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Abstract Background Malaria-associated acute lung injury/acute respiratory distress syndrome (MA-ALI/ARDS) is a fatal complication of Plasmodium falciparum infection that is partially triggered by macrophage recruitment and polarization. As reported, copper exposure increases the risk of malaria infection, and copper accumulation-induced cuproptosis triggers M1 macrophage polarization. It is thus hypothesized that cuproptosis could act as a critical mediator in the pathogenesis of MA-ALI/ARDS, but its underlying mechanism remains unclear. The present study aimed to explore the role of cuproptosis in the severity of murine MA-ALI/ARDS. Methods We utilized an experimental model of MA-ALI/ARDS using female C57BL/6 mice with P. berghei ANKA infection, and treated these animals with the potent copper ion carrier disulfiram (DSF) or copper ion chelator tetrathiomolybdate (TTM). The RAW 264.7 macrophages, which were stimulated with infected red blood cells (iRBCs) in vitro, were also targeted with DSF-CuCl2 or TTM-CuCl2 to further investigate the underlying mechanism. Results Our findings showed a dramatic elevation in the amount of copper and the expression of SLC31A1 (a copper influx transporter) and FDX1 (a key positive regulator of cuproptosis) but displayed a notable reduction in the expression of ATP7A (a copper efflux transporter) in the lung tissue of experimental MA-ALI/ARDS mice. Compared to the P. berghei ANKA-infected control group, mice that were administered DSF exhibited a remarkable increase in parasitemia/lung parasite burden, total protein concentrations in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio, vascular leakage, and pathological changes in lung tissue. Strikingly, the experimental MA-ALI/ARDS mice with DSF treatment also demonstrated dramatically elevated copper levels, expression of SLC31A1 and FDX1, numbers of CD86+, CD68+, SLC31A1+-CD68+, and FDX1+-CD68+ macrophages, and messenger RNA (mRNA) levels of pro-inflammatory cytokines (tumor necrosis factor [TNF-α] and inducible nitric oxide synthase [iNOS]) in lung tissue, but showed a remarkable decrease in body weight, survival time, expression of ATP7A, number of CD206+ macrophages, and mRNA levels of anti-inflammatory cytokines (transforming growth factor beta [TGF-β] and interleukin 10 [IL-10]). In contrast, TTM treatment reversed these changes in the infected mice. Similarly, the in vitro experiment showed a notable elevation in the mRNA levels of SLC31A1, FDX1, CD86, TNF-α, and iNOS in iRBC-stimulated RAW 264.7 cells targeted with DSF-CuCl2, but triggered a remarkable decline in the mRNA levels of ATP7A, CD206, TGF-β, and IL-10. In contrast, TTM-CuCl2 treatment also reversed these trends in the iRBC-stimulated RAW 264.7 cells. Conclusions Our data demonstrate that the activation of cuproptosis with DSF aggravated the severity of MA-ALI/ARDS by partially inducing M1 polarization of pulmonary macrophages, while inhibition of cuproptosis with TTM contrarily ameliorated the severity of MA-ALI/ARDS by promoting macrophage M2 polarization. Our findings suggest that blockage of cuproptosis could be a potential therapeutic strategy for treatment of MA-ALI/ARDS. Graphical Abstract

Abstract Background Fish gut microbiota undergo dynamic changes under the influence of many factors and play an important role in the nutrition, immunity and development in fish. Although common carp (Cyprinus carpio L.) is an economically important freshwater fish, there are few reports on its gut microbiota changes at different early developmental stages. In the present study, the gut microbiota of common carp during the early developmental stages and its correlation with the feed and pond water flora were studied using the Illumina MiSeq sequencing platform. Results The results showed that the gut microbiota of common carp underwent continuous and mild changes over the development process, and the pond water environment might provide bacterial resources and have a certain influence on the changes in the gut microbiota of common carp. However, host selection pressure played a more important role in shaping the gut microbiota. Although the gut microbiota was affected by many factors, the presence of core microbiota indicated that some bacterial species adapt to the gut microenvironment of common carp and played a role in its growth process. Conclusions The dynamic changes of gut microbiota of carp in early development stage were related to the feed, water environment and host selection. The results of this study provide a theoretical basis for healthy farming and disease prevention of common carp.

Abstract We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR deficiency as detected by RAD51 foci formation. This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men.

Abstract Background We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. Methods This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. Results Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI − 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). Conclusions The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Summary Background Tuberculosis (TB) remains a persistent threat to global public health and traditional treatment monitoring approaches are limited by their potential for contamination and need for timely evaluation. Therefore, new biomarkers are urgently required for monitoring the treatment efficacy of TB. Methods This study aimed to elucidate the levels of CXCL10 and CXCL9 in pulmonary TB patients who underwent anti-TB treatment. The data was acquired from five databases, including PubMed, Ovid, Web of Science, Embase, and the Cochrane Library. A meta-analysis of CXCL10 data from all time points was conducted. Furthermore, a trend meta-analysis of temporal data of CXCL10 and CXCL9 from multiple time points was also performed. Results It was revealed that patients who responded poorly to anti-TB treatment had higher serum levels relative to those who responded well (SMD: 1.23, 95% CI: -0.37–2.84) at the end of intensive treatment (2 months). Furthermore, heterogeneity was observed in these results, which might be because patients with a prior history of TB and different treatment monitoring methods than those selected in this study were also included. The analysis of alterations in CXCL10 and CXCL9 levels since the last collection time points indicated that their levels reduced with time. Conclusion In summary, the study revealed that reductions in CXCL10 levels during the first two months of anti-TB treatment are correlated with treatment responses. Furthermore, decreasing levels of CXCL9 during the treatment suggest that it may also serve as a biomarker with a similar value to CXCL10. Future in-depth studies are thus warranted to further probe the relevance of CXCL10 and CXCL9 in monitoring the treatment efficacy of TB.

D-mannose, essential for protein glycosylation, has been reported to have immunomodulatory effects and to maintain intestinal flora homeostasis. In addition to evaluating growth performance, we examined the impact of D-mannose on the structure of epithelial cells and apical junction complexes in the animal intestine. All 1800 grass carp (16.20 ± 0.01 g) were randomly divided into six treatments with six replicates of 50 fish each and fed with six different levels of D-mannose (0.52, 1.75, 3.02, 4.28, 5.50 and 6.78 g/kg diet) for 70 d. The study revealed that D-mannose increased feed intake (P 0.05). D-mannose supplementation at 1.75 g/kg increased crude protein content in fish and lipid production value (P

