Molecular Insights into the Effect of Cholesterol on the Binding of Bicarbonate Ions in Band 3 Protein.

Band 3, or anion exchanger 1 (AE1), is one of the indispensable transmembrane proteins involved in the effective respiratory process of the human body and is primarily responsible for the exchange of bicarbonate and chloride anions across the plasma membrane of erythrocyte. However, the molecular mechanism of ion transport of Band 3 is not completely understood, yet. In this work, we systematically investigate the key binding sites of bicarbonate ions in Band 3 and the impact of cholesterol (CHOL) in lipid bilayers on bicarbonate ion binding using all-atom molecular dynamics (MD) simulations. We examine the dynamics of interactions of bicarbonate ions with Band 3 in the microsecond time scale and calculate the binding free energy of the anion in Band 3. The results indicate that the residue R730 of Band 3 is the most probable binding site for bicarbonate ions. CHOL enhances the bicarbonate ion binding by influencing the conformational stability of Band 3 and compressing the volume of the Band 3 cavity. These findings provide some insights into the bicarbonate ion binding in Band 3 and are helpful for understanding the anion exchange of Band 3.

A bibliometrics study on the status quo and hot topics of pathogenesis of psoriasis based on Web of Science.

BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory skin disease. Great progress has been made in the pathogenesis of psoriasis in recent years, but there is no bibliometric study on the pathogenesis of psoriasis. The purpose of this study was to use bibliometrics method to analyze the research overview and hot spots of pathogenesis of psoriasis in recent 10 years, so as to further understand the development trend and frontier of this field. METHODS: The core literatures on the pathogenesis of psoriasis were searched in the Web of Science database, and analyzed by VOSviewer, CiteSpace, and Bibliometrix in terms of the annual publication volume, country, institution, author, journal, keywords, and so on. RESULTS: A total of 3570 literatures were included. China and the United States were the main research countries in this field, and Rockefeller University was the main research institution. Krueger JG, the author, had the highest number of publications and the greatest influence, and Boehncke (2015) was the most cited local literature. J INVEST DERMATOL takes the top spot in terms of the number of Dermatol articles and citation frequency. The main research hotspots in the pathogenesis of psoriasis are as follows: (1) The interaction between innate and adaptive immunity and the related inflammatory loop dominated by Th17 cells and IL-23/IL-17 axis are still the key mechanisms of psoriasis; (2) molecular genetic studies represented by Long Non-Coding RNA (LncRNA); (3) integrated research of multi-omics techniques represented by gut microbiota; and (4) Exploring the comorbidity mechanism of psoriasis represented by Metabolic Syndrome (MetS). CONCLUSION: This study is a summary of the current research status and hot trend of the pathogenesis of psoriasis, which will provide some reference for the scholars studying the pathogenesis of psoriasis.

FXR1 impedes the development of osteoarthritis by targeting SND1.

OBJECTIVES: To investigate the role of fragile X mental retardation syndrome-related protein 1 (FXR1), an RNA binding protein, in the development of osteoarthritis (OA), to define its mechanism of action in cartilage, and to determine whether targeting FXR1 can prevent OA in mice. METHODS: Western blot analysis and quantitative polymerase chain reaction were performed using cartilage tissue from control and osteoarthritic mice. FXR1 expression was detected by immunofluorescence staining using cartilage tissue from mice. OA was induced by destabilising the medial meniscus in the mice. Infection of mouse chondrocytes with FXR1 lentivirus, as well as viral injection into the mouse knee joint cavity, resulted in high FXR1 protein expression. Chondrocyte apoptosis was detected by TUNEL assay and cell senescence was detected by SA-ß-gal staining assay. RESULTS: FXR1 expression was significantly reduced in cartilage and soft tissue from mice with OA compared with the controls. FXR1 overexpression reduced staphylococcal nuclease domain protein 1 (SND1) levels. Furthermore, FXR1 is able to inhibit apoptosis and senescence of chondrocytes via SND1 and hinder the development of OA in mice. CONCLUSIONS: FXR1 down-regulates SND1 expression, thereby alleviating osteoarthritic symptoms in mice. In summary, FXR1 may have a therapeutic approach to the treatment of OA.

Temperature-dependent variations in toxicity of diamide insecticides against three lepidopteran insects.

