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Abstract The activation of ferroptosis presents a versatile strategy for enhancing the antitumor immune responses in cancer therapy. However, developing ferroptosis inducers that combine high biocompatibility and therapeutic efficiency remains challenging. In this study, we propose a novel approach using biological nanoparticles derived from outer membrane vesicles (OMVs) of Escherichia coli for tumor treatment, aiming to activate ferroptosis and stimulate the immune responses. Specifically, we functionalize the OMVs by anchoring them with ferrous ions via electrostatic interactions and loading them with the STING agonist-4, followed by tumor-targeting DSPE-PEG-FA decoration, henceforth referred to as OMV/SaFeFA. The anchoring of ferrous ions endows the OMVs with peroxidase-like activity, capable of inducing cellular lipid peroxidation by catalyzing H2O2 to •OH. Furthermore, OMV/SaFeFA exhibits pH-responsive release of ferrous ions and the agonist, along with tumor-targeting capabilities, enabling tumor-specific therapy while minimizing side effects. Notably, the concurrent activation of the STING pathway and ferroptosis elicits robust antitumor responses in colon tumor-bearing mouse models, leading to exceptional therapeutic efficacy and prolonged survival. Importantly, no acute toxicity was observed in mice receiving OMV/SaFeFA treatments, underscoring its potential for future tumor therapy and clinical translation.

Abstract Depression questionnaire cutoffs are calibrated for screening accuracy and not to assess prevalence, but the Geriatric Depression Scale (GDS-15) is often used to estimate diagnostic prevalence among older adults, most commonly with scores of ≥ 5. We conducted an individual participant data meta-analysis to compare depression prevalence based on GDS-15 ≥ 5 to Structured Clinical Interview for Diagnostic and Statistical Manual (SCID) diagnoses and assessed whether an alternative cutoff could be more accurate. We used generalized linear mixed models to estimate prevalence. Data from 14 studies (3602 participants, 434 SCID major depression) were included. Pooled GDS-15 ≥ 5 prevalence was 34.2% (95% confidence interval [CI] 27.5–41.6%), and pooled SCID prevalence was 14.8% (95% CI 10.0–21.5%; difference of 17.6%, 95% CI 11.6–23.6%). GDS-15 ≥ 8 provided the closest estimate to SCID with mean difference of − 0.3% (95% prediction interval − 17.0–16.5%). Prevalence estimate differences were not associated with study or participant characteristics. In sum, GDS-15 ≥ 5 substantially overestimated depression prevalence. A cutoff of ≥ 8 was accurate overall, but heterogeneity was too high for implementation in practice. Validated diagnostic interviews should be used to estimate major depression prevalence among older adults.

Abstract Background Studies have confirmed that epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties are conducive to cancer metastasis. In recent years, testes-specific protease 50 (TSP50) has been identified as a prognostic factor and is involved in tumorigenesis regulation. However, the role and molecular mechanisms of TSP50 in EMT and CSC-like properties maintenance remain unclear. Methods The expression and prognostic value of TSP50 in breast cancer were excavated from public databases and explored using bioinformatics analysis. Then the expression of TSP50 and related genes was further validated by quantitative RT-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). In order to investigate the function of TSP50 in breast cancer, loss- and gain-of-function experiments were conducted, both in vitro and in vivo. Furthermore, immunofluorescence (IF) and immunoprecipitation (IP) assays were performed to explore the potential molecular mechanisms of TSP50. Finally, the correlation between the expression of TSP50 and related genes in breast cancer tissue microarray and clinicopathological characteristics was analyzed by IHC. Results TSP50 was negatively correlated with the prognosis of patients with breast cancer. TSP50 promoted CSC-like traits and EMT in both breast cancer cells and mouse xenograft tumor tissues. Additionally, inhibition of PI3K/AKT partly reversed TSP50-induced activation of CSC-like properties, EMT and tumorigenesis. Mechanistically, TSP50 and PI3K p85α regulatory subunit could competitively interact with the PI3K p110α catalytic subunit to promote p110α enzymatic activity, thereby activating the PI3K/AKT signaling pathway for CSC-like phenotypes maintenance and EMT promotion. Moreover, IHC analysis of human breast cancer specimens revealed that TSP50 expression was positively correlated with p-AKT and ALDH1 protein levels. Notably, breast cancer clinicopathological characteristics, such as patient survival time, tumor size, Ki67, pathologic stage, N stage, estrogen receptor (ER) and progesterone receptor (PR) levels, correlated well with TSP50/p-AKT/ALDH1 expression status. Conclusion The effects of TSP50 on EMT and CSC-like properties promotion were verified to be dependent on PI3K p110α. Together, our study revealed a novel mechanism by which TSP50 facilitates the progression of breast cancer, which can provide new insights into TSP50-based breast cancer treatment strategies.

Abstract Adipose tissue plays critical roles in an individual’s aging process. In this research, we use single-nucleus RNA sequencing to create highly detailed transcriptional maps of subcutaneous adipose tissue and visceral adipose tissue in young and aged mice. We comprehensively identify the various cell types within the white adipose tissue of mice, our study has elucidated seven distinct cell types within this tissue. Further analyses focus on adipocytes, fibro-adipogenic progenitors, and immune cells, revealing age-related declines in the synthetic metabolic activity of adipocytes, diminished immune regulation, and reduced maturation or proliferation of fibroblasts in undifferentiated adipocytes. We confirm the presence of distinct subpopulations of adipocytes, highlighting decreases in adipogenesis subgroups due to aging. Additionally, we uncover a reduction in immune cell subpopulations, driven by age-associated immune system dysregulation. Furthermore, pseudo-time analyses indicate that Adipocyte1 represents the 'nascent' phase of adipocyte development, while Adipocyte2 represents the 'mature' phase. We use cell–cell interaction to explore the age-dependent complexities of the interactions between FAPs and adipocytes, and observed increased expression of the inflammation-related Retn-Tlr4 interaction in older mice, while the anti-inflammatory Angpt1-Tek interaction was only detected in young mice. These transcriptional profiles serve as a valuable resource for understanding the functional genomics underlying metabolic disorders associated with aging in human adipose tissue.

In this study, the prepared dish Kung Pao Chicken with soy protein artificial meat (SPAM-KPC) was developed to satisfy the higher demand for nutritious healthy and diversified convence food, and the changes in storage quality of SPAM-KPC at different storage temperatures (4, 25 and 37 ℃) were compared. The shelf life prediction model of the SPAM-KPC was established based on the total number of bacteria as the key quality factor affecting the shelf life of the product. The results showed that the total colony count of SPAM-KPC samples stored at three temperatures for 15 days increased from 0.67 lg(CFU/g) to 2.73, 3.37 and 4.33 lg(CFU/g), respectively. While pH (from 6.22 to 5.88, 5.87, 5.69) and sensory scores (from 25.12 to 22.67, 19.52, 16.84) gradually decreased, as well as hardness and springiness decreased. The shelf life of SPAM-KPC products at three storage temperatures was 28, 20 and 17 days, respectively. According to the findings, low-temperature storage at 4 ℃ was the best storage temperature for SPAM-KPC products. This work could provide a theoretical reference for the application of plant-based protein meat in the field of prepared dishes processing.

