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Abstract Corticosteroid is essential in the treatment regimen for connective tissue disease (CTD); however, its long-term use poses significant risks, including pulmonary infections. The relationship between cumulative corticosteroid doses and adverse pneumonia outcomes requires further investigation. This study aimed to explore the association between cumulative methylprednisolone dosages (CMD) and pneumonia mortality risks among CTD patients. We conducted a retrospective analysis of data from CTD patients treated with intravenous or oral corticosteroids across six academic hospitals over approximately five years in China. We evaluated follow-up outcomes at 30 and 90 days after the onset of pneumonia. Piecewise linear regression, Cox regression analysis, and survival analysis were employed to investigate the relationship between CMD and 30-day and 90-day mortality risks. Among 335 CTD patients with pneumonia, the mean CMD was 12 g. The 30-day and 90-day mortality rates were 25.07% and 29.55%, respectively. After adjusting for potential confounders, smooth curve fitting analysis revealed a specific nonlinear relationship between CMD and 30-day and 90-day mortality risks. Cox regression analysis indicated that the lowest pneumonia mortality risk occurred when CMD ranged from 11 to 24 g (30-day adjusted hazard ratio (aHR) 0.33, 95% CI 0.14–0.77; 90-day aHR 0.37, 95% CI 0.17–0.81). Patients in the 11–24 g CMD group demonstrated significantly lower cumulative hazard and death rates compared to both the low CMD ( 24 g) groups (P

BackgroundRecurrent spontaneous abortion (RSA) is a multifactorial disease, the exact causes of which are still unknown. Environmental, maternal, and genetic factors have been shown to contribute to this condition. The aim of this study was to investigate the presence of mutations in the ANXA4 gene in patients with RSA.MethodsGenomic DNA was extracted from 325 patients with RSA and 941 control women with a normal reproductive history for whole-exome sequencing (WES). The detected variants were annotated and filtered, and the pathogenicity of the variants was predicted through the SIFT online tool, functional enrichment analyses, Sanger sequencing validation, prediction of changes in protein structure, and evolutionary conservation analysis. Furthermore, plasmid construction, Western blotting, RT–qPCR, and cell migration, invasion and adhesion assays were used to detect the effects of ANXA4 mutations on protein function.ResultsAn ANXA4 mutation (p.G8D) in 1 of the 325 samples from patients with RSA (RSA-219) was identified through WES. This mutation was not detected in 941 controls or included in public databases. Evolutionary conservation analysis revealed that the amino acid residue affected by the mutation (p.G8D) was highly conserved among 13 vertebrate species, and the SIFT program and structural modeling analysis predicted that this mutation was harmful. Furthermore, functional assays revealed that this mutation could inhibit cell migration, invasion and adhesion.ConclusionOur study suggests that an unreported novel ANXA4 mutation (p.G8D) plays an important role in the pathogenesis of RSA and may contribute to the genetic diagnosis of RSA.

Breast cancer is the most common malignancy in women worldwide, and major challenges in its treatment include drug resistance and metastasis. Three-dimensional cell culture systems have received widespread attention in drug discovery studies but existing models have limitations, that warrant the development of a simple and repeatable three-dimensional culture model for high-throughput screening. In this study, we designed a simple, reproducible, and highly efficient microencapsulated device to co-culture MCF-7 cells and HUVECs in microcapsules to establish an in vitro vascularized micro-tumor model for chemotherapeutic drug screening. First, to construct a three-dimensional micro-tumor model, cell encapsulation devices were created using three different sizes of flat-mouthed needles. Immunohistochemistry and immunofluorescence assays were conducted to determine vascular lumen formation. Cell proliferation was detected using the Cell Counting Kit-8 assay. Finally, to observe the drug reactions between the models, anticancer drugs (doxorubicin or paclitaxel) were added 12 h after the two-dimensional cultured cells were plated or 7 days after cell growth in the core-shell microcapsules. Vascularized micro-tumors were obtained after 14 days of three-dimensional culture. The proliferation rate in the three-dimensional cultured cells was slower than that of two-dimensional cultured cells. Three-dimensional cultured cells were more resistant to anticancer drugs than two-dimensional cultured cells. This novel sample encapsulation device formed core-shell microcapsules and can be used to successfully construct 3D vascularized micro-tumors in vitro . The three-dimensional culture model may provide a platform for drug screening and is valuable for studying tumor development and angiogenesis.

