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Abstract Panax japonicus, a traditional medicinal plant from the Araliaceae family, produces bioactive triterpenes with health benefits. In Traditional Chinese Medicine, its roots have been used, but the chemical basis of its medicinal use is unclear, particularly regarding the metabolism and regulation of triterpene saponin biosynthesis. This study employed an integrative approach using Ultra Performance Liquid Chromatography (UPLC) and transcriptome analysis. Our UPLC analysis showed that ginsenoside Ro and chikusetsusaponin IVa were mainly detected in P. japonicus root. Subsequently, a comparative transcriptome analysis of four P. japonicus tissues (roots, leaves, flowers and fruits) was conducted using Illumina sequencing. As a result, 90,985 unigenes were functionally annotated from a total of 211,650 assembled non-redundant transcripts. Among these, 42,829 unigenes were annotated in NR database. Tissue-specific gene analysis revealed that roots had the highest number of specifically expressed unigenes (11,832). The majority of these unigenes were associated with metabolic processes. Additionally, tissue expression patterns analysis for three common transcription factor families indicated that WRKY family genes showed a significantly root-specific expression pattern, potentially playing a role in triterpene saponin biosynthesis. Notably, we investigated the expression profiles of genes related to the biosynthesis of triterpene saponins and found that four genes, ACCT, HMGS, HMGR and SS, encoding key enzymes in triterpene saponins biosynthesis pathway, were primarily expressed in the root. Overall, our study provides a set of P. japonicus tissue transcriptome data, which will aid in the discovery of triterpene saponin biosynthetic genes and offers valuable genetic information for this medical plant.

Abstract Background and aims Previous study found that estimated glucose disposal rate (eGDR) was significantly associated with cardiovascular disease (CVD). However, little is known about the change in eGDR over time and its association with the development of CVD. The aim of this study was to investigate the association of change in eGDR with CVD risk. Methods This study used data of two prospective cohorts: UK Biobank and China Health and Retirement Longitudinal Study (CHARLS) with two measurements of eGDR. Changes in the eGDR were classified using K‑means clustering analysis, and the cumulative eGDR was also calculated. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders. Results A total of 11,682 individuals from the UK Biobank, and 4,974 individuals from the CHARLS were included. The median follow-up periods were 9.7 years in the UK Biobank and 3.0 years in the CHARLS. Compared with persistently high level of eGDR (class 1), individuals with low level increasing (class 3) and persistently low level of eGDR (class 4) showed elevated risks of incident CVD in both UK Biobank (HR = 2.79, 95% 2.15–3.62 for class 3; HR = 3.19, 95% 2.50–4.08 for class 4) and CHARLS (HR = 1.66, 95% 1.29–2.13 for class 3; HR = 1.69, 95% 1.34–2.14 for class 4). In addition, lower level of cumulative eGDR were associated with elevated risks of incident CVD. The dose-response curve between cumulative eGDR and CVD risk showed a negative linear relationship. Conclusion Different changes in eGDR level are associated with different risks of incident CVD. Dynamic monitoring of eGDR level is of significant importance for the CVD prevention and treatment.

Buxus sinica var. parvifolia is a shrub or small arbor of the Buxaceae family, rich in various medicinal alkaloids and of great horticultural value. In this study, we sequenced, assembled, and annotated the complete chloroplast genome of B. sinica var. parvifolia for the first time. The length of the chloroplast genome is 158,995 bp with 38.1% overall GC content. It includes a large single-copy (LSC) region of 88,140 bp, a small single-copy (SSC) region of 17,761 bp, and two inverted repeat regions of 26,547 bp. Additionally, 132 functional genes in the genome are identified, including 87 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. Phylogenetic analysis showed that B. sinica var. parvifolia is closely related to Buxus microphylla. The complete chloroplast genome sequence of B. sinica var. parvifolia and its phylogenetic analysis provides useful genomic information for the further study of B. sinica var. parvifolia and other Buxus species.

Abstract Laminectomy is one of the most common posterior spinal operations. Since the lamina is adjacent to important tissues such as nerves, once damaged, it can cause serious complications and even lead to paralysis. In order to prevent the above injuries and complications, ultrasonic bone scalpel and surgical robots have been introduced into spinal laminectomy, and many scholars have studied the recognition method of the bone tissue status. Currently, almost all methods to achieve recognition of bone tissue are based on sensor signals collected by high‐precision sensors installed at the end of surgical robots. However, the previous methods could not accurately identify the state of spinal bone tissue. Innovatively, the identification of bone tissue status was regarded as a time series classification task, and the classification algorithm LSTM‐FCN was used to process fusion signals composed of force and cutting depth signals, thus achieving an accurate classification of the lamina bone tissue status. In addition, it was verified that the accuracy of the proposed method could reach 98.85% in identifying the state of porcine spinal laminectomy. And the maximum penetration distance can be controlled within 0.6 mm, which is safe and can be used in practice.

Objective Compared to Mimas pigeons, Shiqi pigeons exhibit greater tolerance to coarse feeding because of their abundant gut microbiota. Here, to investigate the potential of utilizing intestinal flora derived from Shiqi pigeons, the intestinal flora and body indices of Mimas squabs were evaluated after fecal microbiota transplantation (FMT) from donors. Methods A total of 90 one-day-old squabs were randomly divided into the control group (CON), the low-concentration group (LC) and the high-concentration group (HC): gavaged with 200 μL of bacterial solution at concentrations of 0, 0.1, and 0.2 g/15 mL, respectively. Results The results suggested that FMT improved the body weight of Mimas squabs in the HC and LC groups (p

Abstract Aquilaria yunnanensis is an endangered agarwood-producing tree currently listed on the IUCN Red List of Threatened Species. The agarwood it produces has important medicinal and economic value, but its population has sharply declined due to human destruction and habitat reduction. Therefore, obtaining genomic information on A. yunnanensis is beneficial for its protection work. We assembled a chromosome-level reference genome of A. yunnanensis by using BGI short reads, PacBio HiFi long reads, coupled with Hi-C technology. The final genome assembly of A. yunnanensis is 847.04 Mb, with N50 size of 99.68 Mb, in which 805.49 Mb of the bases were anchored on eight pseudo-chromosomes. Two gapless pseudo-chromosomes were detected in the assembly. A total of 27,955 protein-coding genes as well as 74.65% repetitive elements were annotated. These findings may provide valuable resources in conservation, functional genomics, and molecular breeding of A. yunnanensis, as well as the molecular phylogenetics and evolutionary patterns in Aquilaria.

