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In order to improve the edible quality of pork patties during storage, this experiment employed different types of polysaccharides (konjac glucomannan, soybean polysaccharide, and purple yam polysaccharide) as film-forming matrices, with glycerol as a plasticizer. Seaweed polyphenols were added to prepare a composite preservation coating solution. The coating solution was applied to the pork patties using an immersion method. Various indicators, such as total viable count, total volatile basic nitrogen (TVB-N), and thiobarbituric acid reactive substances (TBARS), were measured after refrigerating the pork patties at 4±1 ℃. The study aimed to investigate the effect of seaweed polyphenol-polysaccharide composite preservation coating on the storage quality of pork patties. The results showed that after 7 days of storage, compared with the untreated group, the composite coatings of konjac glucomannan, soybean polysaccharide, and purple yam polysaccharide reduced the total viable count by 24.65%, 30.41%, and 35.02%, respectively. The TVB-N values decreased by 26.90%, 33.40%, and 44.68%, respectively, while the TBARS values decreased by 22.94%, 29.44%, and 38.10%, respectively. The pH values decreased by 4.38%, 5.14%, and 6.19%, respectively. Additionally, there were significant improvements (P

Abstract Background To explore the changes of iris-trabecular contact (ITC) and intraocular pressure (IOP) in patients who underwent penetrating keratoplasty (PK) during early postoperative period. Methods This prospective study finally included 46 eyes of 46 patients who underwent PK or triple surgery. Slit lamp examinations, IOP and anterior segment optical coherence tomography (AS-OCT) scans were examined before surgery, and at one-day, one-week, and one-month follow-ups. The parameters of anterior segment, IOP values and ITC ranges were compared. Additionally, the correlation analyses were performed to reveal risk factors of high IOP and postoperative ITC. Results The anterior segment underwent a significant reconstruction in the early postoperative period. Preoperative ITC was present in one-third of subjects. ITC significantly decreased on the first postoperative day, but showed marked regression at one-week follow-up. For patients without preoperative ITC, there was a small incidence (10%) of new ITC occurrence. The correlation analysis indicated that the most related factor of postoperative ITC was the presence of preoperative ITC. A high IOP was measured in 15 patients during one month, and it was inclined to occur on the first postoperative day and in patients who accepted triple surgery. Conclusions The incidence of new ITC was relatively low, but unfortunately, the preoperative ITC ranges would predominantly reoccur during one month. ITC was not associated with IOP elevation during the early postoperative period in this study. Thus, AS-OCT were helpful to monitor changes of anterior segment and forecast postoperative ITC.

Abstract Background Radiomic models combining intratumoral with peritumoral features are potentially beneficial to enhance the predictive performance. This study aimed to identify the optimal 18F-FDG PET/CT-derived radiomic models for prediction of prognosis in hepatocellular carcinoma (HCC). Methods A total of 135 HCC patients from two institutions were retrospectively included. Four peritumoral regions were defined by dilating tumor region with thicknesses of 2 mm, 4 mm, 6 mm, and 8 mm, respectively. Based on segmentation of intratumoral, peritumoral and integrated volume of interest (VOI), corresponding radiomic features were extracted respectively. After feature selection, a total of 15 intratumoral radiomic models were constructed based on five ensemble learning algorithms and radiomic features from three image modalities. Then, the optimal combination of ensemble learning algorithms and image modality in the intratumoral models was selected to develop subsequent peritumoral radiomic models and integrated radiomic models. Finally, a nomogram was developed incorporating the optimal radiomic model with clinical independent predictors to achieve an intuitive representation of the prediction model. Results Among the intratumoral radiomic models, the one which combined PET/CT-based radiomic features with SVM classifier outperformed other models. With the addition of peritumoral information, the integrated model based on an integration of intratumoral and 2 mm-peritumoral VOI, was finally approved as the optimal radiomic model with a mean AUC of 0.831 in the internal validation, and a highest AUC of 0.839 (95%CI:0.718–0.960) in the external test. Furthermore, a nomogram incorporating the optimal radiomic model with HBV infection and TNM status, was able to predict the prognosis for HCC with an AUC of 0.889 (95%CI: 0.799–0.979). Conclusions The integrated intratumoral and peritumoral radiomic model, especially for a 2 mm peritumoral region, was verified as the optimal radiomic model to predict the overall survival of HCC. Furthermore, combination of integrated radiomic model with significant clinical parameter contributed to further enhance the prediction efficacy. Trial registration This study was a retrospective study, so it was free from registration.

Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is likely to relapse due to aberrant eosinophil infiltration. The deficiency of Vitamin D (VD) is associated with increased eosinophil infiltration in eosinophilic oesophagitis. However, the role of VD in eosinophilic CRSwNP (ECRSwNP) remains unclear. This study aims to explore the effects of VD on eosinophil chemotaxis in ECRSwNP and the underlying mechanisms. Methods Human nasal mucosal tissues were collected from the control group, patients with non-ECRSwNP and those with ECRSwNP. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of VD and CCL26 in the nasal mucosa, plasma, or human primary nasal epithelial cells (hNECs). hNECs and eosinophils from patients were cultured to investigate the effect of VD on eosinophil chemotaxis and CCL26 expression via eosinophil migration assay, Western blot, and ELISA. Transcriptome sequencing, pathway enrichment analysis, Western blot and immunohistochemical staining were used to determine the key signaling pathway involved in eosinophil chemotaxis. Results A significant decrease in VD levels was observed in the nasal mucosa of patients with ECRSwNP, which correlated with increased local eosinophil infiltration. Furthermore, pathway enrichment analysis suggested that glycolysis signaling was promoted in the ECRSwNP group, verified by enhanced expression of glycolytic key enzymes that were positively correlated with eosinophil infiltration in nasal mucosa from patients with ECRSwNP. VD suppressed eosinophil chemotaxis in vitro by inhibiting CCL26 expression. Glycolysis regulated CCL26 expression via the ERK pathway and lactate, which promoted the expression and stability of CCL26 protein. VD attenuated glycolysis, leading to decreased production of lactate and inactivation of the ERK pathway. The decrease in lactate production suppressed eosinophil chemotaxis. Moreover, the ERK pathway activator reversed the inhibitory effect of VD on eosinophil chemotaxis. Conclusions VD impedes eosinophil chemotaxis by inhibiting glycolysis - induced CCL26 expression via attenuating the activation of the ERK pathway and reducing lactate production. VD supplementation may be a novel strategy to treat ECRSwNP.

Abstract Traffic flow data has been used in various disciplines, including geography, transportation, urban planning, and public health. However, existing datasets often have limitations such as low spatiotemporal resolution and inconsistent quality due to data collection methods and the need for an adequate data cleaning process. This paper introduces a long-term traffic flow dataset at an intra-city scale with high spatio-temporal granularity. The dataset covers the Glasgow City Council area for four consecutive years spanning the COVID-19 pandemic, from October 2019 to September 2023, providing comprehensive temporal and spatial coverage. Such detailed information facilitates diverse applications, including traffic dynamic analysis, traffic management, infrastructure planning, and urban environment improvement. Also, it provides a valuable dataset to understand traffic flow change during a once-in-a-lifetime pandemic event.

