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Evidence of active tuberculosis (ATB) in patients with rheumatic diseases are research priorities but limited data from China have been reported. Research targeting patients not taking anti-TNF biologics are especially insufficient. We aimed to investigate the prevalence and risk factors of ATB in this at-risk population. We conducted a tertiary hospital-based, multi-center, cross-sectional study by using stratified multi-stage cluster sampling strategy to screen ATB in patients with rheumatic diseases. We estimated the prevalence of ATB in patients with rheumatic diseases and identified risk factors among those who were not taking anti-TNF biologic. A total of 13,550 eligible patients were enrolled, and the result showed the standardized prevalence of ATB according to the composition ratio of various types of rheumatic disease was 882/100000 (95% confidence interval (CI): 706-1057). Multivariable logistic regression analysis in patients not taking anti-TNF biologics showed that the independent risk factors of ATB were having systemic lupus erythematosus (SLE) (OR=2.722, 95% CI: 1.437-5.159, p=0.002), having Behcet’s disease (BD) (OR= 5.261, 95% CI: 2.071-13.365, p

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The AP2/ERF gene family is one of the most conserved and important transcription factor families mainly occurring in plants with various functions in regulating plant biological and physiological processes. However, little comprehensive research has been conducted on the AP2/ERF gene family in Rhododendron (specifically, Rhododendron simsii), an important ornamental plant. The existing whole-genome sequence of Rhododendron provided data to investigate the AP2/ERF genes in Rhododendron on a genome-wide scale. A total of 120 Rhododendron AP2/ERF genes were identified. The phylogenetic analysis showed that RsAP2 genes were classified into five main subfamilies, AP2, ERF, DREB, RAV and soloist. Cis-acting elements involving plant growth regulators, response to abiotic stress and MYB binding sites were detected in the upstream sequences of RsAP2 genes. A heatmap of RsAP2 gene expression levels showed that these genes had different expression patterns in the five developmental stages of Rhododendron flowers. Twenty RsAP2 genes were selected for quantitative RT-PCR experiments to clarify the expression level changes under cold, salt and drought stress treatments, and the results showed that most of the RsAP2 genes responded to these abiotic stresses. This study generated comprehensive information on the RsAP2 gene family and provides a theoretical basis for future genetic improvement.

To overcome the high flammability and brittleness of epoxy resins without sacrificing their glass transition temperature (Tg) and mechanical properties, three epoxy-terminated hyperbranched flame retardants (EHBFRs) with a rigid central core and different branches, named EHBFR-HB, EHBFR-HCM, and EHBFR-HBM, were synthesized. After chemical structure characterization, the synthesized EHBFRs were introduced into the diglycidyl ether of bisphenol A (DGEBA) and cured with 4, 4-diaminodiphenylmethane (DDM). The compatibility, thermal stability, mechanical properties, and flame retardancy of the resultant resins were evaluated. Results showed that all three EHBFRs could significantly improve the fire safety of cured resins, and 30 wt. % of EHBFRs (less than 1.0 wt. % phosphorus content) endowed cured DGEBA with a UL-94 V-0 rating. In addition, the increased rigidity of branches in EHBFRs could increase the flexural strength and modulus of cured resins, and the branches with appropriate rigidity were also beneficial for improving their room temperature impact strength and Tg.

Propolis is resinous natural product produced by Western honeybees using beeswax and plant and bud exudates, which has a wide range of biological activities, including antioxidation, antibacterial, anti-inflammation, immune regulation, antitumor, and so on. Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer, and accounts for about 30% of all lymphomas. The effect of poplar propolis on DLBCL has not been reported. The IC50 of propolis on the proliferation of DLBCL SU-DHL-2 cell line and its proteins and gene expressions were detected by CCK-8 kit, label-free proteomic, and RT-PCR. The results showed that the IC50 of propolis at the 5 × l05/mL cell for 24 h was 5.729 μg/mL. Label-free-based proteomics analysis showed that there were 115 differentially expressed proteins (61 up-regulated and 54 down-regulated proteins) between IC50 dose-treated and solvent control groups. There were 32.47% differential proteins located in the nucleus, 20.78% in the cytoplasm, and 14.29% in mitochondria. The most significant different pathway (p = 0.0016) of protein enrichment was ferroptosis (including glutamate–cysteine ligase regulatory subunit, ferritin, and heme oxygenase). The relative expression trend of 17 of the total 22 genes selected according to proteomics results was in line with their encoded protein. The highest protein–protein interaction was serine/threonine-protein kinase PLK, which interacted with 16 differential proteins. In conclusion, poplar propolis inhibited SU-DHL-2 cells via ferroptosis pathway, accelerating cell death and down-regulated serine/threonine-protein kinase PLK1, affecting apoptosis of cell. This result provides a theoretical basis for the treatment of DLBCL using propolis.

Abstract Pollution of heavy metals in agricultural environments is a growing problem to the health of the world’s human population. Green, low-cost, and efficient detection methods can help control such pollution. In this study, a protein biosensor, mApple-D6A3, was built from rice-derived Cd2+-binding protein D6A3 fused with the red fluorescent protein mApple at the N-terminus to detect the contents of heavy metals. Fluorescence intensity of mApple fused with D6A3 indicated the biosensor’s sensitivity to metal ions and its intensity was more stable under alkaline conditions. mApple-D6A3 was most sensitive to Cu2+, then Ni2+, then Cd2+. Isothermal titration calorimetry experiments demonstrated that mApple-D6A3 successfully bound to each of these three metal ions, and its ability to bind the ions was, from strongest to weakest, Cu2+ > Cd2+ > Ni2+. There were strong linear relationships between the fluorescence intensity of mApple-D6A3 and concentrations of Cd2+ (0–100 μM), Cu2+ (0–60 μM) and Ni2+ (0–120 μM), and their respective R2 values were 0.994, 0.973 and 0.973. When mApple-D6A3 was applied to detect concentrations of heavy metal ions in water (0–0.1 mM) or culture medium (0–1 mM), its accuracy for detection attained more than 80%. This study demonstrates the potential of this biosensor as a tool for detection of heavy metal ions.

Abstract Zinc‐ion hybrid supercapacitors (ZHSCs) have garnered increasing attention as promising energy storage devices in recent years, as they combine the advantages of high‐energy Zn‐ion batteries and high‐power supercapacitors. However, the development of ZHSCs is still in its infancy and there are many bottlenecks to overcome. In particular, the challenge induced by the limited ion adsorption capability of carbon‐positive electrodes severely restricts the energy density of ZHSCs. Therefore, it has become a key issue to design novel carbon‐positive electrodes that enable high energy density yet do not deteriorate the intrinsic power capability and long‐term durability. This study focuses on recent achievements in synthesis, morphology, and electrochemical performance of various carbon materials applied in ZHSCs. The modification strategies to optimize their electrochemical performance are briefly summarized. In addition, current challenges and future opportunities in this field are also outlined. This review will be beneficial to provide an organized framework for the research systems of carbon‐positive electrodes and develop novel ZHSCs with high energy density.