Abstract This study was aimed to explore the longitudinal association of five early life factors (breastfeeding, maternal smoking around birth, birth weight, being born in a multiple birth, and adoption) during the in-utero, perinatal, and early childhood development stages with incidence of depression and anxiety in adults aged 40–69 years. We used data from the UK biobank, 5,02,394 participants aged 40–69 years were recruited between 2006 and 2010. Participants provided information on early life exposures through touchscreen questionnaires or verbal interviews at baseline. The primary outcomes, depression, and anxiety, were defined according to the International Classification of Diseases, 10th Revision. Hazard ratios (HR) and 95% confidence intervals (CI) for each factor were reported. During a median follow-up of 13.6 years, 16,502 (3.55%) participants developed depression, and 15,507 (3.33%) developed anxiety. After adjusting for potential confounders, increased risk of depression was found to be significantly associated with non-breastfeeding (HR, 1.08; 95% CI, 1.04–1.13), maternal smoking around birth (HR, 1.19; 95% CI, 1.14–1.23), being born in multiple births (HR, 1.16; 95% CI, 1.05–1.27), low birth weight (HR, 1.14; 95% CI, 1.07–1.22), and being an adoptee (HR, 1.42; 95% CI, 1.28–1.58). Increased risk of anxiety was associated with non-breastfeeding (HR, 1.09; 95% CI, 1.04–1.13), maternal smoking around birth (HR, 1.11; 95% CI, 1.07–1.16), being born in a multiple births (HR, 1.05; 95% CI, 0.95–1.17), low birth weight (HR, 1.12; 95% CI, 1.05–1.20), and being an adoptee (HR, 1.25; 95% CI, 1.10–1.41). Each of these five early life factors can be considered as early life risk factors for incident depression and anxiety in adulthood independently. The dose-response relationship was also observed, suggesting that with an increase in the number of early life risk factors, the likelihood of experiencing depression and anxiety also increased. These findings highlighted the imperative consideration of early life factors in comprehending the susceptibility to mental health disorders later in life, including non-breastfeeding, maternal smoking around birth, being born in multiple births, low birth weight, and being an adoptee.

The complete mitochondrial genome of Pealius mori (Hemiptera: Aleyrodidae) was determined in this study. The mitogenome was 15,654 bp long with 37 typical Insecta mitochondrial genes and one non-coding control region. Its gene content and order were different to other Hemiptera mitochondrial genomes. The overall nucleotide composition of the mitogenome was 42.62% A, 32.73% T, 11.12% G and 13.54% C, with an A + T bias of 75.34%. Phylogenetic analyses of 14 species in Aleyrodidae, 2 species in Lepidoptera and 1 species in Thysanoptera by Maximum Likelihood showed that P. mori China had been more closely related to P. mori France, closely related to Pealius machili. This result well supported the taxonomic position of Aleyrodidae and their close relationship with the Pealius category.

Abstract Background Nosocomial infections with heavy disease burden are becoming a major threat to the health care system around the world. Through long-term, systematic, continuous data collection and analysis, Nosocomial infection surveillance (NIS) systems are constructed in each hospital; while these data are only used as real-time surveillance but fail to realize the prediction and early warning function. Study is to screen effective predictors from the routine NIS data, through integrating the multiple risk factors and Machine learning (ML) methods, and eventually realize the trend prediction and risk threshold of Incidence of Nosocomial infection (INI). Methods We selected two representative hospitals in southern and northern China, and collected NIS data from 2014 to 2021. Thirty-nine factors including hospital operation volume, nosocomial infection, antibacterial drug use and outdoor temperature data, etc. Five ML methods were used to fit the INI prediction model respectively, and to evaluate and compare their performance. Results Compared with other models, Random Forest showed the best performance (5-fold AUC = 0.983) in both hospitals, followed by Support Vector Machine. Among all the factors, 12 indicators were significantly different between high-risk and low-risk groups for INI (P

Abstract Background Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia. Methods We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022. We estimated the risk of dementia using Cox proportional hazard models, and assessed the changes of cognitive functions and brain structural measures using logistic regression models and linear regression models. Mendelian randomization (MR) analyses were performed to examine the association between genetically determined computer gaming and dementia. Results High frequency of playing computer games was associated with decreased risk of incident dementia (HR, 0.81 [95% CI: 0.69, 0.94]). Individuals with high frequency of playing computer games had better performance in prospective memory (OR, 1.46 [1.26, 1.70]), reaction time (beta, -0.195 [-0.243, -0.147]), fluid intelligence (0.334 [0.286, 0.382]), numeric memory (0.107 [0.047, 0.166]), incorrect pairs matching (-0.253 [-0.302, -0.203]), and high volume of gray matter in hippocampus (0.078 [0.023, 0.134]). Genetically determined high frequency of playing computer games was associated with a low risk of dementia (OR, 0.37 [0.15, 0.91]). Conclusions Computer gaming was associated with a decreased risk of dementia, favorable cognitive function, and better brain structure, suggesting that computer gaming could modulate cognitive function and may be a promising target for dementia prevention.

Background The association of lipid‐lowering drug targets and their gene variants with cardiovascular diseases has been previously clarified. However, the relationship between gene variants of lipid‐lowering drug targets and the adverse prognosis of ischemic stroke patients remains unclear. Methods and Results Multiple single‐nucleotide polymorphisms associated with 6 lipid‐lowering drug targets were genotyped for patients with ischemic stroke. The primary outcome was death or major disability within 2 years after ischemic stroke. Genetic risk score was constructed from significant single‐nucleotide polymorphisms identified via additive models, which was calculated by multiplying the number of risk alleles at each locus by the corresponding beta coefficient and then summing the products. The rs2006760‐C of the HMGCR, rs11206510‐T of PCSK9, and rs1864163‐G and rs9929488‐G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Each additional risk allele was associated with higher odds of adverse outcomes. Genetic risk score was positively associated with the odds of primary outcome (odds ratio [OR], 1.48 [95% CI, 1.15–1.90]; Ptrend = 0.001), major disability (OR, 1.56 [95% CI, 1.16–2.08]; Ptrend = 0.002), death (hazard ratio [HR], 1.58 [95% CI, 1.12–2.25]; Ptrend = 0.011), and the composite outcome of death or cardiovascular events (HR, 1.41 [95% CI, 1.08–1.85]; Ptrend = 0.010) when 2 extreme quartiles were compared. Conclusions rs2006760‐C of HMGCR, rs11206510‐T of PCSK9, and rs1864163‐G and rs9929488‐G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Furthermore, higher GRS was positively related to the odds of poor outcomes in patients with ischemic stroke. Registration: URL: https://www.clinicaltrials.gov; Identifier: NCT01840072.

Background As a risk factor of cardiovascular diseases, homocysteine can be effectively lowered by folate. However, the associations of folate and homocysteine levels with the prognosis of ischemic stroke remained unclear. Methods and Results A total of 3530 patients with ischemic stroke were included. Serum folate and homocysteine levels were measured at admission. The primary outcome was composite of death and major disability (modified Rankin Scale score≥3) at 3 months after stroke onset. Univariate and multivariate logistic regression models were used. The mediation effect of homocysteine was examined. During follow‐up, 1056 participants developed the primary outcome. In the univariate model, participants in the highest quartile of folate had a 29% (95% CI, 0.58–0.87) decreased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with the highest quartile of folate was 0.58 (95% CI, 0.46–0.73) for primary outcome. In contrast, participants in the highest quartile of homocysteine had a 52% (95% CI, 1.24–1.98) increased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with highest quartile of homocysteine was 1.57 (95% CI, 1.24–1.98) for primary outcome. In addition, 25.5% of the observed associations between folate and primary outcome was mediated through homocysteine (P=0.012). Conclusions High folate levels were associated with low risks of death and major disability among Chinese patients with ischemic stroke, and homocysteine partially mediated the observed potential beneficial role of folate.

