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Summary: Thymocyte development requires precise control of PI3K-Akt signaling to promote proliferation and prevent leukemia and autoimmune disorders. Here, we show that ablating individual clusters of the miR-17∼92 family has a negligible effect on thymocyte development, while deleting the entire family severely impairs thymocyte proliferation and reduces thymic cellularity, phenocopying genetic deletion of Dicer. Mechanistically, miR-17∼92 expression is induced by Myc-mediated pre-T cell receptor (TCR) signaling, and miR-17∼92 promotes thymocyte proliferation by suppressing the translation of Pten. Retroviral expression of miR-17∼92 restores the proliferation and differentiation of Myc-deficient thymocytes. Conversely, partial deletion of the miR-17∼92 family significantly delays Myc-driven leukemogenesis. Intriguingly, thymocyte-specific transgenic miR-17∼92 expression does not cause leukemia or lymphoma but instead aggravates skin inflammation, while ablation of the miR-17∼92 family ameliorates skin inflammation. This study reveals intricate roles of the miR-17∼92 family in balancing thymocyte development, leukemogenesis, and autoimmunity and identifies those microRNAs (miRNAs) as potential therapeutic targets for leukemia and autoimmune diseases.

BackgroundBetel quid (BQ) chewing is a prevalent habit in the Asian and Pacific regions. It is deeply intertwined within cultural customs, and has been reported to result in oral potentially malignant disorders (OPMDs) and malignant disorders (MDs).ObjectiveWe aim to present a summative and broad overview of the burden that BQ chewing has imposed on the residents of the Southeast Asian, Pacific, and Australasian regions, allowing us to quantify the level of impact it is currently causing on the risk of people developing oral cancer.MethodsThis scoping review and meta-analysis screened databases such as PubMed, MEDLINE, and Google Scholar for publications that investigated the association between BQ and OPMDs and MDs. The search strategy involved MeSH headings relating to BQ, OPMDs, and MDs, and a search for results during the period between January 2010 and June 2023 within the set geographical boundaries of the Southeast Asian and Pacific regions. This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement for Scoping Reviews (PRISMA-ScR). R software was used to screen outliers. The included studies were further analysed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.ResultsNine articles (n = 19,312 participants) presented odds ratio outcomes from 11 regionally different study groups. We indicated a strong correlation between BQ chewing and the increased risk of OMPDs and MDs. The risk was quantified through meta-analyses with an odds ratio (OR) of 8.18 (5.27–12.72) and an increased OR of 9.93 (7.36–13.39) when the outlier was removed. BQ chewing was further identified within various Australian communities and discovered to be produced locally in North Queensland.DiscussionA meta-analysis of two outcomes revealed substantial heterogeneity and minor evidence of publication bias, thus the association effect was included with and without these articles. The overall GRADE quality of evidence ranged from moderate to very high and highlighted five studies with a high level of imprecision.ConclusionThe lingering high prevalence of BQ in the Southeast Asia and Pacific regions, as well as its rising acceptance among non-ethnic Australians, is alarming and requires prompt and rigorous intervention to prevent the risk of oral cancer.Systematic Review RegistrationPROSPERO (CRD42023429694).

As a new engine to promote global economic and social development, information and communication technology (ICT) plays a key role in the field of modern economy. The aim of this paper is to investigate the nexus between ICT and green total factor productivity (GTFP) on a global scale. An extended data envelopment analysis model (DEA), named WINDOWS-US-SBM, was constructed for calculating the GTFP of 65 countries from 2007 to 2019. This paper empirically analyzes the spatial effect and the transmission mechanism of ICT development on GTFP in countries from different income groups. The results show a prominent imbalance between ICT development and GTFP in various countries. ICT can effectively improve GTFP and play a crucial role in lower middle-income countries. The development of ICT can improve GTFP through technological progress, energy intensity, and trade openness. This paper is helpful to provide policy guidance for the development of ICT and give a new perspective of global green development. First published online 20 May 2024

Summary: Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid and oleic acid, respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. We show that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of DsfR that control bacterial virulence as a response regulator of QS signal.

Purpose: The objective of this study was to provide theoretically feasible strategies by understanding the relationship between the immune microenvironment and the diagnosis and prognosis of AML patients. To this end, we built a ceRNA network with lncRNAs as the core and analyzed the related lncRNAs in the immune microenvironment by bioinformatics analysis. Methods: AML transcriptome expression data and immune-related gene sets were obtained from TCGA and ImmPort. Utilizing Pearson correlation analysis, differentially expressed immune-related lncRNAs were identified. Then, the LASSO-Cox regression analysis was performed to generate a risk signature consisting immune-related lncRNAs. Accuracy of signature in predicting patient survival was evaluated using univariate and multivariate analysis. Next, GO and KEGG gene enrichment and ssGSEA were carried out for pathway enrichment analysis of 183 differentially expressed genes, followed by drug sensitivity and immune infiltration analysis with pRRophetic and CIBERSORT, respectively. Cytoscape was used to construct the ceRNA network for these lncRNAs. Results: 816 common lncRNAs were selected to acquire the components related to prognosis. The final risk signature established by multivariate Cox and stepwise regression analysis contained 12 lncRNAs engaged in tumor apoptotic and metastatic processes: LINC02595, HCP5, AC020934.2, AC008770.3, LINC01770, AC092718.4, AL589863.1, AC131097.4, AC012368.1, C1RL-AS1, STARD4-AS1, and AC243960.1. Based on this predictive model, high-risk patients exhibited lower overall survival rates than low-risk patients. Signature lncRNAs showed significant correlation with tumor-infiltrating immune cells. In addition, significant differences in PD-1/PD-L1 expression and bleomycin/paclitaxel sensitivity were observed between risk groups. Conclusion: LncRNAs related to immune microenvironment were prospective prognostic and therapeutic options for AML.

