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Abstract Background Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. Objective To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. Methods This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris. Results A total of 1617 patients were enrolled. At week 12, patients in the adapalene–clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (− 66.85%), compared with adapalene alone (− 50.82%) or clindamycin gel alone (− 57.61%). The difference in the least square means of the adapalene–clindamycin gel group and adapalene group, or clindamycin gel group was − 16.08% (95% CI − 19.95% to − 12.21%) and − 9.38% (95% CI − 13.25% to − 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene–clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. Conclusion Adapalene 0.1%–clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. Trial Registration ClinicalTrials.gov identifier NCT03615768.

BackgroundWith the events reporting on odors in drinking water, odorous substances in water have become a hot topic in water quality analysis. Due to the low concentration of the odor threshold and the complexity of the odor components in water, it is difficult to make accurate qualitative and quantitative analysis. So it is necessary to develop a highly sensitive and accurate qualitative and quantitative analysis method. ObjectiveTo establish a method for simultaneous determination of four odorous substances, including dimethyl disulfide, dimethyl trisulfide, 2-methylisoborneol, and geosmin in water by purge and trap-gas chromatography-tandem mass spectrometry. MethodsA certain amount of water sample was stored in the sample vial of a purge and trapinstrument. Through nitrogen purging, the odorous substances in water were purged out and enriched in the trap. Subsequently, the odorous substances were rapidly released at high temperatures after heating the trap, and then carried by carrier gas into gas chromatograph. After temperature programming, the substances were separated by an Agilent DB-624 capillary chromatographic column (30 m×0.25 mm, 1.4 μm) and determined by tandem mass spectrometry in multiple reaction monitoring modes, with internal standard method for quantification. The current project optimized purge time, sodium chloride concentration in water sample, desorption temperature, desorption time, and split ratio during the experimental process. Under the optimized experimental conditions, the standard curve, detection limit, and quantification limit were validated. Recovery tests with spiking concentrations of 5.0, 10.0, 30.0, 80.0 ng·L−1 and precision tests were conducted on water samples. Finally, the established method was applied to detect odorous substances in source water, finished water, and pipeline water in Deqing County of Huzhou City. ResultAfter the optimization, the purge time was 20 min, the desorption temperature was 280 ℃, the desorption time was 2 min, the split ratio was 10∶1, and no sodium chloride was added during the purge process. Under the optimized experimental conditions, the calibration curves for the four odorous substances showed an excellent linearity in the range of 1 to 100 ng·L−1 (R>0.999), with 0.3 ng·L−1 limit of detection and 1.0 ng·L−1 limit of quantitation. The average recoveries were from 85.5% to 102.4% and relative standard deviations (RSD) from 1.6% to 5.2%. After applying this method to detect local source water, finished water, and pipeline water, it was found that the positive rates of 2-methylisoborneo, and geosmin were relatively high, while the positive rates of dimethyl disulfide and dimethyl trisulfide were relatively low. Only one sample of source water tested positive for dimethyl disulfide, and all samples were negative for dimethyl trisulfide. ConclusionCombined with the superiority of purge and trap and tandem mass spectrometry, the method has the advantages of easy to perform, strong anti-interference ability, good accuracy and precision, which meet the limit requirements of the four odorous substances in the expanded indices and reference indices of Hygienic standards for drinking water (GB 5749-2022). It also provides technical support for water quality assessment and analysis of odorous substances.

Abstract The NOD2 signaling pathway, which plays an important role in the mechanisms of inflammatory bowel disease (IBD) development, has been closely associated with ubiquitination. It was revealed in this study that NOD2 receptor activation could obviously affect the expression of 19 ubiquitination-related genes, with N4BP3 being the most prominently expressed and upregulated. In addition, N4BP3 knockdown was found to reduce the mRNA levels of MDP-induced inflammatory factors, while N4BP3 overexpression elevated their mRNA levels as well as the levels of phospho-ERK1/2, phospho-JNK, phospho-P38 and phospho-NF-κB P65 proteins. Immunoprecipitation tests showed that N4BP3 could pull down RIPK2 and promote its K63-linked ubiquitination. In human tissue specimen assays and mouse experiments, we found that the expression of N4BP3 was significantly elevated in Crohn’s disease (CD) patients and IBD mice, and N4BP3 knockdown reduced the dextran sulfate sodium-induced pathological score and the expression of inflammatory factors in the mouse colon tissue. In conclusion, N4BP3 is able to interact with RIPK2 and promote its K63-linked ubiquitination, to further promote the NOD2-MAPK/NF-κB pathway, thereby increasing promoting the release of inflammation factors and the degree of IBD inflammation.

Abstract The occurrence and progression of tumors are linked to the process of pyroptosis. However, the precise involvement of pyroptosis-associated genes (PRGs) in endometrial cancer (EC) remains uncertain. 29 PRGs were identified as being either up-regulated or down-regulated in EC. PRGs subgroup analysis demonstrated distinct survival outcomes and diverse responses to chemotherapy and immune checkpoint blockade therapy. A higher expression of GPX4 and NOD2, coupled with lower levels of CASP6, PRKACA, and NLRP2, were found to be significantly associated with higher overall survival (OS) rates (p

Aim: This Mendelian randomisation (MR) study endeavoured to delineate the causal relationship between periodontitis and adverse pregnancy outcomes (APOs), encompassing low birthweight (LBW), pre-term birth (PTB), stillbirth, miscarriage, and gestational hypertension (GH). Methods: Utilising genetic instruments for periodontitis (acute and chronic periodontitis) from the Genome-Wide Association Study (GWAS) database among individuals of European descent, this study explored the causal relationship with adverse pregnancy outcomes, and vice versa. The Inverse Variance Weighted (IVW) method was employed as the primary analytical approach to assess causality, with MR-Egger serving as a sensitivity analysis method. Results: The primary analytical method employed in this study, IVW, did not reveal any impact of periodontitis (acute and chronic periodontitis) on PTB, stillbirth, miscarriage, and gestational hypertension, and vice versa. Heterogeneity testing using the MR-Egger method confirmed the null causal hypothesis, with odds ratios (OR) approximating 1, and P-values exceeding 0.05. Notably, the results from the IVW analysis (OR 1.410, CI 1.039-1.915, P-value 0.028) indicate statistically significant evidence supporting a causal relationship between chronic periodontitis and LBW. However, caution is advised in interpreting the causal relationship, considering the non-significant P-values obtained from other methods. Conclusion: Within the limitations of this MR study, the findings do not support the influence of periodontitis on LBW, PTB, stillbirth, miscarriage, and GH, nor vice versa.

In order to prevent the occurrence of coal mine roof accidents, it is of great significance to realize the knowledge discovery of accident causes and the network analysis of disaster chain. Taking the accident causes in the coal mine roof accident report as the data set, the knowledge map of accident causes was constructed. Further, based on the complex network theory, the causal disaster chain network is constructed and analyzed. The research results show that 22 factors, such as roof collapse, empty roof and support deformation, are the main disaster causing factors of coal mine roof accidents; the side with the greatest risk is from illegal command to illegal operation of operators in disaster chain network analysis. The control of key nodes and edges can effectively control the occurrence or derivative development of coal mine roof accidents.

