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Abstract The Chinese mitten crab (Eriocheir sinensis) holds significant importance as a popular aquaculture food source; however, there are concerns about its potential contamination with polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) from both food and aquatic environment. To assess the associated health risks and identify potential sources of contamination in crabs, a comprehensive investigation was conducted, including a total of 70 samples from the crab food web. The results demonstrated that crabs predominantly exhibited elevated concentrations of PCBs and dl-PCBs, with mean concentrations of 12 207 ± 11 962 pg g-1 and 554 ± 203 pg g-1, respectively, while PCDD/Fs concentrations were comparatively lower at 20 ± 17 pg g-1. The accumulation of PCBs in crabs significantly surpassed that of PCDD/Fs. The material balance of PCDD/Fs and PCBs in the crab food web was estimated, indicating that sediments and feeds likely constitute the two primary sources of PCDD/Fs and PCBs in crabs. The monthly intake of PCDD/Fs and PCBs through crab consumption accounted for 30% of the dietary intake, which was well below the provisional tolerable monthly intake (PTMI) limit. The weekly intake of PCDD/Fs and PCBs for adults consuming one crab (100 g) does not pose health risks and the recommended weekly intake of white crabmeat and brown crabmeat is 443 g and 21 g, respectively.

Abstract Flow cytometry is a vital tool in biomedical research and laboratory medicine. However, its accuracy is often compromised by undesired fluctuations in fluorescence intensity. While fluorescence lifetime imaging microscopy (FLIM) bypasses this challenge as fluorescence lifetime remains unaffected by such fluctuations, the full integration of FLIM into flow cytometry has yet to be demonstrated due to speed limitations. Here we overcome the speed limitations in FLIM, thereby enabling high-throughput FLIM flow cytometry at a high rate of over 10,000 cells per second. This is made possible by using dual intensity-modulated continuous-wave beam arrays with complementary modulation frequency pairs for fluorophore excitation and acquiring fluorescence lifetime images of rapidly flowing cells. Moreover, our FLIM system distinguishes subpopulations in male rat glioma and captures dynamic changes in the cell nucleus induced by an anti-cancer drug. FLIM flow cytometry significantly enhances cellular analysis capabilities, providing detailed insights into cellular functions, interactions, and environments.

【Objective】The effects of operation parameters of multi-rotor plant protection unmanned aerial vehicle (UAV) at different growth stages of maize on deposition quality and the control efficacy of Spodoptera frugiperda were compared to select the optimal operation parameters, with an aim to provide scientific basis for precise pesticide application of S. frugiperda.【Method】DJI T20 six-rotor plant protection UAV was used as the research object, the operation parameters including flight altitude, flight speed and nozzle type were tested for optimization of deposition distribution at the trumpet stage and heading stage of maize, and the population decline rate and control effect of S. frugiperda 7 d after the application of pesticides were investigated.【Result】At trumpet stage of maize, when a SX110015VS nozzle operated at a flight speed of 4 m/s and at a flight altitude of 2.5 m above the maize canopy, the maximum normalized average droplet deposition was 0.45 μL/cm2. When a SX110015VS nozzle operated at a flight speed of 4 m/s and a flight altitude of 1.5 m, both average droplet coverage and average droplet density were the highest, which were 44.92 drops/cm2 and 9.31%, respectively. At heading stage of maize, the normalized average droplet deposition, average droplet coverage and average droplet density were the highest when a SX110015VS nozzle operated at a flight speed of 4 m/s and a flight altitude of 2.5 m, which were 0.50 μL/cm2, 82.92 drops/cm2 and 7.67%, respectively.【Conclusion】The actual occurrence level of pests should be taken into consideration in the selection of operation parameters at trumpet stage and heading stage of maize. The highest droplet deposition was achieved when the UAV flew at a speed of 4 m/s, an altitude of 2.5 m and a nozzle type of SX110015VS, the corrected control efficiency was more than 85% after 7 days of application.

Abstract Background Contactin-associated protein-2(CASPR2) antibody-associated autoimmune encephalitis(AE) is rare in children. This study aimed to report the clinical characteristics and long-term outcome of CASPR2 autoimmunity in children to expand the disease spectrum. Methods Children who were hospitalized in our hospital with clinically suspected AE from May 2015 to April 2022 and underwent neuronal surface antibodies detections were retrospectively analyzed. Clinical data of patients with CASPR2 autoimmunity were collected. Results Patients who were positive for NMDAR-IgG, CASPR2-IgG, LGI1-IgG and IgLON5-IgG occupied 95.2%(119/125),3.2%(4/125),0.8%(1/125) and 0.8%(1/125), respectively.The median onset age of the 4 patients with CASPR2-IgG was 5.6 years. The most common symptoms were psychiatric symptoms/abnormal behavior(3/4) and sleep dysfunction(3/4). One patient developed a phenotype of Rasmussen encephalitis(RE). Tumor was absent in our patients. Two patients showed abnormal findings on initial brain magnetic resonance imaging(MRI) scans. All the patients showed favorable response to immunotherapy except the patient with RE experienced recurrent symptoms who finally achieved remission after surgery. All the patients had a favorable long-term outcome at the last follow-up(33-58months). Conclusions CASPR2 autoimmunity may be the second most common anti-neuronal surface antibodies associated neurological disease in children. Psychiatric symptoms/abnormal behavior and sleep disorder were common in children with CASPR2-associated AE. Tumor was rare in those patients. Most pediatric patients had a favorable long-term outcome.

Abstract Background Describing the transmission dynamics of infectious diseases across different regions is crucial for effective disease surveillance. The multivariate time series (MTS) model has been widely adopted for constructing cross-regional infectious disease transmission networks due to its strengths in interpretability and predictive performance. Nevertheless, the assumption of constant parameters frequently disregards the dynamic shifts in disease transmission rates, thereby compromising the accuracy of early warnings. This study investigated the applicability of time-varying MTS models in multi-regional infectious disease monitoring and explored strategies for model selection. Methods This study focused on two prominent time-varying MTS models: the time-varying parameter-stochastic volatility-vector autoregression (TVP-SV-VAR) model and the time-varying VAR model using the generalized additive framework (tvvarGAM), and intended to explore and verify their applicable conditions for the surveillance of infectious diseases. For the first time, this study proposed the time delay coefficient and spatial sparsity indicators for model selection. These indicators quantify the temporal lags and spatial distribution of infectious disease data, respectively. Simulation study adopted from real-world infectious disease surveillance was carried out to compare model performances under various scenarios of spatio-temporal variation as well as random volatility. Meanwhile, we illustrated how the modelling process could help the surveillance of infectious diseases with an application to the influenza-like case in Sichuan Province, China. Results When the spatio-temporal variation was small (time delay coefficient: 0.1–0.2, spatial sparsity:0.1–0.3), the TVP-SV-VAR model was superior with smaller fitting residuals and standard errors of parameter estimation than those of the tvvarGAM model. In contrast, the tvvarGAM model was preferable when the spatio-temporal variation increased (time delay coefficient: 0.2–0.3, spatial sparsity: 0.6–0.9). Conclusion This study emphasized the importance of considering spatio-temporal variations when selecting appropriate models for infectious disease surveillance. By incorporating our novel indicators—the time delay coefficient and spatial sparsity—into the model selection process, the study could enhance the accuracy and effectiveness of infectious disease monitoring efforts. This approach was not only valuable in the context of this study, but also has broader implications for improving time-varying MTS analyses in various applications.

Abstract Objective Since in the cancer setting, tumor cells may use cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to evade the immune system. This study aimed to identify CTLA-4-related long non-coding RNAs (lncRNAs) and assess their roles in lung adenocarcinoma (LUAD) development. Methods Clinical and genomic data were obtained from The Cancer Genome Atlas (TCGA), MSigDB and Gene Weaver. CTLA-4-related lncRNA-based gene signatures (CTLA4LncSigs) were identified using Cox regression, establishing a risk score model and an independent prognostic model. Enrichment analysis (GO/KEGG) was performed. Mendelian randomization (MR) analysis investigated the nitrogen metabolism and lung cancer relationship, with Bayesian weighted MR (BWMR) addressing uncertainties. Correlations with tumor microenvironment and drug sensitivity were explored. Results Nineteen CTLA4LncSigs significantly influenced LUAD prognosis. The risk score demonstrated independence as a prognostic factor. Functional analysis revealed lncRNAs' impact on nitrogen metabolism. MR and BWMR confirmed the protective role of the nitrogen metabolism pathway in lung cancer. Conclusion Our study identifies CTLA-4-related lncRNAs associated with LUAD prognosis and uncovers a previously undiscovered protective role of the nitrogen metabolism pathway in combating LUAD development, providing new insights into potential therapeutic targets and prognostic biomarkers for this aggressive cancer subtype.