Background The digital transformation of medical data enables health systems to leverage real‐world data from electronic health records to gain actionable insights for improving hypertension care. Methods and Results We performed a serial cross‐sectional analysis of outpatients of a large regional health system from 2010 to 2021. Hypertension was defined by systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or recorded treatment with antihypertension medications. We evaluated 4 methods of using blood pressure measurements in the electronic health record to define hypertension. The primary outcomes were age‐adjusted prevalence rates and age‐adjusted control rates. Hypertension prevalence varied depending on the definition used, ranging from 36.5% to 50.9% initially and increasing over time by ≈5%, regardless of the definition used. Control rates ranged from 61.2% to 71.3% initially, increased during 2018 to 2019, and decreased during 2020 to 2021. The proportion of patients with a hypertension diagnosis ranged from 45.5% to 60.2% initially and improved during the study period. Non‐Hispanic Black patients represented 25% of our regional population and consistently had higher prevalence rates, higher mean systolic and diastolic blood pressure, and lower control rates compared with other racial and ethnic groups. Conclusions In a large regional health system, we leveraged the electronic health record to provide real‐world insights. The findings largely reflected national trends but showed distinctive regional demographics and findings, with prevalence increasing, one‐quarter of the patients not controlled, and marked disparities. This approach could be emulated by regional health systems seeking to improve hypertension care.

Spatial optimization is an interdisciplinary field dedicated to the scientific and rational allocation of resources spatially, which has received tremendous attention across various disciplines including geography, operations research, management science, and computer science. Spatial optimization provides important theoretical foundations and solutions for determining optimal spatial arrangements or configurations of entities, resources, or goods. However, the complexity of spatial optimization problems poses critical challenges in spatial optimization problems modeling, and efficiently solving. Recently, the surge of multi-source geospatial big data, the emerging technologies such as geospatial artificial intelligence (GeoAI), and the advancements of computing technologies along with the ever-expanding capabilities of computer and data storage resources, have created significant opportunities to the effective and efficient addressing of spatial optimization issues, even though numerous challenges still exist. Therefore, this paper aims to revisit the existing literature of spatial optimization quantitatively and qualitatively, as well as reflect on the opportunities and challenges, especially posed by geospatial big data and GeoAI. Through these efforts, we seek to stimulate greater engagement in spatial optimization research and practices, accelerate the integration of novel technologies and methods, as well as collectively advance the development of the field.

Introduction Various approaches are employed to expedite the passage of meconium in preterm infants within the neonatal intensive care unit (NICU), with glycerine enemas being the most frequently used. Due to the potential risk of high osmolality-induced harm to the intestinal mucosa, diluted glycerine enema solutions are commonly used in clinical practice. The challenge lies in the current lack of knowledge regarding the safest and most effective concentration of glycerine enema. This research aims to ascertain the safety of different concentrations of glycerine enema solution in preterm infants.Methods and analysis This study protocol is for a single-centre, two-arm, parallel-group, double-blind and non-inferiority randomised controlled trial. Participants will be recruited from a NICU in a teriary class A hospital in China, and eligible infants will be randomly allocated to either the glycerine (mL): saline (mL) group in a 3:7 ratio or the 1:9 ratio group. The enema procedure will adhere to the standardised operational protocols. Primary outcomes encompass necrotising enterocolitis and rectal bleeding, while secondary outcomes encompass feeding parameters, meconium passage outcomes and splanchnic regional oxygen saturation. Analyses will compare the two trial arms based on an intention-to-treat allocation.Ethics and dissemination This trial is approved by the ethics committee of the Medical Ethics Committee of West China Second University Hospital of Sichuan University. The results will be published in a peer-reviewed journal.Trial registration number ChiCTR2300079199.

This review highlighted the pivotal role of zyxin, an essential cell focal adhesions protein, in cellular biology and various diseases. Zyxin can orchestrate the restructuring and dynamic alterations of the cellular cytoskeleton, which is involved in cell proliferation, adhesion, motility, and gene transcription. Aberrant zyxin expression is closely correlated with tumor cell activity and cardiac function in both tumorigenesis and cardiovascular diseases. Moreover, in fibrotic and inflammatory conditions, zyxin can modulate cellular functions and inflammatory responses. Therefore, a comprehensive understanding of zyxin is crucial for deciphering signal transduction networks and disease pathogenesis. Investigating its role in diseases holds promise for novel avenues in early diagnosis and therapeutic strategies. Nevertheless, targeting zyxin as a therapeutic focal point presents challenges in terms of specificity, safety, drug delivery, and resistance. Nonetheless, in-depth studies on zyxin and the application of precision medicine could offer new possibilities for personalized treatment modalities.

Abstract Lithium‐Sulfur (Li‐S) batteries as the next‐generation battery system have an ultrahigh theoretical energy density. However, the limited conversion of polysulfides in sulfur cathodes deteriorates the performance of Li‐S batteries. In this study, we develop a novel titanium nitride (TiN) catalyst for sulfur cathodes via atomic layer deposition (ALD). The synthesized ALD‐TiN catalyst shows controllable ultrafine particle size (

Intracranial aneurysms (IAs), as a common cerebrovascular disease, claims a worldwide morbidity rate of 3.2%. Inflammation, pivotal in the pathogenesis of IAs, influences their formation, growth, and rupture. This review investigates aspirin's modulation of inflammatory pathways within this context. With IAs carrying significant morbidity and mortality upon IAs rupture and current interventions limited to surgical clipping and endovascular coiling, the quest for pharmacological options is imperative. Aspirin's role in cardiovascular prevention, due to its anti-inflammatory effects, presents a potential therapeutic avenue for IAs. In this review, we examine aspirin's efficacy in experimental models and clinical settings, highlighting its impact on the progression and rupture risks of unruptured IAs. The underlying mechanisms of aspirin's impact on IAs are explored, with its ability examined to attenuate endothelial dysfunction and vascular injury. This review may provide a theoretical basis for the use of aspirin, suggesting a promising strategy for IAs management. However, the optimal dosing, safety, and long-term efficacy remain to be established. The implications of aspirin therapy are significant in light of current surgical and endovascular treatments. Further research is encouraged to refine aspirin's clinical application in the management of unruptured IAs, with the ultimate aim of reducing the incidence of aneurysms rupture.

