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Abstract The incidence of Early-Onset Colorectal Cancer (EOCRC) is increasing. However, the prognosis of EOCRC compared to Late-Onset Colorectal Cancer (LOCRC), and the ideal age for initial colorectal cancer (CRC) screening are not clear. In this study, we identified the pathological differences between the groups and determined the optimal screening age for CRC patients. We included 10,172 patients diagnosed with CRC from January 2011 to December 2021 in this study. Survival differences were compared by plotting Kaplan–Meier survival curves and conducting landmark analysis. Additionally, the diagnostic age of CRC patients was analyzed using age cumulative curves. Compared to LOCRC patients, EOCRC patients had a higher proportion of deficient mismatch repair (dMMR) and more advanced TNM staging (P

Abstract Some studies have identified influencing factors of COVID-19 illness in elderly, such as underlying diseases, but research on the effect of nutritional status is still lacking. This study retrospectively examined the influence of nutritional status on the outcome of elderly COVID-19 inpatients. A retrospective analysis of the clinical data of 4241 COVID-19 patients who were admitted to a third-class hospital of Nanchang between November 1, 2022 and January 31, 2023 was conducted. Nutritional status was assessed using the prognostic nutritional index (PNI) and controlling nutritional status score (CONUT). The influence of nutritional status on the outcome of COVID-19 patients was determined through multivariate adjustment analysis, restrictive cubic spline, and receiver operating characteristic curve (ROC). Compared with mild/no malnutrition, severe malnutrition substantially increased the critical outcome of COVID-19. A linear relationship was observed between the odds ratio (OR) and PNI and CONUT (P > 0.05). The area under the ROC curve indicated that PNI was the better predictor. The optimal cutoff value of PNI was 38.04 (95%CI: 0.797 ~ 0.836, AUC = 0.817), with a sensitivity of 70.7% and a specificity of 79.6%. The critical illness of elderly COVID-19 patients shows a linear relationship with malnutrition at admission. The use of PNI to assess the prognosis of COVID-19 eldeely patients is reliable, highlighting the importance for doctors to closely pay attention to the nutritional status of COVID-19 patients. Focusing on nutritional status in clinical practice can effectively reduce the critical illness of elderly COVID-19 patients.

Abstract Background Stroke-associated pneumonia (SAP) is a common complication in stroke patients, and the Barthel Index (BI) is a well-established metric for assessing activities of daily living (ADL). However, the association between BI and SAP in acute ischemic stroke (AIS) patients remains unclear. This study aims to investigate the relationship between BI at admission and SAP, and explore the factors in AIS elderly patients. Method Retrospective data were collected from ischemic stroke patients hospitalized at the Second Affiliated Hospital of Nanchang University between January 2018 and July 2021, including their basic demographic and laboratory test results. Restricted cubic spline regression, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were employed to investigate the relationship between BI and SAP. Additionally, the Shapley Additive exPlanations (SHAP) method was used to identify the factors influencing SAP. Results The study included 7,548 eligible stroke patients with a mean age of 75.1 ± 7.6 years, among which 41.14% were female. The SAP group demonstrated significantly lower BI compared to the non-SAP group (50.86 ± 35.60 vs. 75.27 ± 26.33, P

Abstract Younger premenopausal women are more prone to developing ovarian metastases (OM) of gastric cancer (GC) than metastases of other organs; however, the molecular mechanisms remain unclear. Here we perform single-cell RNA sequencing on 45 tumor samples from 18 GC patients with OM. Interestingly, fibroblasts in OM of GC express high levels of estrogen receptor (ER) and midkine (MDK), interacting with tumor cells through activating ER-MDK-LRP1 (low-density lipoprotein receptor-related protein 1) signaling axis. Functional experiments demonstrate that estrogen stimulation induces MDK secretion by ovarian fibroblasts, and binding of MDK to LRP1 increases GC cell migration and invasion. Furthermore, in vivo, estrogen stimulation remarkably augments ovarian engraftment and metastasis of LRP1+ GC cells. Collectively, our findings reveal that ER+ ovarian fibroblasts secrete MDK under estrogen influence, driving OM of GC via the MDK-LRP1 axis. Our study holds the potential to catalyze innovative therapeutic strategies aimed at intercepting and managing OM in GC.

Abstract Background Many studies have shown that adverse childhood experiences (ACEs) lead to adverse social relations in middle-aged and older adults and harm physical and mental health, but few studies have focused on the impact of ACEs on marital status in middle-aged and older adults and the potential influence of marital status between ACEs and depressive symptoms. Purpose This study aimed to analyze the effect of ACEs on marital status and depressive symptoms in the Chinese middle-aged and older adults, and to explore the mediating role of marital status in the association between ACEs and depressive symptoms in middle-aged and older adults. Method This study used the China Health and Retirement Longitudinal Study (CHARLS) 2014 life history survey and 2015 and 2018 follow-up data to analyze, ten ACEs conditions and marital status were collected by questionnaire, using the Center for Epidemiological Studies Depression Scale (CESD-10) 10-item short form to assess depressive symptoms. The association between cumulative ACEs and marital status was assessed by constructing a multinomial logistic regression (MLR) model, as well as a binary logistic regression model to assess the association between ACEs and depressive symptoms. The mediating role of marital status in the association between ACEs and depressive symptoms was also assessed. Results A total of 10,246 individuals aged 45 years or older were included in the analysis. Compared to individuals who did not experience ACEs, those who experienced two or more ACEs had a higher risk of being unmarried (seperated/divorced/never married) (OR = 1.67, 95% CI=[1.10,2.51]) and a higher risk of depressive symptoms (OR = 1.66, 95% CI=[1.49,1.84]) in middle and old age. Unmarried status partially mediated the association of ACEs with depressive symptoms. Conclusion Chinese middle-aged and older people who experienced two or more ACEs have higher risks of unmarried status and depressive symptoms, and unmarried status partially mediated the ACEs-depressive symptom association. These findings reveal the fact that we need to develop life-cycle public health strategies to reduce exposure to ACEs and society should give more attention to the marital status of older people, thereby reducing the risk of depression among middle-aged and older adults in China.

Abstract Background Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. Methods The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. Results We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient’s imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. Conclusions Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.

