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In order to improve the physicochemical properties of oat protein-based composite film, the natural oat protein (OP) was modified to prepare oat protein amyloid aggregates (OPA), and then the composite film was prepared with sodium carboxymethyl cellulose (CMCNa). The microstructure and properties of the composite films were studied by Fourier infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The mechanical properties, optical properties, moisture content, water solubility and water vapor permeability of the composite films were also determined. The results showed that the structure of the modified oat protein changed significantly. Compared with the OP/CMCNa composite film, the surface of the OPA/CMCNa composite film was smoother and the structure was more compact. Compared with OP/CMCNa composite film, the water solubility of OPA/CMCNa composite film was reduced by 7.02% to 15.84%, and the water resistance of OPA/CMCNa composite film was significantly improved. Among them, the puncture distance of the composite film prepared by OPA8 was increased to 6.513 mm, the force was increased to 701.2 g, and the mechanical properties were significantly improved. In conclusion, oat protein amyloid aggregates can effectively improve the transparency, water resistance and mechanical properties of natural oat protein-based composite films. The results can provide reference for the preparation and properties of modified oat protein composite film.

Gamma spectrometry analysis of uranium enrichment is an important technical tool for international nuclear safeguards verification. As a kind of special nuclear materials，235U is an important verification object of nuclear safeguards verification. In addition，the determination of uranium enrichment in samples is a key measurement for product process control，process measurement and waste characterization in uranium enrichment production facilities，uranium conversion facilities，fuel manufacturing plants and reprocessing plants，as well as a key technical means for tracking illicit trafficking in nuclear materials and responding to terrorist threats and attacks in homeland security activities. Simulated annealing algorithm is aiming to simulate the solid annealing process，and iteratively solve the solution problem by continuously reducing the annealing temperature and combining with the Metropolis criterion. The result has been proved to converge to the global optimal solution according to probability 1，which is one of the common solutions for solving optimization problems. In the article，a uranium enrichment calculation method based on simulated annealing algorithm is proposed for gamma spectrometry analysis. A corresponding mathematical model is established for the practical problem of enrichment calculation，the generation and iterative process of algorithmic solutions are improved by using the sampling theory and the forbidden searching strategy，and the iterative solution is combined with the nonlinear least-squares fitting for the enrichment of the samples，which realizes the relative efficiency of the curve fitting and the calculation of the enrichment degree within the energy range of 143 keV to 1001 keV. The performance test of the algorithm and the results of sample analysis show that the uranium enrichment calculation method based on the improved simulated annealing algorithm has the ability to escape the local optimal problem in uranium enrichment calculation，and can be applied to the enrichment calculation of different uranium samples，the relative deviation of the results of the enrichment analysis over all measured samples is within ±5%.

The influence of xanthan gum (XG) and psyllium husk powder (PHP) at different ratios on the emulsification and oxidative stability of myofibrillar protein (MP) emulsions were studied under the low-salt conditions. The results showed that, in comparison to the emulsions added with XG or PHP alone and the control, the MP emulsions supplemented with the mixture of XG and PHP manifested higher apparent viscosity and Zeta potential, while having lower oil droplet size. Therefore, the emulsions containing XG and PHP mixtures showed the best creaming stability. Microstructure images further showed that the oil droplets in the emulsion containing the XG and PHP mixtures were evenly distributed and small in size. The rates of lipid and protein oxidation of the emulsions with the mixture of XG and PHP were remarkably lower than those of the emulsions with XG or PHP alone after being stored for 7 days. The emulsification and oxidative stability of emulsions were the highest when the mass ratio of XG to PHP was 1:3 (w/w). In conclusion, the mixture of XG and PHP might be a promising food additive for improving emulsion stability and oxidation stability under low-salt conditions.

Abstract Background House dust mite (HDM) is the leading allergen for allergic rhinitis (AR). Although allergic sensitisation by inhaled allergens renders susceptible individuals prone to developing AR, the molecular mechanisms driving this process remain incompletely elucidated. Objective This study aimed to elucidate the molecular mechanisms underlying HDM‐induced AR. Methods We examined the expression of cytidine/uridine monophosphate kinase 2 (CMPK2), STING and the NLRP3 inflammasome in both AR patients and mice. Additionally, we investigated the role of CMPK2 and STING in the activation of the NLRP3 inflammasome in AR. Results The expression of CMPK2, STING and the NLRP3 inflammasome was significantly increased in the nasal mucosa of AR patients compared to non‐AR controls. A positive correlation was found between CMPK2 expression and the levels of STING, NLRP3, ASC, CASP1 and IL‐1β. HDM treatment up‐regulated the expression of CMPK2, and CMPK2 overexpression enhanced NLRP3 inflammasome activation in human nasal epithelial cells (HNEPCs). Additionally, mitochondrial reactive oxygen species (mtROS) production following HDM exposure contributed to mitochondrial dysfunction and the release of mitochondrial DNA (mtDNA), which activated the cyclic GMP‐AMP synthase (cGAS)‐STING pathway. Remarkably, depletion of mtDNA or inhibition of STING signalling reduced HDM‐induced NLRP3 inflammasome activation in HNEPCs. In vivo, genetic knockout of CMPK2 or STING alleviated NLRP3 inflammasome activation and ameliorated clinical symptoms of AR in mice. Conclusions Our results suggest that HDM promotes the activation of NLRP3 inflammasome through the up‐regulation of CMPK2 and ensuing mtDNA‐STING signalling pathway, hence revealing additional therapeutic target for AR. Key points Cytidine/uridine monophosphate kinase 2 (CMPK2) expression is up‐regulated in the nasal mucosa of patients and mice with allergic rhinitis (AR). CMPK2 caused NLRP3 inflammasome activation via mitochondrial DNA (mtDNA)‐STING pathway. Blocking CMPK2 or STING signalling significantly reduced the activation of NLRP3 in house dust mite (HDM)‐challenged mice and human nasal epithelial cells (HNEPCs).