Meteorological disasters occur frequently, and Gansu Province is a sensitive area for food production. Potatoes are a major crop in this province. As a result, executing risk zoning and risk prediction for potato production is quite important. However, in existing risk assessment and prediction research, the dynamic nature of risks and improving the accuracy of risk prediction are urgent scientific issues that must be addressed. Weighting, spatial econometric analysis, climate diagnosis technology, and machine learning models were used to provide a refined spatiotemporal evolution of potato disaster risk in China's Gansu Province, as well as predict future potato production risk. The findings indicate that there are significant interdecadal fluctuations in the potato disaster loss, which has decreased considerably since 2000. The average yield decrease rate in the 1980s, 1990s, 2000s, and 2010s was -13.9%, -15.4%, -9.1%, and -7.3%, respectively, and the county percentage susceptible to severe yield loss was 26.1%, 39.1%, 22.9%, and 12.9%. Second, most counties' potato production falls within the medium–low or low risk region. Eastern and southern Gansu are particularly vulnerable to catastrophic calamities. High risk counties are primarily clustered in Qingyang and Longnan, whereas low risk counties are concentrated in Wuwei and Gannan. Third, high risk locations have altered, and the migration trajectory of the risk indicator’s barycenter shows significant differences in direction and distance. The comprehensive risk moves in a southeast-west-northern direction, but the distance is short. Overall, disaster losses in most counties are decreasing, and future trends will be similar with previous patterns. The Interpolation-EMD-SVM scheme greatly increases the accuracy of the disaster loss risk prediction. The technology and methods provide a scientific foundation for accurately assessing risk dynamic characteristics, managing regional disaster risks, and preventing and mitigating disasters.

N,N′-Substituted p-phenylenediamines (PPDs) are widely used as antioxidants in the rubber industry and are released into the environment in large quantities during the production and use of rubber products. We quantified PPDs and PPD quinone derivatives (PPD-Qs) in rubber consumer products, including car tires, rubber belts, rubber gloves, rubber cables, and rubber hoses, to obtain information on the degree of weathering over time during their use. Additionally, we investigated the occurrences and sources of PPDs and PPD-Qs in dust samples collected from four typical urban environments (roads, parking lots, automotive repair shops, and residences). The detected compounds included the highly toxic N-(1,3-dimethylbutyl)-N′-phenyl-1,4-phenylenediamine quinone, which can cause acute mortality of coho salmon (Oncorhynchus kisutch). Concentrations of PPDs in the automotive repair shops reached 56.0 μg/g, and were much higher than in the other environments, while the residential samples had the lowest contaminant concentrations. In road and residential samples, N,N′-di-2-naphthyl-p-phenylenediamine accounted for 17 %–30 % of the PPDs, and may have originated from different sources. We preliminarily identified 32 transformation products, and 11 of these were N,N′-di-2-naphthyl-p-phenylenediamine transformation products. The average daily intakes of PPDs and PPD-Qs were calculated to assess the health risks of dust exposure in each environment. Workers had high total intakes of PPD [60.3 ng/(kg day)] and PPD-Qs [20.1 ng/(kg day)], and were at some risk of occupational exposure. These results improve our understanding of the environmental occurrences, sources, transformation, and health risks of PPDs and PPD-Qs.

The reliable operation of railway embankments traversing degrading permafrost regions is challenged by climate warming. This study examines performances of four main types of railway embankments on the Qinghai-Tibet Plateau in thermally stabilizing permafrost foundation over warm permafrost using numerical modelling and 10-year monitoring data. Then, a reinforcement measure that combines a thermal conductivity variable system (TCVS) was designed to improve the cooling capacity of the crushed-rock sloped embankment (CRSE) by countering the heat absorption of slopes during summers. A coupled thermal-fluid-solid model was built to simulate and assess the cooling performance and reinforcing capacity of the new design. Results show that the crushed-rock embankments can produce convection cooling on the permafrost subgrade but the performances vary with different structures. The CRSE has insufficient cooling capacity to withstand the underlying permafrost degradation in warm permafrost regions. The optimized CRSE that combines the TCVS can effectively cool the underlying warm permafrost and decrease the shady-sunny slope effect under a warming climate, and can be used as an effective reinforcement measure. This study confirms the application of air-cooled embankments in protecting permafrost subgrade and provides guidance for structural design of embankment traversing degrading permafrost.

Dysregulation of apoptosis occurs in different types of malignant tumors and is likely to influence the tumor evolution, as well as clinical prognosis. However, the limited number of studies investigating the predictive power of apoptosis-related genes (ARGs) in gastric cancer indicates a gap in the current research. 174 ARGs who differentially expressed were screened using public databases, including the Gene Expression Omnibus and the Molecular Signatures Database. Univariate and LASSO regression analyses were rigorous approaches to recognize the 12 optimal genes (CTHRC1, PDGFRL, VCAN, GJA1, LOX, UPP1, ANGPT2, CRIM1, HIF1A, APOD, RNase1, and ID1) that make up the prognostic risk model. Molecular mutations, related signaling pathways, and immune system characteristics in different subgroups defined by the risk model were analyzed using different R packages. Moreover, based on the database of Genomics of Drug Sensitivity in Cancer, chemotherapy sensitivity was predicted among the risk subgroups. As a result, there were differences in mutation profiles, signaling pathways, and infiltrated immune cells between patients in various risk groups. Moreover, the low-risk group displayed greater sensitivity to chemotherapy than the high-risk group. Risk model provided a better prognostic value than the T, N, and M stages, according to the receiver operating characteristic curve. Finally, in a nomogram, the risk model and clinical factors were combined to visualize the survival rates of patients with GC. In response to the differential expression of apoptosis-related genes, a novel model for predicting the prognosis of GC patients was developed. This model may be highly valuable for guiding doctors to deliver treatment plans tailored to the need of patients with GC.

Background: Chronic subdural hematoma (CSDH) is a prevalent form of intracranial haemorrhage encountered in neurosurgical practice, and its incidence has notably risen in recent years. Currently, there is a lack of studies that have comprehensively classified the cells present in hematomas removed during surgery, and their correlation with CSDH recurrence remains elusive. This study aims to analyse the subcellular populations and occupancy levels within peripheral blood. Methods: This study analyses the subcellular populations and occupancy levels within peripheral blood and postoperatively removed hematomas by single-cell sequencing and attempts to analyse the effect of different cell occupancies within peripheral blood and intraoperatively removed hematomas on CSDH. Results: The single-cell sequencing results showed that the cells were classified into 25 clusters by differential gene and UMAP dimensionality reduction clustering analyses and further classified into 17 significant cell populations by cell markers: pDCs, CD8 T cells, CD4 T cells, MigDCs, cDC2s, cDC1s, plasma cells, neutrophils, naive B cells, NK cells, memory B cells, M2 macrophages, CD8 Teffs, CD8 MAIT cells, CD4 Tregs, CD19 B cells, and monocytes. Further research showed that the presence of more cDC2 and M2 macrophages recruited at the focal site in patients with CSDH and the upregulation of the level of T-cell occupancy may be a red flag for further brain damage. ROS, a marker of oxidative stress, was significantly upregulated in cDC2 cells and may mediate the functioning of transcription proteins of inflammatory factors, such as NFκB, which induced T cells' activation. Moreover, cDC2 may regulate M2 macrophage immune infiltration and anti-inflammatory activity by secreting IL1β and binding to M2 macrophage IL1R protein. Conclusion: The detailed classification of cells in the peripheral blood and hematoma site of CSDH patients helps us to understand the mechanism of CSDH generation and the reduction in the probability of recurrence by regulating the ratio of cell subpopulations.

Abstract This study aims to investigate the relationship between the healthy eating index (HEI) and the prevalence of stroke within a diverse United States population. Employing a cross-sectional design, we utilized data sourced from the National Health and Nutrition Examination Survey (NHANES). Dietary information was collected from participants and HEI scores were computed. NHANES employed stratified multistage probability sampling, with subsequent weighted analysis following NHANES analytical guidelines. Thorough comparisons were made regarding the baseline characteristics of individuals with and without stroke. Weighted multivariable logistic regression analysis and restricted cubic spline (RCS) methods were employed to ascertain the association between stroke risk and HEI, with LASSO regression utilized to identify dietary factors most closely linked to stroke risk. Additionally, we constructed a nomogram model incorporating key dietary factors and assessed its discriminatory capability using the receiver operating characteristic (ROC) curve. Our study encompassed 43,978 participants, representing an estimated 201 million U.S. residents. Participants with a history of stroke exhibited lower HEI scores than their non-stroke counterparts. Logistic regression analysis demonstrated a robust association between lower HEI scores and stroke, even after adjusting for confounding variables. RCS analysis indicated a nonlinear negative correlation between HEI and stroke risk. Furthermore, detailed subgroup analysis revealed a significant gender-based disparity in the impact of dietary quality on stroke risk, with females potentially benefiting more from dietary quality improvements. Sensitivity analysis using unweighted logistic regression yielded results consistent with our primary analysis. The nomogram model, based on key dietary factors identified through LASSO regression, demonstrated favorable discriminatory power, with an area under the curve (AUC) of 79.3% (95% CI 78.4–81.2%). Our findings suggest that higher HEI scores are inversely related to the risk of stroke, with potential greater benefits for women through dietary quality enhancement. These results underscore the importance of improving dietary quality for enhanced stroke prevention and treatment.