On September 5, 2022, the Luding M6.8 earthquake occurred in the Moxi-Shimian segment of the Xianshuihe fault, coinciding with the historical ruptured zone of the 1786 Moxi earthquake. Its seismogenic environment provides a foundation for comprehending the mechanism of the earthquake and its future hazard. In the Moxi-Shimian segment, we establish a series of near-field Global Navigation Satellite Systems (GNSS) stations to enhance the spatial resolution of observational data for the inversion of the interseismic kinematic parameters. In this study, with an elastic screw dislocation model constrained by GNSS observations, the slip rate of the Moxi-Shimian segment is estimated to be 10.9 ± 1.0 mm/yr, while the locking depth is 15.7 ± 6.2 km. Additionally, we utilize a block-dislocation model to invert the interseismic fault coupling along the Kangding-Moxi-Shimian segment. The result indicates a gradual deepening of the locking depth along the section from Kangding to Shimian. The coseismic rupture of the 2022 event occurred within the high coupling regions in the Kangding-Moxi-Shimian segment, which indicates that the rupture kinematics in this event might be controlled by the interseismic deformation. The seismic moment accumulated within the ruptured zone of the Luding earthquake since 1786 ranges in [1.42–3.40] × 1019 N·m, which is significantly greater than the seismic moment released during the 2022 event. As a result, we infer that the Luding earthquake released only a portion of the accumulated energy within the original rupture zone since 1786, indicating that the 2022 event has not caused a complete rupture in the Moxi-Shimian segment. Consequently, there remains a substantial seismic hazard in this area.

Abstract Background Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality. Methods We collected a prospective study cohort of 110 stage I–II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation. Results Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942–0.982) in the study cohort, 0.972 (95% CI: 0.953–0.992) in the first validation cohort and 0.937 (95% CI: 0.890–0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified. Conclusions We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer. Trial registration This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.

Largemouth bass (Micropterus salmoides, LB) is an important aquaculture and fishing species in the world. LB has been introduced into China since 1983, and its aquaculture production has increased year by year. The total yield of LB in China reached 802,486 tons in 2022, ranking seventh in China's freshwater fish aquaculture. However, the LB is facing threats such as degradation of germplasm resources and disease susceptibility due to limitations in the scale of introduction, coupled with the effects of high-density aquaculture, inbreeding, and species hybridization. This paper summarizes the current status of LB germplasm resources, variety genetic improvement, nutrition and fodder, aquaculture mode and diseases, and circulation and processing. This paper also provides recommendations on how to fully explore and utilize the existing germplasm resources of LB; culture new LB germplasm that combines excellent resistance and growth characteristics through innovations in breeding techniques; reduce the morbidity rate and improve the efficiency of cultured LB through the optimization of fodder formulations and innovation of aquaculture modes; and shift the processing of LB toward standardization, efficient nutrition and safety through the integration of high-tech and large-scale production. This paper provides a reference for the sustainable and healthy development of the LB industry.

BackgroundPostoperative fever frequently indicates surgical complications and is commonly used to evaluate the efficacy of interventions against surgical stress. However, the presence of circadian rhythms in body temperature may compromise the accurate detection of fever. ObjectiveThis study aimed to investigate the detection rate of fever under intermittent measurement. MethodsWe retrospectively reviewed the clinical records of patients who underwent nonemergency gastrointestinal surgery between November 2020 and April 2021. Patients’ temperature data were continuously collected every 4 seconds using a wireless axillary thermometer, and fever was defined as a temperature exceeding 38 °C within a day. To simulate intermittent measurement in clinical practice, the body temperature at each hour was selected from the continuously collected temperature dataset. Considering that temperatures are measured multiple times per day, all possible measurement plans using intermittent measurement were composed by combining 1-24 time points from the 24-hour daily cycle. Fever was clinically diagnosed based on the temperature readings at the selected time points per day. The fever detection rates for each plan, with varying measurement times, were listed and ranked. ResultsBased on the temperature data continuously collected by the thermometer, fever occurred in 60 (40.8%) of the 147 included patients within 3 days after surgery. Of the measurement plans that included 1-24 measurements daily, the fever detection rates ranged from 3.3% (2/60) to 85% (51/60). The highest detection rates and corresponding timings for measurement plans with 1, 2, 3, and 4 measurements daily were 38.3% (23/60; at 8 PM), 56.7% (34/60; at 3 AM and 7 or 8 PM), 65% (39/60; at 3 AM, 8 PM, and 10 or 11 PM), and 70% (42/60; at 12 AM, 3 AM, 8 PM, and 11 PM), respectively; and the lowest detection rates were 3.3% (2/60), 6.7% (4/60), 6.7% (4/60), and 8.3% (5/60), respectively. Although fever within 3 days after surgery was not correlated with an increased incidence of postoperative complications (5/60, 8.3% vs 6/87, 6.9%; P=.76), it was correlated with a longer hospital stay (median 7, IQR 6-9 days vs median 6, IQR 5-7 days; P

Background: RNA modifications represent a novel category of biological molecule alterations, characterized by three primary classes of proteins: writers, erasers, and readers. Numerous studies indicate that the dysregulation of these RNA modifications is linked to cancer development and may offer new therapeutic avenues for treatment. In our research, we focused on eight specific genes associated with RNA modifications (RMRGs) to comprehensively analyze their distinct functions in gastric cancer (GC). Furthermore, we aimed to elucidate the roles of RMRGs concerning clinicopathological characteristics, tumor microenvironment, and patient prognosis. Methods: In this study, we examined the expression and mutations of RMRGs in gastric cancer (GC) using data from TCGA-STAD (The Cancer Genome Atlas; Stomach adenocarcinoma) and the gene expression omnibus (GSE66229). We identified two subtypes of RMRGs and three gene clusters through consensus clustering analysis, assessing their differences in prognosis and immune cell infiltration patterns. Subsequently, we developed an RMRGs score to evaluate GC prognosis and highlight general immune features within the tumor microenvironment (TME). Lastly, we focused on MAMDC2 to validate its expression in GC and explore the effects of a MAMDC2 inhibitor on GC tumor cells. Results: We discovered 94 differentially expressed RMRGs common to both the TCGA-STAD and GEO datasets. Notable differences in prognosis and immune cell infiltration were observed between the two RMRGs subtypes and three gene clusters. The RMRGs score emerged as an independent prognostic factor related to the tumor microenvironment (TME) characteristics in gastric cancer (GC). Reducing MAMDC2 levels enhanced cell migration and invasion while decreasing proliferation in vitro. Conclusions: In conclusion, this study comprehensively analyzed the role of RMRGs on GC. Our study firstly proposed RMRGs score and demonstrated its potential to be biomarkers for prognosis and immune characteristics. Consequently, RMRGs score is of great clinical significance and can be utilized to develop individualized.