Abstract Crop residues and their derived biochar are frequently used for their potential to improve grain yield, soil fertility and carbon (C) sequestration. However, the effects of root are often overlooked, and the effects of chemical fertilizer (NPK) combined with root or its biochar on microbial community structure need further study. This study used 13C-labeled maize root, its biochar and soil with different fertilization for 8 years as materials and substrates. A 112-day incubation experiment was conducted to explore the effects of microbial community on the C processing. During incubation, the root-C (54.9%) mineralized significantly more than biochar-C (12.8%), while NPK addition significantly increased the root-C mineralization. Adding biochar alone did not significantly change the microbial community. Compared to the biochar treatment (BC), the root treatment (R) notably increased the contents of total phospholipid fatty acids (PLFAs), 13C-PLFA and the proportion of fungi and Gram-negative bacteria, but reduced the proportion of actinomycetes. The root mineralization was significantly correlated with the relative content of 13C-Gram-positive bacteria and 13C-fungi, while biochar mineralization was significantly correlated with the relative content of 13C-Gram-positive bacteria and 13C-actinomycetes. Notably, NPK addition significantly increased the contribution of biochar-C to PLFA-C pool, while decreasing the contribution of root-C. In summary, due to microbial adaptation to the lack of bioavailable C in biochar-amended soil, biochar can act as a buffer against the significant disturbance caused by NPK to microbial communities and native soil organic carbon (SOC), which contributes to the steady enhancement in soil C storage. Graphical Abstract

Abstract Antibiotic-induced dysbiosis in the fish gut causes significant adverse effects. We use fecal microbiota transplantation (FMT) to accelerate the restoration of florfenicol-perturbed intestinal microbiota in koi carp, identifying key bacterial populations and metabolites involved in the recovery process through microbiome and metabolome analyses. We demonstrate that florfenicol disrupts intestinal microbiota, reducing beneficial genera such as Lactobacillus, Bifidobacterium, Bacteroides, Romboutsia, and Faecalibacterium, and causing mucosal injuries. Key metabolites, including aromatic amino acids and glutathione-related compounds, are diminished. We show that FMT effectively restores microbial populations, repairs intestinal damage, and normalizes critical metabolites, while natural recovery is less effective. Spearman correlation analyses reveal strong associations between the identified bacterial genera and the levels of aromatic amino acids and glutathione-related metabolites. This study underscores the potential of FMT to counteract antibiotic-induced dysbiosis and maintain fish intestinal health. The restored microbiota and normalized metabolites provide a basis for developing personalized probiotic therapies for fish.

Abstract Background Previous studies have identified a diverse group of microbial taxa that differ between patients with multiple sclerosis (MS) and the healthy population. However, interpreting findings on MS-associated microbiota is challenging, as there is no true consensus. It is unclear whether there is gut microbiota commonly altered in MS across studies. Methods To answer this, we performed a meta-analysis based on the 16S rRNA gene sequencing data from seven geographically and technically diverse studies comprising a total of 524 adult subjects (257 MS and 267 healthy controls). Analysis was conducted for each individual study after reprocessing the data and also by combining all data together. The blocked Wilcoxon rank-sum test and linear mixed-effects regression were used to identify differences in microbial composition and diversity between MS and healthy controls. Network analysis was conducted to identify bacterial correlations. A leave-one-out sensitivity analysis was performed to ensure the robustness of the findings. Results The microbiome community structure was significantly different between studies. Re-analysis of data from individual studies revealed a lower relative abundance of Prevotella in MS across studies, compared to controls. Meta-analysis found that although alpha and beta diversity did not differ between MS and controls, a higher abundance of Actinomyces and a lower abundance of Faecalibacterium were reproducibly associated with MS. Additionally, network analysis revealed that the recognized negative Bacteroides-Prevotella correlation in controls was disrupted in patients with MS. Conclusions Our meta-analysis identified common gut microbiota associated with MS across geographically and technically diverse studies.

Abstract Machine Learning models trained from real-world data have demonstrated promise in predicting suicide attempts in adolescents. However, their transportability, namely the performance of a model trained on one dataset and applied to different data, is largely unknown, hindering the clinical adoption of these models. Here we developed different machine learning-based suicide prediction models based on real-world data collected in different contexts (inpatient, outpatient, and all encounters) with varying purposes (administrative claims and electronic health records), and compared their cross-data performance. The three datasets used were the All-Payer Claims Database in Connecticut, the Hospital Inpatient Discharge Database in Connecticut, and the Electronic Health Records data provided by the Kansas Health Information Network. We included 285,320 patients among whom we identified 3389 (1.2%) suicide attempters and 66% of the suicide attempters were female. Different machine learning models were evaluated on source datasets where models were trained and then applied to target datasets. More complex models, particularly deep long short-term memory neural network models, did not outperform simpler regularized logistic regression models in terms of both local and transported performance. Transported models exhibited varying performance, showing drops or even improvements compared to their source performance. While they can achieve satisfactory transported performance, they are usually upper-bounded by the best performance of locally developed models, and they can identify additional new cases in target data. Our study uncovers complex transportability patterns and could facilitate the development of suicide prediction models with better performance and generalizability.

The grain characteristic and orientation were analyzed using the electron backscatter diffraction (EBSD) for AZ31 hot-rolled alloys. The corrosion initiation of the bimodal microstructure is revealed for the hot-rolled AZ31 alloys obtained by the quasi-in-situ EBSD, showing the preferential corrosion in the fine grain region. Meanwhile, the non-basal crystal plane grain is easier to corrode than the basal crystal plane grain. The adsorption energies of H2O molecule on the crystal planes of magnesium matrix were calculated by the density functional theory method, and a new insight into the corrosion anisotropy of crystal planes was proposed from the surface adsorption energy.

Abstract Background Enhanced glycolysis is a crucial metabolic event that drives the development of liver fibrosis, but the molecular mechanisms have not been fully understood. Lactate is the endproduct of glycolysis, which has recently been identified as a bioactive metabolite binding to G-protein-coupled receptor 81 (GPR81). We then questioned whether GPR81 is implicated in the development of liver fibrosis. Methods The level of GPR81 was determined in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and in transforming growth factor beta 1 (TGF-β1)-activated hepatic stellate cells (HSCs) LX-2. To investigate the significance of GPR81 in liver fibrosis, wild-type (WT) and GPR81 knockout (KO) mice were exposed to CCl4, and then the degree of liver fibrosis was determined. In addition, the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) was supplemented in CCl4-challenged mice and TGF-β1-activated LX-2 cells to further investigate the pathological roles of GPR81 on HSCs activation. Results CCl4 exposure or TGF-β1 stimulation significantly upregulated the expression of GPR81, while deletion of GPR81 alleviated CCl4-induced elevation of aminotransferase, production of pro-inflammatory cytokines, and deposition of collagen. Consistently, the production of TGF-β1, the expression of alpha-smooth muscle actin (α-SMA) and collagen I (COL1A1), as well as the elevation of hydroxyproline were suppressed in GPR81 deficient mice. Supplementation with DHBA enhanced CCl4-induced liver fibrogenesis in WT mice but not in GPR81 KO mice. DHBA also promoted TGF-β1-induced LX-2 activation. Mechanistically, GPR81 suppressed cAMP/CREB and then inhibited the expression of Smad7, a negative regulator of Smad3, which resulted in increased phosphorylation of Smad3 and enhanced activation of HSCs. Conclusion GPR81 might be a detrimental factor that promotes the development of liver fibrosis by regulating CREB/Smad7 pathway.

