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The planning of public charging stations is crucial for the growth of electric vehicles (EVs). To improve the accuracy of predicting EV charging demand in urban areas, we propose a charging decision-making model based on fuzzy logic. Meanwhile, the influence of private charging piles is considered to further enhance the accuracy of predicting public charging demand. To address the issue of optimization algorithms easily getting stuck in local optima due to the vast quantity of variables involved in the location and capacity planning process, this paper introduces a two-layer planning method. In specific, the upper-level location model optimizes the locations of charging stations, while the lower-layer capacity model determines the number of charging piles within each station, leading to a reduction in the number of variables for each layer. Moreover, through iterative exchange results between the upper-layer location model and lower-layer capacity model, the optimal solution can be attained. The simulation results demonstrate that the proposed method can simultaneously consider the perspectives of both EV drivers and charging station investors, while also enhancing the utilization rates of public charging piles.

Shrimp are non-negligible victims of cadmium (Cd) contamination, and there is still a lack of strategies for mitigating Cd toxicity in shrimp. Bacillus cereus, with its significant heavy metal (HM) tolerance and chelating effects, is a representative beneficial bacterium to be investigated for mitigating the toxicity of Cd exposure. This study revealed the effects and potential mechanisms of B. cereus in mitigating chronic Cd toxicity in shrimp by analyzing growth performance, hepatopancreatic Cd accumulation, pathology, as well as comprehensive hepatopancreatic transcriptomics and metabolomics in Litopenaeus vannamei. The results showed that shrimp's growth inhibition, hepatopancreatic Cd accumulation and physiological structure damage in B. cereus+chronic Cd group were effectively alleviated compared with the chronic Cd treatment group. The pathways related to amino acid metabolism, glycolipid metabolism, immune response, and antioxidant stress were significantly activated in the B. cereus+chronic Cd group, including glycolysis, pentose phosphate pathway, oxidative phosphorylation, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids pathways. The key differentially expressed genes (e.g., macrophage migration inhibitory factor, glycine cleavage system H protein, glycine dehydrogenase, phosphoglucomutase-2, asparaginase, ATP synthase subunit, cytochrome c, and 4-hydroxyphenylpyruvate dioxygenase) and metabolites (e.g., L-leucine, D-ribose, gluconic acid, 6-Phosphogluconic acid, sedoheptulose 7-phosphate, 1-Kestose, glyceric acid, arachidic acid, prostaglandins, 12-Keto-tetrahydro-leukotriene B4, and gamma-glutamylcysteine) associated with the above pathways were significantly altered. This study demonstrated that B. cereus is an effective mitigator for the treatment of chronic Cd poisoning in shrimp. B. cereus may play a role in alleviating the toxicity of Cd by enhancing the antioxidant performance, immune defense ability, metabolic stability, and energy demand regulation of shrimp. The study provides reference materials for the study of B. cereus in alleviating Cd toxicity of shrimp and broadens the application of probiotics in treating HM toxicity.

Tracheobronchomegaly (TBM) is a rare condition characterized by the dilatation of the trachea and bronchi due to severe atrophy of elastic fibers, accompanied by the thinning of the muscularis mucosae and the development of diverticula between cartilaginous rings. The etiology of this condition remains unclear. Tracheobronchopathia osteochondroplastica (TO) is another uncommon airway disease with an unknown etiology. The co-occurrence of these two diseases has not been reported. In this study, we report and discuss a case involving an elderly man with TBM and TO with a history of recurrent pneumonia over the past 6 years.

Background: Family-oriented mobility has become increasingly prevalent in recent years, leading to the emergence of a new demographic: older migrants. These individuals, who are often accompanied by their family members, relocate to another place of residence while retaining their household registration in their original location. The existing literature has largely neglected the social perspective on the mental health of this population group. Methods: This study recruited participants from five communities in two cities and employed the Geriatric Social Network Scale, the Self-Rating Anxiety Scale, and the Geriatric Depression Scale to assess their mental health and social networks. Results: Among the 317 qualified participants, 31.23 % reported experiencing anxiety and 15.77 % reported experiencing depression. The mean social network score was 3.83 ± 0.54 points. A negative correlation was observed between social network scores and both anxiety (r = −0.272, P < 0.001) and depression (r = −0.338, P < 0.001). Two distinct types of social networks were identified through latent profile analysis, with a low level of social support and a low-level social network being significantly correlated with depression (P < 0.001). Conclusions: Mental health issues are prevalent among family-oriented older migrants. A medium-level social network was found to be negatively correlated with anxiety and depression. The presence of a low-level social network was found to be associated with depression. It is imperative to prioritize the mental health status of family-oriented older migrants. Collaboration between community nurses and social workers should be encouraged to aid in exploring more effective ways of promoting the mental health status and social networks of this population.

Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the “Fruits-Vegetables-Dairy” pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the “Puffed food-Bakery-Candy” pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the “Grains-Tubers-Legumes”. Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.

Objectives: The recent surge of Mpox outbreaks in multiple countries has garnered global attention. As of July 12, 2023, there have been 88,288 reported cases of Mpox worldwide. Although genetic variation was not found to be the cause of the epidemic outbreak, the reasons for its rapid spread remain unclear. Methods: Using the niche method, this study identified high-risk regions for Mpox and determined that human factors are the primary contributors to global risks. To further investigate, a travel network resistance surface was created based on various modes of transportation and was combined with sea, airline, highway, and railway routes to construct the least cost path for human travel networks in different risk areas. Results: The results indicated that high-risk regions for Mpox are mainly concentrated in Europe and the United States, with large risk ranges and high-risk values. The least cost path revealed three primary transmission paths rely on developed transportation networks, including internal transmission in North America, Europe-Africa, and Europe-Asia-Africa. These findings suggest that human activities, facilitated by developed travel networks, remain the main contributing factor to the spread. Conclusions: In summary, based on the Mpox epidemic report, this study conducted risk prediction and driving factor analysis on Mpox. The research results indicate that human use of transportation for long-distance activities is a key factor leading to the rapid spread of the virus. Subsequently, we focused on studying the global transmission pathways of Mpox and revealed several transmission pathways with high global population migration rates by constructing the LCPs between different high-risk areas. This study also emphasizes the importance of applying early monitoring data of Mpox to model risk prediction in controlling emerging infectious diseases, providing a new perspective for controlling Mpox and similar diseases.

Abstract Diabetic individuals with diabetic cardiomyopathy (DbCM) present with abnormal myocardial structure and function. DbCM cannot be accurately diagnosed due to the lack of suitable diagnostic biomarkers. In this study, 171 eligible participants were divided into a healthy control (HC), type 2 diabetes mellitus (T2DM) patients without DbCM (T2DM), or DbCM group. Serum fibrinogen-like protein 1 (FGL-1) and other biochemical parameters were determined for all participants. Serum FGL-1 levels were significantly higher in patients with DbCM compared with those in the T2DM group and HCs. Serum FGL-1 levels were negatively correlated with left ventricular fractional shortening and left ventricular ejection fraction (LVEF) and positively correlated with left ventricular mass index in patients with DbCM after adjusting for age, sex and body mass index. Interaction of serum FGL-1 and triglyceride levels on LVEF was noted in patients with DbCM. A composite marker including serum FGL-1 and triglycerides could differentiate patients with DbCM from those with T2DM and HCs with an area under the curve of 0.773 and 0.789, respectively. Composite marker levels were negatively correlated with N-terminal B-type natriuretic peptide levels in patients with DbCM. Circulating FGL-1 may therefore be a valuable index reflecting cardiac functions in DbCM and to diagnose DbCM.

Abstract Aims This study assessed diabetes (type 1 and type 2) mortality in China and globally from 1990 to 2019, predicting the next decade's trends. Materials and Methods Data came from the Global Burden of Disease (GBD) database. The annual percentage change (AAPC) in age‐standardized mortality rates (ASMR) for diabetes (type 1 and type 2) during 1990–2019 was calculated. A Bayesian age‐period‐cohort (BAPC) model predicted diabetes (type 1 and type 2) mortality from 2020 to 2030. Results In China, type 1 diabetes deaths declined from 6,005 to 4,504 cases (AAPC −2.827), while type 2 diabetes deaths rose from 64,084 to 168,388 cases (AAPC −0.763) from 1990 to 2019. Globally, type 1 diabetes deaths increased from 55,417 to 78,236 cases (AAPC 0.223), and type 2 diabetes deaths increased from 606,407 to 1,472,934 cases (AAPC 0.365). Both China and global trends showed declining type 1 diabetes ASMR. However, female type 2 diabetes ASMR in China initially increased and then decreased, while males had a rebound trend. Peak type 1 diabetes deaths were in the 40–44 age group, and type 2 diabetes peaked in those over 70. BAPC predicted declining diabetes (type 1 and type 2) mortality burden in China and globally over the next 10 years. Conclusions Type 2 diabetes mortality remained high in China and globally despite decreasing type 1 diabetes mortality over 30 years. Predictions suggest a gradual decrease in diabetes mortality over the next decade, highlighting the need for continued focus on type 2 diabetes prevention and treatment.