Abstract Ovarian metastasis is one of the major causes of treatment failure in patients with gastric cancer (GC). However, the genomic characteristics of ovarian metastasis in GC remain poorly understood. In this study, we enroll 74 GC patients with ovarian metastasis, with 64 having matched primary and metastatic samples. Here, we show a characterization of the mutation landscape of this disease, alongside an investigation into the molecular heterogeneity and pathway mutation enrichments between synchronous and metachronous metastasis. We classify patients into distinct clonal evolution patterns based on the distribution of mutations in paired samples. Notably, the parallel evolution group exhibits the most favorable prognosis. Additionally, by analyzing the differential response to chemotherapy, we identify potential biomarkers, including SALL4, CCDC105, and CLDN18, for predicting the efficacy of paclitaxel treatment. Furthermore, we validate that CLDN18 fusion mutations improve tumor response to paclitaxel treatment in GC with ovarian metastasis in vitro and vivo.

Abstract Garnet-type Li6.5La3Zr1.5Ta0.5O12 (LLZO) is considered a promising solid electrolyte, but the surface degradation in air hinders its application for all-solid-state battery. Recent studies have mainly focused on the final products of the LLZO surface reactions due to lacking of powerful in situ characterization methods. Here, we use ambient pressure X-ray spectroscopies to in situ investigate the dynamical evolution of LLZO surface in different gas environments. The newly developed ambient pressure mapping of resonant Auger spectroscopy clearly distinguishes the lithium containing species, including LiOH, Li2O, Li2CO3 and lattice oxygen. The reaction of CO2 with LLZO to form Li2CO3 is found to be a thermodynamically favored self-limiting reaction. On the contrary, the reaction of H2O with LLZO lags behind that of CO2, but intensifies at high pressure. More interestingly, the results provide direct spectroscopic evidence for the existence of Li+/H+ exchange and reveal the importance of the initial layer formed on clean electrolyte surface in determining their air stability. This work demonstrates that the newly developed in situ technologies pave a new way to investigate the oxygen evolution and surface degradation mechanism in energy materials.

Abstract Deep vein thrombosis (DVT) is a common complication in patients with lower extremity fractures. Once it occurs, it will seriously affect the quality of life and postoperative recovery of patients. Therefore, early prediction and prevention of DVT can effectively improve the prognosis of patients. This study constructed different machine learning models to explore their effectiveness in predicting DVT. Five prediction models were applied to the study, including Extreme Gradient Boosting (XGBoost) model, Logistic Regression (LR) model, RandomForest (RF) model, Multilayer Perceptron (MLP) model, and Support Vector Machine (SVM) model. Afterwards, the performance of the obtained prediction models was evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, F1 score, and Kappa. The prediction performances of the models based on machine learning are as follows: XGBoost model (AUC = 0.979, accuracy = 0.931), LR model (AUC = 0.821, accuracy = 0.758), RF model (AUC = 0.970, accuracy = 0.921), MLP model (AUC = 0.830, accuracy = 0.756), SVM model (AUC = 0.713, accuracy = 0.661). On our data set, the XGBoost model has the best performance. However, the model still needs external verification research before clinical application.

Abstract Cone‐beam computed tomography (CBCT) system can provide real‐time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Asphaltene, the heaviest and most polar non-hydrocarbon component in crude oil, may interact with waxes and affect the flow and gelation behavior of waxy oils. To further study the effect of asphaltene on the flow and gelation behavior of waxy oils, five wax-containing simulated oils with small dosage asphaltene content were prepared. Through pour point and rheometer test, it is found that asphaltenes can improve the low-temperature rheology of waxy oil. There is no critical turning point above which the low-temperature flowability improved. With an increase in asphaltene content from 0 wt% to 0.1 wt%, notable changes were observed in the properties of the waxy oil. The pour point, which measures the temperature at which the oil becomes too viscous to flow freely, exhibited a decrease from 25 ℃ to 13 ℃. Similarly, the gelation temperature, indicating the temperature at which the oil starts forming a gel-like consistency, also decreased from 29.0 ℃ to 27.1 ℃. These modifications can be attributed to the presence of asphaltene in the oil sample. This outcome can be attributed to the interference caused by the presence of asphaltenes, which disrupts the gel network structure of the waxy oil and consequently hinders its gelation process. Simultaneously, within the low asphaltene content range, an increase in asphaltene content resulted in a considerable decrease in the viscosity of the waxy oil at 10 °C, reducing it from 531.5 mPa s to 14 mPa s.

Abstract Approximately 150 Tg of water vapor and 0.42 Tg of sulfur dioxide were injected directly into the stratosphere by the January 2022 Hunga volcanic eruption, which represents the largest water vapor injection in the satellite era. A comparison of numerical simulations to balloon‐borne and satellite observations of the water‐rich plume suggests that particle coagulation contributed to the Hunga aerosol's effective dry radius increase from 0.2 μm in February to around 0.4 μm in March. Our model suggests that the stratospheric aerosol effective radius is persistently perturbed for years by moderate and large‐magnitude volcanic events, whereas extreme wildfire events show limited impact on the stratospheric background particle size. Our analysis further suggests that both the particle optical efficiency and the aerosols' stratospheric lifetime explain Hunga's unusually large aerosol optical depth per unit of the SO2 injection, as compared with the Pinatubo eruption.

Abstract Background The symptoms of functional constipation (FC) were obviously affected by mental symptoms, which was consistent with somatic symptoms. However, the characteristics of FC patients with somatic symptom remains unexplored. Methods Clinical characteristics including somatic symptom (SOM, PHQ-15), depression (PHQ-9), anxiety (GAD-7), quality of life (PAC-QOL), constipation (KESS), demographic variables, anatomical abnormalities and symptoms were investigated. Subsequent analyses encompassed the comparison of clinical parameters between patients with SOM + group (PHQ-15 ≥ 10) and SOM- group (PHQ-15

Bolts are indispensable in power systems, serving a critical function in securely fastening various components and ensuring stable operation of transmission lines. To address the challenges associated with detecting small bolt objects in images captured by unmanned aerial vehicles (UAVs), we propose an enhanced multi-scale YOLOv7 model called multi-scale YOLOv7 (MS-YOLOv7). First, a multi-scale path aggregation network (M-PANet) is developed, which seamlessly integrates multi-scale information and features four detection heads, thereby reducing the miss rate of small objects. Second, a channel-coordinate attention (CCA) mechanism is introduced to enhance the network’s focus on spatial and channel information, thereby augmenting object localization accuracy. Furthermore, in the feature fusion process, the selected convolutions are replaced with a fully self-calibrated convolutional network (FSCNet) to expand the receptive field and enable richer feature extraction. Finally, standard max pooling is replaced with space-to-depth convolution (SPD-Conv) to preserve object detail information during the downsampling phase. Experimental results on a proprietary bolt defect dataset demonstrated significant improvements over the original YOLOv7 model, with a 2.52% increase in mean Average Precision (mAP), a 3.07% improvement in recall, a 1.54% improvement in accuracy, and a 2.41% increase in F1 score. The algorithm also exhibited robust performance on the CSUST Chinese traffic sign detection benchmark (CCTSDB) dataset, demonstrating its strong generalization ability and robustness.

