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Abstract Background Postinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI). Methods Male Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF‐β1, p-Smad2, and p-Smad3 levels. Results The administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-β, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group. Conclusions In an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-β1/Smad signaling pathway.

Abstract Background and purpose Nonvalvular atrial fibrillation (NVAF) is a risk factor for stroke. This study was undertaken to determine the influence of NVAF on the mortality and recurrent stroke after a minor stroke event. Methods Data were derived from the Third China National Stroke Registry (CNSR-III) which enrolled 15,166 subjects during August 2015 through March 2018 in China. Patients with minor stroke (NIHSS ≤ 5) within 24 h after onset were included. Clinical outcomes including all-cause mortality, cardiovascular death, recurrent ischemic stroke, and recurrent hemorrhagic stroke were collected. The Cox proportional hazards models were used to determine the association between NVAF and clinical outcomes. Results A total of 4,753 patients were included in our study. Of them, 222 patients had NVAF (4.7%) (mean age, 71.1 years) and 4,531 patients were without AF (95.3%) (mean age, 61.4 years). NVAF was associated with 12-month cardiovascular mortality in both univariate (hazards ratio [HR], 4.13; 95% confidence interval [CI], 1.84 to 9.31; P

Abstract Background The fungal component of the human gut microbiome, also known as the mycobiome, plays a vital role in intestinal ecology and human health. However, the overall structure of the gut mycobiome as well as the inter-individual variations in fungal composition remains largely unknown. In this study, we collected a total of 3363 fungal sequencing samples from 16 cohorts across three continents, including 572 newly profiled samples from China. Results We identify and characterize four mycobiome enterotypes using ITS profiling of 3363 samples from 16 cohorts. These enterotypes exhibit stability across populations and geographical locations and significant correlation with bacterial enterotypes. Particularly, we notice that fungal enterotypes have a strong age preference, where the enterotype dominated by Candida (i.e., Can_type enterotype) is enriched in the elderly population and confers an increased risk of multiple diseases associated with a compromised intestinal barrier. In addition, bidirectional mediation analysis reveals that the fungi-contributed aerobic respiration pathway associated with the Can_type enterotype might mediate the association between the compromised intestinal barrier and aging. Conclusions We show that the human gut mycobiome has stable compositional patterns across individuals and significantly correlates with multiple host factors, such as diseases and host age. Video Abstract

Abstract Background Rehabilitation improves functional recovery in subarachnoid hemorrhage (SAH) patients, and assessing patients for rehabilitation is the first step in this process. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation for patients with SAH. Methods To identify patients hospitalized with SAH and to analyze rehabilitation assessment rates, we used data for 11,234 SAH patients admitted to 861 hospitals from the China Stroke Center Alliance from August 2015 to July 2019. We examined factors for rehabilitation assessment and analyzed the relationship between rehabilitation assessment and outcomes in these patients. Results Among 11,234 patients with SAH, 6,513 (58.0%) were assessed for rehabilitation. Assessed patients had an increased length of stay (mean ± SD days: 17.3 ± 12.5 versus 11.6 ± 10.5, P = 49.4), a higher Glasgow Coma Scale (GCS) score on admission (mean ± SD GCS score: 12.3 ± 3.8 versus 11.8 ± 4.4, P = 12.2), and were more likely to be admitted to the stroke unit (19.6% versus 13.8%, P = 15.6). In multivariable analysis, factors associated with an increased likelihood of a rehabilitation assessment (p

Abstract Background Prioritizing genes that underlie complex brain disorders poses a considerable challenge. Despite previous studies have found that they shared symptoms and heterogeneity, it remained difficult to systematically identify the risk genes associated with them. Methods By using the CAGE (Cap Analysis of Gene Expression) read alignment files for 439 human cell and tissue types (including primary cells, tissues and cell lines) from FANTOM5 project, we predicted enhancer-promoter interactions (EPIs) of 439 cell and tissue types in human, and examined their reliability. Then we evaluated the genetic heritability of 17 diverse brain disorders and behavioral-cognitive phenotypes in each neural cell type, brain region, and developmental stage. Furthermore, we prioritized genes associated with brain disorders and phenotypes by leveraging the EPIs in each neural cell and tissue type, and analyzed their pleiotropy and functionality for different categories of disorders and phenotypes. Finally, we characterized the spatiotemporal expression dynamics of these associated genes in cells and tissues. Results We found that identified EPIs showed activity specificity and network aggregation in cell and tissue types, and enriched TF binding in neural cells played key roles in synaptic plasticity and nerve cell development, i.e., EGR1 and SOX family. We also discovered that most neurological disorders exhibit heritability enrichment in neural stem cells and astrocytes, while psychiatric disorders and behavioral-cognitive phenotypes exhibit enrichment in neurons. Furthermore, our identified genes recapitulated well-known risk genes, which exhibited widespread pleiotropy between psychiatric disorders and behavioral-cognitive phenotypes (i.e., FOXP2), and indicated expression specificity in neural cell types, brain regions, and developmental stages associated with disorders and phenotypes. Importantly, we showed the potential associations of brain disorders with brain regions and developmental stages that have not been well studied. Conclusions Overall, our study characterized the gene-enhancer regulatory networks and genetic mechanisms in the human neural cells and tissues, and illustrated the value of reanalysis of publicly available genomic datasets.

AIM: To evaluate the macular microcirculation changes in patients with diabetic retinopathy(DR)by optical coherence tomography angiography(OCTA), and correlate the risk factors that may affect the macular microcirculation, so as to provide a clinical basis for early screening, diagnosis and therapeutic intervention for DR.METHODS: Retrospective study. A total of 75 patients(75 eyes)with type 2 diabetes mellitus(DM)who came to the ophthalmology outpatient clinic and ward of Xi'an Central Hospital from May to October 2022 were collected, and the DM patients were further divided into non-DR(NDR)group, non-proliferative DR(NPDR)group and proliferative DR(PDR)group, with 28 eyes, 25 eyes and 22 eyes in each group respectively. OCTA was applied to perform a 3mm×3mm blood flow imaging scan of the macular retina to automatically obtain the vascular density(VD)of the superficial retinal macular foveal, the parafoveal(1～3mm), as well as the macular 3mm×3mm and the area of macular foveal avascular zone(FAZ). Furthermore, the alteration of these parameters in patients with different degrees of DR was analyzed.RESULTS: Compared with the NDR group, the VD of the 3mm×3mm superficial retinal capillary(SCP)in the macular region was decreased in both PDR and NPDR group(all P0.05).CONCLUSION: The microcirculation changes in the macular area of DR patients can be monitored by OCTA, and the systemic condition of DR patients is closely related to their macular microcirculation.

