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Abstract Background The ambitious expansion of social health insurance in China has played a crucial role in preventing and alleviating poverty caused by illness. However, there is no government-sponsored health insurance program specifically for younger children and inequities are more pronounced in healthcare utilization, medical expenditure, and satisfaction in some households with severely ill children. This study assessed the effectiveness of child health insurance in terms of alleviating poverty caused by illness. Methods Data were collected from two rounds of follow-up surveys using the China Family Panel Studies 2016 and 2018 child questionnaires to investigate the relationship between child health insurance and household medical impoverishment (MI). Impoverishing health expenditure (IHE) and catastrophic health expenditure (CHE) were measured to quantify “poverty due to illness” in terms of absolute and relative poverty, respectively. Propensity score matching with the difference-in-differences (PSM-DID) method, robustness tests, and heterogeneity analysis were conducted to address endogeneity issues. Results Social health insurance for children significantly reduced household impoverishment due to illness. Under the shock of illness, the incidences of IHE and CHE were significantly lower in households with insured children. The poverty alleviation mechanism transmitted by children enrolled in social health insurance was primarily driven by hospitalization reimbursements and the proportion of out-of-pocket medical payments among the total medical expenditure for children. Conclusions Children’s possession of social health insurance significantly reduced the likelihood of household poverty due to illness. The poverty-reducing effect of social medical insurance is most significant in rural areas, low-income families, no-left-behind children, and infants. Targeted poverty alleviation strategies for marginalized groups and areas would ensure the equity and efficiency of health system reforms, contributing to the goal of universal health insurance coverage in China.

Abstract Background The development of the human vermiform appendix at the cellular level, as well as its function, is not well understood. Appendicitis in preschool children, although uncommon, is associated with a high perforation rate and increased morbidity. Methods We performed single-cell RNA sequencing (scRNA-seq) on the human appendix during fetal and pediatric stages as well as preschool-age inflammatory appendices. Transcriptional features of each cell compartment were discussed in the developing appendix. Cellular interactions and differentiation trajectories were also investigated. We compared scRNA-seq profiles from preschool appendicitis to those of matched healthy controls to reveal disease-associated changes. Bulk transcriptomic data, immunohistochemistry, and real-time quantitative PCR were used to validate the findings. Results Our analysis identified 76 cell types in total and described the cellular atlas of the developing appendix. We discovered the potential role of the BMP signaling pathway in appendiceal epithelium development and identified HOXC8 and PITX2 as the specific regulons of appendix goblet cells. Higher pericyte coverage, endothelial angiogenesis, and goblet mucus scores together with lower epithelial and endothelial tight junction scores were found in the preschool appendix, which possibly contribute to the clinical features of preschool appendicitis. Preschool appendicitis scRNA-seq profiles revealed that the interleukin-17 signaling pathway may participate in the inflammation process. Conclusions Our study provides new insights into the development of the appendix and deepens the understanding of appendicitis in preschool children. Graphical Abstract

The experimental process of rebound testing of rubber material was simulated using finite element analysis software ABAQUS, and the energy changes during the rebound process were discussed, laying the foundation for further research on viscoelasticity of rubber materials. The results showed that the characterization results of the new method were basically consistent with the actual test results, proving that the fitted intrinsic equation was consistent with the properties of the material itself, and at the same time characterizing the accurate energy changes during the rebound process. During the impact process, the kinetic energy of the pendulum was mainly transformed into the elastic potential energy and dissipation energy of the specimen. In addition, by analyzing the changes in the temperature field of the sample model, it was more intuitive to observe the temperature rise due to the energy loss during rubber deformation, indicating that part of the lost kinetic energy was converted into thermal energy and dissipated into the environment.

Background: The introduction of endovascular repair provides an alternative to traditional open repair of thoracoabdominal aortic aneurysms (TAAA). Its utility is not well defined, however. Using a national database, we studied the treatment patterns and outcomes of TAAA to gain insight into its contemporary surgical practice in the United States. Methods: Records of TAAA patients who received endovascular and open repair were retrieved from the 2002 to 2018 National Inpatient Sample database. Each cohort was stratified into 4 age groups: ≤50, 51 to 60, 61 to 70, and >70 years. Patient characteristics and in-hospital outcomes were compared between the 2 repair modalities. Temporal trends were investigated. Results: Endovascular repair use increased steadily, whereas open repair volume remained stable until 2012, before declining by 50% by 2018. This appears to be associated with a declining number of open repairs in patients age >60 years. Patients who underwent endovascular repair were older and had a higher Charlson Comorbidity Index (mean, 2.8 ± 1.7 vs 2.5 ± 1.5; P 60 years but not for patients age ≤60 years. Conclusions: There has been a shift in the treatment of TAAA in the United States from open repair–dominant to endovascular repair–dominant. It has increased surgical access for older and more comorbid patients and has led to a decline in the use of open repair while lowering in-hospital mortality.

To address the problem of predicting machining quality for critical features in the manufacturing process of mechanical products, a method that combines information entropy and XGBoost (version 2.1.1) hyperparameter optimization is proposed. Initially, machining data of mechanical products are analyzed based on information entropy theory to identify critical quality characteristics. Subsequently, a quality prediction model for these critical features is established using the XGBoost machine learning framework. The model’s hyperparameters are then optimized through Bayesian optimization. This method is applied as a case study to a medium-speed marine diesel engine piston. After the critical quality characteristics in the machining process are identified, the machining quality of these vital characteristics is predicted, and the results are compared with those obtained from a machine learning model without hyperparameter optimization. The findings demonstrate that the proposed method effectively predicts the machining quality of mechanical products.

Aiming at the difficulty in effectively identifying critical quality features in the complex machining process, this paper proposes a critical quality feature recognition method based on a machining process network. Firstly, the machining process network model is constructed based on the complex network theory. The LeaderRank algorithm is used to identify the critical processes in the machining process. Secondly, the Entropy-CRITIC method is used to calculate the weight of the quality features of the critical processes, and the critical quality features of the critical processes are determined according to weight ranking results. Finally, the feasibility and effectiveness of the method are verified by taking the medium-speed marine diesel engine coupling rod machining as an example. The results show that the method can still effectively identify the critical quality features in the case of small sample data and provide support for machining process optimization and quality control, thus improving product consistency, reliability, and machining efficiency.

Machining-induced residual stress (MIRS) in thin-walled components affects their machining accuracy, especially for large-size thin-walled components. This study focuses on the bodies of marine diesel engines, exploring the distribution of MIRS and distortion caused by the gravity-coupled machining residual stress during the boring process of the main bearing hole. The research obtained the distribution of MIRS and the machining distortion based on the finite element method and the mapping method. It examined the influence rules of various parameters, such as the cutting speed, feed, and depth of cut, on MIRS and machining distortion. The study shows that cutting speed, feed, and depth of cut are vital factors affecting MIRS and machining distortion. For the machining distortion of large-size and thin-walled components, their own weight is an essential factor that cannot be ignored. By optimizing the wall thickness, the distortion range can be effectively controlled, supporting the lightweight design of the structure.