Land subsidence is a worldwide geological hazard. Differential land subsidence has posed the major threat to urban infrastructure, linear rail transit and underground space development and utilization, and also restricted the sustainable development of the economy and society. This paper systematically elaborates on the research progresses on land deformation acquisition, evolution mechanism and simulation of land subsidence, and focuses on the land deformation acquisition technology based on InSAR monitoring and multi-source deformation data fusion, as well as the correlation analysis, statistical analysis, machine learning and other methods to analyze the relationship between the evolution of land subsidence and various influencing factors based on geotechnical experiment and long time series observation data. On this basis, the advantages and disadvantages of land subsidence simulation models such as groundwater flow field-land deformation model, mathematical statistical model and machine learning model are explored. It is found that multi-source deformation data fusion can improve the spatiotemporal resolution of land deformation. The differences in geological structure, lithology, groundwater exploitation, and dynamic and static loads are factors contributing to the differential evolution of land subsidence. The difficulty in balancing the computational efficiency and interpretability of mathematical models for land subsidence is the main problem in simulation. According to the literature review, the current researches mainly focus on land subsidence caused by groundwater over-exploitation. This paper further proposes the future research directions for land subsidence, under the background of climate change, new hydrological condition and dataset, and based on the fusion of data through remote sensing and field observations, integrating the latest progress of InSAR, GeoAI, cloud platform and other technologies to reveal the evolution mechanism of land subsidence considering the climate change and anthropic activities and provide technical support for regional land subsidence prevention and urban safety.

IntroductionStudies on the effects of polycyclic aromatic hydrocarbons (PAHs) on hearing loss (HL) are limited and often focus on individual PAH compounds. The present study aimed to explore the individual and combined effects of PAH exposure on hearing loss, with a focus on the mediating role of inflammatory blood cell markers.MethodsThis cross-sectional study included 1,409 participants from 3 cycles of the National Health and Nutrition Examination Survey (2001–2002, 2003–2004, and 2011–2012). Seven monohydroxylated PAH metabolites (OH-PAHs) in the urine were measured. Multivariable logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were applied to assess both the individual and combined effects of OH-PAHs on hearing loss. Moreover, mediation analysis was employed to examine the mediating role of inflammatory blood cell markers in these associations.ResultsAmong the 1,409 participants, 59.1% had hearing loss. The WQS model revealed a positive association between PAH mixtures and HL (OR: 1.290; 95% CI: 1.042, 1.597), LFHL (OR: 1.363; 95% CI: 1.130, 1.644), and HFHL (OR: 1.299; 95% CI: 1.022, 1.626). Additionally, the WQS model identified hydroxynaphthalene (1-OHNAP) primarily contributed to HL and LFHL, while 2-hydroxyfluorene (2-OHFLU) was the primary contributor to HFHL. BKMR analysis demonstrated positive associations between PAH mixtures and all three types of hearing loss. Mediation analysis revealed that the association between OH-PAHs and LFHL was mediated by neutrophil (NEU) and basophil (BAS) counts.DiscussionThese results confirmed that exposure to PAH mixtures was positively associated with the odds of hearing loss and that inflammatory blood cell markers mediated this association.

After wheat harvesting in coastal saline–alkali land, when the straw is returned to the field and the soil is rotary tilled, the lack of reliable discrete element simulation parameter models restricts the optimization and improvement of special tillage and land preparation equipment for saline–alkali land to some extent. In this study, the Hertz–Mindlin with JKR model was used to calibrate the discrete element simulation parameters. Taking the soil-wheat crop residue mixture’s angle of repose as the test index, four groups of parameters that significantly affect the angle of repose and their optimal value ranges were screened out through the Plackett–Burman test and the steepest ascent test. Then, the Box–Behnken test was conducted to obtain the quadratic regression model of the significant parameters and the angle of repose, and the optimal values of the significant parameters were obtained. The optimal parameter combination was used for simulation tests, and the relative errors between the measured values and the simulation test values of the angle of repose and the wheat residue coverage rate were 0.74% and 1.34%. The reliable parameters provide a theoretical basis for the optimization and improvement of the equipment for soil preparation in saline–alkali land.

