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The microstructure and properties of Cu66.6(FeCo)33.4 and Cu60(FeCo)40 alloys were investigated. Microstructural observations show that CuFeCo alloys have formed dual-phase heterostructures comprising face-centered cubic (FCC) and body-centered cubic (BCC) phases. The average grain size of the CuFeCo alloys after cold rolling and aging is less than 10 μm. Cu66.6(FeCo)33.4 has better elongation and electrical conductivity, while Cu60(FeCo)40 has better tensile strength, hardness, saturation magnetization, and electromagnetic interference shielding effectiveness. An increased FeCo content in a finer second phase with a larger volume fraction, leading to more phase boundaries. This enhances the strength of the CuFeCo alloys while simultaneously reducing their elongation. The obtained results can be used for further development of alloys with FCC/BCC dual-phase heterostructures.

Abstract This paper aims to examine the potential link between maternal COVID-19 infection during pregnancy and the increased risk of congenital heart disease (CHD) in newborns. A comparative analysis was conducted involving two groups: mothers infected with COVID-19 during pregnancy and a control group. Data on maternal characteristics, pregnancy-related complications, and newborn outcomes were collected and analyzed. Additionally, the annual incidence rates of CHD from 2020 to 2023 were evaluated to assess trends over time. No significant differences were found between the COVID-19 cases and the control group in terms of maternal age, BMI, gravidity, parity, use of assisted reproductive technology, adverse obstetric history, or complications during pregnancy, including diabetes mellitus, preeclampsia, and thyroid abnormalities. For newborn outcomes, there were no significant differences in sex distribution, rate of cesarean delivery, Apgar scores, or birth weight. However, a significantly higher prevalence of cardiac ultrasound abnormalities was observed in the COVID-19 group (10.08%) compared to the control group (4.13%, p = 0.012). Further analysis revealed that the majority of cardiac abnormalities in the COVID-19 group occurred in mothers infected before 8 weeks of pregnancy. The annual incidence rates of CHD showed a significant increase during the COVID-19 pandemic, with the highest rate in 2023 (5.46%) compared to previous years. Maternal COVID-19 infection during pregnancy may adversely affect the development of the newborn’s heart. This could be due to the inflammatory response caused by the viral infection or other pathological processes. The findings underscore the importance of vigilant prenatal care and early detection of cardiac abnormalities during the pandemic and suggest the need for further research to explore potential mechanisms and intervention strategies.

Abstract Thyroid hormones (THs) may affect chronic thyrotoxic myopathy (CTM). The relationship between TH sensitivity and CTM is inconsistent. We aimed to investigate the associations between TH sensitivity and the risk of CTM and to screen potential CTMs with strength and function tests. A total of 162 Chinese patients (36.58% men) with Graves’ disease were enrolled and divided into CTM and non-CTM groups. TH and sensitivity indices were measured. Muscle power and function were assessed by grip, upper-limb fatigue (ULFT), lower-limb fatigue (LLFT), and squat-up (SUT) tests, and walking pace. Association between sensitivity to TH indices and the risk of developing CTM was assessed via multivariate logistic regression. The diagnostic effectiveness of muscle power and function for predicting CTM was evaluated via receiver operating characteristic (ROC) curves. Thyroid feedback quantile-based index FT3 (TFQIFT3) and the parametric TFQIFT3 (PTFQIFT3), TFQIFT4, and PTFQIFT4 were positively associated with CTM risk by using inverse probability of treatment weighting multivariate logistic regression. For each 1-SD increase in TFQIFT3 and PTFQIFT3, TFQIFT4 and PTFQIFT4, the odds ratios for CTM were 1.67 (95% CI = 1.17–2.48) ,1.64 (95% CI = 1.51–2.93), 1.60 (95%CI = 1.12–2.32), 1.58 (95%CI = 1.11–2.30), respectively. LLFT and SUT best predicted male/female CTM, respectively (AUC = 0.89/0.85). In Graves’ disease patients, TH sensitivity is associated with CTM development, which can be predicted by SUT and LLFT results.

Objective To observe the changes of coagulation factor activity and protein content of the thawed fresh frozen plasma (FFP) and fresh liquid plasma (FLP) during storage at 2-6℃, and to provide reference for exploring the appropriate storage time of FFP at 2-6℃ after thawing. Methods The small-thaw group and the large-thaw group were respectively detected for the activity of coagulation factor FⅤ (FⅤ∶C) and FⅧ(FⅧ∶C), and the levels of fibrinogen (Fib), total protein (TP) and albumin (Alb) in TTP at 1, 2, 3, 4, 5, 6 and 7 days after thawing. And the FLP was detected for FⅤ∶C, FⅧ∶C, Fib, TP and Alb at 1, 2, 3, 4, 5, 6, 7 days and 1, 6, 11, 16, 21, 26 and 31 days after preparation, respectively. Results In FFP group, FⅧ∶C decreased gradually with the prolongation of storage time after melting (P0.05). In FLP group, FⅧ∶C decreased gradually with the prolongation of storage time after melting (P0.05), but it decreased gradually in 31-day storage group (P0.05). Conclusion Although FⅧ∶C is decreased in thawed FFP stored at 2-6℃ for 7 days, it is still about 52.4%, which should be able to play a normal role in clinical practice.

The rapid development of mobile Internet has brought new development opportunities to college education and teaching. Taking university English teaching as the research object, this paper analyses the characteristics of mobile Internet in the classroom, WeChat platform, English learning app and other forms of teaching, the changes and influence of mobile Internet on English teaching, and its application in university English teaching. According to the actual teaching situation, a comprehensive evaluation system based on the learning process and results was established. The results show that the university English teaching model based on mobile Internet and the innovative evaluation and examination system can effectively improve the teaching efficiency and students' independent and sustainable learning ability. Through the reform of university English teaching, students' academic performance and learning ability have been improved. The research results are of great practical significance for promoting the reform and innovative practice of university English teaching.

Abstract CSF1R-related disorder (CSF1R-RD) is a neurodegenerative condition that predominantly affects white matter due to genetic alterations in the CSF1R gene, which is expressed by microglia. We studied an elderly man with a hereditary, progressive dementing disorder of unclear etiology. Standard genetic testing for leukodystrophy and other neurodegenerative conditions was negative. Brain autopsy revealed classic features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), including confluent white matter degeneration with axonal spheroids and pigmented glial cells in the affected white matter, consistent with CSF1R-RD. Subsequent long-read sequencing identified a novel deletion in CSF1R that was not detectable with short-read exome sequencing. To gain insight into potential mechanisms underlying white matter degeneration in CSF1R-RD, we studied multiple brain regions exhibiting varying degrees of white matter pathology. We found decreased CSF1R transcript and protein across brain regions, including intact white matter. Single nuclear RNA sequencing (snRNAseq) identified two disease-associated microglial cell states: lipid-laden microglia (expressing GPNMB, ATG7, LGALS1, LGALS3) and inflammatory microglia (expressing IL2RA, ATP2C1, FCGBP, VSIR, SESN3), along with a small population of CD44 + peripheral monocyte-derived macrophages exhibiting migratory and phagocytic signatures. GPNMB+ lipid-laden microglia with ameboid morphology represented the end-stage disease microglia state. Disease-associated oligodendrocytes exhibited cell stress signatures and dysregulated apoptosis-related genes. Disease-associated oligodendrocyte precursor cells (OPCs) displayed a failure in their differentiation into mature myelin-forming oligodendrocytes, as evidenced by upregulated LRP1, PDGFRA, SOX5, NFIA, and downregulated NKX2-2, NKX6.2, SOX4, SOX8, TCF7L2, YY1, ZNF488. Overall, our findings highlight microglia–oligodendroglia crosstalk in demyelination, with CSF1R dysfunction promoting phagocytic and inflammatory microglia states, an arrest in OPC differentiation, and oligodendrocyte depletion.