The effect of temperature on the toxicities of four diamide insecticides (chlorantraniliprole, cyantraniliprole, flubendiamide, tetraniliprole) against three lepidopteran insects (Helicoverpa armigera, Plutella xylostella, Athetis lepigone) were determined from 15 to 35 °C by exposing third-instar larvae to dip-treated cabbage leaf. The results indicated that increase in temperature led to an increase significantly and regularly in the toxicities of the four diamide insecticides against P. xylostella and H. armigera, but not for A. lepigone. The temperature coefficients (TCs) of the four diamide insecticides increased from 15 to 35 °C. Tetraniliprole for H. armigera (+825.83), chlorantraniliprole for P. xylostella (+315.65) and cyantraniliprole for H. armigera (+225.77) exhibited high positive TCs. For A. lepigone, temperature had a positively weak or no effect on the toxicities of most of the diamide insecticides from 20 to 30 °C, but a higher effect from 30 to 35 °C. In addition, the toxicities of chlorantraniliprole, cyantraniliprole and tetraniliprole all decreased from 15 to 20 °C. This study can guide pest managers in choosing suitable ambient field temperature when spraying diamide insecticides against lepidopteran insects.

The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study.

Objective: To explore the influence of serum metabolites on the risk of psoriasis. Methods: In the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio's odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran's Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages. Results: In the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism. Conclusion: Circulating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment.

[Effect of Lycium ruthenicum anthocyanins on atherosclerosis in mice].

OBJECTIVE: To study the effect of Lycium ruthenicum anthocyanins on atherosclerosis (AS) in mice. METHOD: Normal mice were taken as the control group, and hyperlipemia mice were divided into the model group, Lycium ruthenicum anthocyanins low, medium and high dose groups, and the simvastatin drug control group. After the oral administration, blood lipid indicators were detected by enzymatic analysis. The histomorphological changes in aortas, hearts and livers were observed, and liver-related indicators were determined by using hematoxylin-eosin (HE) staining. RESULT: Compared with the high-fat group, L. ruthenicum anthocyanins low, medium and high dose groups showed significant decrease in total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and atherosclerotic index (AI) (P < 0.05). However, high-density lipoprotein cholesterol (HDL-C) level showed a trend of higher than the model group. Liver's total antioxidant capacity (T-AOC), Glutathione peroxidase (GSH-PX), lipoprotein lipase (LPL) were significantly increased (P < 0.05), malondialdehyde (MDA) was markedly decreased (P < 0.01); the percentage of aortic plaque area of each anthocyanins dose group in the total area was significantly lower than the model group (P < 0.05); severity of aorta, heart and liver were significantly lighter than the high-fat group. But the media dose group was similar with the simvastatin group. CONCLUSION: L. ruthenicum anthocyanins can interfere the formation of AS, while lowering blood lipid levels in mice.

Using QCT to evaluate bone mineral and abdominal adipose changes in patients with primary hyperparathyroidism and comparing it to DXA for bone status assessment: a retrospective case-control study.

Background: Patients with primary hyperparathyroidism (PHPT) show changes in bone metabolism and adipose tissue, but the results are inconsistent. Quantitative computed tomography (QCT) was reported useful for detecting bone mineral and adipose tissue change, but information on the role of QCT in PHPT is limited. We aimed to explore the changes of lumbar bone mineral density (BMD) and abdominal adipose tissue in patients with PHPT using QCT based on existed CT images, and to assess the consistency between QCT and dual-energy X-ray absorptiometry (DXA) in assessing bone status. Methods: This retrospective case-control study was conducted on 48 PHPT patients, with healthy controls (HCs) matched by their age (±3 years) and gender, and the case-to-control ratio was approximately 1:3. Volumetric bone mineral density (vBMD), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT) were measured by QCT in both PHPT and control groups and compared with the independent samples T-test. In the PHPT group, areal bone mineral density (aBMD) was measured by DXA. Pearson correlation analysis was used to investigate the association between QCT-derived vBMD and DXA-derived aBMD. Weighted kappa consistency analysis was used to clarify the agreement between QCT and DXA. Results: Compared with HCs, the PHPT group had significantly lower vBMD (114.30±41.71 vs. 136.92±42.23 mg/cm3; P=0.002) and higher TAT (261.98±74.65 vs. 236.69±69.00 cm2; P=0.033); however, differences in SAT (120.81±40.19 vs. 109.94±36.83 cm2; P=0.085) and VAT (141.17±48.11 vs. 126.75±50.50 cm2; P=0.085) were not statistically significant. There was a strong correlation between QCT-derived vBMD and DXA-derived aBMD (all r>0.68; P<0.001), and a moderate consistency [kappa(w) =0.48; 95% CI: 0.29 to 0.68; P<0.001] was presented when defining bone status according to the respective diagnostic criteria. Conclusions: Our study may provide useful information regarding bone status and abdominal adipose tissue change in patients with PHPT without requiring additional scan and may further extend the clinical application value of QCT.

