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ObjectiveEmerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown.MethodsIn this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method.ResultsThe results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, p = 0.040) and COVID-19 infection (OR = 0.988, p = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, p = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, p = 0.664), hospitalized COVID-19 (OR = 0.872, p = 0.109), and COVID-19 infection (OR = 0.943, p = 0.811) on SLE were found.ConclusionThe findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.

BackgroundMicrobial infection is accompanied by remodeling of the host transcriptome. Involvement of A-to-I RNA editing has been reported during viral infection but remains to be elucidated during intracellular bacterial infections.ResultsHerein we analyzed A-to-I RNA editing during intracellular bacterial infections based on 18 RNA-Seq datasets of 210 mouse samples involving 7 tissue types and 8 intracellular bacterial pathogens (IBPs), and identified a consensus signature of RNA editing for IBP infections, mainly involving neutrophil-mediated innate immunity and lipid metabolism. Further comparison of host RNA editing patterns revealed remarkable similarities between pneumonia caused by IBPs and single-strand RNA (ssRNA) viruses, such as altered editing enzyme expression, editing site numbers, and levels. In addition, functional enrichment analysis of genes with RNA editing highlighted that the Rab GTPase family played a common and vital role in the host immune response to IBP and ssRNA viral infections, which was indicated by the consistent up-regulated RNA editing of Ras-related protein Rab27a. Nevertheless, dramatic differences between IBP and viral infections were also observed, and clearly distinguished the two types of intracellular infections.ConclusionOur study showed transcriptome-wide host A-to-I RNA editing alteration during IBP and ssRNA viral infections. By identifying and comparing consensus signatures of host A-to-I RNA editing, our analysis implicates the importance of host A-to-I RNA editing during these infections and provides new insights into the diagnosis and treatment of infectious diseases.

Objectives: Thrombomodulin (TM) is closely related to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). However, current evidence on circulating TM levels in SLE patients is contradictory. We conducted this meta-analysis to more accurately assess circulating TM levels in patients with SLE and lupus nephritis (LN) and to analyze related influencing factors. Methods: Systematic search of relevant documents was conducted in PubMed, Embase, and The Cochrane Library databases (up to 28 February 2021). Studies on the comparison of circulating TM between SLE patients and controls were screened and evaluated for inclusion. Random-effects model analysis was applied to calculate the combined standardized mean difference (SMD) with a 95% confidence interval (CI). Heterogeneity was estimated by Q statistics and I2. Results: A total of 353 articles were identified, 14 provided adequate information for this study finally. The results illustrated that SLE patients had higher TM levels than healthy controls (SMD=0.38, 95% CI: 0.02 to 0.74, p=0.04). Circulating TM levels were increased in patients with active SLE compared to inactive SLE patients (SMD=1.12, 95% CI: 0.03 to 2.20, p=0.04). In addition, circulating TM levels of SLE patients with LN were higher than those without LN (SMD=4.55, 95% CI: 1.97 to 7.12, p=0.001). Conclusions: The circulating TM levels in SLE patients are enhanced. In addition, circulating TM levels may be practical in reflecting the disease activity and nephritis involvement of SLE patients.

Background In recent years, protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors have been widely studied as important agricultural herbicides. Our research effort was focused on the design and synthesis of novel PPO inhibitor herbicides, done through the linking of a diphenylether pyridine bioisostere structure to substituted coumarins, which aims to enhance environmental and crop safety while retaining high efficacy. The work done in our research are the design and synthesize of a series of phenoxypyridine derivatives. Results In this work, a total of 21 compounds were synthesized via acylation reactions and all the compounds were characterized using IR, 1 H-NMR, 13 C-NMR, and high-resolution mass spectra. The respective configuration of compound IV-6 and IV-12 were also confirmed using single crystal X-ray diffraction. The bioassay results showed that the title compounds displayed notable herbicidal activity, especially compound IV-6 which displayed better herbicidal activity in greenhouse and field experiments, crop selectivity and safety for cotton and soybean as compared to that of the commercial herbicide oxyfluorfen. Conclusion The present work revealed that the compound IV-6 deserves further attention as the candidate structure of novel and safe herbicide. This article is protected by copyright. All rights reserved.

