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Abstract Objectives Evidence suggests that environmental support, personality traits, and psychological factors can influence seasonal changes in human mood and behavior, particularly in rural middle-aged women and older people. This study aimed to quantify the associations between personality traits, seasonal affective disorder symptoms, and sun exposure in rural older people. Methods This study is a cross-sectional analytical study, the participants were 300 rural older persons from 12 natural villages and 5 geriatric service centers in 4 different cities in Jiangxi Province, China. The Eysenck Personality Questionnaire (EPQ), the Personal Inventory of Depression and Seasonal Affective Disorder (PIDS-SA-SimpChi), and the Sunlight Exposure Scale were used to conduct follow-up interviews throughout the year. Spatial analysis was performed using ArcGIS and Geodetic Probes. The data were analyzed using SPSS 21 and Amos 23.0 mediated models. Results Rural older people with low sun exposure exhibited higher personality trait scores (p

Abstract Background Spermatogenesis is a highly regulated and complex process in which DNA methylation plays a crucial role. This study aimed to explore the differential methylation profiles in sperm DNA between patients with asthenospermia (AS) and healthy controls (HCs), those with oligoasthenospermia (OAS) and HCs, and patients with AS and those with OAS. Results Semen samples and clinical data were collected from five patients with AS, five patients with OAS, and six age-matched HCs. Reduced representation bisulfite sequencing (RRBS) was performed to identify differentially methylated regions (DMRs) in sperm cells among the different types of patients and HCs. A total of 6520, 28,019, and 16,432 DMRs were detected between AS and HC, OAS and HC, and AS and OAS groups, respectively. These DMRs were predominantly located within gene bodies and mapped to 2868, 9296, and 9090 genes in the respective groups. Of note, 12, 9, and 8 DMRs in each group were closely associated with spermatogenesis and male infertility. Furthermore, BDNF, SMARCB1, PIK3CA, and DDX27; RBMX and SPATA17; ASZ1, CDH1, and CHDH were identified as strong differentially methylated candidate genes in each group, respectively. Meanwhile, the GO analysis of DMR-associated genes in the AS vs. HC groups revealed that protein binding, cytoplasm, and transcription (DNA-templated) were the most enriched terms in the biological process (BP), cellular component (CC), and molecular function (MF), respectively. Likewise, in both the OAS vs. HC and AS vs. OAS groups, GO analysis revealed protein binding, nucleus, and transcription (DNA-templated) as the most enriched terms in BP, CC, and MF, respectively. Finally, the KEGG analysis of DMR-annotated genes and these genes at promoters suggested that metabolic pathways were the most significantly associated across all three groups. Conclusions The current study results revealed distinctive sperm DNA methylation patterns in the AS vs. HC and OAS vs. HC groups, particularly between patients with AS and those with OAS. The identification of key genes associated with spermatogenesis and male infertility in addition to the differentially enriched metabolic pathways may contribute to uncovering the potential pathogenesis in different types of abnormal sperm parameters.

Abstract Nobiletin, a citrus polymethoxy flavonoid with antiapoptotic and antioxidative properties, could safeguard against cisplatin-induced nephrotoxicity and neurotoxicity. Cisplatin, as the pioneer of anti-cancer drug, the severe ototoxicity limits its clinical applications, while the effect of nobiletin on cisplatin-induced ototoxicity has not been identified. The current study investigated the alleviating effect of nobiletin on cisplatin-induced ototoxicity and the underlying mechanisms. Apoptosis and ROS formation were evaluated using the CCK-8 assay, Western blotting, and immunofluorescence, indicating that nobiletin attenuated cisplatin-induced apoptosis and oxidative stress. LC3B and SQSTM1/p62 were determined by Western blotting, qPCR, and immunofluorescence, indicating that nobiletin significantly activated autophagy. Nobiletin promoted the nuclear translocation of NRF2 and the transcription of its target genes, including Hmox1, Nqo1, and ferroptosis markers (Gpx4, Slc7a11, Fth, and Ftl), thereby inhibiting ferroptosis. Furthermore, RNA sequencing analysis verified that autophagy, ferroptosis, and the NRF2 signaling pathway served as crucial points for the protection of nobiletin against ototoxicity caused by cisplatin. Collectively, these results indicated, for the first time, that nobiletin alleviated cisplatin-elicited ototoxicity through suppressing apoptosis and oxidative stress, which were attributed to the activation of autophagy and the inhibition of NRF2/GPX4-mediated ferroptosis. Our study suggested that nobiletin could be a prospective agent for preventing cisplatin-induced hearing loss.

Background: Exosomes, one of small extracellular vesicles, play a vital role in cell to cell communication and contribute to the advancement of tumors through their cargo molecules. Exosomal circRNAs have emerged as significant players in various types of tumors. Thus, this study aimed to investigate how exosomal circRNAs are involved in the diagnosis and progression of gastric cancer (GC). Methods: Serum exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis and Western blot. CCK-8, colony formation and transwell assays were conducted to study the function of hsa_circ_0050547 (named as circ50547). qRT-PCR was used to quantify the expression of circ50547 in GC tissues and serum exosomes. Fluorescence in situ hybridization was applied to detect the cellular distribution of circ50547. Stemness and drug-resistance were detected by sphere formation, WB, flow cytometry and half-maximal inhibitory concentration analyses. Bioinformatic analyses, luciferase experiments, qRT-PCR and WB were used to investigate molecular mechanisms. Results: We discovered for the first time a new type of GC-derived exosomal circRNA, circ50547. We found that circ50547 is highly expressed in both GC tissues and serum exosomes. Interestingly, we observed that the diagnostic value of exosomal circ50547 is superior to that of serum circ50547. Circ50547 overexpression enhanced the proliferation, migration, invasion, stemness and drug resistance of GC cells, while knockdown of circ50547 showed the opposite effect. Mechanistically, circ50547 acted as a sponge for miR-217 to regulate the expression of HNF1B, which promoted gastric cancer progression. Conclusion: Exosomal circ50547 may be a promising marker for the diagnosis and prognosis prediction of GC. These findings suggest that it plays an oncogenic role through miR-217/HNF1B signaling pathway in GC.