BackgroundThe impact of glucocorticoid use on mortality risk in pneumonia patients remains unclear. This study aimed to investigate the relationship between the accumulated dose of glucocorticoids (ADG) and secondary pneumonia mortality risk among patients receiving oral or intravenous glucocorticoids.MethodsData from the DRYAD database were analyzed, covering pneumonia patients from six academic hospitals over a 5-year period who had been administered oral or intravenous glucocorticoids. Piecewise linear regression and multivariate regression analysis were utilized to assess the association between ADG and mortality risk in pneumonia patients, while adjusting for potential confounders.ResultsAmong the 628 pneumonia patients included, the 30-day mortality rate was 23.1% and the 90-day mortality rate was 26.4%. In the high-dose glucocorticoid group (≥24 mg/day of methylprednisolone or an equivalent glucocorticoid within 30 days before admission), the 30-day and 90-day mortality rates were 31.2% and 35.9%, respectively. Piecewise linear regression analysis demonstrated a non-linear relationship between ADG and mortality risk in pneumonia patients. Multivariate regression analysis revealed a significantly lower mortality risk in patients receiving an ADG of 20–39 g methylprednisolone compared to those receiving lower (

BackgroundPeripheral arteriosclerosis is caused by any atherosclerosis outside the heart and brain. However, the underlying biological mechanisms are not fully understood. This study aims to explore the causal relationship between blood metabolites and peripheral arteriosclerosis.MethodsA Mendelian randomization (MR) analysis was implemented to estimate the causality of blood metabolites on peripheral arteriosclerosis. A genome-wide association study (GWAS) of 1,400 metabolites was used as the exposure, whereas two different GWAS datasets of peripheral arteriosclerosis were the outcomes. Inverse-variance weighted (IVW) was the main analysis of causal analysis. MR-Egger, the simple mode, weighted median and weighted mode were used to increase the stability and robustness of the results. Cochran Q test, MR-Egger intercept test, the funnel plot, and MR-Pleiotropy RESidual Sum and Outlier were used for sensitivity analyses. Furthermore, metabolic pathway enrichment analysis was performed using MetaboAnalyst5.0.ResultsIn this MR study, eight blood metabolites have a strong causal relationship with peripheral arteriosclerosis, including 1-myristoyl-2-arachidonoyl-GPC (14:0/20:4), 1-palmitoyl-2-arachidonoyl-gpc (16:0/20:4n6), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE, 1-palmitoyl-2-dihomo-linolenoyl-GPC, Gamma-glutamylleucine, Deoxycholic acid glucuronide and two named X- (X-24546, X-26111). In addition, five important metabolic pathways in peripheral arteriosclerosis were identified through metabolic pathway analysis.ConclusionThis study provides evidence for the causal relationship between blood metabolites and peripheral arteriosclerosis, and these eight blood metabolites provide new perspectives for screening and prevention of peripheral arteriosclerosis in the future.

Highlights Developing a universal strategy of the p–n homojunction engineering that could significantly boost electron mobility of electron transport layer (ETL) by two orders of magnitude. Proposing a new mechanism based on p–n homojunction to explain inhibited carrier loss at buried interface. Setting a new performance benchmark as high as 25.50% for planar perovskite solar cells employing TiO2 as ETLs.

Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338–5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338–5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338–5p on the progression of breast cancer in vitro and in vivo. Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338–5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338–5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338–5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation.

Objectives To evaluate the frequency and severity of depressive and anxiety symptoms and explore possible risk factors among caregivers of children with congenital ectopia lentis (CEL).Design A prospective cross-sectional study was conducted.Participants 108 patients and 108 informal caregivers (mainly parents) were included. Participants were grouped based on whether patients had systemic abnormalities: group 1 were children without systemic abnormalities and group 2 were children with systemic abnormalities.Outcome measures The 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) were used to assess depressive and anxiety symptoms, respectively.Results More than half of caregivers (51.9%) have depressive or anxiety symptoms of some degree. 38.0% of caregivers suffered from both depressive and anxiety symptoms. 19.4% of caregivers had moderate to severe depressive symptoms (PHQ-9 score ≥10) while 16.7% reported moderate to severe anxiety symptoms (GAD-7 score ≥10). Between the two groups, the mean PHQ-9 and GAD-7 scores significantly differed (p=0.026 in PHQ-9; p=0.018 in GAD-7). The proportion of caregivers with moderate to severe symptoms was greater in group 2 than in group 1. In addition, there was a significant positive correlation between PHQ-9 and GAD-7 scores (r=0.827; p