In a distributed scenario, the process of multiple agents collaborating and interacting with the server to iteratively implement k-means clustering analysis can be easily exploited by attackers, posing a huge privacy threat. Therefore, a local differential privacy k-means method (LDPKmeans) was proposed, which can effectively address the privacy protection problem in multi-agent systems. In this paper, we propose an effective attack method based on multi-agent model, which shows that the basic proposal of LDPKmeans will leak the real information of user agents if the attacker only obtains the cluster information and cluster centroid of each user. Furthermore, we enhance the attack method to crack the improved LDPKmeans method with privacy enhancement, enabling us to infer the cluster information of each user agent in the server. In other words, LDPKmeans seriously leak user agent privacy in distributed multi-agent systems if the server is untrusted. Theoretical analysis and experiments evaluate the effectiveness of our attack scheme. The results show that our method can effectively attack the distributed LDPKmeans scheme compared with the state-of-the-art attack methods. Specifically, our attack method can reduce the average relative error of inferring the true value before k-menas convergence on the 3D Road Network and Shuttle datasets by about 54% and 75% respectively when $k=5$ .

Abstract Purpose To explore the predictive value of radiomics in predicting stroke-associated pneumonia (SAP) in acute ischemic stroke (AIS) patients and construct a prediction model based on clinical features and DWI-MRI radiomics features. Methods Univariate and multivariate logistic regression analyses were used to identify the independent clinical predictors for SAP. Pearson correlation analysis and the least absolute shrinkage and selection operator with ten-fold cross-validation were used to calculate the radiomics score for each feature and identify the predictive radiomics features for SAP. Multivariate logistic regression was used to combine the predictive radiomics features with the independent clinical predictors. The prediction performance of the SAP models was evaluated using receiver operating characteristics (ROC), calibration curves, decision curve analysis, and subgroup analyses. Results Triglycerides, the neutrophil-to-lymphocyte ratio, dysphagia, the National Institutes of Health Stroke Scale (NIHSS) score, and internal carotid artery stenosis were identified as clinically independent risk factors for SAP. The radiomics scores in patients with SAP were generally higher than in patients without SAP (P

Abstract In tokamak, tungsten nitrides (WNx) layers that form on the divertor surface are byproducts of the nitrogen seeding system. The impact of their thermal transport properties is an important issue as they will be subjected to continuous high heat flow during operation. Leveraging density functional theory calculations along with the Kubo-Greenwood method, we investigate how vacancy defects influence the electrical conductivity and thermal conductivity of h-W2N1, β-W1N1, and h-W2N3 compounds, respectively. Our findings suggest that both nitrogen vacancy and tungsten vacancy defects can suppress the electrical and thermal conductivities of β-W1N1 to some extent. The electrical and thermal conductivity of h-W2N1 compound decrease in the presence of W vacancy but are insensitive to N vacancy. Conversely, for h-W2N3, both types of vacancy defects can enhance its electrical and thermal conductivities. Furthermore, we reveal that the fluctuation in the electrical conductivity of the three WNx compounds correlates with the changes in the mean free path of electrons and the density of states at the Fermi energy level induced by the vacancies in each system. The insights gleaned from our findings are beneficial for assessing and comprehending the thermal conductivity performance of WNx layers on the divertor surface.

Al–Li alloy has a wide range of application prospects in aerospace and rail transportation fields. Friction stir welding (FSW) is suitable for joining of Al–Li alloy. The microstructure evolution in FSW of Al–Li alloy determines the final joint properties. However, it is difficult to directly observe the microstructure evolution in FSW of Al–Li alloy only by experimental methods. Therefore, a Monte Carlo model in cooperation with a thermomechanical finite element model was proposed to study the microstructure evolution in FSW of 2195 Al–Li alloy. The validated thermomechanical finite element model was first used to calculate the temperature field, strain rate and strain evolution during the FSW process. Then, the achieved thermomechanical history was used in the Monte Carlo model to predict the transient microstructure evolution and the final morphology of the grain structure. It is found that the plastic materials on the advancing side experience a higher strain compared with that on the retreating side with the same distance from the joint line. The plastic material in the middle of the weld nugget zone (WNZ) experiences a relatively high temperature with more severe plastic deformation. Therefore, fully dynamic recrystallization takes place for the material at this region as it flows across the tool during FSW, which results in a fine recrystallization grain in the middle of WNZ. However, the material on the advancing side at 2 mm away from the joint line experiences a lower strain rate, which results in partial recrystallization with some relatively large grains of the base materials. The simulated average grain size and grain morphology were in good agreement with the measured results by EBSD method.

Abstract Nephrotoxicity is a significant concern during the development of new drugs or when assessing the safety of chemicals in consumer products. Traditional methods for testing nephrotoxicity involve animal models or 2D in vitro cell cultures, the latter of which lack the complexity and functionality of the human kidney. 3D in vitro models are created by culturing human primary kidney cells derived from urine in a 3D microenvironment that mimics the fluid shear stresses of the kidney. Thus, 3D in vitro models provide more accurate and reliable predictions of human nephrotoxicity compared to existing 2D models. In this review, we focus on precision nephrotoxicity testing using 3D in vitro models with human autologous urine-derived kidney cells as a promising approach for evaluating drug safety.

Abstract This letter proposes a millimeter‐wave dual‐polarized (DP) end‐fire frequency scanning antenna utilizing low temperature co‐fired ceramic (LTCC) technology. The antenna features DP radiating elements, each comprising a quasi‐Yagi antenna for horizontal polarization (H‐pol) and a pyramidal horn antenna for vertical polarization (V‐pol). These elements are excited via a mode‐composited transmission line (MCTL), integrating substrate integrated coaxial line (TEM mode) with substrate integrated waveguide (TE10 mode). To mitigate phase imbalances between polarizations during beam scanning, a delay line is embedded in each quasi‐Yagi element, ensuring consistent scanning ranges for the two polarizations. Furthermore, the implementation of amplitude weighting in the feeding networks contributes to the enhancement of antenna efficiency. A 1 × 8‐element prototype was fabricated and its performance is assessed. The results show closely matched beam scanning ranges for the two polarizations (±28° for H‐pol and −30° to +34° for V‐pol) across the 26–29 GHz frequency band, with a measured maximum peak gain exceeding 9.2 dBi for both polarizations. The proposed design emerges as a promising candidate for compact mmW frequency scanning front‐end antenna systems.