Abstract Background The clinical correlates, prognosis and determinants of acute kidney injury (AKI) in patients with coronavirus disease 2019 (Covid-19) remain largely unclear. Methods We retrospectively reviewed medical records of all adult patients with laboratory-confirmed Covid-19 who were admitted to the intensive care unit (ICU) between January 23rd 2020 and April 6th 2020 at Wuhan JinYinTan Hospital and The First Affiliated Hospital of Guangzhou Medical University. Results Among 210 patients, 131 were males (62.4%). The median Age was 64 years (IQR: 56–71). Of 92 (43.8%) patients who developed AKI during hospitalization, 13 (14.1%), 15 (16.3%) and 64 (69.6%) were classified as being at stage 1, 2 and 3, respectively. 54 patients (58.7%) received continuous renal replacement therapy. Age, sepsis, nephrotoxic drug, invasive mechanical ventilation and elevated baseline serum creatinine levels were associated with the occurrence of AKI. Renal recovery during hospitalization was identified among 16 patients with AKI (17.4%), who had a significantly shorter time from admission to AKI diagnosis, lower incidence of right heart failure and higher ratio of partial pressure of oxygen to the fraction of inspired oxygen. Of 210 patients, 93 deceased within 28 days of ICU admission. AKI stage 3, critical disease, greater Age and the lowest ratio of partial pressure of oxygen to the fraction of inspired oxygen being

This article aims to address problems in the current clustering process of low-energy adaptive clustering hierarchy (LEACH) in the wireless sensor networks, such as strong randomness and local optimum in the path optimization. This article proposes an optimal combined weighting (OCW) and improved ant colony optimization (IACO) algorithm for the LEACH protocol optimization. First, cluster head nodes are updated via a dynamic replacement mechanism of the whole network cluster head nodes to reduce the network energy consumption. In order to improve the quality of the selected cluster head nodes, this article proposes the OCW method to dynamically change the weight according to the importance of the cluster head node in different regions, in accordance with the three impact factors of the node residual energy, density, and distance between the node and the sink node in different regions. Second, the network is partitioned and the transmission path among the clusters can be optimized by the transfer probability in IACO with combined local and global pheromone update mechanism. The efficacy of the proposed LEACH protocol optimization method has been verified with MATLAB simulation experiments.

miRNAs play a crucial role in the development and growth of plants by inhibiting the function of targeted genes at the post-transcription level. However, no miRNAs in Pseudostellaria heterophylla have been reported and their function in the morphogenesis of organs is still unclear. In this study, a total of 159 conserved miRNAs (belonging to 64 families) and 303 level miRNAs were identified from P. heterophylla. Some of them showed specifically up or down-regulated expression in different tissues and numbers of unigenes involved in Plant-pathogen interaction and MAPK signaling pathway-plant were targeted. The significant negative correlation of expression profiles between 30 miRNAs and their target genes (37 unigenes) was observed, respectively. Further, a large number of genes involved with signal transduction of auxin, zeatin, abscisic acid and, jasmonic acid were targeted. Predicated targets of two miRNAs were validated by 5′RLM-RACE, respectively. A large number of mRNAs from four pathogens were targeted by miRNAs from P. heterophylla and some of them were targeted by miR414. In summary, we reported a population of miRNAs from four different vegetative tissues of P. heterophylla by high throughput sequencing, which was analyzed by combining with the constructed transcriptome. These results may help to explain the function of miRNAs in the morphogenesis of organs and defense of pathogens, and may provide theoretical basis for breeding and genetic improvement of P. heterophylla.

Objective: Congenital heart diseases (CHDs) are associated with an extremely heavy global disease burden as the most common category of birth defects. Genetic and environmental factors have been identified as risk factors of CHDs previously. However, high volume clinical indicators have never been considered when predicting CHDs. This study aimed to predict the occurrence of CHDs by considering thousands of variables from self-reported questionnaires and routinely collected clinical laboratory data using machine learning algorithms.Methods: We conducted a birth cohort study at one of the largest cardiac centers in China from 2011 to 2017. All fetuses were screened for CHDs using ultrasound and cases were confirmed by at least two pediatric cardiologists using echocardiogram. A total of 1,127 potential predictors were included to predict CHDs. We used the Explainable Boosting Machine (EBM) for prediction and evaluated the model performance using area under the Receive Operating Characteristics (ROC) curves (AUC). The top predictors were selected according to their contributions and predictive values. Thresholds were calculated for the most significant predictors.Results: Overall, 5,390 mother-child pairs were recruited. Our prediction model achieved an AUC of 76% (69-83%) from out-of-sample predictions. Among the top 35 predictors of CHDs we identified, 34 were from clinical laboratory tests and only one was from the questionnaire (abortion history). Total accuracy, sensitivity, and specificity were 0.65, 0.74, and 0.65, respectively. Maternal serum uric acid (UA), glucose, and coagulation levels were the most consistent and significant predictors of CHDs. According to the thresholds of the predictors identified in our study, which did not reach the current clinical diagnosis criteria, elevated UA (>4.38 mg/dl), shortened activated partial thromboplastin time (

Standard echocardiographic view recognition is a prerequisite for automatic diagnosis of congenital heart defects (CHDs). This study aims to evaluate the feasibility and accuracy of standard echocardiographic view recognition in the diagnosis of CHDs in children using convolutional neural networks (CNNs). A new deep learning-based neural network method was proposed to automatically and efficiently identify commonly used standard echocardiographic views. A total of 367,571 echocardiographic image slices from 3,772 subjects were used to train and validate the proposed echocardiographic view recognition model where 23 standard echocardiographic views commonly used to diagnose CHDs in children were identified. The F1 scores of a majority of views were all ≥0.90, including subcostal sagittal/coronal view of the atrium septum, apical four-chamber view, apical five-chamber view, low parasternal four-chamber view, sax-mid, sax-basal, parasternal long-axis view of the left ventricle (PSLV), suprasternal long-axis view of the entire aortic arch, M-mode echocardiographic recording of the aortic (M-AO) and the left ventricle at the level of the papillary muscle (M-LV), Doppler recording from the mitral valve (DP-MV), the tricuspid valve (DP-TV), the ascending aorta (DP-AAO), the pulmonary valve (DP-PV), and the descending aorta (DP-DAO). This study provides a solid foundation for the subsequent use of artificial intelligence (AI) to identify CHDs in children.

BackgroundViral causes of acute respiratory distress syndrome (ARDS) are mostly limited to influenza. However, adenovirus has been emerging as a cause of ARDS with a high mortality rate and described in adults are rare.MethodsWe conducted a prospective, single-center observational study of viral pneumonia with ARDS and confirmed adenovirus-associated ARDS in adults at our quaternary referral institution between March 2019 and June 2020. We prospectively analyzed clinical characteristics, laboratory test results, radiological characteristics, viral load from nasopharyngeal swabs and endotracheal aspirates, treatments, and outcomes for the study participants.ResultsThe study enrolled 143 ARDS patients, including 47 patients with viral pneumonia-related ARDS, among which there were 14 adenovirus-associated ARDS patients, which accounted for 29.79% of the viral pneumonia-related ARDS cases. Among the adenovirus-associated ARDS patients, 78.57% were men with a mean age of 54.93 ± 19.04 years, younger than that of the non-adenovirus associated ARDS patients. Adenovirus-associated ARDS patients had no specific clinical characteristics, but they presented with decrease in the number of CD3+CD4+ T cells and higher serum creatinine during the early stage. The viral load and the positivity rate in the lower respiratory tract were higher than that of the upper respiratory tract in the patients with adenovirus-associated ARDS. All patients required invasive mechanical ventilation treatment. The average time from shortness of breath to the application of invasive ventilation was 24 h. Ten patients (71.43%) complicated by acute kidney injury, while 13 patients (71.43%) in the non-adenovirus associated ARDS group (P = 0.045). Additionally, 85.71% of the 14 adenovirus-associated ARDS patients survived. No significant differences were detected between the two groups regarding duration of ventilation, length of ICU stay and mortality.ConclusionAdenovirus infection is an important cause of virus-related ARDS. The positivity rate of adenovirus infection in lower respiratory tract secretions was higher than that in upper respiratory tract secretions in these patients. Age, lower CD3+CD4+ T cells, and high serum creatinine may be were associated with adenovirus induce ARDS in adults required mechanical ventilation. Early identification and intervention to prevent disease progression are essential for reducing the mortality rate in these patients.

Water supply prediction and control is one of the key issues in exploitation of coal mine underground reservoirs (CMUR). In order to investigate the water supply for underground reservoirs in coal mines, the aquifers were classified into three types (types I, II, and III) according to the relative location of aquifers. The discrete element fluid structure coupling numerical simulation model is constructed according to the classification results. The numerical simulation parameters are inversed based on the surface subsidence data and the advance support pressure, and then, the disturbed characteristics and water pressure variation law of different types of aquifers are studied. The research results show that the maximum water inflow of type III, type II, and type I aquifers is 739 m3/h, 377 m3/h, and 279 m3/h, respectively. The dynamic calculation process of underground reservoir capacity under mining disturbance is refined, and the regulation and storage methods of underground reservoir are preliminarily put forward.