Abstract Background and Aims Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. Methods In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. Results As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. Conclusions TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.

Abstract Nanocrystalline metallic materials have the merit of high strength but usually suffer from poor ductility and rapid grain coarsening, limiting their practical application. Here, we introduce a core-shell nanostructure in a multicomponent alloy to address these challenges simultaneously, achieving a high tensile strength of 2.65 GPa, a large uniform elongation of 17%, and a high thermal stability of 1173 K. Our strategy relies on an ordered superlattice structure that excels in dislocation accumulation, encased by a ≈3 nm disordered face-centered-cubic nanolayer acting as dislocation sources. The ordered superlattice with high anti-phase boundary energy retards dislocation motions, promoting their interaction and storage within the nanograins. The disordered interfacial nanolayer promotes dislocation emission and effectively accommodates the plastic strain at grain boundaries, preventing intergranular cracking. Consequently, the order-disorder core-shell nanostructure exhibits enhanced work-hardening capability and large ductility. Moreover, such core-shell nanostructure exhibits high coarsening resistance at elevated temperatures, enabling it high thermal stability. Such a design strategy holds promise for developing high-performance materials.

The novel Ni–Cr–W–Gd alloy have the gadolinium neutron absorption unit and the tungsten gamma ray shielding unit, which can be used for thermal neutron and gamma ray co-shielding. This Ni–Cr–W–Gd alloy have good strength and fracture elongation, however, its corrosion performance has not been reported yet. In this work, the corrosion behavior for Ni–Cr–W–Gd alloys was studied in the boric acid solution at 40 °C. Electrochemical measurement techniques, long-term immersion tests, corrosion morphology and composition analysis, and first principles calculation have been used. After 4000 h immersing, the maximum steady state corrosion rate among all alloys is only 0.3221 μm/yr. The increasing Gd promotes the increase in corrosion current density and make the weight loss of alloys more serve. Both the results of relative potential test and first principles calculation demonstrate the NiCrW matrix is the anode and Ni5Gd is the cathode in micro galvanic corrosion. The matrix around the interface of matrix/Ni5Gd suffer preferential anodic dissolution, resulting in the detachment of the Ni5Gd phase and formation of pores on the surfaces. The passive films are composed of Cr2O3 and WO3, moreover, the intensity of Gd2O3 increases with Gd content. This work contributes to the promotion of the novel alloys in spent fuel storage environments.

Abstract The membrane-delimited receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2 (ACE2), which is expressed in the intestine, collaborates with broad neutral amino acid transporter 1 (B0AT1). Tryptophan (Trp) is transported into intestinal epithelial cells by ACE2 and B0AT1. However, whether ACE2 and its binding protein B0AT1 are involved in Trp-mediated alleviation of intestinal injury is largely unknown. Here, we used weaned piglets and IPEC-J2 cells as models and found that ACE2/B0AT1 alleviated lipopolysaccharide (LPS)-induced diarrhea and promoted intestinal barrier recovery via transport of Trp. The levels of the aryl hydrocarbon receptor (AhR) and mechanistic target of rapamycin (mTOR) pathways were altered by ACE2. Dietary Trp supplementation in LPS-treated weaned piglets revealed that Trp alleviated diarrhea by promoting ACE2/B0AT1 expression, and examination of intestinal morphology revealed that the damage to the intestinal barrier was repaired. Our study demonstrated that ACE2 accompanied by B0AT1 mediated the alleviation of diarrhea by Trp through intestinal barrier repair via the mTOR pathway.

Fine terrain classification is one of the main applications of Synthetic Aperture Radar (SAR). In the multiband fully polarized SAR operating mode, obtaining information on different frequency bands of the target and polarization response characteristics of a target is possible, which can improve target classification accuracy. However, the existing datasets at home and abroad only have low-resolution fully polarized classification data for individual bands, limited regions, and small samples. Thus, a multidimensional SAR dataset from Hainan is used to construct a multiband fully polarized fine classification dataset with ample sample size, diverse land cover categories, and high classification reliability. This dataset will promote the development of multiband fully polarized SAR classification applications, supported by the high-resolution aerial observation system application calibration and verification project. This paper provides an overview of the composition of the dataset, and describes the information and dataset production methods for the first batch of published data (MPOLSAR-1.0). Furthermore, this study presents the preliminary classification experimental results based on the polarization feature classification and classical machine learning classification methods, providing support for the sharing and application of the dataset.

Abstract Sterile inflammation occurs in various chronic diseases due to many nonmicrobe factors. Examples include endometrial hyperplasia (EH), endometriosis, endometrial cancer, and breast cancer, which are all sterile inflammation diseases induced by estrogen imbalances. However, how estrogen‐induced sterile inflammation regulates EH remains unclear. Here, a single‐cell RNA‐Seq is used to show that SHP2 upregulation in endometrial endothelial cells promotes their inflammatory activation and subsequent transendothelial macrophage migration. Independent of the initial estrogen stimulation, IL1β and TNFα from macrophages then create a feedforward loop that enhances endothelial cell activation and IGF1 secretion. This endothelial cell–macrophage interaction sustains sterile endometrial inflammation and facilitates epithelial cell proliferation, even after estradiol withdrawal. The bulk RNA‐Seq results and phosphoproteomic analysis show that endothelial SHP2 mechanistically enhances RIPK1 activity by dephosphorylating RIPK1Tyr380. This event activates downstream activator protein 1 (AP‐1) and instigates the inflammation response. Furthermore, targeting SHP2 using SHP099 (an allosteric inhibitor) or endothelial‐specific SHP2 deletion alleviates endothelial cell activation, macrophage infiltration, and EH progression in mice. Collectively, the findings demonstrate that SHP2 mediates the transition of endothelial activation from estradiol‐driven acute inflammation to macrophage‐amplified chronic inflammation. Targeting sterile inflammation mediated by endothelial cell activation is a promising strategy for nonhormonal intervention in estrogen‐related diseases.