Abstract Background Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication in patients with sepsis and is associated with high mortality. Therefore, early recognition of SA-AKI is essential for administering supportive treatment and preventing further damage. This study aimed to identify and validate metabolite biomarkers of SA-AKI to assist in early clinical diagnosis. Methods Untargeted renal proteomic and metabolomic analyses were performed on the renal tissues of LPS-induced SA-AKI and sepsis mice. Glomerular filtration rate (GFR) monitoring technology was used to evaluate real-time renal function in mice. To elucidate the distinctive characteristics of SA-AKI, a multi-omics Spearman correlation network was constructed integrating core metabolites, proteins, and renal function. Subsequently, metabolomics analysis was used to explore the dynamic changes of core metabolites in the serum of SA-AKI mice at 0, 8, and 24 h. Finally, a clinical cohort (28 patients with SA-AKI vs. 28 patients with sepsis) serum quantitative metabolomic analysis was carried out to build a diagnostic model for SA-AKI via logistic regression (LR). Results Thirteen differential renal metabolites and 112 differential renal proteins were identified through a multi-omics study of SA-AKI mice. Subsequently, a multi-omics correlation network was constructed to highlight five core metabolites, i.e., 3-hydroxybutyric acid, 3-hydroxymethylglutaric acid, creatine, myristic acid, and inosine, the early changes of which were then observed via serum time series experiments of SA-AKI mice. The levels of 3-hydroxybutyric acid, 3-hydroxymethylglutaric acid, and creatine increased significantly at 24 h, myristic acid increased at 8 h, while inosine decreased at 8 h. Ultimately, based on the identified core metabolites, we recruited 56 patients and constructed a diagnostic model named IC3, using inosine, creatine, and 3-hydroxybutyric acid, to early identify SA-AKI (AUC = 0.90). Conclusions We proposed a blood metabolite model consisting of inosine, creatine, and 3-hydroxybutyric acid for the early screening of SA-AKI. Future studies will observe the performance of these metabolites in other clinical populations to evaluate their diagnostic role.

Abstract Background Tuberous sclerosis complex is a genetic disorder caused by mutations in the TSC1 or TSC2 genes, affecting multiple systems. These genes produce proteins that regulate mTORC1 activity, essential for cell function and metabolism. While mTOR inhibitors have advanced treatment, maintaining long-term therapeutic success is still challenging. For over 20 years, significant progress has linked TSC1 or TSC2 gene mutations in stem cells to tuberous sclerosis complex symptoms. Methods A comprehensive review was conducted using databases like Web of Science, Google Scholar, PubMed, and Science Direct, with search terms such as “tuberous sclerosis complex,” “TSC1,” “TSC2,” “stem cell,” “proliferation,” and “differentiation.” Relevant literature was thoroughly analyzed and summarized to present an updated analysis of the TSC1-TSC2 complex’s role in stem cell fate determination and its implications for tuberous sclerosis complex. Results The TSC1-TSC2 complex plays a crucial role in various stem cells, such as neural, germline, nephron progenitor, intestinal, hematopoietic, and mesenchymal stem/stromal cells, primarily through the mTOR signaling pathway. Conclusions This review aims shed light on the role of the TSC1-TSC2 complex in stem cell fate, its impact on health and disease, and potential new treatments for tuberous sclerosis complex. Graphical abstract

Abstract Objectives This study aims to investigate the prognostic significance of dynamic hematological and clinical characteristics and to construct nomograms to predict overall survival (OS) in patients with cervical carcinoma who underwent radical radiotherapy. Methods The study analyzed patients with cervical cancer who underwent radical radiotherapy at The University of Hong Kong-Shenzhen Hospital between January 2015 and June 2022 and were staged as IB1 to IVA according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system. We identified predictive factors through univariate and multivariate cox regression analyses. Two multivariate analyses integrating different groups of variables were conducted independently. Concordance index (C-index), receiver operating characteristic (ROC), and Kaplan-Meier curves were used to evaluate the nomograms. Bootstrap validation was performed to determine the accuracy of the nomogram using 1000 resamples. The performances of proposed nomograms and FIGO 2018 staging system were compared to assess the prognostic value of hematological and inflammatory markers. Results One hundred fifty-nine patients were included in this retrospective analysis. The median follow-up time was 41.37 months, and the 3-year OS rate was 82.6%. The first multivariate analysis of pre-treatment clinical factors and all hematological variables showed that FIGO2018 staging, and pre-treatment albumin levels were associated with 3-year OS. The final multivariate analysis incorporating all clinical factors, hematological variables, and inflammatory markers identified the following prognostic factors: FIGO2018 staging, rate of tumor shrinkage before brachytherapy, pre-treatment albumin levels, treatment times, minimum neutrophils during treatment, concurrent chemotherapy cycles, and lymphopenia grade. Calibration plots showed agreement between the OS predicted by the nomograms and actual OS. Kaplan–Meier curves demonstrated that patients in the high-risk group had shorter OS than those in the low-risk group (P ≤ 0.001). The C-index for the two nomograms was superior to that of the current FIGO2018 staging system, with values of 0.709 (95% Confidence Interval [CI], 0.622–0.795) and 0.803 (95% CI, 0.729–0.877), compared to 0.593 (95% CI, 0.508–0.678) for the FIGO system. Conclusion We developed and validated nomograms to predict OS in cervical cancer patients staged IB1 to IVA who underwent radical radiotherapy RT. The prognostic significance of dynamic changes in blood and inflammatory markers has been confirmed. The proposed nomogram exhibits robust predictive capabilities for estimating OS in these patients, facilitating risk stratification and individualized treatment.

Abstract Sphingolipid, ceramide for example, plays an essential role in regulating cancer cell death. Defects in the generation and metabolism of ceramide in cancer cells contribute to tumor cell survival and resistance to chemotherapy. Ceramide Transfer Protein (CERT) determines the ratio of ceramide and sphingomyelin in cells. Targeting CERT sensitizes solid cancer cells to chemotherapy. However, whether targeting CERT to induce ceramide accumulation thereby improving AML therapy efficiency remains elusive. Here, we show that knocking down CERT inhibits the growth and promotes the apoptosis of AML cells carrying FLT3-ITD mutation. Combining CERT inhibitor with FLT3 inhibitor exhibits synergistic effects on FLT3-ITD mutated acute myeloid leukemia (AML) cells. Additionally, co-treatment of HPA-12 and Crenolanib is effective in FLT3-ITD+ and FLT3-TKD+ AML patients. The synergistic effects are found to be mediated by the endoplasmic reticulum stress-GRP78/ATF6/CHOP axis and mitophagy. Our data provide an effective strategy to enhance the efficacy of FLT3 inhibitors in AML.

Abstract. Background:. The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. Methods:. This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. Results:. Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [n = 278] vs. 43.7% [n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45–0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs. 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82–2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. Conclusion:. This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.

In response to the specific requirements of space-borne gravitational wave detectors (SGWD) for laser frequency stability, this work systematically analyzes and investigates the frequency noise of Fabry-Pérot (FP) cavity-based ultra-stable lasers (USL). Aiming at the detection frequency band of SGWD (0.1 mHz $\sim$ 1Hz), a refined laser frequency noise model of USL is proposed. Based on the model, corresponding simulations and experiments yield an approach to identify the primary noise sources within segmented frequency bands, revealing the overlooked role of temperature fluctuations on cavity noise, and emphasizing the importance of the control loop. The proposed model will provide valuable guidance for improving laser frequency stability in space gravitational wave detectors.

Assessing the invasiveness of thyroid nodules, particularly whether they have metastasized to lymph nodes, is crucial for guiding treatment decisions. Current diagnostic methods, including ultrasound imaging, are limited by operator dependence and interpretative variability, complicating accurate evaluation of nodule invasiveness. To address these limitations, this study introduces the UTV-ST Swin Transformer, a deep learning model that combines ultrasound video data with standardized clinical information to predict the invasiveness of thyroid nodules. The model classifies nodules into three categories: non-invasive, central lymph node metastasis (CLNM), and central plus lateral lymph node metastasis (CLNM+LLNM). By analyzing ultrasound video features using the Video Swin Transformer and clinical data using a text analysis module based on the KAN network, and then fusing these features, the model achieves a classification accuracy of 82.1% and an average AUC of 94.2%. These results surpass the performance of traditional methods, particularly in distinguishing different degrees of invasiveness, even under noisy conditions. This study highlights the potential of the UTV-ST Swin Transformer model in improving the accuracy of thyroid nodule assessment, reducing reliance on operator expertise, and providing a more consistent and automated method for evaluating nodule invasiveness.