Abstract Background Differences of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. In more than 50% of human DSD cases, a molecular diagnosis is not available. In intensively farmed pig populations, the incidence of XX DSD pigs is relatively high, leading to economic losses for pig breeders. Interestingly, in the majority of 38, XX DSD pigs, gonads still develop into testis-like structures or ovotestes despite the absence of the testis-determining gene (SRY). However, the current understanding of the molecular background of XX DSD pigs remains limited. Methods Anatomical and histological characteristics of XX DSD pigs were analysed using necropsy and HE staining. We employed whole-genome sequencing (WGS) with 10× Genomics technology and used de novo assembly methodology to study normal female and XX DSD pigs. Finally, the identified variants were validated in 32 XX DSD pigs, and the expression levels of the candidate variants in the gonads of XX DSD pigs were further examined. Results XX DSD pigs are characterised by the intersex reproductive organs and the absence of germ cells in the seminiferous tubules of the gonads. We identified 4,950 single-nucleotide polymorphisms (SNPs) from non-synonymous mutations in XX DSD pigs. Cohort validation results highlighted two specific SNPs, “c.218T > C” in the “Interferon-induced transmembrane protein 1 gene (IFITM1)” and “c.1043C > G” in the “Newborn ovary homeobox gene (NOBOX)”, which were found exclusively in XX DSD pigs. Moreover, we verified 14 candidate structural variants (SVs) from 1,474 SVs, identifying a 70 bp deletion fragment in intron 5 of the WW domain-containing oxidoreductase gene (WWOX) in 62.5% of XX DSD pigs. The expression levels of these three candidate genes in the gonads of XX DSD pigs were significantly different from those of normal female pigs. Conclusion The nucleotide changes of IFITM1 (c.218T > C), NOBOX (c.1043 C > G), and a 70 bp deletion fragment of the WWOX were the most dominant variants among XX DSD pigs. This study provides a theoretical basis for better understanding the molecular background of XX DSD pigs. Plain language summary DSD are conditions affecting development of the gonads or genitalia. These disorders can happen in many different types of animals, including pigs, goats, dogs, and people. In people, DSD happens in about 0.02–0.13% of births, and in pigs, the rate is between 0.08% and 0.75%. Pigs have a common type of DSD where the animal has female chromosomes (38, XX) but no SRY gene, which is usually found on the Y chromosome in males. XX DSD pigs may look like both males and females on the outside and have testis-like or ovotestis (a mix of ovary and testis) gonads inside. XX DSD pigs often lead to not being able to have piglets, slower growth, lower chance of survival, and poorer meat quality. Here, we used a method called whole-genome de novo sequencing to look for variants in the DNA of XX DSD pigs. We then checked these differences in a larger group of pigs. Our results reveal the nucleotide changes in IFITM1 (c.218T > C), NOBOX (c.1043 C > G), and a 70 bp deletion fragment in intron 5 of the WWOX, all linked to XX DSD pigs. The expression levels of these three genes were also different in the gonads of XX DSD pigs compared to normal female pigs. These variants are expected to serve as valuable molecular markers for XX DSD pigs. Because pigs are a lot like humans in their genes, physiology, and body structure, this research could help us learn more about what causes DSD in people.

Abstract Reactor pressure vessel (RPV) studs are key components of nuclear reactors, and their connection with flange ensures the sealing of the RPV under high-pressure and high-temperature conditions. In the present work, the external threads of the RPV stud were prepared by triaxial rolling, and the texture evolution of the external thread root material of an RPV stud was predicted by finite element analysis coupled with viscoplastic self-consistent simulations. The microstructure of the external thread root material of RPV stud was characterized by scanning electron microscope and electron back-scattered diffraction. The installation characteristics of the turned and rolled parts of the RPV stud were tested by installation and pretightening tests. It was found that the dynamic recrystallization at the external thread root formed ultrafine tempered sorbite grains, high-angle grain boundaries (47%), and strong {111} and {111} textures. In the installation and pretightening test, the residual elongation of rolled parts was reduced by 6% under the same loading pressure. The triaxial rolling process distributed the microstructure of the external thread root of the RPV stud in a gradient manner, resulting in improved stud installation characteristics.

The thymus, a vital immune organ in humans, plays a crucial role in the differentiation and development of T cells. Its normal development commences around the fourth week of gestation, originating from the ectoderm of the third branchial cleft and the endoderm of the third parotid pouch. By the 7-8th week of gestation, the primary thymus migrates towards the central axis. However, various factors may disrupt this process, leading to congenital anomalies such as incomplete descent of thymus tissue. Persistence of residual thymus tissue can result in the formation of ectopic thymus. Although ectopic thymus is rare in clinical practice, sporadic cases have been reported in the neck or mediastinum, with fewer occurrences in the pericardium, chest wall, axilla, and thyroid gland. It is estimated that ectopic thymus accounts for approximately 0.4% of neck masses, and improper removal may predispose the child to immune deficiencies. This article focuses on a neonatal patient presenting with respiratory failure, where a foreign body was discovered in the oral cavity during weaning from mechanical ventilation. Subsequently, the tumor progressively enlarged postextubation. Surgical excision of the tumor revealed pathological abnormalities upon hematoxylin-eosin (HE) staining, confirming ectopic thymus tissue. B-ultrasound examination confirmed the presence of thymus tissue, and the child's condition improved, leading to hospital discharge. Follow-up assessments showed no evidence of immune deficiency in the child.

Abstract Background Facilitating factors are potential factors that encourage the uptake of maternal health services, while limiting factors are those potential factors that limit women’s access to maternal health services. Though cultural norms or values are significant factors that influence health-seeking behaviour, there is a limited exploration of the facilitating and limiting factors of these cultural norms and values on the use of maternal health services in primary health care facilities. Aim To understand the facilitating and limiting factors of cultural values and norms that influence the use of maternal health services in primary healthcare facilities. Methods The study was conducted in two primary healthcare facilities (rural and urban) using a focused ethnographic methodology described by Roper and Shapira. The study comprised 189 hours of observation of nine women from the third trimester to deliveries. Using purposive and snowballing techniques, data was collected through 21 in-depth interviews, two focus group discussions comprising 13 women, and field notes. All data was analyzed using the steps described by Roper and Shapira (Ethnography in nursing research, 2000). Results Using the enabler and nurturer constructs of the relationships and the expectations domain of the PEN-3 cultural model, four themes were generated: 1, The attitude of healthcare workers and 2, Factors within primary healthcare facilities, which revealed both facilitating and limiting factors. The remaining themes, 3, The High cost of services, and 4, Contextual issues within communities revealed factors that limit access to facility care. Conclusion Several facilitating and limiting factors of cultural norms and values significantly influence women’s health-seeking behaviours and use of primary health facilities. Further studies are needed on approaches to harness these factors in providing holistic care tailored to communities' cultural needs. Additionally, reinvigoration and strengthening of primary health facilities in Nigeria is critical to promoting comprehensive care that could reduce maternal mortality and enhance maternal health outcomes.

Abstract Evidence from previous studies have demonstrated that gut microbiota are closely associated with occurrence of interstitial cystitis/bladder pain syndrome (IC/BPS), yet the causal link between the two is not well known. In this study, we performed a two-sample Mendelian randomization (MR) analysis to determine the possible causal association between gut microbiota with IC/BPS. Gut microbiota summary level data were derived from the genome-wide association study (GWAS) conducted by MiBioGen and the IC/BPS GWAS summary level data were obtained from the GWAS Catalog. Next, we performed an MR study to investigate the causal link between gut microbiota and IC/BPS. The primary method for causal analysis was the inverse variance weighted (IVW), and the MR results were validated through multiple sensitivity analyses. A positive association was found between IC/BPS and eight gut microbial taxa, including genus Bacteroides, genus Haemophilus, genus Veillonella, genus Coprococcus1, genus Butyricimonas, family Bacteroidaceae, family Christensenellaceae, and order Lactobacillales. Sensitivity analysis revealed lack of significant pleiotropy or heterogeneity in the obtained results. This MR analysis reveals that a causal association exists between some gut microbiota with IC/BPS. This finding may is expected to guide future research and development of IC/BPS preventions and treatments based on the bladder-gut axis. However, given the clinical complexity and diagnostic challenges of IC/BPS, along with the limitations of using large-scale GWAS summary data for analysis, our MR results require further validation through additional research.