IntroductionThis study investigated the potential link between serum klotho levels and cognitive function in patients with non-alcoholic fatty liver disease (NAFLD).Materials and MethodsUtilizing NHANES data from 2011 to 2014, the research included 356 eligible participants. NAFLD was identified with the United States Fatty Liver Index (US-FLI), and cognition was measured by various tests including the Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), Immediate Recall Test (IRT), and Delayed Recall Test (DRT). Weighted logistic regression and restricted cubic splines were employed to analyze the relationship between klotho levels and cognitive scores.ResultsA significant nonlinear association was observed between klotho levels and the performance in DSST and Delayed Recall Test (DRT). After controlling for confounding factors, the study found a positive association between higher serum klotho levels and improved cognitive performance in both AFT and DSST. However, there was no significant relationship between klotho levels and the IRT or DRT, regardless of whether the natural logarithm or quartile was considered.DiscussionThe findings suggest that a higher serum klotho level may be positively correlated with better cognitive performance in NAFLD patients.

Background Vaccine hesitancy among young Chinese remains a challenge, contributing to low vaccination rates for the nonavalent Human Papillomavirus (HPV) vaccine. This study evaluated the knowledge and acceptance of this vaccine among students at a southern Chinese university and identified factors influencing these outcomes. Methods This cross-sectional, anonymous questionnaire survey was conducted from April to November 2023 at a multi-campus university in southern China. The questionnaire was comprised of three sections: the first collected demographic data; the second evaluated students’ knowledge of the nonavalent HPV vaccine on a scale from 0 to 15, with cut-off points at 5 and 10 delineating low, medium, and high knowledge levels, respectively; the third section assessed vaccine acceptance on a scale from 8 to 40, using scores above the 50th percentile as the benchmark for positive acceptance. Results Among the participants, 18% demonstrated low-level, 40.20% medium-level, and 41.70% high-level knowledge of the nonavalent HPV vaccine. Notably, 71.95% of respondents showed positive acceptance, whereas 28.05% expressed negative acceptance. Male students and those with lower economic conditions (monthly living expenses below 1000 RMB, P = 0.004; 1000-1499 RMB, P = 0.012) exhibited lower knowledge levels. As for acceptance, female students and those with higher monthly living expenses (1000-1499 RMB, P = 0.007; 1500-1999 RMB, P = 0.002; over 2000 RMB, P = 0.002) demonstrated greater vaccine acceptance. A positive correlation was noted between the level of knowledge and vaccine acceptance (r s = 0.256, P < 0.001). Conclusions Gender and economic status are significantly associated with nonavalent HPV vaccine knowledge and acceptance among university students. These findings highlight the potential impact of targeted educational initiatives, especially for economically disadvantaged male students, in enhancing vaccine uptake rates.

Abstract Acetaminophen (APAP) overdose is a major cause of drug‐induced liver injury. Sirtuins 5 (SIRT5) has been implicated in the development of various liver diseases. However, its involvement in APAP‐induced acute liver injury (AILI) remains unclear. The present study aimed to explore the role of SIRT5 in AILI. SIRT5 expression is dramatically downregulated by APAP administration in mouse livers and AML12 hepatocytes. SIRT5 deficiency not only exacerbates liver injury and the inflammatory response, but also worsens mitochondrial oxidative stress. Conversely, the opposite pathological and biochemical changes are observed in mice with SIRT5 overexpression. Mechanistically, quantitative succinylome analysis and site mutation experiments revealed that SIRT5 desuccinylated aldehyde dehydrogenase 2 (ALDH2) at lysine 385 and maintained the enzymatic activity of ALDH2, resulting in the suppression of inflammation and mitochondrial oxidative stress. Furthermore, succinylation of ALDH2 at lysine 385 abolished its protective effect against AILI, and the protective effect of SIRT5 against AILI is dependent on the desuccinylation of ALDH2 at K385. Finally, virtual screening of natural compounds revealed that Puerarin promoted SIRT5 desuccinylase activity and further attenuated AILI. Collectively, the present study showed that the SIRT5‐ALDH2 axis plays a critical role in AILI progression and might be a strategy for therapeutic intervention.

ObjectiveThis study aimed to discover micro-ribonucleic acids (microRNAs) involved in the degeneration of cartilage endplates through next-generation sequencing and lay the foundation for further research.MethodsThe cartilage endplate was obtained from patients who underwent interbody fusion surgery at the Department of Spine Surgery, Shanghai East Hospital Affiliated to Tongji University, from 1 January 2020 to 1 January 2023. Total RNA was extracted from the cartilage endplate tissue. Discover differential genes through NGS. To annotate gene functions, all target genes were aligned against the Kyoto Encyclopedia of Genes (KEGG) and Gene Ontology (GO) databases. The GO enrichment and KEGG enrichment analyses of target genes were performed using phyper, a function of R. The p-value was corrected using the Bonferroni method, and a corrected p-value of ≤0.05 was taken as the threshold. GO terms or KEGG terms fulfilling this condition were defined as significantly enriched terms. The screened miRNAs and their target protein were verified in vitro using quantitative polymerase chain reaction (qPCR) and Western blotting (WB).ResultsRNA was extracted from normal and degenerated cartilage endplate tissues for NGS. Eight downregulated differentially expressed genes (DEGs) and 22 upregulated DEGs were found. The KEGG pathway analysis of these target genes revealed that differential microRNAs and target genes were enriched in different signaling pathways, and the regulated signaling pathways were mainly mitochondrial autophagy and autophagy. The qPCR results demonstrated a significant upregulation of miR-25-3p and miR-345-5p in degenerative cartilage endplate tissues (p ≤ 0.001). Western blot analysis revealed that BRD4 exhibited a marked increase in protein expression levels in degenerative cartilage endplate tissues (p ≤ 0.0001), while BECN1 showed a significant decrease in protein expression levels within these samples (p ≤ 0.0001).ConclusionWe found that DEG hsa-miR-25-3p and hsa-miR-345-5p can be used as diagnostic and therapeutic targets for IDD. The significant target proteins of miR-25-3p and miR-345-5p were BRD4 and BECN1, respectively.

IntroductionAllergic rhinitis (AR) is a widespread upper airway disorder characterized by inflammation of the nasal passages. It is immunologically mediated via the hypersensitivity type I mechanism, which is primarily elicited by the immunoglobulin E (IgE)-linking allergen-induced imbalance of the Th2/Th1 immune response. Owing to the limited efficacy of current medications, probiotics have received attention for their potential in preventing and ameliorating AR.MethodsIn this study, a Lacticaseibacillus paracasei strain, GOLDGUTLpc969 (Lpc969), isolated from the feces of healthy adults, was proven to be effective in preventing AR by LPA-induced RBL-2H3 in-vitro and OVA-induced AR mice in-vivo evaluation.ResultsThe strain significantly attenuated the release of histamine and degranulation in LPS-induced RBL-2H3 cells. In the OVA-induced AR mice, L. paracasei GOLDGUT-Lpc969 also exhibited a significant decrease in disease indicators such as the disease activity index (DAI score), serum IgE, and serum histamine. Treatment with L. paracasei GOLDGUT-Lpc969 led to significant suppression of the Th2-related cytokines IL-4, IL-5, IL-6, IL-13, and TNF-α in the serum of mice.DiscussionFurthermore, a comparison of the genomes of three previously reported AR-effective L. paracasei strains (including GOLDGUTLpc969) and one non-effective L. paracasei strain revealed that the gene K03671 may play a key role in alleviating AR symptoms. In conclusion, this study highlights the efficacy of L. paracasei GOLDGUT-Lpc969 in AR prevention by suppressing the Th2 immune response and proposes the potential involvement of the functional gene K03671 in ameliorating AR symptoms. Therefore, L. paracasei GOLDGUT-Lpc969 shows promise as a probiotic for preventing AR.