Radiofrequency (RF) catheter ablation has emerged as an effective alternative for the treatment of atrial fibrillation (AF), but ablation lesions will result in swelling and hematoma of local surrounding tissue, triggering inflammatory cell infiltration and increased release of inflammatory cytokines. Some studies have shown that the inflammatory response may be related to the early occurrence of AF. The most direct way to inhibit perioperative inflammation is to use anti-inflammatory drugs such as glucocorticoids. Here, we prepared polylactic-co-glycolic acid (PLGA) nanoparticles loaded with budesonide (BUD) and delivered them through irrigation of saline during the onset of ablation. Local high temperature promoted local rupture of PLGA nanoparticles, releasing BUD, and produced a timely and effective local myocardial anti-inflammatory effect, resulting in the reduction of acute hematoma and inflammatory cell infiltration and the enhancement of ablation effect. Nanoparticles would also infiltrate into the local myocardium and gradually release BUD ingredients to produce a continuous anti-inflammatory effect in the next few days. This resulted in a decrease in the level of inflammatory cytokine IL-6 and an increase of anti-inflammatory cytokine IL-10. This study explored an extraordinary drug delivery strategy to reduce ablation-related inflammation, which may prevent early recurrence of AF.

Abstract The ever‐growing market of wearable electronic devices has greatly stimulated the rapid development of flexible Zn‐ion batteries (ZIBs). Manganese oxides are one of the most commonly used hosts for zinc ion accommodation and thus receive particular research interest for high‐performance flexible ZIB constructions. In this review, a comprehensive summary of the recent development of flexible ZIBs with manganese oxides as cathode materials is presented. Apart from the brief introduction of flexible electronic devices and ZIBs, the charge storage mechanisms and crystal structures of various manganese oxides are summarized. Modifications of the cathode materials in terms of morphology, conductivity, structures, and flexibilities are illustrated in detail, together with the demonstration of structure‐performance relationships and applications in flexible ZIBs. Finally, limitations to be overcome are indicated and the future work directions are proposed.

Abstract Background The gut bacteria-derived metabolite trimethylamine-N-oxide (TMAO) has been discussed in various cardiometabolic diseases. However, evidence characterizing the microbial population responsible for TMAO accumulation in patients with atrial fibrillation (AF), an increasingly prevalent arrhythmia, is yet lacking. In order to understand the key gut microorganisms that produce TMAO in AF, trimethylamine (TMA)-synthesis enzymes and metabolic pathways, as well as the potential TMA-producers in gut microbiome were assessed based on metagenomic data-mining in a northern Chinese cohort consisting of 50 non-AF controls and 50 patients with different types of AF. Results Compared to the control subjects, AF patients showed a marked increase in the microbial genes underlying TMA formation in the gut, which included 12 potential TMA-synthesis functional orthologs and 1 module. The specific bacterial genes, including choline-TMA lyase, carnitine monooxygenase, glycine betaine reductase, and TMAO reductase, were elevated in the gut of AF patients. Furthermore, 16 genera were assigned and significantly correlated with TMA-enzymatic genes, where 9 genera were remarkably enriched in the gut communities of AF patients. Neither of these TMA-synthesis pathways nor the microbial players showed a significant discrepancy between different types of AF in the current cohort. These gut microbes might participate in the formation of TMA by activating the key TMA-synthesis enzymes and contributing to the functional pathways in AF patients. Conclusions The present study provides an in-depth insight into the potential bacteria and metabolic pathways involved in TMA production in the gut of AF patients. These findings emphasize a key role of the gut bacteria in driving TMAO formation during AF pathogenesis, thereby indicating its therapeutic potential as an intervention strategy of AF by targeting TMA-synthesis pathways and dysbiotic gut microbiota.

Abstract Background Convalescent plasma administration may be of clinical benefit in patients with severe influenza, but reports on the efficacy of this therapy vary. Methods We conducted a systematic review and meta-analysis assessing randomized controlled trials (RCTs) involving the administration of convalescent plasma to treat severe influenza. Healthcare databases were searched in February 2020. All records were screened against eligibility criteria, and the risks of bias were assessed. The primary outcome was the fatality rate. Results A total of 2861 studies were retrieved and screened. Five eligible RCTs were identified. Pooled analyses yielded no evidence that using convalescent plasma to treat severe influenza resulted in significant reductions in mortality (odds ratio, 1.06; 95% CI, 0.51–2·23; P = 0.87; I 2 = 35%), number of days in the intensive care unit, or number of days on mechanical ventilation. This treatment may have the possible benefits of increasing hemagglutination inhibition titers and reducing influenza B viral loads and cytokine levels. No serious adverse events were reported. The included studies were generally of high quality with a low risk of bias. Conclusions The administration of convalescent plasma appears safe but may not reduce the mortality, number of days in the intensive care unit, or number of days on mechanical ventilation in patients with severe influenza.

Abstract Background CM082 is a novel angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR) and platelet‐derived growth factor receptor (PDGFR). The purpose of this research was to evaluate the antitumor activity of CM082 combined with gefitinib on epidermal growth factor receptor (EGFR) mutant non‐small cell lung cancer (NSCLC) in vitro and in vivo. Methods The effect of CM082 on human umbilical vein endothelial cells (HUVECs) was assessed. In vitro and in vivo efficacy of CM082 combined with gefitinib on EGFR NSCLC cell lines (HCC827 harboring E746_A750 deletion and H3255 harboring L858R) and a xenograft model was evaluated. Results CM082 inhibited VEGF‐induced cell growth, phosphorylation of VEGFR and downstream signaling molecules, tube formation, and cell migration of HUVECs. Furthermore, CM082 combined with gefitinib was more effective in inhibiting growth and colony formation and inducing apoptosis of H3255 and HCC827 cells in vitro than monotherapy. Moreover, tumor growth inhibition by the combination in a H3255 xenograft model was 107.7% more than that by gefitinib (93.6%) (P

Abstract Background COVID-19 (coronavirus disease 2019) has caused a major epidemic worldwide; however, much is yet to be known about the epidemiology and evolution of the virus partly due to the scarcity of full-length SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genomes reported. One reason is that the challenges underneath sequencing SARS-CoV-2 directly from clinical samples have not been completely tackled, i.e., sequencing samples with low viral load often results in insufficient viral reads for analyses. Methods We applied a novel multiplex PCR amplicon (amplicon)-based and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of SARS-CoV-2 from serials dilutions of a cultured isolate, and eight clinical samples covering a range of sample types and viral loads. We also examined and compared the sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. Results We demonstrated that both amplicon and capture methods efficiently enriched SARS-CoV-2 content from clinical samples, while the enrichment efficiency of amplicon outran that of capture in more challenging samples. We found that capture was not as accurate as meta and amplicon in identifying between-sample variations, whereas amplicon method was not as accurate as the other two in investigating within-sample variations, suggesting amplicon sequencing was not suitable for studying virus-host interactions and viral transmission that heavily rely on intra-host dynamics. We illustrated that meta uncovered rich genetic information in the clinical samples besides SARS-CoV-2, providing references for clinical diagnostics and therapeutics. Taken all factors above and cost-effectiveness into consideration, we proposed guidance for how to choose sequencing strategy for SARS-CoV-2 under different situations. Conclusions This is, to the best of our knowledge, the first work systematically investigating inter- and intra-individual variations of SARS-CoV-2 using amplicon- and capture-based whole-genome sequencing, as well as the first comparative study among multiple approaches. Our work offers practical solutions for genome sequencing and analyses of SARS-CoV-2 and other emerging viruses.