IntroductionThis meta-analysis aimed to determine the clinical efficacy of acupuncture combined with core muscle exercises on pain and functional status in patients with chronic nonspecific low back pain.MethodsThis study followed the Preferred Reporting Items for Systematic Reviews and meta-analysis criteria for systematic reviews and meta-analyses. Randomized controlled trials published till November 2023 were searched in PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure, Chinese Biomedical Literature, and Wanfang databases. The search strategy was related to disease type, intervention, and control measures and was structured around the search terms “low back pain,” “acupuncture therapy,” and “exercise.” Two reviewers applied inclusion and exclusion criteria. Sensitivity and fixed effects analyses were performed to determine the primary outcomes.ResultsWe included 11 randomized controlled trials (n = 727) on acupuncture combined with core muscle exercises in patients with chronic nonspecific low back pain. Compared with controls, clinical efficacy was significant, with improvements in pain scores (visual analog pain scale and numerical rating scale) and Oswestry Disability Index in the intervention group.DiscussionAcupuncture therapy combined with core muscle exercises improved pain and functional status in patients with chronic nonspecific low back pain, with favorable clinical outcomes compared with single-core muscle training. Multicenter large-sample trials are required to obtain more reliable conclusions.

Introduction: Terrestrial evapotranspiration (ET) over the Tibetan Plateau (TP) has important implications for the global water cycle, climate change, and ecosystem, and its changes and driving factors have drawn increasing attention. Previous research studies have minimally quantified the effects and identified the pathways of the influencing factors on ET over different land surface types.Methods: In this study, we analyze the spatiotemporal distribution and variation of ET over the TP in 1982–2014 based on multiple datasets. Furthermore, the effects of each influencing factor on ET are quantified over different land surface types, and the major influencing factors and their affecting pathways are identified using structure equation modeling (SEM), which is a statistical method used to analyze relationships among multiple variables.Results: The results show that the climatology of ET decreases gradually from southeastern to northwestern TP, with the maximum spatial averaged value of 379.979 ± 0.417 mm a−1 for the fifth generation of European Reanalysis (ERA5) and the minimum of 249.899 ± 0.469 mm a−1 for the Global Land Data Assimilation System (GLDAS). The most significant differences among the ET datasets mainly occur in the summer. The annual ET averaged over the TP presents an increased trend from 1982 to 2014, as shown by all of the ET datasets. However, there are larger discrepancies in the spatial distribution of the increased trend for these datasets. The assessment result shows that the 0.05° land evapotranspiration dataset for the Qinghai–Tibet Plateau (LEDQTP) has the highest temporal correlation coefficient (0.80) and the smallest root-mean-square error (23.50 mm) compared to the observations. Based on LEDQTP, we find that precipitation is the main influencing factor of ET, which primarily affects ET through direct pathways in bare soil and grassland regions, with standardized estimates of 0.521 and 0.606, respectively. However, in meadow and shrub and forest regions, the primary factor influencing ET is air temperature, which is primarily affected by an indirect pathway through a vapor pressure deficit. Air temperature is also the controlling factor in sparse vegetation regions, but it affects ET through a direct pathway.Discussion: This study may provide some new useful information on the effects of climate change on ET in different land cover types over the TP.

Background: Bruck syndrome (BS) is an extremely rare autosomal-recessive connective tissue disorder mainly characterized by bone fragility, congenital joint contracture, and spinal deformity. It is also considered as a rare form of osteogenesis imperfecta (OI) due to features of osteopenia and fragility fractures. Its two forms, BS1 and BS2, are caused by pathogenic variations in FKBP10 and PLOD2, respectively. Objective: We aimed to improve the clinical understanding of BS by presenting a case from China and to identify the genetic variants that led to this case. Methods: OI was suspected in a Chinese boy with a history of recurrent long bone fractures, lumbar kyphosis, and dentinogenesis imperfecta (DI). Whole-exome sequencing (WES) was performed to identify pathogenic variations. Sanger sequencing was used to confirm the results of the WES. In silico analysis was used to predict the pathogenicity of genetic variants. Results: WES and Sanger sequencing revealed a compound heterozygous variation in the FKBP10 gene (NM_021939, c.23dupG in exon 1, and c.825dupC in exon 5). Both variants resulted in a frameshift and premature stop codon. Of these two variants, c.23dupG has not been previously reported. The patient's parents were heterozygous carriers of one variant. In addition, zoledronic acid treatment improved the vertebral deformity and bone mineral density (BMD) significantly in this patient. Conclusions: A novel compound heterozygous variation of FKBP10, c.23dupG/c.825dupC, was identified in a patient with moderately severe OI. Based on these findings, the patient was diagnosed with BS1 without congenital joint contractures or OI type XI. This study expands the spectrum of FKBP10 genetic variants that cause BS and OI.