BackgroundAcute promyelocytic leukemia (APL) is rarely caused by the PLZF::RARα fusion gene. While APL patients with PLZF::RARα fusion commonly exhibit diverse hematologic symptoms, the presentation of myeloid sarcoma (MS) as an initial manifestation is infrequent.Case presentationA 61-year-old patient was referred to our hospital with 6-month history of low back pain and difficulty walking. Before this admission, spine magnetic resonance imaging (MRI) conducted at another hospital revealed multiple abnormal signals in the left iliac bone and vertebral bodies spanning the thoracic (T11-T12), lumbar (L1-L4), and sacral (S1/S3) regions. This led to a provisional diagnosis of bone tumors with an unknown cause. On admission, complete blood count (CBC) test and peripheral blood smear revealed a slightly increased counts of monocytes. Immunohistochemical staining of both spinal and bone marrow (BM) biopsy revealed positive expression for CD117, myeloperoxidase (MPO), and lysozyme. BM aspirate showed a significant elevation in the percentage of promyelocytes (21%), which were morphologically characterized by round nuclei and hypergranular cytoplasm. Multiparameter flow cytometry of BM aspirate revealed that blasts were positive for CD13, CD33, CD117, and MPO. Through the integrated application of chromosome analysis, fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), and Sanger sequencing, it was determined that the patient possessed a normal karyotype and a rare cryptic PLZF::RARα fusion gene, confirming the diagnosis of APL.ConclusionIn the present study, we report the clinical features and outcome of a rare APL patient characterized by a cryptic PLZF::RARα fusion and spinal myeloid sarcoma (MS) as the initial presenting symptom. Our study not only offers valuable insights into the heterogeneity of APL clinical manifestations but also emphasizes the crucial need to promptly consider the potential link between APL and MS for ensuring a timely diagnosis and personalized treatments.

Abstract Aerosol particles play a critical role in the tropical tropopause layer (TTL) through cloud formation and heterogeneous chemistry, influencing the radiative and chemical balance of the stratosphere. However, aerosol measurements in the TTL are sparse, resulting in poor knowledge of aerosol abundance and distribution in this important region. Here, we present in situ aircraft measurements over the western tropical Pacific, revealing a persistent and altitude‐dependent enhancement of aerosol mass in the TTL compared to the convectively influenced troposphere below. Notably, our data demonstrate a striking positive correlation between aerosol mass and ozone. Model simulations suggest that organic materials constitute a substantial fraction of the total aerosol mass within the TTL. We further derived an empirical parameterization of TTL aerosol mass as a function of ozone based on their linear relationship. This framework holds potential for estimating the TTL aerosol abundance but requires further validation and refinement through future measurements.

Abstract Besides participating in diverse pathological and physiological processes, extracellular vesicles (EVs) are also excellent drug‐delivery vehicles. However, clinical drugs modulating EV levels are still lacking. Here, we show that proton pump inhibitors (PPIs) reduce EVs by enhancing macropinocytosis‐mediated EV uptake. PPIs accelerate intestinal cell endocytosis of autocrine immunosuppressive EVs through macropinocytosis, thereby aggravating inflammatory bowel disease. PPI‐induced macropinocytosis facilitates the clearance of immunosuppressive EVs from tumour cells, improving antitumor immunity. PPI‐induced macropinocytosis also increases doxorubicin and antisense oligonucleotides of microRNA‐155 delivery efficiency by EVs, leading to enhanced therapeutic effects of drug‐loaded EVs on tumours and acute liver failure. Mechanistically, PPIs reduce cytosolic pH, promote ATP6V1A (v‐ATPase subunit) disassembly from the vacuolar membrane and enhance the assembly of plasma membrane v‐ATPases, thereby inducing macropinocytosis. Altogether, our results reveal a mechanism for macropinocytic regulation and PPIs as potential modulators of EV levels, thus regulating their functions.

Seismic landslide hazard assessment plays a very important guiding role during urgent earthquake relief. In August 2017, an Ms 7.0 earthquake in Jiuzhaigou County, Sichuan Province, China, triggered thousands of landslides. Based on the analysis of geological settings and coseismic landslide characteristics, the Newmark model is used to complete the seismic landslide hazard assessment. Three seismic motion parameters, namely, peak ground acceleration (PGA), traditional Arias intensity (Arias_P), and improved Arias intensity (Arias_C), are adopted. A publicly published coseismic landslide catalog is used as the validation samples. The results show that the coseismic landslides are mainly distributed in the deep gullies and steep mountainous slopes on the north and south sides of the epicenter. The seismic landslide hazard accuracy based on Arias_C is the best, followed by that based on PGA and Arias_P. The spatial distribution of seismic landslide hazards based on Arias_C shows an almost standard elliptical ring and is in good agreement with that of coseismic landslides. These results fully reflect the combined influence of the epicenter and seismogenic fault on landslide development. The middle seismic landslide hazard and over are mainly located at areas with seismic intensity of VII degree and above. The Arias intensity is very suitable for rapid seismic landslide hazard assessment in emergency situations. The study results can provide scientific and technological support for rapid earthquake relief and have reference significance for future seismic landslide hazard assessment.

Abstract The initiation and progression of cancer are intricately linked to the tumor microenvironment (TME). Understanding the function of specific cancer-TME interactions poses a major challenge due in part to the complexity of the in vivo microenvironment. Here we predict cancer-TME interactions from single cell transcriptomic maps of both human colorectal cancers (CRCs) and mouse CRC models, ask how these interactions are altered in human tumor organoid (tumoroid) cultures, and functionally recapitulate human myeloid-carcinoma interactions in vitro. Tumoroid cultures suppress gene expression programs involved in inflammation and immune cell migration, providing a reductive platform for re-establishing carcinoma-immune cell interactions in vitro. Introduction of human monocyte-derived macrophages into tumoroid cultures instructs macrophages to acquire immunosuppressive and pro-tumorigenic gene expression programs similar to those observed in vivo. This includes hallmark induction of SPP1, encoding Osteopontin, an extracellular CD44 ligand with established oncogenic effects. Taken together, these findings offer a framework for understanding CRC-TME interactions and provide a reductionist tool for modeling specific aspects of these interactions.