Abstract Background Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population. Methods To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS148); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS183); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRSGenomewide). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants. Results Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS183 demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose–response effect of PRS183 on incident colorectal neoplasms. Incorporating PRS183 with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32). Conclusions Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity. Graphical Abstract

Abstract Actuators based on shape memory polymers and composites incorporating nanomaterial additives have been extensively studied; achieving both high output stress and precise shape change by low‐cost, scalable methods is a long‐term‐desired yet challenging task. Here, conventional polymers (polyurea) and carbon nanotube (CNT) fillers are combined to fabricate reinforced composite fibers with exceptional actuation performance, by a wet‐spinning method amenable for continuous production. It is found that a thermal‐induced shrinkage step could obtain densified strong fibers, and the presence of CNTs effectively promotes the tensile orientation of polymer molecular chains, leading to much improved mechanical properties. Consequently, the CNT/ polyurea composite fibers exhibit stresses as high as 33 MPa within 0.36 s during thermal actuation, and stresses up to 22 MPa upon electrical stimulation enabled by the built‐in conductive CNT networks. Utilizing the flexible thin fibers, various shape change behavior are also demonstrated including the conversion between different structures/curvatures, and recovery of predefined simple patterns. This high‐performance composite fibers, capable of both thermal and electrical actuation and produced by low‐cost materials and fabrication process, may find many potential applications in wearable devices, robotics, and biomedical areas.

Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7–10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximately 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions. In vivo and in vitro results demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex likely through enhancing the voltage-gated K+ and also the leak K+ conductance. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising applications in other nervous system diseases.

Abstract Aggressive triple‐negative breast cancer (TNBC) still lacks approved targeted therapies, requiring more exploration of its underlying mechanisms. Previous studies have suggested a potential role of SAT1 (Spermidine/Spermine N1‐acetyltransferase 1) in cancer, which needs to be further elucidated in breast cancer. In this study, highly expressed SAT1 in TNBC signified worse patient prognoses. And SAT1 knockdown effectively inhibited the proliferation and migration abilities of TNBC cells in vitro and in vivo. In terms of mechanism, the transcription factor JUN enhanced SAT1 transcriptional activity by binding to its promoter region. Then, SAT1 protein in the cytoplasm engaged in directly binding with YBX1 for sustaining YBX1 protein stability via deubiquitylation mediated by the E3 ligase HERC5. Further, SAT1 was found to suppress autophagy remarkably via stabilization of mTOR mRNA with the accumulation of YBX1‐mediated methyl‐5‐cytosine (m5C) modification. These findings proved that SAT1 drives TNBC progression through the SAT1/YBX1/mTOR axis, which may provide a potential candidate for targeted therapy in advanced TNBC.

BackgroundObstructive sleep apnea (OSA) is a common sleep disorder. Inflammatory factors and plasma metabolites are important in assessing its progression. However, the causal relationship between them and OSA remains unclear, hampering early clinical diagnosis and treatment decisions.MethodsWe conducted a large-scale study using data from the FinnGen database, with 43,901 cases and 366,484 controls for our discovery MR analysis. We employed 91 plasma proteins from 11 cohorts (totaling 14,824 participants of European descent) as instrumental variables (IVs). Additionally, we conducted a GWAS involving 13,818 cases and 463,035 controls to replicate the MR analysis. We primarily used the IVW method, supplemented by MR Egger, weighted median, simple mode, and weighted mode methods. Meta-analysis was used to synthesize MR findings, followed by tests for heterogeneity, pleiotropy, and sensitivity analysis (LOO). Reverse MR analysis was also performed to explore causal relationships.ResultsThe meta-analysis showed a correlation between elevated Eotaxin levels and an increased risk of OSA (OR=1.050, 95% CI: 1.008-1.096; p < 0.05). Furthermore, we found that the increased risk of OSA could be attributed to reduced levels of X-11849 and X-24978 (decreases of 7.1% and 8.4%, respectively). Sensitivity analysis results supported the reliability of these findings.ConclusionsIn this study, we uncovered a novel biomarker and identified two previously unknown metabolites strongly linked to OSA. These findings underscore the potential significance of inflammatory factors and metabolites in the genetic underpinnings of OSA development and prognosis.

BackgroundSepsis is an inflammatory disease that leads to severe mortality, highlighting the urgent need to identify new therapeutic strategies for sepsis. Proteomic research serves as a primary source for drug target identification. We employed proteome-wide Mendelian randomization (MR), genetic correlation analysis, and colocalization analysis to identify potential targets for sepsis and sepsis-related death.MethodsGenetic data for plasma proteomics were obtained from 35,559 Icelandic individuals and an initial MR analysis was conducted using 13,531 sepsis cases from the FinnGen R10 cohort to identify associations between plasma proteins and sepsis. Subsequently, significant proteins underwent genetic correlation analysis, followed by replication in 54,306 participants from the UK Biobank Pharma Proteomics Project and validation in 11,643 sepsis cases from the UK Biobank. The identified proteins were then subjected to colocalization analysis, enrichment analysis, and protein-protein interaction network analysis. Additionally, we also investigated a MR analysis using plasma proteins on 1,896 sepsis cases with 28-day mortality from the UK Biobank.ResultsAfter FDR correction, MR analysis results showed a significant causal relationship between 113 plasma proteins and sepsis. Genetic correlation analysis revealed that only 8 proteins had genetic correlations with sepsis. In the UKB-PPP replication analysis, only 4 proteins were found to be closely associated with sepsis, while validation in the UK Biobank sepsis cases found overlaps for 21 proteins. In total, 30 proteins were identified in the aforementioned analyses, and colocalization analysis revealed that only 2 of these proteins were closely associated with sepsis. Additionally, in the 28-day mortality MR analysis of sepsis, we also found that only 2 proteins were significant.ConclusionsThe identified plasma proteins and their associated metabolic pathways have enhanced our understanding of the complex relationship between proteins and sepsis. This provides new avenues for the development of drug targets and paves the way for further research in this field.

Introduction: The treatment of COVID-19 patients, especially high-risk patients, remains a large challenge. Glucocorticoids have been accepted as effective medicines for severe COVID-19. However, the glucocorticoid usage guidelines do not cover all the indications for high-risk patients. Objective: To identify more effective treatments for high-risk patients with COVID-19, this retrospective study analyzed routine epidemiological, clinical, and laboratory data from 33 high-risk patients with COVID-19 in Beijing Gobroad Boren Hospital, Beijing, China, most of whom responded well to treatment. Methods: Severe acute respiratory syndrome coronavirus-2 infection was confirmed via real-time reverse transcriptase polymerase chain reaction assays. Outcome measures such as duration of mechanical ventilation, intensive care unit length of stay, and 28-day mortality were analyzed. Patients were divided into two groups: mild to moderate COVID-19 ( n = 26) and severe COVID-19 ( n = 7). Chest computed tomography images were used to guide methylprednisolone administration or withdrawal. Results: Upon intensive care unit admission, 12.1% of patients were mechanically ventilated with an average partial pressure of oxygen/fraction of inspired oxygen(PaO 2 /FiO 2 ) ratio of 279 ± 146. No coinfections with other endemic viruses were observed. The duration of mechanical ventilation was 16 days (interquartile range: 8–28); the intensive care unit length of stay was 11 (interquartile range: 2–33) days; and the 28-day total mortality was 3.0%. Conclusion: Multivariate regression analysis revealed that low-dose, timely methylprednisolone administration was associated with a lower severe COVID-19 rate and mortality in high-risk patients. For high-risk patients, once there are ground-glass opacities (GGO) in the computed tomography image, continuous and low-dose methylprednisolone administration promotes inflammation remission and protects them from severe COVID-19 or mortality.