Histone methylation can affect chromosome structure and binding to other proteins, depending on the type of amino acid being modified and the number of methyl groups added, this modification may promote transcription of genes (H3K4me2, H3K4me3, and H3K79me3) or reduce transcription of genes (H3K9me2, H3K9me3, H3K27me2, H3K27me3, and H4K20me3). In addition, advances in tumor immunotherapy have shown that histone methylation as a type of protein post-translational modification is also involved in the proliferation, activation and metabolic reprogramming of immune cells in the tumor microenvironment. These post-translational modifications of proteins play a crucial role in regulating immune escape from tumors and immunotherapy. Lysine methyltransferases are important components of the post-translational histone methylation modification pathway. Lysine methyltransferase 2C (KMT2C), also known as MLL3, is a member of the lysine methyltransferase family, which mediates the methylation modification of histone 3 lysine 4 (H3K4), participates in the methylation of many histone proteins, and regulates a number of signaling pathways such as EMT, p53, Myc, DNA damage repair and other pathways. Studies of KMT2C have found that it is aberrantly expressed in many diseases, mainly tumors and hematological disorders. It can also inhibit the onset and progression of these diseases. Therefore, KMT2C may serve as a promising target for tumor immunotherapy for certain diseases. Here, we provide an overview of the structure of KMT2C, disease mechanisms, and diseases associated with KMT2C, and discuss related challenges.

The tumor microenvironment responsive multifunctional nanoplatforms with integrated diagnosis and therapy have recently received great attention in anti-cancer treatment. In this study, we developed biocompatible iron oxide-hydroxide-based nanorods (DOX-FPT NRs) for MR imaging and H2S scavenging assisted synergistic photothermal-chemotherapy of colon cancer, which is fabricated by modifying polydopamine (PDA) and transferrin (Tf) on the surface of iron oxide hydroxide (FeOOH) nanorods. The prepared DOX-FPT NRs could precisely target the colon cancer cells through transferrin ligand-receptor-mediated targeting and effectively scavenge endogenous H2S to prohibit the growth of colon cancer. Meanwhile, the considerable drug loading capability and outstanding photothermal conversion efficiency are permitted by the PDA shell modification. In addition, the H2S scavenging assisted photothermal-chemotherapy showed an excellent therapeutic effect on CT26 cells via in vitro cell test. Therefore, the prepared DOX-PFT NRs will be a promising nanoplatform to enhance the therapeutic effect of colon cancer through the treatment strategy of H2S scavenging-assisted synergistic photothermal chemotherapy.

In order to evaluate the effects of acidifiers and essential oils in drinking water on growth, intestinal digestive capacity, and immune status in broilers, a total of 480, 1-day-old Arbore Acres broilers were randomly assigned to four treatments including normal tap water (Ctr) and tap water supplemented with acidifier I (ACI), acidifier I and essential oils (ACI+EO), and acidifier II (ACII). Both ACI+EO and ACII increased final body weight. The pH value of the crop and gizzards was reduced by ACI+EO, and ACII decreased the pH values of the proventriculus and gizzards (p < 0.05). Compared with control group, ACI, ACI+EO, ACII significantly enhanced lipase activity in jejunum but ACII decreased the level of serum total cholesterol and total triglyceride (p < 0.05). Compared with the control group, ACI+EO and ACII significantly increased the relative weight of the spleen, increased the level of serum IgA and IgM, and decreased E. coli in excreta, while ACII significantly decreased Salmonella in excreta (p Lactobacillus in excreta. In conclusion, ACI+EO improved immune status and ACII was effective in reducing Salmonella and promoting Lactobacillus, contributing to intestinal health.

Little is known about the difference in durability of HBsAg seroclearance induced by nucleoside analogs (NAs) or by interferon (IFN). A real-world, retrospective cohort study was conducted. Patients were assigned into two groups: NAs monotherapy-induced HBsAg seroclearance subjects and IFN monotherapy induced-HBsAg seroclearance subjects. A total of 198 subjects, comprised by 168 NAs monotherapy-induced and 30 IFN monotherapy-induced, who achieved HBsAg seroclearance were included in this study. The one-year probabilities of confirmed HBsAg seroclearance were significantly different in patients with NAs monotherapy and IFN monotherapy (0.960 (with 95% CI 0.922–0.999) vs. 0.691 (with 95% CI 0.523–0.913), log-rank-P = 4.04e-4). 73.3% (11 of 15) HBsAg recurrence occurred within one year after HBsAg seroclearance. The one-year probabilities of confirmed HBsAg seroclearance were higher in IFN monotherapy patients with anti-HBs than in IFN monotherapy patients without anti-HBs (0.839 (with 95% CI 0.657–1.000) vs. 0.489 (with 95% CI 0.251–0.953), log-rank test, P = 0.024). Our study thus provided novel insights into the durability of HBsAg seroclearance induced by NAs or IFN monotherapy. In particular, the HBsAg seroreversion rate was relatively high in IFN monotherapy subjects. The presence of anti-HBs was significantly correlated with a longer durability of functional cure induced by IFN treatment. And one-year follow-up in HBsAg seroclearance achieved individuals is proper for averting HBsAg seroreversion and other liver disease.