Abstract Monkeypox virus (MPXV) is an important zoonotic pathogenic virus, which poses serious threats to public health. MPXV infection can be prevented by immunization against the variola virus. Because of the safety risks and side effects of vaccination with live vaccinia virus (VACV) strain Tian Tan (VTT), we constructed two gene-deleted VTT recombinants (TTVAC7 and TTVC5). The immunogenicity and protective effects of the gene-deleted VTT vaccine were assessed using BALB/C mice challenged with VTT and New Zealand rabbits challenged with MPXV. The results demonstrated strong humoral and cellular immune responses. The VTT-specific and neutralizing antibody titers, specific T cell levels, and degree of dendritic cell maturation of the mice, in addition to the MPXV neutralizing antibody titers and IFN-γ, IL-6, and TNF-α levels of the rabbits were markedly higher in the groups immunized with TTVAC7 and TTVC5 than the control groups (p

Objective: To compare the diagnostic performance between mDixon sequence and WHCA TFE sequence using SPIR for non-contrast-enhanced coronary MRA in patients with suspected coronary artery disease (CAD). Method: This prospective study recruited 45 patients who were scheduled for X-ray coronary angiography (CAG) with suspected CAD in Yantai Yuhuangding hospital. Patients underwent both 3.0T WHCA TFE using SPIR and mDixon coronary MRA examinations before undergoing CAG. Two radiologists independently assessed coronary arteries in terms of subjective image quality (on a scale of 1~5, with 5 denoting the highest image quality), vessel length, vessel diameter, and presence of significant stenoses. CAG was used as the reference standard for detecting the presence of stenoses. Vessel length and diameter were compared between sequences using paired t-tests. Subjective image quality scores were compared between sequences using Wilcoxon tests. Sensitivity, specificity, and accuracy were compared between sequences using McNemar tests. Positive and negative predictive values were compared between sequences using the joint hypotheses test. Results: Two CMRA examinations were successfully performed in 40 (88.9%) of 45 patients for analysis. The objective image quality of 3.0T mDixon assessed by both radiologists was (3.9±0.9), and the 3.0T WHCA TFE using SPIR was (3.7±0.9). The mDixon sequence exhibited higher sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in per-segment analysis (78.5% vs. 66.1%, 96.5% vs. 93.8%, 91.7% vs. 86.6%, 88.6% vs. 78.9%, and 93.4% vs. 88.7%) and higher sensitivity and accuracy in per-vessel analysis (89.4% vs. 81.6% and 89.1% vs. 83.3%). Conclusion: In comparison with 3.0T WHCA TFE sequence using SPIR, mDixon demonstrated superior diagnostic performance.

Abstract Background Carotenoids have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. The data for the effect of dietary specific carotenoids on biological aging is limited. Our study aims to examine the association between dietary carotenoid intake levels and biological aging. Methods This cross-sectional study was performed among 27,338 adults from NHANES 1999–2018. Dietary intake was assessed through two 24-hour dietary recall interviews. Biological aging indices included allostatic load (AL), homeostatic dysregulation (HD), Klemera-Doubal method (KDM), and phenoAge (PA). Multiple linear regression, weighted quantile sum (WQS) regression and quantile g-computation (QG-comp) were used to explore the associations of single carotenoid and mixed carotenoids with biological aging. Results Associations between dietary carotenoid intake levels and biological aging indices were significant among adults across the United States. Multiple linear regression showed that most carotenoids were significantly negatively correlated with AL (β = -0.017 - -0.011), HD (β = -0.045 - -0.032), KDM (β = -0.984 - -0.471), and PA (β = -0.975 - -0.539). Subgroup analysis indicated that male, older individuals, smokers, alcohol drinkers, and less physically active individuals are particularly sensitive populations. Meanwhile, WQS regression and QG-comp analyses consistently indicated a negative association between mixed carotenoids exposure and four biological aging indices, highlighting that lutein/zeaxanthin and β-carotene were responsible for the outcomes. Conclusions Increased dietary intakes of various carotenoids were associated with lower biological aging indices, which was possibly and mainly driven by lutein/zeaxanthin and β-carotene.

Abstract Objectives To systematically evaluate the efficacy of lateral unicompartmental knee arthroplasty (LUKA) and total knee arthroplasty (TKA) in the treatment of isolated lateral compartment knee osteoarthritis (LCKO), and to provide guidance and a basis for selecting surgery in clinical practice. Methods Inclusion and exclusion criteria for literature were established, appropriate effect indicators were selected, and PubMed, Web of Science, Embase, Medline, Cochrane Library, and CNKI databases were searched using a computer. The Newcastle Ottawa scale (NOS) was used to evaluate the quality of the literature. After data extraction, Meta-analysis was performed using Revman5.4 software. Results A total of 8 studies were included in this meta-analysis, involving 490 patients, with 204 in the TKA group and 286 in the LUKA group. Meta-analysis found that, there was no significant statistical difference in operation time between the LUKA group and the TKA group. Nevertheless, LUKA offers advantages such as reduced intraoperative blood loss and shorter hospitalization time. At the same time, the LUKA group also had advantages over the TKA group in postoperative visual analogue scale (VAS) score, knee joint range of motion, Oxford Knee Score (OKS)score and Hospital for Special Surgery (HSS) score. Conclusion When LUKA and TKA are used to treat isolated LCKO, LUKA has the advantages of less intraoperative blood loss, shorter hospital stay, lower postoperative VAS score, and better knee function score and range of motion.

Abstract Background The aim of this study is to evaluate the efficacy and safety of diacylglycerol (DAG) edible oil intervention in patients with chronic metabolic syndrome complicated by asymptomatic hyperuricemia through a multicenter, prospective, double-blind, randomized controlled clinical trial. Methods A multicenter, double-blind, and randomized controlled trial involving 176 patients was designed. All patients with chronic metabolic syndrome complicated by asymptomatic hyperuricemia who meet inclusion and exclusion criteria will be included in the study and will be randomized to either group A or group B. Group A will receive DAG-rich oil (≥ 80%) and group B will receive conventional cooking oil (triacylglycerol (TAG)-rich oil) for 12 weeks. Serum uric acid level is the primary outcome. Fasting blood glucose, 2 h postprandial blood glucose, fasting insulin, glycated hemoglobin, lipid profile, and average carotid intima-media thickness will be evaluated as the secondary outcomes. Blood routine, urine routine, liver enzymes, and electrocardiogram will be tested to assess the safety. The sample size for each group was calculated to be 88 cases. Discussion We will evaluate the efficacy and safety of DAG oil compared with conventional TAG oil in patients with chronic metabolic syndrome with asymptomatic hyperuricemia. The dietary oil with superior efficacy and better safety will be recommended for reference use. Trial registration Chinese Clinical Trial Registry ChiCTR2400085336. Registered on June 5, 2024.

Abstract Macrophages play important roles in maintaining intestinal homeostasis and in the pathogenesis of inflammatory bowel diseases (IBDs). However, the underlying mechanisms that govern macrophage-mediated inflammation are still largely unknown. In this study, we report that RNF128 is downregulated in proinflammatory macrophages. RNF128 deficiency leads to elevated levels of effector cytokines in vitro and accelerates the progression of IBD in mouse models. Bone marrow transplantation experiments revealed that RNF128 deficiency in bone marrow cells contributes to the worsening of DSS-induced colitis. Mechanistically, RNF128 interacts with and destabilizes S100A8 by promoting its autophagic degradation, which is mediated by the cargo receptor Tollip. Moreover, the administration of an S100A8 neutralizing antibody mitigated the development of colitis and improved survival in DSS-treated Rnf128 −/− mice. Overall, our study underscores the anti-inflammatory role of RNF128 in macrophages during the progression of colitis and highlights the potential of targeting the RNF128-Tollip-S100A8 axis to attenuate intestinal inflammation for the treatment of colitis.