Abstract Intervertebral disc degeneration (IDD) is a highly prevalent musculoskeletal disorder affecting millions of adults worldwide, but a poor understanding of its pathogenesis has limited the effectiveness of therapy. In the current study, we integrated untargeted LC/MS metabolomics and magnetic resonance spectroscopy data to investigate metabolic profile alterations during IDD. Combined with validation via a large-cohort analysis, we found excessive lipid droplet accumulation in the nucleus pulposus cells of advanced-stage IDD samples. We also found abnormal palmitic acid (PA) accumulation in IDD nucleus pulposus cells, and PA exposure resulted in lipid droplet accumulation and cell senescence in an endoplasmic reticulum stress-dependent manner. Complementary transcriptome and proteome profiles enabled us to identify solute carrier transporter (SLC) 43A3 involvement in the regulation of the intracellular PA level. SLC43A3 was expressed at low levels and negatively correlated with intracellular lipid content in IDD nucleus pulposus cells. Overexpression of SLC43A3 significantly alleviated PA-induced endoplasmic reticulum stress, lipid droplet accumulation and cell senescence by inhibiting PA uptake. This work provides novel integration analysis-based insight into the metabolic profile alterations in IDD and further reveals new therapeutic targets for IDD treatment.

Abstract Objectives The objectives of this study were to evaluate the cost-effectiveness and cost-benefit of fluoride varnish (FV) interventions for preventing caries in the first permanent molars (FPMs) among children in rural areas in Guangxi, China. Methods This study constituted a secondary analysis of data from a randomised controlled trial, analysed from a social perspective. A total of 1,335 children aged 6–8 years in remote rural areas of Guangxi were enrolled in this three-year follow-up controlled study. Children in the experimental group (EG) and the control group (CG) received oral health education and were provided with a toothbrush and toothpaste once every six months. Additionally, FV was applied in the EG. A decision tree model was developed, and single-factor and probabilistic sensitivity analyses were conducted. Results After three years of intervention, the prevalence of caries in the EG was 50.85%, with an average decayed, missing, and filled teeth (DMFT) index score of 1.12, and that in the CG was 59.04%, with a DMFT index score of 1.36. The total cost of caries intervention and postcaries treatment was 42,719.55 USD for the EG and 46,622.13 USD for the CG. The incremental cost-effectiveness ratio (ICER) of the EG was 25.36 USD per caries prevented, and the cost–benefit ratio (CBR) was 1.74 USD benefits per 1 USD cost. The results of the sensitivity analyses showed that the increase in the average DMFT index score was the largest variable affecting the ICER and CBR. Conclusions Compared to oral health education alone, a comprehensive intervention combining FV application with oral health education is more cost-effective and beneficial for preventing caries in the FPMs of children living in economically disadvantaged rural areas. These findings could provide a basis for policy-making and clinical choices to improve children’s oral health.

The deep coal mining in China is becoming more and more complicated. Under the influence of mining, structure or hard roof and floor, the section coal pillar is easy to induce coal pillar type rock burst. The prevention and control of coal pillar type rock burst has become a difficult problem in coal mine safety and efficient mining. It is of positive significance to study the mechanical properties and impact failure characteristics of section coal pillars under different width-height ratio for the prevention and control of coal pillar type rock burst. Uniaxial compression experiments were carried out on the “rock-coal-rock”combination of coal samples with different width-height ratio. The influence of width-height ratio on the impact failure of coal pillars was studied by analyzing the impact tendency, dynamic failure characteristics, fractal dimension and acoustic emission characteristic parameters of the combination. The results show that: ① The width-height ratio of coal pillar has a significant effect on the impact tendency of the combination. When the width-height ratio is not less than 2∶1, the impact energy index KE is 1.82−2.65, and the impact tendency has no obvious change. When is less than 2∶1, the impact tendency increases first and then decreases. When is 1∶1, KE is the largest, reaching 15.43. ② With the decrease of width-height ratio, the failure characteristics of the composite body are as follows: tension-compression failure-compression-shear failure-tension-shear failure. When the width-height ratio of the coal pillar is 5∶1−3∶1, the damage of the combination is relatively slow. When the width-height ratio is 2∶1, the flake coal chips begin to pop out, and the degree of impact damage is low. When the width-height ratio is 1∶1 and 0.75∶1, it has obvious impact failure characteristics. When the width-height ratio is 0.5∶1, the overall stability of the combination decreases, and the severity of the coal pillar failure of the 0.75∶1 sample combination decreases. ③ The energy release rate of post-peak acoustic emission is similar to that of fractal dimension D, which increases first and then decreases with the decrease of width-height ratio. When the width-height ratio is not less than 2∶1, the energy release time is longer during the failure process of the combination, and the coal pillar failure is gentle. When the width-height ratio is 1∶1, the energy release rate and D value increase significantly. Compared with the energy release rate of the combination with a width-height ratio of not less than 2∶1, the energy release rate increases by about 4 times, and the D value increases by 0.18−0.23. The impact damage of coal pillar is the most severe. The energy release rate and D value of the 0.75∶1 combination were reduced by about 10% and 0.01, respectively, and the damage severity was similar to that of the 1∶1 combination. When the width-height ratio is reduced to 0.5∶1, the reduction of the relevant parameters is about 6 times that of the 0.75∶1 combination, and the degree of damage is relatively small.The results show that the width-height ratio has a significant effect on the impact failure of coal pillars. On the whole, the intensity of impact failure of coal pillars increases first and then decreases gradually with the decrease of width-height ratio (5∶1−0.5∶1). When the width-height ratio of coal pillar is greater than 3∶1, the rock burst risk is relatively small. When the width-height ratio of coal pillar is 1∶1 and 0.75∶1, the rock burst risk is larger, followed by 0.5∶1.

In order to expand the relevant theory of fractional differential equation systems, a class of coupled φ-Hilfer fractional differential systems with integral boundary conditions was studied. Firstly, the coupled φ-Hilfer fractional differential system with integral boundary conditions was transformed into an integral system. Secondly, the appropriate Banach product space and norm were defined, the appropriate integral operator was constructed, and the existence result of the solution of the coupled φ-Hilfer fractional differential system under the integral boundary condition was given by using the compressed image principle and Kransnoselskii's fixed point theorem, respectively. Finally, examples were given to illustrate the correctness of the conclusions obtained. The results show that the solutions of the coupled φ-Hilfer fractional differential system under the integral boundary condition exist. The existence of solutions of coupled φ-Hilfer fractional differential systems is studied for the first time by using the compressed image principle and Kransnoselskii's fixed point theorem, respectively, and some innovative new results are obtained. In addition, the research conclusion enriches the relevant theories of the theoretical solvability of coupled fractional differential systems, and provides certain theoretical reference value for the further study of fractional order differential equations.

On April 3, 2024, at 07:58 (Beijing time), a magnitude 7.3 earthquake occurred in the waters of Hualien County, Taiwan Province. The Institute of Geophysics, China Earthquake Administration initiated a rapid response after the earthquake and organized geophysics researchers to estimate the source model and seismic radiation energy of the earthquake. Based on the source model, the shakemap and coseismic deformation field simulation were carried out. The results indicate that the earthquake occurred at the boundary between the Philippine Sea Plate and the Eurasian Plate, primarily characterized by a thrust mechanism, with energy released predominantly in the first 35 seconds. The earthquake intensity in the extreme seismic area possibly have reached more than X degree, with a potential disaster area of approximately 35000 km2. The earthquake also caused significant coseismic displacements, with the maximum horizontal displacement reaching 0.52 m and the vertical displacement reaching 1.18 m.