Chilled meat is favored by consumers because of its fresh, low price and high nutritive value. However, it is susceptible for microbial contamination in slaughtering, processing, marketing and other links, as well as the change of its color, odor and other qualities, which results in short shelf life, even losing its edible value and other problems of chilled meat, restricting the further development of the fresh meat industry. Therefore, the preservative preservation technology is particularly important in China's meat food, and it has a wide range of application prospects in the development of meat food industry. This paper describes the main reasons for the corruption and deterioration of chilled meat, including microbial contamination, lipid oxidation and discoloration of myoglobin. Besides, it elaborates on chemical preservation technologies such as organic acids, microbial metabolites and physical preservation technologies such as packaging technology, irradiation technology, etc., and their anticorrosion mechanisms. In addition to enumerating the status quo of its application in the preservation of meat, analyzing the advantages of preservation technology and its limitations in the development, and making future research proposals for the development of meat food. In addition, it lists the current status of its application in meat preservation, analyzes the advantages of the preservation technology and its limitations in application, and makes prospects for future preservation technologies, with a view to providing a certain theoretical basis for the further in-depth research on the preservation technology for the preservation of the preservation of cold meat as well as the preservation of fresh meat.

Abstract The clinical effects of Schisandra chinensis against human disease are well-documented; however, studies on its application in controlling plant pathogens are limited. Here, we investigated its inhibitory effect on the growth of Alternaria alternata, a fungus which causes significant post-harvest losses on apples, known as black spot disease. S. chinensis fruit extract exhibited strong inhibitory effects on the growth of A. alternata with an EC50 of 1882.00 mg/L. There were 157 compounds identified in the extract by high performance liquid chromatography-mass spectrometry, where benzocaine constituted 14.19% of the extract. Antifungal experiments showed that the inhibitory activity of benzocaine on A. alternata was 43.77-fold higher than the crude extract. The application of benzocaine before and after A. alternata inoculation on apples prevented the pathogen infection and led to mycelial distortion according to scanning electron microscopy. Transcriptome analysis revealed that there were 4226 genes differentially expressed between treated and untreated A. alternata-infected apples with benzocaine. Metabolomics analysis led to the identification of 155 metabolites. Correlation analysis between the transcriptome and metabolome revealed that benzocaine may inhibit A. alternata growth via the beta-alanine metabolic pathway. Overall, S. chinensis extract and benzocaine are environmentally friendly plant-based fungicides with potential to control A. alternata.

Abstract. Background:. Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA. Methods:. The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4+) T-cell counts, CD8+ T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results:. The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6–6.5 copies/reaction) with linearity over a 5-log10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8–16.6 copies/reaction) with linearity over a 3-log10-unit range. Total HIV DNA in CD4+ T cells was positively associated with integrated HIV DNA (r = 0.76, P

Abstract Immune microenvironment and immunotherapy have become the focus and frontier of tumor research, and the immune checkpoint inhibitors has provided novel strategies for tumor treatment. Malignant pleural effusion (MPE) is a common end-stage manifestation of lung cancer, malignant pleural mesothelioma and other thoracic malignancies, which is invasive and often accompanied by poor prognosis, affecting the quality of life of affected patients. Currently, clinical therapy for MPE is limited to pleural puncture, pleural fixation, catheter drainage, and other palliative therapies. Immunization is a new direction for rehabilitation and treatment of MPE. The effusion caused by cancer cells establishes its own immune microenvironment during its formation. Immune cells, cytokines, signal pathways of microenvironment affect the MPE progress and prognosis of patients. The interaction between them have been proved. The relevant studies were obtained through a systematic search of PubMed database according to keywords search method. Then through screening and sorting and reading full-text, 300 literatures were screened out. Exclude irrelevant and poor quality articles, 238 literatures were cited in the references. In this study, the mechanism of immune microenvironment affecting malignant pleural effusion was discussed from the perspectives of adaptive immune cells, innate immune cells, cytokines and molecular targets. Meanwhile, this study focused on the clinical value of microenvironmental components in the immunotherapy and prognosis of malignant pleural effusion.

Objective The aim of this study was to conduct a comprehensive evaluation of the rehydration efficacy of QSBYD and elucidate its potential underlying mechanism.Design 38 participants were randomly assigned to receive either QSBYD or placebo before and after exercise and heat-induced dehydration. Hydration indicators were measured over time. Blood tests assessed cellular anaerobic respiration metabolites, serum inflammatory markers, and coagulation markers. Perceptual measures of thirst, fatigue, and muscular soreness were also taken.Results QSBYD consumption resulted in lower urine volume (Control vs. QSBYD: 260.83 ± 167.99 ml vs. 187.78 ± 141.34 ml) and smaller decrease in percentage of nude body weight change from baseline (Control vs. QSBYD: −0.52 ± 0.89% vs. −0.07 ± 0.52%). Although no significant differences in urine specific gravity, QSBYD resulted in reduced urine volume at 120 min, suggesting improved fluid retention. Furthermore, QSBYD resulted in lower levels of IL-1β (Control vs. QSBYD: 2.40 ± 0.68 vs. 1.33 ± 0.66 pg/mL), suggesting QSBYD may provide benefits beyond hydration.Conclusion Further investigation into the underlying mechanisms and long-term effects of QSBYD on hydration is warranted. QSBYD may be an effective alternative to commercial sports drinks in mitigating dehydration effects.