Abstract. Background:. Life's Simple 7, the former construct of cardiovascular health (CVH) has been used to evaluate adverse non-communicable chronic diseases (NCDs). However, some flaws have been recognized in recent years and Life's Essential 8 has been established. In this study, we aimed to analyze the association between CVH defined by Life's Essential 8 and risk of 44 common NCDs and further estimate the population attributable fractions (PAFs) of low-moderate CVH scores in the 44 NCDs. Methods:. In the UK Biobank, 170,726 participants free of 44 common NCDs at baseline were included. The Life's Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH score was categorized into low, moderate, and high groups. Participants were followed up for 44 NCDs diagnosis across 10 human system disorders according to the International Classification of Diseases 10th edition (ICD-10) code using linkage to national health records until 2022. Cox proportional hazard models were used in this study. The hazard ratios (HRs) and PAFs of 44 NCDs associated with CVH score were examined. Results:. During the median follow-up of 10.85 years, 58,889 incident NCD cases were documented. Significant linear dose-response associations were found between higher CVH score and lower risk of 25 (56.8%) of 44 NCDs. Low-moderate CVH (

Abstract Background Certain occupations may predispose individuals to urolithiasis, a multi-factorial disease. The study aimed to evaluate the prevalence and related factors of nephrolithiasis in medical staff in Qingdao, China. Methods Physical examination results of 5115 in-service medical staff aged 22–60 years old were retrospectively analyzed. Multivariable logistic regression analysis and stratified analyses by age and gender were applied to explore the related factors of nephrolithiasis in these medical staff. Results The overall nephrolithiasis prevalence in medical staff in Qingdao, China was 4.65%. Doctors were more prone to nephrolithiasis than nurses (5.63% vs. 3.96%, P = 0.013) and the peak prevalence (6.69%) was observed in medical staff working in the emergency department (ED). Male gender (OR = 1.615, 95% CI = 1.123–2.323, P = 0.010), overweight or obesity (OR = 1.674, 95% CI = 1.266–2.214, P

Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still hindered by challenges including excessive release of zinc ions (Zn2+), particularly in the early stage of implantation, and absence of bio-functions related to complex bone repair processes. Herein, a biodegradable aliphatic polycarbonate drug-eluting coating was fabricated on zinc-lithium (Zn–Li) alloys to inhibit Zn2+ release and enhance the osteogenesis, angiogenesis, and bacteriostasis of Zn alloys. Specifically, the photo-curable aliphatic polycarbonates were co-assembled with simvastatin and deposited onto Zn alloys to produce a drug-loaded coating, which was crosslinked by subsequent UV light irradiation. During the 60 days long-term immersion test, the coating showed distinguished stable drug release and Zn2+ release inhibition properties. Benefiting from the regulated release of Zn2+ and simvastatin, the coating facilitated the adhesion, proliferation, and differentiation of MC3T3-E1 cells, as well as the migration and tube formation of EA.hy926 cells. Astonishingly, the coating also showed remarkable antibacterial properties against both S. aureus and E. coli. The in vivo rabbit critical-size femur bone defects model demonstrated that the drug-eluting coating could efficiently promote new bone formation and the expression of platelet endothelial cell adhesion molecule-1 (CD31) and osteocalcin (OCN). The enhancement of osteogenesis, angiogenesis, and bacteriostasis is achieved by precisely controlling of the released Zn2+ at an appropriate level, as well as the stable release profile of simvastatin. This tailored aliphatic polycarbonate drug-eluting coating provides significant potential for clinical applications of Zn alloys implants.

Background: Second-generation antipsychotics (SGAs) frequently cause metabolic syndrome (MetS), which raises the risk of heart disease, type 2 diabetes, morbid obesity, atherosclerosis, and hypertension. MetS also impairs cognitive function in patients with schizophrenia. However, the fundamental reasons of MetS caused by SGAs are not yet fully understood. Thus, we aimed to identify potential therapeutic targets for MetS induced by SGAs. Methods: The serum biochemical parameters and the RNA-sequencing of peripheral blood mononuclear cells were measured in three groups (healthy controls and patients with schizophrenia with and without MetS taking SGAs). The study of the weighted gene co-expression network was utilized to pinpoint modules that were significantly connected to clinical markers. Results: Statistical analysis showed significant differences in triglyceride and high-density lipoprotein among the three groups. The TNF signaling pathway, TGF-β signaling pathway, fatty acid metabolism, NF-kappa B signaling pathway, MAPK signaling pathway, and Toll-like receptor signaling pathway were the pathways that were primarily enriched in the two unique co-expression network modules that were found. Finally, five specific genes (TNF, CXCL8, IL1B, TIMP1, and ESR1) associated with metabolism and immunity pathways were identified. Conclusions: This study indicated that SGAs differentially induced MetS of patients with schizophrenia through metabolic and inflammation-related pathways. Therefore, the potential side effects of drugs on inflammatory processes need to be considered when using SGAs for the treatment of schizophrenia.

Abstract Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

Abstract An equivalent analytical model of sloshing in a two-dimensional (2-D) rigid rectangular container equipped with multiple vertical baffles is presented. Firstly, according to the subdomain partition approach, the total liquid domain is partitioned into subdomains with the pure interface and boundary conditions. The separation of variables is utilized to achieve the velocity potential for subdomains. Then, sloshing characteristics are solved according to continuity and free surface conditions. According to the mode orthogonality of sloshing, the governing motion equation for sloshing under horizontal excitation is given by introducing generalized time coordinates. Besides, by producing the same hydrodynamic shear and overturning moment as those from the original container-liquid-baffle system, a mass-spring analytical model of the continuous liquid sloshing is established. The equivalent masses and corresponding locations are presented in the model. The feasibility of the present approach is verified by conducting comparative investigations. Finally, by utilizing normalized equivalent model parameters, the sloshing behaviors of the baffled container are investigated regarding baffle positions and heights as well as the liquid height, respectively.

Abstract Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ’s role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ’s effectiveness.

Abstract Interactions are mandatory for online or offline music and dance education to improve understandability and learning efficacy. The course designed for such artistic education incorporates multi-point interactions and monotonous presentations. The validation of the key factor: interactivity is thus mandatory for enhancing efficiency. This article introduces an interactivity validation method (IVM) using combined fuzzy neural network (FNN) to aid artistic course development. The output of the existing course and its evaluation criteria are considered in enhancing its grade. The fuzzy performs interaction classification as mandatory and trivial based on the student’s performance. The neural network identifies the chances for maximum performance by increasing or decreasing the interaction rate. If a saturated performance is achieved at a high or low interactivity, then the further course design is performed based on the saturated interactivity factor. The failing factors are used for training the neural network for modifying the interactivity rate from the current course development suggestion. Such a process is keen on classifying and validating the impact of interactivity over artistic course design.