Abstract Background Certain pregnant women suffer from cardiac pathology,and a few of them need cardiac operations under cardiopulmonary bypass during pregnancy. Feto-neonatal and maternal outcomes have not been sufficiently described. Methods We conducted a retrospective review of 22 cases of women undergoing cardiac operations under cardiopulmonary bypass during pregnancy in our hospital from Jan.2014 to Mar.2019. Results All 22 patients were alive after treatment. The types of cardiac disorders included congenital heart defects, rheumatic heart disease,infective endocarditis,aortic dissection, obstruction and/or thrombosis of a prosthetic valve. Only one case was a twin pregnancy,and the other 21 cases were singletons. Four fetuses died in the utero after surgery. Three patients chose termination of the pregnancy after the cardiac operations: one fetus was detected abnormity of the brain and the other two patients abandoned pregnancy. Fourteen fetuses were alive and born without any abnormity. Two fetuses suffered from neonatal intracranial hemorrhage and died after birth. Conclusions Cardiac operation under cardiopulmonary bypass during pregnancy is a challenge for physicians in multidisciplinary teams. Strictly evaluating the indication is vital. On the other hand, some patients can benefit from this management.

Abstract Background Intraoperative Extracorporeal membrane oxygenation (ECMO) is increasingly being applied as life-support for lung transplantation patients. However, factors associated with this procedure in lung transplantation patients have not yet been characterized. The aim of this study was to identify preoperative factors of intraoperative ECMO support during lung transplantation and to evaluated the outcome of lung transplantation patients supported with ECMO. Methods Patients underwent lung transplantation treated with and without ECMO in Guangzhou Institute of Respiratory Diseases between January 2015 to August 2018 were retrospectively reviewed. Patient demographics and clinical variables were collected and analyzed. Multivariate logistic regression was performed to identify factors independently associated with intraoperative extracorporeal membrane oxygenation support during lung transplantation. Results During the study period, 138 patients underwent lung transplantation at our institution, the mean LAS was (56.63 ± 18.39) (range, 32.79 to 88.70). Fourty four patients were treated with veno-venous/veno-arterial ECMO. Among the patients, 32 patients wean successfully ECMO after operation, 12 patients remain ECMO after operation, and 32 patients (62.74%) survived to hospital discharge. In multiple analysis, the following factors were associated with intraoperative ECMO support: advanced age, high PAP before operation, duration of mechanical ventilation before operation, a higher APACHE II and primary diagnosis for transplantation. The overall survival rates at 1, 3, and 12 months were 90.91, 72.73, and 56.81% in the ECMO group, and 95.40, 82.76, and 73.56% in the non-ECMO group, respectively (log-rank P = 0.081). Patients who underwent single lung transplant had a lower survival rates in ECMO group as compared with non-ECMO group at 1, 3, and 12 months (90.47% vs 98.25, 71.43% vs 84.21, and 52.38% vs 75.44%) (log-rank P = 0.048). Conclusions The preoperative factors of intraoperative ECMO support during lung transplantation included age, high PAP before operation, preoperative mechanical ventilation, a higher APACHE II and primary diagnosis for transplantation based on multivariate analysis.

Abstract Background Genomic islands are associated with microbial adaptations, carrying genomic signatures different from the host. Some methods perform an overall test to identify genomic islands based on their local features. However, regions of different scales will display different genomic features. Results We proposed here a novel method “2SigFinder “, the first combined use of small-scale and large-scale statistical testing for genomic island detection. The proposed method was tested by genomic island boundary detection and identification of genomic islands or functional features of real biological data. We also compared the proposed method with the comparative genomics and composition-based approaches. The results indicate that the proposed 2SigFinder is more efficient in identifying genomic islands. Conclusions From real biological data, 2SigFinder identified genomic islands from a single genome and reported robust results across different experiments, without annotated information of genomes or prior knowledge from other datasets. 2SigHunter identified 25 Pathogenicity, 1 tRNA, 2 Virulence and 2 Repeats from 27 Pathogenicity, 1 tRNA, 2 Virulence and 2 Repeats, and detected 101 Phage and 28 HEG out of 130 Phage and 36 HEGs in S. enterica Typhi CT18, which shows that it is more efficient in detecting functional features associated with GIs.

ABSTRACTThe emerging COVID-19 caused by SARS-CoV-2 infection poses severe challenges to global public health. Serum antibody testing is becoming one of the critical methods for the diagnosis of COVID-19 patients. We investigated IgM and IgG responses against SARS-CoV-2 nucleocapsid (N) and spike (S) protein after symptom onset in the intensive care unit (ICU) and non-ICU patients. 130 blood samples from 38 COVID-19 patients were collected. The levels of IgM and IgG specific to N and S protein were detected by ELISA. A series of blood samples were collected along the disease course from the same patient, including 11 ICU patients and 27 non-ICU patients for longitudinal analysis. N and S specific IgM and IgG (N-IgM, N-IgG, S-IgM, S-IgG) in non-ICU patients increased after symptom onset. N-IgM and S-IgM in some non-ICU patients reached a peak in the second week, while N-IgG and S-IgG continued to increase in the third week. The combined detection of N and S specific IgM and IgG could identify up to 75% of SARS-CoV-2 infected patients in the first week. S-IgG was significantly higher in non-ICU patients than in ICU patients in the third week. In contrast, N-IgG was significantly higher in ICU patients than in non-ICU patients. The increase of S-IgG positively correlated with the decrease of C-reactive protein (CRP) in non-ICU patients. N and S specific IgM and IgG increased gradually after symptom onset and can be used for detection of SARS-CoV-2 infection. Analysis of the dynamics of S-IgG may help to predict prognosis.

Abstract Background Cadmium (Cd) is a severely toxic heavy metal to most microorganisms. Many bacteria have developed Cd2+ resistance. Results In this study, we isolated two different Cd2+ resistance Bacillus sp. strains, Bacillus vietamensis 151–6 and Bacillus marisflavi 151–25, which could be grown in the presence of Cd2+ at concentration up to 0.3 mM and 0.8 mM, respectively. According to the genomic sequencing, transcriptome analysis under cadmium stress, and other related experiments, a gene cluster in plasmid p25 was found to be a major contributor to Cd2+ resistance in B. marisflavi 151–25. The cluster in p25 contained orf4802 and orf4803 which encodes an ATPase transporter and a transcriptional regulator protein, respectively. Although 151–6 has much lower Cd2+ resistance than 151–25, they contained similar gene cluster, but in different locations. A gene cluster on the chromosome containing orf4111, orf4112 and orf4113, which encodes an ATPase transporter, a cadmium efflux system accessory protein and a cadmium resistance protein, respectively, was found to play a major role on the Cd2+ resistance for B. vietamensis 151–6. Conclusions This work described cadmium resistance mechanisms in newly isolated Bacillus vietamensis 151–6 and Bacillus marisflavi 151–25. Based on homologies to the cad system (CadA-CadC) in Staphylococcus aureus and analysis of transcriptome under Cd2+ induction, we inferred that the mechanisms of cadmium resistance in B. marisflavi 151–25 was as same as the cad system in S. aureus. Although Bacillus vietamensis 151–6 also had the similar gene cluster to B. marisflavi 151–25 and S. aureus, its transcriptional regulatory mechanism of cadmium resistance was not same. This study explored the cadmium resistance mechanism for B. vietamensis 151–6 and B. marisflavi 151–25 and has expanded our understanding of the biological effects of cadmium.

Background Epidermal growth factor receptor (EGFR) gene mutations predict tumor response to EGFR tyrosine kinase inhibitors (EGFR‐TKIs) in non‐small cell lung cancer (NSCLC). However, even patients with EGFR‐sensitive mutations in NSCLC have limited efficacy with EGFR‐TKI. Studies have shown that long noncoding RNA (lncRNA) is related to diagnosis and prognosis with NSCLC. This study aimed to explore the correlation between lncRNA in NSCLC patients with EGFR mutation status and EGFR‐TKI efficacy. Methods The amplification‐refractory mutation system method was used to test the EGFR mutation status in tumor tissues and pleural effusions of NSCLC patients. Three EGFR‐mutant patients and three EGFR wild‐type patients were selected. Differential lncRNA was performed on the pleural effusions of the two selected groups of patients using Clariom D Human chip technology. Five lncRNAs significantly associated with EGFR mutation status were screened by FC value and GO analysis, and then evaluated by real‐time quantitative polymerase chain reaction in NSCLC patients' pleural effusions. Three were further analyzed in NSCLC patients' plasma. Results There were 61 significant differences in lncRNA between EGFR mutation‐positive and wild‐type patients. Among them, SCARNA7, MALAT1, NONHSAT017369, NONHSAT051892, and FTH1P2 were significantly associated with EGFR mutation status. SCARNA7, MALAT1, and NONHSAT017369 showed consistent results with plasma in pleural effusions compared to EGFR wild‐type, all upregulated in the EGFR mutation group. Conclusion This study shows that lncRNAs can be used not only as potential biomarkers for predicting the mutation status of EGFR and the efficacy of EGFR‐TKI, but also for monitoring the efficacy of EGFR‐TKI.