Abstract A new filter material, manganese oxide film coated clinoptilolite (MOFCC), was characterized and introduced to explore the effect in treating high concentration of manganese (1.71–2.12 mg L−1) from aqueous solution in fixed-bed column. Adsorption behavior of Mn(II) can be approximately described with the Langmuir isotherm. During the continuous 30 days filtration experiment, the removal rate of Mn(II) has maintained to be above 95.51%, the accumulated removal amount (806.42 mg) is much higher than the theoretical adsorption capacity (89.71 mg), which indicated that the removal of manganese by MOFCC includes both adsorption and auto-catalytic oxidation process, and it does not require a start-up period. SEM, EDS, XPS, XRD, ZETA potential and BET analyses were used to observe the surface properties of MOFCC. The manganese oxide film of MOFCC exhibits in clusters, apparently on occupied surface, the main component of the manganese oxide film is (Na0.7Ca0.3)Mn7O14·2.8H2O, the specific surface area of MOFCC is 38.76 m2 g−1, and the pore size is concentrated in the range of 3–40 nm, within the mesoporous range mesopores. pHpzc (point of zero charge) value is about 2.36. The characteristics of MOFCC make it an excellent manganese removal filter material for water treatment plant. Therefore, there is a long-term practical significance to develop new system for deep removal of manganese based on MOFCC.

DNA-PKcs is a crucial protein target involved in DNA repair and response pathways, with its abnormal activity closely associated with the occurrence and progression of various cancers. In this study, we employed a deep learning-based screening and molecular dynamics (MD) simulation-based pipeline, identifying eight candidates for DNA-PKcs targets. Subsequent experiments revealed the effective inhibition of DNA-PKcs-mediated cell proliferation by three small molecules (5025-0002, M769-1095, and V008-1080). These molecules exhibited anticancer activity with IC50 (inhibitory concentration at 50%) values of 152.6 μM, 30.71 μM, and 74.84 μM, respectively. Notably, V008-1080 enhanced homology-directed repair (HDR) mediated by CRISPR/Cas9 while inhibiting non-homologous end joining (NHEJ) efficiency. Further investigations into the structure-activity relationships unveiled the binding sites and critical interactions between these small molecules and DNA-PKcs. This is the first application of DeepBindGCN_RG in a real drug screening task, and the successful discovery of a novel DNA-PKcs inhibitor demonstrates its efficiency as a core component in the screening pipeline. Moreover, this study provides important insights for exploring novel anticancer therapeutics and advancing the development of gene editing techniques by targeting DNA-PKcs.

Abstract Background Ovarian metastasis from gastric cancer (GC) is characterized by aggressive biological behavior and poor outcome. Currently, there is no standard treatment mode for such patients. Thus, we evaluated the efficacy of conversion therapy in patients with synchronous ovarian metastasis from GC in this study. Methods About 219 GC patients with ovarian metastasis in 2011–2020 were enrolled. Two groups were established based on the different treatment: the conversion therapy group (chemotherapy combined with surgical resection, CS group) and the non‐conversion therapy group (NCS group). Propensity score matching (PSM) was used to analyze the efficacy of different treatment modes on the prognosis of these patients. Results Ninety‐two patients were included according to PSM results, with 46 patients each in CS and NCS groups. The median overall survival (OS) in the CS group was notably better than that in the NCS group (p

Abstract Abnormal expression of the potassium channel tetramerization domain containing 12 (KCTD12) is closely related to the occurrence and development of various tumors, but a pan-cancer analysis of KCTD12 has not yet been conducted. We explored the association between KCTD12 and more than 30 human malignancies using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. First, the mRNA and protein levels of KCTD12 were examined and their correlations with tumor stage and survival were explored. Second, we analyzed the infiltration of CD8+ and CD4+ T cells and cancer-associated fibroblasts in tumors and explored the correlation between KCTD12 expression and tumor cell stemness, genomic heterogeneity, and diagnostic specificity. Finally, we explored the molecular mechanisms associated with KCTD12 using KEGG/GO analysis. The results showed that KCTD12 mRNA and protein expression levels decreased in most tumors was significantly associated with the prognosis of tumor patients, and the phosphorylation level of KCTD12 decreased in several tumors, such as S200 and T196, pancreatic adenocarcinoma (PAAD), lung adenocarcinoma (LUAD), and breast invasive cancer (BRCA). The expression of KCTD12 was positively correlated with the degree of cancer-associated fibroblasts infiltration in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), PAAD, and stomach adenocarcinoma (STAD). The relationship between KCTD12 expression and CD8+ and CD4+ T cell infiltration was also clarified. KCTD12 showed high diagnostic sensitivity for various types of tumors and may be involved in tumor cell biology by affecting tumor cell stemness, tumor burden, and other characteristics. Finally, we analyzed the molecular functions of KCTD12 and possible KEGG/GO signaling pathways. In this study, we developed a biological marker for diagnosis, prognosis, and immune infiltration of the pan-cancers.

Abstract Given the leveling off in oxidized nitrogen emissions around the world, the atmospheric deposition of reduced nitrogen (NH x = NH3 + NH4 +) has become progressively critical, especially dry deposition, which presents great threats to plant growth. A combination of historical deposition data of measured wet NH x and modeled dry NH x in China suggests that dry NHx deposition has been increasing substantially (4.50% yr−1, p

Abstract Objective This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g‐NENs). Methods A retrospective enrollment of 142 patients diagnosed with g‐NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine–non‐neuroendocrine neoplasms (g‐NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). Results The study comprised a total of 142 g‐NENs cases, with a male‐to‐female ratio of approximately 2:1. The 5‐year survival rates for g‐NEC and g‐MiNEN were 26.7% and 35.2%, respectively. Corresponding 5‐year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g‐NEC/MiNEN showed a significantly worse prognosis compared to g‐NET (p

Abstract Background Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence. Methods To identify recurrence risk‐related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole‐exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non‐recurrence group (NR, n = 24, recurrence‐free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS

In this paper, the microstructure evolutions and crystallization kinetics of the newly developed Agx-[(Ga2Te3)34(SnTe)66]100−x (x = 6, 8 and 10%) telluride glasses were comprehensively investigated under non-isothermal conditions. The microscopic structure of the investigated samples were analyzed by X-ray diffraction (XRD), transmission electron microscope (TEM) and the selected area electron diffraction (SAED). The crystalline products were identified as the SnTe phase (primary crystalline phase) and Ga6SnTe10 phase. The exothermic crystallization process for any investigated samples was actually on the envelope of two overlapped peaks and could be assigned to the first crystallization event of SnTe precipitation and followed by the second crystallization event of Ga6SnTe10 phase. The crystallization mechanism and activation energies were estimated by Matusita–Sakka model under continuous heating based on the differential scanning calorimeter (DSC). For the first crystallization event, the Avrami exponent n values for each of the three investigated samples was approximately 3, suggesting the crystallization occurred through the two-dimensional growth with increasing number of nucleation. The values of n for the second crystallization event of Ga6SnTe10 phase were close to 4, indicating three-dimensional growth with a increasing number of nuclei. The activation energy Ec for both the first and second crystallization events was gradually decreased as the Ag content increased.