Background Antiphospholipid antibodies (aPLs) have been reported to be involved in platelet‐mediated thrombosis and inflammation, but the impact on the prognosis of ischemic stroke remains unclear. We aimed to examine whether the association between baseline platelet count (PLT) and long‐term clinical outcomes within 2 years after ischemic stroke onset is modulated by aPLs. Methods and Results A total of 2938 patients with ischemic stroke were included in this prospective cohort study. Cox proportional hazards regression models were used to assess the association between the baseline PLT stratified by aPLs status and 2‐year clinical outcomes after stroke onset, and an interaction effect between PLT and aPLs on clinical outcomes was tested by likelihood ratio test. There was a significant interaction effect of aPLs and PLT on recurrent stroke (Pinteraction=0.002) and cardiovascular events (Pinteraction=0.001) within 2 years after stroke onset. After multivariate adjustment, high PLT was associated with increased risks of recurrent stroke (hazard ratio [HR], 2.78 [95% CI, 1.03–7.45]; Ptrend=0.039) and cardiovascular events (HR, 2.58 [95% CI, 1.12–5.90]; Ptrend=0.024) when 2 extreme tertiles were compared among patients with aPL positive, but not among those with aPL negative. Conclusions The aPLs had a modifying effect on the association between PLT and clinical outcomes within 2 years after ischemic stroke onset. Increased PLT was associated with recurrent stroke and cardiovascular events after ischemic stroke onset among patients with aPL positive, but not in those with aPL negative.

Background Corin plays important roles in the regulation of blood volume and pressure and cardiac function by activating natriuretic peptide pathway, exerting multiple cardioprotective effects. But the impacts of soluble corin on clinical outcomes after ischemic stroke are unclear. We aimed to investigate the associations between serum soluble corin and long‐term clinical outcomes after acute ischemic stroke. Methods and Results We measured the concentrations of serum soluble corin in 3162 participants (2010 men and 1152 women) from the China Antihypertensive Trial in Acute Ischemic Stroke. The clinical outcomes were recurrent stroke, cardiovascular events, all‐cause mortality, and unfavorable functional outcome within 24 months after stroke. Risk reclassification for study clinical outcomes of models with soluble corin were evaluated. Serum soluble corin was inversely associated with recurrent stroke, cardiovascular events, and unfavorable functional outcome after ischemic stroke. After adjusting for multiple covariates, each additional SD of log‐corin was associated with a 21% (95% CI, 11–30), 16% (95% CI, 6–26), and 12% (95% CI, 3–21) decreased risk for recurrent stroke, cardiovascular events, and unfavorable functional outcome, respectively. Furthermore, the addition of soluble corin to the basic model with conventional risk factors significantly improved risk discrimination for recurrent stroke, cardiovascular events, and the composite outcome of all‐cause mortality and cardiovascular events, as shown by C‐statistics (all P

Given that there is currently no clinically approved drug or vaccine for parainfluenza 3 (PIV3), we applied a drug repurposing method based on disease similarity and chemical similarity to screen 2,585 clinically approved chemical drugs using PIV3 potential drugs BCX-2798 and zanamivir as our controls. Twelve candidate drugs were obtained after being screened with good disease similarity and chemical similarity (S > 0.50, T > 0.56). When docking them with the PIV3 target protein, hemagglutinin-neuraminidase (HN), only oseltamivir was docked with a better score than BCX-2798, which indicates that oseltamivir has an inhibitory effect on PIV3. After the distance (Zdc) between the drug target of 14 drugs and the PIV3 disease target was measured by the network proximity method based on the PIV3 disease module, it was found that the Zdc values of amikacin, oseltamivir, ribavirin, and streptomycin were less than those of the control. Thus, oseltamivir is the best potential drug because it met all the above screening requirements. Additionally, to explore whether oseltamivir binds to HN stably, molecular dynamics simulation of the binding of oseltamivir to HN was carried out, and the results showed that the RMSD value of the complex tended to be stable within 100 ns, and the binding free energy of the complex was low (−10.60 kcal/mol). It was proved that oseltamivir screened by our drug repurposing method had the potential feasibility of treating PIV3.

IntroductionGenitourinary syndrome of menopause (GSM) describes the symptoms and signs resulting from the effect of estrogen deficiency on the female genitourinary tract, including genital, urinary, and sexual symptoms. However, besides estrogen deficiency, little is known about the etiology of GSM. The objective of this study was to investigate the effects of vaginal microbiota dysbiosis on the occurrence and development of GSM in perimenopausal and postmenopausal women.MethodsIn total, 96 women were enrolled in this cross-sectional study and clinical data were collected. GSM symptoms were divided into three types: genital, urological, and sexual symptoms. Full-length 16S rRNA gene sequencing using the third-generation PacBio sequencing technology was performed to analyze the vaginal microbiome using vaginal swabs of non-GSM and GSM women with different types of GSM symptoms. Live Lactobacillus Capsule for Vaginal Use (LLCVU) treatment was used to verify the effects of Lactobacillus on GSM symptoms.ResultsWe found that 83.58% (56/67) of women experienced GSM symptoms in the perimenopausal and postmenopausal stages. Among these women with GSM, 23.21% (13/56), 23.21% (13/56), and 53.57% (30/56) had one type, two types, and three types of GSM symptoms, respectively. The richness and diversity of vaginal microbiota gradually increased from reproductive to postmenopausal women. There were significant differences in vaginal microbial community among non-GSM women and GSM women with different types of symptoms. Lactobacillus was found to be negatively associated with the onset, severity, and type of GSM while some bacteria, such as Escherichia-shigella, Anaerococcus, Finegoldia, Enterococcus, Peptoniphilus_harei, and Streptococcus, were found to be positively associated with these aspects of GSM, and these bacteria were especially associated with the types of genital and sexual symptoms in GSM women. LLCVU significantly relieved genital symptoms and improved the sexual life of GSM women in shortterm observation.ConclusionsThe onset, severity, and type of GSM symptoms may be associated with changes in vaginal microbiota in perimenopausal and postmenopausal women. Vaginal microbiota dysbiosis probably contributes to the occurrence and development of GSMsymptoms, especially vaginal and sexual symptoms. Lactobacillus used in the vagina may be a possible option for non-hormonal treatment of GSM women with genital and sexual symptoms.Clinical Trial Registrationhttps://www.chictr.org.cn/indexEN.html, identifier ChiCTR2100044237.

IntroductionThis study aims to use machine learning to conduct in-depth analysis of key factors affecting the recurrence of HCC patients with high preoperative systemic immune-inflammation index (SII) levels after receiving ablation treatment, and based on this, construct a nomogram model for predicting recurrence-free survival (RFS) of patients.MethodsThis study included clinical data of 505 HCC patients who underwent ablation therapy at Beijing You’an Hospital from January 2014 to January 2020, and accepted 65 HCC patients with high SII levels from Beijing Ditan Hospital as an external validation cohort. 505 patients from Beijing You’an Hospital were divided into low SII and high SII groups based on the optimal cutoff value of SII scores. The high SII group was further randomly divided into training and validation cohorts in a 7:3 ratio. eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox regression analysis, were used to explore the factors affecting the post-ablation RFS of HCC patients. Based on the identified key factors, a nomogram model were developed to predict RFS in HCC patients, and their performance were evaluated using the concordance index (C index), receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). The optimal cutoff value for nomogram scores was used to divide patients into low- and high-risk groups, and the effectiveness of the model in risk stratification was evaluated using Kaplan-Meier (KM) survival curves.ResultsThis study confirmed that age, BCLC stage, tumor number, and GGT level were independent risk factors affecting RFS in HCC patients. Based on the selected risk factors, an RFS nomogram was successfully constructed. The C-index, ROC curve, calibration curve, and DCA curve each demonstrated the discrimination, accuracy, and decision-making utility of the nomogram, indicating that it has good predictive performance. KM curve revealed the nomogram could significantly differentiate patient populations with different recurrence risk.ConclusionWe developed a reliable nomogram that can accurately predict the 1-, 3-, and 5-year RFS for HCC patients with high SII levels following ablation therapy.