The star chromatic index of a graph $ G $, denoted by $ \chi{'}_{st}(G) $, is the smallest number of colors required to properly color $ E(G) $ such that every connected bicolored subgraph is a path with no more than three edges. A graph is $ K_{2, t} $-free if it contains no $ K_{2, t} $ as a subgraph. This paper proves that every $ K_{2, t} $-free planar graph $ G $ satisfies $ \chi_{st}'(G)\le 1.5\Delta +20t+20 $, which is sharp up to the constant term. In particular, our result provides a common generalization of previous results on star edge coloring of outerplanar graphs by Bezegová et al.(2016) and of $ C_4 $-free planar graphs by Wang et al.(2018), as those graphs are subclasses of $ K_{2, 3} $-free planar graphs.

Abstract Background Chromosomal imbalances of several megabasepair in size are normally deleterious for the carrier. Still, rarely reported are so-called “unbalanced chromosome abnormalities” (UBCAs), which are either gains or losses or equally large genomic regions, but the affected person is not or only minimally clinically affected. The knowledge of such UBCAs is imperative also in chromosomal microarray analysis (CMA) or noninvasive prenatal testing (NIPT). Case presentation A maternally inherited del(18)(p11.32p11.31) was identified in a over two generations in a Chinese family with normal phenotype. The affected region encompasses 19 genes, among which TGIF1 is expressed in fetal and adult nervous system. TGIF1 deletions and /or mutations have been seen in cases with holoprosencephaly but also non-affected individuals, suggesting incomplete penetrance and variable expressivity. Conclusions Deletions in the terminal region of chromosome 18 short arm have been reported previously in clinically healthy persons. Here a further family with an UBCA in 18p11.3 is added to the literature, suggesting a careful genetic counselling in comparable, especially prenatal cases.

IntroductionSince the outbreak of the novel coronavirus pneumonia (COVID-19), China has entered normalization phase of its epidemic prevention and control measures that emphasizes ‘precise prevention and control,’ ‘dynamic zeroing’, and ‘universal vaccination’. However, medical staff continue to face physical and mental stress. The present study aimed to investigate the job satisfaction of medical staff in China, as well as any associated factors.Methods2,258 medical staff completed a questionnaire specially designed for this study. Independent samples t-tests, one-way analysis of variance, and binary logistic regression were used to analyze associated factors.ResultsOverall, 48.4% of the participants expressed satisfaction with their job; the highest-scoring dimension was interpersonal relationships (3.83 ± 0.73), while the lowest scoring dimension was salary and benefits (3.13 ± 0.94). The logistic regression model indicated that job satisfaction among medical staff is associated with being aged 40–49 years [odds ratio (OR) = 2.416] or > 50 years (OR = 2.440), having an above-undergraduate education level (OR = 1.857), holding a position other than doctor [i.e., nurse (OR = 3.696) or ‘other’ (OR = 2.423)], having a higher income (OR = 1.369), and having fewer monthly overtime shifts (OR = 0.735–0.543). Less than half of the medical staff expressed satisfaction with their job, indicating that the overall level is not high.DiscussionThis research enriches the study of medical workers’ job satisfaction during periods when epidemic prevention and control has become familiar and routine. To improve medical workers’ job satisfaction, administrators should seek to enhance medical staff’s remuneration, reduce their work pressure, and meet their needs (where reasonable).

In this study, we investigated the effect of dietary methionine restriction (MR) on the antioxidant function and inflammatory responses in lipopolysaccharide (LPS)-challenged broilers reared at high stocking density. A total of 504 one-day-old male Arbor Acre broiler chickens were randomly divided into four treatments: 1) CON group, broilers fed a basal diet; 2) LPS group, LPS-challenged broilers fed a basal diet; 3) MR1 group, LPS-challenged broilers fed a methionine-restricted diet (0.3% methionine); and 4) MR2 group, LPS-challenged broilers fed a methionine-restricted diet (0.4% methionine). LPS-challenged broilers were intraperitoneally injected with 1 mg/kg body weight (BW) of LPS at 17, 19, and 21 days of age, whereas the CON group was injected with sterile saline. The results showed that: LPS significantly increased the liver histopathological score (p < 0.05); LPS significantly decreased the serum total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity at 3 h after injection (p < 0.05); the LPS group had a higher content of Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF)-α, but a lower content of IL-10 than the CON group in serum (p < 0.05). Compared with the LPS group, the MR1 diet increased catalase (CAT), SOD, and T-AOC, and the MR2 diet increased SOD and T-AOC at 3 h after injection in serum (p < 0.05). Only MR2 group displayed a significantly decreased liver histopathological score (p < 0.05) at 3 h, while MR1 and MR2 groups did so at 8 h. Both MR diets significantly decreased serum LPS, CORT, IL-1β, IL-6, and TNF-α contents, but increased IL-10 content (p < 0.05). Moreover, the MR1 group displayed significantly increased expression of nuclear factor erythroid 2-related factor 2 (Nrf2), CAT, and GSH-Px at 3 h; the MR2 group had a higher expression of Kelch-like ECH-associated protein 1 (Keap1), SOD, and GSH-Px at 8 h (p < 0.05). In summary, MR can improve antioxidant capacity, immunological stress, and liver health in LPS-challenged broilers. The MR1 and MR2 groups experienced similar effects on relieving stress; however, MR1 alleviated oxidative stress more rapidly. It is suggested that precise regulation of methionine levels in poultry with stress may improve the immunity of broilers, reduce feed production costs, and increase production efficiency in the poultry industry.