Aiming at the difficulty of quantitatively evaluating the critical processes in the manufacturing process of complex mechanical products, a critical process identification method based on the PageRank algorithm is proposed with the goal of identifying key processes in the machining process. Based on the complex network theory, the error transfer network model of the machining process is established in this paper. Adopting the actual machining process as the data set of the complex network, the weights of the machining feature nodes are calculated by the PageRank ranking algorithm, and the nodes are ranked according to the weight values to assess the influence and importance of the nodes in the network model. Finally, taking the connecting rod machining process of a medium-speed marine diesel engine as an example, the results show that the method can quickly and effectively identify the key processes in the machining process.

Background: Aidi injection, a classic traditional Chinese medicine (TCM) formula, has been used on a broader scale in treating a variety of cancers. In this study, we aimed to explore the potential anti-tumor effects of Aidi injection in the treatment of neuroblastoma (NB) using network pharmacology (NP).Methods: To elucidate the anti-NB mechanism of Aidi injection, an NP-based approach and molecular docking validation were employed. The compounds and target genes were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database. The protein–protein interaction network was constructed using the STRING database. clusterProfiler (R package) was utilized to annotate the bioinformatics of hub target genes. The gene survival analysis was performed on R2, a web-based genomic analysis application. iGEMDOCK was used for molecular docking validation, and GROMACS was utilized to validate molecular docking results. Furthermore, we investigated the anticancer effects of gomisin B and ginsenoside Rh2 on human NB cells using a cell viability assay. The Western blot assay was used to validate the protein levels of target genes in gomisin B- and ginsenoside Rh2-treated NB cells.Results: A total of 2 critical compounds with 16 hub target genes were identified for treating NB. All 16 hub genes could potentially influence the survival of NB patients. The top three genes (EGFR, ESR1, and MAPK1) were considered the central hub genes from the drug–compound–hub target gene–pathway network. The endocrine resistance and estrogen signaling pathways were identified as the therapeutic pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gomisin B and ginsenoside Rh2 showed a good binding ability to the target protein in molecular docking. The results of cell experiments showed the anti-NB effect of gomisin B and ginsenoside Rh2. In addition, the administration of gomisin B over-regulated the expression of ESR1 protein in MYCN-amplified NB cells.Conclusion: In the present study, we investigated the potential pharmacological mechanisms of Aidi against NB and revealed the anti-NB effect of gomisin B, providing clinical evidence of Aidi in treating NB and establishing baselines for further research.

Background Pediatric medullary thyroid cancer (MTC) is one of the rare pediatric endocrine neoplasms. Derived from C cells of thyroid glands, MTC is more aggressive and more prompt to metastasis than other types of pediatric thyroid cancer. The mechanism remains unclear. Methods We performed single-cell transcriptome sequencing on the samples of the primary tumor and metastases lymph nodes from one patient diagnosed with MTC, and it is the first single-cell transcriptome sequencing data of pediatric MTC. In addition, whole exome sequencing was performed and peripheral blood was regarded as a normal reference. All cells that passed quality control were merged and analyzed in R to discover the association between tumor cells and their microenvironment as well as tumor pathogenesis. Results We first described the landscape of the single-cell atlas of MTC and studied the interaction between the tumor cell and its microenvironment. C cells, identified as tumor cells, and T cells, as the dominant participant in the tumor microenvironment, were particularly discussed in their development and interactions. In addition, the WES signature of tumor cells and their microenvironment were also described. Actively immune interactions were found, indicating B cells, T cells and myeloid cells were all actively participating in immune reaction in MTC. T cells, as the major components of the tumor microenvironment, proliferated in MTC and could be divided into clusters that expressed proliferation, immune effectiveness, and naive markers separately.

Objectives: This study aimed to explore the distribution and differences in the health status of migrant workers in China by gender and age. In addition, it investigated the causes of health inequalities among them.Methods: This paper analyzes the differences in health status across age groups for migrant workers of different genders based on the data from the China Migrant Dynamic Survey in 2018. It also empirically assesses how education level and health insurance impact gender-related health inequalities.Results: The results suggest that female migrant workers in China have significantly lower health levels than males. Furthermore, these differences in health are exacerbated with age. This disparity may be attributed to lower participation in social insurance participation and less educational attainment among female migrant workers than their male counterparts.Conclusion: The government should take effective practical measures to increase the social insurance participation rate of female migrant workers. Moreover, investing in female education to reduce health inequality among migrant workers is essential.

Abstract Background The presence of mixed-lineage leukaemia rearrangement (MLL-r) in paediatric patients with acute myeloid leukaemia (AML) is a poor prognostic predictor. Whether allogeneic haematopoietic stem cell transplantation (allo-HSCT) is beneficial in such cases remains unclear. Methods We evaluated the outcomes and prognostic factors of allo-HSCT in 44 paediatric patients with MLL-r AML in the first complete remission (CR1) between 2014 and 2019 at our institution. Results For all the 44 patients, the 3-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 74.5%, 64.1%, and 29.1%, respectively. Among them, 37 (84.1%) patients received haploidentical (haplo)-HSCT, and the 3-year OS, EFS, and CIR were 73.0%, 65.6%, and 26.4%, respectively. The 100-day cumulative incidence of grade II–IV acute graft-versus-host disease (aGVHD) post-transplantation was 27.3%, and that of grade III–IV aGVHD was 15.9%. The overall 3-year cumulative incidence of chronic graft-versus-host disease (cGVHD) post-transplantation was 40.8%, and that of extensive cGVHD was 16.7%. Minimal residual disease (MRD)-positive (MRD +) status pre-HSCT was significantly associated with lower survival and higher risk of relapse. The 3-year OS, EFS, and CIR differed significantly between patients with MRD + pre-HSCT (n = 15; 48.5%, 34.3% and 59%) and those with MRD-pre-HSCT (n = 29; 89.7%, 81.4% and 11.7%). Pre-HSCT MRD + status was an independent risk factor in multivariate analysis. Conclusions Allo-HSCT (especially haplo-HSCT) can be a viable strategy in these patients, and pre-HSCT MRD status significantly affected the outcomes.

The treated distillate aromatic extract (TDAE) is widely used in tread compounds. However, polycyclic aromatic hydrocarbons (PAHs) contained in TDAE is serious harm to the environment and human. In this paper, liquid polybutadiene (LPB) of different brands was used to replace TDAE to plasticize solution polymerized styrene-butadiene rubber/cis-1,4-polybutadiene rubber (SSBR/BR). The effects of liquid polybutadiene instead of TDAE on crosslinking network and mechanical properties of matrix rubber were studied. LPB could participate in vulcanization reaction (different from TDAE). The results showed that LPB effectively reduced the critical strain amplitude of Payne effect (ameliorated filler dispersion) compared with TDAE plasticizing SSBR/BR. The degree of crosslinking decreased slightly, but there was no significant difference in rolling resistance and wet skid resistance at the same sulfur content. Changing the sulfur content, the wet skid resistance of tread and tensile strength of SSBR/BR vulcanizate plasticized by LPB were significantly improved, and the effect of LPB with high 1,2-vinyl content was better. In a word, LPB as a new environmental protection plasticizer can be used to effectively replace the TDAE plasticizing SSBR/BR. KEYWORDS crosslinking network, liquid polybutadiene, PAHs, styrene-butadiene rubber, TDAE, tire tread compound, 1 | INTRODUCTION In recent years, with people's increasing attention to environmental protection, the successful application of environmental protection materials is the research focus of material science. Since the 1990s, [...]