Many current satellite-derived bathymetry methods usually rely on in-situ water depth, which limits their applications. In this study, an ICESat-2 assisted dual-band model (IDBM) is proposed, which can be used to derive bathymetry independent of in-situ water depth. First, the Sentinel-2 blue and green band diffuse attenuation coefficient is derived using ICESat-2 lidar photon data from adjacent deep water according to the Jerlov ${{K}_d}$ spectral curves and the sensor spectral response function. Then, these two coefficients are applied to the IDBM model to derive the water depth. Datasets for four study areas are used to validate the feasibility of the proposed IDBM model, in addition, the original QAA (quasi-analytical algorithm) assisted dual-band model (QDBM) is also used to derive bathymetry for comparison purposes. Experiment results show that the proposed IDBM model is effective and can achieve higher or similar accuracy compared to the original QDBM model. The average mean absolute error (MAE) and root mean square error (RMSE) of the IDBM model reach 1.23 and 1.67 m, while those of the QDBM model are 1.44 and 1.91 m, respectively. The performance of the IDBM model has improved to some extent. Especially for the SI case, the MAE and RMSE of the QDBM model are 1.46 and 2.00 m, while those of the IDBM model are 0.99 and 1.55 m, which are reduced by 0.47 and 0.45 m. In conclusion, the proposed IDBM model is feasible and effective to derive bathymetry without in-situ water depth.

Abstract Background Several studies have suggested a significant association of hand, foot, and mouth disease (HFMD) with ambient air pollutants. Existing studies have characterized the role of air pollutants on HFMD using only risk ratio measures while ignoring the attributable burden. And whether the geographical context (i.e., diverse topographic features) could modulate the relationships is unclear. Methods Daily reported childhood HFMD counts, ambient air pollution, and meteorological data during 2015–2017 were collected for each of 21 cities in Sichuan Province. A multistage analysis was carried out in different populations based on geographical context to assess effect modification by topographic conditions. We first constructed a distributed lag nonlinear model (DLNM) for each city to describe the relationships with risk ratio measures. Then, we applied a multivariate meta-regression to estimate the pooled effects of multiple air pollutants on HFMD from the exposure and lagged dimensions. Finally, attributable risks measures were calculated to quantify HFMD burden by air pollution. Results Based on 207554 HFMD cases in Sichuan Province, significant associations of HFMD with ambient air pollutants were observed mainly at relatively high exposure ranges. The effects of ambient air pollutants on HFMD are most pronounced on lag0 or around lag7, with relative risks gradually approaching the reference line thereafter. The attributable risks of O3 were much greater than those of other air pollutants, particularly in basin and mountain regions. Conclusions This study revealed significant pooled relationships between multiple air pollutants and HFMD incidence from both exposure and lag dimensions. However, the specific effects, including RRs and ARs, differ depending on the air pollution variable and geographical context. These findings provide local authorities with more evidence to determine key air pollutants and regions for devising and implementing targeted interventions.

Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases. However, a lack of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of these strategies. This review presents the viewpoints from an international conference consisting of several expert working groups. The working groups reviewed a series of questions of particular interest to clinicians taking care of patients with pancreatic neuroendocrine neoplasms with liver metastases by reviewing the existing management strategies and literature, evaluating the evidence on which management decisions were based, developing internationally acceptable recommendations for clinical practice, and making recommendations for clinical and research endeavors. The review for each question will be followed by recommendations from the panel.

BackgroundIn China, bacillary dysentery (BD) is the third most frequently reported infectious disease, with the greatest annual incidence rate of 38.03 cases per 10,000 person-years. It is well acknowledged that temperature is associated with BD and the previous studies of temperature-BD association in different provinces of China present a considerable heterogeneity, which may lead to an inaccurate estimation for a region-specific association and incorrect attributable burdens. Meanwhile, the common methods for multi-city studies, such as stratified strategy and meta-analysis, have their own limitations in handling the heterogeneity. Therefore, it is necessary to adopt an appropriate method considering the spatial autocorrelation to accurately characterize the spatial distribution of temperature-BD association and obtain its attributable burden in 31 provinces of China.MethodsA novel three-stage strategy was adopted. In the first stage, we used the generalized additive model (GAM) model to independently estimate the province-specific association between monthly average temperature (MAT) and BD. In the second stage, the Leroux-prior-based conditional autoregression (LCAR) was used to spatially smooth the association and characterize its spatial distribution. In the third stage, we calculate the attribute BD cases based on a more accurate estimation of association.ResultsThe smoothed association curves generally show a higher relative risk with a higher MAT, but some of them have an inverted “V” shape. Meanwhile, the spatial distribution of association indicates that western provinces have a higher relative risk of MAT than eastern provinces with 0.695 and 0.645 on average, respectively. The maximum and minimum total attributable number of cases are 224,257 in Beijing and 88,906 in Hainan, respectively. The average values of each province in the eastern, western, and central areas are approximately 40,991, 42,025, and 26,947, respectively.ConclusionBased on the LCAR-based three-stage strategy, we can obtain a more accurate spatial distribution of temperature-BD association and attributable BD cases. Furthermore, the results can help relevant institutions to prevent and control the epidemic of BD efficiently.

This investigation delves into the intricacies of the process mechanism for generating a gradient nanostructured surface (GNS) layer on M50 bearing steel, with the aim of augmenting its surface hardness and wear resistance under elevated temperature. The electron backscatter diffraction and transmission electron microscopy substantiate the successful formation of a GNS layer, surpassing 200 µm in thickness, on the M50 bearing steel treated by Ultrasonic shot peening (USP) technology. The severe plastic deformation (SPD) induced by the USP process resulted in a significant refinement of the martensite in M50 bearing steel, leading to a remarkable 32.25 % increase in surface hardness compared to its untreated coarse-grained (CG) counterpart. Pin-on-Disk wear tests were conducted at an elevated temperature of 300 °C on both the as-received CG-M50 and USP-treated M50 bearing steel samples to evaluate the impact of USP treatment on the wear resistance of M50 bearing steel. Experimental results reveal that the volume loss of the USP-treated M50 bearing steel is 94.9 % less than that of the untreated CG-M50 bearing steel after 4 h of wear tests. The improved wear resistance of the USP-treated M50 bearing steel can be attributed to the creation of an ultrastrong and stable GNS layer facilitated by USP.

Abstract Background Among all types of mental disorders, individuals with schizophrenia exhibit the highest frequency of aggressive behavior. This disrupts the healthcare environment and poses threats to family life and social harmony. Present approaches fail to identify individuals with schizophrenia who are predisposed to aggressive behavior. In this study, we aimed to construct a risk prediction model for aggressive behavior in stable patients with schizophrenia, which may facilitate early identification of patients who are predisposed to aggression by assessing relevant factors, enabling the management of high-risk groups to mitigate and prevent aggressive behavior. Methods A convenience sample of stable inpatients with schizophrenia were selected from Daqing Municipal Third Hospital and Chifeng Municipal Anding Hospital from March 2021 to July 2023. A total of 429 patients with stable schizophrenia who met the inclusion criteria were included. A survey was conducted with them using a questionnaire consisting of general information questionnaire, Positive and Negative Symptom Scale, Childhood Trauma Questionnaire-Short Form, Connor-Davidson Resilience Scale and Self-esteem Scale. Patients enrolled in this study were divided into aggressive and non-aggressive groups based on whether there was at least one obvious and recorded personal attack episode (including obvious wounding and self-injurious behavior) following diagnosis. Binary Logistic regression was used to determine the influencing factors, and R software was used to establish a nomogram model for predicting the risk of aggressive behavior. Bootstrap method was used for internal validation of the model, and the validation group was used for external validation. C statistic and calibration curve were used to evaluate the prediction performance of the model. Results The model variables included Age, Duration of disease, Positive symptom, Childhood Trauma, Self-esteem and Resilience. The AUROC of the model was 0.790 (95% CI:0.729–0.851), the best cutoff value was 0.308; the sensitivity was 70.0%; the specificity was 81.4%; The C statistics of internal and external validation were 0.759 (95%CI:0.725–0.814) and 0.819 (95%CI:0.733–0.904), respectively; calibration curve and Brier score showed good fit. Conclusions The prediction model has a good degree of discrimination and calibration, which can intuitively and easily screen the high risk of aggressive behavior in stable patients with schizophrenia, and provide references for early screening and intervention.