Abstract Background To investigate the changes in the unhealthy eye-related behaviors of junior middle school students during the COVID-19 pandemic and the double reduction policy and its relationship with myopia. Methods Data were obtained from the 2019–2022 Tianjin Children and Youth Myopia, Common Diseases and Health Influencing Factors Survey. Latent profile analysis (LPA) and a generalized linear model (GLM) were applied to analyze the effect of eye-related behavior classes on myopia. Results A total of 2508 junior middle school students were included. The types of eye-related behavior were categorized into the medium-healthy behavior group, heavy academic burden and near-eye behavior group, insufficient lighting group and high-healthy behavior group. Students with heavy academic burdens and near-eye behavior were more likely to develop myopia than were those in the high-healthy group (OR = 1.466, 95% CI = 1.203–1.787; P

Food is the top priority for the people, and safety is the top priority for food. The quality and safety of food are related to the national economy and people's livelihood. With the development of Chinese economy and the improvement of people's quality of life, the scale of the food industry has also grown year by year, and the society and consumers have more stringent requirements on the quality of food production and its own safety. However, food quality and safety incidents occur frequently, making food quality and safety management an important task for improving people's livelihoods. Machine learning has been widely applied in the field of food quality and safety, with strong self-learning ability, good non-linear fitting ability, and fast modeling. Among them, neural network models and supervised learning methods can accurately and quickly detect and control the quality of food in the production process. This article focuses on the research progress of machine learning in the field of food quality and safety, and discusses it in three directions: Food quality inspection, food process traceability, and food safety warning. In order to clarify the focus, advantages and disadvantages, and future development direction of machine learning algorithms in food regulation, and provide theoretical support and technical guidance for the intelligent development of ensuring food quality and safety.

Abstract. Background:. Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD). Methods:. In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women. Results:. Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5–4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00–1.16) in men and 1.23 (1.16–1.31) in women. The association between having a birth weight

Abstract This study investigates the impact of geopolitical risk (GPR) on consumption-based carbon (CCO2) emissions as well as the moderating role of environmental policy stringency (EPS) on the above relationship. Based on data collected from 27 countries from 1990 to 2020, the basic results from the sample of the study indicate that GPR accelerates CCO2 emissions. Quantile regression results reveal that the effect of GPR is more pronounced in countries with higher CCO2 emissions. Moreover, EPS weakens the escalating effect of GPR on CCO2 emissions. The robust test results validate the findings reported in the basic regression model. The heterogeneity test indicates that the impact of GPR on CCO2 emissions is greater in developing countries compared in developed countries. The study also proposes these policy implications based on the findings: (1) countries should ensure a stable political environment, establish a robust legal system and promote energy transition; and (2) the scope of environmental taxes should be expanded where different tax rates should be imposed in order to be useful in reducing CCO2 emissions.

ABSTRACT Aim This study aims to investigate the association of glycemia risk index (GRI), a novel composite metric derived from continuous glucose monitoring (CGM), with arterial stiffness in patients with type 2 diabetes. Materials and Methods A total of 342 adults with type 2 diabetes were enrolled between April and June 2023 from 11 communities in Shanghai, China. Medical examinations, including measurements of anthropometric parameters, blood pressure, and venous blood samples were conducted. Brachial‐ankle pulse wave velocity (baPWV) was examined to evaluate arterial stiffness. All the participants underwent a 14 day CGM recording and GRI was calculated from the CGM data. Results The mean age was 70.3 ± 6.8 years, and 162 (47.4%) were male. Participants with a higher baPWV had significantly higher levels of GRI and hyperglycemia component (both P for trend

The rapid development of Chinese potato processing industry can be attributed to the implementation of the potato staple food industrialization strategy. Potato protein, known for its high nutritional value and functionality, exhibits exceptional solubility and contains a significant amount of tyrosines that are scarce in other plant proteins. Consequently, potato protein holds immense potential for various market applications. This paper provides a comprehensive review of the composition, functional properties, modification methods, and modification applications of potato protein. Potato protein exhibits good solubility, foaming and emulsifying properties, gelation, and antioxidant activity. Currently, enzyme treatment and microbial fermentation are the focus of potato protein modification research. Additionally, this article provides an overview of the main issues commonly found in potato protein and proposes future development prospects based on current research progress. In the future, it is necessary to further investigate the relationship between the molecular structure of potato protein and its functional activities. Enhancing the utilization of potato protein and plant proteins, enzymatic methods and microbial fermentation shows promise as a future direction for modification. By harnessing microbial resources, the cost of modification can be effectively reduced.

Objective: To compare the quantitative parameters of lung HRCT and clinical manifestations of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive idiopathic inflammatory myopathy (IIM) patients with different prognoses. Methods: The clinical and imaging data of 19 MDA5 antibody-positive IIM patients admitted to Beijing Shijitan Hospital Affiliated with Capital Medical University between February 2017 and November 2022 were retrospectively analyzed. According to the prognoses, the patients were divided into the good prognoses group (14 cases) and the poor prognoses (intubation or death) group (5 cases). The clinical and laboratory indexes, types of interstitial lung disease (ILD), and CT quantitative indexes were compared between the two groups. Results: There were significant differences in gender; carcinoembryonic antigen; blood oxygen saturation; and the percentages of lymphocytes, monocytes, neutrophils, lymphocytes, and neutrophils between the good versus the poor prognoses groups. The proportion of abnormal respiratory system changes was higher in the poor prognoses group. In terms of the type of ILD, acute interstitial pneumonia (AIP)-like lesions were the main type in the poor prognoses group, and nonspecific interstitial pneumonia (AIP) lesions were the main type in the good prognoses group. For NSIP-like lesions, there was a statistically significant difference between the two groups. The semi-quantitative score of the poor prognoses group was higher, and the volume of whole lung lesions as well as the proportion of whole lung lesions were also higher. Spearman correlation analysis showed that the blood oxygen saturation, monocyte percentage, semi-quantitative score, whole lung lesion volume, and proportion of whole lung lesion were negatively correlated, while carcinoembryonic antigen, neutrophil percentage, and neutrophils were positively correlated with the semi-quantitative score, whole lung lesion volume, and proportion of whole lung lesion. Conclusions: The lung HRCT quantitative indicators, clinical manifestations, and laboratory indicators are different in MDA5 antibody-positive IIM patients with different prognoses. Early evaluation of HRCT imaging manifestations, clinical manifestations, and laboratory indicators is of great significance in determining the prognosis of MDA5 antibody-positive IIM patients, which provides corresponding support for clinical diagnosis and treatment.

Abstract It is important to strengthen the research on urban rail transit (URT) existing line renovation strategies. In this paper, we investigate the optimization of bottlenecks that are less attractive but have strong travel demand in existing URT networks. A URT local line optimization model is constructed. The maximum passenger flow and minimum project cost are chosen as the optimization objective for the benefit of both passengers and operators, and several actual constraints are considered in the proposed model, such as the station interval. In order to obtain higher computational efficiency and accuracy, a passenger flow allocation method is embedded in a genetic algorithm with elitist preservation. Taking the local network of the Beijing URT as a case study, the calculation results show that the designed algorithm can quickly and effectively obtain the optimal solution, and the generated local line scheme is able not only to meet the regional travel demand, but also to optimize the connection relationship of the existing URT network. This study can provide a reference method for increasing the attraction of URT and optimization of existing URT networks.