Background Aortic dissection (AD) during pregnancy and puerperium is a rare catastrophe with devastating consequences for both parent and fetus. Population‐level incidence trends and outcomes remain relatively undetermined. Methods and Results We queried a US population‐based health care database, the National Inpatient Sample, and identified all patients with a pregnancy‐related AD hospitalization from 2002 to 2017. In total, 472 pregnancy‐related AD hospitalizations (mean age, 30.9±0.6 years) were identified from 68 514 000 pregnancy‐related hospitalizations (0.69 per 100 000 pregnancy‐related hospitalizations), with 107 (22.7%) being type A and 365 (77.3%) being type B. The incidence of AD appeared to increase over the 16‐year study period but was not statistically significant (P for trend >0.05). Marfan syndrome, primary hypertension, and preeclampsia/eclampsia were found in 21.9%, 14.4%, and 11.5%, respectively. On multivariable logistic regression analysis, Marfan syndrome was associated with the highest risk of developing AD during pregnancy and puerperium (adjusted odds ratio, 3469.36 [95% CI, 1767.84–6831.75]; P

Osteoclast over-activation leads to bone loss and chloride homeostasis is important for osteoclast function. Here, the authors show that Anoctamin 1 controls bone resorption by coupling Cl− channel activation with RANKL-RANK signaling transduction.

Abstract Background Hirschsprung's disease (HSCR) is a relatively common congenital disability. Accumulating extracellular matrix (ECM) prompts intestinal fibrosis remodelling in the aganglionic segments of HSCR. The contributions of various cellular subsets in the fibrogenesis of HSCR segments are poorly understood. Methods Single‐cell transcriptomics from 8 aganglionic segments and 5 normal segments of 7 HSCR subjects and 26 healthy segments of seven healthy donors were analysed. Fibrotic phenotype and alterations were explored using differential expression analysis and single‐cell trajectory analysis. Fibrosis‐related transcription factors were inferred through single‐cell regulatory network inference. Bulk transcriptomic data, proteomic data, immunohistochemistry (IHC) and real‐time polymerase chain reaction were used to validate the alterations in the HSCR intestine. Results Various collagen, fibronectin and laminin protein‐coding genes expression were up‐regulated in the stromal and glial cells of the HSCR intestine. The number of fibroblasts and myofibroblasts in the aganglionic segments increased, and more myofibroblasts were activated at an earlier stage in HSCR segments, which infers that there is an intestinal fibrosis phenotype in HSCR segments. The fibrotic regulators POSTN, ANXA1 and HSP70 were highly expressed in the ECM‐related cellular subsets in the transitional segments and aganglionic segments. The transcription factor regulatory network revealed that fibrosis‐related and megacolon‐related NR2F1 in the fibroblasts and glial subsets was up‐regulated in the aganglionic segment. Conclusions This work identifies intestinal fibrosis and related regulators in aganglionic segments of HSCR; hence, anti‐fibrotic therapy may be considered to prevent HSCR‐associated enterocolitis (HAEC), relieve intestinal stricture and improve cell therapy.

BackgroundGastric cancer (GC) is a serious threat to human health. The clinical GC characteristics in China may be impacted by changes in people’s lifestyles and the promotion of early GC (EGC) screening. The present study aims to evaluate the recent trends of GC characteristics in South China and search for hazardous factors limiting the survival time of GC patients.MethodsData on GC patients that were hospitalized in the Department of Digestive Center, the First Affiliated Hospital, Sun Yat-sen University, from 1994 to 2019 were collected and divided into two categories according to the time when the EGC screening began in China: the PRE group (previous 13 years, 1994–2006) and the PAS group (past 13 years, 2007–2019).ResultsWe found that, although the 5-year survival rate increased in the PAS group compared with the PRE group (P < 0.0001), patients with age ≥60 years or Borrmann type IV still had a worse prognosis. In the PAS group, the larger percentages of elderly patients and patients with Borrmann type IV in the lymphatic metastases (N1) group (41.0% vs. 51.1%, P = 0.0014) and stage IV subgroup (20.7% vs. 32.2%, P = 0.016), respectively, when compared with the PRE group, may have contributed to the poor outcome of GC. By comparing the odds ratio (OR) of 5-year overall survival (OS) in the two 13-year periods, female sex and T2 turned into risk factors because of a greater proportion of Borrmann type IV or elderly patients in the PAS group (OR = 0.983, 95% CI = 0.723–1.336 vs. OR = 1.277, 95% CI = 1.028–1.586 and OR = 1.545, 95% CI = 0.499–4.775 vs. OR = 2.227, 95% CI = 1.124–4.271, respectively).ConclusionsDespite the GC epidemiology changes, the overall prognosis of GC patients has improved in South China. However, old age and Borrmann type IV are still the major restrictions affecting the survival of GC patients, a situation which calls for additional attention.

Abstract Objective To explore the analgesic effects of different concentrations of ropivacaine in transversalis fascia plane (TFP) block during laparotomy. Methods Ninety patients who underwent laparotomy admitted to our hospital from March 2019 to March 2020 were selected as the study subjects and were divided equally into a low concentration group, a medium concentration group, and a high concentration group according to the randomized grouping method. The low concentration group adopted 0.4% ropivacaine 40 ml, the medium concentration group was given 0.5% ropivacaine 40 ml, and the high concentration group was given 0.6% ropivacaine 40 ml. The hemodynamic indexes and the incidence of adverse reactions in the two groups were compared. The Numerical Rating Scale (NRS) was used to assess the postoperative pain in the three groups, the Bruggrmann comfort scale (BCS) was used to assess the comfort level in the three groups, and the Mini-mental State Examination (MMSE) was used to evaluate the postoperative cognitive function of the three groups of patients. Results The mean artery pressure (MAP) and heart rate (HR) levels at T1 and T2 were significantly lower in the medium concentration group than in the other two groups (P

The emerging and ongoing outbreak of human monkeypox (hMPX) in 2022 is a serious global threat. An understanding of the evolution of the monkeypox virus (MPXV) at the single-gene level may provide clues for exploring the unique aspects of the current outbreak: rapidly expanding and sustained human-to-human transmission. For the current investigation, alleles of 156 MPXV coding genes (which account for >95% of the genomic sequence) have been gathered from roughly 1,500 isolates, including those responsible for the previous outbreaks. Using a range of molecular evolution approaches, we demonstrated that intra-species homologous recombination has a negligible effect on MPXV evolution. Despite the fact that the majority of the MPXV genes (64.10%) were subjected to negative selection at the whole gene level, 10 MPXV coding genes (MPXVgp004, 010, 012, 014, 044, 098, 138, 178, 188, and 191) were found to have a total of 15 codons or amino acid sites that are known to evolve under positive Darwinian selection. Except for MPXVgp138, almost all of these genes encode proteins that interact with the host. Of these, five ankyrin proteins (MPXVgp004, 010, 012, 178, and 188) and one Bcl-2-like protein (MPXVgp014) are involved in poxviruses’ host range determination. We discovered that the majority (80%) of positive amino acid substitutions emerged several decades ago, indicating that these sites have been under constant selection pressure and that more adaptable alleles have been circulating in the natural reservoir. This finding was also supported by the minimum spanning networks of the gene alleles. The three positive amino acid substitutions (T/A426V in MPXVgp010, A423D in MPXVgp012, and S105L in MPXVgp191) appeared in 2019 or 2022, indicating that they would be crucial for the virus’ eventual adaptation to humans. Protein modeling suggests that positive amino acid substitutions may affect protein functions in a variety of ways. Further study should focus on revealing the biological effects of positive amino acid substitutions in the genes for viral adaptation to humans, virulence, transmission, and so on. Our study advances knowledge of MPXV’s adaptive mechanism and provides insights for exploring factors that are responsible for the unique aspects of the current outbreak.