Abstract Background To demonstrate and analyze the 18F-FDG positron emission tomography/computed tomography (PET/CT) findings in this rare nevoid basal cell carcinoma syndrome (NBCCS). Case presentation A 71-year-old woman with the left invasive breast cancer was treated with hormone therapy for six months and underwent the 18F-FDG PET/CT examination for efficacy evaluation. 18F-FDG PET/CT revealed the improvement after treatment and other unexpected findings, including multiple nodules on the skin with 18F-FDG uptake, bone expansion of cystic lesions in the bilateral ribs, ectopic calcifications and dilated right ureter. She had no known family history. Then, the patient underwent surgical excision of the all skin nodules and the postoperative pathology were multiple basal cell carcinomas. Finally, the comprehensive diagnosis of NBCCS was made. The patient was still in follow-up. Additionally, we have summarized the reported cases (n = 3) with 18F-FDG PET/CT from the literature. Conclusions It is important to recognize this syndrome on 18F-FDG PET/CT because of different diagnoses and therapeutic consequences.

An unprecedented electrochemical oxidative trifunctionalization of olefins with diaryl disulfides/aryl thiols and N-chlorosuccinimide in an aqueous system is developed. Two C–Cl bonds, one C–S bond, and one SO bond are produced simultaneously in one step from simple and commercially available starting materials with clean energy. This tandem methodology features as mild reaction conditions, transition metal and additional oxidant free, broad substrate scope, good functional group compatibility, and gram scale preparation.

Abstract In the field of remote sensing image interpretation, automatically extracting water body information from high-resolution images is a key task. However, facing the complex multi-scale features in high-resolution remote sensing images, traditional methods and basic deep convolutional neural networks are difficult to effectively capture the global spatial relationship of the target objects, resulting in incomplete, rough shape and blurred edges of the extracted water body information. Meanwhile, massive image data processing usually leads to computational resource overload and inefficiency. Fortunately, the local data processing capability of edge computing combined with the powerful computational resources of cloud centres can provide timely and efficient computation and storage for high-resolution remote sensing image segmentation. In this regard, this paper proposes PMNet, a lightweight deep learning network for edge-cloud collaboration, which utilises a pipelined multi-step aggregation method to capture image information at different scales and understand the relationships between remote pixels through horizontal and vertical spatial dimensions. Also, it adopts a combination of multiple decoding branches in the decoding stage instead of the traditional single decoding branch. The accuracy of the results is improved while reducing the consumption of system resources. The model obtained F1-score of 90.22 and 88.57 on Landsat-8 and GID remote sensing image datasets with low model complexity, which is better than other semantic segmentation models, highlighting the potential of mobile edge computing in processing massive high-resolution remote sensing image data.

Background Polyamines have been reported to be associated with neurological function, but the associations between polyamines and the prognosis of ischemic stroke remain unclear. We aimed to prospectively investigate whether elevated plasma polyamine levels are associated with adverse outcomes in patients with ischemic stroke. Methods and Results Plasma polyamine levels were measured at admission in 3570 patients with acute ischemic stroke, and clinical outcomes were assessed at 3 months after stroke onset. The primary outcome was a composite outcome of death and major disability (modified Rankin Scale score≥3), and secondary outcomes included the individual outcomes of death and major disability. During a 3‐month follow‐up period, 877 participants (25.1%) experienced the primary outcome. Increased putrescines were associated with a decreased risk of the primary outcome (the highest versus the lowest tertile: odds ratio, 0.72 [95% CI, 0.58–0.91]; P=0.005) and major disability (odds ratio, 0.59 [95% CI, 0.47–0.74]; P

ABSTRACT: Goose creates important economic value depending on their enrich nutrients of meat. Our previous study investigates potential candidate genes associated with variations in meat quality between Xianghai Flying (XHF) Goose and Zi Goose through genomic and transcriptome integrated analysis. Screening of 5 differential expression candidate genes related to muscle development identified by the FST, XP-EHH and RNA-seq in breast muscle from various geese. Among them, C1QTNF1 (C1q and TNF related protein 1), a gene of unknown function in goose, which observed mutations in coding sequence regions in sequencing data. Its function was explored after overexpression and knockdown which designed depending on the genetic sequence of the goose, respectively. Results showed that over-expression of C1QTNF1 significantly enhances cell proliferation and viability. In addition, the expression levels of the fusion marker gene Myomaker and the differentiation marker gene MyoD are significantly upregulated in cells. Knock-down C1QTNF1 leads to down regulated Myomaker and MyoD which involved muscle formation. But, the expression level of muscle atrophy marker MuRF is not significantly changed among different transfection groups. Since protein structures and interactions are closely related to their functions, we further analyzed the C1QTNF1 for physicochemical properties, structural predictions, protein interactions and homology. It can be reasonably inferred that C1QTNF1 has a similar effect to collagen, which may affect muscle development. In summary, we first speculate that C1QTNF1 may play an important regulatory role in muscle growth and development and thereby contributes to the further understanding of the genetic mechanisms that underlie meat quality traits of goose.

To detect historical cumulative changes in land cover, this study introduces a novel time series PolSAR change detection method. The objective is to address the inefficiency of traditional detection methods that use multiple pairwise comparisons, as well as to alleviate false positives and false negatives caused by the insufficient utilization of polarization and spatial context information in previous methods. The proposed method initially constructs a temporal difference matrix for time series PolSAR images and computes the difference image (DI) using the maximum eigenvalue of this matrix to depict the cumulative changes over time. Subsequently, the DI is segmented using an MRF-based image segmentation method with a limited amount of supervised information, yielding the cumulative change binary map. The efficacy of the proposed method is validated using three time series datasets covering different scenes acquired by different sensors, namely GaoFen3, Radarsat2 and Sentinel-1. The experimental results demonstrate that the method effectively characterizes cumulative changes in the time series while simultaneously considering disparities in radar backscatter intensity and polarization correlation. As a result, it significantly reduces erroneous and missed change detections and surpasses the existing methods by achieving the highest Recall, F1-score, IOU, Kappa, and overall accuracy. Furthermore, the DI calculation method serves as a versatile change descriptor applicable not only for capturing cumulative changes in time series but also for describing changes between dual temporal images.

Scrophularia ningpoensis Hemsl. (SN) is an herbal medicine used as a functional food in China. SN has traditionally been used to treat diabetes mellitus (DM), but its mechanism of action is not well understood. Our previous study indicated that the aqueous extract of SN can reduce hepatic insulin resistance and correct the irregular shape of pancreatic islets in diabetic mice. This study aims to investigate whether the aqueous extract of SN can regulate pyroptosis in pancreatic β-cells and explore its underlying mechanisms. Db/db mice were orally given an aqueous extract of SN for eight weeks. Subsequently, their pancreatic tissues were collected for histopathological analysis and immunoblotting. Rat insulinoma (INS-1) cells were cultured either alone or with the aqueous extract of SN and evaluated for cell viability, pyroptotic body formation, AMP-activated protein kinase (AMPK) activity, the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome and gasdermin D (GSDMD) activation, and reactive oxygen species (ROS) production under high glucose (HG) exposure conditions. The aqueous extract of SN reduced insulitis and pancreatic β-cell death in db/db mice. Increased AMPK phosphorylation and decreased NLRP3 inflammasome and GSDMD activation were observed in pancreatic tissues after administration of the aqueous extract of SN. In vitro, the aqueous extract of SN increased cell viability and AMPK phosphorylation in a concentration-dependent manner. Additionally, the aqueous extract of SN corrected excessive ROS generation, NLRP3 inflammasome and GSDMD activation, and pyroptotic body formation. Inhibition of AMPK negated these beneficial effects of the aqueous extract of SN on INS-1 cells. The study concluded that the aqueous extract of SN alleviates β-cell pyroptosis by inhibiting NLRP3/GSDMD activation in an AMPK-dependent manner.