Abstract Background Excessive oxidative stress plays a critical role in the progression of various diseases, including intervertebral disk degeneration (IVDD). Recent studies have found that anemonin (ANE) possesses antioxidant and anti-inflammatory effects. However, the role of ANE in IVDD is still unclear. Therefore, this study investigated the effect and mechanism of ANE on H2O2 induced degeneration of nucleus pulposus cells (NPCs). Methods NPCs were pretreated with ANE, and then treated with H2O2. NOX4 was upregulated by transfection of pcDNA-NOX4 into NPCs. Cytotoxicity was detected by MTT, oxidative stress-related indicators and inflammatory factors were measured by ELISA, mRNA expression was assessed by RT-PCR, and protein expression was tested by western blot. Results ANE attenuated H2O2-induced inhibition of NPCs activity. H2O2 enhanced oxidative stress, namely, increased ROS and MDA levels and decreased SOD level. However, these were suppressed and pretreated by ANE. ANE treatment repressed the expression of inflammatory factors (IL-6, IL-1β and TNF-α) in H2O2-induced NPCs. ANE treatment also prevented the degradation of extracellular matrix induced by H2O2, showing the downregulation of MMP-3, 13 and ADAMTS-4, 5 and the upregulation of collagen II. NOX4 is a key factor regulating oxidative stress. Our study confirmed that ANE could restrain NOX4 and p-NF-κB. In addition, overexpression of NOX4 counteracted the antioxidant and anti-inflammatory activities of ANE in H2O2-induced NPCs, and the inhibition of the degradation of extracellular matrix induced by ANE was also reversed by overexpression of NOX4. Conclusion ANE repressed oxidative stress, inflammation and extracellular matrix degradation in H2O2-induced NPCs by inhibiting NOX4/NF-κB pathway. Our study indicated that ANE might be a candidate drug for the treatment of IVDD.

Abstract Background The incidence and mortality of gastric cancer ranks fifth and fourth worldwide among all malignancies, respectively. Accumulating evidences have revealed the close relationship between mitochondrial dysfunction and the initiation and progression of stomach cancer. However, rare prognostic models for mitochondrial-related gene risk have been built up in stomach cancer. Methods In current study, the expression and prognostic value of mitochondrial-related genes in stomach adenocarcinoma (STAD) patients were systematically analyzed to establish a mitochondrial-related risk model based on available TCGA and GEO databases. The tumor microenvironment (TME), immune cell infiltration, tumor mutation burden, and drug sensitivity of gastric adenocarcinoma patients were also investigated using R language, GraphPad Prism 8 and online databases. Results We established a mitochondrial-related risk prognostic model including NOX4, ALDH3A2, FKBP10 and MAOA and validated its predictive power. This risk model indicated that the immune cell infiltration in high-risk group was significantly different from that in the low-risk group. Besides, the risk score was closely related to TME signature genes and immune checkpoint molecules, suggesting that the immunosuppressive tumor microenvironment might lead to poor prognosis in high-risk groups. Moreover, TIDE analysis demonstrated that combined analysis of risk score and immune score, or stromal score, or microsatellite status could more effectively predict the benefit of immunotherapy in STAD patients with different stratifications. Finally, rapamycin, PD-0325901 and dasatinib were found to be more effective for patients in the high-risk group, whereas AZD7762, CEP-701 and methotrexate were predicted to be more effective for patients in the low-risk group. Conclusions Our results suggest that the mitochondrial-related risk model could be a reliable prognostic biomarker for personalized treatment of STAD patients.

Ginkgo biloba L. leaves are rich in secondary metabolites with important medicinal values; to increase their contents, foliar spraying of micronutrients is a potential strategy. Zinc, a multifunctional element, has a significant impact on the content of secondary metabolites in other plants, but relevant research into ginkgo is still lacking. In our study, different spraying time and concentration strategies were used to investigate the effects of zinc sulfate (ZnSO4) on physiological indicators and secondary metabolites of 2-year-old ginkgo. The results demonstrated that ZnSO4 could increase the contents of hydrogen peroxide, abscisic acid, and free amino acids in ginkgo leaves. It also enhances the antioxidant enzyme activity of ginkgo leaves, decreases the content of plant auxin, and ultimately facilitates the accumulation of ginkgo terpene lactones (TTL). Spraying ZnSO4 in June resulted in a more significant increase in the contents of TTL and flavonoids compared to spraying in August. After spraying 12 mmol/L ZnSO4 in June, the contents of TTL and flavonoids in ginkgo leaves were significantly elevated by 35.95% and 24.30%, respectively, compared to those in the CK (p < 0.05). The contents of ginkgolide A, B, and C were notably increased by 45.93%, 46.56%, and 74.29%, respectively, compared to those in the CK (p < 0.05). Therefore, our study suggests that the optimal timing for spraying ZnSO4 on ginkgo is in June, with a recommended concentration of 12 mmol/L. Our study provides a theoretical basis for the accumulation of secondary metabolites in ginkgo and guides the production of its leaf-utilization plantations.

High-quality Fe-Cr-Ni-W-B spherical powder is crucial for the powder metallurgy preparation of high-strength and tough Fe-Cr-Ni-W-B alloys. In this study, the controlled preparation of high-quality Fe-Cr-Ni-W-B spherical powder was achieved using the vacuum gas atomization method. The effects and mechanisms of atomization gas pressure, the melt nozzle inner diameter, and heat treatment temperature on the microstructure and flowability of Fe-Cr-Ni-W-B spherical powder were systematically investigated. By optimizing process parameters, spherical Fe-Cr-Ni-W-B powder with a sphericity of 95.1% and a flowability of 15.88 s/50 g was obtained, laying the foundation for the powder metallurgy preparation of high-strength and tough Fe-Cr-Ni-W-B alloys.

GPR35 is a G protein-coupled receptor with notable involvement in modulating inflammatory responses. Although the precise role of GPR35 in inflammation is not yet fully understood, studies have suggested that it may have both pro- and anti-inflammatory effects depending on the specific cellular environment. Some studies have shown that GPR35 activation can stimulate the production of pro-inflammatory cytokines and facilitate the movement of immune cells towards inflammatory tissues or infected areas. Conversely, other investigations have suggested that GPR35 may possess anti-inflammatory properties in the gastrointestinal tract, liver and certain other tissues by curbing the generation of inflammatory mediators and endorsing the differentiation of regulatory T cells. The intricate role of GPR35 in inflammation underscores the requirement for more in-depth research to thoroughly comprehend its functional mechanisms and its potential significance as a therapeutic target for inflammatory diseases. The purpose of this review is to concurrently investigate the pro-inflammatory and anti-inflammatory roles of GPR35, thus illuminating both facets of this complex issue.