PurposeGiven the increasing occurrence of stroke and high-sodium diets (DHIS) over the past 30 years, it is crucial to assess the global, national, and regional impact of DHIS on the burden of stroke.Methods and materialsThe Global Burden of Diseases Study 2019 provided the study's data. We used the Bayesian meta-regression tool DisMod-MR 2.1 to evaluate the burden of stroke attributable to DHIS. Age-standardized disability-adjusted life years (ASDR) and age-standardized mortality rate (ASMR) were used to quantify the burden. We perform correlation analysis utilizing the Spearman rank-order correlation method, and we calculate the estimated annual percentage change (EAPC) to evaluate temporal trends.ResultsGlobally, DHIS accounts for 17,673.33 thousand disability-adjusted life years (DALYs) and 700.98 thousand deaths of stroke in 2019. The burden of stroke attributable to DHIS has declined between 1990 and 2019 globally and in the majority of regions, with the largest declines seen in regions with high sociodemographic indexes (SDI). Both ASMR and ASDR were higher regionally in regions with moderate SDI than those in developed regions. Furthermore, the absolute values of EAPC, reflecting the rate of decrease, were notably lower in these regions compared to developed nations. High-income North America, categorized within the SDI regions, notably witnessed the smallest decline in ASDR over the last three decades. Additionally, from 1990 to 2019, males consistently bore a larger burden of stroke attributable to DHIS.ConclusionThe burden of stroke attributable to DHIS remained a major concern despite advancements in public knowledge of stroke and their utilization of emergency medical services. Over the past 30 years, more burden has been placed on males and regions with moderate SDI values; in males, higher EAPC values for both ASMR and ASDR have been found. This underscores the urgent need for effective interventions to alleviate the burden of stroke associated with DHIS.

Abstract Exploiting high‐performance yet low‐cost hard carbon anodes is crucial to advancing the state‐of‐the‐art sodium‐ion batteries. However, the achievement of superior initial Coulombic efficiency (ICE) and high Na‐storage capacity via low‐temperature carbonization remains challenging due to the presence of tremendous defects with few closed pores. Here, a facile hybrid carbon framework design is proposed from the polystyrene precursor bearing distinct molecular bridges at a low pyrolysis temperature of 800°C via in situ fusion and embedding strategy. This is realized by integrating triazine‐ and carbonyl‐crosslinked polystyrene nanospheres during carbonization. The triazine crosslinking allows in situ fusion of spheres into layered carbon with low defects and abundant closed pores, which serves as a matrix for embedding the well‐retained carbon spheres with nanopores/defects derived from carbonyl crosslinking. Therefore, the hybrid hard carbon with intimate interface showcases synergistic Na ions storage behavior, showing an ICE of 70.2%, a high capacity of 279.3 mAh g−1, and long‐term 500 cycles, superior to carbons from the respective precursor and other reported carbons fabricated under the low carbonization temperature. The present protocol opens new avenues toward low‐cost hard carbon anode materials for high‐performance sodium‐ion batteries.

The quaternion cubature Kalman filter (QCKF) algorithm has emerged as a prominent nonlinear filter algorithm and has found extensive applications in the field of GNSS/SINS integrated attitude determination and positioning system (GNSS/SINS-IADPS) data processing for unmanned aerial vehicles (UAV). However, on one hand, the QCKF algorithm is predicated on the assumption that the random model of filter algorithm, which follows a white Gaussian noise distribution. The noise in actual GNSS/SINS-IADPS is not the white Gaussian noise but rather a ubiquitous non-Gaussian noise. On the other hand, the use of quaternions as state variables is bound by normalization constraints. When applied directly in nonlinear non-Gaussian system without considering normalization constraints, the QCKF algorithm may result in a mismatch phenomenon in the filtering random model, potentially resulting in a decline in estimation accuracy. To address this issue, we propose a novel Gaussian sum quaternion constrained cubature Kalman filter (GSQCCKF) algorithm. This algorithm refines the random model of the QCKF by approximating non-Gaussian noise with a Gaussian mixture model. Meanwhile, to account for quaternion normalization in attitude determination, a two-step projection method is employed to constrain the quaternion, which consequently enhances the filtering estimation accuracy. Simulation and experimental analyses demonstrate that the proposed GSQCCKF algorithm significantly improves accuracy and adaptability in GNSS/SINS-IADPS data processing under non-Gaussian noise conditions for Unmanned Aerial Vehicles (UAVs).