IntroductionTP53 is one of the most frequently mutated genes among all cancers, and TP53 mutants occur more than 40% in colorectal cancers (CRCs). Accumulation of mutant p53 may augment colorectal cancer stem cells (CCSCs) phenotype and enhance colorectal tumorigenesis. Thus, reducing the level of mutant p53 protein is an attractive anticancer strategy.MethodsCSC-enriched cancer cells were obtained by tumor sphere formation assay. The effects of USP7 on the proliferation of cancer cells were determined by MTS and colony formation assays. Wound healing assay was used to test cell migratory abilities. qPCR and western blotting assays were performed to verify the mRNA and protein levels of CSC markers, USP7 and p53. Co-immunoprecipitation assay was used to test the interaction effects between USP7 and p53.ResultsIn this study, we found that USP7 and mutant p53 were dramatically elevated in CSC-enriched colorectal cancer cells and USP7 expression was positively associated with self-renewal and maintenance of CCSCs. USP7 regulated cell growth, stemness and migration of colorectal cancer cells. USP7 depletion significantly reduced proliferation of cancer cells and suppressed the self-renewal of CSC-enriched colorectal cancer cells. Further studies indicated that USP7 knockdown could significantly decrease mutant p53 protein levels both in CRCs and CSC-enriched colorectal cancer cells. Moreover, mutant p53 was stabilized by USP7 and they interacted with each other. Furthermore, USP7 inhibitor P5091 also diminished CCSCs self-renewal and reduced mutant p53 levels.ConclusionTaken together, our findings demonstrated that USP7 involved in the modulation of CCSCs stemness, as well as a critical target for clinical treatment of cancers with different p53 mutations.

Objective Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity worldwide. Traditionally, disease surveillance relies on data from surveys, registries, and administrative databases. As medical records undergo global digitization, electronic medical records (EMRs) are emerging as a crucial reservoir of real-world data. However, the extent EMRs are used in CVD surveillance is unknown. We are conducting a scoping review to assess the current state and effectiveness of EMR-based CVD surveillance worldwide. Approach Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews, we searched MEDLINE and EMBASE bibliographic databases to capture studies on prevalence, incidence, and trend measurements of CVDs using EMRs. Assessed factors include CVD types, modelling methodologies, data linkages, advantages, disadvantages, challenges, and solutions. Due to the qualitative nature of the review, collected data will be narratively synthesized to present overall perspectives. Results Our search algorithm yielded 11,979 citations, of which 5,886 abstracts were selected for screening, in progress at the time of this submission. The interim results indicate that most eligible reports came from the USA (49%), followed by the UK (13%), China (6%), Spain (4%) and Canada (3%). The most common diseases were coronary artery diseases (29%), followed by hypertension (26%), stroke (21%), and heart failure (15%). Conclusions Surveillance of CVD is crucial for prevention and health policy development. While EMRs can be a data source for surveillance, such potential has yet to be fully realized. Implications This study will inform existing research challenges and future opportunities of EMR-based CVD surveillance.

Objective To evaluate validity of hospital-discharged abstract administrative health data (DAD) over years through chart reviews. Methods We analyzed three chart review cohorts (4,008 patients in 2003, 3,045 in 2015, and 9,024 in 2022) in Calgary, Canada. Nurse reviewers determined the presence or absence of 17 clinical conditions employing similar protocols. The reviews were linked with DAD using a unique lifetime identifier, chart number, and admission date. We evaluated the validity of DAD, coded in ICD-10-Canada version, in recording conditions by comparing against chart reviews. The C-statistics was calculated in predicting in-hospital mortality. Results The mean difference in prevalence between chart reviews and DAD for these 17 conditions was 2.1% in 2003, 7.6% in 2015, and 6.3% in 2022. However, some conditions were relatively stable, such as diabetes (1.9%, 2.1%, and 1.1%) and metastatic cancer (0.3%, 1.1%, and 0.4%). For 17 conditions, the sensitivity ranged 39.6-85.1% in 2003, 1.3-85.2% in 2015, and 3.0-89.7% in 2022. The C-statistics for in-hospital mortality based on DAD was 0.84 in 2003, 0.81 in 2015, and 0.78 in 2022. Conclusion DAD increasingly under-coded conditions over 19 years. The validity of DAD decreased but remained relatively stable for certain conditions mandated for coding. The under-coding exerted minimal impact on in-hospital mortality prediction. Implications The under-coding could be primarily due to the increase of hospital patient volumes and the limited time allocated to coders. Consequently, there is a need to develop artificial intelligence methods based on electronic medical records to support coding practices and improve coding quality.

Objective Electronic medical records (EMR) are widely available to complement administrative data-based disease surveillance and healthcare performance evaluation. Defining conditions from EMR is labour-intensive, requiring advanced medical informatics knowledge, and is challenging without effective data extraction tools. This study developed a high-throughput pipeline to detect diseases in EMRs. Methods We developed a pipeline that leverages a generative large language model (LLM) to analyze, understand, and interpret EMR notes by following clinical experts’ designed prompts. The pipeline was applied to detect diabetes, hypertension, and acute myocardial infarction (AMI) from the EMRs for a cardiac patient cohort in Calgary, Canada. The performance was compared against clinician-validated diagnoses as the reference standard. Results The cohort consisted of 3,413 patients with 551,095 clinical notes. The prevalence was 27.8%, 66.3%, and 54.3% for diabetes, hypertension, and AMI, respectively. The performance for detecting conditions varied: diabetes had 90.5% sensitivity, 83% specificity, and 67% positive predictive value (PPV); hypertension had 94.2% sensitivity, 30.2% specificity, and 73.8% PPV; and AMI had 86.4% sensitivity, 61% specificity, and 75.3% PPV. The monthly prevalence trends between the detected cases and reference standard showed similar patterns. Conclusion The proposed pipeline demonstrated reasonable accuracy and high efficiency in disease detection without manually curated labels, indicating the potential for automated real-time disease surveillance using EMRs. Implication Variations of documentation practices in clinical note can impact the detection performance of different diseases. Hence, an automated pipeline integrating LLMs with expert knowledge may improve detection accuracy with reduced labour costs while indicating documentation quality.