Abstract Objective Closure surgery of patent foramen ovale (PFO) has been found to effectively control cryptogenic stroke and migraine, but it is uncertain whether PFO closure could also alleviate epileptic seizures. This study aims to observe the therapeutic effect of PFO closure on epileptic seizures. Methods Since July 11th, 2017, in the neurology department of West China Hospital, Sichuan University, Chengdu, we have been regularly monitoring patients with epilepsy who have undergone PFO closure. The patient's clinical information, such as frequency, duration, and severity of seizures, before and after surgery was recorded in detail as well as postoperative safety events. Results Of the 31 epilepsy patients who confirmed PFO observed (27 cases were drug‐resistant epilepsy, 87.10%), average age of surgery was 23.74 years, and 12 cases were female (38.71%). After one‐year follow‐up, 26 patients (83.87%) achieved remission of seizure frequency, and 22 of whom (70.97%) experienced a remission of more than 50%. Additionally, compared to before surgery, 22 cases (70.97%) reported a decrease in the average seizure duration, and 20 cases (64.52%) reported a reduction in seizure severity. In the seizure indicators of frequency, average duration and severity, significant differences were identified between preoperative and postoperative comparisons with all test p values were

Abstract. Background:. Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. Methods:. A total of 3053 healthy Han Chinese adults (1922 women) aged 18–79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere–Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance. Results:. All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction

Abstract Since the Qin terracotta warriors were unearthed, polyamide 650 cross-linked E-44 epoxy resin binder has been employed to bond and restore them. In this paper, the chemical aging of the binders service in indoor natural environment during the past 30 years in the terracotta warriors was studied by means of infrared spectroscopy, X-ray photoelectron spectroscopy and thermogravimetric analysis. The results indicated that the binders did not emerge the characteristic peak of carbonyl stretching vibration at 1700 cm−1 in the IR spectra of all determined binders, and their thermal decomposition curves did not emerge any abnormal changes, and the thermal decomposition mainly occurred above 300 °C. There are evident ceramic grains attached to the surface of the binders being peeled off for sampling. These results that the binders service in the Qin terracotta warriors did not exhibit an observable chemical aging and still has strong adhesion. Generally, discrepancies were observed between natural aging and accelerated artificial aging due to the ineffectiveness of the latter to reproduce the effects of complex weather conditions. Compared to artificially accelerated aging, the evaluation results in a long-term natural aging of the binder which is used for restoration of the life-size Qin terracotta warriors, providing in the present investigation, are more reliable in terms of predicting the safety of restored terracotta warriors.

Abstract Chimeric antigen receptor (CAR)-T-cell therapy is one of the most effective immunotherapies. CAR-T-cell therapy has achieved great success in the treatment of hematological malignancies. However, due to the characteristics of solid malignant tumors, such as on-target effects, off-tumor toxicity, an immunosuppressive tumor microenvironment (TME), and insufficient trafficking, CAR-T-cell therapy for solid tumors is still in the exploration stage. Mesothelin (MSLN) is a molecule expressed on the surface of various solid malignant tumor cells that is suitable as a target of tumor cells with high MSLN expression for CAR-T-cell therapy. This paper briefly described the development of CAR-T cell therapy and the structural features of MSLN, and especially summarized the strategies of structure optimization of MSLN-targeting CAR-T-cells and the enhancement methods of MSLN-targeting CAR-T cell anti-tumor efficacy by summarizing some preclinical experiment and clinical trials. When considering MSLN-targeting CAR-T-cell therapy as an example, this paper summarizes the efforts made by researchers in CAR-T-cell therapy for solid tumors and summarizes feasible treatment plans by integrating the existing research results.

Objective To explore the roles of serum tissue inhibitor of matrix metalloproteinase 3（TIMP3） and sex determining region Y box protein 2（SOX2） in an early diagnosis of renal injury in type 2 diabetes mellitus（T2DM）. Methods From April 2022 to April 2023， 102 T2DM patients visiting General Hospital of North China Petroleum Administration Bureau were recruited as research subjects. Based upon 24 h serum urinary protein excretion rate（UAER）， they were assigned into two groups of renal injury（n = 40） and renal non-injury（n = 62）. Another 50 patients undergoing health examinations at General Hospital of North China Petroleum Administration Bureau were regarded as control group. Enzyme-linked immunosorbent assay（ELISA） was utilized for measuring the serum levels of TIMP3 and SOX2. General profiles， serum levels of TIMP3， SOX2， glycosylated hemoglobin（HbA1c）， UAER， serum creatinine（Scr） and glomerular filtration rate（eGFR） of three groups were compared. Pearson’s correlation was utilized for examining the relationship between serum TIMP3/SOX2 and HbA1c， UAER， Scr and eGFR. Receiver operating characteristic curve（ROC） was applied for examining the diagnostic value of serum TIMP3/SOX2 for renal injury in T2DM patients. Results The serum levels of TIMP3 [（0.68 ± 0.17）μg/L vs （1.35 ± 0.35）μg/L] and eGFR [（105.99 ± 20.56）mL·min−1·（1.73 m2）−1 vs （133.15 ± 26.18）mL·min−1·（1.73 m2）−1] were obviously lower in T2DM patients than those in control group（P＜0.05）. Serum levels of TIMP3 [（0.47 ± 0.11）μg/L vs （0.82 ± 0.21）μg/L] and eGFR [（74.69 ± 10.22）mL·min−1·（1.73 m2）−1 vs （126.18 ± 27.23）mL·min−1·（1.73 m2）−1] were obviously lower in patients with renal injury than those without（P＜0.05）. Serum levels of SOX2 [（8.91 ± 1.82）kU/L vs （5.15 ± 1.31）kU/L]， HbA1c[（8.80 ± 1.55）% vs （5.52 ± 0.83）%]， UAER [（70.13 ± 18.06）mg/24 h vs （13.22 ± 3.61）mg/24 h] and Scr [（82.14 ± 15.23）µmol/L vs （53.19 ± 5.62）µmol/L] were obviously higher than those in control group（P＜0.05）. Serum levels of SOX2 [（10.81 ± 2.13）kU/L vs （5.15 ± 1.31）kU/L]， UAER [（156.83 ± 40.29）mg/24 h vs （13.22 ± 3.61）mg/24 h] and Scr [（113.77 ± 13.58）µmol/L vs （53.19 ± 5.62）µmol/L] were obviously higher in patients with renal injury than in patients without（P＜0.05）. Pearson’s correlation analysis revealed that TIMP3 was obviously correlated negatively with HbA1c， UAER and Scr（P＜0.05） and positively with eGFR（P＜0.05）. SOX2 was obviously correlated positively with HbA1c， UAER and Scr（P＜0.05） and negatively with eGFR（P＜0.05）. An obvious negative correlation existed between serum TIMP3 and SOX2（r = −0.590，P＜0.05）. The results of ROC indicated that the sensitivity and specificity of serum TIMP3 plus SOX2 in the diagnosis of renal injury in T2DM patients were 95.0% and 85.3% respectively. Both were obviously higher than those of TIMP3 and SOX2 alone. Conclusions Serum levels of TIMP3 and SOX2 decline markedly and the two are closely correlated with renal injury in T2DM patients. Both may be used for an early diagnosis of renal injury in T2DM patients.