Abstract Background Modification of root architecture and improvement of root resistance to stresses can increase crop productivity. Functional analyses of root-specific genes are necessary for root system improvement, and root-specific promoters enable research into the regulation of root development and genetic manipulation of root traits. Maize is an important crop species; however, little systematic mining of root-specific genes and promoters has been performed to date. Results Genomic-scale mining based on microarray data sets followed by transcript detection resulted in the identification of 222 root-specific genes. Gene Ontology enrichment analyses revealed that these 222 root-specific genes were mainly involved in responses to chemical, biotic, and abiotic stresses. Of the 222 genes, 33 were verified by quantitative reverse transcription polymerase chain reaction, and 31 showed root-preferential activity. About 2 kb upstream 5 of the 31 identified root-preferential genes were cloned from the maize genome as putative promoters and named p8463, p5023, p1534, p8531 and p6629. GUS staining of transgenic maize-derived promoter-GUS constructs revealed that the five promoters drove GUS expression in a root-preferential manner. Conclusions We mined root-preferential genes and their promoters in maize and verified p8463, p5023, p1534, p8531 and p6629 as root-preferential promoters. Our research enables the identification of other tissue-specific genes and promoters in maize and other species. In addition, the five promoters may enable enhancement of target gene(s) of maize in a root-preferential manner to generate novel maize cultivars with resistance to water, fertilizer constraints, or biotic stresses.

ABSTRACT Hypoxia signaling is a key regulator in the development and progression of many types of human malignancies, including viral cancers. The latency-associated nuclear antigen (LANA), encoded by Kaposi’s sarcoma-associated herpesvirus (KSHV) during latency, is a multifunctional protein that plays an essential role in viral episome maintenance and lytic gene silencing for inducing tumorigenesis. Although our previous studies have shown that LANA contains a SUMO-interacting motif (LANASIM), and hypoxia reduces SUMOylated KAP1 association with LANASIM, the physiological proteomic network of LANASIM-associated cellular proteins in response to hypoxia is still unclear. In this study, we individually established cell lines stably expressing wild-type LANA (LANAWT) and its SIM-deleted mutant (LANAdSIM) and treated them with or without hypoxia, followed by coimmunoprecipitation and mass spectrometry analysis to systemically identify the hypoxia-responsive profile of LANASIM-associated cellular proteins. We found that in hypoxia, the number of cellular proteins associated with LANAWT instead of LANAdSIM was dramatically increased. Functional network analysis revealed that two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, were significantly enriched for 28 LANASIM-associated proteins in response to hypoxia. HNRNPU was one of the proteins consistently identified that interacted with LANASIM in different proteomic screening systems and responded to hypoxia. This study provides a proteomic profile of LANASIM-associated proteins in hypoxia and facilitates our understanding of the role of the collaboration between viral infection and the hypoxia response in inducing viral persistence and tumorigenesis. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) has been reported to be involved in the regulation of host proteins in response to hypoxic stress. LANA, one of the key latent proteins, contains a SUMO-interacting motif (LANASIM) and reduces the association with SUMOylated KAP1 upon hypoxic treatment. However, the physiological systematic network of LANASIM-associated cellular proteins in hypoxia is still unclear. Here, we revealed two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, that were significantly enriched for 28 LANASIM-associated proteins in hypoxia. This discovery not only provides a proteomic profile of LANASIM-associated proteins in hypoxia but also facilitates our understanding of the collaboration between viral infection and hypoxic stress in inducing viral persistence and tumorigenesis.

Background: Active commuting as a contributor to daily physical activity is beneficial for cardiovascular health, but leads to more chances of exposure to ambient air pollution. This study aimed to investigate associations between active commuting to work with cardiovascular disease (CVD), mortality and life expectancy among general Chinese adults, and to further evaluate the modification effect of fine particulate matter (PM2.5) exposure on these associations. Methods: We included 76,176 Chinese adults without CVD from three large cohorts of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project. Information about commuting mode and physical activity were collected by unified questionnaire. Satellite-based PM2.5 concentrations at 1-km spatial resolution was used for estimating PM2.5 exposure of participants. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD incidence, mortality and all-cause mortality were estimated using Cox proportional hazards regression models. Multiplicative interaction term of commuting mode and PM2.5 level was tested to investigate potential effect modification. Results: During 448,499 person-years of follow-up, 2230 CVD events and 2777 all-cause deaths were recorded. Compared with the non-active commuters, the multivariable-adjusted HRs (95% CIs) of CVD incidence and all-cause mortality were 0.95(0.85–1.05) and 0.79(0.72–0.87) for walking commuters, respectively. Corresponding HRs (95% CIs) for cycling commuters were 0.71(0.62–0.82) and 0.67(0.59–0.76). Active commuters over 45 years old were estimated to have more CVD-free years and life expectancy than non-active commuters under lower PM2.5 concentration. However, these beneficial effects of active commuting were alleviated or counteracted by long-term exposure to high PM2.5 concentration. Significant multiplicative interaction of commuting mode and PM2.5 level was showed in all-cause mortality, with the lowest risk observed in cycling participants exposed to lower level of PM2.5. Conclusions: Active commuting was associated with lower risk of CVD, all-cause mortality, and longer life expectancy among Chinese adults under ambient settings with lower PM2.5 level. It will be valuable to encourage active commuting among adults and develop stringent strategies on ambient PM2.5 pollution control for prevention of CVD and prolongation of life expectancy.

Microsatellite instability-high (MSI-H) is widely believed to be a biomarker for immune checkpoint inhibitors (ICIs) such as pembrolizumab in solid tumors. However, due to the low prevalence of MSI-H in most cancers, it tends to be insufficient to identify whether patients should receive ICIs according to this biomarker alone. Here, we report a Chinese esophageal squamous cell carcinoma (ESCC) patient with unusual divergent MSI status between the primary lesion (MSS) and metastatic lesion (MSI-H) which developed after platinum-based therapy and radiotherapy. Both his primary and metastatic tumors responded well to pembrolizumab-containing therapies or pembrolizumab monotherapy and maintained a complete response for over 24 months. Whole-exome sequencing and multiplex immunohistochemistry were used to examine his tissue specimens. Notably, there were multiple high-frequency mutations of DDR (DNA damage repair) genes shared in the primary lesion and metastatic lesion, especially in the latter. Besides, we observed considerable degrees of infiltrating CD3+/CD8+ lymphocytes in both of his primary tumor and metastatic tumor without obvious difference, suggesting that the conversion of microsatellite status had little effect on the infiltration of lymphocytes. Collectively, given the predictive role of DDR alterations for ICIs in other malignancies, the alterations of DDR genes might also be promising biomarkers in ESCC individuals receiving ICIs.

Background: The level of medication literacy is very important to control symptoms and improve the prognosis of patients with coronary heart disease (CHD). The positive role of social support is able to promote patient health outcomes. However, few studies have addressed the association between social support and medication literacy in patients with CHD. The purpose of this study is to investigate the status of medication literacy and social support, and confirm the association between them in patients with CHD.Methods: This cross-sectional study investigated 416 participants, and was conducted in a grade a hospital in China. Three different survey instruments were applied: The Demographic Characteristics Questionnaire, the Chinese Version of the Medication Literacy Scale, and the Social Support Rating Scale. Pearson correlation analysis and ordinal logistic regression analysis were performed to analyze data.Results: The results showed that the mean score of medication literacy among the 416 participants was 4.96 ± 4.68, 48.8% (203) participants with inadequate medication literacy. The independent determinants of medication literacy include gender, education level, course of disease, number of medicines, and subjective support in social support. The mean score of social support was 41.05 ± 6.16. The Pearson correlation analysis indicated that social support was positively correlated with medication literacy (r = 0.398, P < 0.01).Conclusion: The study shows that the level of medication literacy and social support for patients with CHD are inadequate. Social support levels could have a positive effect on medication literacy of patients.