The precise correlation between the pipeline defects and inspection signals is a key issue in the analysis of echo signals in ultrasonic inline inspection. However, the sensitivity of acoustic and electric signals in the transmission, propagation, and reception during the inspection brings great challenges to this problem. Analyzing the direct piezoelectric effect of Lead Zirconate Titanate(PZT) through numerical simulation is an effective way to study the characteristics of the inspection signals. Therefore, a finite element analysis model of the probe was established with the COMSOL software, the echo data were extracted from the simulation results of sound field in the probe array as the initial excitation load of the model for simulation, and the accuracy of the finite element model was verified by comparing with the experimental results of ultrasonic inline inspection. The results show that: The error between the simulation result and the measured data of the ratio of the maximum peak values of the surface echo and the primary bottom echo is 1.36%, indicating that the new model has a relatively high accuracy. The defect depth of the inner wall surface has a significant influence on the amplitude of the second peak in the PZT electrical signal spectrogram, and an effective correlation can be established between them. In addition, based on the simulation results of electric signals, the maximum valley point of the surface echo and the maximum peak point of the primary bottom echo can be extracted in the time-domain diagram of echo as the characteristic points, and the maximum error of the inspected pipeline wall thickness is 3.95%. Generally, the research results could provide reference for the localization of ultrasonic inline inspection tools.

Abstract Background Biliary atresia (BA) is a devastating inflammatory and fibrosing cholangiopathy of neonates with unknown aetiology. We aim to investigate the relationship between these two main characteristics. Methods Single‐cell RNA sequencing and spatial transcriptomics were performed on liver samples from a cohort of 14 objects (BA: n = 6; control: n = 8). We conducted data integration and cell‐type annotation based on gene expression profiling. Furthermore, we identified fibrosis‐related immune cells according to their spatial locations, GO and KEGG analysis. Finally, SPOTlight and CIBERSORTx were used to deconvolute ST data and microarray data of the GSE46960 cohorts, respectively. Results Immune subpopulations inhabiting the ‘fibrotic niche’ (areas of scarring), comprising ‘intermediate’ CD14++CD16+ monocytes, scar‐associated macrophages, natural killer T cells, transitional B cells and FCN3+ neutrophils were identified. GO and KEGG analyses showed that pathways including ‘positive regulation of smooth muscle cell/fibroblast proliferation’ and ‘positive regulation of/response to VEGFR/VEGF/EGFR/FGF’ were enriched in these cell types. Interactions analysis showed that communication among ‘FGF_FGFR’, ‘RPS19‐C5AR1’, ‘CD74_COPA/MIF/APP’ and ‘TNFRSF1A/B_GRN’ was extensive. Finally, the results of deconvolution for ST data and microarray data validated that the proportions of certain identified fibrosis‐related cell types we identified were increased in BA. Discussion Fibrosis is an important feature of BA, in which the immune system plays an important role. Our work reveals the subpopulations of immune cells enriched in the fibrotic niche of BA liver, as well as key related pathways and molecules; some are highlighted for the first time in liver fibrosis. These newly identified interactions might partly explain why the rate of liver fibrosis occurs much faster in BA than in other liver diseases. Conclusion Our study revealed the molecular, cellular and spatial immune microenvironment of the fibrotic niche of BA.

As a neuroendocrine tumor derived from the neural crest, neuroblastoma (NB) is the most common extracranial solid tumor in children. The prognosis in patients with low- and intermediate-risk NB is favorable while that in high-risk patients is often detrimental. However, the management of the considerably large proportion of high-risk patients remains challenging in clinical practice. Among various new approaches, oncolytic virus (OV) therapy offers great advantages in tumor treatment, especially for high-risk NB. Genetic modified OVs can target NB specifically without affecting normal tissue and avoid the widespread drug resistance issue in anticancer monotherapy. Meanwhile, its safety profile provides great potential in combination therapy with chemo-, radio-, and immunotherapy. The therapeutic efficacy of OV for NB is impressive from bench to bedside. The effectiveness and safety of OVs have been demonstrated and reported in studies on children with NB. Furthermore, clinical trials on some OVs (Celyvir, Pexa-Vec (JX-594) and Seneca Valley Virus (NTX-010)) have reported great results. This review summarizes the latest evidence in the therapeutic application of OVs in NB, including those generated in cell lines, animal models and clinical trials.

Abstract As a clean and renewable energy, wave energy has abundant reserves, and its reasonable development and utilization can effectively alleviate the problems of energy shortage and environmental pollution. This paper proposes a mechanical rectification wave energy converter. The reciprocating linear motion of the buoy is directly converted into the rotary motion through the ball screw. The magnetic coupling force transmission system is adopted to ensure the sealing of the device. Using mechanical rectification mechanism to ensure the service life of the generator. In addition, a dynamic model of the mechanical rectification wave energy converter is established. Through simulation analysis, the curve of power with load resistance is obtained. And there is an optimal load resistance value corresponding to the maximum power in different wave conditions. In order to improve the power generation efficiency, the maximum power point tracking control algorithm is designed based on the admittance differentiation method. By controlling the duty cycle of the switch tube in the Buck‐Boost chopper circuit, the variable load is realized, and then the maximum power point tracking control is realized. Finally, simulation analysis verifies the feasibility of the algorithm under different wave conditions.

Legionnaires’ disease (LD), caused by Legionella, including the most prevalent Legionella pneumophila, has been treated primarily with antibiotics. Environmental water and soil are the reservoirs for L. pneumophila. Studying antimicrobial susceptibility using a large number of isolates from various environmental sources and regions could provide an unbiased result. In the present study, antimicrobial susceptibility of 1464 environmental L. pneumophila isolates that were derived from various environmental water and soil sources of 12 cities in China to rifampin (RIF), erythromycin (ERY), clarithromycin (CLA), azithromycin (AZI), ciprofloxacin (CIP), moxifloxacin (MOX), levofloxacin (LEV), and doxycycline (DOX) was investigated, and minimum inhibitory concentration (MIC) data were obtained. We show that regarding macrolides, ERY was least active (MIC90 = 0.5 mg/L), while CLA was most active (MIC90 = 0.063 mg/L). A total of three fluoroquinolones have similar MICs on L. pneumophila. Among these antimicrobials, RIF was the most active agent, while DOX was the most inactive one. We observed different susceptibility profiles between serogroup 1 (sg1) and sg2-15 or between water and soil isolates from different regions. The ECOFFs were ERY and AZI (0.5 mg/L), RIF (0.002 mg/L), CIP, CLA and MOX (0.125 mg/L), LEV (0.063 mg/), and DOX (32 mg/L). Overall, two fluoroquinolone-resistant environmental isolates (0.14%) were first documented based on the wild-type MIC distribution. Not all azithromycin-resistant isolates (44/46, 95.65%) harbored the lpeAB efflux pump. The MICs of the ERY and CLA on the lpeAB + isolates were not elevated. These results suggested that the lpeAB efflux pump might be only responsible for AZI resistance, and undiscovered AZI-specific resistant mechanisms exist in L. pneumophila. Based on the big MIC data obtained in the present study, the same defense strategies, particularly against both CLA and RIF, may exist in L. pneumophila. The results determined in our study will guide further research on antimicrobial resistance mechanisms of L. pneumophila and could be used as a reference for setting clinical breakpoints and discovering antimicrobial-resistant isolates in the clinic, contributing to the antibiotic choice in the treatment of LD.