Introduction Stroke is a leading cause of mortality and disability worldwide. Recurrent strokes result in prolonged hospitalisation and worsened functional outcomes compared with the initial stroke. Thus, it is critical to identify patients who are at high risk of stroke recurrence. This study is positioned to develop and validate a prediction model using radiomics data and machine learning methods to identify the risk of stroke recurrence in patients with acute ischaemic stroke (AIS).Methods and analysis A total of 1957 patients with AIS will be needed. Enrolment at participating hospitals will continue until the required sample size is reached, and we will recruit as many participants as possible. Multiple indicators including basic clinical data, image data, laboratory data, CYP2C19 genotype and follow-up data will be assessed at various time points during the registry, including baseline, 24 hours, 7 days, 1 month, 3 months, 6 months, 9 months and 12 months. The primary outcome was stroke recurrence. The secondary outcomes were death events, prognosis scores and adverse events. Imaging images were processed using deep learning algorithms to construct a programme capable of automatically labelling the lesion area and extracting radiomics features. The machine learning algorithms will be applied to integrate cross-scale, multidimensional data for exploratory analysis. Then, an ischaemic stroke recurrence prediction model of the best performance for patients with AIS will be established. Calibration, receiver operating characteristic and decision curve analyses will be evaluated.Ethics and dissemination This study has received ethical approval from the Medical Ethics Committee of the Second Affiliated Hospital of Nanchang University (medical research review No.34/2021), and informed consent will be obtained voluntarily. The research findings will be disseminated through publication in journals and presented at conferences.Trial registration number ChiCTR2200055209.

Dendritic cells (DC) present tumour antigens to T cells but this process is defective in the tumour microenvironment. Here the authors find that downregulation of cholesterol 25-hydroxylase underlies defective cross presentation of tumour antigens.

Large amounts of water vapour released to the stratosphere during the 2022 Hunga-Tonga hydromagmatic volcanic eruption led to decreased sulfur dioxide aerosol lifetime, increased sulfate particle size and a doubling of stratospheric aerosol optical depth, according to numerical simulations.

Abstract The Pinatubo eruption in 1991 injected 10–20 Tg SO2 into the stratosphere, which formed sulfate aerosols through oxidation. Our modeling results show that volcanic heating significantly perturbs the heterogeneous and homogeneous chemistry including NOx and HOx catalytic cycles in the tropical stratosphere. The simulated tropical chemical ozone tendency is positive at 20 mb while negative at 10 mb in the tropics. The simulated ozone chemical tendency is of the same magnitude as the dynamical ozone tendency caused by the accelerated tropical upwelling, but with the opposite sign. Our study finds that the tropical ozone chemical tendency due to homogeneous chemistry becomes more important than heterogeneous chemistry 3 months after eruption. Sensitivity simulations further suggest that the tropical ozone tendency through heterogeneous chemistry is saturated when the injected amount exceeds 2 Tg.

Abstract Volcanic and wildfire events between 2014 and 2022 injected ∼3.2 Tg of sulfur dioxide and 0.8 Tg of smoke aerosols into the stratosphere. With injections at higher altitudes and lower latitudes, the simulated stratospheric lifetime of the 2014–2022 injections is about 50% longer than the volcanic 2005–2013 injections. The simulated global mean effective radiative forcing (ERF) of 2014–2022 is −0.18 W m−2, ∼40% of the ERF of the period of 1991–1999 with a large‐magnitude volcanic eruption (Pinatubo). Our climate model suggests that the stratospheric smoke aerosols generate ∼60% more negative ERF than volcanic sulfate per unit aerosol optical depth. Studies that fail to account for the different radiative properties of wildfire smoke relative to volcanic sulfate will likely underestimate the negative stratospheric forcings. Our analysis suggests that stratospheric injections offset 20% of the increase in global mean surface temperature between 2014–2022 and 1999–2002.

The structural, elastic, piezoelectric, and electronic properties of K1−xMxNbO3 (M = Li, Na) were investigated by first-principles calculations. The results show that the modifications have effects on the elastic properties of KNbO3 and strengthen the anisotropy. Na and Li doping can slightly improve the piezoelectric stress tensor (e33) and piezoelectric strain tensor (d33) of KNbO3. With the increase in the x value from 0 to 0.5 in K1−xMxNbO3, the d33 value is improved from 24.4 to 36.3 pC/N (M = Na) and 41.5 pC/N (M = Li), and the piezoelectric property is improved by 1.49 and 1.70 times with the modifications of Na and Li, respectively. This conclusion is consistent with the result of Born effective charge and band structure results. The Born effective charge average values (Z*̄) for K and Nb atoms in K0.5M0.5NbO3 (M = Li, Na) are slightly increased compared to those in KNbO3. KNbO3 has an indirect bandgap, while Na and Li doping makes K0.5Na0.5NbO3 or K0.5Li0.5NbO3 a direct bandgap semiconductor. This study may provide a theoretical insight into Na and Li modified KNbO3 for their piezoelectricity.

Stand density affects the potentially superior productivity of forest ecosystems directly by regulating the light and nutrient availability of trees. Understanding how stand density influences the growth and development of trees is crucial for supporting forest management in the context of climate change. We focused on Liriodendron chinense in experimental plantations created in 2003, with planting densities ranging from 277 to 10,000 trees per hectare at six plots. The leaf structure and photosynthetic capacity of L. chinense changed significantly under different stand densities, which had a negative impact on their biomass (leaf mass) and nutrient (total carbohydrate content) accumulation. Transcriptional differences were observed among samples from plots with different planting densities. The expression of 1784 genes was negatively dependent on stand density, participating mainly in the biological processes of “circadian rhythm”, “carbon metabolism”, and “amino acid biosynthesis”. Furthermore, we identified a photosynthesis-related module and constructed a gene regulatory network to discover that the transcription factors of MYB and bHLH may have important roles in the transcriptional regulation of photosynthesis biosynthesis by activating or repressing the expression of petA (Litul.15G096200), psbE (Litul.10G033900), and petD (Litul.17G061600) at different stand densities. Our study quantified the impact of stand density on tree growth at physiological and molecular levels. Our observations provide theoretical support for plantation establishment of L. chinense.