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.

The aim of this study was to evaluate the association between fruit intake and stroke risk considering the genetic predisposition. We used data from 34,871 participants from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR project) from 2007 to 2020. A polygenic risk score comprising 534 genetic variants associated with stroke and its related factors was constructed to categorize individuals into low, intermediate, and high genetic risk groups. The associations of genetic and fruit intake with incident stroke were assessed by the Cox proportional hazard regression. We documented 2586 incident strokes during a median follow-up of 11.2 years. Compared with fruit intake < 200 g/week, similar relative risk reductions in stroke with adherence to fruit intake > 100 g/day across the genetic risk categories were observed (28–32%), but the absolute risk reductions were relatively larger in the highest genetic risk group (p for trend = 0.03). In comparison to those with a fruit intake < 200 g/week, those with a fruit intake >100 g/day in the low, intermediate, and high genetic risk groups had an average of 1.45 (95% CI, 0.61–2.31), 2.12 (1.63–2.59), and 2.19 (1.13–3.22) additional stroke-free years at aged 35, respectively. Our findings suggest that individuals with a high genetic risk could gain more absolute risk reductions and stroke-free years than those with a low genetic risk from increasing fruit intake for the stroke primary prevention.

This study examined the effect of sleep disturbance on gut microbiota (GM), atrial substrate, and atrial fibrillation (AF) inducibility. C57BL/6 mice were subjected to six weeks of sleep deprivation (SD) using the method of modified multiple-platform. Transesophageal burst pacing was performed to evaluate AF inducibility. Feces, plasma, and an atrium were collected and analyzed by 16s rRNA sequencing, liquid chromatography–mass spectrometry (LC-MS)-based metabolome, histological studies, and transcriptome. Higher AF inducibility (2/30 of control vs. 15/30 of SD, p = 0.001) and longer AF duration (p < 0.001), concomitant with aggravated fibrosis, collagen, and lipid accumulation, were seen in the SD mice compared to control mice. Meanwhile, elevated alpha diversity, higher abundance of Flavonifractor, Ruminococcus, and Alloprevotella, as well as imbalanced functional pathways, were observed in the gut of SD mice. Moreover, the global patterns for the plasma metabolome were altered, e.g., the decreased butanoate metabolism intermediates in SD mice. In addition, disrupted metabolic homeostasis in the SD atrium, such as fatty acid metabolism, was analyzed by the transcriptome. These results demonstrated that the crosstalk between GM and atrial metabolism might be a promising target for SD-mediated AF susceptibility.

Background: Accumulating evidence suggests that environmental pollutants may contribute to the occurrence of congenital heart defects (CHDs). However, no previous studies have evaluated the impact of perfluoroalkyl substances (PFAS), persistent environmental pollutants, on CHDs. This exploratory study aimed to generate testable hypotheses of the association between gestational PFAS and the risk of CHDs. Methods: A nested case-control study was conducted in a cohort of 11,578 newborns. Exposure odds ratios were compared between 158 CHD cases and 158 non-malformed controls delivered at the same hospital, individually matched by maternal age (±5 years) and parity. Concentrations of 27 PFAS, including linear and branched isomers, were determined in maternal peripheral blood and cord blood plasma collected before and during delivery using a ultra-performance liquid chromatography coupled to mass spectrometry. Conditional logistic regression was utilized to evaluate associations between individual PFAS and the risk of CHDs, adjusted for confounding variables. Results: Maternal gestational exposure to the highly branched perfluorooctanesulfonate (PFOS) isomer potassium 6-trifluoromethyperfluoroheptanesulfonate [6 m-PFOS, adjusted odds ratio (aOR) (95% CI) = 2.47(1.05,5.83)] and perfluorodecanoic acid [PFDA, aOR (95% CI) = 2.33(1.00,5.45)] were associated with increased odds of septal defects with statistical significance, while linear PFOS [aOR (95% CI) = 3.65(1.09,12.16)] and perfluoro-n-dodecanoic acid [PFDoA, aOR (95% CI) = 6.82(1.75, 26.61)] were associated with conotruncal defects. Effect estimates also suggested associations for higher maternal 6 m-PFOS and PFDA concentrations with ventricular septal defect. However, we did not observe these associations in cord blood. Conclusion: These exploratory findings suggested that gestational exposure to most PFAS, especially linear PFOS, 6 m-PFOS, PFDA, and PFDoA, was associated with greater risks for septal and conotruncal defects. However, a larger, adequately powered study is needed to confirm our findings, and to more comprehensively investigate the potential teratogenic effects of other more recently introduced PFAS, and on associations with individual CHD subtypes.

Background: To find the optimal positive end expiratory pressure (PEEP) in mechanical ventilated patients without Acute Respiratory Distress Syndrome (ARDS), we conducted a Bayesian network meta-analysis and systematic review of randomized controlled trials (RCTs) comparing different level of PEEP based on a novel classification of PEEP level: ZEEP group (PEEP = 0 cm H2O); lower PEEP group (PEEP = 1–6 cm H2O); intermediate PEEP group (PEEP = 7–10 cm H2O); higher PEEP group (PEEP > 10 cm H2O).Result: Twenty eight eligible studies with 2,712 patients were included. There were no significant differences in the duration of mechanical ventilation between higher and intermediate PEEP (MD: 0.020, 95% CI: −0.14, 0.28), higher and lower PEEP (MD: −0.010, 95% CI: −0.23, 0.22), higher PEEP and ZEEP (MD: 0.010, 95% CI: −0.40, 0.22), intermediate and lower PEEP (MD: −0.040, 95% CI: −0.18, 0.040), intermediate PEEP and ZEEP (MD: −0.010, 95% CI: −0.42, 0.10), lower PEEP and ZEEP (MD: 0.020, 95% CI: −0.32, 0.13), respectively. Higher PEEP was associated with significantly higher PaO2/FiO2 ratio(PFR) when compared to ZEEP (MD: 73.24, 95% CI: 11.03, 130.7), and higher incidence of pneumothorax when compared to intermediate PEEP, lower PEEP and ZEEP (OR: 2.91e + 12, 95% CI: 40.3, 1.76e + 39; OR: 1.85e + 12, 95% CI: 29.2, 1.18e + 39; and OR: 1.44e + 12, 95% CI: 16.9, 8.70e + 38, respectively). There was no association between PEEP levels and other secondary outcomes.Conclusion: We identified higher PEEP was associated with significantly higher PFR and higher incidence of pneumothorax. Nonetheless, in terms of other outcomes, no significant differences were detected among four levels of PEEP.Systematic Review Registration: The study had registered on an international prospective register of systematic reviews, PROSPERO, on 09 April 2021, identifier: [CRD42021241745].

ABSTRACT Objective To investigate the clinical characteristics of preterm infants with different severities of bronchopulmonary dysplasia (BPD) and disclose the high-risk factors of exacerbating BPD. Methods Collection of clinical data of 91 preterm infants admitted to the NICU and diagnosed with BPD, categorized in groups according to the disease severity: 41 mild cases,, 24 moderate cases, and 26 severe cases. Comparison and analysis of perinatal risk factors, treatment, complications and prognosis of the infants with different severity degrees. Results The severe group had a higher proportion of infants with congenital heart disease (CHD) higher than the moderate group (P < 0.05), and a higher ratio of pneumonia and mechanical ventilation (MV) ≥ seven days than the mild group (P < 0.05). The severe group also presented higher reintubation incidence than both the mild and moderate groups (P < 0.05). The groups presented different (P < 0.05) incidence rates of hemodynamically significant patent ductus arteriosus (hsPDA) . Ridit analysis suggested that the premature infants (PIs) with hsPDA, multiple microbial pulmonary infections, or Klebsiella pneumoniae pneumonia had more severe illness. Conclusion CHD, hsPDA, MV ≥ seven days, reintubation, pneumonia, especially multiple microbial pulmonary infections, and Klebsiella pneumoniae pneumonia are correlated with the severity of BPD and can be used as BPD progression predictor.