The globe is an organically linked whole, and in the pandemic era, COVID-19 has brought heavy public safety threats and economic costs to humanity as almost all countries began to pay more attention to taking steps to minimize the risk of harm to society from sudden-onset diseases. It is worth noting that in some low- and middle-income areas, where the environment for epidemic detection is complex, the causative and comorbid factors are numerous, and where public health resources are scarce. It is often more difficult than in other areas to obtain timely and effective detection and control in the event of widespread virus transmission, which, in turn, is a constant threat to local and global public health security. Pandemics are preventable through effective disease surveillance systems, with nonpharmacological interventions (NPIs) as the mainstay of the control system, effectively controlling the spread of epidemics and preventing larger outbreaks. However, current state-of-the-art NPIs are not applicable in low- and middle-income areas and tend to be decentralized and costly. Based on a 3-year case study of SARS-CoV-2 preventive detection in low-income areas in south-central China, we explored a strategic model for enhancing disease detection efficacy in low- and middle-income areas. For the first time, we propose an integrated and comprehensive approach that covers structural, social, and personal strategies to optimize the epidemic surveillance system in low- and middle-income areas. This model can improve the local epidemic detection efficiency, ensure the health care needs of more people, reduce the public health costs in low- and middle-income areas in a coordinated manner, and ensure and strengthen local public health security sustainably.

Both subsoiling tillage (ST) and ridge and furrow rainfall harvesting (RF) are widely implemented and play an important role in boosting wheat productivity. However, information about the effects of ST coupled with RF during the summer fallow season on wheat productivity and environmental issues remains limited. This study aims to explore the effects of ST coupled with RF on water harvesting, wheat productivity–yield traits, water and nutrient use efficiency and quality, and soil nitrate-N residue in dryland winter wheat–summer fallow rotation at the intersection of southern Loess Plateau and western Huang–Huai–Hai Plain in China in 2018–2022. Three tillage practices—deep plowing with straw turnover (PTST), subsoiling with straw mulching (STSM), and STSM coupled with RF (SRFSM)—are conducted during the summer fallow season. The results indicated that tillage practices during the summer fallow season significantly impacted wheat productivity and soil nitrate-N residue. Compared to PTST, STSM significantly enhanced rainfall fallow efficiency and water use efficiency by 7.0% and 14.2%, respectively, as well as N, P, and K uptake efficiency by 16.9%, 16.2%, and 15.3%, and thus increased grain yield by 14.3% and improved most parameters of protein components and processing quality, albeit with an increase in nitrate-N residue in the 0- to 300-cm soil depth by 12.5%. SRFSM, in turn, led to a further increase in water storage at sowing, resulting in an increase of water use efficiency by 6.8%, as well as N, P, and K uptake efficiency and K internal efficiency by 11.8%, 10.4%, 8.8%, and 4.7%, thereby significantly promoting grain yield by 10.2%, and improving the contents of all the protein components and enhancing the processing quality in grain, and simultaneously reducing the nitrate-N residue in the 0- to 300-cm soil layer by 16.1%, compared to STSM. In essence, this study posits that employing subsoiling coupled with ridge–furrow rainfall harvesting (SRFSM) during the summer fallow season is a promising strategy for enhancing wheat yield, efficiency, and quality, and simultaneously reducing soil nitrate-N residue within the dryland summer fallow–winter wheat rotation system.

Abstract Background Ichthyosis is a common keratotic skin disease with high clinical, etiological and genetic heterogeneity. There are four types of non‐syndromic hereditary ichthyoses, among which autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of recessive Mendelian disorders. ARCI present with different phenotypes and ABCA12 pathogenic variants have been shown to cause complex ARCI phenotypes, including harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). Methods A sporadic male patient, clinically diagnosed with CIE, was enrolled in this study. Exome sequencing was combined with Sanger sequencing to confirm the diagnosis and identify the pathogenic variants. In silico predictions were made using multiple software programs, and the identified variants were interpreted using the ACMG guidelines. A review of all literature reported ABCA12 variants was performed to explore genotype–phenotype correlations. Results Compound heterozygous ABCA12 variants [c.5381+1G>A and c.5485G>C (p.Asp1829His)] (NM_173076) were identified. The two variants were not detected in the public database. c.5381+1G>A is predicted to affect ABCA12 mRNA splicing and Asp1829 is highly conserved among various species. In silico analysis suggested that these two variants were responsible for the phenotype of the patient. Genotype–phenotype correlation analysis showed that biallelic truncation variants and/or exon/amino acid deletions in ABCA12 are the most common causes of HI. Biallelic missense variants are most common in LI and CIE. Conclusions The compound heterozygous ABCA12 variants caused the CIE phenotype observed in the patient. The spectrum of ABCA12 pathogenic variants were broaden. Genotype–phenotype correlation analysis provided detailed evidence which can be used in future prenatal diagnosis and can inform the need for genetic counselling for patients with ABCA12‐related ARCIs.