BackgroundPolyunsaturated fatty acids (PUFAs) are closely related to osteoporosis. To test their causal relationship, we conducted a Mendelian randomization (MR) analysis.MethodsWe analyzed the causal relationship between four PUFAs measures, n-3 PUFAs (n-3), n-6 PUFAs (n-6), the ratio of n-3 PUFAs to total fatty acids (n-3 pct), and the ratio of n-6 PUFAs to n-3 PUFAs (n-6 to n-3), and five measures of osteoporosis, including estimated bone mineral density (eBMD), forearm (FA) BMD, femoral neck (FN) BMD, lumbar spine (LS) BMD, and fracture, using two-sample MR analysis. In order to verify the direct effect between PUFAs and BMD, we chose interleukin-6 (IL-6), tumor necrosis factor-β (TNF-β), and bone morphogenetic proteins 7 (BMP-7), three markers or cytokines strongly related to BMD, as possible confounding factors, and analyzed the possible causal relationships between them and PUFAs or BMD by MR. Inverse variance weighting (IVW), MR-Egger, weighted and weighted median were conducted. MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and MR-Egger regression methods were used to evaluate the potential pleiotropy of instrumental variables (IVs) and outliers were identified by MR-PRESSO. Cochran’s Q statistic was used to detect the heterogeneity among IVs. Leave-one-out sensitivity analysis was used to find SNPs that have a significant impact on the results. All results were corrected by the Bonferroni correction.ResultsThe IVW results showed that n-3 PUFAs (OR = 1.030, 95% CI: 1.013, 1.047, P = 0.001) and n-6 PUFAs (OR = 1.053, 95% CI: 1.034, 1.072, P < 0.001) were positively correlated with eBMD, while n-6 to n-3 (OR = 0.947, 95% CI: 0.924, 0.970, P < 0.001) were negatively correlated with eBMD. These casual relationships still existed after Bonferroni correction. There were positive effects of n-3 PUFAs on FA BMD (OR = 1.090, 95% CI: 1.011, 1.176, P = 0.025) and LS BMD (OR = 1.056, 95% CI: 1.011, 1.104, P = 0.014), n-3 pct on eBMD (OR = 1.028, 95% CI: 1.002, 1.055, P = 0.035) and FA BMD (OR = 1.090, 95% CI: 1.011, 1.174, P = 0.025), n-6 to n-3 on LS BMD (OR = 1.071, 95% CI: 1.021, 1.124, P = 0.005); negative effects of n-3 pct on fracture (OR = 0.953, 95% CI: 0.918, 0.988, P = 0.009) and n-6 to n-3 on FA BMD (OR = 0.910, 95% CI: 0.837, 0.988, P = 0.025). However, these causal effects all disappeared after Bonferroni correction (all P > 0.0025). None of IL-6, TNF-β, and BMP-7 had a causal effect on PUFA and BMD simultaneously (all P > 0.05).ConclusionEvidence from this MR study supports the genetically predicted causal effects of n-3, n-6, n-3 pct, and n-6 to n-3 on eBMD. In addition, n-3 not only associate with FA BMD and LS BMD through its own level and n-6 to n-3, but also link to fracture through n-3 pct.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause coronavirus disease 2019 (COVID-19), an acute respiratory inflammation that has emerged worldwide since December 2019, and it quickly became a global epidemic. Inflammatory bowel disease (IBD) is a group of chronic nonspecific intestinal inflammatory diseases whose etiology has not been elucidated. The two have many overlapping symptoms in clinical presentation, such as abdominal pain, diarrhea, pneumonia, etc. Imbalance of the autoimmune system in IBD patients and long-term use of immunosuppressive drugs may increase the risk of infection; and systemic symptoms caused by COVID-19 may also induce or exacerbate intestinal inflammation. It has been found that the SARS-CoV-2 receptor angiotensin converting enzyme 2, which is highly expressed in the lung and intestine, is an inflammatory protective factor, and is downregulated and upregulated in COVID-19 and IBD, respectively, suggesting that there may be a coregulatory pathway. In addition, the immune activation pattern of COVID-19 and the cytokine storm in the inflammatory response have similar roles in IBD, indicating that the two diseases may influence each other. Therefore, this review aimed to address the following research questions: whether SARS-CoV-2 infection leads to the progression of IBD; whether IBD increases the risk of COVID-19 infection and poor prognosis; possible common mechanisms and genetic cross-linking between the two diseases; new treatment and care strategies for IBD patients, and the feasibility and risk of vaccination in the context of the COVID-19 epidemic.

The mitogen-activated protein kinase (MAPK) signaling pathways are highly conserved in eukaryotes, regulating various cellular processes. The MAPK kinases (MKKs) are dual specificity kinases, serving as convergence and divergence points of the tripartite MAPK cascades. Here, we investigate the biochemical characteristics and three-dimensional structure of MKK5 in

Lung adenocarcinoma (LUAD) is the most challenging neoplasm to treat in clinical practice. Ankyrin repeat domain 49 protein (ANKRD49) is highly expressed in several carcinomas; however, its pattern of expression and role in LUAD are not known. Tissue microarrays, immunohistochemistry, χ

ObjectiveTo investigate the detection rate and influencing factors of high-risk population of cardiovascular disease in Anhui province.MethodsFrom March 2017 to August 2019, the residents aged 35–75 years old were selected using the multi-stage stratified cluster sampling method in 8 counties and districts of Anhui Province, and questionnaire survey, anthropometric measurement, and collection of biological samples were carried out among them.ResultsA total of 99,821 residents in Anhui Province were finally investigated, and among them 21,426 residents were detected to be high-risk groups of cardiovascular disease. The detection rate of high-risk groups was 21.46%. According to the high-risk types, the high-risk groups can be clustered. 74.57% of them had only one high-risk type, 22.57% of them had two high-risk types, and 2.86% had three or more high-risk types. The results of Generalized Linear Mixed Model (GLMM) showed that male, age ≥45 years old, not married, occupation as a farmer, annual family income P value < 0.05).ConclusionThe detection rate of high-risk groups of cardiovascular disease in Anhui Province is relatively high. Individualized intervention measures as well as comprehensive prevention and control strategies should be adopted focusing on the distribution characteristics of risk factors of high-risk groups.

Directional cell migration involves signaling cascades that stimulate actin assembly at the leading edge, and additional pathways must inhibit actin polymerization at the rear. During neuroblast migration in Caenorhabditis elegans, the transmembrane protein MIG-13/Lrp12 acts through the Arp2/3 nucleation-promoting factors WAVE and WASP to guide the anterior migration. Here we show that a tyrosine kinase, SRC-1, directly phosphorylates MIG-13 and promotes its activity on actin assembly at the leading edge. In GFP knockin animals, SRC-1 and MIG-13 distribute along the entire plasma membrane of migrating cells. We reveal that a receptor-like tyrosine phosphatase, PTP-3, maintains the F-actin polarity during neuroblast migration. Recombinant PTP-3 dephosphorylates SRC-1–dependent MIG-13 phosphorylation in vitro. Importantly, the endogenous PTP-3 accumulates at the rear of the migrating neuroblast, and its extracellular domain is essential for directional cell migration. We provide evidence that the asymmetrically localized tyrosine phosphatase PTP-3 spatially restricts MIG-13/Lrp12 receptor activity in migrating cells.