Background: Evidence of maternal exposure to ambient air pollution on congenital heart defects (CHD) has been mixed and are still relatively limited in developing countries. We aimed to investigate the association between maternal exposure to air pollution and CHD in China. Method: This longitudinal, population-based, case-control study consecutively recruited fetuses with CHD and healthy volunteers from 21 cities, Southern China, between January 2006 and December 2016. Residential address at delivery was linked to random forests models to estimate maternal exposure to particulate matter with an aerodynamic diameter of ≤ 1 µm (PM1), ≤2.5 µm, and ≤10 µm as well as nitrogen dioxides, in three trimesters. The CHD cases were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia ultrasound. The CHD subtypes were coded using the International Classification Diseases. Adjusted logistic regression models were used to assess the associations between air pollutants and CHD and its subtypes. Results: A total of 7055 isolated CHD and 6423 controls were included in the current analysis. Maternal air pollution exposures were consistently higher among cases than those among controls. Logistic regression analyses showed that maternal exposure to all air pollutants during the first trimester was associated with an increased odds of CHD (e.g., an interquartile range [13.3 µg/m3] increase in PM1 was associated with 1.09-fold ([95% confidence interval, 1.01–1.18]) greater odds of CHD). No significant associations were observed for maternal air pollution exposures during the second trimester and the third trimester. The pattern of the associations between air pollutants and different CHD subtypes was mixed. Conclusions: Maternal exposure to greater levels of air pollutants during the pregnancy, especially the first trimester, is associated with higher odds of CHD in offspring. Further longitudinal well-designed studies are warranted to confirm our findings.

Venovenous extracorporeal membrane oxygenation (VV-ECMO) may be a lifesaving rescue therapy for patients with severe coronavirus disease 2019 (COVID-19). However, little is known regarding the efficacy of prolonged ECMO (duration longer than 14 days) in patients with COVID-19. In this case report, we report the successful use of prolonged VV-ECMO (111 days) in a 61-year-old man with severe COVID-19. Given the high mortality rate of severe COVID-19, this case provided evidence for use of prolonged VV-ECMO as supportive care in patients with severe COVID-19.

Microorganisms play an important role in the remediation of cadmium pollution in the soil and their diversity can be affected by cadmium. In this study, the bacterial community in arable soil samples collected from two near geographical sites, with different degrees of cadmium pollution at three different seasons, were characterized using Illumina MiSeq sequencing. The result showed that cadmium is an important factor to affect the bacterial diversity and the microbial communities in the high cadmium polluted area (the site H) had significant differences compared with low cadmium polluted area (the site L). Especially, higher concentrations of Cd significantly increased the abundance of Proteobacteria and Gemmatimonas whereas decreased the abundance of Nitrospirae. Moreover, 42 Cd-resistant bacteria were isolated from six soil samples and evaluated for potential application in Cd bioremediation. Based on their Cd-MIC [minimum inhibitory concentration (MIC) of Cd2+], Cd2+ removal rate and 16S rDNA gene sequence analyses, three Burkholderia sp. strains (ha-1, hj-2, and ho-3) showed very high tolerance to Cd (5, 5, and 6 mM) and exhibited high Cd2+ removal rate (81.78, 79.37, and 63.05%), six Bacillus sp. strains (151-5,151-6,151-13, 151-20, and 151-21) showed moderate tolerance to Cd (0.8, 0.4, 0.8, 0.4, 0.6, and 0.4 mM) but high Cd2+ removal rate (84.78, 90.14, 82.82, 82.39, 81.79, and 84.17%). Those results indicated that Burkholderia sp. belonging to the phylum Proteobacteria and Bacillus sp. belonging to the phylum Firmicutes have developed a resistance for cadmium and may play an important role in Cd-contaminated soils. Our study provided baseline data for bacterial communities in cadmium polluted soils and concluded that Cd-resistant bacteria have potential for bioremediation of Cd-contaminated soils.

IntroductionThe role of reverse trigger (RT) was unknown in ventilated non-acute respiratory distress syndrome (ARDS) patients. So we conducted a retrospective study to evaluate the incidence, characteristics and physiologic consequence of RT in such population.MethodSix ventilated non-ARDS patients were included, the esophageal balloon catheter were placed for measurements of respiratory mechanics in all patients. And the data were analyzed to identified the occurrence of RT, duration of the entrainment, the entrainment pattern or ratio, the phase difference (dP) and the phase angle (θ), phenotypes, Effects and clinical correlations of RT.ResultRT was detected in four patients of our series (66.7%), and the occurrence of RT varying from 19 to 88.6% of their recording time in these 4 patients. One patient (No.2) showed a stable 1:1 ratio and Mid-cycle RT was the most common phenotype. However, the remained patients showed a mixed ratios, and Late RT was the most common phenotype, followed by RT with breath stacking. The average values of mean phase delay and phase angles were 0.39s (0.32, 0.98) and 60.52° (49.66, 102.24). Mean phase delay and phase angles were shorter in early reverse triggering with early and delayed relaxation, and longer in mid, late RT and RT with breath stacking. Pmus was variable between patients and phenotypes, and larger Pmus was generated in Early RT, Delayed Relaxation and mid cycle RT. When the RT occurred, the Peso increased 17.27 (4.91, 19.71) cmH2O compared to the controlled breathing, and the average value of incremental ΔPeso varied widely inter and intra patients (Table 3B and Figure 1). Larger ΔPeso was always generated in Early RT, Delayed Relaxation and mid cycle RT, accompanied by an significant increase of PL with 19.12 (0.75) cmH2O and 16.10 (6.23) cmH2O.ConclusionRT could also be observed in ventilated non-ARDS patients. The characteristics of pattern and phenotype was similar to RT in ARDS patients to a large extent. And RT appeared to alter lung stress and delivered volumes.

Anthocyanin has attracted increasing attention due to its superior biological activity. However, the inherently poor stability of anthocyanin limits its practical applications. In this study, a fast and straightforward method was developed to improve the stability of anthocyanin. Cellulose acetate ultrafine fiber-loaded anthocyanin (CA@Anthocyanin UFs) was prepared by robust electrospinning, and the potential application of cellulose acetate ultrafine fibers (CA UFs) as a bioactive substance delivery system was comprehensively investigated. The experimental results showed that CA@Anthocyanin UFs had protective effects on anthocyanin against temperature, light, and pH. The results of the artificially simulated gastric fluid (pH = 2.0) indicated that the CA@Anthocyanin UFs had a controllable release influence on anthocyanin. A 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay suggested that the CA@Anthocyanin UFs still had an excellent antioxidant activity similar to anthocyanin. This work demonstrated the potential application of robust electrospinning-constructed cellulose acetate ultrafine fibers in bioactive substance delivery and controlled release systems, as well as its prospects in green packaging due to the nature of this environmentally friendly composite.

As global public health events and regional conflicts have greater influence on supply chains nowadays, supplier default in procurement becomes more and more common in practice. However, there is less research on portfolio procurement purchasing decisions in the case of fixed-term contract supplier default. This paper focuses on the optimal purchasing decision of buyers by using a combination of fixed-term contracts and spot transactions, which is a beneficial extension of the classical newsvendor model. When supplier default is not considered, the optimal purchase quantity in the fixed-term contract is first obtained, which maximizes the buyer’s expected profits. Research shows that supplier default has an important impact on the optimal purchasing decision making in portfolio procurement. The optimal purchase quantity of the buyer in the fixed-term contract decreases with the increase in the default rate of the contract supplier, which implies that the default from the contract supplier inhibits a larger purchase quantity in the fixed-term contract. In addition, it is proved that the buyer’s expected profits from portfolio procurement increases with the decrease in the contract supplier’s default rate. Finally, numerical experiments and sensitivity analysis are conducted to prove the result, and some management opinions on the optimal decision-making in portfolio procurement with fixed-term contracts and spot transactions are put forward.