Curriculum ideological and political education is the fundamental task of implementing moral education and cultivating people in colleges and universities, and also the basic requirement for the development in the new era. The concept of OBE is results-oriented education, which is a reverse design education concept of 'output -oriented, student-centered, teacher-led organization and continuous improvement'. Principles of Food Technolog is the core course of food major, which plays a vital role in cultivating high-quality professionals in the food industry. Therefore, it is urgent for teachers to explore the ideological and political elements contained in the knowledge system and penetrate into each teaching link in the teaching process. Based on the characteristics of the course, teaching objectives and teaching content, this paper explores the ideological and political elements in each chapter deeply, and constructs such elements based on the concept of OBE and implements through the combination of online and offline teaching. The teaching of specialized courses and curriculum ideological and political education in the curriculum go in the same direction to achieve a synergistic effect. Through the construction and implementation of the ideological and political elements of the course, students would improve their sense of identity and professional ethics of food major, and form a correct world outlook, outlook on life and values. At the same time, the research results of the course were expected to provide appropriate reference and reference for the construction and effective implementation of other professional courses.

Abstract Background Membranous nephropathy (MN) is a chronic glomerular disease that leads to nephrotic syndrome in adults. The aim of this study was to identify novel biomarkers and immune-related mechanisms in the progression of MN through an integrated bioinformatics approach. Methods The microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between MN and normal samples were identified and analyzed by the Gene Ontology analysis, the Kyoto Encyclopedia of Genes and Genomes analysis and the Gene Set Enrichment Analysis (GSEA) enrichment. Hub The hub genes were screened and identified by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithm. The receiver operating characteristic (ROC) curves evaluated the diagnostic value of hub genes. The single-sample GSEA analyzed the infiltration degree of several immune cells and their correlation with the hub genes. Results We identified a total of 574 DEGs. The enrichment analysis showed that metabolic and immune-related functions and pathways were significantly enriched. Four co-expression modules were obtained using WGCNA. The candidate signature genes were intersected with DEGs and then subjected to the LASSO analysis, obtaining a total of 6 hub genes. The ROC curves indicated that the hub genes were associated with a high diagnostic value. The CD4+ T cells, CD8+ T cells and B cells significantly infiltrated in MN samples and correlated with the hub genes. Conclusions We identified six hub genes (ZYX, CD151, N4BP2L2-IT2, TAPBP, FRAS1 and SCARNA9) as novel biomarkers for MN, providing potential targets for the diagnosis and treatment.

Abstract Background Congenital disorders of glycosylation (CDG) are a type of inborn error of metabolism (IEM) resulting from defects in glycan synthesis or failed attachment of glycans to proteins or lipids. One rare type of CDG is caused by homozygous or compound heterozygous loss‐of‐function variants in mannosidase alpha class 2B member 2 (MAN2B2). To date, only two cases of MAN2B2‐CDG have been reported worldwide. Methods Trio whole‐exome sequencing (Trio‐WES) was conducted to screen for candidate variants. N‐glycan profiles were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). MAN2B2 expression was evaluated by western blotting. MX dynamin like GTPase 1 (MX1) function was estimated via Thogoto virus (THOV) minireplicon assay. Results Trio‐WES identified compound heterozygous MAN2B2 (hg19, NM_015274.1) variants (c.384G>T; c.926T>A) in a CDG patient. This patient exhibited metabolic abnormalities, symptoms of digestive tract dysfunction, infection, dehydration, and seizures. Novel immune dysregulation characterized by abnormal lymphocytes and immunoglobulin was observed. The MAN2B2 protein level was not affected, while LC–MS/MS showed obvious disruption of N‐glycans and N‐linked glycoproteins. Conclusion We described a CDG patient with novel phenotypes and disruptive N‐glycan profiling caused by compound heterozygous MAN2B2 variants (c.384G>T; c.926T>A). Our findings broadened both the genetic and clinical spectra of CDG.

Organic fertilizer substitution is an effective measure for increasing both the quantity and quality of wheat grain while reducing chemical fertilizer input. However, the effects of reducing nitrogen (N) fertilizer combined with organic fertilizer substitution on grain yield, grain protein content and protein yield, plant N accumulation and translocation, N use efficiency, soil fertility, N apparent surplus and nitrate-N residue in rain-fed drought-prone areas remains limited. In this study, field experiments were conducted over four consecutive seasons (2019-2023) at two sites with four treatments: zero N application (ZN), farmer N application (FN), reduced 20% N of FN (RN), and organic fertilizer substituting 20% N of RN (OSN). The results showed that compared with the ZN treatment, the FN, RN and OSN treatments increased grain yield and its components, grain protein content and protein yield, aboveground N accumulation at the anthesis and maturity stages, pre-anthesis N translocation, post-anthesis N accumulation, N use efficiency, soil fertility. Compared with RN and FN, OSN increased grain yield by 17.12% and 15.03%, grain protein yield by 3.31% and 17.15%, grain N accumulation by 17.78% and 15.58%, and N harvest index by 2.63% and 4.45% averaged across years and sites, respectively. Moreover, OSN increased the contents of organic matter, total N, available P and available K in both 0-20 and 20-40 cm soil layers, decreased N apparent surplus and nitrate-N residue in 0-100 cm, and pH in both 0-20 and 20-40 cm soil layer. Fundamentally, this study suggests that integrating a 20% reduction N from conventional farmer practices with the utilization of organic fertilizer to replace 20% of the chemical N fertilizer (OSN) represents an effective strategy. This approach shows promise in enhancing wheat grain yield, grain protein yield, and N use efficiency. Additionally, it supports the improvement of soil fertility while simultaneously reducing soil nitrate-N residues and the apparent surplus of N in rain-fed drought-prone regions.