ObjectiveThis study aims to analyze the value of prenatal ultrasound in the screening, diagnosis, and treatment of double aortic arch (DAA) malformations.MethodsA retrospective analysis was conducted on 31 fetal cases with double aortic arch anomalies over a 12-year period from June 1, 2011 to June 1, 2023. The assessment included combined measurements of fetal tracheal internal diameter Z-score and DAA pinch angle, along with ultrasonographic findings, associated anomalies, genetic abnormalities, postnatal CTA images, and long-term postnatal outcomes.ResultsOf the 31 fetal double aortic arch cases, 15 were right aortic arch dominant, 2 were left aortic arch dominant, and 14 had a balanced double arch. Genetic testing was performed on 19 cases, revealing abnormalities in 2 cases, including one Turner syndrome, and one carrier of ichthyosis gene with heterozygous deletion. Out of the total cases, 29 were delivered, and 2 cases were terminated. Prenatal diagnosis accurately identified 29 cases (29/31, 93.5%), which was confirmed by postnatal pathological anatomy, echocardiography, surgery or CTA. Fetal tracheal internal diameter Z-scores were significantly smaller in the symptomatic group than in the asymptomatic group (−1.27 ± 0.49 vs −0.68 ± 0.60, P = 0.018). The area under the curve was 0.776 (95% confidence interval, 0.593–0.960) using a tracheal internal diameter z-score cutoff of −0.73 with a sensitivity of 90% and specificity of 64.7%. The double arch pinch angle was significantly smaller in the symptomatic group than in the asymptomatic group [52.50° (38.25° to 59.00°) vs 60.00° (53.50° to 70.50°), P = 0.035]. The area under the curve was 0.744 (95% confidence interval, 0.554–0.935), and the sensitivity for determining the presence or absence of symptoms was 90% when the cutoff value was 62.5°, with a specificity of 47.1%. Fifteen cases opted for surgery with favorable surgical outcome.ConclusionPrenatal echocardiography demonstrates good diagnostic efficacy for fetal double aortic arch. It is also essential to detect the presence of other underlying intra- and extracardiac malformations and genetic abnormalities. There is a significant difference in prenatal tracheal internal diameter Z-scores and double arch pinch angle between asymptomatic and symptomatic DAA infants. Symptomatic infants require early surgery, while asymptomatic infants should be monitored.

Abstract Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell‐based vaccination is limited by interference from immunosuppressive senescence‐associated secretory phenotype and pro‐tumorigenic capacity of senescent cells. Here, a senescent cancer cell‐based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane‐coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death‐induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma‐challenged mice with fewer side effects when combined with αPD‐1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell‐based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy.

Background: Various factors play crucial roles in aneurysm development and prognosis. Macrophages have recently emerged as a major research focus. Despite the numerous studies on the role and function of macrophages in aneurysm pathogenesis, no bibliometric analyses have focused on this topic. Objective: This study aimed to analyze articles related to macrophages and aneurysms to reveal trends, hotspots, and new frontiers in macrophage-related aneurysm research. Methods: We retrieved and incorporated 1211 articles from the Science Citation Index Expanded database of the Web of Science Core Collection between 1999 and 2022. The data were analyzed and visualized using CiteSpace and VOSviewer, and Microsoft Excel 2019 was used to plot the data. Results: The most influential articles were published between 1999 and 2022, with a total citation count of 43870. This study encompassed a comprehensive analysis of 74 research directions. The year with the highest number of publications was 2021 when 109 articles were published. 'ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY' journal has made significant contributions by publishing the highest number of articles (99 articles), while funding support primarily came from the National Institutes of Health and United States Department of Health and Human Services. The United States exerted a substantial influence within this field, with a total publication count of 453 publications and the highest centrality value (0.63). Recent studies have focused on understanding the developmental processes underlying aneurysms and devising preventive measures to effectively impede disease progression. Conclusions: Our analysis demonstrates the rapid growth in research exploring the relationship between macrophages and aneurysms over the past two decades. Continued exploration and collaboration among different specialties and manufacturers will facilitate innovative approaches for effective management strategies that target patients with diverse forms of aneurysms.

Thermal barrier coatings (TBCs) applications of yttria-stabilized (YSZ) are widely utilized on turbine blades of aviation engines due to its low thermal conductivity and high electrical conductivity. Predicting the infrared emissivity aids in monitoring blade operating temperatures, ensuring safe engine operation. This paper innovatively introduces a novel three-dimensional columnar EB-PVD coating model and utilizes the FDTD method to predict emissivity. The model exhibits strong consistency with experimental results for predicted emissivity in the short-wave infrared band (1.4–3 μm). The unique microstructure of the EB-PVD thermal barrier coatings significantly influence the infrared emissivity. The results indicate that vertically uniform arranged feathers exhibit higher emissivity levels compared to feathers with varying densities. Additionally, increasing the thickness of the ceramic top coating and reducing spherical closed porosity also enhance the emissivity levels. This research provides guidance for controlling emissivity at the microscale in the preparation of thermal barrier coatings.