The serum ferritin (SF) levels of patients with hepatic alveolar echinococcosis (HAE) were compared to the laboratory reference value, and the correlation between SF and associated parameters in patients with HAE was assessed. Hematological and imaging data of 245 patients with HAE were collected. Patients were classified into the LSF group (SF ≤ 204 ng/ml) or HSF group (SF204 ng/ml) according to the level of SF. There was no significant difference in the serum iron level between groups (P0.05). Significant differences in unsaturated iron-binding capacity (UIBC), liver function, blood coagulation, lipid, blood cell count, and lesion characteristics were observed (P0.05). Correlation analysis showed that SF was related to UIBC, γ-glutamyl transferase, total bilirubin (TBIL), direct bilirubin (DBIL), fibrinogen (FIB), neutrophil count, and maximal lesion diameter (all absolute rs ≥ 0.4). The correlation coefficient between SF and UIBC showed the highest absolute value (rs = -0.556, P0.001). Single-factor linear regression analysis showed that TBIL and DBIL showed the R2 values were 0.221 and 0.220, and the R2 values of UIBC, FIB, and maximal lesion diameter were 0.157, 0.174, and 0.167, respectively, and those of the remaining indicators were0.1. Multi-factor binary logistic regression analysis showed that UIBC (P0.001, OR = 0.909), FIB (P = 0.020, OR = 1.662), hemoglobin (HGB) (P = 0.002, OR = 1.029), and maximal lesion diameter (P = 0.002, OR = 1.146) were significant factors influencing SF abnormalities. SF levels in some patients with HAE were higher than the laboratory reference value. Correlation and regression analysis of SF suggested that the UIBC, FIB, HGB, and maximal lesion diameter were related to SF and affected the SF level. These results may be helpful for the diagnosis and severity assessment of HAE in the future.

High-altitude exposure can negatively impact one’s ability to accurately perceive time. This study focuses on Chinese migrants who have traveled to the Tibetan plateau and explores the effects of high-altitude exposure on their time interval judgment abilities based on three separate studies. In Study 1, it was found that exposure to high altitudes negatively impacted the time interval judgment functions of the migrants compared with a low-altitude control group; they exhibited a prolonged response time (540 ms: p = 0.006, 95% CI (−1.70 −0.32)) and reduced accuracy (1080 ms: p = 0.032, 95% CI (0.06 1.26)) in certain behavioral tasks. In Study 2, the results showed that high-altitude exposure and sleepiness had an interactive effect on time interval judgment (1080 ms) (p < 0.05, 95% CI (−0.83 −0.40)). To further verify our interaction hypothesis, in Study 3, we investigated the time interval judgment of interactions between acute high-altitude exposure and sleepiness level. The results revealed that the adaptation effect disappeared and sleepiness significantly exacerbated the negative effects of high-altitude exposure on time interval judgment (p < 0.001, 95% CI (−0.85 −0.34)). This study is the first to examine the effects of high-altitude exposure on time interval judgment processing functions and the effects of sleep-related factors on individual time interval judgment.

The activity of 5′-adenosine monophosphate-activated protein kinase (AMPK) is inversely correlated with the cellular availability of glucose. When glucose levels are low, the glycolytic enzyme aldolase is not bound to fructose-1,6-bisphosphate (FBP) and, instead, signals to activate lysosomal AMPK. Here, we show that blocking FBP binding to aldolase with the small molecule aldometanib selectively activates the lysosomal pool of AMPK and has beneficial metabolic effects in rodents. We identify aldometanib in a screen for aldolase inhibitors and show that it prevents FBP from binding to v-ATPase-associated aldolase and activates lysosomal AMPK, thereby mimicking a cellular state of glucose starvation. In male mice, aldometanib elicits an insulin-independent glucose-lowering effect, without causing hypoglycaemia. Aldometanib also alleviates fatty liver and nonalcoholic steatohepatitis in obese male rodents. Moreover, aldometanib extends lifespan and healthspan in both Caenorhabditis elegans and mice. Taken together, aldometanib mimics and adopts the lysosomal AMPK activation pathway associated with glucose starvation to exert physiological roles, and might have potential as a therapeutic for metabolic disorders in humans.

The morphology of the hippocampus and amygdala can be significantly affected by a long-term hypoxia-induced inflammatory response. Cardiorespiratory fitness (CRF) has a significant effect on the neuroplasticity of the hippocampus and amygdala by countering inflammation. However, the role of CRF is still largely unclear at high altitudes. Here, we investigated brain limbic volumes in participants who had experienced long-term hypoxia exposure in Tibet (3680 m), utilizing high-resolution structural images to allow the segmentation of the hippocampus and amygdala into their constituent substructures. We recruited a total of 48 participants (48 males; aged = 20.92 ± 1.03 years) to undergo a structural 3T MRI, and the levels of maximal oxygen uptake (VO2max) were measured using a cardiorespiratory function test. Inflammatory biomarkers were also collected. The participants were divided into two groups according to the levels of median VO2max, and the analysis showed that the morphological indexes of subfields of the hippocampus and amygdala of the lower CRF group were decreased when compared with the higher CRF group. Furthermore, the multiple linear regression analysis showed that there was a higher association with inflammatory factors in the lower CRF group than that in the higher CRF group. This study suggested a significant association of CRF with hippocampus and amygdala volume, which may be related to hypoxic stress in high-altitude environments. A better CRF reduced physiological stress and a decrease in the inflammatory response was observed, which may be related to the increased oxygen transport capacity of the body.

We describe a P-containing palladacycle-catalyzed regioselective Heck reaction of 2,3-dihydrofuran with diaryliodonium salts and aryl iodides to afford 2-aryl-2,5-dihydrofurans and 2-aryl-2,3-dihydrofurans, respectively, in good yields. Mechanistic studies revealed that the oxidative addition of diaryliodonium salts to palladacycles to form Pd(IV) species showed high chemoselectivity and that electron-rich aryl moieties were preferentially transferred to the Heck product. DFT calculations indicated that the regioselectivity-determining step is the reductive elimination reaction rather than the isomerization and reinsertion of Pd(IV)-hydride intermediates into the double bond.