Objective: Kidney renal clear cell carcinoma (KIRC) is a common cancer with high morbidity and mortality in renal cancer. Thus, the transcriptome data of KIRC patients in The Cancer Genome Atlas (TCGA) database were analyzed and drug candidates for the treatment of KIRC were explored through the connectivity map (CMap) database. Methods: The transcriptome data of KIRC patients were downloaded from TCGA database, and KIRC-associated hub genes were screened out through differential analysis and protein-protein interaction (PPI) network analysis. Afterward, the CMap database was used to select drug candidates for KIRC treatment, and the drug-targeted genes were obtained through the STITCH database. A PPI network was constructed by combining drug-targeted genes with hub genes that affected the pathogenesis of KIRC to obtain final hub genes. Finally, combining hub genes and KIRC-associated hub genes, the pathways affected by drugs were explored by pathway enrichment analysis. Results: A total of 2,312 differentially expressed genes were found in patients, which were concentrated in immune cell activity, cytokine, and chemokine secretion pathways. Drug screening disclosed 5 drug candidates for KIRC treatment: fedratinib, Ly344864, geldanamycin, AS-605240, and luminespib. Based on drug-targeted genes and KIRC-associated hub genes, 16 hub genes were screened out. Pathway enrichment analysis revealed that drugs mainly affected pathways such as neuroactive ligand pathways, cell adhesion, and chemokines. Conclusion: The above results indicated that fedratinib, LY 344864, geldanamycin, AS-605240, and luminespib could be used as candidates for KIRC therapy. The findings from this study will make contributions to the treatment of KIRC in the future.

Abstract Wire arc additive manufacturing (WAAM) has been investigated to deposit large-scale metal parts due to its high deposition efficiency and low material cost. However, in the process of automatically manufacturing the high-quality metal parts by WAAM, several problems about the heat build-up, the deposit-path optimization, and the stability of the process parameters need to be well addressed. To overcome these issues, a new WAAM method based on the double electrode micro plasma arc welding (DE-MPAW) was designed. The circuit principles of different metal-transfer models in the DE-MPAW deposition process were analyzed theoretically. The effects between the parameters, wire feed rate and torch stand-off distance, in the process of WAAM were investigated experimentally. In addition, a real-time DE-MPAW control system was developed to optimize and stabilize the deposition process by self-adaptively changing the wire feed rate and torch stand-off distance. Finally, a series of tests were performed to evaluate the control system’s performance. The results show that the capability against interferences in the process of WAAM has been enhanced by this self-adaptive adjustment system. Further, the deposition paths about the metal part’s layer heights in WAAM are simplified. Finally, the appearance of the WAAM-deposited metal layers is also improved with the use of the control system.

A strong edge coloring of a graph G is a proper coloring of edges in G such that any two edges of distance at most 2 are colored with distinct colors. The strong chromatic index χs′(G) is the smallest integer l such that G admits a strong edge coloring using l colors. A K4(t)-minor free graph is a graph that does not contain K4(t) as a contraction subgraph, where K4(t) is obtained from a K4 by subdividing edges exactly t−4 times. The paper shows that every K4(t)-minor free graph with maximum degree Δ(G) has χs′(G)≤(t−1)Δ(G) for t∈{5,6,7} which generalizes some known results on K4-minor free graphs by Batenburg, Joannis de Verclos, Kang, Pirot in 2022 and Wang, Wang, and Wang in 2018. These upper bounds are sharp.