This case report describes a patient initially diagnosed with Gaucher disease (GD) with type I with homozygous mutation c.1448T > C p. (Leu483Pro) at age of 2, presenting with hepatosplenomegaly and cytopenia. Imiglucerase replacement therapy was initiated. At age 17, bilateral hearing loss developed, with subsequent Cranial MRI revealing thalamic damage, leading to a reclassification as type 3 GD. By age of 20, the patient presented with a range of symptoms, including abdominal pain, diarrhea, hypoproteinemia, multiple lymphadenopathy, edema, and Gaucher cell infiltration in the lymph nodes. Comprehensive diagnosis identifies Gaucher tumor and protein-losing enteropathy. Imiglucerase therapy at 90‐120 U/kg every 2 weeks significantly improved clinical symptoms, emphasizing the importance of tailored interventions for managing GD manifestations.

Abstract In the field of meteorology, the global radar network is indispensable for detecting weather phenomena and offering early warning services. Nevertheless, radar data frequently exhibit anomalies, including gaps and clutter, arising from atmospheric refraction, equipment malfunctions, and other factors, resulting in diminished data quality. Traditional radar blockage correction methods, such as employing approximate radial information interpolation and supplementing missing data, often fail to effectively exploit potential patterns in massive radar data, for the large volume of data precludes a thorough analysis and understanding of the inherent complex patterns and dependencies through simple interpolation or supplementation techniques. Fortunately, edge computing possesses certain data processing capabilities and cloud center boasts substantial computational power, which together can collaboratively offer timely computation and storage for the correction of radar beam blockage. To this end, an edge-cloud collaborative driven deep learning model named DenMerD is proposed in this paper, which includes dense connection module and merge distribution (MD) unit. Compared to existing models such as RC-FCN, DenseNet, and VGG, this model greatly improves key performance metrics, with 30.7 $$\%$$ % improvement in Critical Success Index (CSI), 30.1 $$\%$$ % improvement in Probability of Detection (POD), and 3.1 $$\%$$ % improvement in False Alarm Rate (FAR). It also performs well in the Structure Similarity Index Measure (SSIM) metrics compared to its counterparts. These findings underscore the efficacy of the design in improving feature propagation and beam blockage accuracy, and also highlights the potential and value of mobile edge computing in processing large-scale meteorological data.

Snow on the Tibetan Plateau (TP) is not only a freshwater resource for the major rivers in Asia but also plays a significant role in adjusting temperature by reflecting solar radiation. Fractional snow cover mapping with fine spatial and temporal resolution is of great significance for clarifying snow resources and accurately managing snow water resources. However, due to the complex TP topography, the existing fractional snow cover (FSC) retrieval methods are affected by a variety of disturbance factors, resulting in a decrease in accuracy. In this study, a deep learning-based FSC retrieval method, FSC U-shape net, is proposed to improve snow cover mapping accuracy. The input images of FengYun-4A advanced geosynchronous radiation imager and geographic data are extracted using the proposed spatial-channel feature extraction module to characterize the shallow features with texture information into high-dimensional feature images. Additionally, an attention mechanism is introduced to improve the feature differences between different FSC degrees. Finally, the correlation of the decoded features in the channel direction is mined using the channel refinement module to obtain the final FSC results. In this study, a backpropagation artificial neural network, random forest, ResNet_FSC, and UNet are trained, compared, and validated against the MOA10A1 FSC product. The results show that the proposed method effectively mitigates the problems of unclear texture of snow edges, poor robustness, and underestimation in some areas, which exist in other models. Additionally, the proposed method has higher accuracy, with an R2 and explained variance score reaching 0.7182 and 0.7332, respectively. Compared to the MOD10A1 snow product, the proposed method exhibits higher detection accuracy in mountainous areas with high snow cover and significantly improves the low snow cover detection rate.

This study examined the agricultural water resource shortage and abundant ditch water resources in the Yinbei region of Ningxia. The effects of ditch water and Yellow River irrigation on the saline–alkali characteristics of soil and paddy were investigated using field monitoring and indoor detection methods in Pingluo County, Ningxia (106°31′ E, 38°51′ N). In addition to monitoring ditch water, four treatment groups were established: direct ditch water irrigation (T1), mixed ditch water and Yellow River water irrigation (T2), alternate ditch water and Yellow River water irrigation (T3), and irrigation solely with Yellow River water (CK). The results show the following: (1) The salinity of ditch water samples collected from the experimental field during the rice growth period was less than 1.60 g/L, and the pH of the samples was lower than 8.62; thus, they were classified as mildly brackish water. The application of ditch water irrigation did not result in soil saline–alkali aggravation and the accumulation of excessive amounts of heavy metals in soils and paddies in Pingluo County, Ningxia. (2) The rice yields for the CK, T1, T2, and T3 treatments were 10,437.5, 8318.4, 9182.1, and 9016.2 kg/hm2, respectively. Compared with Yellow River irrigation, the rice yields for the T1, T2, and T3 treatments were 20.3, 12.1, and 13.6% lower than that of CK, respectively, with minimal differences observed among them. Hence, under the condition of a water resource shortage in the Yellow River region, ditch water can be appropriately applied for mixed or alternate irrigation to ensure food security. This research has revealed the influences of ditch water irrigation on the saline–alkali properties of soil and the heavy metal contents of paddies.

ObjectiveThe study aimed to build and validate a competitive risk nomogram to predict the cumulative incidence of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV)-related cirrhosis.MethodsA total of 1401 HBV-related cirrhosis patients were retrospectively enrolled from January 1, 2011 to December 31, 2014. Application of 20 times imputation dealt with missing data using multiple imputation by chained equations (MICE). The patients were randomly divided into a training set (n = 1017) and a validation set (n = 384) at a ratio of 3:1. A prediction study was carried out using a competing risk model, where the event of interest was HCC and the competing events were death and liver transplantation, and subdistribution hazard ratios (sHRs) with 95% CIs were reported. The multivariate competing risk model was constructed and validated.ResultsThere was a negligible difference between the original database and the 20 imputed datasets. At the end of follow-up, the median follow-up time was 69.9 months (interquartile range: 43.8–86.6). There were 31.5% (442/1401) of the patients who developed HCC, with a 5-year cumulative incidence of 22.9 (95%CI, 20.8%–25.2%). The univariate and multivariate competing risk regression and construction of the nomogram were performed in 20 imputed training datasets. Age, sex, antiviral therapy history, hepatitis B e antigen, alcohol drinking history, and alpha-fetoprotein levels were included in the nomogram. The area under receiver operating characteristic curve values at 12, 24, 36, 60, and 96 months were 0.68, 0.69, 0.70, 0.68, and 0.80, and the Brier scores were 0.30, 0.25, 0.23, 0.21, and 0.20 in the validation set. According to the cumulative incidence function, the nomogram effectively screened out high-risk HCC patients from low-risk patients in the presence of competing events (Fine–Gray test p < 0.001).ConclusionThe competitive risk nomogram was allowed to be used for predicting HCC risk in individual patients with liver cirrhosis, taking into account both the association between risk factors and HCC and the modifying effect of competition events on this association.