Background: Idiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit limited efficacy in achieving remission and may result in notable adverse reactions, warranting the exploration of novel therapeutic approaches for IMN treatment. Traditional Chinese medicine (TCM), which is extensively used for kidney disease management, is a promising alternative. Objective: This study aimed to examine the safety and efficacy of TCM alone or in combination with Western medicine for the management of patients diagnosed with IMN. Methods: This study employed a systematic search of English and Chinese electronic databases to identify randomized controlled trials (RCTs) that examined the application of TCM in the treatment of IMN. RCTs that met the predetermined inclusion and exclusion criteria and assessed the safety and efficacy of TCM alone or in combination with Western medicine in patients with IMN were included in the analysis. The methodological quality of the included studies was evaluated by using a risk-of-bias tool. All statistical analyses were performed using the RevMan software (version 5.4.2). The evidence was evaluated on the https://www.gradepro.org/website. Results: This study included 29 randomized controlled trials (RCTs) involving 1982 patients with moderate methodological quality that met the inclusion criteria. The results showed that, compared to Western medicine alone therapy, the use of TCM alone or in combination with Western medicine significantly improved total remission (TR) rate (risk ratios [RR] 1.38, 95% confidence interval [CI] 1.29–1.46, I2 = 0%, P

Background: Food allergies impose a large psychosocial burden, including mental, emotional, and social aspects, on both patients and their caregivers. Patients, caregivers, and their families often experience anxiety, isolation, and fear around food allergies. Objective: To assess the real-world mental health burden of food allergies, using the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). Methods: Self-reported data from patients with food allergies, and their caregivers, were analyzed from the FARE Food Allergy History and Mental Health Concerns surveys. Odds ratios were also calculated as a measure of association between patient food allergy characteristics and the likelihood of having mental health concerns or a formal mental health diagnosis. Results: The FARE Patient Registry included 1680 patients/caregivers. Anxiety (54%) and panic (32%) were the most common emotions that patients reported as a result of eating the food that produced an allergic reaction. About two-thirds of patients reported mental health concerns related to food allergies (62%), including anxiety after an allergic reaction, anxiety about living with food allergies, and concerns about food avoidance. Caregivers also experienced fear for the safety of their children, and often sought mental health care to cope with worry related to caring for patients with food allergies. The likelihood of having food allergy-related mental health concerns was increased for patients experiencing more than 1 reaction per year (OR 1.68–1.90) and was lowered for patients having a formal mental health diagnosis (OR 0.43). Caregivers filling out the FARE survey for pediatric patients (OR 4.03) and experiencing food allergy-related mental health concerns (OR 2.36) were both significant predictors for having a formal mental health diagnosis. Conclusion: Our study highlights a continuing unmet need for mental health screening and support as part of the management of patients with food allergies.

Background: Food allergies are serious and potentially life-threatening, and often place a large burden on patients and their caregivers, including impacts on quality of life. Objective: To assess the real-world patient burden of food allergies, using self-reported data available from the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). Methods: The FARE Patient Registry is voluntary and captures real-world experiences of adults and pediatric patients in the United States, and their caregivers, through a series of surveys assessing patient health and experiences with food allergies. Self-reported data were descriptively analyzed. Results: The FARE study cohort included 5587 patients with food allergies; 82% had multiple food allergies and 62% were aged 1 food-related allergic reaction per year (42%), with 46% experiencing food-induced anaphylaxis. Half of all food-related allergic reactions occurred at home. Accidental exposures to food allergens were experienced by 77% of patients. The most common allergic comorbidities reported by patients with food allergies were atopic dermatitis (48%), asthma (46%), and allergic rhinitis (39%). The clinical burden of food allergies were found to be greater in patients with multiple food allergies, and different for adults versus pediatric patients. Conclusion: This is the first study to assess patient experience and disease burden information from patients contributing to the FARE Patient Registry, thus providing a unique insight into the lives of patients in the United States with food allergies. These insights may assist clinicians and other public health stakeholders in the management of patients with food allergies.

In this study, the effects of grafting chlorogenic acid (CA) on the antioxidant and probiotic activities of curdlan oligosaccharides (CDOS) were investigated. CDOS with degrees of polymerization of 3–6 was first obtained by degradation of curdlan with hydrogen peroxide and then grafted with CA using a free radical-mediated method under an ultrasonication-assisted Fenton system. The thermal stability and antioxidant ability of CDOS were enhanced after grafting with CA. In vitro fermentation, supplementation of CDOS-CA stimulated the proliferation of Prevotella and Faecalibacterium while inhibiting the growth of harmful microbiota. Notably, the concentration of total short-chain fatty acids and the relative abundance of beneficial bacteria markedly increased after fermentation of CDOS-CA, indicating that CA grafting could improve the probiotic activity of CDOS. Overall, the covalent binding of CDOS and CA could enhance the antioxidant and probiotic activities of CDOS, suggesting potential improvements in gastrointestinal and colonic health.