Abstract Background and purpose To investigate the feasibility of synthesizing computed tomography (CT) images from magnetic resonance (MR) images in multi-center datasets using generative adversarial networks (GANs) for rectal cancer MR-only radiotherapy. Materials and methods Conventional T2-weighted MR and CT images were acquired from 90 rectal cancer patients at Peking University People’s Hospital and 19 patients in public datasets. This study proposed a new model combining contrastive learning loss and consistency regularization loss to enhance the generalization of model for multi-center pelvic MRI-to-CT synthesis. The CT-to-sCT image similarity was evaluated by computing the mean absolute error (MAE), peak signal-to-noise ratio (SNRpeak), structural similarity index (SSIM) and Generalization Performance (GP). The dosimetric accuracy of synthetic CT was verified against CT-based dose distributions for the photon plan. Relative dose differences in the planning target volume and organs at risk were computed. Results Our model presented excellent generalization with a GP of 0.911 on unseen datasets and outperformed the plain CycleGAN, where MAE decreased from 47.129 to 42.344, SNRpeak improved from 25.167 to 26.979, SSIM increased from 0.978 to 0.992. The dosimetric analysis demonstrated that most of the relative differences in dose and volume histogram (DVH) indicators between synthetic CT and real CT were less than 1%. Conclusion The proposed model can generate accurate synthetic CT in multi-center datasets from T2w-MR images. Most dosimetric differences were within clinically acceptable criteria for photon radiotherapy, demonstrating the feasibility of an MRI-only workflow for patients with rectal cancer.

Abstract Background Blended teaching is an effective approach that combines online and offline teaching methods, leading to improved outcomes in medical education compared to traditional offline teaching. In this study, we examined the impact of blended teaching in clinical skills training, a medical practice course. Methods This study involved forty-eight undergraduate students studying clinical medicine in the fifth semester at Wuhan University of Science and Technology. The students were divided into two groups: the control group, which received traditional offline teaching, and the experimental group, which received hybrid teaching. Following the completion of the 4-month course, both groups underwent the Objective Structured Clinical Examination (OSCE) to evaluate their proficiency in clinical skills. Furthermore, the experimental group was given a separate questionnaire to gauge their feedback on the Blended Teaching approach. Results Based on the OSCE scores, the experimental group outperformed the control group significantly (P

ObjectiveTo explore the correlation of molecular pathological grading with WHO grade 1 meningioma recurrence, malignant progression, and patients’ survival. MethodsThe medical records and paraffin-embedded tissues of patients with surgically resected WHO grade 1 meningioma were collected. The molecular pathological risk grading suggested by Maas et al. was adopted, and the patients were graded as low, intermediate, and high risk. Univariate log-rank test and multivariate Cox regression analyses were performed to determine the relationship between molecular risk grading and patient progression-free survival (PFS), malignant progression-free survival (MPFS), and overall survival (OS). ResultsAmong 198 patients, 152 (76.8%) were graded as low risk, showing no 1p deletion; 42 (21.2%) patients were graded as intermediate risk, including 18 patients with 1p deletion, 10 patients with 1p combined with 6q deletion, and 14 patients with 1p combined with 14q deletion; and 4 (2%) patients were graded as high risk, including two patients with TERT promoter mutation, one patient with CDKN2A/B homozygous deletion, and one patient with 1p, 6p, and 14q combined deletion. Multivariate analysis showed that molecular risk grading was negatively associated with PFS (HR: 0.029, 95%CI: 0.011-0.080), MPFS (HR: 0.032, 95%CI: 0.004-0.274), and OS (HR: 0.074, 95%CI: 0.032-0.174; P

Abstract Background Several core breeding and supporting lines of the Qingyuan partridge chicken, a representative local chicken breed in China, have been developed over 20 years. Consequently, its economic traits related to growth and reproduction have been significantly improved by breeding selection and commercial utilization, but some characteristic traits, such as partridge feathers, high meat quality and sufficient flavor, have always been retained. However, effective methods for genetic assessment and functional gene exploration of similar trait groups are lacking. The presence of identical haplotype fragments transmitted from parent to offspring results in runs of homozygosity (ROH), which offer an efficient solution. In this study, genomes of 134 Qingyuan partridge chickens representing two breeding populations and one preserved population were re-sequenced to evaluate the genetic diversity and explore functional genes by analyzing the diversity, distribution, and frequency of ROH. Results The results showed a low level of genomic linkage and degree of inbreeding within both the bred and preserved populations, suggesting abundant genetic diversity and an adequate genetic potential of the Qingyuan partridge chicken. Throughout the long-term selection process, 21 genes, including GLI3, ANO5, BLVRA, EFNB2, SLC5A12, and SVIP, associated with breed-specific characteristics were accumulated within three ROH islands, whereas another 21 genes associated with growth traits including IRX1, IRX2, EGFR, TPK1, NOVA1, BDNF and so on were accumulated within five ROH islands. Conclusions These findings provide new insights into the genetic assessment and identification of genes with breed-specific and selective characteristics, offering a solid genetic basis for breeding and protection of Qingyuan partridge chickens.

Abstract Background Respiratory syncytial virus (RSV)-induced lung inflammation is one of the main causes of hospitalization and easily causes disruption of intestinal homeostasis in infants, thereby resulting in a negative impact on their development. However, the current clinical drugs are not satisfactory. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM), has been used for clinical management of inflammatory diseases. However, its in vivo efficacy against RSV-induced lung inflammation and the underlying mechanism remain unclear. Purpose The present study was designed to confirm the in vivo efficacy of ZTOI against lung inflammation and intestinal disorders in RSV-infected young mice and to explore the potential mechanism. Study design and methods Lung inflammation was induced by RSV, and cytokine antibody arrays were used to clarify the effectiveness of ZTOI in RSV pneumonia. Subsequently, key therapeutic targets of ZTOI against RSV pneumonia were identified through multi-factor detection and further confirmed. The potential therapeutic material basis of ZTOI in target tissues was determined by non-target mass spectrometry. After confirming that the pharmacological substances of ZTOI can reach the intestine, we used 16S rRNA-sequencing technology to study the effect of ZTOI on the intestinal bacteria. Results In the RSV-induced mouse lung inflammation model, ZTOI significantly reduced the levels of serum myeloperoxidase, serum amyloid A, C-reactive protein, and thymic stromal lymphoprotein; inhibited the mRNA expression of IL-10 and IL-6; and decreased pathological changes in the lungs. Immunofluorescence and qPCR experiments showed that ZTOI reduced RSV load in the lungs. According to cytokine antibody arrays, platelet factor 4 (PF4), a weak chemotactic factor mainly synthesized by megakaryocytes, showed a concentration-dependent change in lung tissues affected by ZTOI, which could be the key target for ZTOI to exert anti-inflammatory effects. Additionally, sesquiterpenes were enriched in the lungs and intestines, thereby exerting anti-inflammatory and regulatory effects on gut microbiota. Conclusion ZTOI can protect from lung inflammation via PF4 and regulate gut microbiota disorder in RSV-infected young mice by sesquiterpenes, which provides reference for its clinical application in RSV-induced lung diseases.

Abstract Early insulin therapy is capable to achieve glycemic control and restore β-cell function in newly diagnosed type 2 diabetes (T2D), but its effect on cardiovascular outcomes in these patients remains unclear. In this nationwide real-world study, we analyzed electronic health record data from 19 medical centers across China between 1 January 2000, and 26 May 2022. We included 5424 eligible patients (mean age 56 years, 2176 women/3248 men) who were diagnosed T2D within six months and did not have prior cardiovascular disease. Multivariable Cox regression models were used to estimate the associations of early insulin therapy (defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients) with the incidence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization for heart failure (HF). During 17,158 persons years of observation, we documented 834 incident CHD cases, 719 stroke cases, and 230 hospitalized cases for HF. Newly diagnosed T2D patients who received early insulin therapy, compared with those who did not receive such treatment, had 31% lower risk of incident stroke, and 28% lower risk of hospitalization for HF. No significant difference in the risk of CHD was observed. We found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting models. These findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

The use of next-generation probiotics (NGP) in pigs for combating diseases has been subject to limited research. Here we explored the potential of a well-known NGP candidate Akkermansia muciniphila targeting pig gut health. In the first screening experiment, we found that the abundance of A. muciniphila peaked at 14 d old but decreased at weaning (21 d old; P

Endometrial cancer is a common tumor of the female reproductive system. In recent years, as the age of onset of the disease has gradually become younger, this has caused distress to some young patients with reproductive needs, and the active search for methods of preserving reproductive function has gradually attracted attention. In this paper, we will systematize the current status of progestin-based pharmacotherapy in combination with other drug therapies in the conservative management of early-stage endometrial cancer. With the expectation of providing a reference for the treatment of early stage endometrial cancer patients in China and for the in-depth development of related research in this field.