M2 high speed steel (W6Mo5Cr4V2) is an important engineering material, and with modern industry progressing, increased requirements are put forward for improved performance of high speed steel. To improve its comprehensive properties, M2 high speed steel powder is mixed with nano-sized Y2O3 particles through mechanical alloying. This mixture is then used to create Y2O3 dispersion strengthened M2 high speed steel by selective laser melting (SLM) electrometallurgy technology. The process parameters for SLM are as follows: laser power of 220 W, scanning speed of 800 mm·s−1, powder layer thickness of 0.03 mm, scanning spacing of 0.1 mm, and a substrate preheating temperature of 200 ℃. The effects of Y2O3 particles on the microstructure and mechanical properties of the prepared high speed steel were investigated using various techniques, including optical microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, and mechanical property tests. Experimental results show that after low-energy ball milling, the M2 high speed steel powder remains mostly spherical with minimal deformation, preventing uneven spreading during the powder laying process. The surface of M2 high speed steel powder is coated with a large number of nanometer-sized Y2O3 particles. The relative density of Y2O3 dispersion strengthened samples formed by SLM is 98.3%. These samples exhibit a relatively smooth surface without obvious cracks, and the quality of the top surface quality is better than that of the side surfaces. The material’s basic structure and morphology are influenced by the molten pool and channel. Hexagonal honeycomb grains are evident in the molten channel, with fine grains distributed at the edges and slightly larger grains inside. The molten pool consists mainly of equiaxed crystals at the center and columnar dendrites at the boundaries, with grains growing epitaxially along the molten pool boundary. EDS (energy dispersive spectrometer) results show that elements Y and O are evenly distributed within the matrix, with no significant segregation. Subsequently, phase analysis reveals that adding Y2O3 particles has little effect on the phase composition of M2 high speed steel, which remains mainly martensite, residual austenite, and carbides. Owing to the small amount of Y2O3 added, no diffraction peaks of Y2O3 were found in the detection range. TEM results show that Y2O3 particles are larger at grain boundaries, reaching up to 90 nm, while smaller nanoparticles are diffusely distributed within the grains. Mechanical testing indicates that Y2O3 dispersion strengthened high speed steel samples fabricated by SLM exhibit good mechanical properties, with tensile strength reaching 943 MPa, a 36% increase compared to M2 high speed steel without Y2O3 particles. Its fracture surface is flat with a few cleavage steps and columnar crystals, indicating brittle fracture behavior. The addition of Y2O3 particles produces a larger number of nucleation sites, refines grain size, and hinders dislocation movement, preventing crack propagation along grain boundaries, thereby enhancing the mechanical properties of M2 high speed steel.

Abstract Background The rapid evolution of the COVID-19 pandemic and subsequent global immunization efforts have rendered early metabolomics studies potentially outdated, as they primarily involved non-exposed, non-vaccinated populations. This paper presents a predictive model developed from up-to-date metabolomics data integrated with clinical data to estimate early mortality risk in critically ill COVID-19 patients. Our study addresses the critical gap in current research by utilizing current patient samples, providing fresh insights into the pathophysiology of the disease in a partially immunized global population. Methods One hundred elderly patients with severe COVID-19 infection, including 46 survivors and 54 non-survivors, were recruited in January-February 2023 at the Second Hospital affiliated with Harbin Medical University. A predictive model within 24 h of admission was developed using blood metabolomics and clinical data. Differential metabolite analysis and other techniques were used to identify relevant characteristics. Model performance was assessed by comparing the area under the receiver operating characteristic curve (AUROC). The final prediction model was externally validated in a cohort of 50 COVID-19 elderly critically ill patients at the First Hospital affiliated with Harbin Medical University during the same period. Results Significant disparities in blood metabolomics and laboratory parameters were noted between individuals who survived and those who did not. One metabolite indicator, Itaconic acid, and four laboratory tests (LYM, IL-6, PCT, and CRP), were identified as the five variables in all four models. The external validation set demonstrated that the KNN model exhibited the highest AUC of 0.952 among the four models. When considering a 50% risk of mortality threshold, the validation set displayed a sensitivity of 0.963 and a specificity of 0.957. Conclusions The prognostic outcome of COVID-19 elderly patients is significantly influenced by the levels of Itaconic acid, LYM, IL-6, PCT, and CRP upon admission. These five indicators can be utilized to assess the mortality risk in affected individuals.

Abstract In the realm of modern materials science, horizontally aligned carbon nanotube arrays stand as promising materials for the development of next-generation integrated circuits. However, their large-scale integration has been impeded by the constraints of current fabrication techniques, which struggle to achieve the necessary uniformity, density, and size control of carbon nanotube arrays. Overcoming this challenge necessitates a significant shift in fabrication approaches. Herein, we present a nano-seeding method that revolutionized the preparation of catalyst nanoparticles, crucial for carbon-nanotube-array synthesis. Our approach, underpinned by ion implantation and substrate processing, allows for precise control over catalyst formation. Further development of a vertical spraying chemical vapor deposition system homogenizes the gas flow and ensures the uniform growth of carbon nanotube arrays. This nano-seeding method culminates in the direct growth of one-inch carbon-nanotube-array wafers with the highest density of 140 tubes μm−1. The high density and uniformity of the as-prepared carbon-nanotube-array wafers are validated through an advanced high-throughput characterization technique. The electrical properties of high on-state current, high on/off ratio and low subthreshold swing are demonstrated in field-effect transistors based on the arrays. This study propels the scalability of carbon-nanotube-array fabrication for future carbon-based electronics.

Oil reservoirs contain significant amounts of water. Therefore, the role of water in the in situ hydrocarbon generation of medium- and low-maturity organic-rich shale cannot be ignored. In this study, a self-developed reaction system was used to simulate hydrocarbon generation under supercritical water in situ conversion, examining the influence of water-shale mass ratio changes on organic carbon migration and pore evolution. The results showed that higher water-shale mass ratios were conducive to the conversion of organic carbon in shale and the migration of organic carbon to gas-phase products. As the water-shale mass ratio increased, the proportion of carbon elements in carbon dioxide from organic sources gradually decreased, while that of carbon elements from inorganic sources gradually increased. Increasing the water-shale mass ratio from 0.5 to 5, the porosity and permeability of shale were greatly improved, with porosity increasing more than threefold and permeability more than fivefold.

Meruliaceae is one of the three major families of the phlebioid clade in the Polyporales that consists primarily of wood-decaying species. We undertook an in-depth survey on species diversity, generic delimitations, phylogeny, and divergence times within the Meruliaceae with an emphasis on specimens from East Asia. In total, 26 genera including two new genera, Meruliella and Porophlebia, are recognised; ten new species, viz. Crustodontia vietnamensis, Luteochaete odontoidea, Meruliella hainanensis, Merulius pinicola, Mycoacia beijingensis, Phlebiporia crystallifera, P. odontoidea, Pseudophlebia vesiculosa, Scopuloides ellipsoidea, and S. grandinioides are introduced; eleven new combinations, viz. Allophlebia formosana, Aurantiopileus albidus, A. semisupina, Meruliella lindtneri, Merulius croceum, M. leptospermi, M. serialis, Phlebicolorata austroasiana, Phlebiodontia caspica, P. fissurata and Porophlebia fimbriata, and one new name, Mycoacia neotuberculata, are proposed. Noblesia is placed as a synonymy of Merulius, whereas Ceriporiopsis and Lilaceophlebia are accepted as synonyms of Mycoacia. Descriptions and illustrations are provided for the new genera and species, and discussions are provided for all 26 genera and new taxa. The molecular clock analysis results show that the Meruliaceae emerged with a mean stem age of 186.71 Mya of the early Jurassic, and the genera diverged with a mean stem age between 44.29 to 169.46 Mya.