During the rough marine environment, heave compensation is used to offset the heave motion of the vessel when a marine crane lifts and lands the load. Thus, load motion and vessel motion are realized decoupled. In previous studies, the interference items such as hydraulic cylinder friction, underwater drag force and nonlinear friction in the active heave compensation system of a marine hydraulic crane are compensated as a concentrated interference force to be estimated. In this paper, we disassembled the interference items; the disturbance observer and adaptive rate are designed to estimate unmodeled disturbance force and system uncertain parameters, respectively; and we designed an active heave compensator with the adaptive nonlinear cascade controller which has the disturbance observer (DOB-ANCC). For the heave compensation of load displacement, this paper derived the control law of the nonlinear system model based on the backstepping method. The outer loop control is displacement control and the inner loop control is pressure control. The simulation verifies the effectiveness of the control strategy proposed in this paper and the availability of heave displacement compensation for a marine crane hoisting load. The compensation efficiency of the designed controller (DOB-ANCC) for the heave motion of the load can reach more than 95%, and the maximum displacement tracking error of the controller can reach ± 0.035 m.

Sialoblastoma (SBL) is an infrequent embryonal malignant tumor originating from the salivary gland, resembling primitive salivary gland anlage, whereas hepatoblastoma (HB) is the most common pediatric liver malignancy. The simultaneous occurrence of both tumors is extremely rare. Here we reported a case of a 6-month-old infant diagnosed with synchronous SBL and HB. The patient received neoadjuvant chemotherapy followed by surgical resection. Fresh tissues of both tumors were collected before and after chemotherapy, which were further profiled by whole exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq). WES analysis revealed potential somatic driver mutation PIK3CA p.Glu454Lys for SBL and canonical mutation CTNNB1 p.Ser45Pro for HB. No shared somatic variants or common copy number alterations were found between SBL and HB primary tumor samples. Though scRNA-seq, single-cell atlases were constructed for both tumors. SBL may recapitulate a pre-acinar stage in the development of salivary gland, including basaloid, duct-like, myoepithelial-like, and cycling phenotypes. In the meantime, HB was composed of tumor cells resembling different stages of the liver, including hepatocyte-like, hepatic progenitor-like, and hepatoblast-like cells. After chemotherapy, both tumors were induced into a more mature phenotype. In terms of transcriptional signatures, SBL and HB showed enhanced expression of epithelial markers KRT8, KRT18, and essential embryo development genes SDC1, MDK, indicating the disruption of normal embryo epithelium development. Finally, heterozygous deleterious germline mutation BLM and FANCI were identified which could predispose the patient to higher cancer risk. It partially explained the reason for the co-occurrence of SBL and HB. Taken together, we provided valuable resources for deciphering cellular heterogeneity and adaptive change of tumor cells after chemotherapy for synchronous SBL and HB, providing insights into the mechanisms leading to synchronous pediatric tumors.

A 39-year-old woman with a 3-year human papillomavirus (HPV) 18 infection history was admitted to the hospital for a 16-day history of vaginal bleeding after sex. She was diagnosed with cervical cancer based on the results of the electronic colposcopy, cervical cytology, microscopy, and magnetic resonance imaging (MRI). Then, she received chemotherapy, with paclitaxel 200 mg (day 1), cisplatin 75 mg (day 2), and bevacizumab 700 mg (day 3) twice with an interval of 27 days. During the examination for the diagnosis and treatment, many invasive operations, including removal of intrauterine device, colposcopy, and ureteral dilatation, were done. After that, the patient was discharged and entered the emergency department about 2.5 months later with a loss of consciousness probably caused by septic shock. The patient finally died of multiple organ failure and bacterial infection, although she has received antimicrobial therapy. The blood cultures showed a monobacterial infection with an anaerobic Gram-positive bacterial strain, designated as SAHP1. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI–TOF MS) indicated that the patient was infected with Peptoniphilus asaccharolyticus, while molecular analysis and genome-based taxonomy confirmed the infection with a novel Peptoniphilus species that has a close genetic relationship with Peptoniphilus vaginalis and proposed provisionally as Peptoniphilus septimus sp. nov., which may also act as a commensal of the human vagina. Genomic features of SAHP1 have been fully described, and comparative genomic analysis reveals the known prokaryote relative of Peptoniphilus septimus sp. nov. in the genus Peptoniphilus. The invasive operations on the genital tract during the diagnosis and treatment of the patient and the tumor tissue damage and bleeding may have a certain role in the bloodstream infection. This study casts a new light on the Peptoniphilus bacteria and prompts clinicians to include anaerobic blood cultures as part of their blood culture procedures, especially on patients with genital tract tumors. Furthermore, due to the incomplete database and unsatisfying resolution of the MALDI–TOF MS for Peptoniphilus species identification, molecular identification, especially whole-genome sequencing, is required for those initially identified as bacteria belonging to Peptoniphilus in the clinical laboratory.

ABSTRACT The distribution of pathogenic Legionella in the environmental soil and water of China has not been documented yet. In this study, Legionella was detected in 129 of 575 water (22.43%) and 41 of 442 soil samples (9.28%) by culture. Twelve Legionella species were identified, of which 11 were disease-associated. Of the Legionella-positive samples, 109 of 129 (84.50%) water and 29 of 41 (70.73%) soil were positive for L. pneumophila, which accounted for about 75% of Legionella isolates in both water and soil, suggesting L. pneumophila was the most frequent species. Soil showed a higher diversity of Legionella spp. as compared with water (0.6279 versus 0.4493). In contrast, serogroup (sg) 1 was more prevalent among L. pneumophila isolates from water than from soil (26.66% versus 12.21%). Moreover, many disease-associated sequence types (STs) of L. pneumophila were found in China. Intragenic recombination was acting on L. pneumophila from both water and soil. Phylogeny, population structure, and molecular evolution analyses revealed a probable existence of L. pneumophila isolates with a special genetic background that is more adaptable to soil or water sources and a small proportion of genetic difference between water and soil isolates. The detection of viable, clinically relevant Legionella demonstrates soil as another source for harboring and dissemination of pathogenic Legionella bacteria in China. Future research should assess the implication in public health with the presence of Legionella in the soil and illustrate the genetic and pathogenicity difference of Legionella between water and soil, particularly the most prevalent L. pneumophila. IMPORTANCE Pathogenic Legionella spp. is the causative agent of Legionnaires’ disease (LD), and L. pneumophila is the most common one. Most studies have focused on L. pneumophila from water and clinical samples. However, the soil is another important reservoir for this bacterium, and the distribution of Legionella spp. in water and soil sources has not been compared and documented in China yet. Discovering the distribution of Legionella spp. and L. pneumophila in the two environments may help a deep understanding of the pathogenesis and molecular evolution of the bacterium. Our research systematically uncovered the distributions of Legionella spp. in different regions and sources (e.g., water and soil) of China. Moreover, phylogeny, population structure, and molecular evolution study revealed the possible existence of L. pneumophila with a special genetic background that is more adaptable to soil or water sources, and genetic difference may exist.