Tubocapsicum anomalum, a Chinese medicinal plant rich in anti-tumor withanolides, requires efficient extraction methods. In this paper, an HPLC method was first established for the detection of withanolides, and gradient elution was carried out using a methanol–water solvent system. It was found that the content of withanolides was the highest in the leaves of T. anomalum, followed by the stems and fruits, and almost none in the roots. During the actual picking process, the quantity of leaves collected was relatively small, while the number of stems was the highest. Therefore, the Box-Behnken response surface method was used to optimize the ultrasonic-assisted extraction process of withanolides from the stems of T. anomalum. The optimal extraction conditions were determined as follows: the liquid–solid ratio was 20:1, the extraction solvent was 70 % ethanol, the ultrasonic power was 250 W, the ultrasonic time was 40 min, and the ultrasonic temperature was 50 °C. Under these conditions, the average yields of tubocapsenolide A (Te-A) and tubocapsanolide A (Ta-A) can reach 2.87 ± 0.12 mg/g and 1.18 ± 0.05 mg/g, respectively. We further compared extraction rates of two withanolides from different parts of T. anomalum using ultrasonic and traditional extraction methods. Ultrasonic extraction significantly increased rates, with the highest yields from leaves, followed by stems and fruits. The results show that ultrasonic optimization can improve extraction rate, reduce time, lower costs, enhance quality, and increase yield. Therefore, the optimized ultrasonic-assisted extraction process was adopted to extract the aerial parts of T. anomalum and separate the components. After optimization, the extract underwent several chromatographic separations to isolate eight previously undescribed withanolides (1–8) and two artificial withanolides (9–10), in addition to fifteen known compounds (11–25). Their structures were established through extensive spectroscopic data analysis. The compounds were evaluated for their antiproliferative effects against multiple cancer cell lines, including human hepatocellular carcinoma cells (HepG2, Hep3B, and MHCC97-H), human lung cancer cells (A549), human fibro-sarcoma cancer cells (HT1080), human chronic myeloid leukemia cells (K562), and human breast cancer cells (MDA-MB-231 and MCF7). Compounds 1–3, 5, 7, 11, 13, 15–16, and 22 displayed significant activity with IC50 values of 5.14–19.87 μM. The above results indicate that ultrasonic-assisted extraction technology can be used to obtain new withanolides more efficiently from T. anomalum, thereby enhancing the utilization rate of T. anomalum resources.

Objective This study assesses the physical properties of the silicone rubber (SR) bolus, compares its dosimetric characterization with those of gel and thermoset boluses, aiming to evaluate the feasibility and stability of utilizing SR bolus for head photon-beam radiotherapy. Methods Three types of boluses (gel, thermoset, and SR) were prepared with same dimensions. Firstly, the physical properties of SR bolus (density, tensile strength and hardness) were assessed pre-irradiation and post-irradiation. Secondly, the percentage of depth dose (PDD) curve was calculated using the treatment planning system (TPS) and measured with a plane-parallel. Thirdly, these three boluses were individually placed on the head phantom, followed by computed tomography (CT) scans to delineate the customized target area and organs at risk (OARs) for treatment planning. Over the subsequent three weeks, fan-beam CT (FBCT) images were obtained weekly and registered with the initial CT to modify the target area and OARs. Fourthly, the adhesion differences, dose distributions, and inter-fraction reproducibility of the three boluses were compared and evaluated. Results The results observed that post-irradiated SR bolus exhibited higher hardness values ( p

Abstract Hepatocellular carcinomas (HCCs) are characterized by a vast spectrum of somatic copy number alterations (CNAs); however, their functional relevance is largely unknown. By performing a genome‐wide survey on prognosis‐associated focal CNAs in 814 HCC patients by an integrative computational framework based on transcriptomic data, genomic amplification is identified at 8q24.13 as a promising candidate. Further evidence is provided that the 8q24.13 amplification‐driven overexpression of Rab GTPase activating protein TBC1D31 exacerbates HCC growth and metastasis both in vitro and in vivo through activating Epidermal growth factor receptor (EGFR) signaling. Mechanistically, TBC1D31 acts as a Rab GTPase activating protein to catalyze GTP hydrolysis for Rab22A and then reduces the Rab22A‐mediated endolysosomal trafficking and degradation of EGFR. Notably, overexpression of TBC1D31 markedly increases the resistance of HCC cells to lenvatinib, whereas inhibition of the TBC1D31‐EGFR axis can reverse this resistance phenotype. This study highlights that TBC1D31 at 8q24.13 is a new critical oncogene, uncovers a novel mechanism of EGFR activation in HCC, and proposes the potential strategies for treating HCC patients with TBC1D31 amplification or overexpression.

Abstract BackgroundObtaining and describing semiology efficiently and classifying seizure types correctly are crucial for the diagnosis and treatment of epilepsy. Nevertheless, there exists an inadequacy in related informatics resources and decision support tools. ObjectiveWe developed a symptom entity extraction tool and an epilepsy semiology ontology (ESO) and used machine learning to achieve an automated binary classification of epilepsy in this study. MethodsUsing present history data of electronic health records from the Southwest Epilepsy Center in China, we constructed an ESO and a symptom-entity extraction tool to extract seizure duration, seizure symptoms, and seizure frequency from the unstructured text by combining manual annotation with natural language processing techniques. In addition, we achieved automatic classification of patients in the study cohort with high accuracy based on the extracted seizure feature data using multiple machine learning methods. ResultsData included present history from 10,925 cases between 2010 and 2020. Six annotators labeled a total of 2500 texts to obtain 5844 words of semiology and construct an ESO with 702 terms. Based on the ontology, the extraction tool achieved an accuracy rate of 85% in symptom extraction. Furthermore, we trained a stacking ensemble learning model combining XGBoost and random forest with an F1 ConclusionsThis work demonstrated the feasibility of natural language processing–assisted structural extraction of epilepsy medical record texts and downstream tasks, providing open ontology resources for subsequent related work.

Traffic congestion is a serious problem faced by many cities worldwide today. Congestion warning information is one of the important influencing factors of urban road congestion; To this end, based on the dynamics of infectious diseases, a congestion warning information dissemination model considering the attitudes of travelers and the network structure was constructed. The existence and stability of the equilibrium points of non congestion warning information and congestion warning information in the model were analyzed, and the optimal control strategy of the model was proposed. Numerical simulation was conducted to verify the results of theoretical analysis, simulate and analyze the impact of changes in various parameters in the model on the dissemination of congestion warning information, and perform sensitivity analysis on several parameters. The results indicate that travelers are more inclined towards “fast” modes of transportation and have a stronger willingness to share congestion warning information. The dissemination range of warning information is wider, which can play a positive role in reducing traffic congestion pressure.