This is an article in the field of metallurgical engineering. In this article, TiH2 powder was selected as the experimental raw material to study the sintering behavior of TiH2 powder under different pressing pressure and holding time in cold isostatic pressing, to reveal the effects of pressing pressure and holding time on the shrinkage as well as the relative density of TiH2 sintered specimens, in order to improve the density of the billet and the performance of the products. The results show that the shrinkage of the sintered sample decreases with the increase of the pressing pressure, and when the pressing pressure reaches 400 MPa, the pressing pressure has little effect on the relative density of the sintered sample. For the consideration of the sample preparation efficiency and the pressing pressure limit of the cold isostatic press, the pressing pressure should not exceed 400 Mpa. The shrinkage of sintered samples decreases with the increase of holding time, and when the holding time reaches 20 min, the relative density of sintered samples changes little with the extension of holding time. For the consideration of sample preparation efficiency, the suitable holding time is 15～20 min.

Abstract Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (3R-NC + KFDi.n). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the 3R-NC + KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

Abstract. Background:. The serum vitamin D level varies widely by population, and studies have linked vitamin D levels with the risk of type 2 diabetes mellitus (T2DM). However, the relationship is inconsistent and the impact of vitamin D on T2DM among East Chinese adults is unclear. The study aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) levels and the risk of T2DM and evaluated whether the association is modified by genetic predisposition. Methods:. In the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cohort, 1862 participants free of T2DM at baseline were included. A weighted genetic risk score was calculated with 28 variants associated with T2DM. Hierarchical logistic models were used to examine the association of serum 25(OH)D and genetic risk with T2DM. Results:. After a 5-year follow-up, 132 cases of T2DM were documented. We observed no significant association between quartiles of serum 25(OH)D and T2DM risk after multivariable adjustment (χ2 = 0.571, Pfor trend = 0.426). Compared to those in the lowest quartile of 25(OH)D, the odds ratios (ORs) (95% confidence interval [CI]) for participants with increased quartiles were 1.29 (0.74–2.25), 1.35 (0.77–2.36), and 1.27 (0.72–2.24), respectively. We observed a positive association of glycated hemoglobin (HbA1c) with 25(OH)D at baseline (β = 1.752, P = 0.001) and after follow-up (β = 1.385, P = 0.003), and a negative association of ln conversion homeostasis model assessment (HOMA)-β with 25(OH)D at baseline (β = -0.982, P = 0.021). There was no significant interaction between 25(OH)D and diabetes genetic predisposition on the risk of T2DM (χ2 = 2.710, Pfor interaction = 0.100). The lowest OR (95% CI) of T2DM was among participants with low genetic risk and the highest quartile of 25(OH)D (0.17 [0.05–0.62]). Conclusion:. Serum 25(OH)D may be irrelevant to the risk of incident T2DM among East Chinese adults regardless of genetic predisposition.

Accurate wind power prediction is critical for efficient grid management and the integration of renewable energy sources into the power grid. This study presents an effective deep-learning approach that improves short-term wind power forecasting accuracy. The method incorporates a Variational Autoencoder (VAE) with a self-attention mechanism applied in both the encoder and decoder. This empowers the model to leverage VAE's strengths in time-series modeling and nonlinear approximation while focusing on the most relevant features within the wind power data. The effectiveness of this approach is evaluated through a comprehensive comparison with eight established deep learning methods, including Recurrent Neural Networks (RNNs), Long Short-Term Memory (LSTM) networks, Bidirectional LSTMs (BiLSTMs), Convolutional LSTMs (ConvLSTMs), Gated Recurrent Units (GRUs), Stacked Autoencoders (SAEs), Restricted Boltzmann Machines (RBMs), and vanilla VAEs. Real-world data from five wind turbines in France and Turkey is used for the evaluation. Five statistical metrics are employed to quantitatively assess the prediction performance of each method. The results indicate that the SA-VAE model consistently outperformed other models, achieving the highest average R2 value of 0.992, demonstrating its superior predictive capability compared to existing techniques.

Precise traffic flow prediction is a central component of advancing intelligent transportation systems, providing essential insights for optimizing traffic management, reducing travel times, and alleviating congestion. This study introduces an efficient deep learning approach that synergistically integrates the benefits of wavelet-based denoising and Recurrent Neural Networks (RNNs). This integrated methodology is introduced to effectively capture the inherent nonlinearity and temporal dependencies in time series traffic data. Specifically, Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) are introduced to address the challenges associated with accurately forecasting traffic flow. To enhance prediction quality, traffic flow data is preprocessed using exponential smoothing and wavelet-based filtering as denoising filters, effectively eliminating outliers. The effectiveness of the proposed techniques is evaluated using traffic measurements collected from diverse highway locations across California, including the Old Bayshore highway, situated south of Interstate 880 (I880), and the Ashby Ave highway, positioned west of Interstate 80 (I80) in the San Francisco Bay Area. The results obtained through integrating both architectures, including LSTM and GRU, within the wavelet transform-based filter demonstrate an enhancement in forecasting performance. Specifically, LSTM with wavelet-based denoising using Symlet and Haar wavelets achieved high prediction performance with an average R2 of 0.982 and 0.9811, respectively.

Cell isolation protocols from brain tissue include prolonged ex vivo processing durations, rendering them suboptimal for transcriptomic studies. Particularly for microglia and vascular cells, current isolation methods produce lower yields, necessitating addition of an enrichment step, and use of large tissue volumes - in most cases whole brain tissue - to obtain sufficient yields. Here, we developed a simple, rapid, and reproducible cell isolation method for generating single-cell suspensions from micro-dissected brain regions, enriched for microglia and vascular cells, without an enrichment step. Cells isolated using this method are suitable for molecular profiling studies using 10 × Genomics Chromium single-cell RNA sequencing with high reproducibility. Our method is valuable for longitudinal unbiased molecular profiling of microglia and vascular cells within different brain regions, spanning multiple time points across physiological development or disease progression.