Abstract Objective This study aimed to investigate the clinical infection characteristics and analyze the resistance gene carrying status of carbapenem-resistant Providencia rettgeri via whole genome sequencing (WGS). Methods Carbapenem-resistant P. rettgeri were collected from clinical patients between January 2020 and December 2021, and their susceptibility to 19 antimicrobial drugs was determined using the VITEK 2 Compact system and Kirby–Bauer (KB) disk diffusion method. The Illumina platform was used to perform WGS of the P. rettgeri isolates, and the resistance genes carried by the Carbapenem-resistant P. rettgeri strains were detected via ABRicate software. The phylogenetic tree was constructed by thirty-four strains including twenty-eight strains downloaded from NCBI database and the carbapenem-resistant six P. rettgeri strains in this study. Which based on genomic single nucleotide polymorphism (SNP) to understand the affinities of the carbapenem-resistant P. rettgeri strains. Results Six carbapenem-resistant P. rettgeri strains were isolated from five different clinical departments using the blood, urine, sputum, and secretion specimens. These infected patients are middle-aged and elderly people with a history of severe trauma, tumors, hypertension, and various other underlying diseases, and invasive procedures. Antimicrobial sensitivity testing showed that all strains presented resistance to ampicillin-sulbactam, ceftazidime, ciprofloxacin, levofloxacin, and ertapenem, whereas they exhibited full susceptibility to cefepime and amikacin. Most strains demonstrated high resistance to β-lactams, aminoglycosides, and sulfonamides. Thirty-five resistance genes were identified by ABRicate. All carbapenem-resistant P. rettgeri strains carried aminoglycoside, fluoroquinolone, chloramphenicol, rifampicin, sulfonamide, and β-lactam resistance genes, and most importantly, all strains possessed the carbapenem resistance gene bla NDM−1. The six P. rettgeri strains in this study and the 28 carbapenem-resistant P. rettgeri strains from the NCBI database were divided into four evolutionary groups. The WF3643, WF3849, WF3822, and WF3821 strains in this study were in the same evolutionary group (clade A), while the closely related WF3099 and WF3279 strains were in different evolutionary groups (clade B and clade D), respectively. The WF3099 strain was distantly related to the other five strains. Conclusion Carbapenem-resistant P. rettgeri strains were mostly isolated from middle-aged and older patients with a history of surgery or serious underlying diseases, and they were found to cause multisystem infections. All Carbapenem-resistant P. rettgeri strains in this study carried bla NDM−1 and multiple antimicrobial drug resistance genes. Furthermore, the P. rettgeri strains in this study were closely related, suggesting the possibility of nosocomial infections. Therefore, our study highlights the need for research on P. rettgeri to control the spread of these nosocomial infections.

N-glycans in many proteins are of great concern because of their strong association with food allergies. Triticum aestivum (bread wheat), a major food crop, is known as one of the “Big Eight” allergenic groups. However, little research has been done about N-glycans in wheat glycoproteins. In this study, a soluble wheat glycoprotein was purified from wheat and further identified as globulin-1 S allele (GSA). The wheat GSA displayed significant IgE-binding activity. Moreover, one N-glycosylation site and 6 kinds of N-glycans were identified by mass spectrometry, including 3 high mannose types and 3 complex types. Furthermore, the IgE-binding activity of wheat GSA is proved to be reduced by the removal of N-glycan, thermal treatment (temperatures > 80 °C), and strong acidic treatment (pH 3.0). These findings would provide a better understanding of the effects of N-glycosylation, thermal treatment, and acidic treatment on the molecular characteristics of GSA, and further provide new insights into the development of hypoallergenic wheat products.

Abstract Background By analyzing 23 evaluation indicators included in 14 national basic public health service programs in a region of Hohhot City, Inner Mongolia Autonomous Region, China, the performance of basic public health services in the region in 2021 were analyzed to clarify the implementation and conduct of relevant programs. We also use this study as a basis to radiate the work of municipal basic public health services centered on the region and the outstanding problems reflected and to provide theoretical contents and suggestions that can be referred to for the same regions in central and western China as well as worldwide. Methods Using the TOPSIS method as the basis for the data analysis method, the evaluation indexes are ranked in terms of their proximity to the idealized target, and combined with the entropy value method, Technique for order preference by similarity to an ideal solution (TOPSIS) and rank-sum ratio (RSR) were used to rank 14 basic health care providers by grade. A comprehensive evaluation of the performance of basic public health services in a region of Hohhot City, Inner Mongolia Autonomous Region in 2021 was conducted through a joint model of entropy -weighted TOPSIS and RSR, making full use of the characteristics and advantages of the fuzzy joint, and conducting a comprehensive analysis from the perspective of the ratio weight and the method of graded calculation, making the study more distinguishable and measureable. Results In this study, for the regional basic public health services, a total of 23 evaluation indicators of basic public health service projects were included, among which the top three indicators with the weight of the entropy value method indicators were found to include the rate of Chinese medicine health management for the elderly, the rate of health management for the elderly, and the BCG vaccination rate after the analysis of the weight of the indicators; After the entropy-weighted TOPSIS evaluation showed that the Ci values of the regions were found to be between 0.378 and 0.715 through the calculation of the positive and negative ideal values of each indicator; RSR staging method evaluation showed that three community health centers (X2, X10, X12) had excellent evaluations of basic public health services; The number of evaluations as poor and moderate are 2 (X3, X9) and 9 (X1, X4, X5, X6, X7, X8, X11, X13, X14), respectively; Finally, the results of the entropy-weighted TOPSIS method and the fuzzy joint model of RSR staging method are basically consistent with the overall trend of the above two methods, and the reliability and credibility of the research results are high. Conclusion The entropy-weighted TOPSIS and RSR joint model can evaluate the effectiveness of basic public health services in a more comprehensive and holistic way. The results of the RSR staging results and the related weight ratio analysis show that the basic public health service programs in Hohhot, Inner Mongolia Autonomous Region are relatively balanced, but there are some differences; The same genus of elderly Chinese medicine health management rate, health management rate of the elderly, BCG vaccination rate several indicators accounted for a higher weight, its correlation with the key population-related items is high, suggesting that the future key population health service items should be focused on, and future research should be suggested from two key research.