ObjectiveThe impact of primary biliary cholangitis (PBC) on sleep disturbance is relevant to treatment decision-making processes. Studies on sleep disturbance in Chinese patients with PBC are still lacking.MethodsWe analyzed and compared the health-related quality of life (HRQoL) of 107 PBC patients by using the Pittsburgh Sleep Quality Index (PSQI) questionnaire, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire 9 (PHQ-9), Short Form (36) Health Survey Questionnaire (SF-36), Fatigue Visual Analog Scale (F-VAS). Patients’ biochemical markers were also collected for correlation analysis with HRQoL. Receiver operating characteristic (ROC) curves and area under the curve (AUCs) were used to determine the diagnostic performance of PSQI, GAD-7, and biochemical markers for assessing the impaired liver function (Child–Pugh B–C) of PBC diagnosis.ResultsSixty-two (57.9%) PBC patients suffered from poor sleep quality (PSQI >5). The global PSQI score was positively correlated with GAD-7 (r = 0.561, p

BackgroundA substantial amount of research has explored the intricate relationship between exercise and sleep quality, consistently confirming that exercise can effectively enhance sleep quality. Nevertheless, previous studies have yet to conclusively determine which specific exercise program is most efficacious in improving sleep quality. To address this gap, the present study systematically evaluated the differential effects of various types of exercise, as well as exercise dosages (including duration, intervention period, frequency, and intensity), on sleep outcomes using a network meta-analysis approach. This endeavor aims to provide evidence-based support for the development of scientifically effective exercise programs tailored to improve sleep quality.MethodsThrough the Web of Science, PubMed, Cochrane Library, Embase, and Scopus databases, we conducted a search for randomized controlled trials investigating the effects of exercise interventions on sleep, with a search cutoff date of April 30, 2024. We rigorously selected the literature according to the PICOS principle, and two independent researchers extracted the data. We would like to change this passage to: Bias risk assessment was conducted using the RevMan 5.4 software, and traditional meta-analysis and network meta-analysis were performed using Stata 17.0 software to generate forest plots, network evidence plots, and funnel plots. Furthermore, we adopted the surface under the cumulative ranking curve (SUCRA) to evaluate and rank the intervention effects of different exercise types and dosages on sleep quality. To verify the robustness of our study results, we performed a sensitivity analysis using the leave-one-out method.ResultsThe study strictly adhered to the PRISMA guidelines and included 58 RCT papers with a total of 5,008 participants. The network meta-analysis revealed significant variations in the impact of exercise frequency on sleep outcomes when compared to the control group. Interventions of 1–2 times per week [SMD = −0.85, 95% CI (−1.43, −0.26)], 3 times per week [SMD = −0.45, 95% CI (−0.80, −0.11)], and 4 times per week [SMD = −1.09, 95% CI (−1.92, −0.26)] demonstrated the most notable effects. Interventions lasting ≤30 min and 60–65 min were significantly more effective than the control group, with ≤30 min proving significantly more effective than 40–55 min [SMD = 0.75, 95% CI (0.01, 1.49)]. Interventions lasting 9–10 weeks [SMD = −1.40, 95% CI (−2.37, −0.44)], 12–16 weeks [SMD = −0.55, 95% CI (−0.90, −0.20)], and ≥ 24 weeks [SMD = −0.71, 95% CI (−1.31, −0.10)] were all significantly more effective than the control group. Additionally, the 9–10 weeks intervention period was found to be significantly more effective than the 6–8 weeks period [SMD = −1.21, 95% CI (−2.37, −0.04)]. Furthermore, interventions of moderate intensity [SMD = −1.06, 95% CI (−1.52, −0.61)] and high intensity [SMD = −1.48, 95% CI (−2.55, −0.40)] exercise interventions yielded significantly greater benefits compared to the control group. Specifically, high intensity interventions [SMD = −1.97, 95% CI (−3.37, −0.56)] and moderate intensity [SMD = −1.55, 95% CI (−2.57, −0.54)] exercise interventions were found to be significantly more effective than moderate-high intensity interventions. In terms of exercise types, aerobic exercise [SMD = −0.56, 95% CI (−0.86, −0.27)], traditional Chinese exercises [SMD = −0.57, 95% CI (−0.97, −0.18)], and combined exercise [SMD = −0.99, 95% CI (−1.66, −0.32)] interventions all produced significant improvements compared to the control group. The study determined that the most effective combination of exercise prescription elements for enhancing sleep quality includes a frequency of 4 times per week (SUCRA = 84.7), a duration of ≤30 min (SUCRA = 92.2), a period of 9–10 weeks (SUCRA = 89.9), and high-intensity (SUCRA = 92.9) combined exercise (SUCRA = 82.7).ConclusionThe current evidence indicates that combined exercise with a frequency of 4 times per week, a duration of ≤30 min, a period of 9–10 weeks, and high intensity is most effective for improving sleep quality. Nevertheless, due to the limited number of studies included, further research is needed to enhance the reliability of the findings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42024555428.

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the progressive destruction of the neuromuscular junction (NMJ) and the degeneration of motor neurons, eventually leading to atrophy and paralysis of voluntary muscles responsible for motion and breathing. NMJs, synaptic connections between motor neurons and skeletal muscle fibers, are extremely fragile in ALS. To determine the effects of early electroacupuncture (EA) intervention on nerve reinnervation and regeneration following injury, a model of sciatic nerve injury (SNI) was first established using SOD1G93A mice, and early electroacupuncture (EA) intervention was conducted at Baihui (DU20), and bilateral Zusanli (ST36). The results revealed that EA increased the Sciatic nerve Functional Index, the structural integrity of the gastrocnemius muscles, and the cross-sectional area of muscle fibers, as well as up-regulated the expression of acetylcholinesterase and facilitated the co-location of α7 nicotinic acetate choline receptors and α-actinin. Overall, these results suggested that EA can promote the repair and regeneration of injured nerves and delay NMJ degeneration in SOD1G93A-SNI mice. Moreover, analysis of the cerebral cortex demonstrated that EA alleviated cortical motor neuron damage in SOD1G93A mice, potentially attributed to the inhibition of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway and the release of interferon-β suppressing the activation of natural killer cells and the secretion of interferon-γ, thereby further inhibiting microglial activation and the expression of inflammatory factors. In summary, EA delayed the degeneration of NMJ and mitigated the loss of cortical motor neurons, thus delaying disease onset, accompanied by alleviation of muscle atrophy and improvements in motor function in SOD1G93A mice.

Abstract BackgroundRetinopathy of prematurity (ROP) is a leading cause of visual impairment and blindness in preterm infants. ObjectiveThis study sought to investigate the association between red blood cell (RBC) transfusion and ROP in very preterm infants (VPIs) to inform clinical strategies for ROP prevention and treatment. MethodsWe designed a prospective multicenter cohort study that included VPIs and follow-up data from January 2017 to December 2022 at 3 neonatal clinical medicine centers. They were categorized into a transfusion group (infants who received an RBC transfusion within 4 wk) and a nontransfusion group. The relationship between RBC transfusion and ROP incidence was assessed using binary logistic regression, with subgroup analyses based on gestational age, birth weight, sex, and sepsis status. Inverse probability of treatment weighting and propensity score matching were applied to account for all potential confounding factors that could affect ROP development, followed by sensitivity analysis. ResultsThe study included 832 VPIs, including 327 in the nontransfusion group and 505 in the transfusion group. The transfusion group had a lower average birth weight and gestational age and a greater incidence of ROP, ≥stage 2 ROP, and severe ROP. Logistic regression analysis revealed that the transfusion group had a significantly greater risk of ROP (adjusted odds ratio [aOR] 1.70, 95% CI 1.14‐2.53, PPPP ConclusionsFor VPIs, RBC transfusion significantly increases the risk of ROP, and the risk increases with an increasing number of transfusions and volume of blood transfused.