Abstract In this paper, a fixed support method for a cryogenic monocrystalline silicon Fabry-Pérot cavity of an ultra-stable laser for space applications is proposed. Through finite element analysis, the vibration sensitivity at the center of the cavity is below 10E-12/g; the fundamental frequency is 381 Hz; the thermal deformation is compensated by applying a preload force of about 3 N*m for a variation of 300 K to 124 K. Based on these analyses, an equal-mass cavity simulator was machined and mounted. The mounting process was then explored to keep its support angle mounting error within 40′. Next, the simulator was vibration tested, and the deviation of the cavity after the test was within 10″. Finally, the thermal deformation of the simulator and the support performance of the PEEK cylinders at 77 K was briefly verified. These works provide an alternative solution for future ultra-stable lasers with cryogenic monocrystalline silicon cavities for space applications.

Abstract Oral dissolving film (ODF) emerges as a novel active substance delivery system, offering portability, safety, and compliance. ODF presents superior gastrointestinal absorption compared to conventional food products, making it ideal for providing nutrition and medication support to vulnerable populations such as children, the elderly, and individuals with dysphagia. With promising applications in pharmaceuticals and especially food industry, ODFs offer a highly absorbable method for delivering nutritious and healthy foods. This review underscores the potential of orally dissolving films in active substance delivery, outlining their advantages over traditional oral delivery methods and their current market status. Additionally, the review discusses the formulation procedure, production methods, and quality evaluation methods for film dosage forms of ODFs. Lastly, it examines the limitations of ODFs and speculates on their future trends in the food industry. This study serves as a valuable reference for the development and utilization of orally dissolving films in the food sector. Graphical Abstract

Abstract Background Solid lung lesions are common in clinical practice, and percutaneous thermal ablation has been shown to be an effective treatment for these lesions. While computed tomography (CT)-guided microwave ablation (MWA) therapy is frequently used for adult solid lesions, it is rarely considered for pediatric cases. Case presentation A case of an 8-year-old child with adrenal neuroblastoma and a left upper lung mass. The child successfully underwent lung mass ablation and experienced a long-term progression-free period with good recovery and no recurrence. Conclusions This case suggests that MWA could be a valuable addition to existing treatment options for solid lesions in children.

Abstract Objectives To compare the stress distribution and crack propagation in cracked mandibular first molar restored with onlay, overlay, and two types of occlusal veneers using two different CAD/CAM materials by Finite Element Analysis (FEA). Materials and methods A mandibular first molar was digitized using a micro CT scanning system in 2023. Three-dimensional dynamic scan data were transformed, and a 3D model of a cracked tooth was generated. Finite element models of four different models (onlay, overlay, and two types of occlusal veneer restored teeth) were designed. Two different CAD/CAM materials, including Lava Ultimate (LU) and IPS e.max CAD (EMX), were specified for both models. Each model was subjected to three different force loads on the occlusal surfaces. Stress distribution patterns and the maximum von Mises (VM) stresses were calculated and compared. Results Compared to the base model, all restorations showed that high-stress concentration moved from the lower margin of the crack area towards the top of the crack area. The EMX-restored onlay, overlay, and occlusal veneer 2 had the lower stress in the cracked area and the lower average von Mises stress levels at the lower margin along the cracked line, especially under the 225N lateral force (P

This study integrates knowledge sharing into traditional teacher training to enhance teachers’ professional development. It addresses the research gap in implementing such integration by developing a video cloud platform that supports online training and knowledge-sharing among teachers. The proposed approach combines the SECI model (socialization, externalization, combination, and internalization) with the video cloud platform to create a new model of teacher e-learning, fostering collaborative learning among teachers in a remote and interactive context. To demonstrate the effectiveness of this approach, the study conducted experiments with Chinese primary and secondary school teachers. The new model was applied in an online professional competence-oriented supporting environment. The results showed a significant improvement in organization and management skills, and a moderate increase in technical literacy, learning, and development capabilities among the participating teachers. These findings have important implications for professional development of teachers, particularly in the context of the ongoing epidemic and the shift towards a networked and intelligent world. By integrating knowledge sharing into traditional training, teachers can enhance professional competence and adapt to the changing educational landscape. The video cloud platform is a valuable tool for facilitating collaborative learning and knowledge creation among teachers.

[Objective] This study aimed to assess the impact of the national e-commerce demonstration cities (NEDC) pilot policy on urban carbon emission efficiency (CEE) and its underlying mechanisms. It focused on the moderating effects of e-commerce soft and hard environments, providing policy references for achieving carbon neutrality and peak carbon emissions goals. [Methods] Based on prior research, this study employed multiple-period difference-in-differences and double machine learning models to rigorously identify the causal relationship between the NEDC pilot policy and urban CEE, using panel data of 282 prefecture-level administrative units in China from 2006 to 2022. The analysis integrated the internal mechanisms of the pilot policy’s impact on CEE from supply and demand sides. This study constructed a comprehensive evaluation system of e-commerce soft and hard environments to access their moderating effects on the policy’s impact. [Results] The empirical findings reveal that the NEDC pilot policy significantly promoted urban CEE, with robust results verified through endogeneity test and multiple robustness tests. Both soft and hard environments demonstrated positive moderating effects on the policy’s impact on CEE, where network and logistics infrastructure in the hard environment played a crucial role, while technological innovation, governmental regulation and market environment in the soft environment exhibited strong moderating effects. Furthermore, the policy’s impact exhibited heterogeneity, with more pronounced effects in non-resource cities, growth-regenerative cities, and cities with higher levels of international trade. [Conclusion] To promote policy-enabled CEE, the carbon reduction effect of the pilot policy should be strengthened at both supply and demand sides. The soft and hard environments of e-commerce should be further optimized. It is recommended to advance the construction of pilot cities in an orderly manner, establish industrial e-commerce ecosystem, reinforce the coordinated optimization of soft and hard environments, and develop e-commerce according to local conditions.

Abstract Multiple myeloma (MM) is the second common hematological malignancy characterized by the abnormal proliferation of plasma cells. Although advances in the past decades have led to improved outcomes and longer survival, MM remains largely incurable. New targets and targeted therapy may help to achieve better outcomes. Proton exporter NHE1 is highly expressed by tumor cells to maintain pH gradient for their survival and its inhibitor Hexamethylene amiloride (HA) has been demonstrated anti-tumor effect. However, whether HA could inhibit MM remains unknown. In this study, we firstly demonstrated that elevated expression level of NHE1 is associated with poor prognosis of MM. Moreover, the NHE1 inhibitor HA inhibited growth and induced apoptosis effectively in both MM cell lines and primary bone marrow cells from MM patients. Mechanistically, inhibitory effect was achieved partially through TFE3-mediated lysosomal production. With a MM xenograft mouse model, we verified that HA has a significant anti MM effect in vivo. Importantly, HA induced apoptosis of the carfilzomib-resistant MM cells and enhanced the effect of carfilzomib in MM. In summary, we demonstrated that NHE1 inhibitor HA can effectively inhibit MM growth both in vitro and in vivo, providing a new therapeutic strategy for improved outcome of de novo and resistant MM.