The reliability of the machining process is a vital indicator in the manufacturing process of mechanical parts, and directly related to the machining quality of mechanical products. In order to effectively utilize machining process information and machining quality inspection data to evaluate the reliability of the machining process, this paper extends the relevant concepts of information theory to the field of mechanical manufacturing error analysis and establishes a reliability analysis model of the machining process. The model introduces information entropy into the analysis of machining process reliability by defining vertex entropy to measure the uncertainty of the machining quality of each process, and thus realizing the determination of critical processes using a fully quantitative method. Meanwhile, the transfer coefficient defined by mutual information is used to measure the transfer of machining error between two processes. Through combining vertex entropy and the transfer coefficient, the quantitative analysis of machining process reliability is achieved. The model proposed in this paper addresses the issue that the subjective factors of researchers in other related studies have an impact on the analysis results. Finally, the correctness of the proposed model is verified using Monte Carlo simulations.

An important task in the construction of China’s ecological civilization, the selection and implementation of policy instruments fully reflect the actual effectiveness of the government’s efforts to control air pollution. Based on the content analysis method, this study examines the changing process of air pollution control policy instruments in southwest China from 2010 to 2021 in terms of implementation, synergy, and integration of policy instruments. The results show that, in terms of the degree of mandatory, the frequency of using policy instruments generally increased with time, but the overall balance of the instrument portfolio was poor. In terms of the degree of synergy, a gradual shift occurred from government-led to government-society governance. However, the concept and modes of inter-governmental linkage and cross-regional collaborative governance need to be improved. As for the degree of systemic, a clear trend of instrument integration and more frequent information interaction was found. Emergency-oriented characteristics appear strong, but a regular governance mechanism is lacking. Therefore, this paper provides policy suggestions and academic considerations for further improving the effectiveness of air pollution management in southwest China from three aspects: optimizing the policy tool system, deepening the regional joint prevention and control mechanism of air pollution, and promoting intelligent air pollution management.

Background and ObjectiveIt is urgent to find out an alternative therapy for Kawasaki disease (KD) since around 20% patients are resistant to intravenous immunoglobulin (IVIG) or aspirin. Tanshinone IIA is the active component of the traditional Chinese medicine Danshen (Salvia miltiorrhiza), which has anti-inflammatory and anti-platelet properties; however, whether or not tanshinone IIA has a therapeutic effect on KD remains unclear. Therefore, the present study aimed to examine the effect of tanshinone IIA on KD patients and rabbits with immune vasculitis, and to identify the potential mechanisms with special emphasis on megakaryopoiesis and megakaryocytic apoptosis.MethodsKawasaki disease patients were recruited and prescribed with tanshinone IIA in the absence or presence of aspirin and IVIG, and the inflammatory responses and platelet functions were determined. Megakaryocytes (MKs) isolated from rabbits with immune vasculitis and human megakaryocytic CHRF-288-11 cells were treated with tanshinone IIA to examine the colony forming unit (CFU) and apoptosis, respectively. Microarray assay was conducted to identify potential targets of tanshinone IIA-induced apoptosis.ResultsTanshinone IIA reduced the serum levels of C-reactive protein (CRP), interleukin (IL)-1β, IL-6, and P-selectin in KD patients; such inhibitory effect was more significant compared to aspirin and IVIG. It also dose-dependently lowered the levels of tumor necrosis factor (TNF)-α and IL-8 in peripheral blood mononuclear cells isolated from KD patients. In rabbits with immune vasculitis, tanshinone IIA significantly reduced the serum levels of proinflammatory cytokines and platelet functions. In addition, tanshinone IIA significantly decreased the number of bone marrow MKs and inhibited the Colony Forming Unit-Megakaryocyte (CFU-MK) formation. In human megakaryocytic CHRF-288-11 cells, tanshinone IIA induced caspase-dependent apoptosis, probably through up-regulating TNF receptor superfamily member 9 (TNFRSF9) and the receptor (TNFRSF)-interacting serine/threonine-protein kinase 1 (RIPK1), which may contribute to its anti-platelet and anti-inflammatory properties.ConclusionTanshinone IIA exerts better anti-inflammatory and anti-platelet effects in treating KD patients than aspirin and IVIG. It attenuates immune vasculitis likely by inhibiting IL-mediated megakaryopoiesis and inducing TNFRSF9/RIPK1/caspase-dependent megakaryocytic apoptosis. The findings therefore suggest that tanshinone IIA may be a promising alternative therapy for the treatment of KD.

Wound management remains a worldwide challenge. It is undeniable that patients with problems such as difficulties in wound healing, metabolic disorder of the wound microenvironment and even severely infected wounds etc. always suffer great pain that affected their quality of lives. The selection of appropriate wound dressings is vital for the healing process. With the advances of technology, hydrogels dressings have been showing great potentials for the treatment of both acute wounds (e.g., burn injuries, hemorrhage, rupturing of internal organs/aorta) and chronic wounds such as diabetic foot and pressure ulcer. Particularly, in the past decade, polysaccharide-based hydrogels which are made up with abundant and reproducible natural materials that are biocompatible and biodegradable present unique features and huge flexibilities for modifications as wound dressings and are widely applicable in clinical practices. They share not only common characteristics of hydrogels such as excellent tissue adhesion, swelling, water absorption, etc., but also other properties (e.g., anti-inflammatory, bactericidal and immune regulation), to accelerate wound re-epithelialization, mimic skin structure and induce skin regeneration. Herein, in this review, we highlighted the importance of tailoring the physicochemical performance and biological functions of polysaccharide-based hydrogel wound dressings. We also summarized and discussed their clinical states of, aiming to provide valuable hints and references for the future development of more intelligent and multifunctional wound dressings of polysaccharide hydrogels.

Summary: Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) play critical roles in tumorigenesis. However, the mechanisms underlying MDSC and TAM development and function remain unclear. In this study, we find that myeloid-specific activation of Notch/RBP-J signaling downregulates lactate transporter MCT2 transcription via its downstream molecule Hes1, leading to reduced intracellular lactate levels, blunted granulocytic MDSC (G-MDSC) differentiation, and enhanced TAM maturation. We identify c-Jun as a novel intracellular sensor of lactate in myeloid cells using liquid-chromatography-mass spectrometry (LC-MS) followed by CRISPR-Cas9-mediated gene disruption. Meanwhile, lactate interacts with c-Jun to protect from FBW7 ubiquitin-ligase-mediated degradation. Activation of Notch signaling and blockade of lactate import repress tumor progression by remodeling myeloid development. Consistently, the relationship between the Notch-MCT2/lactate-c-Jun axis in myeloid cells and tumorigenesis is also confirmed in clinical lung cancer biopsies. Taken together, our current study shows that lactate metabolism regulated by activated Notch signaling might participate in MDSC differentiation and TAM maturation.