Objective: To investigate a case of neurodevelopmental disorder caused by mutation of FBXW7.Methods: Clinical data were collected from the patient, trio-WES (whole-exome sequencing) was performed on the patient and his parents (trio), and the results were verified by Sanger sequencing. RESULTS: The patient was a 2-year and 1-month old male who presented with facial dysmorphism (prominent forehead, ocular hypertelorism, and low nasal bridge), global developmental delay, language impairment, hypertonia, labial hemangioma, hydrocele, and overgrowth. The trio-WES confirmed that the child had a pathogenic de novo FBXW7 gene variant, c.1612C>T (p.G1n538*), a heretofore unreported locus.Conclusion: This case of developmental delay, hypotonia, and impaired language (OMIM: #620012) related to a mutation in FBXW7, is a rare genetic disorder, newly identified in recent years, and seldom reported. The presence of hypertonia, labial hemangioma, and hydrocele in this child suggests significant phenotypic heterogeneity of the disease, and the discovery of new mutant loci enriches the spectrum of pathogenic variants of the disease.

Chelidonii herba is a traditional Chinese medicinal herb with effects including antispasmodic, analgesic, antitussive, and bronchodilator properties. Alkaloids are the main bioactive ingredients in Chelidonii herba. In this study, a two-dimensional nuclear magnetic resonance (Heteronuclear Singular Quantum Correlation, HSQC-2D-NMR) technique was employed to quantitatively analyze the total alkaloid content and three major active alkaloid monomers in Chelidonii herba from eleven different sources. The quantification results of the three monomeric alkaloids were also verified using conventional quantitative control methods such as HPLC. Experimental findings indicate that the total alkaloid content is not directly correlated with the content of the three monomeric alkaloids. Furthermore, the content of any individual monomeric alkaloid does not accurately reflect the overall quality of Chelidonii herba. It was demonstrated that the 2D-Q-NMR NMR can be applied as an alternative method. While maintaining the same levels of accuracy and precision, the 2D-Q-NMR method is simpler to operate and provides more comprehensive results with higher reproducibility in some cases.

Improving corporate carbon emission performance is an important driving force for realising the low-carbon development of China's economy. Carbon information disclosure is an environmental regulatory tool proposed in the context of carbon neutrality, this study examines whether carbon information disclosure effectively influences carbon emission performance. Based on the data from 30 provinces in China from 2012 to 2021, this paper examines the structural characteristics of carbon information disclosure using social network analysis, accounting for the carbon emission performance of industrial enterprises in each province in China. Using the spatial econometric model, we apply the undesirable slacks-based measure model and examine the impact of the spatial network characteristics of carbon information disclosure on carbon emission performance. Results show that the overall density of carbon information disclosure networks of industrial enterprises in Chinese provinces is low, so there is much room for improvement. Additionally, there is spatial dependence on carbon emission performance among neighbouring provinces. Moreover, the out-degree centrality and betweenness centrality of carbon information disclosure networks significantly negatively affect carbon emission performance. However, the inhibitory effect of the in-degree centrality of carbon information disclosure networks on carbon emission performance is not significant. The unique findings of this paper are relevant to environmental policy formulation and assessment.

There is a currently a lack of large-area plasma sterilization devices that can intelligently identify the shape of a wound for automatic sterilization. For this reason, in this work, a plasma sterilization device with wound-edge recognition was developed using a field-programmable gate array (FPGA) and a high-performance image-processing platform to realize intelligent and precise sterilization of wounds. SOLIDWORKS was used to design the mechanical structure of the device, and it was manufactured using 3D printing. The device used an improvement of the traditional Sobel detection algorithm, which extends the detection of edges in only the x and y directions to eight directions (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°), completing the wound-edge detection by adaptive thresholding. The device can be controlled according to different shapes of sterilization area to adjust the positioning of a single plasma-jet tube in the horizontal plane for two-dimensional movement; the distance between the plasma-jet tube and the surface of the object to be sterilized can be also adjusted in the vertical direction. In this way, motors are used to move the plasma jet and achieve automatic, efficient, and accurate plasma sterilization. It was found that a good sterilization effect could be achieved at both the culture-medium level and the biological-tissue level. The ideal sterilization parameters at the culture-medium level were a speed of 2 mm/s and a flow rate of 0.6 slm, while at the biological-tissue level, these values were 1 mm/s and 0.6 slm, respectively.

Assessing carbon emissions in China’s swine industry and understanding its spatial–temporal characteristics under carbon peak and carbon neutrality goals are vital for promoting low-carbon farming. This study measures the swine industry’s carbon emissions across 30 provinces in China from 2006 to 2022 using life cycle assessment and IPCC coefficient methods. Spatial and temporal patterns were analyzed with exploratory spatial data analysis, and an XGBoost model was used to predict emissions from 2023 to 2032. The results show a “W”-shaped oscillating trend in total carbon emissions, with phases of rapid decline, fluctuating rise, fluctuating decline, and rapid resurgence. Emissions were highest in the Central region, followed by the West, East, and Northeast. Manure management and Feed crop cultivation were the primary emission sources, accounting for 59.7% and 29.9% of total emissions, respectively. The spatial pattern of high and low emission regions remained stable, with dynamic changes in moderate emission regions. High emissions were concentrated in the major grain-producing and livestock-raising and the South China coastal farming regions. The XGBoost model projects that China’s green development measures in the swine industry will have a significant future impact. The carbon emission intensity shows a trend of initial decline followed by stabilization, whereas total carbon emissions are projected to remain high and gradually increase, primarily due to continuous growth in production capacity. The conclusions of this study provide a reference basis for the green and low-carbon transformation of the swine industry and the optimization of the regional layout of the livestock industry.

[Introduction] Pulse inductor is an important component of the oscillation discharge circuit in the quench protection system. In the oscillating discharge circuit, the pulse inductor and charging capacitor are used to oscillate and generate high pulse currents, causing the current flowing through the vacuum circuit breaker to reverse and create an artificial zero-crossing point, thus completing the switch breaking. However, under the condition of 120 kA current, due to the action of the electromagnetic force, the connecting bar below the pulse inductor will deform, causing equipment damage and greatly reducing the reliability of the auxiliary oscillation zero-crossing circuit. Therefore, it is necessary to conduct electromagnetic field analysis on the 120 kA pulse inductor and optimize the electromagnetic field distribution around it. [Method] Firstly, the commutation process of the auxiliary oscillation zero-crossing circuit was analyzed to establish a three-dimensional model of the pulse inductor, and the concept of magnetic field shielding percentage was introduced. Secondly, the influence of shielding plates with different materials and shapes on electromagnetic field distributions was calculated by using finite element simulation. Then the influence of different materials and shapes on shielding percentage was analyzed, and eddy current losses under different shapes were calculated. Finally, the deformation degree of the connecting bar under different shielding structures was calculated in the structural module. [Result] The results show that the use of different materials or structures in the shielding plates influences the magnetic induction intensity and electromagnetic force received by the connecting bar. [Conclusion] The circular aluminum shielding plate has a better optimization effect for the electromagnetic field distribution. This method also lays a foundation for the electromagnetic shield design of pulse inductors.