BackgroundHepatitis B surface antigen (HBsAg) clearance is associated with improved long-term outcomes and reduced risk of complications. The aim of our study was to identify the effects of levels of HBsAg in HCC patients undergoing TACE and sequential ablation. In addition, we created a nomogram to predict the prognosis of HCC patients with high levels of HBsAg (≥1000U/L) after local treatment.MethodThis study retrospectively evaluated 1008 HBV-HCC patients who underwent TACE combined with ablation at Beijing Youan Hospital and Beijing Ditan Hospital from January 2014 to December 2021, including 334 patients with low HBsAg levels and 674 patients with high HBsAg levels. The high HBsAg group was divided into the training cohort (N=385), internal validation cohort (N=168), and external validation cohort (N=121). The clinical and pathological features of patients were collected, and independent risk factors were identified using Lasso-Cox regression analysis for developing a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves in the training and validation cohorts. Patients were classified into high-risk and low-risk groups based on the risk scores of the nomogram.ResultAfter PSM, mRFS was 28.4 months (22.1-34.7 months) and 21.9 months (18.5-25.4 months) in the low HBsAg level and high HBsAg level groups (P

Background Poststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance. Methods and Results This prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity‐2 receptor), GDF‐15 (growth differentiation factor‐15), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini‐Mental State Examination score of

ABSTRACTA significant increase of hospital-acquired bacterial infections during the COVID-19 pandemic has become an urgent medical problem. Clostridioides difficile is an urgent antibiotic-resistant bacterial pathogen and a leading causative agent of nosocomial infections. The increasing recurrence of C. difficile infection and antibiotic resistance in C. difficile has led to an unmet need for the discovery of new compounds distinctly different from present antimicrobials, while antimicrobial peptides as promising alternatives to conventional antibiotics have attracted growing interest recently. Protein synthesis is an essential metabolic process in all bacteria and a validated antibiotic target. Initiation factor 1 from C. difficile (Cd-IF1) is the smallest of the three initiation factors that acts to establish the 30S initiation complex to initiate translation during protein biosynthesis. Here, we report the solution nuclear magnetic resonance (NMR) structure of Cd-IF1 which adopts a typical β-barrel fold and consists of a five-stranded β-sheet and one short α-helix arranged in the sequential order β1-β2-β3-α1-β4-β5. The interaction of Cd-IF1 with the 30S ribosomal subunit was studied by NMR titration for the construction of a structural model of Cd-IF1 binding with the 30S subunit. The short α-helix in IF1 was found to be critical for IF1 ribosomal binding. A peptide derived from this α-helix was tested and displayed a high ability to inhibit the growth of C. difficile and other bacterial strains. These results provide a clue for the rational design of new antimicrobials.IMPORTANCEBacterial infections continue to represent a major worldwide health hazard due to the emergence of drug-resistant strains. Clostridioides difficile is a common nosocomial pathogen and the causative agent in many infections resulting in an increase in morbidity and mortality. Bacterial protein synthesis is an essential metabolic process and an important target for antibiotic development; however, the precise structural mechanism underlying the process in C. difficile remains unknown. This study reports the solution structure of C. difficile translation initiation factor 1 (IF1) and its interaction with the 30S ribosomal subunit. A short α-helix in IF1 structure was identified as critically important for ribosomal binding and function in regulating the translation initiation, which allowed a rational design of a new peptide. The peptide demonstrated a high ability to inhibit bacterial growth with broad-spectrum antibacterial activity. This study provides a new clue for the rational design of new antimicrobials against bacterial infections.

IntroductionThe aims of this study is to analyze the risk of major adverse cardiovascular events (MACEs) in patients with psoriasis treated with secukinumab and ixekizumab.MethodologyWe systematically identified randomized controlled trials (RCTs) that focused on the treatment of psoriasis with secukinumab and ixekizumab by conducting computerized searches of PubMed, Embase, and the Cochrane Library databases, spanning from their inception to October 31st, 2022. The search terms used included psoriasis, secukinumab, ixekizumab, and randomized controlled trial. Two independent evaluators conducted literature screening, data extraction, and assessed the quality of included studies based on predetermined inclusion and exclusion criteria. The gather data was subjected to meta-analysis using the statistical software RevMan 5.4.ResultsA total of 20 articles, encompassing 23 randomized controlled trials involving 10,746 psoriasis patients were included in the analysis. During the double-blind treatment period, the meta-analysis results indicated the following: There was no significant difference in the incidence of MACEs between the secukinumab and placebo groups [RR = 0.61, 95% CI (0.26, 1.44), p = 0.26]. Similarly, there was no significant difference in the incidence of MACEs with ixekizumab compared to the placebo group [RR = 0.47, 95% CI (0.15, 1.47), p = 0.20]. Furthermore, no significant difference in the incidence of MACEs was observed between secukinumab 300 mg and secukinumab 150 mg treatment groups [RR = 1.00, 95% CI (0.23, 4.35), p = 1.00]. Likewise, there was no significant difference in the incidence of MACEs between the ixekizumab Q4W (every 4 weeks) and ixekizumab Q2W (every 2 weeks) administration groups [RR = 4.01, 95% CI (0.45, 35.89), p = 0.21].ConclusionThe findings of this study suggest that neither secukinumab nor ixekizumab is significantly associated with the risk of MACEs in patients with psoriasis during double-blind treatment.Systematic review registration: Unique Identifier: CRD42022373756 https://www.crd.york.ac.uk/.

Abstract Osteosarcoma is the most common bone sarcoma in children and young adults. While universally delivered, chemotherapy only benefits roughly half of patients with localized disease. Increasingly, intratumoral heterogeneity is recognized as a source of therapeutic resistance. In this study, we develop and evaluate an in vitro model of osteosarcoma heterogeneity based on phenotype and genotype. Cancer cell populations vary in their environment-specific growth rates and in their sensitivity to chemotherapy. We present the genotypic and phenotypic characterization of an osteosarcoma cell line panel with a focus on co-cultures of the most phenotypically divergent cell lines, 143B and SAOS2. Modest environmental (pH, glutamine) or chemical perturbations dramatically shift the success and composition of cell lines. We demonstrate that in nutrient rich culture conditions 143B outcompetes SAOS2. But, under nutrient deprivation or conventional chemotherapy, SAOS2 growth can be favored in spheroids. Importantly, when the simplest heterogeneity state is evaluated, a two-cell line coculture, perturbations that affect the faster growing cell line have only a modest effect on final spheroid size. Thus the only evaluated therapies to eliminate the spheroids were by switching therapies from a first strike to a second strike. This extensively characterized, widely available system, can be modeled and scaled to allow for improved strategies to anticipate resistance in osteosarcoma due to heterogeneity.