Abstract Klebsiella pneumoniae carbapenemase-producing Pseudomonas aeruginosa (KPC-PA) isolates have quickly expanded in China, especially the high-risk clone ST463. We aimed to explore the evolution of KPC-related plasmids driving ST463 clone success. Whole-genome sequencing of 1258 clinical P. aeruginosa strains (2011–2020) identified 106 ST463-PA isolates, with a KPC prevalence of 90.6%. Early on (2011-2012), ST463-PA obtained the KPC-encoding type II (pT2-KPC) or type I plasmid (pT1-KPC) to overcome carbapenem stress. Between 2012 and 2017, pT1-KPC plasmid dominated due to its lower fitness costs and IS26-driven bla KPC amplification ability. By 2017-2020, large fragment deletions in pT1-KPC formed pT1del-KPC plasmid. It conferred even lower fitness costs, enhanced bla KPC-2 gene stability, and greater copy-number flexibility, while maintaining horizontal transmission ability. Consequently, pT1del-KPC plasmid finally succeeded, making ST463 the dominant ST in China. Our findings highlight evolutionary pressures driving ST463 dominance and emphasize the need for targeted strategies to control its spread and antibiotic resistance development.

Dendrobium devonianum is an important medicinal plant, rich in flavonoid, with various pharmacological activities such as stomachic and antioxidant properties. In this study, we integrated metabolome and transcriptome analyses to reveal metabolite and gene expression profiles of D. devonianum, both green (GDd) and purple-red (RDd) of semi-annual and annual stems. A total of 244 flavonoid metabolites, mainly flavones and flavonols, were identified and annotated. Cyanidin and delphinidin were the major anthocyanidins, with cyanidin-3-O-(6″-O-p-Coumaroyl) glucoside and delphinidin-3-O-(6″-O-p-coumaroyl) glucoside being the highest relative content in the RDd. Differential metabolites were significantly enriched, mainly in flavonoid biosynthesis, anthocyanin biosynthesis, and flavone and flavonol biosynthesis pathways. Transcriptomic analysis revealed that high expression levels of structural genes for flavonoid and anthocyanin biosynthesis were the main reasons for color changes in D. devonianum stems. Based on correlation analysis and weighted gene co-expression network analysis (WGCNA) analysis, CHS2 (chalcone synthase) and UGT77B2 (anthocyanidin 3-O-glucosyltransferase) were identified as important candidate genes involved in stem pigmentation. In addition, key transcription factors (TFs), including three bHLH (bHLH3, bHLH4, bHLH5) and two MYB (MYB1, MYB2), which may be involved in the regulation of flavonoid biosynthesis, were identified. This study provides new perspectives on D. devonianum efficacy components and the Dendrobium flavonoids and stem color regulation.

Bacillus mojavensis KRS009 was identified as an antagonistic strain with a strong inhibitory effect on various phytopathogenic fungi. To provide further insight into its biocontrol mechanisms and ability to improve plant salt tolerance, the high quality complete genome of KRS009 was sequenced by PacBio platform and assembled using PacBio-HiFiReads. The KRS009 genome consists of one circular chromosome of 4,089,687 bp with 43.5% GC content and 4,062 open reading frames, of which 3,920 protein-coding genes, 86 transfer RNA, 10 ribosomal RNA, and 26 small RNA were identified in this genome. Among them, genes related to compatible solutes, including treC, galU, proX, and proW, are involved in the synthesis of trehalose, proline, and betaine metabolism and play an important role in relieving osmotic stress. In addition, the KRS009 genome contains genes associated with high salinity tolerance, including those responsible for Na+/H+ antiporters, K+ transporters, TrkH thiamin phosphate synthase, K+-sensing histidine kinase, aryl-phospho-beta-D-glucosidase, flavoprotein CzcO associated with the cation diffusion facilitator CzcD, and chaperonin GroEL. Together, the high-quality genome resource of strain KRS009 would provide a molecular basis for further research on its biocontrol and plant salt tolerance mechanisms. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

The development of high-performance optically transparent radio frequency (RF) radiators is limited by the intrinsic loss issue of transparent conductive films (TCFs). Instead of pursuing expensive endeavors to improve the TCFs’ electrical properties, this study introduces an innovative approach that leverages leaky-wave mode manipulation to mitigate the TCFs’ attenuating effect and maximize the RF radiation. Our finding reveals that the precise control of the mode confinement on glass-coated TCFs can create a low-attenuation window for leaky-wave propagation, where the total attenuation caused by TCF dissipation and wave leakage is effectively reduced. The observed low-attenuation leaky-wave state on lossy TCFs originates from the delicate balance between wave leakage and TCF dissipation, attained at a particular glass cladding thickness. By leveraging the substantially extended radiation aperture achieved under suppressed wave attenuation, this study develops an optically transparent antenna with an enhanced endfire realized gain exceeding 15 dBi and a radiation efficiency of 66%, which is validated to offer competitive transmission performance for advancing ubiquitous wireless communication and sensing applications.

Abstract Endometrial cancer is the most prevalent form of gynecologic malignancy, with a significant surge in incidence among youngsters. Although the advent of the immunotherapy era has profoundly improved patient outcomes, not all patients benefit from immunotherapy; some patients experience hyperprogression while on immunotherapy. Hence, there is a pressing need to further delineate the distinct immune response profiles in patients with endometrial cancer to enhance prognosis prediction and facilitate the prediction of immunotherapeutic responses. The ssGSEA method was used to evaluate the activities of the immune response pathways in patients with endometrial cancer. Unsupervised clustering was employed to identify the different immune response patterns. WGCNA was employed to identify the genes that highly correlated with the immune response patterns observed. Ninety-five machine learning combinations were utilized to identify the optimal prognosis model and the novel biomarker, SLC38A3. Experiments such as cell invasion, migration, scratch, and in vivo tumorigenicity were performed to determine the function of SLC28A3. Molecular docking techniques were employed to determine the targeted action of periodate-oxidized adenosine on SLC38A3. Patients exhibited both immune response-suppressing C1 phenotypes and immune response-activating C2 phenotypes, with significant differences in prognosis between these two phenotypes. WGCNA identified 418 genes that highly correlated with the immune response phenotypes, of which 69 genes were associated with prognosis. The immune response-related score (IRRS) established by multiple machine learning frameworks demonstrated stability in predicting patient prognosis and immune status. High expression of SLC38A3 contributes to cellular malignant traits, and periodate-oxidized adenosine bound stably to SLC38A3. IRRS accurately predicts disease prognosis and immune status in patients with endometrial cancer. SLC38A3 serves as a prognostic marker for these patients and can be stably targeted by periodate-oxidized adenosine.

Abstract Objectives Neonatal necrotizing enterocolitis (NEC) is a common intestinal disease that threatens the lives of newborns and is characterized by ischemic necrosis of the small intestine and colon. As early diagnosis of NEC improves prognosis, the identification of new or complementary biomarkers is of great importance. In this study, we evaluate the diagnostic value of CCL3 in NEC and compare its effectiveness with other commonly used biomarkers, such as procalcitonin (PCT) and C-reactive protein (CRP). Participants and design Serum samples were collected from 64 patients with NEC and 38 jaundice neonatal controls. Before initiating therapy, blood samples for the whole blood count, CRP, PCT and CCL3 were obtained from all neonates. Receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. Setting Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University. Results The serum CCL3 level of the NEC group was significantly higher than that of the Control group. The ROC area under the curve (AUC) was 0.8614 (95%confidence interval (CI) 0.7863–0.936; p

Abstract Converting natural vegetation to croplands alters the local land surface energy budget. Here, we use two decades of satellite data and a physics-based framework to analyse the biophysical mechanisms by which croplands influence daily mean land surface temperature (LST). Globally, 60% of croplands exhibit an annual warming effect, while 40% have a cooling effect compared to their surrounding natural ecosystems. Aerodynamic resistance is identified as the dominant biophysical factor impacting LST by adjusting latent heat flux. The magnitude of cropland-induced LST change is negatively correlated with the difference in leaf area index between croplands and their surrounding biome types. The strongest warming occurs in temperate dry regions where croplands are surrounded by savannas. However, a lower-than-expected LST disturbance is seen in hot and wet regions where croplands are surrounded by rainforests, attributed to lower cropland fraction and energy limitations. These findings highlight the complex interplay of land use, vegetation, and regional climate, providing valuable insights into sustainable agriculture and land-based climate change mitigation.