In order to clarify the mechanisms underlying dryland wheat quality improvement through sowing technology, the effects of wide space sowing (WSS), furrow sowing (FS), and drill sowing (DS) on soil moisture dynamics and grain protein formation in dryland wheat field were studied in Wenxi, Shanxi Province in 2017-2018 (normal year) and 2018-2019 (dry year). The results showed that compared with the DS, FS significantly increased soil water storage in the 0-200 cm depth at anthesis stage (8.2%-18.7%), and increased the soil water storage in 0-60 cm layer during the two years, 60-120 cm layer in normal year, and 120-200 cm layer in dry year. WSS significantly increased soil water storage in 0-200 cm layer at anthesis stage in normal year (5.2%). Compared with DS, FS significantly increased water consumption of anthesis to mature stage, while WSS significantly increased water consumption from sowing to anthesis stage in dry year. Compared with DS, the glutamine synthetase (GS) activity of grains at 15-35 days after anthesis was significantly increased by FS and WSS, while the glutamate synthase (GOGAT) activity of flag leaves and grains at 5-35 days after anthesis was significantly increased by FS in the dry year. Compared with DS, FS significantly increased grain yield by 20.4%-44.8%, grain protein yield by 25%-49%, and increased grain albumin and globulin contents. WSS significantly increased grain yield by 9%-40%, and increased grain gliadin content. Under different sowing modes of dryland wheat, GS and GOGAT activities in flag leaves and grains after anthesis were significantly correlated with water consumption at anthesis to maturity stage. There were significant correlations between GS and GOGAT activities in flag leaves and grains and 0-120 cm soil layers in the normal water year, and between GS and GOGAT activities and 0-60 cm, 120-200 cm soil layers in the dry year. The contents of grain albumin, globulin and total protein were significantly correlated with soil water storage in 0-60 cm layer at anthesis stage, as well as soil water storage in 120-200 cm layer at anthesis stage in the dry year. In conclusion, FS was beneficial to increasing soil water storage at anthesis and water consumption after anthesis of dryland wheat, improving GS and GOGAT activities of flag leaf and grain, with positive consequences on yield and grain protein content. In addition, deep water storage was more conducive to quality improvement in the late growth period in the dry year.为明确旱地小麦品质提升的播种技术及其机理,于2017—2018年(平水年)、2018—2019年(欠水年)在山西闻喜开展宽幅播种、探墒沟播和常规条播对旱地麦田土壤水分变化和籽粒蛋白质形成影响的研究。结果表明: 与常规条播相比,探墒沟播显著提高了开花期0～200 cm土壤蓄水量(增幅8.2%～18.7%),其中提高了两年度0～60 cm土层,平水年60～120 cm土层,欠水年120～200 cm土层土壤蓄水量;宽幅播种显著提高了平水年开花期0～200 cm土壤蓄水量(增幅5.2%)。探墒沟播显著提高了开花-成熟阶段耗水量,宽幅播种显著提高了欠水年播种-开花阶段耗水量。探墒沟播和宽幅播种显著提高了花后15～35 d籽粒谷氨酰胺合成酶(GS)活性,探墒沟播还显著提高了欠水年花后5～35 d旗叶和籽粒谷氨酸合成酶(GOGAT)活性。探墒沟播显著提高了产量(增幅20.4%～44.8%),籽粒清蛋白、球蛋白含量,籽粒蛋白质含量(增幅3.1%～5.8%)和蛋白质产量(增幅25%～49%);宽幅播种显著提高了产量(增幅9%～40%)和籽粒醇溶蛋白含量。旱地小麦不同播种方式下,花后旗叶和籽粒GS、GOGAT活性与开花-成熟阶段耗水量呈显著相关,且与平水年开花期0～120 cm土层和欠水年开花期0～60、120～200 cm土层土壤蓄水量呈显著相关;籽粒清蛋白、球蛋白和总蛋白质含量均与开花期0～60 cm土层土壤蓄水量呈显著相关,欠水年还与开花期120～200 cm土层土壤蓄水量呈显著相关。总之,探墒沟播有利于提高旱地小麦开花期土壤蓄水量和花后耗水量,提高旗叶和籽粒GS、GOGAT活性,从而提高产量和籽粒蛋白质含量,且欠水年生育后期深层土壤蓄水更有利于小麦品质提升。.

CoCuNiTi high-entropy alloy coatings with an equal molar ratio were prepared on 45 steel substrates using the laser-cladding method. The effect of CeO2 doping on phase structure, microstructure and corrosion behavior of CoCuNiTi coatings were investigated by X-ray diffraction, optical microscope, scanning electron microscope, and electrochemical workstation. The results show that the phase structure of CoCuNiTi coating doped with 1 w/% CeO2 is transformed from the original dual-phase structure of FCC main phase and BCC phase to the dual-phase structure of BCC main phase and FCC phase, mainly because CeO2 addition helps to improve the temperature gradient and solidification rate during solidification, reduce the nucleation resistance and the diffusion distance of the alloying elements, and provide a liquid environment with longer time, lower viscosity and higher diffusion rate. The microstructure of the two coatings is composed of BCC-phase dendrite and FCC-phase interdendrite. The widths of the primary dendrites of the columnar dendrites in CoCuNiTi cladding layer before and after CeO2 doping are about 8.10 µm and 6.51 µm, respectively. The CoCuNiTi coating doped with 1 w/% CeO2 has the smallest corrosion current density, the largest capacitive reactance arc radius and polarization resistance, and the best corrosion resistance in 3.5 w/% NaCl solution, which is mainly due to making the alloy structure refined and the element distribution uniform after the CeO2 addition.

Our previous study identified a new β-galactosidase in Erwinia sp. E602. To further understand the lactose metabolism in this strain, de novo genome assembly was conducted by using a strategy combining Illumina and PacBio sequencing technology. The whole genome of Erwinia sp. E602 includes a 4.8 Mb chromosome and a 326 kb large plasmid. A total of 4,739 genes, including 4,543 protein-coding genes, 25 rRNAs, 82 tRNAs and 7 other ncRNAs genes were annotated. The plasmid was the largest one characterized in genus Erwinia by far, and it contained a number of genes and pathways responsible for lactose metabolism and regulation. Moreover, a new plasmid-borne lac operon that lacked a typical β-galactoside transacetylase (lacA) gene was identified in the strain. Phylogenetic analysis showed that the genes lacY and lacZ in the operon were under positive selection, indicating the adaptation of lactose metabolism to the environment in Erwinia sp. E602. Our current study demonstrated that the hybrid de novo genome assembly using Illumina and PacBio sequencing technologies, as well as the metabolic pathway analysis, provided a useful strategy for better understanding of the evolution of undiscovered microbial species or strains.