Background This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score and renal venous Doppler waveform (RVDW) pattern in predicting acute kidney injury (AKI) in critically ill patients and establish prediction models.Methods This prospective observational study included 234 critically ill patients. Renal ultrasound was measured within 24 h after intensive care unit admission. The main outcome was the highest AKI stage within 5 days after admission according to the Kidney Disease Improving Global Outcomes criteria.Results Patients in the AKI stage 3 group had significantly higher RRI, RVDW pattern and lower PDU score (p

ABSTRACTCross-cohort validation is essential for gut-microbiome-based disease stratification but was only performed for limited diseases. Here, we systematically evaluated the cross-cohort performance of gut microbiome-based machine-learning classifiers for 20 diseases. Using single-cohort classifiers, we obtained high predictive accuracies in intra-cohort validation (~0.77 AUC), but low accuracies in cross-cohort validation, except the intestinal diseases (~0.73 AUC). We then built combined-cohort classifiers trained on samples combined from multiple cohorts to improve the validation of non-intestinal diseases, and estimated the required sample size to achieve validation accuracies of >0.7. In addition, we observed higher validation performance for classifiers using metagenomic data than 16S amplicon data in intestinal diseases. We further quantified the cross-cohort marker consistency using a Marker Similarity Index and observed similar trends. Together, our results supported the gut microbiome as an independent diagnostic tool for intestinal diseases and revealed strategies to improve cross-cohort performance based on identified determinants of consistent cross-cohort gut microbiome alterations.

The impact of intraocular scatter and higher order aberrations (HOAs) on ocular optical quality was investigated. An optical eye model was constructed using the measured ocular aberrations, corneal surfaces, axial length, and scatter fraction, and the impact of HOAs and scatter on modulation transfer functions (MTFs) was studied based on the newly established optical eye model. For uniform intraocular scatter, the monochromatic and polychromatic MTF decreased as the HOAs or scatter fractions increased independently at each spatial frequency, which implied that both were essential for visual quality. In addition, the scatter effect on MTF was more significant for the eye with less HOA. The combined deterioration effect of these two factors on the MTF was less than their summation, suggesting a potential compensatory mechanism between HOAs and scatter.

Abstract DNA methylation plays a crucial role in the survival of bacteriophages (phages), yet the understanding of their genome methylation remains limited. In this study, DNA methylation patterns are analyzed in 8848 metagenome‐assembled high‐quality phages from 104 fecal samples using single‐molecule real‐time sequencing. The results demonstrate that 97.60% of gut phages exhibit methylation, with certain factors correlating with methylation densities. Phages with higher methylation densities appear to have potential viability advantages. Strikingly, more than one‐third of the phages possess their own DNA methyltransferases (MTases). Increased MTase copies are associated with higher genome methylation densities, specific methylation motifs, and elevated prevalence of certain phage groups. Notably, the majority of these MTases share close homology with those encoded by gut bacteria, suggesting their exchange during phage–bacterium interactions. Furthermore, these MTases can be employed to accurately predict phage–host relationships. Overall, the findings indicate the widespread utilization of DNA methylation by gut DNA phages as an evasion mechanism against host defense systems, with a substantial contribution from phage‐encoded MTases.

After the Kigali Amendment (KA) came into effect, HCFC-22 plants are obliged to limit HFC-23 emissions. Therefore, the study of cost-effective mitigation pathways for HFC-23 is important for the sustainable implementation of KA in China and other HCFC-22 producing countries. This study constructed an inventory of HFC-23 by-production, emissions, and abatement for HCFC-22 plants in China from 2006 to 2020, and predicted the costs and climate benefits of HFC-23 abatement in China's compliance with the KA between 2021 and 2060. Results showed that HFC-23 emissions from HCFC-22 plants in China contributed about 60% of the growth in global atmospheric mole fraction of HFC-23 observed by Advanced Global Atmospheric Gases Experiment (AGAGE) from 2007 to 2020. Furthermore, China's cumulative HFC-23 abatement was about 109 kt (1613 Mt CO2-eq) from 2006 to 2019, accounting for 53% of total by-production, which allowed the global atmospheric mole fraction and radiative forcing of HFC-23 in 2020 to avoid an uplift of 9.2 × 10−9 and 1.7 mW m−2, respectively, contributing to climate change mitigation. Under the baseline of the Kigali Amendment, less emission (LE), and resource utilization (RU) scenarios, the cumulative HFC-23 abatement from 2021 to 2060 would be 683 ± 29 kt (10,107 ± 431 Mt CO2-eq), 694 ± 29 kt (10,277 ± 427 Mt CO2-eq), and 702 ± 29 kt (10,385 ± 426 Mt CO2-eq), respectively. The cumulative net abatement costs for the KA, LE, and RU scenarios would be (5.0 ± 0.2) billion, (2.9 ± 0.2) billion, and (−2.7 ± 0.2) billion CNY (2021 prices), respectively. In the future, applying resource utilization technology to reduce HFC-23 emissions can achieve both climate and economic benefits.

Properties of cytidine and adenosine deaminases lead to off-target effects for cytosine base editors (CBEs) and adenine base editors (ABEs). Here the authors report that 25 TadA orthologs could be engineered to generate functional ABEs, CBEs or ACBEs via single/double mutations with minimised off-targets.

Hypercompact CRISPR-Cas12f systems have been engineered to generate miniABEs but these have limitations. Here the authors generate Cas12f-derived miniCBEs and develop miniABEs with improved editing and targeting scopes; they use these to correct pathogenic mutations in cell lines and introduce mutations in vivo.

Studies have shown that human hair keratin (HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secrete nerve growth factor, which promotes neural regeneration. Therefore, HHK with Schwann cells may be a more effective approach to repair nerve defects than HHK without Schwann cells. In this study, we established an artificial nerve graft by loading an HHK skeleton with activated Schwann cells. We found that the longitudinal HHK microfilament structure provided adhesion medium, space and direction for Schwann cells, and promoted Schwann cell growth and nerve fiber regeneration. In addition, interleukin-1β not only activates Schwann cells, but also strengthens their activity and increases the expression of nerve growth factors. Activated Schwann cells activate macrophages, and activated macrophages secrete interleukin-1β, which maintains the activity of Schwann cells. Thus, a beneficial cycle forms and promotes nerve repair. Furthermore, our studies have found that the newly constructed artificial nerve graft promotes the improvements in nerve conduction function and motor function in rats with sciatic nerve injury, and increases the expression of nerve injury repair factors fibroblast growth factor 2 and human transforming growth factor B receptor 2. These findings suggest that this artificial nerve graft effectively repairs peripheral nerve injury.