BackgroundSerious games (SGs) have emerged as engaging and instructional digital simulation tools that are increasingly being used for military medical training. SGs are often compared with traditional media in terms of learning outcomes, but it remains unclear which of the 2 options is more efficient and better accepted in the process of knowledge acquisition. ObjectiveThis study aimed to create and test a scenario-based system suitable for enhancing rescue reasoning skills in tactical combat casualty care. MethodsTo evaluate the effectiveness of the SGs, a randomized, observational, comparative trial was conducted. A total of 148 members from mobile medical logistics teams were recruited for training. Pre- and posttraining assessments were conducted using 2 different formats: a video-based online course (n=78) and a game simulation (n=70). We designed 3 evaluation instruments based on the first 2 levels of the Kirkpatrick model (reaction and learning) to measure trainees’ satisfaction, knowledge proficiency, and self-confidence. ResultsThere were 4 elements that made up the learning path for the SGs: microcourses (video-based online courses), self-test, game simulation, and record query. The knowledge test scores in both groups were significantly higher after the intervention (t154=–6.010 and t138=–7.867, respectively; P

BackgroundArtesunate (ART), a natural compound derived from Artemisia annua, has shown promising clinical potentials in the treatment of various tumors, but the exact mechanism is unclear. Choroidal melanoma (CM) is a major malignant ocular tumor in adults, known for its significant malignancy and poor prognosis, with limited efficacy in current treatments. This study explored the anti-CM effects and mechanisms of ART using a combination of network pharmacology, molecular docking and experimental validation.MethodsPotential targets of ART were screened in PubChem, Swiss Target Prediction and Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database Analysis Platform databases, while target genes related to CM prognosis were selected from Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNET databases. The intersection of these two groups of datasets yielded the target genes of ART involved in CM. Protein-protein interaction (PPI) network analysis of the intersecting targets, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were conducted to identify core targets and critical pathways. Molecular docking methods were performed to predict the binding interactions between ART and core targets. The effects of ART on CM were evaluated through CCK8, colony formation, transwell, as well as flow cytometry assays to detect apoptosis, cell cycle, reactive oxygen species (ROS). Western blot (WB) assays were conducted to investigate the impact of ART on key proteins and pathways associated with CM. Finally, in vivo assays were conducted to further validate the effects of ART on subcutaneous tumors in nude mice.ResultsResearch has shown that key pathways and core targets for ART in treating CM were identified through a network pharmacology approach. Molecular docking results verified the strong binding affinity between ART and these core targets. The analysis and predicted results indicated that ART primarily exerted its effects on CM through various tumor-related pathways like apoptosis. The assays in vitro confirmed that ART significantly inhibited the proliferation and migration of CM cells. This was achieved by promoting apoptosis through activation of the p53 signaling pathway, causing cell cycle arrest at the G0/G1 phase by inhibiting the PI3K/AKT/mTOR signaling pathway and increasing the intracellular level of ROS by activating the NRF2/HO-1 signaling pathway. Additionally, the assays in vivo further validated the significant proliferation-inhibitory effect of ART on CM.ConclusionThis study, making the initial exploration, illustrated through network pharmacology combined with molecular docking and in vitro/in vivo assays, confirmed that ART exerted potential anti-cancer effects on CM by promoting apoptosis, inducing cell cycle arrest and increasing intracellular levels of ROS. These findings suggested that ART held significant therapeutic potential for CM.

Pregnane X receptor (PXR) is a heterologous biosensor that is involved in the metabolic pathway of environmental pollutants, regulating the transcription of genes involved in biotransformation. There are significant differences in the selectivity and specificity of organic pollutants (OPs) toward polar bear PXR (pbPXR) and human PXR (hPXR), but the detailed dynamical characteristics of their interactions are unclear. Homology Modeling, molecular docking, molecular dynamics simulation, and free energy calculation were used to analyze the recognition of pbPXR and hPXR by three OPs: BPA, chlordane and toxaphene. Comparing interaction patterns along with binding free energy of pbPXR and hPXR with these three OPs revealed that although pbPXR and hPXR interact similar with these three OPs, these OPs have different effects on the internal dynamics of pbPXR and hPXR. This results in significant alterations in the interaction of key residues near Leu209, Met243, Phe288, Met323, and His407 with OPs, thereby influencing their binding energy. Non-polar interactions, especially van der Waals interactions, were found to be the dominating factors in interacting of these OPs with PXRs. The region surrounding these key residues facilitates hydrophobic contacts with PXR, which are crucial for the selective activation of PXRs in different species by these three OPs. These findings are of significant guidance in understanding the impacts of environmental endocrine disruptors on different organisms.

BackgroundEfgartigimod (Efgartigimod alpha fcab, Vyvgart™) is a pioneering neonatal Fc receptor (FcRn) antagonist for the treatment of severe autoimmune diseases mediated by pathogenic immunoglobulin G (IgG) autoantibodies, including myasthenia gravis (MG). It is a well-tolerated drug with minor side effects, such as headache and upper respiratory (lung) and urinary tract infections. Here, we present a case of Kaposi’s varicelliform eruption (KVE) and herpetic conjunctivitis related to efgartigimod in a 60-year-old patient with ocular MG (OMG).Case descriptionA 60-year-old Chinese male suffered from acetylcholine receptor antibody positive (AChR Ab+) OMG for 8 years. During this period, he underwent first-line treatment with systemic corticosteroids, cyclosporine, cyclophosphamide, and so on, but had poor symptom improvement. On the recommendation of his attending neurologist, he received one cycle of intravenous efgartigimod (10mg/kg, once weekly for 4 weeks). The patient experienced fever, widespread painful blisters, and edema on the face on the third day after his last intravenous infusion. The patient also complained of increased secretions and a foreign body sensation in both eyes. Laboratory tests confirmed infection with herpes simplex virus (HSV). A diagnosis of efgartigimod-associated KVE and herpetic conjunctivitis was made. After intravenous administration (5mg/kg, 3 times a day, every 8 hours) for 10 days, the patient was cured without residual complications.ConclusionsThis case is the first report of a patient with KVE and herpetic conjunctivitis related to efgartigimod in PubMed. This is rare and unusual. Clinicians should be alert to the rare symptoms related to efgartigimod.

Accurate mapping of irrigated croplands is crucial for a comprehensive understanding of agricultural practices and land management. Despite recent advancements, there remains room for further exploration of the effective fusion of temporal information from multitemporal remote sensing images, which is essential for capturing the dynamic nature of agricultural landscapes. Many existing irrigation mapping methods concatenate multitemporal images in a direct way and thus neglect the temporal relationships within the image time series, especially the sequence and interdependencies of the temporal dimension. To address this gap, a novel deep learning model, named the attention-enhanced spatial–temporal high-resolution network (AEST-HRNet), which incorporates parallel processing and a fusion mechanism of multiresolution information streams, three-dimensional (3D) spatial–temporal convolution, and temporal attention modules, was proposed. When applied to irrigated regions in Washington and California, USA, AEST-HRNet effectively extracted irrigated areas using multitemporal Sentinel-2 images obtained with the Google Earth Engine (GEE). To validate the results, 208 representative sample patches were selected, and the AEST-HRNet maps were compared against third-party ground reference data and statistics from the United States National Agricultural Statistics Survey (NASS). Quantitative assessment revealed an impressive F1-score of 0.956, an intersection over union (IoU) value of 0.867, and an overall accuracy (OA) value of 0.973 in Washington, outperforming publicly released maps. Comparative evaluations demonstrated that AEST-HRNet outperforms pixel-based classification using the random forest (RF) model and convolution-based semantic segmentation methods based on metrics such as F1-score, IoU, and Kappa. This study introduces a promising solution for precise irrigation mapping, offering increased accuracy and efficiency in producing reliable irrigation maps.