Abstract The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop eight candidate PPSs. Further using an independent cohort with 470 patients, we identify the 287 variants-derived PPS (i.e., PPS287) achieving an optimal prediction performance [hazard ratio (HR) per SD = 1.99, P = 1.76 × 10−8], accompanied by additional tests in two external cohorts, with HRs per SD of 1.90 (P = 3.21 × 10−14; 543 patients) and 1.80 (P = 1.11 × 10−9; 713 patients). Notably, the detrimental impact of pathologic characteristics and genetic risk could be attenuated by a healthy lifestyle, yielding a 7.62% improvement in the 5-year overall survival rate. Therefore, our findings demonstrate the integrated contribution of pathologic characteristics, germline variants, and lifestyle exposure to the prognosis of colorectal cancer patients.

On January 23，2024 at 02:09 (Beijing time), the MS7.1 earthquake occurred in Wushi county, Aksu Prefecture, Xinjiang. The Institute of Geophysics, China Earthquake Administration initiated a rapid response after the earthquake, organized researchers in related fields to estimate the source parameters, seismic radiation energy, and repositioned the aftershock sequence. At the same time, seismic map simulation and co-seismic deformation field simulation were carried out based on the source model. The results indicate that the earthquake occurred within the Tianshan Mountains, mainly through a thrust mechanism, with energy concentrated and released within the first 25 seconds; The seismic intensity in the extreme earthquake zone may reach over Ⅸ degrees, with a possible disaster area of nearly 65000 km2; This earthquake caused significant coseismic displacement, with a maximum horizontal displacement of 21 cm and a vertical displacement of 38 cm.

Abstract Background Type 2 diabetes mellitus (T2DM) causes severe bone loss after tooth extraction as a hyperglycemic environment causes aberrant bone homeostasis. Artesunate (ART) is known to possess anti-inflammation and osteogenic properties. However, its osteogenesis property in alveolar bone remains unclear. This study aimed to explore the osteogenic and immunoregulatory effects of artesunate-loaded thermosensitive chitosan hydrogel (ART-loaded TCH) on maxilla tooth extraction in T2DM rats. Methods T2DM rats were induced by a high-fat diet and streptozotocin. Different concentrations of ART-loaded TCH were applied in tooth extraction sockets. Bone loss and the expression of osteogenic regulatory factors (OPG, ALP, RANK) were evaluated. The immunoregulatory effects of ART-loaded TCH were observed through detecting the infiltration of T lymphocytes and their cytokines. The underlying mechanisms were explored. Results Results showed that the 150 mg/ml ART-loaded TCH group significantly ameliorated maxilla bone height and bone mineral density when compared with the T2DM group (p

Abstract Background Although previous studies have found that parenting style significantly predicts emotional and behavioral problems (EBPs) among Chinese adolescents, the mechanism between different parenting styles and EBPs requires in-depth investigation. In our study, we aimed to investigate the mediating effect of resilience, a positive psychological characteristic, between parenting style and EBPs among Chinese adolescents. Methods In this cross-sectional study, we used a multistage stratified cluster random sampling method to collect data in Shenyang, Liaoning Province from November to December 2019. Self-developed questionnaires were distributed to 1028 adolescents aged 10–18. Finally, the study consisted of 895 participants. The bootstrap method was used to investigate the role of resilience as a mediator in the relationship between different parenting styles and EBPs from a positive psychology perspective. Results The mean score of EBPs was 12.71 (SD = 5.77). After controlling for variables such as gender, age, left-behind children, family type and family income, resilience partially played a mediating role in the associations of paternal rejection (a × b = 0.051 BCa95%CI:0.023,0.080), maternal rejection (a × b = 0.055 BCa95%CI: 0.024, 0.086), paternal emotional warmth (a × b = -0.139 BCa95%CI: -0.182, -0.099) and maternal emotional warmth (a × b = -0.140 BCa95%CI: -0.182, -0.102), with EBPs. The effect sizes were11.28%, 11.51%, 40.76%, and 38.78%, respectively. Conclusions Resilience could partially mediate the relationship between parenting style and EBPs, highlighting that parents should adopt a positive parenting style and that resilience improvement could be effective in reducing EBPs among Chinese adolescents.

Based on the simulation results of ProCAST software for the filling and solidification process, the formation mechanism of the VIM electrode ingot's pipe and porosities and the influence of the casting process on the formation of electrode shrinkage were studied in detail. The research results indicate that the critical condition for the formation of 200 kg grade C650R heat-resistant alloy is verified to be G/R≤5.0 (K·s)0.5/cm. In addition to the alloy's inherent characteristics, the substantial height to diameter ratio (H/D) of the VIM electrode ingot is the primary factor contributing to the formation of deep pipe and severe porosities. Simply adjusting the casting time or casting speed alone does not significantly improve the solidification quality of the ingot. While the use of a hot top can eliminate pipe, its effectiveness is limited, as the alloy melt at the hot top location has minimal influence on the solidification process in the lower regions of the electrode ingot, thereby failing to effectively reduce the formation of porosities. Properly reducing the casting speed and casting superheat lead to the formation of a V-shaped melt at localized positions during the final stage of solidification. This enhances the ability of the liquid phase for further feeding, ultimately significantly decreasing both the depth of pipe and the porosity rate. The optimal casting process optimization solution for C650R alloy electrode ingot with a size of Φ130 mm × 1240 mm is the casting speed of 60 kg/min and the superheat of 40 °C.

Sorafenib is a first-line drug for liver cancer treatment, but its clinical efficacy is still limited by drawbacks such as drug tolerance, toxic effects, and low bioavailability. Therefore, it is urgent to find efficient ways to synergize sorafenib with other agents and increase its bioavailability in order to enhance its clinical efficacy. Herein, we report the successful development of a carrier-free nanoplatform of an artesunate prodrug to potentiate the efficacy of sorafenib against hepatocellular carcinoma. The artesunate prodrug was synthesized by conjugating artesunate and linoleic acid through a thioketone (TK) bond. This prodrug can self-assemble in an aqueous solution via a one-step precipitation method. Furthermore, the inclusion of sorafenib during the self-assembly process results in a carrier-free artesunate/sorafenib mixed nanomedicine (SA@NPs) with a uniform and stable particle size. In addition, SA@NPs possess ROS-responsive drug-releasing ability by breaking up thioketone bonds under high H2O2 levels in tumors. The synergistic anticancer effects of SA@NPs have been demonstrated both in vivo and in vitro. SA@NPs can achieve significantly enhanced synergetic ferroptosis of tumor cells and show potentiated sorafenib efficacy against hepatocellular carcinoma. Moreover, SA@NPs have a tumor inhibition rate of 84.2%, which is 1.63-, 4.22-, and 1.29-fold higher than that in the experimental groups treated with free sorafenib, artesunate, and the simplified combined medication of sorafenib/artesunate, respectively. Overall, this work presents a significant advancement in the clinical chemotherapy of liver cancer and may pave the way for promising developments in the compatibility and clinical combination application of traditional Chinese medicine.