Abstract Noninvasive prenatal diagnosis (NIPD) aims to detect fetal-related genetic disorders before birth by detecting markers in the peripheral blood of pregnant women, holding the potential in reducing the risk of fetal birth defects. Fetal-nucleated red blood cells (fNRBCs) can be used as biomarkers for NIPD, given their remarkable nature of carrying the entire genetic information of the fetus. Here, we review recent advances in NIPD technologies based on the isolation and analysis of fNRBCs. Conventional cell separation methods rely primarily on physical properties and surface antigens of fNRBCs, such as density gradient centrifugation, fluorescence-activated cell sorting, and magnetic-activated cell sorting. Due to the limitations of sensitivity and purity in Conventional methods, separation techniques based on micro-/nanomaterials have been developed as novel methods for isolating and enriching fNRBCs. We also discuss emerging methods based on microfluidic chips and nanostructured substrates for static and dynamic isolation of fNRBCs. Additionally, we introduce the identification techniques of fNRBCs and address the potential clinical diagnostic values of fNRBCs. Finally, we highlight the challenges and the future directions of fNRBCs as treatment guidelines in NIPD. Graphical Abstract

Abstract Evaluating the quality of metagenomic assemblies is important for constructing reliable metagenome-assembled genomes and downstream analyses. Here, we present metaMIC ( https://github.com/ZhaoXM-Lab/metaMIC ), a machine learning-based tool for identifying and correcting misassemblies in metagenomic assemblies. Benchmarking results on both simulated and real datasets demonstrate that metaMIC outperforms existing tools when identifying misassembled contigs. Furthermore, metaMIC is able to localize the misassembly breakpoints, and the correction of misassemblies by splitting at misassembly breakpoints can improve downstream scaffolding and binning results.

AIM: To gather baseline data on visual acuity by screening students from different stages in the same administrative district of Xi'an, as well as to analyze and investigate disparities in myopia rates among students from different stages in this area.METHODS: A total of 13 707 students from 21 elementary schools, 3 middle schools, 3 general high schools and 1 vocational high school were randomly selected for uncorrected distance visual acuity and computerized refraction testing in 28 schools with a random sampling approach.RESULTS: The detection rate of myopia in elementary, middle, high and vocational high schools in the same region of Xi'an were 32.27%, 72.07%, 81.22% and 65.12%, respectively; The total myopia rate of students was 47.81%; The myopia rate of girls was higher than that of boys in all grades; The myopia rates of elementary and middle schools increased with the growth of grades; The percentage of high myopia increased from 2.40% in elementary schools to 16.51% in high schools with the growth of grades.CONCLUSION: The myopia rate in different stages of the same region is different, and it tends to rise with the gronth of grades; Girls have a higher myopia rate than boys; Compared to the results of the national survey on myopia in different grades of children and adolescents in 2018, the myopia rate in the same region has decreased significantly in 2021 of the elementary school level, although myopia rate of middle school and high school stage do not rise, the decline is not obvious.

With the Kigali Amendment (KA) coming into effect in China, the control of hydrofluorocarbons (HFCs) emissions has become more imperative. The mobile air-conditioning (MAC) sector is one of the important HFCs consumer sectors, and therefore studying its feasible mitigation paths and costs is of great significance to China's successful implementation of KA. This study used the bottom-up method with updated emission factors to re-evaluate the emission inventory of HFCs from the MAC sector in China from 2005 to 2020. The average annual growth rate of HFCs consumption in the MAC sector is 9.8%, and HFCs emissions have increased from 5.8 (5.3–6.2) kt in 2005 to 22.2 (20.6–23.8) kt in 2020, with an average annual growth rate of 8.8%. Using the Gompertz model combined with the Weibull function of vehicle survival rate, the ownership and new registrations of internal combustion engine vehicles (ICEVs) and electric vehicles (EVs) in China are predicted. The ownership of ICEVs and EVs is projected to be 310 million and 91 million in 2030, respectively and 2 million and 641 million in 2060, respectively. HFCs emissions in the MAC sector would reach 59.8 (55.3–64.3) kt (80.0–93.0 Mt CO2-eq) in 2060 if without any control measure. To implement the KA, the cumulative of 1.6 Gt CO2-eq emissions would be reduced. Under the other two accelerated mitigation scenarios, the MAC sector's HFCs will reach their emissions peak in 2028 and 2025 and achieve zero emissions in 2050 and 2046, respectively. Under the accelerated mitigation with recovery scenario, the cumulative emissions are only 15.0% of the business as usual (BAU) scenario. Using HFO-1234yf as the substitute, the unit abatement cost of the MAC sector is 27.3–37.4 USD t−1 CO2-eq.

Abstract Background Alzheimer’s disease (AD), a progressive neurodegenerative disease, is the most common cause of dementia worldwide. Accumulating data support the contributions of the peripheral immune system in AD pathogenesis. However, there is a lack of comprehensive understanding about the molecular characteristics of peripheral immune cells in AD. Methods To explore the alterations of cellular composition and the alterations of intrinsic expression of individual cell types in peripheral blood, we performed cellular deconvolution in a large-scale bulk blood expression cohort and identified cell-intrinsic differentially expressed genes in individual cell types with adjusting for cellular proportion. Results We detected a significant increase and decrease in the proportion of neutrophils and B lymphocytes in AD blood, respectively, which had a robust replicability across other three AD cohorts, as well as using alternative algorithms. The differentially expressed genes in AD neutrophils were enriched for some AD-associated pathways, such as ATP metabolic process and mitochondrion organization. We also found a significant enrichment of protein-protein interaction network modules of leukocyte cell-cell activation, mitochondrion organization, and cytokine-mediated signaling pathway in neutrophils for AD risk genes including CD33 and IL1B. Both changes in cellular composition and expression levels of specific genes were significantly associated with the clinical and pathological alterations. A similar pattern of perturbations on the cellular proportion and gene expression levels of neutrophils could be also observed in mild cognitive impairment (MCI). Moreover, we noticed an elevation of neutrophil abundance in the AD brains. Conclusions We revealed the landscape of molecular perturbations at the cellular level for AD. These alterations highlight the putative roles of neutrophils in AD pathobiology.

In order to mitigate the impact of supply interruption on enterprises,a dual objective closed-loop supply chain network model considering fuzzy pricing and interruption risk under competitive environment is proposed.The uncertain demand is defined as the price function provided to customers by the supply chain and its competitors,so that the supply chain can maximize the total profit and minimize the carbon emission in the competitive environment.In this paper,the proposed model is solved based on the possibility theory,and the dual-objective model is transformed into a single-objective model.Finally,a real case is used for numerical example analysis.The conclusion shows that the proposed model can not only enhance the ability of supply chain to resist risks,but also help to improve the strategic position in market.