Hybrid wheel–track systems have found extensive applications due to the advantages a combination of wheels and tracks. However, the coupling influence between the wheeled and tracked mechanisms poses a challenge to stable and efficient controller design and implementation. This paper focuses on the lateral dynamic control of a vehicle in scenarios where both tracks and wheels are in contact with the ground. A dynamic model of a vehicle is first established based on the tire brush model and linearized general track model. Based on the dynamic model, a novel adaptive model predictive control (AMPC) method is designed considering the coupling and nonlinearity of the wheels and tracks to simultaneously regulate both mechanisms. Compared with traditional model predictive control approaches, the AMPC controller takes the side-slip angle and slip ratio as constraints to prevent the vehicle from reaching unstable states. Simulations are conducted to validate the effectiveness of the controller, and the results indicate that the controller has the capacity to optimize the objective’s yaw-rate response while maintaining lateral vehicle stability and preventing slip by imposing constraints.

To address the question of which posture trailing-arm vehicles (TAVs) should be adopted while driving, this study introduces an innovative active posture controller (APC) to improve both path-following and handling stability performance. Leveraging a nonlinear tire model that considers corner load variation and wheel camber, alongside the kinematics and double-track model of TAVs, the impact of vehicle body posture on handling performance has been investigated. To fully utilize the four-wheel independent drive and posture adjustable characteristics of the TAV mechanisms, an integrated nonlinear model predictive control (NMPC) combining APC and tire forces distribution is devised. Through simulations conducted using Simulink-Multibody (2023a), the effectiveness of the proposed controller is demonstrated, particularly when compared to the scheme that does not account for the unique posture adjustment mechanisms of TAVs.

As the common varieties of chopper pepper process, “La Feng 33” was selected as the research object. Five different growth stages of pepper from Shandong and Shanxi provinces were analyzed to explore the quality changes of pepper fruit during the growth process, which was essential for regulating the quality of chopped pepper and expanding the raw material sources. The results showed that the change trend of quality characteristics of pepper in the two regions was basically the same during the growth process. The content of VC and total capsaicin increased with fruit growth to some extent; soluble solids, acidity, total polyphenols, DPPH· scavenging capacity, FRAP, ABTS+· scavenging capacity decreased first and then increased with fruit growth; organic acids, total ash, Mg, Ca, Mn and Fe decreased with fruit growth. In addition, the contents of VC, soluble solids, organic acids and total capsaicin in Shandong producing area were higher than those in Shanxi producing area (P

Abstract Background In the current treatment of non-small cell lung cancer (NSCLC), traditional chemotherapy causes high toxicity, so it is necessary to develop safe chemical drug delivery vehicles clinically. Chemotherapy monotherapy is prone to drug resistance. Chemotherapy combined with other therapies such as nucleic acid drugs is an effective way to avoid drug resistance and the toxicity of continuous chemotherapy. In this study, chemotherapy and siRNA therapy were combined to treat paclitaxel-resistant NSCLC in order to increase efficacy and reduce toxicity. This study aims to develop a cabazitaxel-loaded human serum albumin nanoparticles (CTX-HSA-NPs) to improve the toxicity of traditional CTX-Tween 80 and increase targeting, and to develop a TGFβ-1 siRNA lipid Nanoparticles (TGFβ-1 siRNA LNP) combined with chemotherapy in the treatment of paclitaxel-resistant NSCLC. Results This study prepared CTX-HSA-NPs and TGFβ-1 siRNA LNP had small particle size, high encapsulation efficiency (EE). CTX-HSA-NPs lyophilized powder has high stability after dissolved. The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was 1.8 times lower than that of CTX-Tween. More importantly, the combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC in vivo and in vitro. The results of tumor immunohistochemistry showed that TGFβ-1 siRNA LNP significantly inhibited the expression of TGFβ-1, and compared with other groups, the expression of P-gp after low-dose CTX-HSA-NPs treatment was lower, which did not cause obvious drug resistance. Conclusions The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was lower than that of CTX-Tween. TGFβ-1 siRNA LNP can treat paclitaxel-resistant NSCLC by inhibiting the express of TGFβ-1 mRNA. The combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC. A combination therapy of chemotherapy and nucleic acid drugs could be an effective approach for treating paclitaxel-resistant NSCLC.

Magnesium alloys, as the lightest structural alloys, provide the possibility of solving environmental problems by improving energy efficiency. Developing and maintaining nanocrystalline matrix is a huge challenge, and the key to achieving ultra-high strength. The nanocrystalline Ti/AZ61 composite prepared by hot pressing was annealed, and its microstructural evolution was characterized via SEM, XRD, and TEM, including the changes in magnesium matrix, Ti dispersions, and nano-scale precipitates. The density and mechanical properties of annealed composites were tested and analyzed. After annealing treatment at 623 K for 80 h, the average grain size of nanocrystalline Ti/AZ61 composites was 102 nm. 97% of Ti dispersions were submicron sized, and Ti3Al precipitates remained nanometer-sized. Ti dispersions and Ti3Al precipitates were uniformly distributed in the magnesium matrix. Compared with hot pressed composites, the crack that originated from the prior particle boundary (PPB) was restrained for annealed composites. The improved density and PPB bonding strength of annealed Ti/AZ61 composites had a positive impact on strength and plasticity. After annealing treatment for 40 h, the density increased from ∼2.041 g/cm3 to 2.066 g/cm3. The hardness, yield strength, and FFS were 146 HV, 493 MPa, and 5.6%, respectively, with corresponding increasing rates of 7%, 12%, and 65%, respectively.