This work used electroshocking treatment (EST) plus external loading to regulate the microstructure of titanium matrix composites (TMCs). The external loading was 0.3 MPa. After EST plus external loading with 0.3 MPa, the α was reduced to 2.53 μm in size. The percentage of high angle grain boundaries (HAGBs) in α increased first and then decreased. The percent of HAGBs in TiB decreased, mainly due to the introduction of abundant dislocations in the TiB/matrix interface after EST. After EST, the maximum texture strength of TiB decreased from 13.09 to 12.97, and that of α decreased from 3.11 to 1.58. After EST under external loading with 0.3 MPa, the maximum texture strength of TiB decreased to 8.10. The orientation of TiB experienced significant variation. TEM results showed that TiB and α formed a distorted interface after EST under external loading with 0.3 MPa. The interplanar spacing of TiB and α was varied. All results show that the texture of TMCs can be relieved by EST plus external loading with 0.3 MPa. It is mainly attributed to the thermal and athermal effects and the imposed external loads with EST. EST plus external loading provides a new method for manipulating the microstructure of TMCs.

Detoxification genes are crucial to insect resistance against chemical pesticides, yet their expression may be altered by exposure to biopesticides such as spores and insecticidal proteins of Bacillus thuringiensis (Bt). Increased enzymatic levels of selected detoxification genes, including glutathione S-transferase (GST), cytochrome P450 (CYP450), and carboxylesterase (CarE), were detected in chlorantraniliprole (CAP)-resistant strains of the diamondback moth (DBM, Plutella xylostella) from China when compared to a reference susceptible strain. These CAP-resistant DBM strains displayed distinct expression patterns of GST 1, CYP6B7, and CarE-6 after treatment with CAP and a Bt pesticide (Bt-G033). In particular, the gene expression analysis demonstrated significant upregulation of the CYP6B7 gene in response to the CAP treatment, while the same gene was downregulated following the Bt-G033 treatment. Downregulation of CYP6B7 using RNAi resulted in increased susceptibility to CAP in resistant DBM strains, suggesting a role of this gene in the resistant phenotype. However, pretreatment with a sublethal dose of Bt-G033 inducing the downregulation of CYP6B7 did not significantly increase CAP potency against the resistant DBM strains. These results identify the DBM genes involved in the metabolic resistance to CAP and demonstrate how their expression is affected by exposure to Bt-G033.

Wheat Fusarium head blight is one of the major diseases affecting the yield and quality of wheat. Accurate and rapid estimation of disease severity is crucial for implementing disease-resistant breeding and scientific management strategies. Traditional methods for estimating disease severity are complex and inefficient, often failing to provide accurate assessments under field conditions. Therefore, this paper proposes a method using a lightweight U-Net model for segmenting wheat spike disease spots to estimate disease severity. Firstly, the model employs MobileNetv3 as its backbone for feature extraction, significantly reducing the number of parameters and computational demand, thus enhancing segmentation efficiency. Secondly, the backbone network has been augmented with a lightweight Coordinate Attention (CA) module, which integrates lesion position information through channel attention and aggregates features across two spatial dimensions. This allows the model to capture long-range feature correlations and maintain positional information, effectively enhancing the segmentation of wheat spike disease spots while ensuring the model’s lightweight and efficient characteristics. Lastly, depthwise separable convolutions have been introduced in the decoder in place of standard convolutions, further reducing the model’s parameter count while maintaining performance. Experimental results show that the model’s segmentation Mean Intersection over Union (MIoU) reached 88.87%, surpassing the U-Net model by 3.49 percentage points, with a total parameter count of only 4.52 M, one-sixth of the original model. The improved model demonstrates its capability to segment individual wheat spike disease spots under field conditions and estimate the severity of infestation, providing technical support for disease identification research.

Abstract Background Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing. Methods The paraffin‐embedded tissue specimens of 38 patients with rectal NENs after surgery were subjected to whole gene sequencing (WGS), and mutation profilings were drawn to identify high‐frequency mutation genes, copy‐number variations (CNVs), tumor mutation burden (TMB), signal pathways, mutation signatures, DNA damage repair (DDR) genes, and molecular types. The differences of mutated genes and signaling pathways in different pathological grades and metastatic/non‐metastatic groups were compared. It helped to search for potential targets. Results C > T and T > C transitions are the most common base substitutions in rectal NENs. DNA mismatch repair deficiency, DNA base modifications, smoking and exposure to ultraviolet light might play a role in the occurrence of rectal NENs. DAXX, KMT2C, BCL2L1, LTK, MERTK, SPEN, PKN1, FAT3, and LRP2 mutations were found in only low‐grade rectal NETs, whereas APC, TP53, NF1, SOX9, and BRCA1 mutations were common in high‐grade rectal NECs/MiNENs. These genes helped in distinguishing poorly‐differentiated or well‐differentiated rectal NENs. Alterations in P53, Wnt and TGFβ signaling pathways were more pronounced in rectal NECs and MiNENs. Alterations in Wnt, MAPK and PI3K/AKT signaling pathways promoted metastases. Rectal NENs were classified into two molecular subtypes by cluster analysis based on the mutant genes and signaling pathways combined with clinicopathological features. Patients with mutations in the LRP2, DAXX, and PKN1 gene showed a trend of well‐differentiated and early‐stage tumors with less metastasis (p = 0.000). Conclusions This study evaluated risk factors for regional lymphatic and/or distant metastases, identified high‐frequency mutated genes, mutation signatures, altered signaling pathways through NGS. Rectal NENs were divided into two molecular types. This helps to evaluate the likelihood of metastasis, formulate follow‐up strategies for patients and provide a target for future research on precision treatment of rectal NENs. PARP inhibitors, MEK inhibitors, mTOR/AKT/PI3K and Wnt signaling pathway inhibitors may be effective drugs for the treatment of metastatic rectal NENs.

It is well known that the mechanical properties of Ti-6.5Al-3.5Mo-1.5Zr-0.3Si are closely related to its microstructure and texture. In this work, a novel treatment of electroshocking treatment (EST) was adopted to optimize the microstructure and improve the mechanical properties of this titanium alloy. The grain orientation, texture, and mechanical properties of Ti-6.5Al-3.5Mo-1.5Zr-0.3Si alloy under EST were characterized and analyzed. With the increase of EST time to 0.04 s, the resultant acicular secondary αs shows a tendency of spheroidization and the increase in grain diameter, which leads to a little decrease in hardness and yield strength. The increase in EST time to 0.06 s resulted in the precipitation of martensitic phases with high aspect ratios and a reduction in grain size in Ti-6.5Al-3.5Mo-1.5Zr-0.3Si alloy, as well as generating a more uniform texture distribution. The optimization of microstructure and texture significantly enhances the hardness and yield strength. The results in this work demonstrate that EST can serve as a novel method to regulate the microstructure and mechanical properties of Ti-6.5Al-3.5Mo-1.5Zr-0.3Si alloy.

Abstract Immunogenic cell death (ICD) is a form of cell death that stimulates the immune system to produce an immune response by releasing tumour-associated antigens and tumour-specific antigens and is considered to play an important role in tumour immunotherapy. In the present study, we identified two ICD-related subtypes in osteosarcoma (OS) by consensus clustering. The ICD-low subtype was associated with favourable clinical outcomes, abundant immune cell infiltration, and high activity of immune response signalling. We also established and validated an ICD-related prognostic model, which could not only be used to predict the overall survival of OS patients but was also found to be closely related to the tumour immune microenvironment of OS patients. Overall, we established a new classification system for OS based on ICD-related genes, which can be used to predict the prognosis of OS patients and to select appropriate immunotherapy drugs.

Aluminum alloy sheets with higher isotropy and finer grains possess larger post-formability and better mechanical properties. However, it is extremely difficult to simultaneously realize the isotropy improvement and grain refinement by conventional plastic deformation process. In this paper, a multidirectional rotary forging (MRF) process was applied to tune the isotropy degree and grain structure of Al7075 sheets. The isotropy behaviors of microstructure and mechanical property along different testing directions were investigated, and the grain refinement behaviors were studied. The microstructure analysis indicates that initial anisotropic textures firstly transform to different single textures individually, and then the lattice orientations of all these different single textures strongly rotate along 〈110〉 crystal direction to form the same multiple textures along 〈110〉//normal fiber, i.e. isotropic τ-fiber. The mechanical property analysis indicates that isotropic yield strength and tensile strength were obtained by MRF deformation, which was mainly attributed to the combined effect of texture isotropy and dislocation density isotropy. Strong grain refinement was achieved under the deformation amount of 70 %, and the final grain size was ∼ 0.8 μm, which were mainly contributed to the interaction effects of strong lattice rotation, complex slip system activation and dislocation gliding.