Abstract Background Chimeric antigen receptor (CAR)-T cell therapy has been used to treat pediatric refractory or relapsed mature B-cell non-Hodgkin lymphoma (r/r MB-NHL) with significantly improved outcomes, but a proportion of patients display no response or experience relapse after treatment. To investigate whether tumor-intrinsic somatic genetic alterations have an impact on CAR-T cell treatment, the genetic features and treatment outcomes of 89 children with MB-NHL were analyzed. Methods 89 pediatric patients treated at multiple clinical centers of the China Net Childhood Lymphoma (CNCL) were included in this study. Targeted next-generation sequencing for a panel of lymphoma-related genes was performed on tumor samples. Survival rates and relapse by genetic features and clinical factors were analyzed. Survival curves were calculated using a log-rank (Mantel-Cox) test. The Wilcox sum-rank test and Fisher’s exact test were applied to test for group differences. Results A total of 89 driver genes with somatic mutations were identified. The most frequently mutated genes were TP53 (66%), ID3 (55%), and ARID1A (31%). The incidence of ARID1A mutation and co-mutation of TP53 and ARID1A was high in patients with r/r MB-NHL (P = 0.006; P = 0.018, respectively). CAR-T cell treatment significantly improved survival in r/r MB-NHL patients (P = 0.00081), but patients with ARID1A or ARID1A and TP53 co-mutation had poor survival compared to those without such mutations. Conclusion These results indicate that children with MB-NHL harboring ARID1A or TP53 and ARID1A co-mutation are insensitive to initial conventional chemotherapy and subsequent CAR-T cell treatment. Examination of ARID1A and TP53 mutation status at baseline might have prognostic value, and risk-adapted or more effective therapies should be considered for patients with these high-risk genetic alterations.

In the current study, Bacillus coagulants had a role in combating oxidative stress by inhibiting the growth of intestinal pathogens. However, there are few studies on reducing the mechanisms of oxidative stress. Therefore, this study aimed to explore the effects and underlying mechanisms of B. coagulant HYI (BC-HYI) treatment on growth and intestinal functions in laying chickens under LPS-induced oxidative stress. The in vivo experimental group included five groups of laying chicks: normal control, LPS group, B6 group, B7 group and B8 group. The test consisted of six repetitions in each group, with six animals in each repetition. In the in vitro experiment, an LPS-induced oxidative stress model of chicken fibroblast DF-1 cells was established, and the DF-1 cells were divided into control group, LPS-treated group, B5 group, B6 group and B7 group. On the one hand, we found that BC-HYI can inhibit pathological changes in some intestinal tissues. On the other hand, BC-HYI supplementation has a dual effect on the gut microbiota, promoting the proliferation of beneficial microbes such as Barbarella, Lactobacillus, and Antibacterial while maintaining symbiotic balance. The abundance of Barbarella, Bactericide, and Cloistral was significantly different between the LPS group and the BC-HYI group (p < 0.01). Moreover, compared with the LPS group, BC-HYI significantly decreased reactive oxygen species levels and prevented cell apoptosis (p < 0.01). It used to prevent oxidative stress by activating the Nrf2-ARE/HO-1 signaling pathway, enhancing the scavenging of free radicals, and reducing oxidative damage. BC-HYI alleviated oxidative stress in laying chickens by modulating the gut microbiota and activating the Nrf2-ARE/HO-1 signaling pathway. In summary, laying chickens and cell experiments indicate that BC-HYI supplementation can improve the enzyme function of antioxidants, regulate intestinal barrier function and activate the Nrf2-ARE/HO-1 signaling pathway to regulate intestinal barrier function.

Abstract Background and objectives Evidence on the associations between baseline stromal cell-derived factor (SDF)-1 and clinical outcomes in acute ischemic stroke patients is lacking. The present study aimed to examine the relationship between plasma SDF-1 levels and clinical outcomes based on a large multicenter study of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Methods Secondary analysis was conducted among 3,255 participants from the CATIS trial with a baseline measurement of plasma SDF-1 levels. We evaluated the associations between plasma SDF-1 levels and one-year recurrent stroke, cardiovascular events, and all-cause mortality using Cox regression models. We further investigated the prognostic effect of SDF-1 on clinical outcomes in patients with different characteristics. Results Higher plasma SDF-1 levels were not associated with recurrent stroke, cardiovascular events, and all-cause mortality at one-year after ischemic stroke (all P trend ≥ 0.05). There were significant interactions between plasma SDF-1 levels and history of diabetes mellitus on recurrent stroke (P = 0.005), cardiovascular events (P = 0.007) and all-cause mortality (P = 0.04) at one year. In patients with diabetes mellitus, plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events after adjustment for confounders. For example, 1-SD higher log–SDF-1 was associated with a hazard ratio (95% confidence interval) of 1.65 (1.18–2.32) for recurrent stroke and 1.47 (1.08–1.99) for the cardiovascular events, but not all-cause mortality 1.36 (0.96–1.93) at one year. However, there were no associations between plasma SDF-1 and clinical outcomes in patients without diabetes mellitus (all P > 0.05). The addition of plasma SDF-1 to the conventional risk factors model significantly improved the risk prediction of all outcomes. Similarly, findings between elevated SDF-1 levels and two-year outcomes were found only in patients with diabetes mellitus. Conclusions Elevated plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events only in ischemic patients with diabetes mellitus.

Abstract To eliminate unnecessary background information, such as soft tissues in original CT images and the adverse impact of the similarity of adjacent spines on lumbar image segmentation and surgical path planning, a two‐stage approach for localising lumbar segments is proposed. First, based on the multi‐scale feature fusion technology, a non‐linear regression method is used to achieve accurate localisation of the overall spatial region of the lumbar spine, effectively eliminating useless background information, such as soft tissues. In the second stage, we directly realised the precise positioning of each segment in the lumbar spine space region based on the non‐linear regression method, thus effectively eliminating the interference caused by the adjacent spine. The 3D Intersection over Union (3D_IOU) is used as the main evaluation indicator for the positioning accuracy. On an open dataset, 3D_IOU values of 0.8339 ± 0.0990 and 0.8559 ± 0.0332 in the first and second stages, respectively is achieved. In addition, the average time required for the proposed method in the two stages is 0.3274 and 0.2105 s respectively. Therefore, the proposed method performs very well in terms of both precision and speed and can effectively improve the accuracy of lumbar image segmentation and the effect of surgical path planning.

The integrity of a pressure vessel (PRV) is affected by the decay heat of the molten pool in the lower head, so it is very important to study the natural convection heat transmission in the lower head. Scholars from all over the world have carried out a lot of experimental studies and calculations to determine the convection mechanism and heat transmission characteristics of the molten pool. Most of them were based on the empirical formula of convective heat transmission on the wall of a hemispherical molten pool based on two-dimensional slice experiments and simulation calculations. In this study, FLUENT 2021R1 software was used to simulate the three-dimensional convective heat transmission process of the hemispherical molten pool, and the temperature, velocity and wall heat transmission coefficients of the flow field were analyzed. The results were in good agreement with experimental data from UCLA (University of California, Los Angeles). Through research on the heat transmission of the lower head, the results showed that in the region where the wall angle was θ between approximately 72 and 90 degrees, heat transmission coefficients had larger fluctuations, and a more reasonable empirical relation was proposed. Comparing between the simulation results of CFD and the two-dimensional empirical formula, it was found that the latter one was smaller under the same θ angle condition. Finally, the convection phenomena of different external temperatures were simulated, and the main factors affecting the flow field by temperature were analyzed.