Objective Administrative data often underrepresents hospital adverse events (AEs) due to limitations in International Classification of Diseases (ICD) coding. By leveraging electronic medical records (EMRs), we aim to mitigate these discrepancies and enhance the precision of healthcare surveillance and performance evaluations. To this end, we have developed a machine learning (ML)-based approach that utilizes EMR text data to detect common AEs. Methods We sampled adult admissions from four Calgary hospitals (2017 - 2022). Registered nurses assessed charts for 17 AEs, and the results were used as reference standard. We compared two AE detection methods: the standard ICD-based method following Canadian guidelines, and our ML algorithm applied to EMR narratives. Sensitivity, positive predictive value (PPV), negative predictive value (NPV), and specificity for both methods were calculated and compared against the reference standard. Results We analyzed 9,566 patients, of whom 1,506 were identified with AEs. Of the 17 AEs, the sensitivity in ICD-coded data ranged from 0-37%, and in EMRs, it was between 75-100%. Both showed low PPV (0-50% ICD vs.1-34% EMR). ICD data had high specificity ranging from 99-100% and NPV (99%-100%), while EMRs had specificity between 68-94% and an NPV of 100%. Conclusion and Implications ML significantly enhances sensitivity for AE detection compared to ICD-10-CA coding, despite both methods experiencing low PPV due to imbalances in EMR data. This marked improvement in sensitivity highlights ML's potential to transform AE surveillance and reporting, promising significant advancements in patient safety and healthcare quality by enabling more accurate and comprehensive identification of AEs.

Background & aims: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) has long been recognized as an adipokine. However, the exact role of eNAMPT in alcoholic liver disease (ALD) and its relevance to brown adipose tissue (BAT) remain largely unknown. This study aimed to evaluate the impact of eNAMPT on liver function and the underlying mechanisms involved in BAT-Liver communication. Methods: Serum eNAMPT levels were detected in the serum of both ALD patients and mice. Chronic and binge ethanol feeding was used to induce alcoholic liver injury in mice. An eNAMPT antibody, a coculture model of brown adipocytes and hepatocytes, and BAT-specific Nampt knockdown mice were used to investigate the role of eNAMPT in ALD. Results: Serum eNAMPT levels are elevated in ALD patients and are significantly positively correlated with the liver injury index. In ALD mice, neutralizing eNAMPT reduced the elevated levels of circulating eNAMPT induced by ethanol and attenuated liver injury. In vitro experiments revealed that eNAMPT induced hepatocyte ferroptosis through the TLR4-dependent mitochondrial ROS-induced ferritinophagy pathway. Furthermore, ethanol stimulated eNAMPT secretion from brown adipocytes but not from other adipocytes. In the coculture model, ethanol-induced release of eNAMPT from brown adipocytes promoted hepatocyte ferroptosis. In BAT-specific Nampt-knockdown mice, ethanol-induced eNAMPT secretion was significantly reduced, and alcoholic liver injury were attenuated. These effects can be reversed by intraperitoneal injection of eNAMPT. Conclusion: Inhibition of ethanol-induced eNAMPT secretion from BAT attenuates liver injury and ferroptosis. Our study reveals a previously uncharacterized critical role of eNAMPT-mediated BAT-Liver communication in ALD and highlights its potential as a therapeutic target.

Abstract Background The implementation of antibiotic intravenous-to-oral switch (IVOS) therapy in hospitals can slow down the development of drug resistance, reduce the occurrence of adverse reactions, and bring significant economic benefits. The aim of this study is to investigate the understanding of physicians at the Second Affiliated Hospital of Soochow University in Suzhou, China towards the antibiotic IVOS therapy. Methods 15 physicians working in 9 different departments of the Second Affiliated Hospital of Soochow University participated in this study. A semi-structured face-to-face interview was conducted to collect interview information about the antibiotic IVOS therapy. NVivo12 software was used to organize the entire interview content, and the interview data was analyzed and summarized using the Colaizzi seven step method. Results 60% of participants were not familiar with antibiotic IVOS therapy. Barriers of antibiotic IVOS therapy were included by three key issues: (i) Physicians’ potential cognition: ‘Iv is always better than oral’; (ii) Subjective infusion intention of patients; and (iii) Limitations of drug selection. 60% of participants expressed welcome for pharmacists to help them perform antibiotic IVOS treatment. And electronic recognition technology may be a feasible method for prompting IVOS conversion that recognized by all participants in the interview. Participants also provided some suggestions for pharmacists and IVOS computer reminders. Conclusion Physicians’ in China still have insufficient understanding of antibiotic IVOS therapy. The promotion of antibiotic IVOS therapy in China faces many challenges and obstacles. Strategies such as IVOS therapy computer reminders and clinical pharmacists’ medication guidance were worth studying to help physicians develop antibiotic IVOS treatment.

Abstract Purpose This study aimed to assess the health-related quality of life (HRQoL) of the Chinese population by using the Chinese medicine quality of life-11 dimensions (CQ-11D) questionnaire and to identify factors associated with HRQoL. Methods The data was derived from a survey conducted by the Institute of Pharmacoeconomics Evaluation at Beijing University of Chinese Medicine on the quality of life of the Chinese population. The sex and age of respondents were considered through quota sampling. Demographic, socioeconomic, and health indicators were collected using the structured questionnaire. We performed bivariate analyses first to examine the associations between the above factors and the HRQoL of respondents measured by the CQ-11D. Multivariate linear regression and ordinal logistic regression models were established to analyze the factors (demographic, socioeconomic, and health indicators) differences in HRQoL, as well as the risk of each group reporting problems across the 11 dimensions of CQ-11D. Results From February 2021 to November 2022, a total of 7,604 respondents were involved and 7,498 respondents were included. The sample approximated the general adult Chinese population in terms of age, sex, and district of residence, and each geographic distribution ranged from 9.71 to 25.54%. Of the respondents, 45.84% were male, and 89.82% were Han ethnicity. The mean utility score ranged from 0.796 to 0.921 as age increased. According to the respondents, most health problems were identified in the PL (fatigue) (70.16%) and SM (quality of sleep) (63.63%) dimensions. The CQ-11D index scores varied with the demographic and socioeconomic characteristics of respondents, except for ethnicity (p > 0.05) and income (p > 0.05). The multivariate analysis revealed significant negative associations between health utility scores and various factors. These factors include sex (female), age over 65, belonging to ethnic minorities, rural household registration, being widowed or divorced, having a primary school education or below, being a student or unemployed, having a low income of 0–1,300, engaging in smoking or drinking, limited participation in physical activities, experiencing changes in self-perceived health status compared to the previous year, and having chronic diseases. The odds of respondents reporting problems in 11 dimensions varied among different socio-demographic groups. Conclusions This study reports the first Chinese population norms for the CQ-11D derived using a representative sample of the Chinese general population. Self-reported health status measured by the CQ-11D varies among different socio-economic groups. In addition to participation a physical activity and the presence of chronic disease, smoking and drinking also significantly influence HRQoL.