BackgroundTo investigate the correlation between albumin-corrected anion gap(ACAG) within the first 24 hours of admission and in-hospital mortality in trauma patients in intensive care unit(ICU).Materials and methodsWe utilized the MIMIC-Ⅲ and MIMIC-Ⅳ databases to examine trauma patients admitted to the ICU. The relationship between ACAG and in-hospital mortality in trauma patients was analyzed using Receiver Operating Characteristic(ROC) curve, Kaplan-Meier (K-M) survival curve, and Cox regression model. Propensity score matching (PSM) and subgroup analysis were conducted to enhance stability and reliability of the findings. Mortality at 30-day and 90-day served as secondary outcomes.ResultsThe study enrolled a total of 1038 patients. The AUC for ACAG (0.701, 95%CI: 0.652-0.749) was notably higher than that for anion gap and albumin. The Log-rank test revealed that the optimal cut-off point of ACAG for predicting in-hospital mortality was determined to be 20.375mmol/L. The multivariate Cox regression analysis demonstrated an independent association between high ACAG level and a higher risk of in-hospital mortality (HR = 3.128, 95% CI: 1.615-6.059). After PSM analysis, a matched cohort consisting of 291 subjects was obtained. We found no signifcant interaction in most stratas. Finally, The in-hospital, 30-day, and 90-day survival rates in the high ACAG group exhibited a statistically decrease compared to those in the low ACAG group both pre- and post-matching.ConclusionThe elevated level of ACAG was found to be independently associated with increased in-hospital mortality among trauma patients in the ICU.

BackgroundHand, foot, and mouth disease (HFMD) has remained a serious public health threat since its first outbreak in China. Analyzing the province-level spatiotemporal distribution of HFMD and mapping the relative risk in mainland China will help determine high-risk provinces and periods of infection outbreaks for use in formulating new priority areas for prevention and control of this disease. Furthermore, our study examined the effect of air pollution on HFMD nationwide, which few studies have done thus far.MethodsData were collected on the number of provincial monthly HFMD infections, air pollution, meteorological variables, and socioeconomic variables from 2014 to 2017 in mainland China. We used spatial autocorrelation to determine the aggregate distribution of HFMD incidence. Spatiotemporal patterns of HFMD were analyzed, risk maps were developed using the Bayesian spatiotemporal model, and the impact of potential influencing factors on HFMD was assessed.ResultsIn our study, from 2014 to 2017, the HFMD annual incidence rate in all provinces of mainland China ranged from 138.80 to 203.15 per 100,000 people, with an average annual incidence rate of 165.86. The temporal risk of HFMD for 31 Chinese provinces exhibited cyclical and seasonal characteristics. The southern and eastern provinces had the highest spatial relative risk (RR > 3) from 2014 to 2017. The HFMD incidence risk in provinces (Hunan, Hubei, and Chongqing) located in central China increased over time. Among the meteorological variables, except for the mean two-minute wind speed (RR 0.6878; 95% CI 0.5841, 0.8042), all other variables were risk factors for HFMD. High GDP per capita (RR 0.9922; 95% CI 0.9841, 0.9999) was a protective factor against HFMD. The higher the birth rate was (RR 1.0657; 95% CI 1.0185, 1.1150), the higher the risk of HFMD. Health workers per 1,000 people (RR 1.2010; 95% CI 1.0443, 1.3771) was positively correlated with HFMD.ConclusionsFrom 2014 to 2017, the central provinces (Hunan, Hubei, and Chongqing) gradually became high-risk regions for HFMD. The spatiotemporal pattern of HFMD risk may be partially attributed to meteorological and socioeconomic factors. The prevalence of HFMD in the central provinces requires attention, as prevention control efforts should be strengthened there.

Abstract Background Hand, foot and mouth disease (HFMD) caused by a variety of enteroviruses remains a major public health problem in China. Previous studies have found that social factors may contribute to the inconsistency of the relationship patterns between meteorological factors and HFMD, but the conclusions are inconsistent. The influence of social factors on the association between meteorology and HFMD is still less well understood. We aimed to analyze whether social factors affected the effect of meteorological factors on HFMD in Sichuan Province. Method We collected daily data on HFMD, meteorological factors and social factors in Sichuan Province from 2011 to 2017. First, we used a Bayesian spatiotemporal model combined with a distributed lag nonlinear model to evaluate the exposure-lag-response association between meteorological factors and HFMD. Second, by constructing the interaction of meteorological factors and social factors in the above model, the changes in the relative risk (RR) under different levels of social factors were evaluated. Results The cumulative exposure curves for average temperature, relative humidity, and HFMD were shaped like an inverted “V” and a “U” shape. As the average temperature increased, the RR increased and peaked at 19 °C (RR 1.020 [95% confidence interval CI 1.004–1.050]). The urbanization rate, per capita gross domestic product (GDP), population density, birth rate, number of beds in health care centers and number of kindergartens interacted with relative humidity. With the increase in social factors, the correlation curve between relative humidity and HFMD changed from an “S” shape to a “U” shape. Conclusions Relative humidity and average temperature increased the risk of HFMD within a certain range, and social factors enhanced the impact of high relative humidity. These results could provide insights into the combined role of environmental factors in HFMD and useful information for regional interventions.

Abstract Cylindrical shells are widely used in public buildings and military protection fields, and it has a high risk of terrorist attacks and military attacks, it is of great social benefit to carry out the anti-blast design of cylindrical shells, which needs to consider building shape and the shape of blast waves. In this paper, cylindrical charges in five directions were detonated on the outer ground of the scaled cylindrical shell, blast loads of the cylindrical shell were measured and blast waves were photographed. The variation of blast load is analyzed by combining the test and simulation results, the difference in peak overpressure of the blast waves on the end face between five orientations is nearly twice. The blast loads in the axial direction of cylindrical charges have a secondary peak phenomenon, and the blast loads between the axial direction and radial direction of cylindrical charges change abruptly at a specific angle. The experimental and simulation methods provide a reference for establishing a blast load database of typical buildings.

Abstract Hand, foot, and mouth disease (HFMD) is a major public health concern in the Asia–Pacific region. Previous studies have implied that ambient air pollution may affect the incidence of HFMD, but the results among different regions are inconsistent. We aimed to deepen the understanding of the associations between air pollutants and HFMD by conducting a multicity study. Daily data on childhood HFMD counts and meteorological and ambient air pollution (PM2.5, PM10, NO2, CO, O3, and SO2) concentrations in 21 cities in Sichuan Province from 2015 to 2017 were collected. A spatiotemporal Bayesian hierarchical model framework was established, and then a distributed lag nonlinear models (DLNMs) was constructed to reveal exposure-lag-response relationships between air pollutants and HFMD while controlling for spatiotemporal effects. Furthermore, given the differences in the levels and seasonal trends of air pollutants between the basin region and plateau region, we explored whether these associations varied between different areas (basin and plateau). The associations between air pollutants and HFMD were nonlinear, with different lag responses. Low NO2 concentrations and both low and high PM2.5 and PM10 concentrations were associated with a decreased risk of HFMD. No significant associations between CO, O3, and SO2 and HFMD were found. The associations between air pollutant concentrations and HFMD were different between the basin and plateau regions. Our study revealed associations between PM2.5, PM10, and NO2 concentrations and HFMD, deepening the understanding of the relationships between air pollutants and HFMD. These findings provide evidence to support the formulation of relevant prevention measures and the establishment of an early warning system.

Abstract Background We aimed to analyze the genotype-phenotype correlations of STXBP1 pathogenic variants, prognostic factors and the treatment choices in a case-series of STXBP1-related disorders from China. Methods The clinical data and genetic results of the children diagnosed with STXBP1-related disorders at Xiangya hospital from 2011 to 2019 were collected retrospectively, and analyzed. We divided our patients into groups for comparison purposes: patients with missense variants and nonsense variants, patients who are seizure-free and not seizure-free, patients with mild to moderate intellectual disability (ID) and severe to profound global developmental delay (GDD). Results Nineteen patients were enrolled: 17 (89.5%) unrelated and 2 (10.5%) familial. Twelve (63.2%) were females. Developmental epileptic encephalopathy (DEE) was observed in 18 (94.7%) patients and ID alone in 1 (5.3%) individual. Thirteen patients (68.4%) had profound ID/GDD, 4 (23.53%) severe, 1 (5.9%) moderate and 1 (5.9%) mild. Three patients (15.8%) with profound ID died. A total of 19 variants were detected: pathogenic (n = 15) and likely pathogenic (n = 4). Seven were novel variants: c.664-1G>-, M486R, H245N, H498Pfs*44, L41R, L410del, and D90H. Of the 8 previous reported variants, 2 were recurrent: R406C and R292C. Anti-seizure medications were used in combinations, and 7 patients became seizure-free, and most of them achieved seizure freedom within the first 2 years of life irrespective of the type of the mutation. Effective medications for the seizure-free individuals included adrenocorticotropic (ACTH) and/or levetiracetam and/or phenobarbital and/or sodium valproate and/or topiramate and/or vigabatrin and/or nitrazepam. There was no correlation between the types of pathogenic variants and the phenotypes. Conclusion Our case-series showed that there is no genotype-phenotype correlation in patients with STXBP1-related disorders. This study adds 7 novel variants which expand the spectrum of STXBP1-related disorders. Combinations of levetiracetam and/or sodium valproate and/or ACTH and/or phenobarbital and/or vigabatrin and/or topiramate and/or nitrazepam were more often associated with seizure freedom in our cohort within 2 years of life.