Abstract Objective Our study aims to investigate the mechanism of the miR-129-5p/SPN axis in clear cell renal cell carcinoma (ccRCC), providing a novel direction for the targeted therapy of ccRCC. Methods Bioinformatics methods were implemented to find the differentially expressed genes (DEGs) associated with ccRCC from TCGA database. qRT-PCR was performed to detect miR-129-5p and SPN mRNA expression, while western bot was carried out for the detection of protein expression of SPN. Bioinformatics analysis was used to predict the binding sites of miR-129-5p on SPN 3’UTR, while dual-luciferase assay was conducted to verify their binding relationship. CCK-8 assay, colony formation assay, wound healing assay and Transwell assay were employed to measure ccRCC cell proliferative ability, cell formation ability, cell migratory and invasive abilities. Flow cytometry was implemented to assess cell cycle and apoptosis. Results miR-129-5p exhibited a significantly down-regulated expression level in ccRCC, while SPN showed a remarkably up-regulated expression level. Overexpressed miR-129-5p inhibited ccRCC cell proliferative, invasive and migratory capacities while induced cell cycle arrest in G0/G1 phase and promoted cell apoptosis. Dual-luciferase assay confirmed that there was a binding relationship between miR-129-5p and SPN. Moreover, overexpressed miR-129-5p remarkably reduced SPN expression in cancer cells, weakened the promoting effect of SPN on cell proliferation, migration, invasion and cell cycle progress, and led to enhanced cell apoptotic activity. Conclusions Our study proves the regulatory effect of the miR-129-5p/SPN axis in ccRCC, and provides a novel potential target for precise treatment of patients with ccRCC.

This study aimed to investigate the effects of dietary organic trace minerals on egg quality and intestinal microflora of laying hens during the late production stage. In total, 1,080 Jinghong-1 laying hens aged 57 weeks were randomly assigned to five treatment groups: CON, basal diet containing about 6, 29, 49, and 308 mg·kg−1 of Cu, Mn, Zn, and Fe; IT100, basal diet supplemented with 10, 80, 80, and 60 mg·kg−1 of Cu, Mn, Zn, and Fe (each as inorganic sulfates), respectively; OT20, basal diet supplemented with 2, 16, 16, and 12 mg·kg−1 of Cu, Mn, Zn, and Fe (each as organic trace minerals chelated with lysine and methionine in the ratio of 2:1 amino acid: organic trace minerals), respectively; OT30, basal diet supplemented with 3, 24, 24, and 18 mg·kg−1 of organic Cu, Mn, Zn, and Fe, respectively; and OT50, basal diet supplemented with 5, 40, 40, and 30 mg·kg−1 of organic Cu, Mn, Zn, and Fe, respectively. Overall, OT20, OT30, and OT50 had equal or higher potential to promote Cu, Mn, Zn, and Fe deposition in egg yolks compared with IT100. In addition, OT50 enhanced the eggshell breaking strength and the antioxidant status of the eggshell gland. Cecal microbiota, including Barnesiellaceae and Clostridia, were significantly decreased in IT100- and OT50-treated hens compared with the CON group. Clostridia UCG-014 was negatively correlated with eggshell weight and OCX-32. In conclusion, reduced supplementation of organic trace minerals can improve the eggshell quality and trace mineral deposition, possibly by modulating genes involved in the eggshell formation in the eggshell gland and by controling of the potentially harmful bacteria Barnesiellaceae and Clostridiales in the cecum. Inorganic trace minerals may be effectively replaced by low level of complex organic trace minerals in laying hens during the late production stage.

ObjectivesCRISPR-Cas13a system-based nucleic acid detection methods are reported to have rapid and sensitive DNA detection. However, the screening strategy for crRNAs that enables CRISPR-Cas13a single-base resolution DNA detection of human pathogens remains unclear.MethodsA combined rational design and target mutation-anchoring CRISPR RNA (crRNA) screening strategy was proposed.ResultsA set of crRNAs was found to enable the CRISPR-Cas13 system to dramatically distinguish fluroquinolone resistance mutations in clinically isolated Mycobacterium tuberculosis strains from the highly homologous wild type, with a signal ratio ranging from 8.29 to 38.22 in different mutation sites. For the evaluation of clinical performance using genomic DNA from clinically isolated M. tuberculosis, the specificity and sensitivity were 100 and 91.4%, respectively, compared with culture-based phenotypic assays.ConclusionThese results demonstrated that the CRISPR-Cas13a system has potential for use in single nucleotide polymorphism (SNP) detection after tuning crRNAs. We believe this crRNA screening strategy will be used extensively for early drug resistance monitoring and guidance for clinical treatment.

Walnuts are rich in fat and proteins that become oxidized during the processing and storage conditions of their kernels. In this study, the effect of three packaging materials (e.g., polyethylene sealed packaging, polyamide/polyethylene vacuum packaging, and polyethylene terephthalate/aluminum foil/polyethylene vacuum packaging) were investigated on the oxidation, structural and digestive properties of walnut kernel proteins. Results showed that the amino acid content gradually decreased and carbonyl derivatives and dityrosine were formed during storage. The protein molecule structure became disordered as the α-helix decreased and the random coil increased. The endogenous fluorescence intensity decreased and the maximum fluorescence value was blue-shifted. After 15 days of storage, surface hydrophobicity decreased, while SDS-PAGE and HPLC indicated the formation of large protein aggregates, leading to a reduction in solubility. By simulating gastrointestinal digestion, we found that oxidation adversely affected the digestive properties of walnut protein isolate and protein digestibility was best for polyethylene terephthalate/aluminum foil/polyethylene vacuum packaging. The degree of protein oxidation in walnuts increased during storage, which showed that except for fat oxidation, the effect of protein oxidation on quality should be considered. The results of the study provided new ideas and methods for walnut quality control.