Our previous study identified a new β-galactosidase in Erwinia sp. E602. To further understand the lactose metabolism in this strain, de novo genome assembly was conducted by using a strategy combining Illumina and PacBio sequencing technology. The whole genome of Erwinia sp. E602 includes a 4.8 Mb chromosome and a 326 kb large plasmid. A total of 4,739 genes, including 4,543 protein-coding genes, 25 rRNAs, 82 tRNAs and 7 other ncRNAs genes were annotated. The plasmid was the largest one characterized in genus Erwinia by far, and it contained a number of genes and pathways responsible for lactose metabolism and regulation. Moreover, a new plasmid-borne lac operon that lacked a typical β-galactoside transacetylase (lacA) gene was identified in the strain. Phylogenetic analysis showed that the genes lacY and lacZ in the operon were under positive selection, indicating the adaptation of lactose metabolism to the environment in Erwinia sp. E602. Our current study demonstrated that the hybrid de novo genome assembly using Illumina and PacBio sequencing technologies, as well as the metabolic pathway analysis, provided a useful strategy for better understanding of the evolution of undiscovered microbial species or strains.

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Human Immunodeficiency Virus 1 (HIV-1) co-receptor usage, called tropism, is associated with disease progression towards AIDS. Furthermore, the recently developed and developing drugs against co-receptors CCR5 or CXCR4 open a new thought for HIV-1 therapy. Thus, knowledge about tropism is critical for illness diagnosis and regimen prescription. To improve tropism prediction accuracy, we developed two novel methods, the extreme gradient boosting based XGBpred and the hidden Markov model based HMMpred. Both XGBpred and HMMpred achieved higher specificities (72.56% and 72.09%) than the state-of-the-art methods Geno2pheno (61.6%) and G2p_str (68.60%) in a 10-fold cross validation test at the same sensitivity of 93.73%. Moreover, XGBpred had more outstanding performances (with AUCs 0.9483, 0.9464) than HMMpred (0.8829, 0.8774) on the Hivcopred and Newdb (created in this work) datasets containing larger proportions of hard-to-predict dual tropic samples in the X4-using tropic samples. Therefore, we recommend the use of our novel method XGBpred to predict tropism. The two methods and datasets are available via http://spg.med.tsinghua.edu.cn:23334/XGBpred/. In addition, our models identified that positions 5, 11, 13, 18, 22, 24, and 25 were correlated with HIV-1 tropism.

To seek novel and safe protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors with excellent herbicidal activity. A series of novel phenoxypyridine derivatives containing natural product coumarins with allelopathy were designed and synthesized based on bioisosterism and active subunit combination in this research. Compounds W3.1 and W3.4, with the half-maximal inhibitory concentration (IC50) value of 0.02653 mg/L and 0.01937 mg/L, respectively, displayed excellent herbicidal activity in greenhouse. Their herbicidal activity was similar to commercial herbicide oxyfluorfen (IC50 = 0.04943 mg/L). The best field inhibitory effect of compounds W3.1 and W3.4 recorded was at doses of 450 g ai/ha and 300 g ai/ha, respectively. Compound W3.4 had the best herbicidal activity among all the target compounds in this paper. Molecular docking analysis revealed that compounds W3.1 and W3.4 could form a hydrogen bonds with the amino acid AGR-98 and a π-π superposition with the amino acid PHE-398, respectively, which was similar to the oxyfluorfen. The crop selectivity tests results indicated that maize, cotton and soybean showed high tolerance to compound W3.4. Compound W3.4 reduced the Ca and Cb contents of wheat and rice, but had less effect on maize, cotton and soybean. Selectivity of compound W3.4 in maize, cotton and soybean were appeared to be due to reduced absorption of the herbicide compared to wheat and rice. Compound W3.4 deserves further attention as a candidate structure for new herbicides.

To effectively predict the life of high voltage dc power relay, the authors design the structure of the relay to extending its life. The contact failure mechanism of relay products is analyzed by observing the appearance of several contact failures. The electromagnetic-thermal field coupling model is established and the state of heat flow and distribution of temperature increase between electrical and thermal coupling contacts are analyzed through simulations and experiments. An adaptive neural network control system is established to conduct sample training, obtain the best stiffness coefficient of the main spring, and optimize the design of the main spring structure composed of composite springs. The action voltage, release voltage, contact resistance, contact pressure, action time, and release time as characteristic parameters, and the relative error, correlation degree, variance ratio, and small error probability of each characteristic parameter, are calculated. The precision grade index of contact resistance and action time is defined as level 1. The two characteristic parameters are selected as the prediction variables to establish the life-prediction model based on gray theory. The relative error between the predicted and test life is 5.31%–5.6%, indicating that the life-prediction model has high accuracy. The test results show that the combined main spring structure can extend the life of a relay by 18.15%.

To explore the efficacy of microwave ablation (MWA) in the treatment of hepatic alveolar echinococcosis (HAE) with a diameter of ≤5 cm.From June 2014 to January 2020, patients diagnosed with HAE were retrospectively analyzed. After balancing the confounding factors by propensity score matching (PSM) , the patients were divided into MWA group (n = 20) and radical operation group (n = 20) by 1:1 matching. The safety and effectiveness of MWA were assessed by comparing the differences between the two groups in terms of postoperative general laboratory indices, grading of postoperative complications, length of postoperative hospitalization, the outcome of treatment, and disease recurrence.After PSM, all confounders were not statistically different (P0.05) . Compared with the radical surgery group, patients in the MWA group had lower postoperative ALT and WBC elevations (P0.001) , shorter postoperative hospital stay (P0.001) ) , lower hospital costs (P0.001) . The effective rate of the two groups was 100%. There was no statistical difference in the incidence of postoperative complications and recurrence rate (P0.05).MWA is a safe and effective means of treating HAE ≤ 5 cm in diameter.