Abstract Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Abstract Background Programmed cell death (PCD) functions critically in cancers and PCD-related genes are associated with tumor microenvironment (TME), prognosis and therapeutic responses of cancer patients. This study stratified hepatocellular carcinoma (HCC) patients and develop a prognostic model for predicting prognosis and therapeutic responses. Methods Consensus clustering analysis was performed to subtype HCC patients in The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) among the subtypes were filtered and subjected to the least absolute shrinkage and selection operator (LASSO) regression analysis and univariate Cox regression analysis to filter prognostic genes. A PCD-related prognostic gene signature in TCGA was constructed and validated in ICGC-LIRI-JP and GSE14520 datasets. TME was analyzed using CIBERSORT, MCP-counter, TIMER and EPIC algorithms. Drug sensitivity was predicted by oncoPredict package. Spearman analysis was used to detect correlation. Results Four molecular subtypes were categorized based on PCD-related genes. Subtype C1 showed the poorest prognosis, the most infiltration of Fibroblasts, dentritic cell (DC) and cancer-associated fibroblasts (CAFs), and the highest TIDE score. C4 had a better prognosis survival outcome, and lowest immune cell infiltration. The survival outcomes of C2 and C3 were intermediate. Next, a total of 69 co-DEGs were screened among the four subtypes and subsequently we identified five prognostic genes (MCM2, SPP1, S100A9, MSC and EPO) for developing the prognostic model. High-risk patients not only had unfavorable prognosis, higher clinical stage and grade, and more inflammatory pathway enrichment, but also possessed higher possibility of immune escape and were more sensitive to Cisplatin and 5. Fluorouracil. The robustness of the prognostic model was validated in external datasets. Conclusion This study provides new insights into clinical subtyping and the PCD-related prognostic signature may serve as a useful tool to predict prognosis and guide treatments for patients with HCC.

The effect of yttrium on the 475 °C brittleness and microstructure stability of Fe–13Cr–6Al–2Mo-0.5Nb-0.15Zr alloy after long-term aging at 475 °C has been investigated. At the early stage of aging, the nanoscale metastable transition phase precipitates in large quantities. After aging for 10,000 h, the nanophase in the Y-free alloy has completely disappeared, and only a great deal of granular Laves phases are left, while a large number of nanoscale phases still exist in the grain of Y-containing alloys. This is because the addition of yttrium combines with vacancies, hinders the diffusion of Laves phase-forming elements, and has the result that the transformation of nanoscale phases Fe2(Mo0.3Nb0.7)Al to Laves phase is inhibited during the aging process of the Y-containing alloys. During aging, precipitation-free zones (PFZ) are formed in the surrounding area where the Laves phase and grain boundaries exist. The elongation of Y-containing alloys decreases with yttrium content, but it is still higher than that of Y-free alloy. The addition of yttrium improves the aging plasticity and weakens the degree of 475 °C brittleness of the alloy, and the effectiveness is diminished with the yttrium. This plays a key role in the further study of Fe–Cr–Al alloys for fuel cladding materials.

Abstract This study aimed to investigate differences in clinical characteristics and laboratory findings between children infected with Macrolide-Sensitive Mycoplasma pneumoniae (MSMP) and Macrolide-Resistant Mycoplasma pneumoniae (MRMP). Additionally, the research sought to identify laboratory markers for rapidly distinguishing refractory Mycoplasma pneumoniae pneumonia (RMPP) from ordinary Mycoplasma pneumoniae pneumonia (OMPP). In total, 265 Mycoplasma pneumoniae (MP) patients were included, with MRMP identified by specific point mutations in domain V of the 23S rRNA gene. A retrospective analysis compared the clinical courses and laboratory data, revealing that MRMP patients experienced prolonged febrile days (P = 0.004), elevated CRP levels (P

New neutron-absorbing Ni-based functional alloys that depend on the gadolinium and dysprosium neutron absorption units were fabricated using vacuum induction melting. The effects of Gd and Dy contents on the microstructure characteristics and properties of Ni-based alloys were investigated. Adding Gd, Dy, and Gd + Dy into Ni-based alloys formed Ni5Gd, Ni5Dy and Ni5(Gd,Dy), respectively, and their volume fraction increased with increasing of Gd/Dy content. Different type of elements, Gd or Dy, had no obvious influence on mechanical properties and corrosion resistance, while the amount of Gd and Dy elements played an important role. The shielding properties were calculated by the Monte Carlo method, and the alloys possessed high efficiency and high durability performance due to the high contents of Gd and Dy elements. The developed alloys are expected to be good functional materials for use in the field of nuclear shielding.

Our objective was to systematically evaluate the impact of substituting fish meal (FM) with poultry by-product meal (PBM) in fish feed on the growth and hepatic health of loach. Six diets with different levels of PBM (0 %-PBM0, 10 %-PBM10, 30 %-PBM30, 50 %-PBM50, 70 %-PBM70 and 90 %-PBM90 were formulated. After 8 weeks feeding trial, the highest weight gain (WG) was observed in 55 % PBM replacement ratio. Meanwhile, the lowest feed conversion ratio (FCR) were observed in 41.56 % PBM replacement ratio. In addition, dietary PBM induced hepatic oxidative stress including increasing the activity of aminotransferase from PBM0 to PBM50 group, whereas the activity of those enzymes was decreased from PBM50 to PBM90 group. Meanwhile, histological analysis showed that the lipid vacuoles in the liver were increased from PBM0 to PBM50 group, then decreased from PBM50 to PBM90 group (P< 0.05). Moreover, primary bile acid biosynthesis was the only one pathway enriched in top 20 significant pathways by transcriptomic and metabolomic analysis. Specifically, the key bile acid synthesis gene CYP7a1 was down-regulated, while CYP7b1 evinced an up-regulated pattern in PBM50 group compared to PBM0 group. In short, the PBM replacement ratio of up to 50 % in diets was appropriate for rearing loach, while higher PBM replacement ratio resulted in extremely oxidative stress in the liver.

Varicella is a vaccine-preventable disease caused by the varicella zoster virus (VZV), but the varicella incidence among children has increased in recent years. This was a retrospective birth cohort study based on the Zhejiang Provincial Immune Information System (ZJIIS) and the China Information System for Disease Control and Prevention (CISDCP) in Quzhou. A total of 1,291 clinically diagnosed varicella cases born from 2009 to 2014 were collected during 2009–2023, which were analyzed the impact of changes in vaccination strategy on the incidence of varicella based on the Cox-proportional hazards model. It was observed that the onset age of varicella shifted to the older age group and later to 9–11 years. After the change to the two-dose varicella vaccination strategy, the population affected by varicella was concentrated among students and received more than one dose of live attenuated varicella vaccine (VarV). Based on the Coxproportional hazards model and adjusting for all covariates, the risk of varicella infection in children decreased after the introduction of the two-dose varicella vaccination strategy (HR = 0.04, 95% CI: 0.03–0.05). Meanwhile, the Kaplan–Meier curves also showed that the hazards were lower after the change in vaccination strategy. It is recommended that two doses of VarV should be included in the national immunization schedule and that full vaccination should be completed approximately four years after the first dose.