Background: Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human inflammation. Objectives: To examine the association between real-ambient bedroom LAN exposure with systemic inflammation and circadian rhythm of inflammatory markers. Methods: Using data from a prospective cohort study of Chinese young adults. At baseline, bedroom LAN exposure was measured with a portable illuminance meter; fasting blood sample for high-sensitivity C-reactive protein (hs-CRP) assay was collected. At 3-year follow-up, 20 healthy young adults (10 LANavg < 5 lx, 10 LANavg ≥ 5 lx) were recruited from the same cohort; time-series venous blood samples were sampled every 4 h over a 24 h-cycle for the detection of 8 inflammatory markers. Circadian rhythm of inflammatory markers was assessed using cosinor analysis. Results: At baseline, the average age of the 276 participants was 18.7 years, and 33.3 % were male. Higher levels of bedroom LAN exposure were significantly associated with increased hs-CRP levels. The association between bedroom LAN exposure and systemic inflammation was only significant in the inactive group (MVPA < 2 h/d) but not in the physically active group (MVPA ≥ 2 h/d). In addition, exposure to higher levels of nighttime light (LANavg ≥ 5 lx) disrupted circadian rhythms (including rhythmic expression, circadian amplitude and circadian phase) of some inflammatory cytokines and inflammatory balance indicators. Conclusion: Exposure to bedroom nighttime light increases systemic inflammation and disrupts circadian rhythm of inflammatory markers. Keep bedroom darkness at night may represent important strategies for the prevention of chronic inflammation. Additionally, for people living a community with higher nighttime light pollution, regular physical activity may be a viable option to counteract the negative impacts of LAN exposure on chronic inflammation.

BackgroundIt is unclear whether patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are allowed variable low levels of alcohol. This study aimed to evaluate the effect of mild-moderate alcohol consumption on the biochemical and histological characteristics of patients with MASLD.MethodsAlcohol consumption was assessed in 713 patients with steatotic liver disease (SLD) who underwent liver biopsy. Non-drinking, mild-moderate drinking, and excessive drinking were defined as 0 g/day, 1-20 g/day for women and 0 g/day, 1-30 g/day for men, respectively. Liver biopsies were scored according to the NASH CRN system.ResultsA total of 713 participants (median age 39.0 years and 77.1% male) with biopsy-proven SLD were enrolled, including 239 nondrinkers, 269 mild-moderate drinkers and 205 excessive drinkers. Excessive drinking was associated with increased risks for lobular inflammation and liver fibrosis compared to nondrinkers and mild-moderate drinkers. Compared with non-drinkers, mild-moderate drinkers had significantly lower odds for steatosis (OR = 0.60, 95% CI = 0.38–0.93, p = 0.025), hepatocellular ballooning (OR = 0.52, 95% CI = 0.29–0.91, p = 0.020) and fibrosis (OR = 0.50, 95% CI = 0.31–0.81, p = 0.005). However, in non-excessive drinkers with type 2 diabetes mellitus (T2DM), there was no association between mild-moderate alcohol consumption and liver fibrosis (OR = 0.562, 95% CI = 0.207–1.530, p = 0.257).ConclusionsMild-moderate alcohol consumption might be protective against liver fibrosis in MASLD patients, which is modified by the presence of T2DM. However, further longitudinal studies are needed to determine the effect of ongoing alcohol consumption on disease severity.

Abstract Objective To explore the influence of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation. Methods This retrospective observational cohort study included 196 patients, 75–102‐years‐old, with nonvalvular atrial fibrillation, hospitalized in our hospital. The nutritional status was assessed using Mini‐Nutritional Assessment—Short Form (MNA‐SF). Patients with MNA‐SF scores of 0–11 and 12–14 were included in the malnutrition and nonmalnutrition groups, respectively. Results The average age of the malnutrition group was higher than that of the nonmalnutrition group, and the levels of body mass index (BMI), hemoglobin (HGB), and albumin (ALB) were significantly lower than those of the nonmalnutrition group, with statistical significance (p

Depression is a prevalent psychiatric disorder with accumulating evidence implicating dysregulation of extracellular adenosine triphosphate (ATP) levels in the medial prefrontal cortex (mPFC). It remains unclear whether facilitating endogenous ATP production and subsequently increasing extracellular ATP level in the mPFC can exert a prophylactic effect against chronic social defeat stress (CSDS)-induced depressive-like behaviors and enhance stress resilience. Here, we found that nicotinamide mononucleotide (NMN) treatment effectively elevated nicotinamide adenine dinucleotide (NAD+) biosynthesis and extracellular ATP levels in the mPFC. Moreover, both the 2-week intraperitoneal (i.p.) injection and 3-week oral gavage of NMN prior to exposure to CSDS effectively prevented the development of depressive-like behavior in mice. These protective effects were accompanied with the preservation of both NAD+ biosynthesis and extracellular ATP level in the mPFC. Furthermore, catalyzing ATP hydrolysis by mPFC injection of the ATPase apyrase negated the prophylactic effects of NMN on CSDS-induced depressive-like behaviors. Prophylactic NMN treatment also prevented the reduction in GABAergic inhibition and the increase in excitability in mPFC neurons projecting to the lateral habenula (LHb). Collectively, these findings demonstrate that the prophylactic effects of NMN on depressive-like behaviors are mediated by preventing extracellular ATP loss in the mPFC, which highlights the potential of NMN supplementation as a novel approach for protecting and preventing stress-induced depression in susceptible individuals.

Abstract This study investigates the impact of macroprudential policies on ecological footprint (EF) in the top 11 largest countries. This study uses country-level panel data from these countries, covering the period from 1992 to 2020. Findings indicate that macroprudential policies alleviates ecological footprint in the sample. Macroprudential policies primarily reduce the ecological footprint before medium quantile (50%) while the environmental benefits of the policies end in the later quantiles. Moreover, environmental policy stringency (EPS) amplifies the positive influence of macroprudential policies on environmental sustainability. Estimate results stay the same with basic regression results in the post-global financial crisis (GFC) period while the impact is positive in the pre-GFC period. Finally, other robust tests validate the findings reported in basic regression model. This study suggests that governments should customize various types of macroprudential policies while also considering environmental concerns. The achievement of a sustainable environment can be facilitated by the combined effects of macroprudential policies and EPS.