Highlights 1. Female patients with HCM showed worse LV remodeling with a higher indexed LV mass and a smaller indexed LV end-diastolic volume (measured by CMR) at the time of ASA. 2. Both men and women exhibited the LV reverse remodeling, however, men experienced more favorable LV reverse remodeling than women after ASA. The overall percentage of the LVM index regression was greater among men than women. 3. Women with HCM had worse relative composite endpoint than men. Sex and LV mass preablation were independent predictors of cardiovascular outcomes. 4. Sex appears to be a significant modifier in HCM patients receiving ASA treatment and highlighted the need for a different approach to women with HCM, such as improving women’s awareness of diagnosis and follow-up management as well as earlier referral for advanced therapies (e.g., septal reduction therapy and ICD implantation).

Abstract Introduction A high residual risk of subsequent stroke suggested that the predictive ability of Stroke Prognosis Instrument‐II (SPI‐II) and Essen Stroke Risk Score (ESRS) may have changed over the years. Aim To explore the predictive values of the SPI‐II and ESRS for 1‐year subsequent stroke risk in a pooled analysis of three consecutive national cohorts in China over 13 years. Results In the China National Stroke Registries (CNSRs), 10.7% (5297/50,374) of the patients had a subsequent stroke within 1 year; area under the curve (AUC) of SPI‐II and ESRS was .60 (95% confidence interval [CI]: .59–.61) and .58 (95% CI: .57–.59), respectively. For SPI‐II, the AUC was .60 (95% CI: .59–.62) in CNSR‐I, .60 (95% CI: .59–.62) in CNSR‐II, and .58 (95% CI: .56–.59) in CNSR‐III over the past 13 years. The declining trend was also found in ESRS scale (CNSR‐I: .60 [95% CI: .59–.61]; CNSR‐II: .60 [95% CI: .59–.62]; and CNSR‐III: .56 [95% CI: .55–.58]). Conclusions The predictive power of the traditional risk scores SPI‐II and ESRS was limited and gradually decreased over the past 13 years, thus the scales may not be useful for current clinical practice. Further derivation of risk scales with additional imaging features and biomarkers may be warranted.

Aging is a biological process of progressive deterioration of physiological functions, which poses a serious threat to individual health and a heavy burden on public health systems. As population aging continues, research into anti-aging drugs that prolong life and improve health is of particular importance. In this study, the polysaccharide from stems and leaves of Chuanminshen violaceum was obtained with water extraction and alcohol precipitation, and then separated and purified with DEAE anion exchange chromatography and gel filtration to obtain CVP-AP-I. We gavaged natural aging mice with CVP-AP-I and performed serum biochemical analysis, histological staining, quantitative real-time PCR (qRT-PCR) and ELISA kit assays to analyze inflammation and oxidative stress-related gene and protein expression in tissues, and 16SrRNA to analyze intestinal flora. We found that CVP-AP-I significantly improved oxidative stress and inflammatory responses of the intestine and liver, restored the intestinal immune barrier, and balanced the dysbiosis of intestinal flora. In addition, we revealed the potential mechanism behind CVP-AP-I to improve intestinal and liver function by regulating intestinal flora balance and repairing the intestinal immune barrier to regulate the intestinal-liver axis. Our results indicated that C. violaceum polysaccharides possessed favorable antioxidant, anti-inflammatory and potentially anti-aging effects in vivo.

Abstract One‐step deposition approaches have been widely applied and developed in the fabrication of quasi‐2D perovskites. However, the regulation of quantum wells (QWs) and crystalline orientation is difficult and complicated when using this methodology. Sequential deposition is another widespread synthetic approach for preparing perovskite films and perovskite dimension engineering. In this article, δ‐CsPbI3 intermediate phase assisted sequential (IPAS) deposition is successfully carried out to fabricate MA‐free quasi‐2D ACI perovskites. The amount of the δ‐CsPbI3 intermediate phase in the PbI2 layer and the concentration of GAI molecule in the IPA solution both play important roles in the production of MA‐free quasi‐2D ACI perovskite films. The n value of the MA‐free quasi‐2D ACI perovskites can be adjusted, which affects the photovoltaic performance and device stability. Compared with one‐step deposition, the MA‐free quasi‐2D ACI perovskites prepared via IPAS deposition have opposite reverse‐graded QW distribution and improved vertical orientation, leading to a remarkable PEC of up to 18.86% and allowing the preparation of unpackaged devices with prominent working stability (80%, ~400 h). The underlying mechanism and crystallization pathway of IPAS deposition confirm that sequential deposition has unique superiority in regulating the QW distribution and crystalline orientation of quasi‐2D perovskites.

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

Abstract Background Computer-assisted preoperative planning, combined with PSI has become an effective technique for treating complex limb deformities. The purpose of this study was to evaluate the efficacy and safety of the novel technique in corrective osteotomy for intra-articular varus ankle deformities associated with osteoarthritis and ankle instability. Methods Nineteen patients with intra-articular varus ankle arthritis were reviewed between April 2017 and June 2019, including ten men and nine women with a mean age of 58.3 ± 9.9 years (range, 38 to 76 years). All patients underwent intra-articular opening wedge osteotomy assisted by 3D virtual planning and PSI. Weight-bearing radiographs were used to assess the radiographic results, including TAS angle, TT angle, TMM angle, TC angle, TLS angle, opening-wedge angle, and wedge height. Functional outcomes were assessed by the AOFAS score, VAS score, and ROM of the ankle. Results The average follow-up time was 32.2 ± 9.0 months (range, 22 to 47 months). The average union time was 4.4 ± 0.9 months (range, 3.0 to 6.5 months). The TAS angle significantly changed from 84.1 ± 4.6° preoperatively to 87.7 ± 3.1° at the 1-year follow-up and 86.2 ± 2.6° at the latest follow-up. Similarly, the TT angle, TMM angle and TC angle changed significantly at the 1-year follow-up compared with the preoperative assessment and remained stable until the last follow-up. However, the TLS was not corrected significantly. The postoperative obtained opening-wedge angle, and wedge height showed no significant change with preoperative planning. The overall complication rate was 15.8%. The mean VAS score improved from 5.3 ± 0.6 to 2.7 ± 0.7. The mean AOFAS score improved from 56.2 ± 7.6 to 80.6 ± 4.6. However, the ROM showed no significant change. Conclusions Accurate correction and satisfactory functional recovery were attained with computer-assisted planning and PSI in the corrective osteotomy of intra-articular varus ankle deformities.