Chemoresistance is a main cause of chemotherapy failure and tumor recurrence. The effects of global protein SUMOylation on chemoresistance in colorectal cancer (CRC) remains to be investigated. Herein, we have proposed that the elevated SUMO2/3-modified proteins confer 5-fluorouracil (5-FU) chemoresistance acquisition in CRC. The SUMOylation levels of global proteins in CRC cell lines were elevated compared with normal colon cell line NCM460. 5-FU treatment obviously reduced SUMOylation of global proteins in 5-FU-sensitive CRC cells including HT29, HCT116 and HCT-8. However, in 5-FU-resistant HCT-8/5-FU cells, the expression level of SUMO2/3-modified proteins was increased under 5-FU exposure in a concentration-dependent manner. 5-FU treatment combined with SUMOylation inhibitor ML-792 significantly increased the sensitivity of 5-FU-resistant cells to 5-FU and reduced colony formation numbers in HCT-8/5-FU cells. And UBC9-mediated SUMOylation elevation contributes to 5-FU resistance in HCT116 cells. Moreover, we also identified RREB1 as a regulator of SUMOylation profiling of global cellular proteins via directly binding to the promoter of UBC9. Overexpression of RREB1 promoted 5-FU resistance in CRC, which was partially abolished by treatment of inhibitor ML-792. In conclusion, RREB1-enhanced protein SUMOylation contributes to 5-FU resistance acquisition in CRC.

Adaptive gradient algorithms have been successfully used in deep learning. Previous work reveals that adaptive gradient algorithms mainly borrow the moving average idea of heavy ball acceleration to estimate the first- and second-order moments of the gradient for accelerating convergence. However, Nesterov acceleration which uses the gradient at extrapolation point can achieve a faster convergence speed than heavy ball acceleration in theory. In this article, a new optimization algorithm which combines adaptive gradient algorithm with Nesterov acceleration by using a look-ahead scheme, called NALA, is proposed for deep learning. NALA iteratively updates two sets of weights, i.e., the ‘fast weights’ in its inner loop and the ‘slow weights’ in its outer loop. Concretely, NALA first updates the fast weights k times using Adam optimizer in the inner loop, and then updates the slow weights once in the direction of Nesterov’s Accelerated Gradient (NAG) in the outer loop. We compare NALA with several popular optimization algorithms on a range of image classification tasks on public datasets. The experimental results show that NALA can achieve faster convergence and higher accuracy than other popular optimization algorithms.

This study aims to examine the effects of various aluminum alloy constitutive models on the behavior of concrete-filled aluminum tubular stub columns under axial compression. The bi-linear model with hardening, the Baehre model, and the Ramberg-Osgood (R-O) model, which follow the European standard (EC9) were analyzed and compared in terms of their ability to describe the stress-strain behavior of aluminum alloy tensile coupons over the full range, and their respective application scenarios were discussed. A total of 74 sets of experimental data results were collected to examine the effects of these three models on the ultimate load of concrete-filled aluminum tubular stub columns. Furthermore, a full-scale model was constructed to analyze the effect of the hardening exponent n in the R-O model on the load-displacement curves. The results show that, apart from the bi-linear model with hardening, the other two aluminum alloy constitutive models are capable of accurately predicting the stress-strain behavior of aluminum alloys throughout the full range. The accuracy of the R-O model is significantly influenced by the calculation methods of n. The Baehre model is found to be more suitable for non-heat-treated aluminum alloys. The simulated ultimate load values obtained from the three constitutive models fall within a deviation range of ±10%, indicating their suitability for practical engineering applications. Among the three models, the R-O model exhibits the highest stability, as changes in the hardening exponent n do not affect the ultimate load but have a significant effect on the load-displacement curves beyond the ultimate load.

Clostridioides difficile is an emerging pathogen of One Health significance. Its highly variable genome contains mobile genetic elements (MGEs) such as transposons and prophages that influence its biology. Systematic deletion of each genetic element is required to determine their precise role in C. difficile biology and contribution to the wider mobilome. Here, Tn5397 (21 kb) and ϕ027 (56 kb) were deleted from C. difficile 630 and R20291, respectively, using allele replacement facilitated by CRISPR-Cas9. The 630 Tn5397 deletant transferred PaLoc at the same frequency (1 × 10−7) as 630 harboring Tn5397, indicating that Tn5397 alone did not mediate conjugative transfer of PaLoc. The R20291 ϕ027 deletant was sensitive to ϕ027 infection, and contained two unexpected features, a 2.7 kb remnant of the mutagenesis plasmid, and a putative catalase gene adjacent to the deleted prophage was also deleted. Growth kinetics of R20291 ϕ027 deletant was similar to wild type (WT) in rich medium but marginally reduced compared with WT in minimal medium. This work indicates the commonly used pMTL8000 plasmid series works well for CRISPR-Cas9-mediated gene deletion, resulting in the largest deleted locus (56.8 kb) described in C. difficile. Removal of MGEs was achieved by targeting conjugative/integrative regions to promote excision and permanent loss. The deletants created will be useful strains for investigating Tn5397 or ϕ027 prophage contribution to host virulence, fitness, and physiology, and a platform for other mutagenesis studies aimed at functional gene analysis without native transposon or phage interference in C. difficile 630 and R20291.