BACKGROUND: When a seizure occurs, the distribution of purine receptors in different cell types at various time points remains poorly understood. Our literature review revealed that P2X7, P2Y6, and P2Y12 are expressed in different cells during epilepsy pathogenesis. Therefore, we studied the protein expression patterns of the purinergic receptors P2X7, P2Y6, and P2Y12 in the normal mice hippocampus, as well as during or after pilocarpine-induced status epilepticus (DPISE or APISE). MATERIALS AND METHODS: Immunohistochemical staining and double-labeling immunofluorescence staining were used to study the cellular distribution of various purinergic receptors across several groups: control, 2-hour DPISE, 1-day APISE, 2-day APISE, 3-day APISE, and 1-week APISE. RESULTS: In the normal mouse brain, P2X7, P2Y6, and P2Y12 were predominantly expressed in the neurons. Microglia and astrocytes were found to express these receptors at the onset of seizures. Immunofluorescence analysis showed that P2X7 and P2Y12 are expressed in microglia, whereas P2Y6 is mainly expressed in astrocytes. CONCLUSION: Different purinergic receptors are expressed in neurons, microglia, and astrocytes, mediate their interactions, and are involved in epileptogenesis.

Abstract Objective To assess the efficacy and safety of perampanel (PER) as primary monotherapy in patients aged 4–18 years old with epilepsy. Methods A single‐center, prospective, observational study was conducted from October 2021 to October 2023, to evaluate PER monotherapy's efficacy and safety as initial therapy for pediatric epilepsy. Changes in seizure frequency, safety, and retention rate were observed at 3, 6, 9, and 12 months after initiating PER primary monotherapy. Results A total of 124 children aged 4–15 years (mean age = 8.25 ± 2.50 years) were included in the Analysis Sets. The retention rates at 3, 6, 9, and 12 months were 88.71% (110/124), 84.68% (105/124), 78.26% (90/115), and 71.58% (68/95), respectively. Seizure freedom rates at 3, 6, 9, and 12 months were 85.45%, 79.09%, 76.24%, and 75.31%, respectively. The responder rates (≥50% but 0.05) but associated with duration of treatment (p = 0.001) and maintenance dose (p = 0.022). Additionally, 124 patients were included in the safety analysis set. The overall adverse event rate was 38.71% (48/124), with irritability (19 cases, 15.32%) and dizziness (18 cases, 14.52%) being the most common adverse effects. One patient discontinued PER monotherapy within 1 month due to unbearable itching of the skin. Significance PER monotherapy as the primary anti‐seizure medication (ASM) for pediatric epilepsy demonstrates high efficacy and safety in real‐world clinical treatment. Patients who respond well to this drug and adhere to long‐term treatment can achieve favorable seizure control. Furthermore, patients achieving seizure freedom with a relatively lower dose can opt for the same dose as the maintenance dose. Plain Language Summary This study provided the efficacy and safety of PER monotherapy as the primary ASM for Chinese pediatric epilepsy. In total, 124 patients took part. The seizure freedom rates were over 70% at different observation points (OPs), along with a retention rate of 71.58% at the 12‐month OP. Most of adverse effects observed were mild to moderate.

Abstract Salmonella enteritidis plays a significant role in zoonotic infections. This pathogen settles in the intestinal tract of poultry and contaminates meat and egg products during production for slaughter. Consequently, it can also be transmitted to humans along the food chain, posing a significant risk to public health. Bacteriophages offer a viable substitute for antibiotics in treating Salmonella enteritidis due to their specific bactericidal effect and safety. This study aimed to investigate the protective effect of bacteriophage against Salmonella enteritidis infection in chicken intestinal epithelial cells. Chicken intestinal epithelial cells were treated with various concentrations of bacterial suspension, and the impact on cell damage was assessed by measuring changes in cell viability and observing structural changes via transmission electron microscopy. In the phage protection experiment, the phages were co-incubated with Salmonella enteritidis for 2, 4, and 6 h. Thereafter, the adhesion rate and invasion rate of bacteria and gene transcription levels of Occludin, Claudin-1, ZO-1, NF-κB p65, TNF-α and IL-6 in cells were determined. The results indicated that the phage could significantly reduce both adhesion and invasion rates of Salmonella enteritidis at MOI = 10 (P

Abstract How can harmonious communication, integration, and coexistence among different ethnicities with distinct cultures be achieved in a multi-ethnic country? What lessons can we draw from China’s multi-ethnic cultural exchanges throughout history? Are Confucianism, Daoism, and Buddhism exclusive to the culture of the Central Plains? These questions are essential for forging a sense of the Chinese nation as one community and building a shared cultural home of the Chinese nation. Throughout Chinese history, the Han, Tibetan, and Mongolian ethnicities have engaged in mutual exchanges and integrations of their respective religious-cultures, fostering mutual promotion and collective growth, leaving behind valuable experiences that shaped the Chinese cultural pattern of “Diversified Communication and Harmony.” Drawing upon extensive literature and materials documenting the religious-culture exchanges and interactions among the Han, Tibetan, and Mongolian ethnicities since the Tang and Song dynasties, this article investigates the interaction, exchange, and integration history of religious-culture among these ethnicities, aiming to explore the historical evolution of this pattern of “Diversified Communication and Harmony”.

Abstract Historically, China’s religious culture centered on the triumvirate of Confucianism, Taoism, and Buddhism, fostering a diverse, multi-ethnic, and multi-faceted communication model. Whether through grand narratives of official diplomacy, subtle and organic grassroots interactions, or the catalytic efforts of scholars, these exchanges consistently promoted interaction, exchange, and integration among numerous ethnic groups in China. The harmonious coexistence and vibrant interactions of multiple ethnicities and diverse religious beliefs not only enriched and expanded the mainstreams of traditional Chinese culture, namely Confucianism, Taoism, and Buddhism—developing flourishing branches and generating new innovations—but also infused fresh vitality into each ethnicity’s cultural practices. Together, these exchanges formed the profound, enduring, diverse and unified Chinese culture. This article primarily examines the types and characteristics of Interaction-Exchange-Integration History among diverse religious cultures of ethnic groups such as the Han, Tibetan, and Mongolian in Chinese history and derives insights from them for the contemporary era.

Abstract The class C orphan G-protein-coupled receptor (GPCR) GPR156, which lacks the large extracellular region, plays a pivotal role in auditory function through Gi2/3. Here, we firstly demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and further reveal the structural basis of the sustained role of GPR156. We present the cryo-EM structures of human apo GPR156 and the GPR156–Gi3 complex, unveiling a small extracellular region formed by extracellular loop 2 (ECL2) and the N-terminus. The GPR156 dimer in both apo state and Gi3 protein-coupled state adopt a transmembrane (TM)5/6-TM5/6 interface, indicating the high constitutive activity of GPR156 in the apo state. Furthermore, C-terminus in G-bound subunit of GPR156 plays a dual role in promoting G protein binding within G-bound subunit while preventing the G-free subunit from binding to additional G protein. Together, these results explain how GPR156 constitutive activity is maintained through dimerization and provide a mechanistic insight into the sustained role of GPR156 in maintaining auditory function.