Fecal microbiota transplantation (FMT) of human fecal samples into germ-free (GF) mice is useful for establishing causal relationships between the gut microbiota and human phenotypes. However, due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms, it may not be possible to replicate human phenotypes in mice through FMT; similarly, treatments that are effective in mouse models may not be effective in humans. In this study, we aimed to identify human gut microbes that undergo significant and consistent changes (i.e., in relative abundances) after transplantation into GF mice in multiple experimental settings. We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota profiles from 1713 human–mouse pairs. Strikingly, on average, we found that only 47% of the human gut microbes could be re-established in mice at the species level, among which more than 1/3 underwent significant changes (referred to as “variable taxa”). Most of the human gut microbes that underwent significant changes were consistent across multiple human–mouse pairs and experimental settings. Consequently, about 1/3 of human samples changed their enterotypes, i.e., significant changes in their leading species after FMT. Mice fed with a controlled diet showed a lower enterotype change rate (23.5%) than those fed with a noncontrolled diet (49.0%), suggesting a possible solution for rescue. Most of the variable taxa have been reported to be implicated in human diseases, with some recognized as the causative species. Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes, provide useful information for researchers using mice in gut microbiota studies, and call for additional validations after FMT. An online database named FMT-DB is publicly available at http://fmt2mice.humangut.info/#/.

Abstract Background The accumulation of advanced glycation end products (AGEs) occurring in skin tissues can be measured by AGE Reader. Here, we assessed the correlation between AGEs values and the development of type 2 diabetic peripheral neuropathy (DPN). Methods The basic clinical information of 560 patients with T2DM was collected through an electronic system. AGEs and diabetic complication risk score was measured by AGE Reader, a non-invasive optical signal detector. All of the participants were classified into 4 groups based on Dyck criteria: grade 0 (non-DPN group), grade 1 (early stage group), grade 2 (middle stage group) and grade 3 (advanced group). Pearson correlation analysis and Spearman correlation analysis were used to evaluate the correlation between AGEs and other indexes. The sensitivity and specificity of glycosylated products were evaluated by ROC curve. Results With the increase of DPN severity, the accumulative AGEs showed an increasing trend. Significant differences (P = 0.000) of AGEs were found among grades 0, 1, 2, and 3 of DPN, and significant differences (P = 0.000) of AGEs were found between grades 1 and 3. There were significant differences in DPN risk score between grades 0, 1, 2, and 3, between grades 1, 2, and 3, and between grades 2 and 3 (P

Here, the authors present SemiBin, a siamese deep neural network framework that incorporates information from reference genomes, able to extract better metagenome-assembled genomes (MAGs) in several host-associated and environmental habitats.

Abstract Inhibition of hypoxia‐induced cardiomyocyte apoptosis is considered as an important treatment method for ischemic heart diseases, but related drugs are still insufficient. The present study aims to explore the protective function and mechanism of the key Chinese medicine monomer diosmetin (DIOS) on the injury of cardiomyocytes induced by hypoxia. Here, AC16 and HCM‐a cells were treated with 40 μM of DIOS under hypoxic environment and a hypoxic rat model was built to study the role of DIOS. The viability and autophagy of cardiomyocytes were increased, but the apoptosis of cells was suppressed by 40 μM DIOS, under hypoxic environment. Intriguingly, 10 mM 3‐methyladenine, an inhibitor of autophagy, reversed the effect of DIOS on autophagy and apoptosis of the cardiomyocytes under hypoxia. Furthermore, DIOS induced AMP‐activated protein kinase (AMPK) activation and Compound C (5 μM), an AMPK inhibitor, attenuated the inhibition of DIOS on the apoptosis of cardiomyocytes under hypoxia environment. In isoprenaline‐induced hypoxic rats, it was verified that DIOS inhibited apoptosis, accelerated autophagy, and activated AMPKα pathway in vivo. Our findings indicated that DIOS alleviated hypoxia‐induced myocardial apoptosis via inducing the activation of AMPK‐induced autophagy. In summary, the study suggested that DIOS inhibited the apoptosis and induced the autophagy of hypoxia‐induced cardiomyocytes through AMPK activation.

Abstract Bean pod mottle virus (BPMV) is a destructive virus that causes serious economic losses in many countries every year, highlighting the importance of its effective detection. In this study, we developed a fast reverse transcription-cross-priming amplification (RT-CPA) coupled with lateral flow dipstick (LFD) diagnostic method for BPMV detection. The RT-CPA-LFD assay that targets the coat protein gene of BPMV was highly specific against diagnosing four other common viruses transmitted by soybean seeds, i.e., Southern bean mosaic virus (SBMV), Tomato ringspot virus (ToRSV), Arabis mosaic virus (ArMV), and Tobacco ringspot virus (TRSV). The sensitivities of the real-time fluorescent RT-CPA and the RT-CPA-LFD assay were at least 50 pg/μl and 500 pg/μl, respectively. Despite a compromise in the limit of detection of the RT-CPA method compared with TaqMan-MGB real-time RT-PCR, our results demonstrated a notably better performance in the detection of field samples of BPMV-infested soybean seeds. With the advantages of efficiency and convenience by visual determination, the RT-CPA-LFD assay presents a potential application for the rapid and accurate detection of BPMV in routine tests.

Exogenous insulin therapy is the mainstay treatment for Type-1 diabetes (T1D) caused by insulin deficiency. A fine-tuned insulin supply system is important to maintain the glucose homeostasis. In this study, we present a designed cell system that produces insulin under an AND gate control, which is triggered only in the presence of both high glucose and blue light illumination. The glucose-sensitive GIP promoter induces the expression of GI-Gal4 protein, which forms a complex with LOV-VP16 in the presence of blue light. The GI-Gal4:LOV-VP16 complex then promotes the expression of UAS-promoter-driven insulin. We transfected these components into HEK293T cells, and demonstrated the insulin was secreted under the AND gate control. Furthermore, we showed the capacity of the engineered cells to improve the blood glucose homeostasis through implantation subcutaneously into Type-1 diabetes mice.