This study aimed to evaluate the efficacy of organic acids (OAs) in starter broilers and to investigate whether supplemental OAs could alleviate the high stocking density (HSD) stress condition in grower broilers. A total of 408 1-day-old Arbor Acres broilers were assigned into two groups without or with liquid OAs in the starter phase. In the grower phase, each group in the starter phase was divided into a normal stocking density and an HSD. The OA dose was 0.16% at the starter and grower phases. The results showed that at the starter phase, OAs decreased the chyme pH in gizzard and duodenum and increased the activities of chymotrypsin and α-amylase in the duodenal chyme (p < 0.05). In the grower phase, an HSD decreased the growth performance and the ether extract digestibility (p < 0.01). The supplementation of OAs decreased the chyme pH in the gizzard, proventriculus, and duodenum and increased the lipase and α-amylase activities (p < 0.05). The supplemental OAs increased the dry matter and total phosphorous digestibility and the contents of acetic acids, butyric acids, isovaleric acids, and valeric acids (p < 0.05). For cecal microbial compositions at the genus level, an HSD decreased the relative abundance of Blautia, Norank_f__norank_o__RF39, and Alistipes, while supplemental OAs increased the relative abundance of Norank_f__norank_o__RF39 (p < 0.05). In conclusion, although there were no interaction effects between OAs and stocking densities in the present study, it was clear that the supplementation of OAs has beneficial effects on the chyme pH, enzymes activities, and nutrient digestibility in broilers, while an HSD existed adverse effects on the growth performance, nutrient digestibility, and gut microbiota balance in grower broilers.

Walnut protein is a key plant protein resource due to its high nutritional value, but walnuts are prone to oxidation during storage and processing. This article explored the oxidative modification and digestion mechanism of walnut protein isolates by peroxyl radical and obtained new findings. SDS-PAGE and spectral analysis were used to identify structural changes in the protein after oxidative modification, and LC-MS/MS was used to identify the digestion products. The findings demonstrated that as the AAPH concentration increased, protein carbonyl content increased from 2.36 to 5.12 nmol/mg, while free sulfhydryl content, free amino content, and surface hydrophobicity decreased from 4.30 nmol/mg, 1.47 μmol/mg, and 167.92 to 1.72 nmol/mg, 1.13 μmol/mg, and 40.93 nmol/mg, respectively. Furthermore, the result of Tricine-SDS-PAGE in vitro digestion revealed that protein oxidation could cause gastric digestion resistance and a tendency for intestinal digestion promotion. Carbonyl content increased dramatically during the early stages of gastric digestion and again after 90 min of intestine digestion, and LC-MS/MS identified the last digestive products of the stomach and intestine as essential seed storage proteins. Oxidation causes walnut proteins to form aggregates, which are then re-oxidized during digestion, and proper oxidative modification may benefit intestinal digestion.

This study was conducted to investigate the effects of different levels of yeast chromium on growth performance, organ index, antioxidant capacity, immune performance and liver health of broilers under high stocking density. A total of 684 1-day-old Arbor Acres broilers were selected and fed a common diet from 1 to 22 days of age. At the end of 22 days, broilers with similar weight were randomly divided into six treatments, with six replications in each treatment. The broilers in control groups were fed with a control diet and raised at low stocking density of broilers (14 broilers/m2, LSD) and high stocking density (20 broilers/m2, HSD). The broilers in treatment groups were fed with diets supplemented with 200, 400, 800 and 1600 µg Cr/kg chromium yeast (Cr-yeast) under HSD, respectively. The experimental period was 23~42 days. Compared with the LSD group, the HSD group significantly decreased the liver index (ratio of liver weight to live weight of broilers) of broilers (p < 0.05), the HSD group significantly increased the content of corticosterone (CORT) and the activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and decreased the prealbumin (PA) level in the serum (p < 0.05). HSD decreased the total antioxidant capacity (T-AOC) contents in the serum, liver and breast, serum glutathione peroxidase (GSH-Px) activities, breast total superoxide dismutase (T-SOD) activities and liver catalase (CAT) activities of broilers (p < 0.05). The HSD group significantly increased the total histopathological score (p < 0.05). Compared with the HSD group, adding 200, 400, and 1600 Cr-yeast significantly increased the liver index of broilers (p < 0.05), all HSD + Cr-yeast groups decreased the ALT activities (p < 0.05), and the HSD + 800 group significantly decreased the CORT contents and the ALP activities of the serum (p < 0.05); the HSD + 400, 800 and 1600 groups increased the PA contents of the serum (p < 0.05); HSD + 800 group significantly reduced the tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β) contents of the serum (p < 0.05); moreover, the HSD + 400 group increased the GSH-Px activities of the serum (p < 0.05), the T-AOC and the T-SOD activities of the breast (p < 0.05) and the T-AOC and CAT activities of the liver (p < 0.05). Adding 800 Cr-yeast significantly decreased the total histopathological score (degree of hepatocyte edema and inflammatory cell infiltration) under HSD (p < 0.05). In summary, Cr-yeast can improve the antioxidant capacity and immune traits, and liver health of broilers under HSD. Based on the results of the linear regression analysis, the optimal supplementation of Cr-yeast in antioxidant capacity, immunity ability and liver health were at the range of 425.00–665.00, 319.30–961.00, and 800.00–1531.60 µg Cr/kg, respectively.