M50 bearing steel, as a typical high-carbon and high-alloy steel, exhibits low cold working capacity with high susceptibility to produce voids during the ring rolling process. In this paper, the deformation behavior and microstructure evolution during the pulse electro-assisted tensile of M50 bearing steel was studied. The results show that the maximum flow stress of the pulse electro-assisted deformation (PEAD) specimen decreases by 24.4% compared with that of the traditional deformation (TD) specimen. However, the section shrinkage rate of the PEAD specimen is increased by 32.2%, which is even higher than that of the hot deformation (HD) specimens. This indicates the positive role of pulse current on the increase of plasticity. Besides, a constitutive model of the PEAD process was established by fitting the experimental data. With the assistance of pulse current, the deformation resistance and work hardening are reduced, so the number of voids is significantly reduced due to the easier metal flow. Moreover, the energy barrier of recrystallized grain nucleation is decreased, while the nucleation rate is increased under pulse current. As a result, the occurrence of recrystallization leads to the reduction of average grain size from 4.51 μm to 1.62 μm. According to the high-resolution transmission electron microscopy (HRTEM) and electron backscatter diffraction (EBSD) characterizations, the dislocation density decreases by 24% under the applied current, which should be ascribed to the increase of atomic flux and lattice diffusion coefficient. This work provides a new idea for solving the plastic deformation problem of M50 bearing steel.

Objective: Previous studies are insufficient to confirm a causal association between physical activity (PA) and low back pain (LBP), intervertebral disc degeneration (IDD), and sciatica. The present study used a two-sample Mendelian randomization (MR) analysis method to demonstrate whether or not there was a causal connection.Methods: First, four PA phenotypes were selected [accelerometer-based PA (average acceleration), accelerometer-based PA (acceleration fraction >425 mg), self-reported moderate-to-vigorous PA, and self-reported vigorous PA], setting thresholds for single nucleotide polymorphisms (SNPs) significantly concerned with PA p < 5 × 10−8, linkage disequilibrium (LD) r2 < 0.01, genetic distance >5,000 kb, and F-value >10. SNPs associated with the outcome and confounding factors were then excluded using the PhenoScanncer database. Finally, after coordinating the genetic instruments from genome-wide association studies (GWAS) effect alleles for exposure and outcomes, multiplicative random effects inverse variance weighting (IVW), MR-Egger, weighted median method (WMM), and weighted mode method were used to assess exposure-outcome causality and perform sensitivity analysis on the estimated results.Results: The current study’s IVW findings revealed proof of a causal connection between PA and LBP. While there was a positive causal tie between accelerometer-based PA (acceleration fraction >425 mg) and LBP [OR: 1.818, 95% CI:1.129–2.926, p = 0.012], there was a negative causal link between accelerometer-based PA (average acceleration) and LBP [OR: 0.945, 95% CI: 0.909–0.984, p = 0.005]. However causal relationship between PA and IDD or sciatica was not found.Conclusion: Increasing average PA but needing to avoid high-intensity PA may be an effective means of preventing low back pain. Although PA is not directly causally related to disc degeneration and sciatica, it can act through indirect pathways.

Due to the lack of statistical methods, few studies have investigated the spatial autocorrelated distribution in the association between short-term exposure to PM2.5 and mortality and used a statistical manner to explore the association-clustered regions, which play important roles in identifying high-sensitivity/susceptibility regions. The Sichuan Basin (SCB) is one of the most PM2.5-polluted areas, and the extreme economic imbalance may cause considerable spatial heterogeneity and clustering in PM2.5-mortality association. In this work, we used a recently proposed strategy by us to investigate the spatially autocorrelated and clustered association between daily PM2.5 and cardiorespiratory mortality from 2015 to 2019 in 130 counties of the SCB. First, generalized additive models were independently constructed to obtain the county-level association estimations. Then, an estimation-error-based spatial scan statistic was used to detect the association-clustered regions. Third, multivariate conditional meta autoregression was used to obtain the spatially autocorrelated association distribution, based on which the attributable deaths were mapped and their inequality was evaluated using the Gini coefficient and Lorenz curve. Results showed that two significantly association-clustered regions were detected. One is mainly located in the megacity Chengdu where PM2.5 presented a significantly stronger association with no threshold effect at low-level PM2.5 but a threshold at high-level PM2.5. In the other cluster, a threshold effect at low-level PM2.5 but no threshold at high-level PM2.5 were found. The mortality risk at low/middle-level PM2.5 decreased from Chengdu as the center to the surrounding areas. A total of 29,129 (2.0 %) deaths were attributable to the excess PM2.5 exposure. The attributable deaths also decreased from Chengdu as the center to the surrounding areas with Gini coefficients of 0.43 and 0.3 for absolute and relative attributable deaths, respectively. This novel strategy provided a new epidemiological perspective regarding the association and implicated that Chengdu is significantly deserving of more attention regarding PM2.5-related health loss.

BackgroundHand, foot and mouth disease (HFMD) is a public health concern that threatens the health of children. Accurately forecasting of HFMD cases multiple days ahead and early detection of peaks in the number of cases followed by timely response are essential for HFMD prevention and control. However, many studies mainly predict future one-day incidence, which reduces the flexibility of prevention and control.MethodsWe collected the daily number of HFMD cases among children aged 0-14 years in Chengdu from 2011 to 2017, as well as meteorological and air pollutant data for the same period. The LSTM, Seq2Seq, Seq2Seq-Luong and Seq2Seq-Shih models were used to perform multi-step prediction of HFMD through multi-input multi-output. We evaluated the models in terms of overall prediction performance, the time delay and intensity of detection peaks.ResultsFrom 2011 to 2017, HFMD in Chengdu showed seasonal trends that were consistent with temperature, air pressure, rainfall, relative humidity, and PM10. The Seq2Seq-Shih model achieved the best performance, with RMSE, sMAPE and PCC values of 13.943~22.192, 17.880~27.937, and 0.887~0.705 for the 2-day to 15-day predictions, respectively. Meanwhile, the Seq2Seq-Shih model is able to detect peaks in the next 15 days with a smaller time delay.ConclusionsThe deep learning Seq2Seq-Shih model achieves the best performance in overall and peak prediction, and is applicable to HFMD multi-step prediction based on environmental factors.

Osteosarcoma survival rates have been largely unchanged for several decades, and treatment response is variable. Here, the authors analyzed genomic, transcriptomic and epigenomic data from 121 osteosarcoma patients and identify subtypes related to treatment outcome.

Abstract Two‐dimensional transition metal dichalcogenides (2D TMDs) present promising applications in various fields such as electronics, optoelectronics, memory devices, batteries, superconductors, and hydrogen evolution reactions due to their regulable energy band structures and unique properties. For emerging spintronics applications, materials with excellent room‐temperature ferromagnetism are required. Although most transition metal compounds do not possess room‐temperature ferromagnetism on their own, they are widely modified by researchers using the emerging strategies to engineer or modulate their intrinsic properties. This paper reviews recent enhancement approaches to induce magnetism in 2D TMDs, mainly using doping, vacancy defects, composite of heterostructures, phase modulation, and adsorption, and also by electron irradiation induction, O plasma treatment, etc. On this basis, the produced effects of these methods for the introduction of magnetism into 2D TMDs are compressively summarized and constructively discussed. For perspective, research on magnetic doping techniques for 2D TMDs materials should be directed toward more reliable and efficient directions, such as exploring advanced design strategies to combine dilute magnetic semiconductors, antiferromagnetic semiconductors, and superconductors to develop new types of heterojunctions; and advancing experimentation strategies to fabricate the designed materials and enable their functionalities with simultaneously pursuing the upscalable growth methods for high‐quality monolayers to multilayers.