Background: Chukrasia tabularisis, a well-known tropical tree native to southeastern China, has anti-inflammatory and antioxidant activities, and contains large amounts of limonoids and triterpenoids. Objective: The aim of this study was to investigate the potential anti-inflammatory activity of limonoids from C. tabularis on lipopolysaccharide (LPS)-mediated RAW264.7 cells. Methods and results: Using a bioassay-guided approach, the chemical fraction with high anti-inflammatory activity was found and its chemical constituents were investigated. Phytochemical studies on active extracts resulted in the separation of three novel phragmalin limonoids (1–3), together with two known limonoids (4–5) and 11 tirucallane triterpenes (6–16). The activity of these isolated compounds in the production of nitric oxide (NO) on LPS-reated macrophages was evaluated. Limonoid 2 indicated significant anti-inflammatory activities with IC50 value of 4.58 μM. Limonoid 2 notably inhibited the production of NO, interleukin- 6 and tumor necrosis factor-α on macrophage. Signal transduction and activation of STAT and NF-κB activators were effectively blocked by limonoid 2. Conclusions: These results indicate that limonoid 2 has an anti-inflammatory effect by the inhibiting JAK2/STAT3, iNOS/eNOS, and NF-κB signaling pathways and regulating inflammatory mediators.

Abstract The high cost of feed and nitrogen pollution caused by high-protein diets have become major challenges restricting sustainable development in China's animal husbandry sector. Properly reducing protein levels and improving protein utilization in feed are effective approaches to solving this problem. To determine the optimal dose of methionine hydroxyl analogue chelated zinc (MHA-Zn) in broiler diets with a 1.5% reduction in crude protein (CP), a total of 216 1-day-old broilers were randomly assigned into 4 groups (each group consisted of 3 replications with 18 broilers per replicate), and growth and development indexes were assessed after 42 days. The broilers in control group were fed a basic diet, whereas those in the three test groups were fed diets with a 1.5% reduction in CP. The results showed no significant difference in the edible parts of broilers between low-protein (LP) diet group (90 mg/kg MHA-Zn) and normal diet group (p > 0.05), and adding 90 mg/kg MHA-Zn to LP diet significantly improved ileum morphology and apparent total tract digestibility (ATTD) of nutrient (p

Abstract Background DNA methylation has previously been associated with ischemic stroke, but the specific genes and their functional roles in ischemic stroke remain to be determined. Here we aimed to identify differentially methylated genes that play a functional role in ischemic stroke in a Chinese population. Results Genome-wide DNA methylation assessed with the Illumina Methylation EPIC Array in a discovery sample including 80 Chinese adults (40 cases vs. 40 controls) found that patients with ischemic stroke were characterized by increased DNA methylation at six CpG loci (individually located at TRIM6, FLRT2, SOX1, SOX17, AGBL4, and FAM84A, respectively) and decreased DNA methylation at one additional locus (located at TLN2). Targeted bisulfite sequencing confirmed six of these differentially methylated probes in an independent Chinese population (853 cases vs. 918 controls), and one probe (located at TRIM6) was further verified in an external European cohort (207 cases vs. 83 controls). Experimental manipulation of DNA methylation in engineered human umbilical vein endothelial cells indicated that the identified differentially methylated probes located at TRIM6, TLN2, and FLRT2 genes may play a role in endothelial cell adhesion and atherosclerosis. Conclusions Altered DNA methylation of the TRIM6, TLN2, and FLRT2 genes may play a functional role in ischemic stroke in Chinese populations.

Background Patients with stroke are often affected by varying degrees of functional disability and have different evolution patterns in functional disability. However, little is known about the predictive usefulness of disability changes after stroke. We aimed to describe 1‐year disability trajectories and to assess the associations of longitudinal disability trajectories with 24‐month clinical outcomes after ischemic stroke. Methods and Results A total of 3533 patients with ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) were studied. Distinct trajectories of disability were identified by the group‐based trajectory model, as measured by modified Rankin Scale score within 12 months. Cox proportional hazards regression models were used to examine the associations of disability trajectories with 24‐month cardiovascular events and all‐cause mortality. We identified 4 distinct disability trajectories: no significant disability (562 participants [15.9%]), slight disability to recovery (1575 participants [44.6%]), severe to moderate disability (1087 participants [30.8%]), and persistent severe disability (309 participants [8.7%]). Compared with no significant disability trajectory, the multivariable adjusted hazard ratios (95% CIs) of patients within the persistent heavy–severe trajectory were 2.63 (1.20–5.76) for cardiovascular events, 2.55 (1.12–5.79) for recurrent stroke, and 6.10 (2.22–16.72) for all‐cause mortality; notably, the hazard ratios (95% CIs) for patients within the severe to moderate disability trajectory were 1.99 (1.01–3.94) for cardiovascular events and 1.85 (1.03–3.33) for the composite outcome of cardiovascular events and all‐cause mortality. Conclusions Functional disability trajectories within 12 months after stroke onset were associated with the risk of 24‐month adverse outcomes. Patients with persistent severe disability or severe to moderate disability had higher risk of cardiovascular events and all‐cause mortality. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072

Salmonella is a primary cause of foodborne diseases globally. Despite food contamination and clinical infections garnering substantial attention and research, asymptomatic Salmonella carriers, potential sources of infection, have been comparatively overlooked. In this study, we conducted a comparative analysis of serotype distribution, antimicrobial resistance phenotypes, and genetic profiles of archived Salmonella strains isolated from food (26), asymptomatic carriers (41), and clinical cases (47) in Shiyan City, China. Among the 114 Salmonella strains identified, representing 31 serotypes and 34 Sequence Types (STs), the most prevalent serovars included Typhimurium, Derby, Enteritidis, Thompson, and London, with the most predominant STs being ST11, ST40, ST26, ST34, and ST155. Antimicrobial resistance testing revealed that all strains were only sensitive to meropenem, with 74.6% showing antimicrobial resistance (AMR) and 53.5% demonstrating multidrug resistance (MDR). Strains resistant to five and six classes of antibiotics were the most common. Pearson's chi-square test showed no statistically significant difference in the occurrence of AMR (p = 0.105) or MDR (p = 0.326) among Salmonella isolates from the three sources. Our findings underscore associations and diversities among Salmonella strains isolated from food, asymptomatic carriers, and clinical patients, emphasizing the need for increased vigilance towards asymptomatic Salmonella carriers by authorities.

BackgroundTraditional Chinese medicine (TCM) has been garnering ever-increasing worldwide attention as the herbal extracts and formulas prove to have potency against disease. Fuzhengjiedu San (FZJDS), has been extensively used to treat viral diseases in pigs, but its bioactive components and therapeutic mechanisms remain unclear.MethodsIn this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the mechanisms underlying FZJDS's action in treating porcine reproductive and respiratory syndrome virus (PRRSV). We constructed PPI network and screened the core targets according to their degree of value. GO and KEGG enrichment analyses were also carried out to identify relevant pathways. Lastly, qRT-PCR, flow cytometry and western blotting were used to determine the effects of FZJDS on core gene expression in PRRSV-infected monkey kidney (MARC-145) cells to further expand the results of network pharmacological analysis.ResultsNetwork pharmacology data revealed that quercetin, kaempferol, and luteolin were the main active compounds of FZJDS. The phosphatidylinositol-3-kinase (PI3K)/Akt pathway was deemed the cellular target as it has been shown to participate most in PRRSV replication and other PRRSV-related functions. Analysis by qRT-PCR and western blotting demonstrated that FZJDS significantly reduced the expression of P65, JNK, TLR4, N protein, Bax and IĸBa in MARC-145 cells, and increased the expression of Bcl-2, consistent with network pharmacology results. This study provides that FZJDS has significant antiviral activity through its effects on the PI3K/AKT signaling pathway.ConclusionWe conclude that FZJDS is a promising candidate herbal formulation for treating PRRSV and deserves further investigation.