IntroductionData on the management of patients aged more than 85 years with chronic hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequential infections are lacking.MethodsThe current study described the management of an older couple aged more than 85 years with these above-mentioned two diseases treated with 12 weeks of sofosbuvir/velpatasvir (Epclusa®) and 5 days of nirmatrelvir/ritonavir (Paxlovid®) sequentially. The effectiveness and safety profiles were closely monitored during therapy and till 9 months posttreatment.ResultsIn late March 2023, the husband with the main complaint of repeated gingival bleeding and asymptomatic wife were 86 and 85 years old, and had HCV RNA levels of 91,800 and 6,630,000 IU/mL, respectively. On the fourth day of sofosbuvir/velpatasvir treatment, the husband had a moderate headache, and the wife had severe headache and moderate fever and dizziness. We then found that their SARS-CoV-2 test results were positive. After careful consideration, the expert panel decided to treat the couple with oral nirmatrelvir/ritonavir (300 mg/100 mg, twice daily) beginning on the fifth day of sofosbuvir/velpatasvir treatment for 5 days. During the 5 days of nirmatrelvir/ritonavir treatment, the patient’s symptoms and signs gradually improved, and the patient was negative for SARS-CoV-2 RNA on the fifth day of nirmatrelvir/ritonavir therapy. Meanwhile, the husband’s HCV RNA was not detectable after one week of sofosbuvir/velpatasvir treatment till posttreatment month 9, and his ALT level was normal beginning at week 1 of sofosbuvir/velpatasvir treatment. Moreover, the wife’s HCV RNA was not detectable after week 4 of sofosbuvir/velpatasvir treatment till posttreatment month 9. Notably, no other symptoms or signs occurred during the treatment or follow-up period, and other serum biochemical parameters remained stable until 9 months after the discontinuation of sofosbuvir/velpatasvir treatment.ConclusionThe older couple aged more than 85 years with chronic HCV and SARS-CoV-2 sequential infection were safely cured by the sofosbuvir/velpatasvir and nirmatrelvir/ritonavir sequential treatment.DiscussionThis study suggested that old age should not be a barrier to HCV/SARS-CoV-2 treatment. Given that the proportion of older HCV-infected patients is increasing, clinical trials of direct-acting antiviral agents should include older HCV-infected individuals.

This study takes a nearby foundation pit project of a high-speed railway in Yancheng City, Jiangsu Province as an example to investigate the impact of deep foundation pit projects on groundwater and the surrounding environment. Through on-site monitoring, in-situ testing, and numerical simulation, we conducted a comprehensive study of the impact of foundation pit projects on groundwater and the surrounding environment. The evolution of groundwater levels and surface displacement during the excavation of foundation pits was analyzed, and a method for measuring the permeability of target soil layers in situ was studied. The simulation of recharge under various soil conditions was performed, and the outcomes demonstrated the effective isolation of hydraulic connections between the interior and exterior of the foundation pit by the water-resistant curtain. Precipitation head and constant head recharging tests were employed to ascertain the actual permeability. The characteristic time method calculation exhibited remarkable efficiency and accuracy in determining the permeability coefficient of the recharging soil layer. Recharging phreatic and confined water layers has differing degrees of influence on surface deformation, with the impact of confined water layers requiring more time to stabilize. These findings contribute significantly to a more comprehensive understanding of the environmental repercussions associated with deep excavation projects, thereby enhancing safety and environmental protection measures in excavation construction practices.

IntroductionImmune cells are involved in the onset and progression of Sjögren’s syndrome (SS). This study explored the causal relationship between immune signature cells and SS, which has not been fully elucidated.MethodsWe conducted univariate, multivariate, and bidirectional Mendelian randomization to investigate the causal relationship between 731 immunological feature characteristic cells and SS pairs and explore the interaction of immune cells in SS.ResultsAfter false discovery rate correction, six immune cells were significantly associated with SS risk. Among them, four contributed to SS (CD24 on memory B cell, CD27 on IgD + CD24 + B cell, CD28 on CD39+ secreting CD4 Treg cell, and CD80 on CD62L + mDC); two appeared to reduce SS risk (CD3 on CD39 + CD8 + T cell and CD38 on IgD + CD38 + B cell). Pleiotropy and heterogeneity were not observed. Three immune cells exerted independent effects for SS (CD27 on IgD + CD24 + B cell, CD80 on CD62L + mDC, and CD38 on IgD + CD38 + B cell); two were risk factors (CD27 on IgD + CD24 + B cell and CD80 on CD62L + mDC); and one was a protective factor (CD38 on IgD + CD38 + B cell). Twenty-three immune cells showed a reverse causal relationship with SS.ConclusionThese findings demonstrate the influence of immune cells on SS risk and the effects of SS on immune cells, providing new clues for further research on the mechanisms underlying SS.

Abstract Background Particulate β‐glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown. Methods C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF). Results The 150 mg/kg OAW treatment mitigated OVA‐induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)‐α and IL‐6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF. Conclusion These results highlight OAW's robust anti‐inflammatory properties, suggesting potential benefits in treating MC‐dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.

Background: Traditional working procedures requires a lot of clinical processes and processing time. Methods: The orthodontic metal appliances were made by applying oral scanners, digital images, computer-aided design and computer-aided manufacturing (CAD-CAM) printers. Results: The computer digital technology simplified the manufacturing process for dental appliances and shorten the duration for clinical operation and technical processing. Conclusions: The technique described in this paper can guarantee the accuracy of orthodontic appliances and bring revolution the field. Clinical significance: The CAD-CAM technology provides a fully digital workflow for manufacturing metal orthodontic appliances, which saves a considerable amount of labor and material costs, and significantly reduces heavy metal pollution in the working environment of dental technicians.

High-entropy alloys (HEAs) demonstrate superior mechanical properties at room temperature, highlighting potential for engineering applications. With the increasing demand for advanced materials, especially in modern applications facing rigorous conditions, it becomes imperative to gain profound insights into the dynamic behavior of HEAs. In this study, the (FeCoNi)86Al7Ti7 HEA, renowned for exceptional printability and room-temperature mechanical properties, has been fabricated by selective laser melting (SLM), and its tensile and impact behaviors at ambient and cryogenic temperatures are systematically investigated. Experimental results reveal enhanced tensile properties as temperature decreases, achieving a high ultimate strength of 1313.6 MPa and impressive ductility of 24.8 % at 77 K. This improvement is attributed to the synergistic deformation mechanisms, including dislocation slip, stacking faults, Lomer and Lomer-Cottrell locks, which maintain a high strain-hardening rate and thus suppress strain localization. In contrast, impact properties deteriorate due to constrained dislocation mobility at high strain rates and low temperatures, with Charpy impact energy decreasing from 8.1 J at 293 K to 5.1 J at 77 K. Consequently, cracks readily initiate at cellular boundaries or defects, propagating in an intergranular manner and inducing localized deformation. This study provides valuable insights for the future applications of 3D-printed HEAs in extreme operational environments.