BackgroundGenotype–phenotype correlations of the CACNA1A-related neurodevelopmental disorders such as global developmental delay (GDD)/intellectual disability (ID), epileptic encephalopathy (EE), and autism spectrum disorder (ASD) are unknown. We aimed to summarize genotype–phenotype correlations and potential treatment for CACNA1A-related neurodevelopmental disorders.MethodsSix children diagnosed with CACNA1A-related neurodevelopmental disorders at Xiangya Hospital, Central South University from April 2018 to July 2021 were enrolled. The PubMed database was systematically searched for all reported patients with CACNA1A-related neurodevelopmental disorders until February 2023. Thereafter, we divided patients into several groups for comparison.ResultsSix patients were recruited from our hospital. Three cases presented with epilepsy, five with GDD/ID, five with ataxia, and two with ASD. The variants included p.G701R, p.R279C, p.D1644N, p.Y62C, p.L1422Sfs*8, and p. R1664Q [two gain-of-function (GOF) and four loss-of-function (LOF) variants]. About 187 individuals with GDD/ID harboring 123 variants were found (case series plus data from literature). Of those 123 variants, p.A713T and p.R1664* were recurrent, 37 were LOF, and 7 were GOF. GOF variants were linked with severe-profound GDD/ID while LOF variants were associated with mild–moderate GDD/ID (p = 0.001). The p.A713T variant correlated with severe-profound GDD/ID (p = 0.003). A total of 130 epileptic patients harboring 83 variants were identified. The epileptic manifestations included status epilepticus (n = 64), provoked seizures (n = 49), focal seizures (n = 37), EE (n = 29), absence seizures (n = 26), and myoclonic seizures (n = 10). About 49 (42.20%) patients had controlled seizures while 67 (57.80%) individuals remained with refractory seizures. Status epilepticus correlated with variants located on S4, S5, and S6 (p = 0.000). Among the 83 epilepsy-related variants, 23 were recurrent, 32 were LOF, and 11 were GOF. Status epilepticus was linked with GOF variants (p = 0.000). LOF variants were associated with absence seizures (p = 0.000). Six patients died at an early age (3 months to ≤5 years). We found 18 children with ASD. Thirteen variants including recurrent ones were identified in those 18 cases. GOF changes were more linked to ASD.ConclusionThe p.A713T variant is linked with severe-profound GDD/ID. More than half of CACNA1A-related epilepsy is refractory. The most common epileptic manifestation is status epilepticus, which correlates with variants located on S4, S5, and S6.

Abstract Background CHKB mutations have been described in 49 patients with megaconial congenital muscular dystrophy, which is a rare autosomal recessive disorder, of which 40 patients showed homozygosity. Methods Peripheral blood genomic DNA samples were extracted from patients and their parents and were tested by whole exome sequencing. Quantitative PCR was performed to detect deletion. Single nucleotide polymorphism analysis was performed to identify uniparental disomy. Quantitative PCR and western blot were used to measure the expression level of CHKB in patient 1‐derived immortalized lymphocytes. Mitochondria were observed in lymphocytes by electron microscopy. Results Two unrelated cases born to non‐consanguineous parents were diagnosed with megaconial congenital muscular dystrophy due to apparently homozygous mutations (patient 1: c.225‐2A>T; patient 2: c.701C>T) in the CHKB gene using whole exome sequencing. Quantitative PCR revealed that patient 1 had a large deletion encompassing the CHKB gene, inherited from the mother. Single nucleotide polymorphism analysis revealed patient 2 had paternal uniparental isodisomy containing the CHKB gene. In the immortalized lymphocytes from patient 1, decreased expression of CHKB was revealed by quantitative PCR and western blot, and giant mitochondria were observed using electron microscopy. Conclusion We provide a possibility to detect giant mitochondria in other cells when muscle was not available. Moreover, clinicians should be aware that homozygous variants can be masqueraded by uniparental disomy or large deletions in offspring of non‐consanguineous parents, and excessive homozygosity may be misdiagnosed.

BackgroundSeveral studies have examined the effects of city-level meteorological conditions on the associations between meteorological factors and hand, foot, and mouth disease (HFMD) risk. However, evidence that city-level meteorological conditions modify air pollutant-HFMD associations is lacking.MethodsFor each of the 17 cities in the Sichuan Basin, we obtained estimates of the relationship between exposures to multiple air pollutants and childhood HFMD risk by using a unified distributed lag nonlinear model (DLNM). Multivariate meta-regression models were used to identify the effects of city-level meteorological conditions as effect modifiers. Finally, we conducted subgroup analyses of age and sex to explore whether the modification effects varied in different subgroups.ResultsThe associations between PM2.5/CO/O3 and HFMD risk showed moderate or substantial heterogeneity among cities (I2 statistics: 48.5%, 53.1%, and 61.1%). Temperature conditions significantly modified the PM2.5-HFMD association, while relative humidity and rainfall modified the O3-HFMD association. Low temperatures enhanced the protective effect of PM2.5 exposure against HFMD risk [PM2.5 100 μg/m3, at the 99th percentile: relative risk (RR) = 0.14, 95% CI: 0.03–0.60]. Low relative humidity increased the adverse effect of O3 exposure on HFMD risk (O3 >128.7 μg/m3, at the 99th percentile: RR = 2.58, 95% CI: 1.48–4.50). However, high rainfall decreased the risk of HFMD due to O3 exposure (O3: 14.1–41.4 μg/m3). In addition, the modification effects of temperature and relative humidity differed in the female and 3–5 years-old subgroups.ConclusionOur findings revealed moderate or substantial heterogeneity in multiple air pollutant-HFMD relationships. Temperature, relative humidity, and rainfall modified the relationships between PM2.5 or O3 exposure and HFMD risk.

Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare subtype of follicular dendritic cell sarcoma (FDCS) that primarily occurs in the liver and spleen. The etiology of IPT-like FDCS is unknown, and it has nonspecific clinical manifestations, imaging performance and laboratory test results. Recently, a patient with IPT-like FDCS was admitted to our hospital because of abdominal distension and anemia. Over the past 3 years, the patient has been followed up after a liver mass was found in a physical examination. The lesion gradually enlarged and caused compression symptoms. In November 2022, a tumor with a diameter of approximately 20 cm was found in the right posterior lobe of the liver after abdominal enhanced Magnetic resonance imaging (MRI) in our hospital. Liver tumor biopsy before the operation revealed a large number of hyperplastic plasma cells and a small number of spindle cells, and the spindle cells were atypical. After a complete examination, the patient underwent liver resection. Pathology after surgery confirmed liver IPT-like FDCS.

Abstract Background HCFC1 encodes transcriptional co‐regulator HCF‐1, which undergoes an unusual proteolytic maturation at a centrally located proteolysis domain. HCFC1 variants were associated with X‐linked cobalamin metabolism disorders and mental retardation‐3. This study aimed to explore the role of HCFC1 variants in common epilepsy and the mechanism underlying phenotype heterogeneity. Methods Whole‐exome sequencing was performed in a cohort of 313 patients with idiopathic partial (focal) epilepsy. Functional studies determined the effects of the variants on the proteolytic maturation of HCF‐1, cell proliferation and MMACHC expression. The role of HCFC1 variants in partial epilepsy was validated in another cohort from multiple centers. Results We identified seven hemizygous HCFC1 variants in 11 cases and confirmed the finding in the validation cohort with additional 13 cases and six more hemizygous variants. All patients showed partial epilepsies with favorable outcome. None of them had cobalamin disorders. Functional studies demonstrated that the variants in the proteolysis domain impaired the maturation by disrupting the cleavage process with loss of inhibition of cell growth but did not affect MMACHC expression that was associated with cobalamin disorder. The degree of functional impairment was correlated with the severity of phenotype. Further analysis demonstrated that variants within the proteolysis domain were associated with common and mild partial epilepsy, whereas those in the kelch domain were associated with cobalamin disorder featured by severe and even fatal epileptic encephalopathy, and those in the basic and acidic domains were associated with mainly intellectual disability. Conclusion HCFC1 is potentially a candidate gene for common partial epilepsy with distinct underlying mechanism of proteolysis dysfunction. The HCF‐1 domains played distinct functional roles and were associated with different clinical phenotypes, suggesting a sub‐molecular effect. The distinct difference between cobalamin disorders and idiopathic partial epilepsy in phenotype and pathogenic mechanism, implied a clinical significance in early diagnosis and management.

ObjectiveTo investigate the pathogenesis of three novel de novo CACNA1C variants (p.E411D, p.V622G, and p.A272V) in causing neurodevelopmental disorders and arrhythmia.MethodsSeveral molecular experiments were carried out on transfected human embryonic kidney 293 (HEK 293) and Chinese hamster ovary (CHO) cells to explore the effects of p.E411D, p.V622G, and p.A272V variants on electrophysiology, mitochondrial and lysosomal functions. Electrophysiological studies, RT-qPCR, western blot, apoptosis assay, mito-tracker fluorescence intensity, lyso-tracker fluorescence intensity, mitochondrial calcium concentration test, and cell viability assay were performed. Besides, reactive oxygen species (ROS) levels, ATP levels, mitochondrial copy numbers, mitochondrial complex I, II, and cytochrome c functions were measured.ResultsThe p.E411D variant was found in a patient with attention deficit-hyperactive disorder (ADHD), and moderate intellectual disability (ID). This mutant demonstrated reduced calcium current density, mRNA, and protein expression, and it was localized in the nucleus, cytoplasm, lysosome, and mitochondria. It exhibited an accelerated apoptosis rate, impaired autophagy, and mitophagy. It also demonstrated compromised mitochondrial cytochrome c oxidase, complex I, and II enzymes, abnormal mitochondrial copy numbers, low ATP levels, abnormal mitochondria fluorescence intensity, impaired mitochondrial fusion and fission, and elevated mitochondrial calcium ions. The p.V622G variant was identified in a patient who presented with West syndrome and moderate global developmental delay. The p.A272V variant was found in a patient who presented with epilepsy and mild ID. Both mutants (p.V622G and p.A272V) exhibited reduced calcium current densities, decreased mRNA and protein expressions, and they were localized in the nucleus, cytoplasm, lysosome, and mitochondria. They exhibited accelerated apoptosis and proliferation rates, impaired autophagy, and mitophagy. They also exhibited abnormal mitochondrial cytochrome c oxidase, complex I and II enzymes, abnormal mitochondrial copy numbers, low ATP, high ROS levels, abnormal mitochondria fluorescence intensity, impaired mitochondrial fusion and fission, as well as elevated mitochondrial calcium ions.ConclusionThe p.E411D, p.V622G and p.A272V mutations of human CACNA1C reduce the expression level of CACNA1C proteins, and impair mitochondrial and lysosomal functions. These effects induced by CACNA1C variants may contribute to the pathogenesis of CACNA1C-related disorders.