BackgroundPrevious observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM.MethodsTo investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO.ResultsThe results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41–0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings.ConclusionThis study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

Small interference RNA (siRNA) is a class of short double-stranded RNA molecules that cause mRNA degradation through an RNA interference mechanism and is a promising therapeutic modality. RBD1016 is a siRNA drug in clinical development for the treatment of chronic Hepatitis B Virus (HBV) infection, which contains a conjugated with N-acetylglucosamine moiety that can facilitate its hepatic delivery. We aimed to construct a semi-mechanistic model of RBD1016 in pre-clinical animals, to elucidate the pharmacokinetic/pharmacodynamic (PK/PD) profiles in mice and PK profiles in monkeys, which can lay the foundation for potential future translation of RBD1016 PK and PD from the pre-clinical stage to the clinic stage. The proposed semi-mechanistic PK/PD model fitted PK and PD data in HBV transgenic mice well and described plasma and liver concentrations in the monkeys well. The simulation results showed that our model has a reasonable predictive ability for Hepatitis B surface antigen (HBsAg) levels after multiple dosing in mice. Further PK and PD data for RBD1016, including clinical data, will assist in refining the model presented here. Our current effort focused on model building for RBD1016, we anticipate that the model could apply to other GalNAc-siRNA drugs.

Abstract To explore the optimal cut-off values of Klotho for predicting all-cause and cardiovascular mortality among chronic kidney disease (CKD) patients. Klotho was measured in 40–79-year-old individuals in the NHANES 2007–2016. A total of 2418 patients with stage 1–4 CKD were included. The optimal cut-off values of Klotho were utilized using receiver operator characteristic (ROC) curves and be verified on the effects of all-cause and cardiovascular mortality. Restricted cubic splines were used to examine the relationship between Klotho and all-cause and cardiovascular mortality with the optimal cutpoints as the reference. After a mean follow-up period of 87.9 months, 535 deaths occurred and 188 died of cardiovascular disease. Cubic splines showed that the risk of all-cause and cardiovascular mortality increased gradually for Klotho

Abstract Objectives To investigate the rate of adverse events (AEs) caused by intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications retrospectively and to explore practical measures for prevention and treatment of them. Materials and methods This study enrolled 83,778 contrast-enhanced ultrasound (CEUS) examinations using sulfur hexafluoride microbubbles intravenously performed during 11 years. Age, gender, and target organs of all CEUS patients were recorded. For cases of AEs, their medical history and laboratory results were also collected. The process of AEs was assessed and categorized. Besides, the management of AEs were recorded. Results Twenty patients had sulfur hexafluoride microbubbles-related AEs. The AE rate was 0.024%. No significant difference was observed between patients with AEs and the whole group for age and sex distribution. All AEs happened in liver examinations. Among them, 7 (35%) were mild, 8 (40%) were moderate, and 5 (25%) were severe. They were categorized into 15 allergic-like reactions and 5 physiologic reactions. The manifestations of mild and moderate AEs mainly include urticaria, chills, and mild hypoxia, which could be eased by simple management. Severe cases had anaphylactic shock, generalized convulsions, and diffuse erythema with hypotension respectively. They need close monitoring and oxygen inhalation with anti-shock and anti-anaphylactic treatment. Most cases started within 30 min and recovered within 1 day. Conclusions Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications was safe with rare AEs. AEs were more likely to happen in abdominal applications than superficial ones. A well-designed emergency plan should be available for clinical use of sulfur hexafluoride microbubbles to reduce AEs and to deal with AEs properly. Critical relevance statement Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications reported few AEs and could be considered safe but severe AEs are life-threatening. We analyzed the influence factors of AEs and propose some methods for prevention and treatment of them, which can further improve the safety of sulfur hexafluoride microbubbles in clinical practice. Key points • The AE rate of sulfur hexafluoride microbubbles in abdominal and superficial applications was 0.024%. • Patients were more likely to have AEs in abdominal applications than superficial ones. • Severe AEs are life-threatening and need prompt identification and treatment. • We summarized some detailed suggestions for clinical prevention and treatment of AEs. Graphical Abstract