Abstract During the ex vivo expansion of umbilical cord-derived mesenchymal stem cells (hUCMSCs) in a stirred tank bioreactor, the formation of cell–microcarrier aggregates significantly affects cell proliferation and physiological activity, making it difficult to meet the quantity and quality requirements for in vitro research and clinical applications. In this study, computational fluid dynamic (CFD) simulations were used to investigate the effect of an impeller structure in a commercial spinner flask on flow field structure, aggregate formation, and cellular physiological activity. By designing a modified impeller, the aggregate size was reduced, which promoted cell proliferation and stemness maintenance. This study showed that increasing the stirring speed reduced the size of hUCMSC-microcarrier aggregates with the original impeller. However, it also inhibited cell proliferation, decreased activity, and led to spontaneous differentiation. Compared to low stirring speeds, high stirring speeds did not alter the radial flow characteristics and vortex distribution of the flow field, but did generate higher shear rates. The new impeller’s design changed the flow field from radial to axial. The use of the novel impeller with an increased axial pumping rate (Qz) at a similar shear rate compared to the original impeller resulted in a 43.7% reduction in aggregate size, a 37.4% increase in cell density, and a better preservation of the expression of stemness markers (SOX2, OCT4 and NANOG). Increasing the Qz was a key factor in promoting aggregate suspension and size reduction. The results of this study have significant implications for the design of reactors, the optimisation of operating parameters, and the regulation of cellular physiological activity during MSC expansion. Graphical Abstract

IntroductionSalmonella is a major foodborne pathogen worldwide that causes severe morbidity and mortality. It is mainly caused by consuming contaminated food, with retail food considered the primary source.MethodsIn Guizhou, China, 102 Salmonella strains isolated from 2016 to 2021 underwent phenotypic antimicrobial resistance testing and whole-genome sequencing (WGS) to understand Salmonella diversity, including serotypes, sequencing types (STs), antimicrobial genes, virulence genes, plasmid types, multi-locus sequence types (MLST), and core genome MLST (cgMLST).Results and discussionS.Typhimurium was the dominant serotype, and O:4(B) was the leading serogroup. The most prevalent genotype was ST40. Phenotypic antimicrobial resistance identified 66.7% of the sampled isolates as multi-drug resistant (MDR). S.Enteritidis (n = 7), S.Typhimurium (n = 1), S.Indiana (n = 1), S.Kentucky (n = 1), S.Uganda (n = 1), all of which were MDR, were resistant to Colistin. Resistance rates varied significantly across different strains and food types, particularly meat products exhibiting higher resistance. Notably, significant increases in resistance were observed from 2016 to 2021 for the following: ≥ 1 resistant (P = 0.001), MDR (P = 0.001), ampicillin (P = 0.001), tetracycline (P

Abstract Objective Human placenta-derived exosomes (pExo) were generated, characterized, and evaluated as a therapeutic candidate for the treatment of osteoarthritis (OA). Methods pExo was generated from full-term human placenta tissues by sequential centrifugation, purification, and sterile filtration. Upon analysis of particle size, cytokine composition, and exosome marker expression, pExo was further tested in cell-based assays to examine its effects on human chondrocytes. In vivo therapeutic efficacies were evaluated in a medial meniscal tear/medial collateral ligament tear (MCLT + MMT) rat model, in which animals received pExo injections intraarticularly and weight bearing tests during in-life stage while histopathology and immunohistochemistry were performed as terminal endpoints. Results pExo displayed typical particle size, expressed maker proteins of exosome, and contained proteins with pro-proliferative, pro-anabolic, anti-catabolic, or anti-inflammatory activities. In vitro, pExo promoted chondrocyte migration and proliferation dose-dependently, which may involve its activation of cell growth-related signaling pathways. Expression of inflammatory and catabolic genes induced in a cellular OA model was significantly suppressed by pExo. In the rat OA model, pExo alleviated pain burden, restored cartilage degeneration, and downregulated expressions of pro-inflammatory, catabolic, or apoptotic proteins in a dose-dependent manner. Conclusions Our study demonstrates that pExo has multiple potential therapeutic effects including symptom control and disease modifying characteristics. This may make it an attractive candidate for further development as an anti-OA therapeutic.

AIM: To investigate the impact of meteorological factors in different environments in the eastern and western regions of China on the incidence of lipid-abnormal dry eye.METHODS: This is a multicenter retrospective study. From March 1, 2021 to February 28, 2022, all patients with dry eye were selected from the ophthalmology clinic of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine and Friendship Hospital of Xinjiang Yili Kazakh Autonomous Prefecture. General data(gender, age, employment and education)and climate data for outdoor environments(temperature, humidity, air quality index and wind)on the day of the visit were collected. Patients who met the inclusion and exclusion criteria were selected. Single factor, multiple factors and nonlinear model analysis were applied to identify environmental factors of lipid-abnormal dry eye in both regions.RESULTS: There was no significant difference in the incidence of lipid-abnormal dry eye between Nanjing and Yili in different seasons. The incidence of lipid-abnormal dry eye in Yili was significantly higher in all seasons than in Nanjing(P