The application value of computed tomography and magnetic resonance imaging sinography/fistulography in evaluating chronic wounds: a prospective study.

BACKGROUND: Chronic wounds are a worldwide health problem, with traditional imaging techniques failing in their accurate evaluation. Therefore, an effective imaging evaluation method is needed for the diagnosis and treatment or chronic wounds. This study is to investigate the application value of computed tomography (CT) and magnetic resonance imaging (MRI) sinography/fistulography in assessing the morphology and deep features of chronic wounds. METHODS: We prospectively enrolled 43 chronic wounds patients who received both CT and MRI sinography/fistulography. The morphology and deep features of chronic wound on CT and MRI images were independently evaluated by 2 experienced radiologists. Kappa value and intraclass correlation coefficient (ICC) were calculated to evaluate the interobserver agreement and the consistency between CT and MRI sinography/fistulography in assessing the shape, number of branches, and involvement of body cavity and bones of chronic wounds. RESULTS: There were substantial to almost perfect interobserver agreements for both CT and MRI sinography/fistulography in evaluating the morphology and deep features of chronic wounds. The consistency between CT and MRI was almost perfect for the 2 readers in evaluating the shape (reader 1, kappa value =1.000; reader 2, kappa value =0.932) and the number of branches [reader 1, ICC =0.951 (95% confidence interval: 0.909-0.973, P<0.001); reader 2, ICC =0.874 (95% confidence interval: 0.768-0.932, P<0.001)], and substantial to almost perfect when evaluating the involvement of body cavity (reader 1, kappa value =0.728; reader 2, kappa value =0.775) and bones (reader 1, kappa value =0.659; reader 2, kappa value =0.860). CONCLUSIONS: There was good interobserver agreement and consistency between CT and MRI sinography/fistulography in evaluating the morphology and deep features of chronic wounds.

Pulmonary vascular enlargement on thoracic CT for diagnosis and differential diagnosis of COVID-19: a systematic review and meta-analysis.

BACKGROUND: The 2019 coronavirus disease (COVID-19) has become a global pandemic. To date, although many studies have reported on the computed tomography (CT) manifestations of COVID-19, the vascular enlargement sign (VES) of COVID-19 has not been deeply examined, with the few available studies reporting an inconsistent prevalence. We thus performed a systematic review and meta-analysis based on the best available studies to estimate the prevalence and identify the underlying differential diagnostic value of VES. METHODS: We searched nine English and Chinese language databases up to April 23, 2020. Studies that evaluated CT features of COVID-19 patients and reported VES, with or without comparison with other pneumonia were included. The methodologic quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Meta-analyses with random effects models were performed to calculate the aggregate prevalence and pooled odds ratios (ORs) of VES. We also conducted meta-regression and subgroup analyses to analyze heterogeneity. RESULTS: VES findings from a total of 1969 patients were summarized and pooled across 22 studies. Our analysis demonstrated that the prevalence of VES among COVID-19 patients was 69.37% [95% confidence interval (CI): 57.40-79.20%]. Compared with non-COVID-19 patients, VES manifestation was more frequently observed in confirmed COVID-19 patients (OR =6.43, 95% CI: 3.39-12.22). Studies that explicitly defined distribution of VES in the lesion area demonstrated a significantly higher prevalence (P=0.03). Subgroup analyses also revealed a relatively higher VES rate in studies with a sample size larger than 50, but the difference was not statistically significant. No significant difference in VES rates was found between different countries (China/Italy), regions (Hubei/outside Hubei), average age groups (over/less than 50-year-old), or slice thicknesses of CT scan. Extensive heterogeneity was identified across most estimates (I2>80%). Some of the variations (R2=19.73%) could be explained by VES distribution, and sample size. No significant publication bias was seen (P=0.29). CONCLUSIONS: VES on thoracic CT was found in almost two-thirds of COVID-19 patients, and was more prevalent compared with that of the non-COVID-19 patients, supporting a promising role for VES in identifying pneumonia caused by coronavirus.