The adhesion on the food surface of lactic acid bacteria (LAB) plays an important role in their colonization and biological control. The inoculated conditions of LAB Lac 9-3 (including the inoculum concentration, bacterial growth stage, soaking time, and inoculum pH) were optimized using the random-centroid optimization (RCO) method. Meanwhile, the effect of LAB Lac 9-3 on the growth and microflora of spoilage bacteria of Litopenaeus vannamei was also investigated using the high throughput sequencing technology during the storage time at 0, 8, and 14 days. The results indicated that the optimal inoculated conditions of LAB Lac 9-3 were as follows: The inoculum concentration was 108 CFU/mL, the growth stage was 14.1 h (corresponding to the early stabilization period), the soaking time was 17.41 min, and the inoculum pH was 6.51. The adhesion quantity of LAB Lac 9-3 reached 2.08×109 CFU/g under the optimal inoculated conditions, which obtained a 72.65% increase compared to that of the control group at the same concentration. Besides, the growth of Shewanella, Carnobacterium, Aliivibrio, and Vibrio in L. vannamei treated by LAB Lac 9-3 was significantly inhibited, indicating that improving the adhesion of LAB Lac 9-3 could increase the adhesion quantity on the surface of L. vannamei. The LAB Lac 9-3 might process the application potential in food preservation due to its regulating role in microflora and the spoilage process of aquatic products.

Introduction Recombinant fusion protein linking coagulation factor IX (FIX) with albumin (rIX-FP) has been shown to be an effective, well-tolerated treatment for patients with severe hemophilia B who had previously received factor replacement therapy. This study investigated the safety and efficacy of rIX-FP in previously untreated patients (PUPs).

Aim: Improved management of chronic lymphocytic leukemia (CLL) has resulted in a growing population of CLL survivors; these patients have a higher risk of developing second primary malignancies (SPMs) versus the general population. This retrospective cohort study aims to assess the timing, frequency, incidence and types of SPMs in treated and untreated patients with CLL in the USA, using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, which links a nationally representative cancer registry with Medicare claims data. Patients & methods: Patients aged ≥66 years with newly diagnosed CLL between 1 January 2010 and 31 December 2016, who were enrolled in Parts A and B of Medicare for ≥12 months pre-diagnosis of CLL were selected from the database. Patients were assessed for ≥36 months until the end of continuous enrollment in Medicare Parts A, B and D, a switch to a health maintenance organization, death, or end of the study period (December 2019). Results: Of 3053 patients included in the analyses, 620 (20.3%) were treated and 2433 (79.7%) were untreated within 36 months of diagnosis. Overall, 638 (20.9%) patients developed a SPM, 26.8% of patients in the treated cohort and 19.4% of patients in the untreated cohort. The most common SPMs for both cohorts were squamous cell carcinoma and acute myeloid leukemia. Among the 166 treated patients who developed a SPM, a greater proportion developed their first SPM after treatment initiation versus those who developed their first SPM prior to treatment initiation (p < 0.001). A significantly lower percentage of patients who received targeted therapy developed a SPM (p < 0.05) versus patients treated with anti-CD20 + chemotherapy. Conclusion: Findings indicate that treatment type and timing can affect SPM development in patients with CLL. Combined with previous findings, this can help inform best practices in monitoring for SPM in patients with CLL.

BackgroundThe central nervous system (CNS) is the most common site of extramedullary invasion in acute lymphoblastic leukemia (ALL), and involvement of the CNS is often associated with relapse, refractory disease, and poor prognosis. Chimeric antigen receptor-T (CAR-T) cell therapy, a promising modality in cancer immunotherapy, has demonstrated significant advantages in the treatment of hematological malignancies. However, due to associated adverse reactions such as nervous system toxicity, the safety and efficacy of CAR-T cell therapy in treating CNSL remains controversial, with limited reports available.Case reportHere, we present the case of a patient with confirmed B-ALL who experienced relapse in both bone marrow (BM) and cerebrospinal fluid (CSF) despite multiple cycles of chemotherapy and intrathecal injections. The infusion of autologous CD19 CAR-T cells resulted in complete remission (CR) in both BM and CSF for 40 days. However, the patient later experienced a relapse in the bone marrow. Subsequently, allogeneic CD19 CAR-T cells derived from her brother were infused, leading to another achievement of CR in BM. Significantly, only grade 1 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events were detected during the treatment period and showed improvement with symptomatic management. During subsequent follow-up, the patient achieved a disease-free survival of 5 months and was successfully bridged to hematopoietic stem cell transplantation.ConclusionOur study provides support for the argument that CNS involvement should not be deemed an absolute contraindication to CAR-T cell therapy. With the implementation of suitable management and treatment strategies, CAR-T therapy can proficiently target tumor cells within the CNS. This treatment option may be particularly beneficial for relapsed or refractory patients, as well as those with central nervous system involvement who have shown limited response to conventional therapies. Additionally, CAR-T cell therapy may serve as a valuable bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in these patients.