Objective. As a noninvasive and nonpharmacological therapeutic approach, superficial acupuncture (SA) is a special method of acupuncture. In this study, using nonlinear dynamics and multivariate statistics, we studied the electroencephalography (EEG) of primary insomnia under SA intervention to investigate how brain regions change. Method. This study included 30 adults with primary insomnia. They underwent superficial acupuncture at the Shangen acupoint. The EEG signals were collected for 10 minutes at each state, including the resting state, the intervention state, and the postintervention state. The data were conducted using nonlinear dynamics (including approximate entropy (ApEn) and correlation dimension (CD)) and multivariate statistics. Result. The repeated-measures ANOVA results showed that both ApEn and CD values were not significantly different at the three states p > 0.05 . The paired t-test results showed that the ApEn values of electrodes O2 (the right occipital lobe) at the postintervention state have decreased, compared with the resting state p < 0.05 , and no difference was detected in CD p > 0.05 . The cluster analysis results of ApEn showed that patients’ EEG has changed from the right prefrontal lobe (electrode Fp2) to the right posterior temporal lobe (electrode T6) and finally to the right occipital lobe (electrode O2), before, during, and after the SA intervention. In addition, the factor analysis results of CD revealed that patients’ EEG of all brain regions except for the occipital lobes has changed to the frontal lobes and anterior temporal and frontal lobes from pre- to postintervention. Conclusion. SA activated the corresponding brain regions and reduced the complexity of the brain involved. It is feasible to use nonlinear dynamics analysis and multivariate statistics to examine the effects of SA on the human brain.

At present, tight oil reservoirs account for more than 60% of the remaining un-used reserves in Daqing Oilfield. The development mode is mainly vertical well large-scale fracturing or horizontal well volume fracturing, which is affected by low oil price and has poor economic benefits. In order to reduce the decision-making risk of Oilfield productivity capacity investment, a practical and effective economic evaluation method is needed. Through the analysis of development indexes of large-scale fracturing in vertical wells and volume fracturing in horizontal wells, the changing rules of development indexes are clarified, and the calculation methods of some economic parameters of development effect evaluation are optimized. The economic evaluation methods of productivity projects in tight reservoirs are formed, and the calculation program is compiled. The program is used to evaluate the production investment limits of compact oil blocks under different daily production of single well for large-scale vertical well fracturing and volume fracturing under multi-oil price conditions. Based on the evaluation results, the investment limits of single well and single well daily production under different oil prices are plotted, and the sensitivity of investment limits is analyzed. Under the condition of low oil price, the result of benefit evaluation can be improved by reducing investment, and under the condition of high oil price, the effect of increasing daily production of single well on improving economic benefit of block is greater. This method can effectively predict the risk of capacity investment decision-making, ensure the smooth implementation of tight oil production projects, and release more development potential. The research results can be applied in the submission of proven reserves, the evaluation of unused reserves and the planning and deployment of oilfields.

Due to their high thermal efficiency, good reliability and durability, low fuel consumption, and low carbon dioxide emission, diesel engines are widely used in both stationary and mobile applications. However, the inherent combustion mode of diesel engines results in high particulate matter (PM) emissions. In order to meet the increasingly stringent PM emission standard, the diesel particulate filter (DPF) has become a necessary configuration to remove PM for diesel engines. Increasing damage of fuel consumption with DPF soot loading leads to the requirement of regeneration process. DPF active regeneration is a process from hydrocarbon (HC) oxidation in diesel oxidation catalyst (DOC) to deposited particle oxidation in DPF, involving the whole aftertreatment system. First, previous studies mainly focused on single converter, and have rarely explored the regeneration process considering the whole aftertreatment system. Second, few studies have conducted in-depth introductions to the microscopic oxidation characteristics of deposited particles during regeneration. Third, the high temperature resulted from the active regeneration has an important impact on the performance of selective catalytic reduction (SCR), which may be a problem to be considered in the next emission regulations, but few studies have reported this aspect. This study focuses on full course evolution process under DPF active regeneration considering the whole aftertreatment system. Taking the HC concentration as the research variables, the HC slip phenomenon, the microscopic oxidation characteristics of deposited particles, the temperature field characteristics, and the influence of active regeneration on SCR performance are systematically investigated. This study can provide valuable guidance for further understanding of DPF active regeneration characteristics, regeneration control strategy formulation and DPF durability improvement.

Key Clinical Message This article mainly reports the process of clinical diagnosis and treatment of a misdiagnosed Listeria monocytogenes meningoencephalitis. The patient's condition is aggravated because of the ineffective prophase therapy. In the later stage, we were mainly through combined antibiotics and given proper routes of administration, so that patient can recover quickly.

A new Keggin sandwich-type polyoxometalate (POM) estertin derivative Na8K6[{Sn(CH2)2COO}2(B-α-AsW9O33)2]·27H2O (compound 1) has been successfully synthesized from K14[As2W19O67(H2O)]·nH2O ({As2W19}) and Cl3SnCH2CH2COOCH3, and characterized by physico-chemical and spectroscopic methods. The corrosion inhibition behavior of compound 1 for carbon steel in 0.4 mol L− 1 NaAc-HAc buffer solution with pH = 6.0 was evaluated by polarization curves and electrochemical impedance spectroscopy (EIS), and its catalytic activity towards the oxidation of cyclohexanol to cyclohexanone was also studied.

An efficient synthesis of 1-vinyl/aryl benzotriazole 3-oxides via the copper-promoted coupling of N-hydroxybenzotriazoles with alkenyl or aryl boronic acids is reported. This strategy features mild reaction conditions, good functional group tolerance, broad substrate scope and rapid introduction of benzotriazole N-oxides moieties into molecules. Density functional theory calculations revealed that the formation of the favored N-coupling product depends on the kinetically more favorable C−N bond formation pathway.