Research on megaplasmids that contribute to the spread of antimicrobial resistance (AMR) in Pseudomonas aeruginosa strains has grown in recent years due to the now widely used technologies allowing long-read sequencing. Here, we systematically analyzed distinct and consistent genetic characteristics of megaplasmids found in P. aeruginosa. Our data provide information on their phylogenetic distribution and hypotheses tracing the potential evolutionary paths of megaplasmids. Most of the megaplasmids we found belong to the IncP-2-type, with conserved and syntenic genetic backbones carrying modules of genes associated with chemotaxis apparatus, tellurite resistance and plasmid replication, segregation, and transmission. Extensively variable regions harbor abundant AMR genes, especially those encoding β-lactamases such as VIM-2, IMP-45, and KPC variants, which are high-risk elements in nosocomial infection. IncP-2 megaplasmids act as effective vehicles transmitting AMR genes to diverse regions. One evolutionary model of the origin of megaplasmids claims that chromids can develop from megaplasmids. These chromids have been characterized as an intermediate between a megaplasmid and a chromosome, also containing core genes that can be found on the chromosome but not on the megaplasmid. Using in silico prediction, we identified the “PABCH45 unnamed replicon” as a putative chromid in P. aeruginosa, which shows a much higher similarity and closer phylogenetic relationship to chromosomes than to megaplasmids while also encoding plasmid-like partition genes. We propose that such a chromid could facilitate genome expansion, allowing for more rapid adaptations to novel ecological niches or selective conditions, in comparison to megaplasmids.

In view of the problem of floor water inrush in the process of deep coal seam mining, propose to establish a risk assessment model for coal seam floor water inrush using GIS and combined weight TOPSIS method. Take coal 12-1 of level −950 in Donghuantuo Coal Mine as an example, the coal seam hosting thickness, coal seam burial depth, fault intensity index, aquifer thickness, water-rich aquifer thickness, first aquiclude thickness and second aquiclude thickness are taken as decisive indexes. Based on actual engineering exploration, the entropy weighted AHP weighted TOPSIS method is used to determine the partition threshold and classification level, analyse the risk of water inrush from coal seam floor, and visualise it based on GIS platform. The results show that the combined weight values of coal seam burial depth and fault scale index are 0.4008 and 0.2201, which have a significant impact on water inrush from the coal seam floor. The zoning threshold for the risk coefficient of water inrush from the 12–1 coal seam floor is 0.478, The overall water inrush risk of the mine field is less. Only a few areas in the southwest of the mine field are water inrush risk areas.

Objectives: Studies have increasingly focussed on the relationship between periodontitis (PD) and preeclampsia (PE). However, conclusions have not been consistent, and it is unclear whether any causal relationship exists between them and whether causality is bidirectional. This study employed Mendelian randomisation (MR) analysis to investigate the potential bidirectional causal relationship between PD and PE. Methods: Genetic variants strongly linked to PD (17,353 cases and 28,210 controls), chronic periodontitis (CP; 1817 cases and 2215 controls), aggressive periodontitis (AgP; 851 cases and 6580 controls), and PE (7212 cases and 194,266 controls) in the genome-wide association study (GWAS) of European ancestry were used as instrumental variables (IVs). Inverse variance weighting (IVW) served as the primary method for causal inference. MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) was utilised to analyse horizontal pleiotropy. Cochrane Q tests and leave-one-out analyses were used to assess heterogeneity and stability amongst IVs. Results: The MR analysis revealed no causal impacts of PD or its 2 subtypes—CP and AgP—on PE. Similarly, no significant causal effect of PE on PD was found in the reverse-MR analysis (IVW odds ratio, 0.97; 95% confidence interval, 0.91–1.05; P = .58). The findings from MR–Egger, weighted median, weighted mode, and the simple modelling approaches, as well as the pleiotropy and sensitivity analyses, aligned with those of the IVW method. Conclusions: The MR analysis suggests no bidirectional causal relationship between PD and PE; hence, PD and PE might not increase or prevent the risk of one other. Clinical Relevance: Genetically, periodontitis or its subtypes chronic periodontitis and aggressive periodontitis may not require specific clinical attention to prevent the development of preeclampsia.

BackgroundIn vitro-in vivo extrapolation (IVIVE) is an approach utilizing in vitro experimental data to predict in vivo phenomena. It is a promising tool for chemical risk assessment.ObjectiveTo learn the hotspots, evolution path, and trend of IVIVE in risk assessment by literature search and bibliometric analysis, and provide reference and data support for subsequent research. MethodsPubMed and Web of Science Core Collection were selected as foreign databases to search for literature about IVIVE applied in risk assessment published by December 31, 2023. The number of relevant documents in CNKI and Wanfang database was too small, so the Chinese databases were not included in this study. This study employed bibilometric analysis using VOSviewer and CiteSpace for visualizing networks categorized by author, institution, country, journal, keyword, and co-citation.ResultsA total of 189 articles were included in this study. The first article was published in 2006, and since then the number of publications overall showed an upward trend and increased significantly after 2016. The institution with the most publications was the United States Environmental Protection Agency (28 articles). The United States was the most productive country (87 articles), and had a close cooperation with the United Kingdom. The journal with the most publications and the highest number of citations per article was Archives of Toxicology (19 articles). The keyword co-occurrence analysis suggested that research on IVIVE in risk assessment mainly studied the methods and models of IVIVE and prediction of chemical toxicity, and toxicity, in vitro, and models were the research hotspots in this field. Keyword timeline cluster analysis suggested that the assessment objects gradually expanded from drugs to environmental chemicals, organic chemicals and food additives. The co-citation analysis suggested that articles about IVIVE in risk assessment mostly cited journals in the environment, food, and drug fields, and these articles were mainly methodological studies followed by literature reviews. ConclusionThe research of IVIVE in risk assessment has developed rapidly. With the improvement of prediction models and the expansion of application scope, animal experiments in risk assessment may be greatly reduced and the efficiency of risk assessment can be increased. At present, the United States has a leading position in this field, while China has few relevant studies and needs to actively carry out international cooperation to improve the level of applied research of IVIVE. In the future, it is hoped that the IVIVE method can be further refined to improve its application and expand its research fields.

Abstract The Loess Plateau is a region of importance in geomorphologic research because of its typical loess layers and intense surface erosion. Analysing the landforms on the Loess Plateau is helpful for understanding changes in the surface environment. However, geomorphologic data with high resolution are lacking for the Loess Plateau, which limits the progress of geomorphologic studies at finer scales. This study provides the first 30 m resolution landform classification and characteristics dataset for the Loess Plateau (LPL30). Considering morphological characteristics, dominant dynamics, and material conditions, the landforms on the Loess Plateau were categorized into three levels with 28 landform types. Moreover, we calculated 6 metrics to quantify the spatial distribution and category composition of the landforms in 16 analytical units with different scales and shapes, resulting in 96 geomorphologic descriptors. This dataset provides fundamental data for the study of landform formation processes and evolution mechanisms at various scales and can be employed as a geomorphological gradient to support ecology and environmental research.

Abstract Amyloid myopathy often occurs in the context of systemic amyloidosis, as a rare manifestation of “light chain” (AL) amyloidosis, accounting for 1% of its incidence. A 58-year-old man with two years history of weakness and edema of lower extremity, elevated creatine kinase (CK), and inflammatory lesions from muscle biopsy which was misdiagnosed as inflammatory myopathy. After immunotherapy, the original symptoms worsened. We later confirmed the disease through MRI, Congo red staining and bone marrow puncture results. Our purpose is that to increase awareness of amyloid myopathy to minimize the risk of misdiagnosis and emphasize the importance of Congo red staining in diagnosing similar conditions.