Background: Actinic keratoses (AK) may progress into squamous cell carcinoma. Many combination therapies were used to improve the clearance rate. However, there are limited studies on the efficacy and safety of lesion-directed Liquid nitrogen cryotherapy combined with field-directed photodynamic therapy (PDT). Objective: This study is aimed to determine the efficacy and safety of Liquid nitrogen cryotherapy combined with PDT in Chinese patients with actinic keratosis. Methods: A total of 61 patients with AK were selected at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College between August 2018 and August 2023. They were randomly divided into PDT plus Liquid nitrogen cryotherapy group (LN-PDT) and control PDT group (C-PDT) with 30 patients and 31 patients, respectively. 27 patients in the LN-PDT group and 28 patients in the C-PDT group completed the clinical sessions. Efficacy, adverse effects, and cosmetic outcomes were recorded and compared between the two groups. Results: 3 months after the final treatment, the clearance rates for total AK lesions were 97.4 % (449/461) in the LN-PDT group and 93.4 % (456/488) in the C-PDT group (P < 0.05). For grade I AK lesions, the clearance rates were 99.2 % (234/237) for the LN-PDT group and 98.3 % (237/241) for the C-PDT group (P >0.05). For grade II lesions, the clearance rates were 97.5 % (156/160) for the LN-PDT group and 91.9 % (172/186) for the CPDT group (P < 0.05). For grade III lesions, the clearance rates of the LN-PDT and C-PDT groups were 87.5 % (58/64) and 78.7 % (47/61), respectively (P < 0.05). The two groups had no significant differences in pain, erythema, edema, hyperpigmentation and scarring. Cosmetic outcomes mainly were excellent or good in both groups with no significant difference. Conclusion: Liquid nitrogen cryotherapy combined with PDT showed higher efficacy on grade II and grade III AK lesions than PDT alone. The two groups have similar adverse effects and cosmetic outcomes.

Prosocial behaviour is a bedrock of humane societies. Although previous studies have shown that parental style is an important contributing factor for children's prosocial behaviour, the psychological mechanism underlying this association in specific cultural background remains unclear. Based on the ecological systems theory, this study sought to explore the influence of parental warmth on children's prosocial behaviour, and the mediating effect of self-efficacy, as well as the moderating role of teachers' incentive evaluation in the link between self-efficacy and children's prosocial behaviour. This cross-sectional, survey-based study collected data from parents and teachers of 414 Chinese preschoolers (5–6 years old). Parents of these children finished questionnaires on the Chinese version of the short-form Egna minnen av. Barndoms uppfostran (s-EMBU-C), Child Behaviour Scale (CBS), and the revised General Self-efficacy Scale (GSES), while Incentive evaluation questionnaire was finished by their teachers. Results indicated that children who experience high parental warmth were more likely to act prosocially (b = 0.61, p

Abstract Background Deafness autosomal dominant 2A (DFNA2A) is related to non‐syndromic genetic hearing impairment. The KCNQ4 (Potassium Voltage‐Gated Channel Subfamily Q Member 4) can lead to DFNA2A. In this study, we report a case of autosomal dominant non‐syndromic hearing loss with six family members as caused by a novel variant in the KCNQ4 gene. Methods The whole‐exome sequencing (WES) and pure tone audiometry were performed on the proband of the family. Sanger sequencing was conducted on family members to determine if the novel variant in the KCNQ4 gene was present. Evolutionary conservation analysis and computational tertiary structure protein prediction of the wild‐type KCNQ4 protein and its variant were then performed. In addition, voltage‐gated channel activity of the wild‐type KCNQ4 protein and its variant were tested using whole‐cell patch clamp. Results It was observed that the proband had inherited autosomal dominant, non‐syndromic sensorineural hearing loss as a trait. A novel co‐segregating heterozygous missense variant (c.902C>A, p.Ala301Asp) of the KCNQ4 gene was identified in the proband and other five affected family members. This variant was predicted to cause an alanine‐to‐aspartic acid substitution at position 301 in the KCNQ4 protein. The alanine at position 301 is well conserved across different species. Whole‐cell patch clamp showed that there was a significant difference between the WT protein currents and the mutant protein currents in the voltage‐gated channel activity. Conclusion In the present study, performing WES in conjunction with Sanger sequencing enhanced the detection of a novel, potentially causative variant (c301 A>G; p.Ala301Asp) in exon 6 of the KCNQ4 gene. Therefore, our findings contributed to the mutation spectrum of the KCNQ4 gene and may be useful in the diagnosis and gene therapy of deafness autosomal dominant 2A.

PurposeThis study aimed to establish and evaluate the value of integrated models involving 18F-FDG PET/CT-based radiomics and clinicopathological information in the prediction of pathological complete response (pCR) to neoadjuvant therapy (NAT) for non-small cell lung cancer (NSCLC).MethodsA total of 106 eligible NSCLC patients were included in the study. After volume of interest (VOI) segmentation, 2,016 PET-based and 2,016 CT-based radiomic features were extracted. To select an optimal machine learning model, a total of 25 models were constructed based on five sets of machine learning classifiers combined with five sets of predictive feature resources, including PET-based alone radiomics, CT-based alone radiomics, PET/CT-based radiomics, clinicopathological features, and PET/CT-based radiomics integrated with clinicopathological features. Area under the curves (AUCs) of receiver operator characteristic (ROC) curves were used as the main outcome to assess the model performance.ResultsThe hybrid PET/CT-derived radiomic model outperformed PET-alone and CT-alone radiomic models in the prediction of pCR to NAT. Moreover, addition of clinicopathological information further enhanced the predictive performance of PET/CT-derived radiomic model. Ultimately, the support vector machine (SVM)-based PET/CT radiomics combined clinicopathological information presented an optimal predictive efficacy with an AUC of 0.925 (95% CI 0.869–0.981) in the training cohort and an AUC of 0.863 (95% CI 0.740–0.985) in the test cohort. The developed nomogram involving radiomics and pathological type was suggested as a convenient tool to enable clinical application.ConclusionsThe 18F-FDG PET/CT-based SVM radiomics integrated with clinicopathological information was an optimal model to non-invasively predict pCR to NAC for NSCLC.

Introduction This study aimed to assess the causal relationship between diabetes and frozen shoulder by investigating the target proteins associated with diabetes and frozen shoulder in the human plasma proteome through Mendelian randomization (MR) and to reveal the corresponding pathological mechanisms.Research design and methods We employed the MR approach for the purposes of establishing: (1) the causal link between diabetes and frozen shoulder; (2) the plasma causal proteins associated with frozen shoulder; (3) the plasma target proteins associated with diabetes; and (4) the causal relationship between diabetes target proteins and frozen shoulder causal proteins. The MR results were validated and consolidated through colocalization analysis and protein–protein interaction network.Results Our MR analysis demonstrated a significant causal relationship between diabetes and frozen shoulder. We found that the plasma levels of four proteins were correlated with frozen shoulder at the Bonferroni significance level (p

Abstract Clamping bushing structure is an internode connection mechanism designed for the standard section of tubular truss tower. In this paper, the clamping bushing structure of the connecting mechanism of super-large tower crane is taken as the research object, a three-dimensional model of clamping bushing structure is established and imported into ABAQUS, and its multi-body contact model is further constructed to study the contact and bearing relationship of the structure under multiple working conditions, and the accuracy of the calculation results of the model is verified by the experimental stress test under tensile working conditions. In addition, this study is based on the control variable method, and through the design of orthogonal test table, the influence degree of five variable parameters of clamping bushing on the bearing capacity of the structure is investigated. Finally, through the range analysis, the optimal horizontal combination of variables and parameters of clamping bushing structure is obtained, and the optimal matching relationship between the shape of the tower connecting mechanism and the bearing capacity is obtained. The results show that, compared with the original model, the stress concentration at the most dangerous section of the optimized joint and the bushing is obviously alleviated, in which the stress peaks of the upper and lower joints are kept below 500 MPa, and the stress peaks of the bushing groove are also reduced to between 573 and 722 MPa. Moreover, the designed and optimized lower joint can reduce the maximum equivalent plastic strain of the joint root circumference by 56.05% under the original maximum tensile condition, and the overall distribution trend of equivalent plastic strain is more uniform, and a more reliable structural design is obtained, which plays an important guiding role in the design, optimization and analysis of the connecting mechanism of the tower body of large tower crane.