BackgroundThe use of low-dose aspirin for women with twin pregnancies remains controversial. This study was to describe the frequency of preeclampsia and aspirin use in twin pregnancies in real practice.MethodsThis retrospective cohort study based on real-world data was conducted in the Obstetrics and Gynecology Hospital of Fudan University between 2013 and 2020. Women with twin pregnancies who received prenatal care before 20 weeks of gestational age were included. They were divided into those using low-dose aspirin (LDA group) and those not using aspirin group (N-LDA group). The primary outcome was the frequency of preeclampsia, and secondary outcomes included early-onset and preterm mild and severe preeclampsia.ResultsA total of 2,946 women had twin pregnancies, and 241 were excluded due to missing information. Of 2,705 eligible women, 291 (10.75%) were administered aspirin and the other 2,414 (89.25%) did not. The patients in the LDA group were significantly more likely to be older, have a higher rate of use of ART, have a previous history of hypertension, and have gestational diabetes (p < 0.05). In the LDA group, aspirin compliance ≥50% was relatively low (14.43%, 42/291). Preeclampsia occurred in 106 of 291 participants (36.43%) in the LDA group, as compared to 449 of 2,411 (18.62%) in the N-LDA group (OR: 2.15, 95% CI: 1.62–2.82; p < 0.01). The association was confirmed (OR: 1.74, 95% CI: 1.26–2.4; p < 0.01) in the 1:2 case-matched analysis. Higher odds of ratio in the LDA group were demonstrated (aORs > 1, p < 0.01), except for early-onset and preterm mild preeclampsia (p > 0.05). This association was confirmed in a subgroup analysis of methods of conception (aORs ≥ 1, p > 0.05).ConclusionAspirin prescription of 75 to 100 mg in twin pregnancies was associated with no significant reduction of preeclampsia, which may be due to poor compliance with the aspirin used. Further randomized controlled or prospective cohort studies are required.

Abstract When the soft rock roadway in underground mine is supported by steel frame, the bearing capacity of steel structure is the key to the success of roadway support. Taking the soft rock roadway support in Mengnuo lead‐zinc mine as an example, this paper studies the displacement and stress change law of U‐shaped steel, I‐shaped steel, rail steel, and surrounding rock, analyzes the bearing capacity characteristics of steel structure support, and conducts field application tests. The results show that: (a) the deformation resistance of U‐shaped steel is the best, the overall deformation of which is 85.0% of that of track steel, followed by that of I‐shaped steel, which is 92% of that of track steel, and the deformation resistance of track steel is the weakest in comparison; (b) the main stress positions of the three kinds of supporting steel structures are the joint of the support shoulder and the waist. When simulating the support of 10 m roadway, the deformation of the middle 4‐6 m roadway is larger than that of the surrounding rock of the head and tail roadway; (c) when the horizontal stress of the deep soft rock roadway is larger, the floor heave of the roadway is larger than that of the shallow roadway only when the side and top support are used; (d) by the analysis of three different forms and stress states of support steel structures, it is found that the shape of support has a great impact on the bearing mechanical characteristics. It is of great value to study the shape of support with more bearing advantages under the same amount of steel.

Objective To investigate the efficacy of modified percutaneous Achilles tendon lengthening for severe ankle joint deformity. Methods This retrospective case series study included 33 patients with an average age of 25.2 years who underwent surgery in our hospital from April 1, 2010 to March 1, 2018. Triple hemisection percutaneous Achilles tendon lengthening was performed. One stage surgery, other soft tissue surgery or bone correction surgery could be performed. After surgery, a plaster cast was used to fix the functional position, and rehabilitation training was carried out as planned. Complications during the perioperative period were recorded. Statistical analysis of the patients' visual analogue scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) score before and at the last follow‐up was performed. The recurrence rate of Achilles tendon contracture at the last follow‐up and the patients' satisfaction rate were investigated. Results All patients were followed up, with an average follow‐up period of 56.31 months (8–104 months). All achieved good ankle joint function and appearance improvement And there were no infection or skin necrosis complications. In two cases, the incision was poorly healed at non‐Achilles tendon site and was cured by change of dressing. The average VAS score at the last follow‐up was reduced from (2 ± 1.48) points before surgery to (0.26 ± 0.51) points (P = 0.001), and the average AOFAS score was increased from (64.97 ± 13.56) points before surgery to (90.06 ± 10.06) points (P = 0.001). During the follow‐up period, there was no chronic rupture of Achilles tendon. There were two cases of recurrence of foot drop (5.7%), and the patients' satisfaction rate was 93.9%. Conclusion In the surgical treatment of severe ankle joint deformity, the application of triple hemisection percutaneous Achilles tendon lengthening for Achilles tendon contracture has the advantages of less trauma, beautiful incision, and reliable efficacy. The satisfaction rate of patients with this treatment is high, and it is worth promoting in the clinic.

Rib fracture is the most common injury in chest trauma. Most of patients with rib fractures were treated conservatively, but up to 50% of patients, especially those with combined injury such as flail chest, presented chronic pain or chest wall deformities, and more than 30% had long-term disabilities, unable to retain a full-time job. In the past two decades, surgery for rib fractures has achieving good outcomes. However, in clinic, there are still some problems including inconsistency in surgical indications and quality control in medical services. Before the year of 2018, there were 3 guidelines on the management of regional traumatic rib fractures were published at home and abroad, focusing on the guidance of the overall treatment decisions and plans; another clinical guideline about the surgical treatment of rib fractures lacks recent related progress in surgical treatment of rib fractures. The Chinese Society of Traumatology, Chinese Medical Association, and the Chinese College of Trauma Surgeons, Chinese Medical Doctor Association organized experts from cardiothoracic surgery, trauma surgery, acute care surgery, orthopedics and other disciplines to participate together, following the principle of evidence-based medicine and in line with the scientific nature and practicality, formulated the Chinese consensus for surgical treatment of traumatic rib fractures (STTRF 2021). This expert consensus put forward some clear, applicable, and graded recommendations from seven aspects: preoperative imaging evaluation, surgical indications, timing of surgery, surgical methods, rib fracture sites for surgical fixation, internal fixation method and material selection, treatment of combined injuries in rib fractures, in order to provide guidance and reference for surgical treatment of traumatic rib fractures.

Shockwaves from fuel-air explosive (FAE) cloud explosions may cause significant casualties. The ground overpressure field is usually used to evaluate the damage range of explosion shockwaves. In this paper, a finite element model of multi-sources FAE explosion is established to simulate the process of multiple shockwaves propagation and interaction. The model is verified with the experimental data of a fourfold-source FAE explosion, with the total fuel mass of 340 kg. Simulation results show that the overpressure fields of multi-sources FAE explosions are different from that of the single-source. In the case of multi-sources, the overpressure fields are influenced significantly by source scattering distance and source number. Subsequently, damage ranges of overpressure under three different levels are calculated. Within a suitable source scattering distance, the damage range of multi-sources situation is greater than that of the single-source, under the same amount of total fuel mass. This research provides a basis for personnel shockwave protection from multi-sources FAE explosion.