Establishing a standardized FUO emergency department: design and practice in dealing with COVID-19.

BACKGROUND: Since the outbreak of COVID-19 in January, 2020, the fever of unknown origin (FUO) emergency department has become the first station for disease prevention and identification in hospitals. Establishing a standardized FUO emergency department within a short period of time has become the key to preventing and controlling COVID-19 in densely populated Chinese cities. METHODS: Based on the lean management model, the research group established a process of less-link visits, which sees reduced contact between patients and physicians during diagnosis and treatment, and zero-contact consultation through lean workflow and value stream analysis. Three steps were implemented to improve the operations of the FUO emergency department: the rapid establishment of an isolation zone, the refinement of duty and protection configuration, and the use of Internet and technology to establish a full-process follow-up consultation system. RESULTS: (I) Tests related to COVID-19 screening are all completed in the FUO emergency department; (II) 12 new isolated observation rooms have been built; (III) hospital visiting time, waiting time for consultation, and the time from pre-examination to virus screening has been shortened from 18 to 8 hours, from 2 hours to 10 minutes, and from 34 to 3 hours, respectively; (IV) the transfer distance has been shortened from 450 to 20 m, and the observation time has been shortened from 72 to 26 hours. The median waiting time for image examination has been reduced from 40 to 3 minutes, and the moving distance has been shortened from 800 to 10 m; (V) the diagnosis and treatment process is facilitated by 5G, achieving zero contact between doctors and patients. CONCLUSIONS: Through the implantation of information technology, the local transformation of the site, the rational allocation of medical teams and the planned distribution of protective equipment, in a short period of time, individual medical institutions can set up a safe FUO emergency department to provide 24-hour screening and detention services. Establishing an FUO emergency department with lean management and realizing the management approach of combining daily operation with prevention and control could help China and other countries to handle the outbreak of fulminant infectious diseases.

The effect of physician educational intervention on venous thromboembolism pharmacological prophylaxis in medical inpatients from the respiratory department: a retrospective cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a serious health problem for which pharmacological prophylaxis has been proven to be effective. However, there are significant gaps between the guidelines and clinical practice. This study is to evaluate the effect of physician educational intervention (PEI) on VTE pharmacological prophylaxis in medical inpatients from the respiratory department. METHODS: Medical inpatients from the respiratory department between February 2014 and December 2016 were recruited in this retrospective cohort study. They were assigned to the PEI group or the control group according to whether their physicians undertook a quality improvement (QI) project carried out in hospital to raise physician awareness of pharmacological thromboprophylaxis by educational intervention. Any and appropriate pharmacological VTE prophylaxis rates, the use of appropriate anticoagulants, and the occurrence of VTE events in the two groups were calculated and compared using a chi-square test and continuity correction. Poisson regression analysis was used to evaluate the relative risk (RR) of PEI on the occurrence of VTE events. RESULTS: The any pharmacological VTE prophylaxis rate (11.3% vs. 5.9%, P=0.048) and appropriate pharmacological VTE prophylaxis rate (9.3% vs. 5.5%, P=0.036) in high-risk patients without high major bleeding risk were both significantly higher than the control group. Compared with the control group, appropriate anticoagulants in the PEI group took up a larger proportion of all used anticoagulants (90.3% vs. 78.7%, P=0.007). In anticoagulants used for high-risk patients without high major bleeding, appropriate anticoagulants show no statistical difference between the two groups (93.8% vs. 77.8%, P=0.153). There was no difference in the occurrence of VTE events between the two study groups in overall patients (0.5% vs. 0.6%, P=0.913), and among those with high VTE risk (1.7% vs. 1.0%, P=0.554). PEI had no association with the probability of VTE event occurrence (RR, 1.246; 95% CI, 0.478-2.188, P=0.954). CONCLUSIONS: Educational intervention effectively increased physician awareness of VTE prophylaxis in the respiratory department. Further interventions are still necessary since the guidelines were implemented to a relatively low degree.