Abstract Background Environmental factors play an important role in developing mental disorders. This study aimed to investigate the associations of metal and nonmetal elements in drinking water with the risk of depression and anxiety and to assess whether diets modulate these associations. Methods We conducted a prospective cohort study including 24,285 participants free from depression and anxiety from the Yinzhou Cohort study in the 2016–2021 period. The exposures were measured by multiplying metal and nonmetal element concentrations in local pipeline terminal tap water samples and total daily drinking water intakes. Cox regression models adjusted for multi-level covariates were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95%CIs). Results During an average follow-up period of 4.72 and 4.68 years, 773 and 1334 cases of depression and anxiety were identified, respectively. A 1 standard deviation (SD) increase in manganese exposure reduced the incidence of depression by 8% (HR 0.92, 95%CI 0.88 to 0.97). In contrast, with a 1 SD increase in copper and cadmium exposure, the incidence of depression increased by 6% (HR 1.06, 95%CI 1.01 to 1.11) and 8% (HR 1.08, 95%CI 1.00 to 1.17), respectively. The incidence of anxiety increased by 39% (HR 1.39, 95%CI 1.20 to 1.62), 33% (HR 1.33, 95%CI 1.03 to 1.71), and 14% (HR 1.14, 95%CI 1.03 to 1.25) respectively for a 1 SD increase in manganese, iron, and selenium exposure. Diets have a moderating effect on the associations of metal and nonmetal elements with the risk of anxiety. Stronger associations were observed in older, low-income groups and low-education groups. Conclusions We found significant associations between exposure to metal and nonmetal elements and depression and anxiety. Diets regulated the associations to some extent.

Abstract Background In the global trend of actively promoting the participation of older adults in the digital age, the relevant negative issues featuring potential Internet Addiction (IA) among them has risen to be a new challenge facing the global public health. However, there is a severe lack of related research. This study aimed to gain a comprehensive understanding of the phenomenon and process of IA among the elderly. The purpose of this paper is to introduce factors that may influence IA in the demographic. Methods This study employed qualitative descriptive research methods to investigate older adults’ perceptions and experiences of IA. Semi-structured in-depth personal interviews were conducted between March and June 2023 with 36 senior citizens from urban communities in Chongqing, Southwest China. Data were analyzed via inductive content analysis methods. Results Through data analysis, 2 main categories concerning IA in older adults were identified: risk factors and protective factors. The risk factor categories include 5 individual factors (e.g., Internet as the major avenue for pursuing personal hobbies and interests, etc.), 3 family factors (e.g., household WIFI increasing the risk of prolonged Internet use indoors, etc.), 2 peer factors (e.g., peer recommendation and guidance as catalysts for intensified Internet engagement, etc.), 2 socio-environmental factors (e.g., the widespread daily Internet use spurs offline intolerance, etc.), and 3 Internet platform factors (e.g., the plenitude of online content triggers endless viewing/browsing behaviors, etc.). The category of protective factors encompasses 2 individual factors (e.g., a higher level of perceived risk regarding internet health hazards, etc.) and 2 family factors (e.g., more family commitment, etc.). Conclusions Older adults’ Internet addictive behaviors are shaped by multiple and complex internal and external factors. A higher level of online health risk perception is a key protective factor to effectively avoid the occurrence and deterioration of IA among the aged, a distinct finding from this study. It is believed that the “individual-family-peer-community” synergy strategy is expected to become an essential direction for IA intervention for older adults, in order to promote healthy Internet use among older adults.

At 22:37 on December 2, 2023 (Beijing time), a M7.6 earthquake occurred in the eastern waters of Mindanao，Philippines. The Institute of Geophysics, China Earthquake Administration initiated the response mechanism after this earthquake and organized geophysics researchers to estimate the source parameters, focal mechanism，rupture process and earthquake radiation energy of this earthquake. Based on the source model, the Shakemap and the coseismic deformation field simulation are carried out. Product results demonstrate that this earthquake occurred on the subduction zone slab where the Philippine Sea Plate collided with the Eurasian Plate/Sunda Block. This earthquake is of dominant thrusting mechanism. The energy was concentrated and released in the first 40 seconds. The maximum slip of the fault rupture is up to 7 m. The efficiency of the earthquake source in radiating seismic energy is low and the slowness coefficient is slightly lower than the average level of the global same moment magnitude earthquake, and the feeling of the earthquake is relatively weak. The earthquake intensity in the extreme seismic area possibly reaches more than Ⅸ, and the approximate disaster range is up to 27000 km2. This earthquake caused apparent coseismic displacement with the maximum displacements reaching 0.6 m and 1.2 m in the horizontal and vertical directions respectively. Comprehensive analysis shows that this earthquake can’t produce a large-scale tsunami.

Abstract Adventitious root formation is a key step in vegetative propagation via cuttings. It is crucial for establishing birch plantations and preserve birch varieties. Although previous studies have highlighted role of WOX11 in controlling adventitious root formation, no such study has been conducted in birch. Understanding the mechanism of adventitious root formation is essential for improvement of rooting or survival rate using stem cuttings in birch. In this study, we cloned BpWOX11 and produced BpWOX11 overexpression (OE) transgenic lines using the Agrobacterium-mediated plant transformation. OE lines exhibited early initiated adventitious root formation, leading to increase the rooting rate of stem cuttings plants. RNA sequencing analysis revealed that OE lines induced the gene expression related to expansin and cell division pathway, as well as defense and stress response genes. These may be important factors for the BpWOX11 gene to promote adventitious root formation in birch cuttings. The results of this study will help to further understand the molecular mechanisms controlling the formation of adventitious roots in birch.

AbstractCyperus malaccensis Lam is a perennial herbaceous plant that is distributed over a large area along the southern coast of China. Some plants of the Cyperaceae family are highly similar morphologically, which makes them difficult to classify and identify. In this study, the complete chloroplast genome of C. malaccensis was sequenced and assembled. The chloroplast genome is 186,098 bp long with a 33.18% content of GC. The structure of chloroplast genome includes a quadripartite structure that is composed of a pair of inverted repeats (IRs) of 37,434 bp, a small single copy (SSC) region of 10,296 bp, and a large single copy (LSC) region of 100,934 bp. The genome contains 141 genes, including 94 protein-coding genes, 39 tRNA genes, and 8 rRNA genes. A phylogenetic analysis showed that C. malaccensis is the most closely related to the congeneric species C. rotundus. These results enrich the genetic resources of the Cyperaceae and provide a molecular basis for further study on the phylogeny of this family.