[Introduction] In recent years, as the installed capacity of the fusion device has been increasing, the power supply system of the device requires high-amplitude and long-pulse power output, which causes a strong power impact on the grid, and even power supply disconnection in severe cases to pose a serious threat to the safety of the fusion device. Additionally, the high-amplitude pulses also result in a lot of redundancy in the power supply system design. [Method] To solve these problems, this paper proposed a novel fusion power supply topology with energy storage, that is, the power supply system was designed with energy storage to mitigate the impact of pulse power on the grid. During the operation of the power supply, the grid provided steady-state power while the energy storage device delivered pulse power, effectively reducing the cost of the power supply. [Result] According to the experience in industrial power supply and distribution, this paper presents the calculation formulas for the selection of key components in different topologies and conducts a cost analysis and comparison for different power supply topologies based on simulation data. [Conclusion] The experimental results show that the new power supply topology not only reduces the power impact on the grid and improves the energy utilization of the power supply system, but also reduces transformer capacity, thus it is cost-efficient.

Abstract Background Carcass traits are crucial indicators of meat production efficiency. However, the molecular regulatory mechanisms associated with these traits remain unclear. Results In this study, we conducted comprehensive transcriptomic and genomic analyses on 399 Tiannong partridge chickens to identify key genes and variants associated with carcass traits and to elucidate the underlying regulatory mechanisms. Based on association analyses with the elastic net (EN) model, we identified 12 candidate genes (AMY1A, AP3B2, CEBPG, EEF2, EIF4EBP1, FGFR1, FOXD3, GOLM1, LOC107052698, PABPC1, SERPINB6 and TBC1D16) for 4 carcass-related traits, namely live weight, dressed weight, eviscerated weight, and breast muscle weight. SERPINB6 was identified as the only overlapping gene by 3 analyses, EN model analysis, weighted gene co-expression network analysis and differential expression analysis. Cell-level experiments confirmed that SERPINB6 promotes the proliferation of chicken DF1 cells and primary myoblasts. Further expression genome-wide association study and association analysis indicated that rs317934171 is the critical site that enhances SERPINB6 expression. Furthermore, a dual-luciferase reporter assay proved that gga-miR-1615 targets the 3′UTR of SERPINB6. Conclusions Collectively, our findings reveal that SERPINB6 serves as a novel gene for chicken carcass traits by promoting fibroblast and myoblast proliferation. Additionally, the downstream variant rs317934171 regulates SERPINB6 expression. These results identify a new target gene and molecular marker for the molecular mechanisms of chicken carcass traits.

In order to clarify the quality differences of existing commercially available stewed pork ball products, this study comprehensively analyzed the quality traits of commercially available stewed pork ball of six different brands (A1-Mouth Edge, A2-Wutting Bridge, A3-Kijin, A4-Lao Yangcheng, A5-Sanzhenzhai, and A6-Huangjue) on the physicochemical indices of organoleptic, colour and lustre, textural characteristics, water loss rate and fat oxidation, combined with the free fatty acids and volatile flavour compounds to characterize. The results showed that the sensory score of the A1 stewed pork ball was as high as 34 points, and the redness value of A4 was as high as 3.46±0.08 among the six types of commercially available stewed pork balls, while the fat oxidation value of A1 was the lowest at 0.44 mg MDA/kg, and the masticatory of A5 and A6 was lower at 0.21±0.02 and 0.32±0.11 mJ, respectively. The free fatty acids composition of the six commercially available stewed pork balls, which were mainly composed of oleic acid and secondly composed of saturated fatty acids such as palmitic acid and stearic acid. The polyunsaturated fatty acids in stewed pork balls were decomposed into aldehydes and other substances by a large number of oxidation reactions, while the content of saturated fatty acids was significantly increased. γ-Pinene, hexanal, linalool, nonanal, etc. were the common volatile flavor substances, in addition, the main key volatile flavor substances of A1 were 2-pentyl furan, the main volatile flavor compounds of A2 were Valencia orange alkene, methyl heptane, isovaleraldehyde, while A4 was ethyl caprylate, A5 was 4-terpineol, undecyl alcohol, methyl mercaptan, furfuryl alcohol, furfural, methyl stearate, anethole, and A6 was undecyl alcohol, phenylpropanoid. Thus, hydrocarbons and aldehydes, along with alcohols and ketones, might be the major factors affecting the flavor quality of various commercially available stewed pork ball products. The results of this study may provide a theoretical reference for the construction of the product quality evaluation system for commercially available stewed pork ball products, as well as flavor unification and product development and production.

Abstract Protein induced by vitamin K absence or antagonist II (PIVKA-II) plays a critical role in the diagnosis of hepatocellular carcinoma (HCC), however, studies on its efficacy in diagnosing recurrent HCC were rarely found. A multicenter, retrospective, and observational study was conducted. During the overall follow-up of 5 years, HCC patients who had curative resection were monitored every 3 months in the first year post-surgery and every 6 months thereafter if no recurrence occurred. Tumor markers were collected at the diagnosis of recurrence for those with recurrence and at the last follow-up for those without recurrence. The median serum levels of PIVKA-II and AFP in the recurrence group were significantly higher than those in the non-recurrence group (PIVKA-II: 84.62 vs. 18.76 mAU/ml, p

Abstract Background Syncope is a common condition that increases the risk of injury and reduces the quality of life. Abdominal pain as a precursor to vasovagal syncope (VVS) in adults is rarely reported and is often misdiagnosed.​. Methods We present three adult patients with VVS and presyncopal abdominal pain diagnosed by synchronous multimodal detection (transcranial Doppler [TCD] with head-up tilt [HUT]) and discuss the relevant literature. Results Case 1: A 52-year-old man presented with recurrent decreased consciousness preceded by six months of abdominal pain. Physical examinations were unremarkable. Dynamic electrocardiography, echocardiography, head and neck computed tomography angiography, magnetic resonance imaging (MRI), and video electroencephalogram showed no abnormalities. Case 2: A 57-year-old woman presented with recurrent syncope for 30 + years, accompanied by abdominal pain. Physical examination, electroencephalography, and MRI showed no abnormalities. Echocardiography showed large right-to-left shunts. Case 3: A 30-year-old woman presented with recurrent syncope for 10 + years, with abdominal pain as a precursor. Physical examination, laboratory analysis, head computed tomography, electrocardiography, and echocardiography showed no abnormalities. Syncope secondary to abdominal pain was reproduced during HUT. Further, HUT revealed vasovagal syncope, and synchronous TCD showed decreased cerebral blood flow; the final diagnosis was VVS in all cases. Conclusions Abdominal pain may be a precursor of VVS in adults, and our findings enrich the clinical phenotypic spectrum of VVS. Prompt recognition of syncopal precursors is important to prevent incidents and assist in treatment decision-making. Abdominal pain in VVS may be a sign of sympathetic overdrive. Synchronous multimodal detection can help in diagnosing VVS and understanding hemodynamic mechanisms.

Abstract Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation.

Organophosphorus poisoning is a critical condition that can cause central nervous system depression, respiratory failure, and death early on. As its clinical manifestations closely resemble those of carbamate pesticide poisoning, the aim of this case study is to present a case of misdiagnosis, initially identifying carbofuran poisoning as organophosphate in a patient suspect of a heatstroke. We also present a case of intentional self-poisoning with organophosphate dichlorvos to underline the likelihood of pesticide poisoning in patients exhibiting acute cholinergic symptoms when the ingested substance is not known. In such cases, empirical treatment with atropine and oxime can be started pending timely differential diagnosis to adjust treatment as necessary.