The agglomeration of aluminum particles usually occurs on the burning surface of aluminized composite propellants. It leads to low propellant combustion efficiency and high two-phase flow losses. To reach a thorough understanding of aluminum agglomeration behaviors, agglomeration processes, and particles size distribution of Al/AP/RDX/GAP propellants were studied by using a cinephotomicrography experimental technique, under 5 MPa. Accumulation, aggregation, and agglomeration phenomena of aluminum particles have been inspected, as well as the flame asymmetry of burning agglomerates. Results reveals that the dependency of the mean and the maximum agglomeration diameter to the burning rate and the virgin aluminum size have the same trend. A second-time mergence of multiple agglomerates on the burning surface is unveiled. Two typical modes of second mergence are concluded, based upon vertical and level movement of agglomerates, respectively. The latter mode is found to be dominant and sometimes a combination of the two modes may occur. A new model of aluminum agglomeration on the burning surface of composite propellants is derived to predict the particulates size distribution with a low computational amount. The basic idea is inspired from the well-known pocket models. The pocket size of the region formed by adjacent AP particles is obtained through scanning electron microscopy of the propellant cross-section coupled to an image processing method. The second mergence mechanism, as well as the effect of the burning rate on the agglomeration processes, are included in the present model. The mergence of two agglomerates is prescribed to occur only if their separation distance is less than a critical value. The agglomerates size distribution resulting from this original model match reasonably with the experimental data. Moreover, the present model gives superior results for mean agglomeration diameter compared to common empirical and pocket models. The average prediction error is lower than 5% for the four propellants tested. Results of this study are expected to provide better insight and enrich in the theoretical frame of aluminum agglomeration.

Pimpinella smithii Wolff is endemic in China. In this study, the complete chloroplast genome of P. smithii was determined. The total genome size was 147,130 bp in length. It was found to possess th...

Exposure to a high altitude hypoxia environment has significant negative effects on human central nervous system. Many previous studies have explored the influence of the high altitude environment on human color perception in a simulated high altitude environment or in an environment acutely exposed to high altitude, but little has been done in migrators and natives exposed to high altitude and low oxygen for a long period of time. In this study, the minimal-change method was used to examine whether the color perception of red, green, blue and yellow was affected by the high altitude in 30 plain residents, 30 Han migrators who have lived in the high altitude for 2 years, and 28 high-altitude-adapted Tibetan natives. The results showed that long-term high altitude exposure had the most significant effect on the blue and red color perception in the natives and the migrators, with the effect on the blue color being significantly greater than that on the red color. However, the effects on green color processing only happened to the natives. The results suggest that there is an internal correlation between blood supply and selectivity changes of visual color processing caused by exposure to the plateau environment.

The goat genome is the research basis for the protection and utilization of goat resources, which is important for breeding and improving goat breeds. At present, with the continuous improvement of goat reference genome, various important research progress in goat origin, evolution and adaptability has been achieved. In this review, we summarize the research progress in the goat genome in detail, encompassing goat genome structure, genome map (genetic, physical and comparative maps), goat high throughput sequencing and SNP chip development. We aim to provide a theoretical foundation for the development of goat genome selection.

The Western Liaoning area, where a large number of Jurassic-Cretaceous volcanic rocks are exposed, is one of the typical areas for studying the Mesozoic Paleo-Pacific and Mongolia-Okhotsk subduction process, and lithospheric destruction of North China Craton. The identification and investigation of Early Jurassic adakitic volcanic rocks in the Xintaimen area of Western Liaoning is of particular significance for exploring the volcanic magma source and its composition evolution, tracking the crust-mantle interaction, and revealing the craton destruction and the subduction of oceanic plates. Detailed petrography, zircon U–Pb dating, geochemistry, and zircon Hf isotope studies indicate that the Early Jurassic intermediate-acidic volcanic rocks are mainly composed of trachydacites and a few rhyolites with the formation ages of 178.6–181.9 Ma. Geochemical characteristics show that they have a high content of SiO2, MgO, Al2O3, and total-alkali, typical of the high-K calc-alkaline series. They also show enrichment of light rare earth elements (LREEs) and large ion lithophile elements (LILEs), depletion of heavy rare earth elements (HREEs) and high field strength elements (HFSEs), and have a high content of Sr and low content of Y and Yb, suggesting that they were derived from the partial melting of the lower crust. The εHf(t) values of dated zircons and two-stage model ages (TDM2) vary from −11.6 to −7.4 and from 1692 to 1958 Ma, respectively. During the Early Jurassic, the study area was under long-range tectonic effects with the closure of the Mongolia-Okhotsk Ocean and the subduction of the Paleo-Pacific plate, which caused the basaltic magma to invade the lower crust of the North China Craton. The mantle-derived magma was separated and crystallized while heating the Proterozoic lower crust, and part of the thickened crust melted to form these intermediate-acidic adakitic volcanic rocks.

The SAD (synapses of amphids defective) kinases, including SAD-A and SAD-B, play important roles in the regulation of neuronal development, cell cycle, and energy metabolism. Our recent study of mouse SAD-A identified a unique autoinhibitory sequence (AIS), which binds at the junction of the kinase domain (KD) and the ubiquitin-associated (UBA) domain and exerts autoregulation in cooperation with UBA. Here, we report the crystal structure of the mouse SAD-B C-terminal fragment including the AIS and the kinase-associated domain 1 (KA1) at 2.8 Å resolution. The KA1 domain is structurally conserved, while the isolated AIS sequence is highly flexible and solvent-accessible. Our biochemical studies indicated that the SAD-B AIS exerts the same autoinhibitory role as that in SAD-A. We believe that the flexible isolated AIS sequence is readily available for interaction with KD-UBA and thus inhibits SAD-B activity.

In the downhill braking process, the high temperature of the service brake of heavy-duty trucks can lead to braking failure. To solve this problem, a brake heating model for heavy-duty truc...