Abstract Background Transaxillary access (TAx) has shown promise as an excellent alternative TAVR option, but data on the Edwards SAPIEN 3 in TAx-TAVR is limited. We sought to study the safety and efficacy of TAx-TAVR using this current-generation balloon-expandable valve. Methods A retrospective study of our first 24 TAx and 20 transthoracic (TT) TAVR patients treated with the SAPIEN 3 valve was performed, and the patients’ preoperative characteristics, procedural outcomes, and clinical outcomes were compared to our first 100 transfemoral (TF) patients using the SAPIEN 3 device. Results There were no statistical differences observed for outcomes between the TAx and TF groups, despite the TAx patients having more comorbidities (STS-PROM 11.3 ± 7.6 versus 7.3 ± 5.2, p = 0.042). In addition, no significant difference was found in the fluoroscopy time and contrast amount between the two groups. The patients’ baseline characteristics were similar between the TAx and TT groups. Their procedural and clinical outcomes were comparable, but there was a trend towards lower incidence of acute kidney injury (13.0% versus 23.5%), new-onset atrial fibrillation (5.6% versus 33.3%), shorter median length of stay postoperatively (4 versus 6 days), fewer discharges to rehabilitation (16.7% versus 35.0%), and a lower rate of readmission within 30-days (8.3% versus 35.0%), all favoring TAx access. Conclusions TAx-TAVR with the SAPIEN 3 valve is a safe alternative to TF access. It offers advantages of improved recovery over TT access, and appears to be a superior alternative-access option for TAVR. TAx access could be preferred when TF access is not feasible.

Abstract. The homeostasis of the gut-brain axis has been shown to exert several effects on physiological and psychological health. The gut hormones released by enteroendocrine cells scattered throughout the gastrointestinal tract are important signaling molecules within the gut-brain axis. The interaction between gut microbiota and gut hormones has been greatly appreciated in gut-brain cross-talk. The microbiota plays an essential role in modulating many gut-brain axis-related diseases, ranging from gastrointestinal disorders to psychiatric diseases. Similarly, gut hormones also play pleiotropic and important roles in maintaining health, and are key signals involved in gut-brain axis. More importantly, gut microbiota can affect the release and functions of gut hormones. This review highlights the role of gut microbiota in the gut-brain axis and focuses on how microbiota-related gut hormones modulate various physiological functions. Future studies could target the microbiota-hormones-gut brain axis to develop novel therapeutics for different psychiatric and gastrointestinal disorders, such as obesity, anxiety, and depression.

Lung cancer is one of the most common and mortal malignancies, usually with a poor prognosis in its advanced or recurrent stages. Recently, immune checkpoint inhibitors (ICIs) immunotherapy has revolutionized the treatment of human cancers including lung adenocarcinoma (LUAD), and significantly improved patients’ prognoses. However, the prognostic and predictive outcomes differ because of tumor heterogeneity. Here, we present an effective method, GDPLichi (Genes of DNA damage repair to predict LUAD immune checkpoint inhibitors response), as the signature to predict the LUAD patient’s response to the ICIs. GDPLichi utilized only 7 maker genes from 8 DDR pathways to construct the predictive model and classified LUAD patients into two subgroups: low- and high-risk groups. The high-risk group was featured by worse prognosis and decreased B cells, CD8+ T cells, CD8+ central memory T cells, hematopoietic stem cells (HSC), myeloid dendritic cells (MDC), and immune scores as compared to the low-risk group. However, our research also suggests that the high-risk group was more sensitive to ICIs, which might be explained by increased TMB, neoantigen, immune checkpoint molecules, and immune suppression genes’ expression, but lower TIDE score as compared to the low-risk group. This conclusion was verified in three other LUAD cohort datasets (GSE30219, GSE31210, GSE50081).

Pathogenic species of Legionella can infect human alveolar macrophages through Legionella-containing aerosols to cause a disease called Legionellosis, which has two forms: a flu-like Pontiac fever and severe pneumonia named Legionnaires’ disease (LD). Legionella is an opportunistic pathogen that frequently presents in aquatic environments as a biofilm or protozoa parasite. Long-term interaction and extensive co-evolution with various genera of amoebae render Legionellae pathogenic to infect humans and also generate virulence differentiation and heterogeneity. Conventionally, the proteins involved in initiating replication processes and human macrophage infections have been regarded as virulence factors and linked to pathogenicity. However, because some of the virulence factors are associated with the infection of protozoa and macrophages, it would be more accurate to classify them as survival factors rather than virulence factors. Given that the molecular basis of virulence variations among non-pathogenic, pathogenic, and highly pathogenic Legionella has not yet been elaborated from the perspective of virulence factors, a comprehensive explanation of how Legionella infects its natural hosts, protozoans, and accidental hosts, humans is essential to show a novel concept regarding the virulence factor of Legionella. In this review, we overviewed the pathogenic development of Legionella from protozoa, the function of conventional virulence factors in the infections of protozoa and macrophages, the host’s innate immune system, and factors involved in regulating the host immune response, before discussing a probably new definition for the virulence factors of Legionella.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly resistant to current treatments. ESCC harbors a subpopulation of cells exhibiting cancer stem-like cell (CSC) properties that contribute to therapeutic resistance including radioresistance, but the molecular mechanisms in ESCC CSCs are currently unknown. Here, we report that ribosomal S6 protein kinase 4 (RSK4) plays a pivotal role in promoting CSC properties and radioresistance in ESCC. RSK4 was highly expressed in ESCC CSCs and associated with radioresistance and poor survival in patients with ESCC. RSK4 was found to be a direct downstream transcriptional target of [DELTA]Np63[alpha], the main p63 isoform, which is frequently amplified in ESCC. RSK4 activated the [beta]-catenin signaling pathway through direct phosphorylation of GSK-3[beta] at Ser9. Pharmacologic inhibition of RSK4 effectively reduced CSC properties and improved radiosensitivity in both nude mouse and patient-derived xenograft models. Collectively, our results strongly suggest that the [DELTA]Np63[alpha]/RSK4/GSK-3[beta] axis plays a key role in driving CSC properties and radioresistance in ESCC, indicating that RSK4 is a promising therapeutic target for ESCC treatment., Introduction Esophageal cancer is one of the most frequently occurring cancers and ranks as the seventh leading cause of cancer-related mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most [...]