ABSTRACTDrug addiction can seriously damage human physical and mental health, while detoxification is a long and difficult process. Although studies have reported changes in the oral microbiome of methamphetamine (METH) users, the role that the microbiome plays in the process of drug addiction is still unknown. This study aims to explore the function of the microbiome based on analysis of the variations in the oral microbiome and metabolome of METH users. We performed the 16S rRNA sequencing analysis based on the oral saliva samples collected from 278 METH users and 105 healthy controls (CTL). In addition, the untargeted metabolomic profiling was conducted based on 220 samples. Compared to the CTL group, alpha diversity was reduced in the group of METH users and the relative abundances of Peptostreptococcus and Gemella were significantly increased, while the relative abundances of Campylobacter and Aggregatibacter were significantly decreased. Variations were also detected in oral metabolic pathways, including enhanced tryptophan metabolism, lysine biosynthesis, purine metabolism, and steroid biosynthesis. Conversely, the metabolic pathways of porphyrin metabolism, glutathione metabolism, and pentose phosphate were significantly reduced. It was speculated that four key microbial taxa, i.e., Peptostreptococcus, Gemella, Campylobacter, and Aggregatibacter, could be involved in the toxicity and addiction mechanisms of METH by affecting the above metabolic pathways. It was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders was gradually increased. Our study provides novel insights into exploring the toxic damage and addiction mechanisms underlying the METH addiction.IMPORTANCEIt was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders gradually increased. The prediction models based on oral microbiome and metabolome could effectively predict the methamphetamine (METH) smoking. Our study provides novel insights into the exploration of the molecular mechanisms regulating the toxic damage and addiction of METH as well as new ideas for early prevention and treatment strategies of METH addiction.

Abstract Background Blood transfusion and previous stroke history are two independent risk factors of venous thromboembolism (VTE) in stroke patients. Whether the potential interaction of transfusion history and previous stroke history is associated with a greater risk of VTE remains unclear. This study aims to explore whether the combination of transfusion history and previous stroke history increases the risk of VTE among Chinese stroke patients. Methods A total of 1525 participants from the prospective Stroke Cohort of Henan Province were enrolled in our study. Multivariate logistic regression models were used to explore the associations among transfusion history, previous stroke history and VTE. The interaction was evaluated on both multiplicative and additive scales. The odds ratio (95% CI), relative excess risk of interaction (RERI), attributable proportion (AP), and synergy index (S) of interaction terms were used to examine multiplicative and additive interactions. Finally, we divided our population into two subgroups by National Institutes of Health Stroke Scale (NIHSS) score and re-evaluated the interaction effect in both scales. Results A total of 281 (18.4%) participants of 1525 complicated with VTE. Transfusion and previous stroke history were associated with an increased risk of VTE in our cohort. In the multiplicative scale, the combination of transfusion and previous stroke history was statistically significant on VTE in both unadjusted and adjusted models (P 5 points (P

Objective: Chitosan-coated nuciferine liposomes (CS-LP) were prepared and their hypolipidemic effects in vivo were investigated. Methods: The CS-LP were prepared by thin film dispersion and pH gradient methods, and their particle size and potential distribution, encapsulation rate, microscopic morphology and in vitro release curves were determined, and their hypolipidemic effects on obese mice were investigated. Results: The CS-LP was produced in a homogeneous spherical structure with a particle size of 253.54±4.25 nm, a zeta potential of 32.50±3.44 mV. The encapsulation rate of CS-LP was 83.46%. Compared with nuciferine liposomes (LP), the stability of CS-LP in the simulated digestive solution was improved after adding the chitosan. Compared with the high-fat group, mice gavaged with CS-LP for 11 weeks showed a 12.91% and 41.03% significant reduction in body weight and adipose tissue weight, respectively (P

Background Most of the existing studies on the influencing factors of pulmonary tuberculosis incidence are based on temporal or spatial regression models, and the results are limited. Objective To explore the temporal and spatial heterogeneity of pulmonary tuberculosis in China, and to analyze the temporal and spatial correlations between the incidence of pulmonary tuberculosis and meteorological and air quality factors, offering a scientific reference for the development of measures containing tuberculosis. Methods Monthly statistical data of pulmonary tuberculosis in China from 2016 to 2018 were collected. After being tested with multicollinearity and spatial-autocorrelation between incidence of pulmonary tuberculosis and meteorological and air quality factors, the incidence of pulmonary tuberculosis was used as the dependent variable, and meteorological and air quality factors as independent variables to construct OLS, GWR and GTWR models, respectively. Then the goodness of the three models was evaluated, and the optimal model was selected to describe the incidence of pulmonary tuberculosis. Kernel density plot and spatio-temporal graph were used to describe the spatio-temporal specificity of the fitting coefficients of each variable. Results The overall incidence of pulmonary tuberculosis in China during 2016-2018 decreased annually, with clustered spatial distribution. The GTWR model had higher R2 value and lower AICc value compared to other two models, indicating that it had better performance in explaining the influence of meteorological and air quality factors on the incidence of pulmonary tuberculosis. The kernel density plot of each variable showed that the increase of wind speed was associated with decreased pulmonary tuberculosis incidence in most cities. But the increase of humidity and air pollutant concentration was associated with increased incidence of pulmonary tuberculosis, and the strength of association varied across cities. Conclusion Meteorological and air quality factors may significantly influence the incidence of pulmonary tuberculosis, and the influence had spatio-temporal specificity. So prevention methods for pulmonary tuberculosis should be developed according to region-specific factors influencing the disease.