Metastasis is the leading lethal factor severely restraining the effectiveness of clinical treatment. TGF-beta is the key regulator for metastasis and influences paradoxically on cancer progression. The known TGF-beta blockers exert little selectivity on its functions, indiscriminately causing the anti-metastatic and pro-growth effects. Under such circumstances, specifically rebalancing the oncological function of TGF-beta provides a crucial oncotarget against metastasis. In our study, we established the screening platform targeting cell motility and identified a potential flavonoid, Chamaejasmenin B (ICJ), extracted from Stellera chamaejasme L..It suppressed the migration and invasion in breast cancer cells in vitro. Moreover, by dynamical quantification of breast cancer progression in small-animal imaging system, ICJ was proved to be a potent inhibitor of metastasis with minimal toxic side effects. Mechanism study further revealed that ICJ efficiently blocked TGF-beta induced EMT, disrupted the interaction between β3 integrin-TβRII complex and, consequently, resulted in the selective inhibition of FAK:Src:p38 pathway. Meanwhile, specific blockage of this pathway largely attenuated the anti-metastatic function of ICJ. Importantly, in contrast with the antagonistic effects on TGF-beta induced metastasis, ICJ obviously sensitized its cytostatic activity, suggesting that it was not a pan-blocker but a rebalancer for the functional output of TGF-beta. Collectively, by targeting TGF-beta Paradox, we experimentally provided a promising candidate for metastatic intervention.

Currently, liver cancer is the sixth most prevalent cancer and the third most common cause of cancer-related death. However, effective chemotherapeutic drugs with low drug resistance and few side-effects for the clinical treatment of liver cancer are lacking. Therefore, the search for novel drugs to compensate for the defects of existing drugs is urgently needed. Herein, we successfully screened an extract named from Stellera chamaejasme L. (SCL), a historically confimed antitumor plant, through a novel extraction platform. In the present study, we firstly screened the anticancer effect of ESC by the sulforhodamine B (SRB) cell proliferation assay in a wide range of malignant cell lines, including A549, NCI-H157, NCI-H460, SK-HEP-1 and HepG2. With the highest inhibitory rate in hepatocarcinoma cells, we further identified the tumor-suppressive efficacy and the safety of ESC in an H22 hepatocarcinoma xenograft model in vivo. In a mechanistic study, flow cytometry and western blot analysis were performed to evaluate the effects of ESC on the induction of cell apoptosis, intervention of cell cycle distribution and its influence on key G2/M-phase regulators. The results showed that ESC significantly inhibited the cell growth of liver cancer cell lines. Accordingly, the tumor inhibition rate was also increased following ESC administration with little systemic toxicity in H22-transplanted mice. Mechanistically, ESC caused obvious G2/M-phase arrest in both the SK-HEP-1 and HepG2 cell lines without cell apoptosis. Furthermore, cyclin B1 was downregulated, while the phosphorylation level of CDK1 was increased in response to ESC treatment. All these data confirmed that ESC possesses potent anti-proliferative efficacy for hepatocarcinoma through the induction of cyclin-mediated cell cycle arrest. Thus, ESC is a promising candidate for hepatocarcinoma treatment in the future.

Stellera chamaejasme, a famous toxic herb, has been used in traditional Chinese medicine to treat various diseases. For decades, increasing attention in modern pharmacological studies has been drawn to S. chamaejasme because of its potential anti-tumor, anti-virus, and anti-fungus activities. However, due to the intrinsic complexity of chemical constitutes, hardly any investigations formed an overall recognition for the chemical profiles of this herb. In this study, a rapid and sensitive ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry method was developed to characterize the chemical components of S. chamaejasme extracts. Based on optimized ultra-high performance liquid chromatography and mass spectrometry conditions and systematic fragment ions-based strategy, a total of 47 components including flavones, diterpenes, coumarins, and lignans were simultaneously detected and identified or tentatively identified for the first time. The MS(n) fragmentation patterns of all the characterized compounds in positive or negative electrospray ionization modes were also explored and summarized. These results provided essential data for further pharmacological research on S. chamaejasme. Moreover, the method was demonstrated to be an efficient tool for rapid qualitative analysis of secondary metabolites from natural resources.

The Ca(2+)/calmodulin-dependent protein phosphatase calcineurin (CN), a heterodimer composed of a catalytic subunit A and an essential regulatory subunit B, plays critical functions in various cellular processes such as cardiac hypertrophy and T cell activation. It is the target of the most widely used immunosuppressants for transplantation, tacrolimus (FK506) and cyclosporin A. However, the structure of a large part of the CNA regulatory region remains to be determined, and there has been considerable debate concerning the regulation of CN activity. Here, we report the crystal structure of full-length CN (β isoform), which revealed a novel autoinhibitory segment (AIS) in addition to the well-known autoinhibitory domain (AID). The AIS nestles in a hydrophobic intersubunit groove, which overlaps the recognition site for substrates and immunosuppressant-immunophilin complexes. Indeed, disruption of this AIS interaction results in partial stimulation of CN activity. More importantly, our biochemical studies demonstrate that calmodulin does not remove AID from the active site, but only regulates the orientation of AID with respect to the catalytic core, causing incomplete activation of CN. Our findings challenge the current model for CN activation, and provide a better understanding of molecular mechanisms of CN activity regulation.

Smad proteins are important intracellular mediators of TGF-β signalling, which transmit signals directly from cell surface receptors to the nucleus. The MH1 domain of Smad plays a key role in DNA recognition. Two types of DNA sequence were identified as Smad binding motifs: the Smad binding element (SBE) and the GC-rich sequence. Here we report the first crystal structure of the Smad5 MH1 domain in complex with the GC-rich sequence. Compared with the Smad5-MH1/SBE complex structure, the Smad5 MH1 domain contacts the GC-rich site with the same β-hairpin, but the detailed interaction modes are different. Conserved β-hairpin residues make base specific contacts with the minimal GC-rich site, 5′-GGC-3′. The assembly of Smad5-MH1 on the GC-rich DNA also results in distinct DNA conformational changes. Moreover, the crystal structure of Smad5-MH1 in complex with a composite DNA sequence demonstrates that the MH1 domain is targeted to each binding site (GC-rich or SBE) with modular binding modes, and the length of the DNA spacer affects the MH1 assembly. In conclusion, our work provides the structural basis for the recognition and binding specificity of the Smad MH1 domain with the DNA targets.