Abstract Background The number and proportion of the elderly population have been continuously increasing in China, leading to the elevated prevalence of chronic diseases and multimorbidity, which ultimately brings heavy burden to society and families. Meanwhile, the status of multimorbidity tends to be more complex in elderly inpatients than community population. In view of the above concerns, this study was designed to investigate the health status of elderly inpatients by analyzing clinical data in Chinese People's Liberation Army (PLA) General Hospital from 2008 to 2019, including the constitution of common diseases, comorbidities, the status of multimorbidity, in-hospital death and polypharmacy among elderly inpatients, so as to better understand the diseases spectrum and multimorbidity of elderly inpatients and also to provide supporting evidence for targeted management of chronic diseases in the elderly. Methods A clinical inpatients database was set up by collecting medical records of elderly inpatients from 2008 to 2019 in Chinese PLA General Hospital, focusing on diseases spectrum and characteristics of elderly inpatients. In this study, we collected data of inpatients aged ≥ 65 years old, and further analyzed the constitution of diseases, multimorbidity rates and mortality causes in the past decade. In addition, the prescriptions were also analyzed to investigate the status of polypharmacy in elderly inpatients. Results A total of 210,169 elderly patients were hospitalized from January 1st, 2008 to December 31st, 2019. The corresponding number of hospitalizations was 290,833. The average age of the study population was 72.67 years old. Of the total population, 73,493 elderly patients were re-admitted within one year, with the re-hospitalization rate of 25.27%. Malignant tumor, hypertension, ischemic heart disease, diabetes mellitus and cerebrovascular disease were the top 5 diseases. Among the study population, the number of patients with two or more long-term health conditions was 267,259, accounting for 91.89%, with an average of 4.68 diseases. In addition, the average number of medications taken by the study population was 5.4, among which, the proportion of patients taking more than 5 types of medications accounted for 55.42%. Conclusions By analyzing the constitution of diseases and multimorbidity, we found that multimorbidity has turned out to be a prominent problem in elderly inpatients, greatly affecting the process of healthy aging and increasing the burden on families and society. Therefore, multidisciplinary treatment should be strengthened to make reasonable preventive and therapeutic strategies to improve the life quality of the elderly. Meanwhile, more attention should be paid to reasonable medications for elderly patients with multimorbidity to avoid preventable side effects caused by irrational medication therapy.

Abstract Background About 25% of pregnant women experience bleeding in the early stage, and half of them eventually progress to pregnancy loss. Progesterone serves as a useful biomarker to predict miscarriage in threatened miscarriage, yet its performance is still debated. Aim To evaluate the performance of single serum progesterone predicting miscarriage in early pregnant patients with threatened miscarriage. Method The online database was searched to yield the literature using the terms of ‘Abortion’, ‘Miscarriage’, and ‘serum Progesterone’, including PubMed, Scopus, Embase, Cochrane library, and China national knowledge infrastructure. Receiver operating characteristic (ROC) curve, likelihood ratio (LLR) and diagnostic odds ratio (DOR) and 95% confidence interval (CI) were computed. Publication bias was assessed by the deeks funnel plot asymmetry test. Subgroup analyses were conducted according to the progesterone level (

Hyperspectral image (HSI) is pivotal in ground object classification, owing to its rich spatial and spectral information. Recently, convolutional neural networks and graph neural networks have become hotspots in HSI classification. Although various methods have been developed, the problem of detail loss may still exist when extracting complex features within homogenous regions. To solve this issue, in this article, we proposed a double-hop graph attention multiview fusion network. This model is adept at pinpointing precise attention features by integrating a double-hop graph with the graph attention network, thereby enhancing the aggregation of multilevel node information and surmounting the limitations of a restricted receptive field. Furthermore, the spectral-coordinate attention module (SCAM) is presented to seize more nuanced spectral and spatial attention features. SCAM harnesses the coordinate attention mechanism for in-depth pixel-level global spectral–spatial view. Coupled with the multiscale Gabor texture view, we forge a multiview fusion network that meticulously highlights edge details across varying scales and captures beneficial features. Our experimental validation across four renowned benchmark HSI datasets showcases our model's superiority, outstripping comparative methods in classification accuracy with limited labeled samples.

Based on a power supply system, a repairable K-out-of- $N+W$ : G system with c repairmen and warm spares is considered, where each repairman asynchronously takes multiple working vacations and vacation interruption policy. Total load of the system is shared equally by all the operating generators, the failure rate of each operating generator increases with the decreasing of the number of operating generators. Using Markov process and matrix-analytic method, steady-state probabilities and important performance indices are obtained. The mean time to first failure and reliability function are given by using the definition of PH-distribution. Numerical examples are given to illustrate the effect of system parameters on these reliability indices. In addition, machine learning (ML) methods including decision tree regression (DTR), random forest regression (RFR) and multilayer perceptron regression (MLPR) are used to predict the steady-state availability of the system, which shows that RFR is the optimal prediction model, and feature importances of system parameters are also provided.