At 23:59 on December 18, 2023 (Beijing time), a M6.2 earthquake occurred in the Gansu Province of Jishishan. The Institute of Geophysics，China Earthquake Administration initiated the response mechanism after this earthquake and organized geophysics researchers to estimate the source parameters, focal mechanism, rupture process, earthquake radiation energy and earthquake relocation of this earthquake. Based on the source model, the Shakemap and the coseismic deformation field simulation are carried out. The results demonstrate that the earthquake is of dominant thrusting mechanism. The energy was concentrated and released in the first 8 seconds. The earthquake intensity in the extreme seismic area possibly exceeded Ⅷ, resulting in an estimated disaster range of approximately 6000 km2. This earthquake caused apparent horizontal coseismic displacement with maximum displacements reaching 7.8 cm and 15.8 cm.

Abstract To evaluate the possible thermal risks associated with the storage of octogen (HMX), non-isothermal differential scanning calorimetry (DSC) experiments were conducted in order to ascertain the kinetic model and parameters governing its thermal decomposition. DSC measurements indicate that HMX underwent a crystal transformation prior to thermal decomposition. A kinetic model for the autocatalytic thermal decomposition process was developed through the analysis of its primary exothermic peaks. Subsequently, numerical simulations were performed using the aforementioned kinetic model to assess the potential thermal explosion hazard of HMX under two distinct storage conditions. The comparison was made between the models of HMX autocatalytic decomposition temperature and thermal explosion critical temperature under two distinct storage conditions. The prediction of the influence of ambient temperature on the critical temperature of thermal explosion is conducted simultaneously. Finally, the thermal hazard parameters of HMX under different package quality are given.

This is an essay in the field of mineral processing engineering. Based on the process mineralogy, a mixed process containing roasting-water quenching-hot pressure leaching was applied to purify a white pegmatite ore from Inner Mongolia. The optimum condition was obtained via various tests. The content of SiO2 in the final product was increased from 99.917% to 99.994%, while the total impurity content was decreased from 419.9 to 54.79 g/t, with a total removal of 86.95%. The main impurity element of Al was decreased from 250.9 g/t to 26.09 g/t, with a removal of 89.60%. Therefore, this study provides a good purification approach for high-purity quart preparation.

Abstract Target trial emulation is the process of mimicking target randomized trials using real-world data, where effective confounding control for unbiased treatment effect estimation remains a main challenge. Although various approaches have been proposed for this challenge, a systematic evaluation is still lacking. Here we emulated trials for thousands of medications from two large-scale real-world data warehouses, covering over 10 years of clinical records for over 170 million patients, aiming to identify new indications of approved drugs for Alzheimer’s disease. We assessed different propensity score models under the inverse probability of treatment weighting framework and suggested a model selection strategy for improved baseline covariate balancing. We also found that the deep learning-based propensity score model did not necessarily outperform logistic regression-based methods in covariate balancing. Finally, we highlighted five top-ranked drugs (pantoprazole, gabapentin, atorvastatin, fluticasone, and omeprazole) originally intended for other indications with potential benefits for Alzheimer’s patients.

Spatiotemporal big data contain information in multiple dimensions such as space and time. Spatiotemporal data have the characteristics of large volume, intricate spatiotemporal relationship, and uneven spatiotemporal distribution. Index structure is one of the most important technologies used to improve system data analysis and workload. However, it is difficult to dynamically adjust with data density, resulting in increased maintenance costs and retrieval complexity. At the same time, maintaining the proximity of spatiotemporal data in spatial or temporal dimensions is crucial for efficient spatiotemporal analysis. To address these challenges, this paper proposes a learned index method, GLMI (Geohash and piecewise linear model-based index for spatiotemporal data). GLMI uses dynamic space partitioning based on the Hilbert curve to reduce the impact of data skew on index performance. In the time dimension, a piecewise linear model was constructed using the ShrinkingCone algorithm, and a buffer was designed to support the fast writing of spatiotemporal data. Compared with the current mainstream traditional high-dimensional indexes and the ZM index, GLMI has a smaller space consumption and shorter construction time compared to high-dimensional learned indexes on real traffic itinerary and trajectory record datasets. Meanwhile, GLMI also has an advantage in query efficiency.

Arsenic (As) pollution in rice (Oryza sativa L.), a staple food for over 3.5 billion people, is a global problem. Mixed effects of Zn, Cu, and Si amendments on plant growth and yield, including in the presence of As pollution have been reported in previous studies. To better investigate the effectiveness of these amendments on rice growth, yield, and As accumulation, we conducted a rice greenhouse experiment with 11 treatments, including control pots with and without As contamination and pots with amendments of ZnO, CuO, and SiO2 nanoparticles (ZnO NPs, CuO NPs, and SiO2 NPs), their ionic counterparts (ZnSO4, CuSO4, and Na2SiO3), and bulk particles (ZnO BPs, CuO BPs, and SiO2 BPs). Compared with the background soil, the treatment of adding As decreased rice plant height, panicle number, and grain yield by 16.5%, 50%, and 85.7%, respectively, but significantly increased the As accumulation in milled rice grains by 3.2 times. Under As contamination, the application of Zn amendments increased rice grain yield by 4.6–7.3 times; among the three Zn amendments, ZnSO4 performed best by fully recovering grain yield to the background level and significantly reducing grain AsIII/total As ratio by 46.9%. Under As contamination, the application of Cu amendments increased grain yield by 3.8–5.6 times; all three Cu amendments significantly reduced grain AsIII/total As ratio by 20.2–65.6%. The results reveal that Zn and Cu amendments could promote rice yield and prevent As accumulation in rice grains under As contamination. Despite the observed reduction in As toxicity by the tested NPs, they do not offer more advantages over their ionic counterparts and bulk particles in promoting rice growth under As contamination. Future field research using a broader range of rice varieties, investigating various As concentrations, and encompassing diverse climate conditions will be necessary to validate our findings in achieving more extensive understanding of effective management of arsenic contaminated rice field.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown etiology. Pirfenidone (PFD) and nintedanib (NDN) were both conditionally recommended in the clinical practice guideline published in 2015. Safety and tolerability are related to the risk of treatment discontinuation. Therefore, this study evaluated and compared the adverse events (AEs) of PFD and NDN in a large real-world population by analyzing data from the FDA Adverse Event Reporting System (FAERS) to provide a reference for their rational and safe use.MethodsThe AEs of PFD and NDN were extracted from the FAERS database. The pharmacovigilance online analysis tool OpenVigil 2.1 was used to retrieve data from the FAERS database from the first quarter of 2012 to the second quarter of 2022. The reporting odds ratio (ROR) and proportional reporting ratio were used to detect the risk signals.ResultsThe database included 26,728 and 11,720 reports for PFD and NDN, respectively. The most frequent AEs of PFD and NDN were gastrointestinal disorders. The RORs for these drugs were 5.874 and 5.899, respectively. “Cardiac disorders” was the most statistically significant system order class for NDN with an ROR of 9.382 (95% confidence interval = 8.308–10.594). Furthermore, the numbers of designated medical events of PFD and NDN were 552 and 656, respectively. Notably, liver injury was reported more frequently for NDN (11.096%) than for PFD (6.076%).ConclusionThis study revealed differences in the reporting of AEs between PFD and NDN. The findings provide reference for physicians in clinical practice. Attention should be paid to the risks of cardiac disorders and liver injury associated with NDN.