Although Iron (Fe) is an essential nutrient that plays a vital role in respiratory processes, excessive Fe in the diet can affect the health of broilers. We investigated the effects of diet supplemented with high levels of iron chelates with lysine and glutamic acid (Fe–LG) on the growth performance, serum biochemical parameters, antioxidant status, and duodenal mRNA expression of Fe transporters in broilers. A total of 800 1-day-old male Arbor Acres broilers were assigned to 5 groups, with 8 replicates each. Broilers were fed a corn–soybean meal basal diet or basal diets supplemented with 40, 80, 400, or 800 mg Fe/kg as Fe–LG for 6 weeks. The body weight (BW) was increased in the 80 mg Fe/kg treatment group, but decreased in the 800 mg Fe/kg treatment group on day 21. During days 1–21, compared with the control group, the supplementation of the 80 mg Fe/kg increased the average daily gain (ADG) and average daily feed intake (ADFI); however, the supplementation of the 800 mg Fe/kg group decreased the ADG and increased the FCR in broilers (p < 0.05). The heart, liver, spleen, and kidney indices were reduced in the 800 mg Fe/kg treatment group (p < 0.05). The supplementation of the 800 mg Fe/kg group increased the serum aspartate aminotransferase activity and the levels of creatinine and urea nitrogen on day 42 (p < 0.05). The broilers had considerably low liver total superoxide dismutase activity and total antioxidant capacity in the 800 mg Fe/kg treatment group (p < 0.05). Serum and liver Fe concentrations were elevated in the 400 and 800 mg Fe/kg treatment groups, but were not affected in the 40 and 80 mg Fe/kg treatment groups. The duodenal Fe transporters divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1) were downregulated in the Fe–LG treatment groups (p < 0.05). We conclude that a high dietary supplement of 800 mg Fe/kg in broilers leads to detrimental health effects, causing kidney function injury and liver oxidative stress.

The prevalence of allergic rhinitis (AR) and obesity in children increased concurrently during recent decades. However, the molecular pathway involved in the interaction between obesity and AR is still unclear. We aimed to investigate the interaction between leptin and osteopontin (OPN) and their effect on T helper (TH) response in the development of AR in children. Thirty AR and 30 healthy children with or without obesity were enrolled. Serum leptin and OPN levels were measured and their relationship with TH1/2 cytokines was analyzed. TH cell differentiation and cytokine production in peripheral blood mononuclear cells (PBMCs) stimulated by leptin and/or OPN were analyzed by enzyme linked immunosorbent assay (ELISA). Obese AR mice models were established to verify the effect of obesity on leptin and OPN as well TH regulation. Immunoprecipitation was performed to confirm the interaction between OPN and leptin in CD4+ T cells. Our results showed elevated serum leptin and OPN in AR children correlated with TH2 cytokines expression. Leptin and OPN enhanced TH2 inflammation in house dust mite stimulated PBMCs from AR children synergistically. Obese AR mice showed as more severe inflammatory reaction, symptoms and expression of nasal leptin and OPN compared with other groups. Immunoprecipitation suggested that OPN and leptin may interact with each other and this process may be mediated by α4 integrin and PI3K/AKT pathway in CD4+ T cells. Our data provide evidence that leptin-mediated OPN upregulation promote TH2 inflammation in AR and this process is achieved through the α4 integrin and PI3K/AKT signaling pathways. Keywords: Allergic rhinitis, Leptin, Osteopontin, Obesity, T helper cell

Fas–Fas ligand (FasL) signaling plays an important role in the development of allergic inflammation, but the cellular and molecular mechanisms are still not well known. By using the bone marrow-derived dendritic cell (BMDC) transfer-induced pulmonary inflammation model, we found that house dust mite (HDM)-stimulated FAS-deficient BMDCs induced higher Th2-mediated allergic inflammation, associated with increased mucus production and eosinophilic inflammation. Moreover, FAS-deficient BMDCs promoted Th2 cell differentiation upon HDM stimulation in vitro. Compared to wild-type BMDCs, the Fas-deficient BMDCs had increased ERK activity and decreased IL-12 production upon HDM stimulation. Inhibition of ERK activity could largely increase IL-12 production, consequently restored the increased Th2 cytokine expression of OT-II CD4+ T cells activated by Fas-deficient BMDCs. Thus, our results uncover an important role of DC-specific Fas signaling in Th2 differentiation and allergic inflammation, and modulation of Fas signaling in DCs may offer a useful strategy for the treatment of allergic inflammatory diseases.