Abstract Objective This study aims to investigate the relationship between abnormal vaginal microecology and human papillomavirus (HPV) infection, as well as the squamous intraepithelial lesions (SIL) progression. Methods A total of 383 patients diagnosed with HPV infection in our hospital between March 2017 and February 2022 were selected as the experimental group. In addition, several volunteers (n = 898) who underwent physical examination during the same period were randomly selected as the control group. Subsequently, we conducted several investigations, such as HPV detection and gene typing, examined vaginal microecological imbalances, and performed cytological examinations to analyze the correlation between microecological changes, different types of HPV infection, and SIL progression. Results HPV detection primarily included single and high-risk types of HPV infections. Moreover, significant disparities in the vaginal microecological environment between patients with persistent HPV infection and the control group, as well as patients with low-grade and high-grade SIL (LSIL and HSIL), were observed. The regression analysis revealed a correlation between LSIL and microflora density, diversity, bacteriological vaginosis (BV), vulvovaginal candidiasis (VVC), trichomonas vaginalis (TV), sialidase, as well as Lactobacillus. In addition, we identified an association between HSIL and pH, flora density, diversity, BV, VVC, candida vaginitis (CV), leukocyte esterase, catalase, and Lactobacillus levels. Conclusion These findings revealed a significant association between abnormal vaginal microecology and both HPV infection and the SIL progression.

Abstract Inulin, as a prebiotic, could modulate the gut microbiota. Burn injury leads to gut microbiota disorders and skeletal muscle catabolism. Therefore, whether inulin can improve burn-induced muscle atrophy by regulating microbiota disorders remains unknown. This study aimed to clarify that inulin intake alleviates gut microbiota disorders and skeletal muscle atrophy in burned rats. Rats were divided into the sham group, burn group, prebiotic inulin intervention group, and pseudo-aseptic validation group. A 30% total body surface area (TBSA) third-degree burn wound on dorsal skin was evaluated in all groups except the sham group. Animals in the intervention group received 7 g/L inulin. Animals in the validation group received antibiotic cocktail and inulin treatment. In our study inulin intervention could significantly alleviate the burn-induced skeletal muscle mass decrease and skeletal myoblast cell apoptosis. Inulin intake increased the abundances of Firmicutes and Actinobacteria but decreased the abundance of Proteobacteria. The biosynthesis of amino acids was the most meaningful metabolic pathway distinguishing the inulin intervention group from the burn group, and further mechanistic studies have shown that inulin can promote the phosphorylation of the myogenesis-related proteins PI3K, AKT and P70S6K and activate PI3K/AKT signaling for protein synthesis. In conclusion, inulin alleviated burn induced muscle atrophy through PI3K/AKT signaling and regulated gut microbiota dysbiosis.

Abstract Alagille Syndrome (ALGS) is a complex genetic disorder characterized by cholestasis, congenital cardiac anomalies, and butterfly vertebrae. The variable phenotypic expression of ALGS can lead to challenges in accurately diagnosing affected infants, potentially resulting in misdiagnoses or underdiagnoses. This study highlights novel JAG1 gene mutations in two cases of ALGS. The first case with a novel p.Pro325Leufs*87 variant was diagnosed at 2 months of age and exhibited a favorable prognosis and an unexpected manifestation of congenital hypothyroidism. Before the age of 2, the second patient was incorrectly diagnosed with liver structural abnormalities, necessitating extensive treatment. In addition, he exhibited delays in language acquisition that may have been a result of SNAP25 haploinsufficiency. The identification of ALGS remains challenging, highlighting the importance of early detection and genetic testing for effective patient management. The variant p.Pro325Leufs*87 is distinct from reported variants linked to congenital hypothyroidism in ALGS patients, thereby further confirming the clinical and genetic complexity of ALGS. This emphasizes the critical need for individualized and innovative approaches to diagnosis and medical interventions, uniquely intended to address the complexity of this syndrome.

Abstract Background Cadmium (Cd) pollution in agricultural soils has become a priority environmental concern globally. A reasonable application of passivators is critical to address the problem. In this study, we examined the remediation effects of rice husk biochar (rBC) and sepiolite (Sep) as single and combined (rBC + Sep) treatments on Cd pollution in a weakly alkaline soil using three maize cultivars (Liyu 16, Zhengdan 958, and Sanbei 218) as test crops. We also explained the mechanisms involved in the remediation effects. Results The pseudo-second-order kinetic equation and Langmuir model could well describe the adsorption process of rBC + Sep for Cd2+. Compared with the control treatment (CK), soil available Cd concentration decreased by 29.51–36.34% under rBC + Sep treatment (p 0.05). Conclusions The application of 0.2% rBC + 0.5% Sep composite passivation material to weakly alkaline Cd-contaminated soil can effectively reduce the Cd concentration of soil and maize.