Abstract Background Multimorbidities greatly increase the global health burdens, but the landscapes of their genetic risks have not been systematically investigated. Methods We used the hospital inpatient data of 385,335 patients in the UK Biobank to investigate the multimorbid relations among 439 common diseases. Post-GWAS analyses were performed to identify multimorbidity shared genetic risks at the genomic loci, network, as well as overall genetic architecture levels. We conducted network decomposition for the networks of genetically interpretable multimorbidities to detect the hub diseases and the involved molecules and functions in each module. Results In total, 11,285 multimorbidities among 439 common diseases were identified, and 46% of them were genetically interpretable at the loci, network, or overall genetic architecture levels. Multimorbidities affecting the same and different physiological systems displayed different patterns of the shared genetic components, with the former more likely to share loci-level genetic components while the latter more likely to share network-level genetic components. Moreover, both the loci- and network-level genetic components shared by multimorbidities converged on cell immunity, protein metabolism, and gene silencing. Furthermore, we found that the genetically interpretable multimorbidities tend to form network modules, mediated by hub diseases and featuring physiological categories. Finally, we showcased how hub diseases mediating the multimorbidity modules could help provide useful insights for the genetic contributors of multimorbidities. Conclusions Our results provide a systematic resource for understanding the genetic predispositions of multimorbidities and indicate that hub diseases and converged molecules and functions may be the key for treating multimorbidities. We have created an online database that facilitates researchers and physicians to browse, search, or download these multimorbidities ( https://multimorbidity.comp-sysbio.org ).

Abstract. Background:. Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established. Methods:. A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set. Results:. The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613–0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635–0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865–0.917). It had an AUC of 0.888 (95% CI: 0.842–0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509–0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544–0.675) (P

Summary: Background: Subjective or objective subtle cognitive decline (SCD) is considered the preclinical manifestation of Alzheimer's disease (AD), which is a potentially crucial window for preventing or delaying the progression of the disease. Methods: To explore the potential mechanism of disease progression and identify relevant biomarkers, we comprehensively assessed the peripheral blood transcriptomic alterations in SCD, covering lncRNA, mRNA, and miRNA. Findings: Dysregulated protein-coding mRNA at both gene and isoform levels implicated impairment in the type I interferon signaling pathway in SCD. Specifically, this pathway was regulated by the transcription factor STAT1 and ncRNAs NRIR and has-miR-146a-5p. The miRNA-mRNA-lncRNA co-expression network revealed hub genes for the interferon module. Individuals with lower interferon signaling activity and lower expression of a hub gene STAT1 exhibited a higher conversion rate to mild cognitive impairment (MCI). Interpretation: Our findings illustrated the down-regulation of interferon signaling activity would potentially increase the risk of disease progression and thus serve as a pre-disease biomarker. Funding: This work was partly supported by National Key R&D Program of China (2020YFA0712403), National Natural Science Foundation of China (61932008), Shanghai Municipal Science and Technology Major Project (2018SHZDZX01), the 111 Project (No. B18015) of China, Greater Bay Area Institute of Precision Medicine (Guangzhou) (Grand No. IPM21C008), Natural Science Foundation of Shanghai (21ZR1403200), and Shanghai Center for Brain Science and Brain-Inspired Technology.

In this study, three acidic polysaccharides from different plant parts of Codonopsis pilosula var. Modesta (Nannf.) L. T. Shen were obtained by ion exchange chromatography and gel filtration chromatography, and the yields of these three polysaccharides were different. According to the preliminary experimental results, the antioxidant activities of the polysaccharides from rhizomes and fibrous roots (CLFP-1) were poor, and was thus not studied further. Due to this the structural features of polysaccharides from roots (CLRP-1) and aerial parts (CLSP-1) were the object for this study and were structurally characterized, and their antioxidant activities were evaluated. As revealed by the results, the molecular weight of CLRP-1and CLSP-1 were 15.9 kDa and 26.4 kDa, respectively. The monosaccharide composition of CLRP-1 was Ara, Rha, Fuc, Xyl, Man, Gal, GlcA, GalA in a ratio of 3.8: 8.4: 1.0: 0.8: 2.4: 7.4: 7.5: 2.0: 66.7, and Ara, Rha, Gal, GalA in a ratio of 5.8: 8.9: 8.0: 77.0 in for CLSP-1. The results of structural elucidation indicated that both CLRP-1 and CLSP-1 were pectic polysaccharides, mainly composed of 1, 4-linked galacturonic acid with long homogalacturonan regions. Arabinogalactan type I and arabinogalactan type II were presented as side chains. The antioxidant assay in IPEC-J2 cells showed that both CLRP-1 and CLSP-1 promoted cell viability and antioxidant activity, which significantly increase the level of total antioxidant capacity and the activity of superoxide dismutase, catalase, and decrease the content of malondialdehyde. Moreover, CLRP-1 and CLSP-1 also showed powerful antioxidant abilities in Caenorhabditis elegans and might regulate the nuclear localization of DAF-16 transcription factor, induced antioxidant enzymes activities, and further reduced reactive oxygen species and malondialdehyde contents to increase the antioxidant ability of Caenorhabditis elegans. Thus, these finding suggest that CLRP-1 and CLSP-1 could be used as potential antioxidants.

Background: Previous studies had reported that vitamin D receptor (VDR) gene polymorphisms were related to the development of several inflammatory disorders. However, potential links between such variations and the risk of developing a bone infection and underlying mechanisms remain unclear. This study aimed to analyze potential associations between VDR genetic variations and susceptibility to extremity osteomyelitis (OM) in a Chinese Han population and investigate potential mechanisms.Methods: Between January 2016 and August 2020, altogether 398 OM patients and 368 healthy controls were genotyped for six VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), TaqI (rs731236), GATA (rs4516035), and Cdx-2 (rs11568820) by the SNaPshot genotyping method. Then, male C57BL/6 mice were randomly divided into vitamin D–standard, –excess, –deficient, and –rescued groups. One week after making the model surgery, OM occurrence and severity were assessed using the bacterial count and histopathological staining. In vitro, phagocytosis, apoptosis, and bactericidal ability of macrophages were evaluated by overexpression or knockdown of VDR protein.Results: Significant associations were found among rs7975232, rs1544410, and OM development by the recessive model (AA vs. AC + CC, p = 0.037, OR = 0.594), homozygous model (AA vs. CC, p = 0.033, OR = 0.575), and heterozygous model (CT vs. CC, p = 0.049, OR = 0.610), respectively. Patients with the AA genotype of rs7975232 had a relatively higher mean level of vitamin D than those with AC and CC genotypes (22.5 vs. 20.7 vs. 19.0 ng/ml). Similarly, patients with CT genotype of rs1544410 had a relatively higher mean vitamin D level than those with CC genotype (20.94 vs. 19.89 ng/ml). Outcomes of in vivo experiments showed that the femoral bacterial load of vitamin D–deficient mice was highest among different vitamin D dose groups, with the most severe histopathological features of infection, and vitamin D supplementation partly reversed the changes. While in vitro experiment results revealed that active vitamin D promoted phagocytosis and sterilization of macrophages and inhibited apoptosis during infection. Reactive oxygen species (ROS) inhibitor inhibited apoptosis of macrophages induced by bacterial infection. Active vitamin D inhibited excessive ROS production in macrophages via the VDR-Bmi1 signaling pathway.Conclusion: In this Chinese cohort, ApaI and BsmI are associated with a decreased risk of OM development by influencing serological vitamin D level, the latter of which reduced macrophage apoptosis with inhibition of excessive ROS production via the VDR-Bmi1 signaling pathway.