Study region: The Xilin River Basin in the Inner Mongolia Autonomous Region, China. Study focus: This study aims to identify the components and change patterns of runoff in the basin, and quantitatively assess the impacts of climate change and overgrazing on runoff. Future changes in river basin runoff were simulated under three climate change scenarios. New hydrological insights for the region: This study quantitatively assessed the impacts of climate change and overgrazing on runoff in the Xilin River Basin using the HYPE model and five attribution scenarios. The assessment results are as follows: (1) Monthly runoff in the basin shows typical bimodal characteristics. Snowmelt is the primary contributor to runoff from March to mid-April, while precipitation has the largest contribution in the remaining months. (2) During the growing season, overgrazing has a more significant impact in reducing runoff than climate change, and runoff changes caused by climate change are more complex on a monthly scale than at the annual scale. (3) Among the three development scenarios, SSP126 with low levels of greenhouse gas emissions appeared to be the most suitable for the sustainable and healthy development of the grassland inland river basin.

With the increasing level of automation of autonomous vehicles, it is important to conduct comprehensive and extensive testing before releasing autonomous vehicles into the market. Traditional public road and closed-field testing failed to meet the requirements of high testing efficiency and scenario coverage. Therefore, scenario-based autonomous vehicle simulation testing has emerged. Many scenarios form the basis of simulation testing. Generating additional scenarios from an existing scenario library is a significant problem. Taking the scenarios of a proceeding vehicle cutting into an adjacent lane on highways as an example, based on an autoencoder and a generative adversarial network (GAN), a method that combines Transformer to capture the features of a long-time series, called SceGAN, is proposed to model and generate scenarios of autonomous vehicles on highways. An evaluation system is established to analyze the reliability of SceGAN using discriminative and predictive scores and further evaluate the effect of scenario generation in terms of similarity and coverage. Experiments showed that compared with TimeGAN and AEGAN, SceGAN is superior in data fidelity and availability, and their similarity increased by 27.22% and 21.39%, respectively. The coverage increased from 79.84% to 93.98% as generated scenarios increased from 2,547 to 50,000, indicating that the proposed method has a strong generalization capability for generating multiple trajectories, providing a basis for generating test scenarios and promoting autonomous vehicle testing.

Abstract Background Congenital ectopia lentis is characterized by dislocation of the lens caused by partial or complete abnormalities in the zonular fibers. It can be caused by either systemic diseases or isolated ocular diseases. Gene detection techniques can provide valuable information when an etiological diagnosis is challenging. Herein, we report the case of a six-year-old girl with a confirmed diagnosis of isolated ectopia lentis caused by a compound heterozygous ADAMTSL4 gene mutation. Case presentation The patient was a 6-year-old Chinese Han girl with strabismus in the right eye. Slit lamp examination revealed that the lens in the right eye was opacified and dislocated, without an ectopic pupil. Gene detection demonstrated the presence of a compound heterozygous mutation in the ADAMTSL4 gene [c. 2270dupG (p.Gly758Trpfs *59) and c. 2110A > G (p.Ser704Gly)], and the diagnosis of isolated ectopia lentis was confirmed. She underwent lens extraction, and a sutured scleral-fixated posterior chamber intraocular lens (IOL) was placed in the right eye. The best-corrected visual acuity was 0.1 one month postoperatively. Conclusion Gene detection plays a crucial role in diagnosing disorders with similar symptoms, such as isolated ectopia lentis and Marfan syndrome. In this study, we used whole exons sequencing to diagnose isolated ectopia lentis and identified the variant c.2110A > G (p.Ser704Gly), which may be associated with the development of ectopia lentis and early-onset cataract in the patient. These pathogenic gene mutations have significant implications for the genetic diagnosis of congenital ectopia lentis, treatment, surveillance, and hereditary and prenatal counseling for the patient and their family members.

Abstract In order to reveal the effect of activated carbon (AC) properties on the adsorption of chlorophyll a (Chl a) and chlorophyll b (Chl b) in Andrographis paniculata extract, four commercial activated carbons were first tested and characterized. The results showed that activated carbon 1 (AC1) had the best surface area, pore structure and adsorption capacity. Therefore, adsorption isotherms, adsorption kinetics and adsorption mechanism were further carried out on AC1. The application of Langmuir model (R 2 > 0.978) and Freundlich model (R 2 > 0.977) indicated that the adsorption process of Chl a and Chl b on AC1 may be a complex adsorption process of single-layer and multilayer adsorption. The adsorption kinetics indicated that the pseudo-second-order kinetic model (R 2 > 0.999) was dominant and was mainly chemisorption. The intra-particle diffusion model (R 2 > 0.937) shows that the intra-particle diffusion is the rate-limiting step. The decrease of adsorption of AC1 to Chl a and Chl b due to the oxidation of acrylic acid proves the importance of π–π interaction.

Abstract Background Liver stiffness (LS) is regarded as an indicator of the stages of liver fibrosis and liver cirrhosis. Numerous studies have investigated the relationship between body mass index (BMI) and LS; however, the conclusions remain controversial. In the current study, we utilized transient elastography (TE) technique, which could measure LS in a non-painful and noninvasive way, to explore the relationship between BMI and the risk of elevated LS in common community residents. Methods 5791 participants were included in the present study. To calculate BMI value, height and weight of the participants were carefully measured. Liver stiffness measurement (LSM) > 9.1 kPa was considered as a cutoff suggesting elevated LS. The relationship of BMI and risk of elevated LS was derived using generalized linear regression models, and the threshold effect was then analyzed by smooth curve fitting and segmented regression model. Results Elevated LS was detected in 230 participants (3.97%) using the TE technique. After potential confounders were adjusted according to the individual’s demographic variables, underlying comorbidities and blood biochemical test results, we observed a J-shaped relationship between BMI and the risk of elevated LS, with the inflection point at 23.05 kg/m2. The effect size (and confidence interval) was 0.84 (0.71, 0.98) on the left side of the inflection point, and 1.32 (1.24, 1.41) on the right side of it. Conclusions Our study found a novel J-shaped relationship between BMI and the risk of elevated LS assessed by TE technique. Abnormal BMI, either higher or lower, was associated with an increased risk of elevated LS.