Effector proteins translocated by the Dot/Icm type IV secretion system determine the virulence of Legionella pneumophila (L. pneumophila). Among these effectors, members of the SidE family (SidEs) regulate several cellular processes through a unique phosphoribosyl ubiquitination mechanism mediated by another effector, SidJ. Host-cell calmodulin (CaM) activates SidJ to glutamylate the SidEs of ubiquitin (Ub) ligases and to make a balanced Ub ligase activity. Given the central role of SidJ in this regulatory process, studying the nature of evolution of sidJ is important to understand the virulence of L. pneumophila and the interaction between the bacteria and its hosts. By studying sidJ from a large number of L. pneumophila strains and using various molecular evolution algorithms, we demonstrated that intragenic recombination drove the evolution of sidJ and contributed to sidJ diversification. Additionally, we showed that four codons of sidJ which are located in the N-terminal (NTD) (codons 58 and 200) and C-terminal (CTD) (codons 868 and 869) domains, but not in the kinase domain (KD) had been subjected to strong positive selection pressure, and variable mutation profiles of these codons were identified. Protein structural modeling of SidJ provided possible explanations for these mutations. Codons 868 and 869 mutations might engage in regulating the interactions of SidJ with CaM through hydrogen bonds and affect the CaM docking to SidJ. Mutation in codon 58 of SidJ might affect the distribution of main-chain atoms that are associated with the interaction with CaM. In contrast, mutations in codon 200 might influence the α-helix stability in the NTD. These mutations might be important to balance Ub ligase activity for different L. pneumophila hosts. This study first reported that intragenic recombination and positive Darwinian selection both shaped the genetic plasticity of sidJ, contributing to a deeper understanding of the adaptive mechanisms of this intracellular bacterium to different hosts.

With global warming and regional decreases in precipitation, drought has become a problem worldwide. As the number of arid regions in the world is increasing, drought has become a major factor leading to significant crop yield reductions and food crises. Soybean is a crop that is relatively sensitive to drought. It is also a crop that requires more water during growth and development. The aim of this study was to identify the quantitative trait locus (QTL) that affects drought tolerance in soybean by using a recombinant inbred line (RIL) population from a cross between the drought-tolerant cultivar ‘Jindou21’ and the drought-sensitive cultivar ‘Zhongdou33’. Nine agronomic and physiological traits were identified under drought and well-watered conditions. Genetic maps were constructed with 923,420 polymorphic single nucleotide polymorphism (SNP) markers distributed on 20 chromosomes at an average genetic distance of 0.57 centimorgan (cM) between markers. A total of five QTLs with a logarithm of odds (LOD) value of 4.035–8.681 were identified on five chromosomes. Under well-watered conditions and drought-stress conditions, one QTL related to the main stem node number was located on chromosome 16, accounting for 17.177% of the phenotypic variation. Nine candidate genes for drought resistance were screened from this QTL, namely Glyma.16G036700, Glyma.16G036400, Glyma.16G036600, Glyma.16G036800, Glyma.13G312700, Glyma.13G312800, Glyma.16G042900, Glyma.16G043200, and Glyma.15G100700. These genes were annotated as NAC transport factor, GATA transport factor, and BTB/POZ-MATH proteins. This result can be used for molecular marker-assisted selection and provide a reference for breeding for drought tolerance in soybean.

Elderly with comorbidities have shown a higher rate of fatal outcomes when suffering coronavirus disease 2019 (COVID-19). However, a delineation of clinical significances of hematologic indices and underlying comorbidities in the progression and outcome of COVID-19 remains undefined. Six hundred two COVID-19 patients with established clinical outcomes (discharged or deceased) from Hankou Hospital of Wuhan, China between January 14, 2020 and February 29, 2020 were retrospectively analyzed. Of the 602 patients with COVID-19, 539 were discharged and 63 died in the hospital. The deceased group showed higher leukocyte and neutrophil counts but lower lymphocyte and platelet counts. Longer activated partial thromboplastin time (APTT) and prothrombin time (PT), as well as higher D-dimer and C-reactive protein levels, were found in non-survivors. Our observations suggest that these parameters could serve as potential predictors for the fatal outcome and in the discharged group. A higher neutrophil count and D-dimer level but lower lymphocyte were associated with a longer duration of hospitalization. A multivariable Cox regression analysis showed that higher neutrophil count, prolonged PT, and low lymphocyte count were risk factors for patients with COVID-19. Also, we found an association of lower lymphocyte count and higher C-reactive protein levels with the elderly group and those with cardiovascular-related comorbidities. The significantly different hematologic profiles between survivors and non-survivors support that distinct hematologic signatures in COVID-19 patients will dictate different outcomes as a prognostic marker for recovery or fatality. Lymphopenia and aggressive inflammatory response might be major causes for fatal outcomes in the elderly male and especially those with cardiovascular-related comorbidities.

Background Transcatheter aortic valve replacement (TAVR) has become the preferred treatment for symptomatic patients with aortic stenosis and elevated procedural risk. Many deaths following TAVR are because of noncardiac causes and comorbid disease burden may be a major determinant of postprocedure outcomes. The prevalence of comorbid conditions and associations with outcomes after TAVR has not been studied. Methods and Results This was a retrospective single‐center study of patients treated with TAVR from January 2015 to October 2018. The association between 21 chronic conditions and short‐ and medium‐term outcomes was assessed. A total of 341 patients underwent TAVR and had 1‐year follow‐up. The mean age was 81.4 (SD 8.0) years with a mean Society of Thoracic Surgeons predicted risk of mortality score of 6.7% (SD 4.8). Two hundred twenty (65%) patients had ≥4 chronic conditions present at the time of TAVR. There was modest correlation between Society of Thoracic Surgeons predicted risk of mortality and comorbid disease burden (r=0.32, P

Abstract As major environment factors, drought or high salinity affect crop growth, development and yield. Transgenic approach is an effective way to improve abiotic stress tolerance of crops. In this study, we comparatively analyzed gene structures, genome location, and the evolution of syntaxin proteins containing late embryogenesis abundant (LEA2) domain. GmSYP24 was identified as a dehydration-responsive gene. Our study showed that the GmSYP24 protein was located on the cell membrane. The overexpression of GmSYP24 (GmSYP24ox) in soybean and heteroexpression of GmSYP24 (GmSYP24hx) in Arabidopsis exhibited insensitivity to osmotic/drought and high salinity. However, wild type soybean, Arabidopsis, and the mutant of GmSYP24 homologous gene of Arabidopsis were sensitive to the stresses. Under the abiotic stresses, transgenic soybean plants had greater water content and higher activities of POD, SOD compared with non-transgenic controls. And the leaf stomatal density and opening were reduced in transgenic Arabidopsis. The sensitivity to ABA was decreased during seed germination of GmSYP24ox and GmSYP24hx. GmSYP24hx induced up-regulation of ABA-responsive genes. GmSYP24ox alters the expression of some aquaporins under osmotic/drought, salt, or ABA treatment. These results demonstrated that GmSYP24 played an important role in osmotic/drought or salt tolerance in ABA signal pathway.

This study constructs comprehensive panel data based on the China City Statistical Yearbook and environmental indicators disclosed by the Ministry of Ecology and Environment from 2013 to 2017, using a difference-in-difference (DID) model to empirically validate the effects of the ecological environmental damage compensation system on urban air quality, followed by a further analysis of the system’s effect mechanism, namely, how the system has generated effects on reducing environmental pollution. This study finds that: (1) the ecological environmental damage compensation system can significantly improve urban air quality, and small cities are more sensitive to the pilot policy; and (2) the main impact is that the pilot policy mechanism improved the urban pollutant treatment capacity and reduced the proportion of the secondary industry. After multiple robustness tests, this conclusion still holds. This study provides empirical evidence for fully implementing an ecological environmental damage compensation system.