Abstract Background Different metabolic compounds give pepper leaves and fruits their diverse colors. Anthocyanin accumulation is the main cause of the purple color of pepper leaves. The light environment is a critical factor affecting anthocyanin biosynthesis. It is essential that we understand how to use light to regulate anthocyanin biosynthesis in plants. Result Pepper leaves were significantly blue–purple only in continuous blue light or white light (with a blue light component) irradiation treatments, and the anthocyanin content of pepper leaves increased significantly after continuous blue light irradiation. This green-to-purple phenotype change in pepper leaves was due to the expression of different genes. We found that the anthocyanin synthesis precursor-related genes PAL and 4CL, as well as the structural genes F3H, DFR, ANS, BZ1, and F3’5’H in the anthocyanin synthesis pathway, had high expression under continuous blue light irradiation. Similarly, the expression of transcription factors MYB1R1-like, MYB48, MYB4-like isoform X1, bHLH143-like, and bHLH92-like isoform X3, and circadian rhythm-related genes LHY and COP1, were significantly increased after continuous blue light irradiation. A correlation network analysis revealed that these transcription factors and circadian rhythm-related genes were positively correlated with structural genes in the anthocyanin synthesis pathway. Metabolomic analysis showed that delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside were significantly higher under continuous blue light irradiation relative to other light treatments. We selected 12 genes involved in anthocyanin synthesis in pepper leaves for qRT-PCR analysis, and the accuracy of the RNA-seq results was confirmed. Conclusions In this study, we found that blue light and 24-hour irradiation together induced the expression of key genes and the accumulation of metabolites in the anthocyanin synthesis pathway, thus promoting anthocyanin biosynthesis in pepper leaves. These results provide a basis for future study of the mechanisms of light quality and photoperiod in anthocyanin synthesis and metabolism, and our study may serve as a valuable reference for screening light ratios that regulate anthocyanin biosynthesis in plants.

Abstract The advent of intelligent reflecting surface (IRS) technology has revolutionized the landscape of wireless communication systems, offering promising opportunities for enhancing the performance of Internet of Things (IoT) applications. This paper presents a comprehensive performance evaluation of multi-agent IoT monitoring systems leveraging IRS technology. We focus on three criteria for selecting IRS units and assess the impact on system performance. Specifically, we analyze the system performance by deriving an outage probability expression for each criterion. Our study begins by introducing the concept of IRS and its role in IoT monitoring. We then present three IRS unit selection criteria: optimal selection (OS), partial selection (PS), and random selection (RS). For each criterion, we mathematically model and analyze the system outage probability, shedding light on the reliability and connectivity of IoT devices. The outage probability expressions derived in this work offer valuable insights into the trade-offs associated with IRS unit selection criteria in the context of IoT monitoring. Additionally, our findings contribute to the optimization of multi-agent IoT monitoring systems, enabling improved communication performance and enhanced reliability.

Abstract Background Developmental and epileptic encephalopathy-50 (DEE-50) is a rare clinical condition believed to be caused by a mutation in the CAD gene and is associated with a bleak prognosis. CAD-related diseases have a wide range of clinical manifestations and other symptoms that may be easily overlooked. Like other rare diseases, the clinical manifestations and the treatment of DEE-50 necessitate further investigation. Case presentation A 1-year-old male patient presented with developmental delay, seizures, and anaemia at 3 months of age. He further developed refractory status epilepticus (SE), rapid deterioration of cognitive and motor function, and even became comatose at 5 months of age. Whole-exome sequencing of trios (WES-trios) revealed a compound heterozygous variant in the CAD gene, with one locus inherited from his father (c.1252C>T: p.Q418* nonsense mutation) and one from his mother (c.6628G>A: p.G2210S, missense mutation). This compound heterozygous CAD variant was unreported in the Human Gene Mutation Database. After uridine treatment, his cognitive faculties dramatically improved and he remained seizure-free. Forty two cases with CAD gene mutation reported in the literatures were reviewed. Among them, 90% had onset before 3 years of age, with average of 1.6±1.8 years old. The average age of diagnosis was 7.7 ± 10 years. The mortality rate was approximately 9.5%, with all reported deaths occurring in patients without uridine treatment. The clinical entity could be improved dramatically when the patient treated with uridine. Conclusions We present a boy with DEE 50 caused by novel CAD gene mutations and reviewed the clinical features of 42 patients reported previously. DEE 50 has early onset, refractory seizures, even status epilepticus leading to death, with favorable response to treatment with oral uridine. Early uridine treatment is recommended if CAD defect is suspected or genetically diagnosed. This study enhances the knowledge of DEE 50 and expands the spectrum of CAD gene mutations.

Abstract Soft carbon has been recognized as a promising anode material for potassium-ion batteries (PIBs), due to low cost, high conductivity and low voltage platform. However, their practical application is hampered by slow storage kinetics and unsatisfactory cycle life. In this work, pitch-derived needle coke, a typical soft carbon, was incorporated with oxygenated functional groups through liquid phase oxidation by using H2O2 oxidant. When used as anode materials for PIBs, the oxidized needle coke delivers a high reversible capacity of 322.7 mAh g−1, significantly superior to that of the needle coke (237.9 mAh g−1). The enhanced electrochemical performance can be attributed to the abundant oxygenated functional groups and resultant defects on the surface of oxidized needle coke, which not only serve as extra active sites for potassium storage, but also provide sufficient pathways for K+ migration across the adjacent carbon layers. Moreover, the expanded interlayer spacing derived from H2O2 oxidation facilitates rapid K+ intercalation and deintercalation. This work offers an effective modification strategy for the fabrication of high-performance pitch-based soft carbon anodes for PIBs. Graphical Abstract

Magnetic materials with non-collinear spin orderings provide an outstanding platform to probe spintronic phenomena owing to their strong spin-orbit coupling (SOC) and unique Berry phase. It is thus important to obtain a non-collinear antiferromagnetic (AFM) phase at room temperature (RT). Significantly, the discovery of novel materials with nearly zero thermal expansion (ZTE) property near RT is required and pursued for avoiding thermal stress and fracture in spintronic devices. Herein, the doping of Sn (Ge) at the Ag site in the triangular lattice Mn3Ag1−xSn(Ge)xN compounds increases effectively the Néel point and makes the interesting non-collinear Γ5g AFM phase exist above RT. The magnetic phase diagrams with Γ5g phase up to 498 K were built by the combined analysis of neutron powder diffraction (NPD), magnetic measurements, electronic transport, and differential scanning calorimetry (DSC). The thermal expansion behaviors of Mn3Ag1−xSn(Ge)xN were modulated, and the nearly ZTE above RT was achieved in Mn3Ag0.5Ge0.5N within Γ5g AFM ordering. Our findings offer an effective way to tailor the non-collinear AFM ordering and correlated thermal expansion behavior for potential use in the emerging field of thermal stress-free magnetic chip materials.

The matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) diagnostic tool was used to rapidly detect and identify three foodborne pathogens, Salmonella, Staphylococcus aureus and Bacillus cereus in ready-to-eat bulk foods in this study. The best method was identified by optimizing and screening various experimental conditions such as spot sampling method, pre-treatment method, different media and culture time, and its detection limit and stability were evaluated. Meanwhile, the established method was compared with multiplex PCR and the other biochemical identification methods such as VITEK 2 to contrast the consistency of the three identification results. Finally, batch food sample testing was carried out to explore the applicability of using MALDI-TOF MS to test ready-to-eat bulk foods. Results indicated that all the identification scores of the three bacteria were higher than 95% for the same batch and different passages, with a coefficient of variation of less than 2%. It demonstrated that the established method had good repeatability and stability, and the detection limit was 105 CFU/mL. The results of strain identification by MALDI-TOF MS were highly consistent with those of multiplex PCR and biochemical identification methods. Moreover, the MALDI-TOF MS method was more specific and efficient. Regarding spot sampling, the three covering methods showed higher average identification scores than the sandwich and mixed methods, all of which scored 99.9%. The 1 μL+1 μL covering method spot sampling approach obtained higher average peak numbers, and more complex and stronger characteristic peaks. Regarding pre-treatment, the formic-acid-acetonitrile method obtained a higher peak volume and peak intensity than other bacterial treatment methods, with an average identification score of 98% or higher. At the same time, the matching degree with the database spectrum was higher. In summary, MALDI-TOF MS method was not only sensitive, specific, accurate and rapid in foodborn pathogen identification, but also had simple operation and intuitive in results. As a powerful supplement to the national standard method, it provided a viable alternative for analysing, identifying and typing foodborne pathogens.