Abstract Background Avian bornavirus (ABV) is a neurotropic virus, it has been established as the primary causative agent of proventricular dilatation disease (PDD). However, substantial international trade and transnational trafficking of wild birds occur, potentially enabling these birds to harbor and transmit pathogens to domestic poultry, adversely affecting their well-being. Real-time RT-PCR was employed to detect the presence of PaBV-4 in parrots imported to China in 2022. Results In 2022, a total of 47 cloacal swabs from 9 distinct species of parrots were collected at the Wildlife Rescue Monitoring Center in Guangdong, China. The purpose of this collection was to detect the presence of PaBV-4. Using real-time PCR techniques, it was determined that the positive rate of PaBV-4 was 2.12% (1 out of 47) in parrots. The PaBV-4 virus was detected in a Amazona aestiva that had been adopted for one month. Conversely, all other species tested negative for the virus. Subsequently, the whole genome of the PaBV-4 GD2207 strains was sequenced, and the homology and genetic evolution between these strains and previously published PaBV-4 strains on GenBank were analyzed using DNAStar and MEGA7.0 software. The findings revealed that the full-length genome of PaBV-4 consisted of 8915 nucleotides and encoded six proteins. Additionally, it exhibited the highest nucleotide similarity (99.9%) to the GZ2019 strain, which causes death and severe clinical symptoms in Aratinga solstitialis. Furthermore, when compared to other strains of PaBV-4, the GD2207 strain demonstrated the highest amino acid homology with GZ2019. The phylogenetic analysis demonstrated that the GD2207 strain clustered with various strains found in Japanese, American, and German parrots, indicating a close genetic relationship with PaBV-4, but it revealed a distant relationship with PaBV-5 Cockg5 from America. Notably, the GD2207 was closely associated with the GZ2019 strain from Aratinga solstitialis in China. Conclusion This study presents the preliminary identification of PaBV-4 in Amazona aestiva parrots, emphasizing its importance as the predominant viral genotype linked to parrot infections resulting from trade into China. Through genetic evolution analysis, it was determined that the GD2207 strain of PaBV-4 exhibits the closest genetic relationship with GZ 2019 (Aratinga solstitialis, China), M14 (Ara macao, USA), AG5 (Psittacus erithacus, USA) and 6758 (Ara ararauna, Germany) suggesting a shared ancestry.

AbstractPerturbation of transcriptome in viral infection patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent transcriptome and identification of robust biomarkers is not complete. In this study, we manually collected 23 datasets related to 6,197 blood transcriptomes across 16 types of respiratory virus infections. We applied a comprehensive systems biology approach starting with whole-blood transcriptomes combined with multilevel bioinformatics analyses to characterize the expression, functional pathways, and protein-protein interaction (PPI) networks to identify robust biomarkers and disease comorbidities. Robust gene markers of infection with different viruses were identified, which can accurately classify the normal and infected patients in train and validation cohorts. The biological processes (BP) of different viruses showed great similarity and enriched in infection and immune response pathways. Network-based analyses revealed that a variety of viral infections were associated with nervous system diseases, neoplasms and metabolic diseases, and significantly correlated with brain tissues. In summary, our manually collected transcriptomes and comprehensive analyses reveal key molecular markers and disease comorbidities in the process of viral infection, which could provide a valuable theoretical basis for the prevention of subsequent public health events for respiratory virus infections.

Abstract HS6ST2 has ability to encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS and a crucial regulator of cell growth, differentiation, adhesion, and migration. Although mounting evidence supports a vital role for HS6ST2 in tumorigenesis of some cancers, no pan-cancer analysis of HS6ST2 has been reported. Therefore, we aimed to explore the prognostic value of HS6ST2 in 33 cancer types and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Lines Encyclopedia, Genotype Tissue Expression, and GSCA, we used a range of bioinformatics approaches to explore the potential carcinogenic role of HS6ST2, analysis of HS6ST2 and prognosis, DNA methylation, RNA methylation, microsatellite instability (MSI), tumor mutation burden (TMB), and immune cell infiltration in different tumors. The results show that HS6ST2 was highly expressed in most cancers but lower in Breast invasive carcinoma, Kidney Chromophobe, Kidney renal clear cell carcinoma, Kidney renal papillary cell carcinoma, and Uterine Corpus Endometrial Carcinoma. Moreover, HS6ST2 is positively or negatively associated with prognosis in different cancers. HS6ST2 expression was not only associated with MSI in 5 cancer types and associated with TMB in 10 cancer types, and it's significantly correlated with DNA methylation in 13 types of cancer, but it's correlated with RNA methylation related genes in most cancer. HS6ST2 expression was correlated with immune cell infiltration, immune-related genes, tumor immune microenvironment, and drug resistance in various cancers. Eventually, HS6ST2 was validated in human lung adenocarcinoma tissues. Our study reveals that HS6ST2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.

Abstract Background Intelligent cardiotocography (CTG) classification can assist obstetricians in evaluating fetal health. However, high classification performance is often achieved by complex machine learning (ML)-based models, which causes interpretability concerns. The trade-off between accuracy and interpretability makes it challenging for most existing ML-based CTG classification models to popularize in prenatal clinical applications. Methods Aiming to improve CTG classification performance and prediction interpretability, a hybrid model was proposed using a stacked ensemble strategy with mixed features and Kernel SHapley Additive exPlanations (SHAP) framework. Firstly, the stacked ensemble classifier was established by employing support vector machines (SVM), extreme gradient boosting (XGB), and random forests (RF) as base learners, and backpropagation (BP) as a meta learner whose input was mixed with the CTG features and the probability value of each category output by base learners. Then, the public and private CTG datasets were used to verify the discriminative performance. Furthermore, Kernel SHAP was applied to estimate the contribution values of features and their relationships to the fetal states. Results For intelligent CTG classification using 10-fold cross-validation, the accuracy and average F1 score were 0.9539 and 0.9249 in the public dataset, respectively; and those were 0.9201 and 0.8926 in the private dataset, respectively. For interpretability, the explanation results indicated that accelerations (AC) and the percentage of time with abnormal short-term variability (ASTV) were the key determinants. Specifically, the probability of abnormality increased and that of the normal state decreased as the value of ASTV grew. In addition, the likelihood of the normal status rose with the increase of AC. Conclusions The proposed model has high classification performance and reasonable interpretability for intelligent fetal monitoring.