Abstract Backgroud The current diagnostic criteria for refractory Mycoplasma pneumoniae pneumonia (RMPP) among Mycoplasma pneumoniae Pneumonia (MPP) are insufficient for early identification, and potentially delayed appropriate treatment. This study aimed to develop an effective individualized diagnostic prediction nomogram for pediatric RMPP. Methods A total of 517 hospitalized children with MPP, including 131 with RMPP and 386 without RMPP (non-RMPP), treated at Lianyungang Maternal and Child Health Care Hospital from January 2018 to December 2021 were retrospectively enrolled as a development (modeling) cohort to construct an RMPP prediction nomogram. Additionally, 322 pediatric patients with MPP (64 with RMPP and 258 with non-RMPP, who were treated at the Affiliated Hospital of Xuzhou Medical University from June 2020 to May 2022 were retrospectively enrolled as a validation cohort to assess the prediction accuracy of model. Univariable and multivariable logistic regression analyses were used to identify RMPP risk factors among patients with MPP. Nomogram were generated based on these risk factors using the rms package of R, and the predictive performance was evaluated based on receiver operating characteristic (ROC) curves and using decision curve analysis (DCA). Results Multivariate analysis revealed five significant independent predictors of RMPP among patients with MPP: age (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.08–1.33, P = 0.038), fever duration (HR 1.34, 95%CI 1.20–1.50, P

Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration. Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication; however, recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments. Specifically, oncolytic vaccinia virus (OVV) has gained popularity owing to its safety, potential for systemic delivery, and large gene insertion capacity. This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo, and provides an overview of ongoing clinical trials and combination therapies. In addition, we discuss the potential benefits and drawbacks of OVV as a cancer therapy, and explore different perspectives in this field.

Thermal infrared imaging could detect hidden faults in various types of high-voltage power equipment, which is of great significance for power inspections. However, there are still certain issues with thermal-imaging-based abnormal heating detection methods due to varying appearances of abnormal regions and complex temperature interference from backgrounds. To solve these problems, a contour-based instance segmentation network is first proposed to utilize thermal (T) and visual (RGB) images, realizing high-accuracy segmentation against complex and changing environments. Specifically, modality-specific features are encoded via two-stream backbones and fused in spatial, channel, and frequency domains. In this way, modality differences are well handled, and effective complementary information is extracted for object detection and contour initialization. The transformer decoder is further utilized to explore the long-range relationships between contour points with background points, and to achieve the deformation of contour points. Then, the auto-encoder-based reconstruction network is developed to learn the distribution of power equipment using the proposed random argument strategy. Meanwhile, the UNet-like discriminative network directly explores the differences between the reconstructed and original image, capturing the deviation of poor reconstruction regions for abnormal heating detection. Many images are acquired in transformer substations with different weathers and day times to build the datasets with pixel-level annotation. Several extensive experiments are conducted for qualitative and quantitative evaluation, while the comparison results fully prove the effectiveness and robustness of the proposed instance segmentation method. The practicality and performance of the proposed abnormal heating detection method are evaluated on image patches with different kinds of insulators.

The evaluation of typhoon disaster risk is a widely discussed global topic. Currently, the index system method has become a common approach for the evaluation of typhoon disaster risk. However, the indices within the system are calculated independently, and subjective human factors significantly influence the assignment of index weights. The existing studies lack purely quantitative assessment methods, which makes the studies less precise and more difficult for other researchers to replicate. To bridge this gap, this study employs emergy analysis methods based on thermodynamics to develop a typhoon disaster risk evaluation index system for China’s coastal zone. Without the interference of weights and other human factors, the system contains various quantitative indices, including aggregate impelling energy, typhoon intensity emergy, adaptability emergy, the vulnerability index, and the integrated typhoon hazard index. Subsequently, these indices and socio-economic data were spatialized, and the evaluation of typhoon disaster risk was conducted at the city grid level in the coastal zone of China. The findings reveal that the high-risk areas for typhoon disasters in China are concentrated in prefecture-level cities along the southeast coast. The typhoon disaster risk index is higher in the southern region compared to the northern region, with a decreasing trend in the distribution of the integrated typhoon hazard index from coastal to inland areas. The aim of this study is to use a new quantitative evaluation method (emergy) to evaluate typhoon disasters. It also serves as a theoretical foundation and technical support for national and local governments in the formulation of policies for disaster prevention and reduction.