Treating wheat seeds with neonicotinoid insecticides does not harm the rhizosphere microbial community.

Wheat aphids damage wheat plants directly by feeding on them and indirectly by transmitting plant pathogenic viruses, both of which result in low yield and plant death. Due to their high root absorption and systemic characteristics, neonicotinoid insecticidal seed treatments are increasingly applied to control wheat aphids throughout the growing season in China. Ecological concerns are raised in some research, because neonicotinoids can persist and accumulate in soils. They are prone to leach into waterways, and are found in crop nectars and pollens, where they may be harmful to pollinators. Less information is available about the effect of neonicotinoid seed treatments on soil microorganisms. Here, we posed the hypothesis that neonicotinoids are not harmful to soil microbial communities. We tested our hypothesis by evaluating the effects of two neonicotinoids, imidacloprid and clothianidin, on soil microbiomes using high-throughput sequencing during three points in the wheat growth season. Except for the imidacloprid-treated soil in the seedling stage, the community richness and diversity were not affected according to Chao1, ACE and the Shannon indices, and species distribution histogram at the phylum level. However, Beta diversity indices showed that the species richness of the bacterial and fungal community was suppressed by neonicotinoids in seedling stage (high neonicotinoids concentrations), whereas by the reviving period, the changes reverted into stimulation of the soil microorganisms (low neonicotinoids concentrations). Overall, the general microbiome recovered at the end of the wheat planting season. Generally, wheat seed dressing with neonicotinoid insecticides control aphids during the entire growth period, and have no lasting adverse effects on the soil microbiome. This study provides an understanding of the influence of neonicotinoids on crop land ecology at the level of soil microbe communities.

[Study on antioxidant activity of pigment of Lycium ruthenicum].

OBJECTIVE: To elvaulate the antioxidant activity of the pigment of Lycium ruthenicum. METHOD: The antioxidant activities were measured by the effects of the reducing ability, scavenging DPPH. H2O2-induced hemolysis of mice erythrocyte, serum resistance of reactive oxygen species, content of MDA in liver tissue, and swelling effect of mitochondria in liver tissue. RESULT: The pigment of L. ruthenicum could scaveng DPPH* remarkably with IC50 0.164 mg x mL(-1), inhibitte hemolysis of mice erythrocyte evidently with IC50 0.112 mg x mL(-1). The resistant of reactive oxygen species was enhanced by the tested substances, simultanously. The concentration of MDA of peroxidation of lipid in mice liver could be reduced, and the swelling of mice liver mitochondria alse be restrained. CONCLUSION: The pigment of L. ruthenicum has antioxidant activity in tested concentration.

Distinguishing the importance between habitat specialization and dispersal limitation on species turnover.

Understanding what governs community assembly and the maintenance of biodiversity is a central issue in ecology, but has been a continuing debate. A key question is the relative importance of habitat specialization (niche assembly) and dispersal limitation (dispersal assembly). In the middle of the Loess Plateau, northwestern China, we examined how species turnover in Liaodong oak (Quercus wutaishanica) forests differed between observed and randomized assemblies, and how this difference was affected by habitat specialization and dispersal limitation using variation partitioning. Results showed that expected species turnover based on individual randomization was significantly lower than the observed value (P < 0.01). The turnover deviation significantly depended on the environmental and geographical distances (P < 0.05). Environmental and spatial variables significantly explained approximately 40% of the species composition variation at all the three layers (P < 0.05). However, their contributions varied among forest layers; the herb and shrub layers were dominated by environmental factors, whereas the canopy layer was dominated by spatial factors. Our results underscore the importance of synthetic models that integrate effects of both dispersal and niche assembly for understanding the community assembly. However, habitat specialization (niche assembly) may not always be the dominant process in community assembly, even under harsh environments. Community assembly may be in a trait-dependent manner (e.g., forest layers in this study). Thus, taking more species traits into account would strengthen our confidence in the inferred assembly mechanisms.