Abstract Background The range of mandibular invasion by a tumour needs to be determined accurately to minimize unnecessary damage to the mandible. This study aimed to compare tumour boundary lines on computed tomography/magnetic resonance (CT/MR) images with those from pathological findings during the preoperative assessment of mandibular invasion by oral squamous cell carcinoma (OSCC). By comparing the methods, the potential of CT/MR for this application could be further elucidated. Methods Eight patients with OSCC were imaged with CT/MR, mandibular specimens were collected, and the material site was measured. Haematoxylin–eosin staining was used for histopathological assessment. The presence and boundaries of bone invasion were evaluated. The CT/MR and histopathological boundaries of bone invasion were delineated and merged to compare and calculate the deviation of CT/MR and histopathological boundaries using the Fréchet distance. Results The mean Fréchet distance between the CT and pathological tumour boundaries was 2.69 mm (standard error 0.46 mm), with a minimum of 1.18 mm, maximum of 3.64 mm, median of 3.10 mm, and 95% confidence interval of 1.40–3.97 mm. The mean Fréchet distance between the tumour boundaries on the MR and pathological images was 3.07 mm (standard error 0.56 mm), with a minimum of 1.53 mm, maximum of 4.74 mm, median of 2.90 mm, and 95% confidence interval of 1.53–4.61 mm. Conclusions CT/MR imaging can provide an effective preoperative assessment of mandibular invasion of OSCC. Pathology images can be positioned on CT/MR scans with the help of computer software to improve the accuracy of the findings. The introduction of the Fréchet distance to compare tumour boundary lines is conducive to computer image diagnosis of tumour invasion of jaw boundaries.

Building change detection on remote sensing images is an important approach to monitoring the urban expansion and sustainable development of natural resources. In conventional building change detection tasks, only changed regions between two time phases are typically concerned. The relevance and trend of spatiotemporal changes between multiple time phases are neglected in most cases. In this article, we propose a two-stage continual urbanization detector (COUD) for time series urban building change detection task. The COUD method employs self-supervised pretraining for feature refinement, and performs optimization through temporal distillation approach. Consequently, multitemporal feature extraction and changing regions localization of urban building complexes are conducted. Considering the gap in available dataset for time series change detection task, we produce and release a time series dataset named “TSCD”. Chengdu region of China is selected as the study area in this research, which is partially covered by the proposed TSCD dataset. By applying the proposed COUD method to the selected study area for exploring the changing pattern from 2016 to 2022, a comprehensive analysis is conducted in conjunction with actual planning policies published by the management department. Extensive experimental results confirm the reliability of our proposed method.

The 3D human pose estimation is a technique used to determine the position of the human body in a three-dimensional space. This involves identifying body rotations, joint angles, and other pose-related information from image or video data. In this paper, we propose an end-to-end 3D human pose estimation network that is based on multi-level feature fusion.The network is composed of two main components. The first component utilizes the deepest features extracted by the backbone network. These features undergo initial data encoding and are then processed by the Semantic Information Extraction Module, which primarily consists of a multi-head self-attention mechanism. This module extracts deeper features, resulting in primary human body feature data. The second component focuses on the shallowest features and inputs them into the Global Information Processing Module, which performs global feature extraction.The features extracted from both components, along with the Bbox info (bounding box information), are collectively fed into the Iterative Regression Module. This module generates human pose data, which is then utilized to reconstruct and generate the human body using a human pose model. To evaluate the performance of our method, we train and test it on well-known benchmark datasets such as 3DPW, AGORA and MPII. Our method demonstrates exceptional performance, as it achieves a reduction of approximately 5.3% on the PA-MPJPE metric and approximately 5.1% on the MPJPE metric compared to the best model we referenced.

Abstract Background Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. Methods Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-β were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. Results In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1 −/− rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-β, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic β cells. Conclusions Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.

Abstract Background Precise prediction of esophageal squamous cell carcinoma (ESCC) invasion depth is crucial not only for optimizing treatment plans but also for reducing the need for invasive procedures, consequently lowering complications and costs. Despite this, current techniques, which can be invasive and costly, struggle with achieving the necessary precision, highlighting a pressing need for more effective, non-invasive alternatives. Method We developed ResoLSTM-Depth, a deep learning model to distinguish ESCC stages T1-T2 from T3-T4. It integrates ResNet-18 and Long Short-Term Memory (LSTM) networks, leveraging their strengths in spatial and sequential data processing. This method uses arterial phase CT scans from ESCC patients. The dataset was meticulously segmented by an experienced radiologist for effective training and validation. Results Upon performing five-fold cross-validation, the ResoLSTM-Depth model exhibited commendable performance with an accuracy of 0.857, an AUC of 0.901, a sensitivity of 0.884, and a specificity of 0.828. These results were superior to the ResNet-18 model alone, where the average accuracy is 0.824 and the AUC is 0.879. Attention maps further highlighted influential features for depth prediction, enhancing model interpretability. Conclusion ResoLSTM-Depth is a promising tool for ESCC invasion depth prediction. It offers potential for improvement in the staging and therapeutic planning of ESCC.

Abstract Background Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. Methods We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. Results Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P

The wear resistance of the part surface has become an important factor affecting its own service life. Laser cladding (LC), as a surface modification technology, can prepare a coating with good metallurgical bonding with the substrate, which can significantly improve the wear resistance of the material surface. High entropy alloys (HEAs) are an emerging coating material with excellent wear resistance. Therefore, this paper reviews the latest development status in wear resistance of laser cladding-high-entropy alloy coatings (LC-HEACs) in terms of the HEAs material system, LC process parameters, strengthening phase, amorphous phase strengthening, assisted cladding, and post-treatment. At the same time, this paper also expounds on the mechanism of LC-HEACs enhancing the surface wear resistance of materials, and the current research status of LC-HEACs in different engineering materials and application environments. Finally, the current research deficiencies, challenges, and future development trends of LC-HEACs in the field of wear resistance are also elaborated, and it is expected to provide some references for their future development and applications.

Abstract The archaeal ancestor of eukaryotes apparently belonged to the phylum Asgardarchaeota, but the ecology and evolution of Asgard archaea are poorly understood. The optimal GDP-binding temperature of a translation elongation factor (EF-1A or EF-Tu) has been previously shown to correlate with the optimal growth temperature of diverse prokaryotes. Here, we reconstruct ancestral EF-1A sequences and experimentally measure the optimal GDP-binding temperature of EF-1A from ancient and extant Asgard archaea, to infer the evolution of optimal growth temperatures in Asgardarchaeota. Our results suggest that the Asgard ancestor of eukaryotes was a moderate thermophile, with an optimal growth temperature around 53 °C. The origin of eukaryotes appears to coincide with a transition from thermophilic to mesophilic lifestyle during the evolution of Asgard archaea.

Chitosan (CTS) as an environment-friendly biological macromolecule was applied to investigate its effect in improving the property of zirconium-based Cr(III) conversion coating on Zn-55Al-1.6Si coated steel sheet (Zn55Al). High-resolution transmission electron microscope gave the key evidence that CTS can effectively wrap the main film-forming substances and participate in the construction of Zr@CTS-TCC. A comparative analysis of electrochemical measurements showed that the addition of 0.2 g·L–1 CTS can improve the corrosion resistance of Zr@CTS-TCC and decrease the surface density of micro defects. Surface spectroscopy characterization provided a theoretical explanation for the role of CTS as an electron supplier in reduction of Cr(VI). Results demonstrate the potential of CTS as an environmentally friendly and effective cross-linking additive, which provides an alternative approach in developing next generation of trivalent chromium or chromium-free passivator for nonferrous alloy and their coatings.