Abstract Background Amnestic mild cognitive impairment (aMCI) is considered a prodromal phase of Alzheimer’s disease (AD). However, little is known about the neuropsychological characteristic at pre-MCI stage. This study aimed to investigate which neuropsychological tests could significantly predict aMCI from a seven-year longitudinal cohort study. Methods The present study included 123 individuals with baseline cognitive normal (NC) diagnosis and a 7-year follow-up visit. All the subjects were from the China Longitudinal Aging Study (CLAS) study. Participants were divided into two groups, non-converter and converter based on whether progression to aMCI at follow-up. All participants underwent standardized comprehensive neuropsychological tests, including the mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), auditory verbal learning test (AVLT), the digital span test, the verbal fluency test, the visual recognition test, the WAIS picture completion task, and WAIS block design. Logistic regression analysis was used to evaluate the predictive power of baseline cognitive performance for the transformation of amnestic mild cognitive impairment. Receiver operating characteristic (ROC) curve was used to test the most sensitive test for distinguishing different groups. Results Between the non-converter group and converter group, there were significant differences in the baseline scores of AVLT-delayed recall (AVLT-DR) (8.70 ± 3.61 vs. 6.81 ± 2.96, p = 0.001) and WAIS block design (29.86 ± 7.07 vs. 26.53 ± 8.29, p = 0.041). After controlling for gender, age, and education level, converter group showed lower baseline AVLT-DR than non-converter group, while no significant difference was found in WAIS block design. Furthermore, converter group had lower AVLT-DR score after controlling for somatic disease. The area under the curve of regression equation model was 0.738 (95%CI:0.635–0.840), with a sensitivity 83.9%, specificity of 63.6%. Conclusions Our results proved the value of delayed recall of AVLT in predicting conversion to aMCI. Early and careful checking of the cognitive function among older people should be emphasized.

Abstract Background Age-related hearing loss (ARHL) signifies the bilateral, symmetrical, sensorineural hearing loss that commonly occurs in elderly individuals. Several studies have suggested a higher risk of dementia among patients diagnosed with ARHL. Although the precise causal association between ARHL and cognitive decline remains unclear, ARHL has been recognized as one of the most significant factors that can be modified to reduce the risk of developing dementia potentially. Mild cognitive impairment (MCI) typically serves as the initial stage in the transition from normal cognitive function to dementia. Consequently, the objective of our randomized controlled trial (RCT) is to further investigate whether the use of hearing aids can enhance cognitive function in older adults diagnosed with ARHL and MCI. Methods and design This study is a parallel-arm, randomized controlled trial conducted at multiple centers in Shanghai, China. We aim to enlist a total of 688 older adults (age ≥ 60) diagnosed with moderate-to-severe ARHL and MCI from our four research centers. Participants will be assigned randomly to either the hearing aid fitting group or the health education group using block randomization with varying block sizes. Audiometry, cognitive function assessments, and other relevant data will be collected at baseline, as well as at 6, 12, and 24 months post-intervention by audiologists and trained researchers. The primary outcome of our study is the rate of progression to dementia among the two groups of participants. Additionally, various evaluations will be conducted to measure hearing improvement and changes in cognitive function. Apart from the final study results, we also plan to conduct an interim analysis using data from 12-month follow-up. Discussion In recent years, there has been a notable lack of randomized controlled trials (RCTs) investigating the possible causal relationship between hearing fitting and the improvement of cognitive function. Our findings may demonstrate that hearing rehabilitation can be a valuable tool in managing ARHL and preventing cognitive decline, which will contribute to the development of a comprehensive framework for the prevention and control of cognitive decline. Trial registration Chinese Clinical Trial Registry chictr.org.cn ChiCTR2000036139. Registered on 21 August 2020.

Geobacter grbiciae can grow via coupling oxidation of ethanol to the reduction of various forms of soluble Fe(III) and poorly crystalline Fe(III) oxide, suggesting that G. grbiciae can act as an electron-donor microbe for forming co-cultures through direct interspecies electron transfer (DIET). In this report, potential co-cultures through DIET of G. grbiciae and Methanosarcina barkeri 800, G. sulfurreducens Δhyb, or Methanospirillum hungatei, as electron-acceptor microbes, were examined. Co-cultures of G. grbiciae and G. sulfurreducens Δhyb were performed with ethanol as the sole electron-donor substance and fumarate as the electron-acceptor substance in the presence of granular activated carbon (GAC), magnetite, or polyester felt. The conditions for co-culturing G. grbiciae and M. barkeri 800 (or M. hungatei) were the same as those for G. grbiciae and G. sulfurreducens Δhyb, except fumarate was absent and different cultivation temperatures were used. All co-cultures were anaerobically cultivated. Samples were regularly withdrawn from the co-cultures to monitor methane, fumarate, and succinate via gas or high-performance liquid chromatography. G. grbiciae formed functional co-cultures with M. barkeri 800 in the presence of GAC or magnetite. No co-culture of G. grbiciae with the H2/formate-utilizing methanogen M. hungatei was observed. Additionally, G. grbiciae formed functional co-cultures with H2/formate-un-utilizing G. sulfurreducens Δhyb without the GAC or magnetite supplement. These findings indicate electron transfer between G. grbiciae and M. barkeri 800/G. sulfurreducens Δhyb is via DIET rather than H2/formate, confirming that G. grbiciae acts as an electron-donor microbe. Although the co-cultures of G. grbiciae and M. barkeri 800 syntrophically converted ethanol to methane through DIET, the conversion of propionate or butyrate to methane was not observed. These findings expand the range of microbes that can act as electron donors for interaction with other microbes through DIET. However, propionate and butyrate metabolism through DIET in mixed microbial communities with methane as a product requires further analysis. This study provides a framework for finding new electron-donor microbes.