Atom localization enables a high-precision imaging of the atomic position, which has provided vast applications in fundamental and applied science. In the present work, we propose a scheme for realizing two-dimensional off-axis atom localization in a three-level Λ system. Benefiting from the use of a hybrid coupling field, which consists of one Gaussian beam and one Laguerre–Gaussian beam, our scheme shows that the atoms can be localized at arbitrary position with high spatial resolution. Considering realistic experimental parameters, our numerical simulation predicts that the atoms can be precisely localized with a spatial resolution of ∼200 nm in the range of a radial distance of a few micrometers to the beam core. Our results provide a more flexible way to localize atoms in a two-dimensional system, possibly paving one-step closer to the nanometer scale atom lithography and ultraprecise microscopy.

ObjectiveTo investigate the adjuvant efficacy of metformin treatment to achieve pathological complete response (CR) in patients with endometrial complex hyperplasia (CH) and complex atypical hyperplasia (CAH), and secondarily, to evaluate their pregnancy outcomes after following assisted reproductive technology (ART).Study DesignThis prospective cohort study analyzed 219 patients diagnosed with infertility and CH/CAH from January 2016 to December 2020. Among these patients, 138 were assigned to the control group (progesterone alone) and 81 were assigned to the study group (progesterone+metformin). After 8/12 weeks of therapy, the treatment responses were assessed by histological examination of curettage specimens obtained by hysteroscopy. Once the pathological results indicated CR, the patients were able to receive ART. The ART treatment and follow-up data of these patients were collected and analyzed.Results116 patients in the control group achieved CR, compared with 76 patients in the study group. The CR rate in the control group was significantly lower than that in the study group (P=0.034). We then divided the patients into subgroups to compare the treatment responses. In the subgroup analyses, patients with body mass index (BMI) ≥25 kg/m2 and patients with polycystic ovarian syndrome (PCOS) had higher CR rates in the metformin group compared with the control group (P=0.015, P=0.028 respectively). Subsequently, 68 patients in the control group and 47 patients in the study group received an ART cycle. We examined the pregnancy indications and found no significant differences in the clinical pregnancy rate and live birth rate between the two groups (P>0.05).ConclusionRegression of CH/CAH may be improved by progesterone+metformin compared with progesterone alone. The effect was particularly pronounced in patients with BMI ≥25 kg/m2 and patients with PCOS. Metformin had no obvious effect on subsequent ART outcomes. The trial is registered on the publicly accessible website:Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=15372, identifier ChiCTR-ONR-16009078.

Summary: Background: Attention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with longer screen time utilization (STU) at the behavioral level. However, whether there are shared neural links between ADHD symptoms and prolonged STU is not clear and has not been explored in a single large-scale dataset. Methods: Leveraging the genetics, neuroimaging and behavioral data of 11,000+ children aged 9–11 from the Adolescent Brain Cognitive Development cohort, this study investigates the associations between the polygenic risk and trait for ADHD, STU, and white matter microstructure through cross-sectionally and longitudinal analyses. Findings: Children with higher polygenic risk scores for ADHD tend to have longer STU and more severe ADHD symptoms. Fractional anisotropy (FA) values in several white matter tracts are negatively correlated with both the ADHD polygenic risk score and STU, including the inferior frontal-striatal tract, inferior frontal-occipital fasciculus, superior longitudinal fasciculus and corpus callosum. Most of these tracts are linked to visual-related functions. Longitudinal analyses indicate a directional effect of white matter microstructure on the ADHD scale, and a bi-directional effect between the ADHD scale and STU. Furthermore, reduction of FA in several white matter tracts mediates the association between the ADHD polygenic risk score and STU. Interpretation: These findings shed new light on the shared neural overlaps between ADHD symptoms and prolonged STU, and provide evidence that the polygenic risk for ADHD is related, via white matter microstructure and the ADHD trait, to STU. Funding: This study was mainly supported by NSFC and National Key R&D Program of China.

Summary: Background: Post-stroke inflammation biomarker high-sensitivity C-reactive protein (hsCRP) increases cerebral infarct size and results in functional disability directly, it also contributes to the formation and maturation of atherosclerotic plaques, which increase the risk of stroke recurrence and results in functional disability indirectly. However, no study has quantified how much functional disability was mediated by stroke recurrence. Methods: Patients with acute ischaemic stroke within 7 days and admitted to 169 hospitals in the Third China National Stroke Registry were analyzed. Blood samples were collected within 24 h of admission. Stroke recurrence and functional disability (defined as a modified Rankin scale score ≥ 2) were assessed via face-to-face interviews at three months. Mediation analysis under the counterfactual framework was performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between hsCRP and functional outcome. Sensitivity analyses were performed across different subgroups and on different scales of hsCRP measurement. Findings: Of the 7603 analyzed patients (mean [SD] age, 62.3 [11.3] years; 2392 [31.5%] women), the median (interquartile range [IQR]) of NIHSS score was 3.0 (1.0–6.0). The median (IQR) level of hsCRP was 1.73 (0.81–4.38) mg/L. A total of 496 (6.5%) cases of stroke recurrence and 1884 (24.8%) cases of functional disability were observed at the 90-day follow-up. Each SD increase in the concentration of hsCRP was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.11; 95% CI, 1.04–1.18) and disability (aOR, 1.14; 95% CI, 1.08–1.20) within 90 days. Of 1884 functionally disabled patients, only 16.0 % (n = 302) of patients experienced stroke recurrence before functional disability. Stroke recurrence during follow-up explained 16.52% (95% CI, 5.79%–27.25%) of the relationship between hsCRP and functional disability. Sensitivity analyses in different subgroups and on different scales of hsCRP measurement showed comparable results. Interpretation: Stroke recurrence mediates less than 20% of the association between hsCRP and functional disability at 90 days among patients with acute ischaemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes. Funding: Beijing Natural Science Foundation, the National Key R&D Program of China, the National Natural Science Foundation of China, and the Beijing Municipal Science & Technology Commission.