IntroductionDestruxin A (DA) is a mycotoxin isolated from the entomopathogenic fungus Metarhizium anisopliae which has demonstrated inhibitory activity against various insect species. However, the mechanism of inhibition on target sites in insects remains unknown.MethodsIn this research, the dose-response relationship between DA and morphological changes in body tissues and organs of domestic silkworm, Bombyx mori, were investigated by histopathological methods to identify the target sites that responded to DA.Results and DiscussionThe results showed that responses of individual tissues and organs varied with DA dosage and treatment time. At low doses (i.e., 0.01μg/g), the hemocytes were the most sensitive to DA with morphological changes apparent at 6 h after treatment. However, the muscle cells, fat body, and Malpighian tubules were unaltered. At higher doses (i.e., > 0.1μg/g), morphological changes were observed in muscle cells, fat body, and Malpighian tubules at 24 h after treatment. The results indicated that DA can be an immunosuppressant by damaging host cells like hemocytes, and at higher doses may potentially impact other physiological processes, including muscle function, metabolism, and excretion. The information presented in the current study will facilitate development of mycopesticides and novel immunosuppressants.

Plutella xylostella, a destructive crucifer pest, can rapidly develop resistance to most classes of pesticides. This study investigated the molecular resistance mechanisms to chlorpyrifos, an organophosphate pesticide. Two P. xylostella genes, ace1 and ace2, were described. The nucleotide sequence results revealed no variation in ace2, while the resistant strain (Kar-R) had four amino acid alterations in ace1, two of which (A298S and G324A) were previously shown to confer organophosphate resistance in P. xylostella. In the present study, the 3D model structures of both the wild-type (Gu-S) and mutant (Kar-R) of P. xylostella ace1 strains were studied through molecular dynamics (MDs) simulations and molecular docking. Molecular dynamics simulations of RMSD revealed less structural deviation in the ace1 mutant than in its wild-type counterpart. Higher flexibility in the 425–440 amino acid region in the mutant active site (Glu422 and Acyl pocket) increased the active site’s entropy, reducing the enzyme’s affinity for the inhibitors. Gene expression analysis revealed that the relative transcription levels of ace1 were significantly different in the Kar-R strain compared with the Gu-S strain. This study enhances the understanding of the mechanisms governing ace1′s resistance to insecticide and provides essential insights for new insecticides as well as valuable insights into environmentally conscious pest management techniques.

Ultrasonic shot peening (USP) is a surface treatment technology used in the mechanical properties strengthening of the engineering material and components during manufacturing. TC4 titanium alloy is a commonly used engineering material in the aerospace industry. In this study, a gradient nanostructured surface layer was successfully fabricated on the TC4 titanium alloy via USP technology at room temperature. The microstructure evolution of TC4 titanium alloy during USP was investigated. The surface microhardness was elevated from 330 HV to 438 HV with a penetrating depth of around 900 μm after USP with the duration of 8 min. EBSD characterization results confirmed the presence of high-density grain boundaries within the gradient structure in the region of 0–200 μm, accompanied by proliferation of dislocation density. TEM characterization indicated a substantial amount of nanograin with an average size of 74.58 nm. Furthermore, the USP process was also investigated by the finite element method to evaluate the surface-strengthening effect. The calculated maximum residual stress reached 973 MPa after multi-ball impact. The impact behavior of the shots during the USP process was studied. The effect of the parameters on the USP strengthening intensity was explored based on the validated model. This work provided a clearer understanding of the USP strengthening process of TC4 titanium alloy through an effective method of evaluating the process parameters.

Abstract Background Epidemiological studies have investigated the short-term effects of meteorological factors and air pollution on the incidence of hand, foot, and mouth disease (HFMD). Several meteorological indicators, such as relative humidity and the diurnal temperature range (DTR), significantly modify the relationship between short-term exposure to temperature and HFMD incidence. However, it remains unclear whether (and how) long-term air pollution levels modify the short-term relationships of HFMD incidence with meteorological factors and air pollution. Methods We obtained daily data on meteorological factors, air pollutants, and HFMD counts in children from 21 prefecture-level cities in Sichuan Province in Southwest China from 2015 to 2017. First, we constructed a distributed lag nonlinear model (DLNM) at each prefecture-level site to evaluate the short-term impacts of meteorological variables and air pollutants on HFMD incidence. Then, we assessed the pooled effects of the exposures and incorporated long-term city-specific air pollutant indicators as meta-predictors to examine their potential modification effects by performing multivariate meta-regression models. Results We found that long-term SO2 and CO concentrations significantly modified the short-term relationships between climatic variables and HFMD incidence. Specifically, high concentrations of CO (P = 0.027) and SO2 (P = 0.039) reduced the risk of HFMD at low temperatures. The relationship between relative humidity and HFMD incidence was weakened at high SO2 concentrations (P = 0.024), especially when the relative humidity was below the median level. When the minimum relative humidity (32%) was compared to the median relative humidity (77%), the risk ratio (RR) was 0.77 (95% CI: 0.51–1.17) in the 90th percentile of SO2 (19.6 μg/m3) and 0.41 (95% CI: 0.27–0.64) in the 10th percentile of SO2 (10.6 μg/m3). Conclusion Our results indicated that long-term SO2 and CO levels modified the short-term associations between HFMD incidence in children and meteorological variables. These findings may inform health authorities to optimize targeted public health policies including reducing ambient air pollution and reinforcing self-protective actions to weaken the adverse health impacts of environmental factors on HFMD incidence.

Background Severe multiple trauma prevalence has been increasing recently, which has become the leading cause of labor force loss. Early and rapid assessment of patients' conditions will greatly affect their prognosis, which could be significantly supported by a concise and effective visual scoring system. Objective To identify and Screen the prognostic factors of severe multiple trauma, and use them to develop two nomograms, then improve them, and verify their clinical application values. Methods Patients with severe multiple trauma were recruited from the general ICU and EICU, Suzhou Ninth People's Hospital, including 321 treated during December 2015 to December 2020 (model group) , and 136 treated during January to August 2021 (validation group) . General data at admission and clinical data within 24 hours of admission were retrospectively collected. Prognosis (successful or unsuccessful treatment result) was assessed at discharge. Prognostic factors of severe multiple trauma were Screened using univariate and LASSO regression, and used to develop models using multivariate Logistic regression with restricted cubic splines, then based on this, two nomograms were developed, and their calibration accuracies were estimated using the bootstrap approach and decision curve analysis (DCA) . The receiver operating characteristic (ROC) analysis with associated AUC values was used to estimate the prognostic value of two nomograms in severe multiple trauma. External verification of the nomograms was carried out in the validation group to evaluate their clinical application values. Results (1) In the model group, successful and unsuccessful treatment results occurred in 244 and 77 cases, respectively. LASSO regression with multivariate Logistic regression analyses showed that age (OR=1.028) , Glasgow Coma Score (GCS) (OR=0.616) , arterial lactate (OR=1.202) , platelet count (OR=3.888) and Injury Severity Score (ISS) (OR=1.104) were associated with the prognosis of severe multiple trauma (P

At present, most machine learning bathymetry retrieval models use the band reflectance as the inversion feature only, without considering features related to the water substrate and pixel spatial correlation. In this study, in addition to band reflectance, two features, Depth-Invariant Index (DII) and pixel location, are taken into account. Two machine learning algorithms, Random Forest (RF) and Back Propagation (BP) neural network are used to retrieve bathymetry. The effects of the two features on the accuracy and performance of bathymetry retrieval are explored. The results show that: (i) Machine learning algorithms are generally superior to the widely used Stumpf model. Stumpf model performs better only in the depth range of 8–16 m, with a Root Mean Square Error (RMSE) of 0.85 m, but has poor performance in other depth ranges. (ii) Compared with models that use Band Reflectance (BR) only, DIIb,g (blue-green DII) + BR model, Location and Location + BR models are all superior to the BR model for RF and BP algorithms. It means that DII and location features are very effective in improving the bathymetry retrieval accuracy.