Red phosphorus has been well-recognized as promising anode materials for lithium-ion batteries (LIBs) and potassium-ion batteries (PIBs) due to its extremely high theoretical capacity and low cost. However, the huge volume change and poor electric conductivity severely limit its further practical application. Herein, the nanoscale ultrafine red phosphorus has been successfully confined in a three-dimensional pitch-based porous carbon skeleton composed of well-interconnected carbon nanosheets through the vaporization-condensation method. Except for the traditional requirement of high electric conductivity and stable mechanical stability, the micropores and small mesopores in the porous carbon matrix centered at 1 to 3 nm and the abundant amount of oxygen-containing functional groups are also beneficial for the high loading and dispersion of red phosphorus. As anode for LIBs, the composite exhibits high reversible discharge capacities of 968 mAh g−1, excellent rate capabilities of 593 mAh g−1 at 2 A g−1, and long cycle performance of 557 mAh g−1 at 2 A g−1. More impressively, as the anode for PIBs, the composite presents a high reversible capacity of 661 mAh g−1 and a stable capacity of 312 mAh g−1 at 0.5 A g−1 for 500 cycles with a capacity retention up to 84.3%. This work not only sheds light on the structure design of carbon hosts with specific pore structure but also open an avenue for high value-added utilization of coal tar pitch.

Abstract Bacteriophage therapy is one potential strategy to treat antimicrobial resistant or persistent bacterial infections, and the year 2021 marked the centennial of Felix d’Hérelle’s first publication on the clinical applications of phages. At the Center for Phage Biology & Therapy at Yale University, a preparatory modular approach has been established to offer safe and potent phages for single-patient investigational new drug applications while recognizing the time constraints imposed by infection(s). This study provides a practical walkthrough of the pipeline with an Autographiviridae phage targeting Pseudomonas aeruginosa (phage vB_PaeA_SB, abbreviated to ΦSB). Notably, a thorough phage characterization and the evolutionary selection pressure exerted on bacteria by phages, analogous to antibiotics, are incorporated into the pipeline.

Abstract In the field of world heritage conservation, there has been broad consensus on carrying out heritage conservation research on the basis of spatial integration and interregional and international cooperation. However, there are still many deficiencies in the integration of culture with the environment, regional economic and social development, and the regional, holistic and multimodal conservation and utilization of cultural heritage sites. In China, the Dongjiang-Hanjiang River Basin is a representative area of substantial cultural and ecological value for both Guangdong Province and the whole country. This paper uses the morphological spatial pattern analysis and the minimum cumulative resistance model to integrate cultural ecology sources and establish a cross-regional and large-scale cultural ecology network system that includes 1 main corridor, 22 important corridors and 17 secondary corridors. In addition, based on identified cultural landscape nodes and cultural ecology services, the economy of the cultural ecology corridor could be developed with large-scale co-construction, co-governance and shared working mechanisms to overcome administrative limits and realize the conservation and utilization of multimodal and large-scale heritage sites. This approach has strong theoretical and practical significance for innovative methods in cultural ecology research, as well as for new content in the research of Lingnan culture, ecosystem restoration, and the economic and social development of towns and villages. This article supplements unilateral studies of regional culture and ecology and demonstrates an in-depth application of cultural ecology theory.

Abstract This paper investigates the integration of relay-assisted Internet of Things (IoT) systems, focusing on the use of multiple relays to enhance the system performance. The central metric of interest in this study is system outage probability, evaluated in terms of latency. Our research provides a comprehensive analysis of system outage probability, considering different relay selection criteria to optimize the system’s transmission performance. Three relay selection strategies are employed to enhance the system transmission performance. Specifically, the first strategy, optimal relay selection, aims to identify the relay that minimizes the latency and maximizes the data transmission reliability. The second approach, partial relay selection, focuses on selecting a subset of relays strategically to balance the system resources and achieve the latency reduction. The third strategy, random relay selection, explores the potential of opportunistic relay selection without prior knowledge. Through a rigorous investigation, our paper evaluates the impact of these relay selection criteria on the performance of relay-assisted edge computing systems. By assessing the system outage probability in relation to latency, we provide valuable insights into the trade-offs and advantages associated with each selection strategy. Our findings contribute to the design and optimization of reliable and efficient edge computing systems, with implications for various applications, including the IoT and intelligent data processing.

In the last few decades, the particle swarm optimization (PSO) algorithm has been demonstrated to be an effective approach for solving real-world optimization problems. To improve the effectiveness of the PSO algorithm in finding the global best solution for constrained optimization problems, we proposed an improved composite particle swarm optimization algorithm (ICPSO). Based on the optimization principles of the PSO algorithm, in the ICPSO algorithm, we constructed an evolutionary update mechanism for the personal best position population. This mechanism incorporated composite concepts, specifically the integration of the $ \varepsilon $-constraint, differential evolution (DE) strategy, and feasibility rule. This approach could effectively balance the objective function and constraints, and could improve the ability of local exploitation and global exploration. Experiments on the CEC2006 and CEC2017 benchmark functions and real-world constraint optimization problems from the CEC2020 dataset showed that the ICPSO algorithm could effectively solve complex constrained optimization problems.

This paper studies the time-dependent cold chain logistics vehicle routing problem considering both traffic congestion and carbon emissions. A cold chain logistics model with time-dependent green vehicle paths with time windows (TDGVRPTW) was developed to fulfil the demands of green logistics and to take comprehensive account of consideration should be given to factors such as road congestion and carbon emissions. The objective of the model is to minimise total costs, which include carbon emission costs, penalty costs, fuel consumption costs, fixed costs, damage costs and refrigeration costs. Two-phase hybrid search algorithm was developed to solve this model. During the initial stage of the algorithm, a dual-population ant colony optimization (DACO) algorithm sharing the optimal individual is employed to optimize the distribution route of the vehicle. During the second phase, an adaptive golden section search (AGSS) algorithm is used to optimise the departure time of the vehicle from the distribution centre to avoid traffic congestion time periods. To validate the effectiveness of the suggested two-phase hybrid search algorithm, it is applied to the improved Solomon benchmark test set. The experimental findings demonstrate that the two-phase hybrid search algorithm can reasonably plan the driving routes and departure times for each vehicle, effectively avoiding peak traffic congestion periods in the city, and reducing the overall delivery cost.