Abstract Previous studies have demonstrated that bis-(3',5')-cyclic diguanosine monophosphate (bis-3',5'-c-di-GMP) is a ubiquitous second messenger employed by bacteria. Here, we report that 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) controls the important biological functions, quorum sensing (QS) signaling systems and virulence in Ralstonia solanacearum through the transcriptional regulator RSp0980. This signal specifically binds to RSp0980 with high affinity and thus abolishes the interaction between RSp0980 and the promoters of target genes. In-frame deletion of RSp0334, which contains an evolved GGDEF domain with a LLARLGGDQF motif required to catalyze 2',3'-cGMP to (2',5')(3',5')-cyclic diguanosine monophosphate (2',3'-c-di-GMP), altered the abovementioned important phenotypes through increasing the intracellular 2',3'-cGMP levels. Furthermore, we found that 2',3'-cGMP, its receptor and the evolved GGDEF domain with a LLARLGGDEF motif also exist in the human pathogen Salmonella typhimurium. Together, our work provides insights into the unusual function of the GGDEF domain of RSp0334 and the special regulatory mechanism of 2',3'-cGMP signal in bacteria.

Abstract Background Excellent blood glucose management is a key guarantee for successful progress of surgery. However, the impact of clinical pharmacists on blood glucose management of perioperative patients needs to be further investigated. To investigate the effectiveness regarding the participation of pharmacists in blood glucose management via the informatized glucose management system (iGMS) on perioperative patients with type 2 diabetes mellitus (T2DM). Methods The working mode of clinical pharmacists participating in blood glucose management of perioperative patients with diabetes was constructed. A total of 300 patients with T2DM who underwent elective surgery were recruited and divided into a clinical pharmacist management group (intervention group) of 150 patients (94 men and 56 women; mean age: 44.38 ± 14.03 years) and a control group of 150 patients (101 men and 49 women; mean age: 47.85 ± 12.26 years) between September 2019 to April 2020. The outcomes of perioperative blood glucose management, and healthcare indicators such as preoperative waiting time, total hospitalization time, postoperative infection rate and other indicators were analyzed statistically between the two groups. Result In the blood glucose management team of the whole hospital, the physicians, clinical pharmacists and nurses of blood glucose management in endocrinology department were the core members, and were responsible for perioperative blood glucose management of the participants in the intervention group. All subjects had lower blood glucose after 3 days of management compared to the time of admission, and blood glucose was significantly lower in the intervention group compared to the control group (P 0.05). Conclusion The involvement of clinical pharmacists in blood glucose management utilizing the iGMS can control the blood glucose level of patients with T2DM in the perioperative period more stably and effectively, thereby leading to an improvement in the quality of healthcare.

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca2+ ([Ca2+]i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca2+]i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca2+]i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca2+]i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca2+ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca2+]i.

AIM: To explore the risk factors for acute acquired comitant esotropia (AACE). METHODS: A retrospective cohort study was conducted by analyzing 83 patients (case group) with AACE who underwent strabismus correction surgery from January 1, 2021 to June 30, 2022. Totally 73 outpatient volunteers were recruited during the same period as the normal control group. The case group's binocular vision time, near and distance esotropia angle, and near stereo vision function were recorded, and the age, gender, refractive status, and best-corrected visual acuity (BCVA) of both groups were analyzed. Additionally, multiple logistic regression analysis was conducted using an eye usage condition questionnaire to determine the independent risk factors for AACE. RESULTS: In the case group, 61 patients (73.49%) had myopia, with a mean equivalent spherical power (SE) of -3.35±3.31 D (range: +2.75 to -10.62 D) of the right eye and -2.87±3.35 D (range: +2.75 to -11.12 D) of the left eye. The average duration of diplopia in the case group was 29.83±35.72mo, of which 80 patients (96.39%) were primarily with distance diplopia. The near and distance esotropia angle after wearing glasses were 52.36±20.95 prism degree (PD) and 56.71±19.54 PD, respectively, and there was no statistically significant difference between the two (t=1.38, P=0.169). The incidence of improper glasses wearing and unhealthy eye habits in the case group was significantly higher than those in the control group (P

Abstract Aim To analyse the risk factors for falls in vascular patients and methods to mitigate fall risk in hospitalised patients receiving vascular surgery. Design This study is a multicentre, retrospective study. Methods A total of 112 inpatients that underwent vascular surgery in five hospitals in Shanxi Province from April 2018 to April 2022 were selected. They were divided into two groups according to whether they had fallen or not; 56 patients who fell were taken as the observation group and 56 patients who did not fall were taken as the control group. The risk factors of falls were analysed by univariate and logistic regression. Results There was no significant difference between the observation and the control groups in male patients and the incidence of falls without family members. In the observation group, the percentage of patients aged ≥65 years old, with a history of falls and/or fractures, long‐term medications and a history of osteoporosis was higher than in the control group and showed a statistically significant difference. Multivariate logistic regression analysis showed that advanced age, a history of falls and fractures, long‐term medications and a history of osteoporosis were independent risk factors for falls, and the differences were statistically significant. Conclusion Older age, a history of falls and/or fractures, continuous medication for more than 3 months and a history of osteoporosis are the risk factors for falls in hospitalised patients undergoing vascular surgery.