Hantavirus causes hemorrhagic fever with renal syndrome, thus posing a major threat to human health in Jiangxi Province, China. Both Hantaan virus (HTNV) and Seoul virus (SEOV) have been found to be endemic in the province. Rodents were trapped from Gaoan Anyi and Tonggu counties in Jiangxi Province in 2020–2021. Hantavirus specific antibodies in the blood and RNA in the lung samples from the captured mammals were detected and analyzed. A total of 889 small mammals from seven species were collected. Positive detection was observed for hantavirus antibodies in 9.8% (87/889), SEOV RNA in 1% (9/889) and HTNV RNA in 2.6% (23/889). The difference in detection rates between regions was significant. Phylogenetic analysis of the obtained partial sequences of M and S segments revealed that two distinct genotypes of HTNV and three genotypes of SEOV were co-circulating in the captured mammals, with a regionally specific distribution. Multiple distinct genotypes of hantavirus are co-circulating in the province. Further studies in broader areas remain needed to reveal the diversity of hantaviruses.

As a functional beverage, selenium (Se)-enriched green tea (Se-GT) has gained increasing popularity for its superior properties in promoting health. In this study, we compared the brewing characteristics, in vitro digestion profiles, and protective effects on neurotoxicity induced through the amyloid-beta (Aβ) peptide of two typical Se-GTs (Enshi Yulu (ESYL) and Ziyang Maojian (ZYMJ), representing the typical low-Se green tea and high-Se green tea, respectively). ESYL and ZYMJ showed similar chemical component leaching properties with the different brewing methods, and the optimized brewing conditions were 5 min, 90 °C, 50 mL/g, and first brewing. The antioxidant activities of the tea infusions had the strongest positive correlation with the tea polyphenols among all of the leaching substances. The tea infusions of ESYL and ZYMJ showed similar digestive behaviors, and the tea polyphenols in the tea infusions were almost totally degraded or transferred after 150 min of dynamic digestion. Studies conducted in a cell model of Alzheimer’s disease (AD) showed that the extract from the high-Se green tea was more effective for neuroprotection compared with the low-Se green tea. Overall, our results revealed the best brewing conditions and digestion behaviors of Se-GT and the great potential of Se-GT or Se-enriched green extract (Se-GTE) to be used as promising AD-preventive beverages or food ingredients.

Early detection and treatment of visual impairment diseases are critical and integral to combating avoidable blindness. To enable this, artificial intelligence–based disease identification approaches are vital for visual impairment diseases, especially for people living in areas with a few ophthalmologists. In this study, we demonstrated the identification of a large variety of visual impairment diseases using a coarse-to-fine approach. We designed a hierarchical deep learning network, which is composed of a family of multi-task & multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy. A multi-level disease–guided loss function was proposed to learn the fine-grained variability of eye disease features. The proposed framework was trained for both ocular surface and retinal images, independently. The training dataset comprised 7,100 clinical images from 1,600 patients with 100 diseases. To show the feasibility of the proposed framework, we demonstrated eye disease identification on the first two levels of the eye disease taxonomy, namely 7 ocular diseases with 4 ocular surface diseases and 3 retinal fundus diseases in level 1 and 17 subclasses with 9 ocular surface diseases and 8 retinal fundus diseases in level 2. The proposed framework is flexible and extensible, which can be inherently trained on more levels with sufficient training data for each subtype diseases (e.g., the 17 classes of level 2 include 100 subtype diseases defined as level 3 diseases). The performance of the proposed framework was evaluated against 40 board-certified ophthalmologists on clinical cases with various visual impairment diseases and showed that the proposed framework had high sensitivity and specificity with the area under the receiver operating characteristic curve ranging from 0.743 to 0.989 in identifying all identified major causes of blindness. Further assessment of 4,670 cases in a tertiary eye center also demonstrated that the proposed framework achieved a high identification accuracy rate for different visual impairment diseases compared with that of human graders in a clinical setting. The proposed hierarchical deep learning framework would improve clinical practice in ophthalmology and broaden the scope of service available, especially for people living in areas with a few ophthalmologists.

Background: Niemann-Pick disease type C1 (NP-C1) is a rare, autosomal-recessive neurodegenerative disorder with no United States Food and Drug Administration (FDA)-approved drug. Lithium has been shown to have considerable neuroprotective effects for neurological disorders such as bipolar disorder, Alzheimer’s disease and stroke and has been tested in many clinical trials. However, the pharmacological effect of lithium on NP-C1 neurodegenerative processes has not been investigated. The aim of this study was to provide an initial evaluation of the safety and feasibility of lithium carbonate in patients with NP-C1.Methods: A total of 13 patients diagnosed with NP-C1 who met the inclusion criteria received lithium orally at doses of 300, 600, 900, or 1,200 mg daily. The dose was reduced based on tolerance or safety observations. Plasma 7-ketocholesterol (7-KC), an emerging biomarker of NP-C1, was the primary endpoint. Secondary endpoints included NPC Neurological Severity Scores (NNSS) and safety.Results: Of the 13 patients with NP-C1 (12–33 years) enrolled, three withdrew (discontinuation of follow-up outpatient visits). The last observed post-treatment values of 7-KC concentrations (128 ng/ml, SEM 20) were significantly lower than pretreatment baselines values (185 ng/ml, SEM 29; p = 0.001). The mean NNSS was improved after lithium treatment at 12 months (p = 0.005). Improvement in swallowing capacity was observed in treated patients (p = 0.014). No serious adverse events were recorded in the patients receiving lithium.Conclusion: Lithium is a potential therapeutic option for NP-C1 patients. Larger randomized and double-blind clinical trials are needed to further support this finding.Clinical Trial Registration:ClinicalTrials.gov, NCT03201627.

Objective: To retrospectively investigate the comparative efficacy, safety and cost-benefits of three nutritional treatment schemes including short peptide jejunal nutrition (SPJN), whole protein jejunal nutrition (WPJN), and partial parenteral nutrition (PPN) in patients underwent esophagectomy for esophageal cancer in our hospital. This study was carried out in accordance with the conceptual framework of nutritional therapy in fast-track rehabilitation surgery.Methods: We retrospectively reviewed 305 patients who were assigned to receive esophagectomy for esophageal cancer. Eligible patients was naturally divided into SPJN group [n = 98 (32.1%)], WPJN group [n = 95 (31.1%)], and PPN group [n = 112 (36.7%)] according to the type of nutritional scheme which was actually prescribed to patients by the attendingphysician in clinical practice. The differences of the serum total protein (TP), albumin (ALB), pre-albumin (PA), hemoglobin (HGB), white blood cells (WBCs), red blood cells (RBCs) and neutrophils were compared among 3 nutritional schemes groups. We also investigated the relationship of the fluid intake, urine output, gastric juice drainage volume and thoracic drainage volume among 3 nutritional groups at 3 days after surgery. Moreover, the differences of cost-benefit indexes, complications, length of hospitalization and hospital expenditure were also compared.Results: The serum TP, ALB, and PA in the SPJN group were all higher than those in the WPJN and PPN groups (p < 0.05). The gastric juice volume of gastrointestinal decompression drainage and fluid volume of thoracic drainage in the SPJN group were all less than that in the WPJN group (p < 0.05). The overall hospital stay and post-operative hospital stay in the SPJN group were all shorter than that in WPJN group (p < 0.05). Moreover, the incidence of post-operative complications including anastomotic leakage, infection, and gastrointestinal reaction was remarkably lower in the SPJN group compared to the WPJN group (p < 0.05). Interesting, hospital expenditure in the PPN group was less than that in the SPJN and the WPJN groups (p < 0.001).Conclusion: Patients may obtain benefits in improving protein level after receiving SPJN scheme at the early stage after esophagectomy. Meanwhile, patients may obtain benefits in improving post-operative complications and hospital stay after receiving SPJN or PPN compared to WPJN protocol. However, the difference between SPJN and PPN requires further study because no difference was detected in terms of clinical outcomes including complications and the length of hospitalization although PPN may achieve a possible decrease of medical expenditure.