment process. The rapid detection method is the better method to solve the screening of limited contaminations. In this paper, taking melamine as the research object, the surface enhanced Raman spectrum of melamine in liquid milk were collected by portable Raman spectrometer, and melamine was qualitatively identified and semi-quantitatively analyzed by Raman characteristic peak and Raman intensity, and a simple and efficient rapid screening method for limited contaminations was developed. The limit of detection is 0.25 mg/kg. The probability of detection is 100% at 2.5 mg/kg, which is the same between the two laboratories, indicating that the semi-quantitative method has good repeatability. The method of melamine proposed in this study can meet the rapid screening requirements of limited contaminations at the maximum residue limit, and has a good application prospect.

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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.

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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.

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BACKGROUND: Neuraminidase is a pathogenic protein of the avian influenza virus. Previous studies have shown that silibinin has the potential to inhibit neuraminidase activity. OBJECTIVE: This study aims to explore the interaction between silibinin and neuraminidase and the effect of silibinin on the structure and activity of neuraminidase. METHODS: In this study, two-dimensional fluorescence spectrum, three-dimensional fluorescence spectrometry, Uv-vis spectroscopy, and circular dichroism analysis were used. RESULTS: Silibinin alters the secondary structure of neuraminidase and inhibits the activity of neuraminidase. CONCLUSION: Silibinin can interact with neuraminidase and inhibit its activity.

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Diabetes mellitus has become a serious life-threatening disease. As one of the new drugs for the treatment of diabetes, GLP-1 receptor agonists have attracted a lot of attention. Compared with traditional hypoglycemic drugs, GLP-1 receptor agonists have good safety and tolerability. To a certain extent, they overcome the problem of the short half-life of natural GLP-1 in vivo and can exist stably in patients for a long time, achieving good results in the treatment of diabetes, as well as improving the symptoms of some complications. The GLP-1 receptor agonists in the market are all peptide drugs. Compared with peptide drugs, small molecule agonists have the advantages of low cost and oral administration. In this article, we review the recent research progress of GLP-1 receptor agonists.

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A novel chiral group functionalized metal-organic framework, Cyclodextrin-NH-MIL-53, was synthesized and modified on the inner wall of a capillary column via a post-synthetic process. The prepared chiral metal-organic framework was utilized as a chiral capillary stationary phase and used in an open-tubular capillary electrochromatography method to enantioseparate several racemic amino acids. Excellent enantioseparation of five pairs of enantiomers was obtained in this chiral separation system (Resolutions of D/L-Alanine = 16.844, D/L-Cysteine = 3.617, D/L-Histidine = 9.513, D/L-Phenylalanine = 8.133, and D/L-Tryptophan = 2.778). The prepared Cyclodextrin-NH-MIL-53 and the Cyclodextrin-NH-MIL-53-based capillary columns were characterized by scanning electron microscopy, X-ray diffraction, Fourie-transform infrared spectroscopy, and circular dichroism. The chiral capillary electrochromatography conditions, such as separation conditions, amount of Cyclodextrin-NH-MIL-53, and electroosmotic flow, were optimized. This research is estimated to present a novel insight and method for the design and use of metal-organic framework-based capillaries for enantioseparation.