Synovial sarcoma, a rare malignant neoplasm with a poor prognosis, accounts for approximately 5%-10% of all primary soft-tissue malignancies worldwide. Typically affecting adolescents and young adults, it primarily manifests near the joints of the lower extremities. This study aimed to demonstrate that this tumor can also affect the prevertebral space. A 32-year-old male patient presented at our outpatient clinic with a 2-month history of upper limb numbness and a 1-month complaint of palpable neck mass. Imaging studies revealed a bulky, lobulated, and heterogeneous mass exhibiting heterogeneous enhancement. Furthermore, the mass caused expansion of the neuroforamen in the neck, initially suggesting a diagnosis of malignant schwannoma. However, a histopathologic examination suggested synovial sarcoma. The article provided a comprehensive review of the clinical, pathological, and radiological features of this condition. Additionally, it explored current treatment options and prognoses by referencing relevant literature.

Objective: Establish a high throughput method for the determination of 57 organic pollutants in edible vegetable oil. Methods: The target compounds were extracted by acetonitrile-hexane solution and purified by disperse solid phase extraction and solid phase extraction, after that the contents of 16 polycyclic aromatic hydrocarbons, 17 phthalates, 8 organochlorines and 16 polychlorinated biphenyls in edible oil were detected by gas chromatography triple quadrupole mass spectrometry. Results: All target components had an excellent linearity within the linear range of 0.001~0.1 μg/mL （r2＞0.998）, and the limits of detection was between 0.16~2.0 μg/kg, meanwhile the average recovery rate of matrix addition was between 71.0%~119.5%, and the relative standard deviation was below 12.6% （n=6）. Furthermore, the method was used to analyze 24 baches of edible oils, and 25 types of target substances were founded. Conclusion: This method is high efficiency, accuracy, high sensitivity, which has great significance for the monitoring of persistent organic pollutants and phthalates in edible oil.

Abstract Background Hypomethylation of the perforin gene promoter in CD4 + T cells, inflammation and oxidative stress, might be involved in alveolar septal cell apoptosis associated with emphysema in rats. This study aimed to investigate the effects of S-adenosylmethionine (SAM) on this kind of apoptosis in rats with autoimmune emphysema. Methods Twenty-four rats were randomly divided into three groups: a normal control group, a model group, and a SAM group. Pathological changes in lung tissues were observed, and the mean linear intercept (MLI) and mean alveolar number (MAN) were measured. The levels of anti-endothelial cell antibodies (AECA) in serum, alveolar septal cell apoptosis, perforin gene promotor methylation in CD4 + T cells in the spleen, and the levels of cytokines, malondialdehyde (MDA), and glutathione (GSH) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in bronchoalveolar lavage fluid (BALF) were investigated. Results The MLI, apoptosis index (AI) of alveolar septal cells, levels of AECA in serum, and levels of tumour necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9) and MDA in BALF were increased, while the MAN, methylation levels, and the activities of GSH, SOD and GSH-Px in BALF were decreased in the model group compared with those in the normal control group and the SAM group (all P

Abstract Studies considering the relationship between non-obesity-related body composition and lung function are few; therefore, this study aimed to explore these correlations and effects. This cross-sectional study conducted in rural Qingtongxia City and Pingluo County, Ningxia, China, included 776 participants aged 30–75 years. Body composition and lung function were measured using direct segmental multifrequency bioelectrical impedance analysis and a digital spirometer, respectively. Their correlation was assessed using partial correlation analysis, controlling for age and smoking status, and the body composition effect on lung function was analyzed using binomial logistic regression analysis. The body components total body water content, protein content, mineral content, muscle mass, fat-free mass (FFM), skeletal muscle mass, basal metabolic volume, and chest circumference (CC) positively correlated with pulmonary function (forced vital capacity and forced expiratory volume in one second) in both sexes. Neck circumference and hip circumference positively correlated with pulmonary function in women. Additionally, lung function declines more slowly in women (odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.44–0.98, p = 0.04); CC (OR = 0.92, 95% CI = 0.86–0.98, p = 0.01) increased as a protective factor for decreased lung function. Increased waist circumference (OR = 1.04, 95% CI = 1.00–1.09, p = 0.04) was a risk factor for reduced lung function. FFM contains body composition indicators positively correlating with lung function, excluding fat-related body composition. Abdominal obesity increases the risk of decreased lung function.

Abstract As an essential component of the maternal-fetal interface, the placental syncytiotrophoblast layer contributes to a successful pregnancy by secreting hormones necessary for pregnancy, transporting nutrients, mediating gas exchange, balancing immune tolerance, and resisting pathogen infection. Notably, the deficiency in mononuclear trophoblast cells fusing into multinucleated syncytiotrophoblast has been linked to adverse pregnancy outcomes, such as preeclampsia, fetal growth restriction, preterm birth, and stillbirth. Despite the availability of many models for the study of trophoblast fusion, there exists a notable disparity from the ideal model, limiting the deeper exploration into the placental development. Here, we reviewed the existing models employed for the investigation of human trophoblast fusion from several aspects, including the development history, latest progress, advantages, disadvantages, scope of application, and challenges. The literature searched covers the monolayer cell lines, primary human trophoblast, placental explants, human trophoblast stem cells, human pluripotent stem cells, three-dimensional cell spheres, organoids, and placenta-on-a-chip from 1938 to 2023. These diverse models have significantly enhanced our comprehension of placental development regulation and the underlying mechanisms of placental-related disorders. Through this review, our objective is to provide readers with a thorough understanding of the existing trophoblast fusion models, making it easier to select most suitable models to address specific experimental requirements or scientific inquiries. Establishment and application of the existing human placental trophoblast fusion models.