Publications by authors named "Ling Yang"

1,346 Publications

  • Page 1 of 1

Autophagy in liver diseases: A review.

Mol Aspects Med 2021 Jun 10:100973. Epub 2021 Jun 10.

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA. Electronic address:

The liver is a highly dynamic metabolic organ that plays critical roles in plasma protein synthesis, gluconeogenesis and glycogen storage, cholesterol metabolism and bile acid synthesis as well as drug/xenobiotic metabolism and detoxification. Research from the past decades indicate that autophagy, the cellular catabolic process mediated by lysosomes, plays an important role in maintaining cellular and metabolic homeostasis in the liver. Hepatic autophagy fluctuates with hormonal cues and the availability of nutrients that respond to fed and fasting states as well as circadian activities. Dysfunction of autophagy in liver parenchymal and non-parenchymal cells can lead to various liver diseases including non-alcoholic fatty liver diseases, alcohol associated liver disease, drug-induced liver injury, cholestasis, viral hepatitis and hepatocellular carcinoma. Therefore, targeting autophagy may be a potential strategy for treating these various liver diseases. In this review, we will discuss the current progress on the understanding of autophagy in liver physiology. We will also discuss several forms of selective autophagy in the liver and the molecular signaling pathways in regulating autophagy of different cell types and their implications in various liver diseases.
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http://dx.doi.org/10.1016/j.mam.2021.100973DOI Listing
June 2021

Influence of herb-partitioned moxibustion at Qihai (CV6) and bilateral Tianshu (ST25) and Shangjuxu (ST37) acupoints on toll-like receptors 4 signaling pathways in patients with ulcerative coliti.

J Tradit Chin Med 2021 Jun;41(3):479-485

Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China.

Objective: To evaluate the efficacy of herb-partitioned moxibustion (HPM) at Qihai (CV6), Tianshu (ST25) and Shangjuxu (ST37) acupoints in relieving symptoms and the immune regulation of HPM on the toll-like receptors 4 (TLR4) signaling pathway in ulcerative colitis (UC) patients.

Methods: A randomized, single-blind study was conducted 63 patients to receive HPM or sham HPM treatment. The efficacy outcomes included scores of the Mayo, Baron, inflammatory bowel disease questionnaire (IBDQ), self-rating depression scale (SDS), self-rating anxiety scale (SAS). HE staining was used to observe the histopathological changes of the colon. The expression of inflammatory cytokines and TLR4 signaling pathway related molecules were determined by enzyme-linked immunosorbent assay and immunohistochemistry.

Results: Baron, SDS, SAS scores were significantly decreased in moxibustion group (P < 0.05), IBDQ score was significantly greater in the moxibustion group than in the sham moxibustion group (P < 0.05). Histopathology of mucosal biopsies showed that both two groups improved in mucosa after treatment. The expression levels of tumor necrosis factor-α, interleukin-2, interleukin-12, interferon-γ, and TLR4, lipopolysaccharide, myeloid differentiation factor 88, interleukin receptor associated kinase, tumor necrosis factor receptor associated factor 6 and nuclear factor kappa-B p65 were significantly lower in the moxibustion group than in the sham moxibustion group (P < 0.05).

Conclusion: This study showed that HPM at Qihai?(CV6),?Tianshu?(ST25) and?Shangjuxu (ST37) acupoints is effective to relieve symptoms, anxiety, depression and improving life quality in UC patients, which may be related to the immune regulation of HPM on TLR4 signaling pathway.
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http://dx.doi.org/10.19852/j.cnki.jtcm.20210310.001DOI Listing
June 2021

A porcine brain-wide RNA editing landscape.

Commun Biol 2021 Jun 10;4(1):717. Epub 2021 Jun 10.

Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Shenzhen, China.

Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is an essential post-transcriptional modification. Although hundreds of thousands of RNA editing sites have been reported in mammals, brain-wide analysis of the RNA editing in the mammalian brain remains rare. Here, a genome-wide RNA-editing investigation is performed in 119 samples, representing 30 anatomically defined subregions in the pig brain. We identify a total of 682,037 A-to-I RNA editing sites of which 97% are not identified before. Within the pig brain, cerebellum and olfactory bulb are regions with most edited transcripts. The editing level of sites residing in protein-coding regions are similar across brain regions, whereas region-distinct editing is observed in repetitive sequences. Highly edited conserved recoding events in pig and human brain are found in neurotransmitter receptors, demonstrating the evolutionary importance of RNA editing in neurotransmission functions. Although potential data biases caused by age, sex or health status are not considered, this study provides a rich resource to better understand the evolutionary importance of post-transcriptional RNA editing.
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http://dx.doi.org/10.1038/s42003-021-02238-3DOI Listing
June 2021

[The value of circulating microRNA-1 in the early diagnosis of coronary atherosclerotic plaque rupture in patients with stable coronary heart disease].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 May;33(5):568-572

Department of Cardiology, the Second People's Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi 214000, Jiangsu, China. Corresponding author: Su Tong, Email:

Objective: To evaluate the diagnostic value of circulating microRNA-1 (miR-1) in early coronary artery plaque rupture in patients with stable coronary artery disease (SCAD).

Methods: A prospective cohort study was conducted. Sixty-seven patients with SCAD admitted to the department of cardiology of the Third Affiliated Hospital of Soochow University from January to June in 2019 were enrolled. All patients had completed coronary angiography (CAG), percutaneous coronary intervention (PCI) single stent implantation or only CAG was performed according to the CAG results. Blood samples were collected before (0 hour) and 3 hours after the procedure. The expression of plasma miR-1 was detected by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR), and electrocardiogram was used to detect cardiac troponin I (cTnI) levels. The difference of miR-1 and cTnI levels in PCI or CAG patients before and after procedure were compared, and the value for early diagnosis of coronary artery plaque rupture in SCAD patients was evaluated. The diagnostic efficacy was evaluated by the receiver operating characteristic curve (ROC curve).

Results: There were 38 CAG patients and 29 PCI patients. There were no significant differences in gender, age, previous history (without hypertension history) and baseline data of cardiac function between the two groups. The expression of miR-1 after PCI was significantly higher than that before PCI [2: 2.11 (1.56, 2.73) vs. 1.26 (1.07, 1.92), P < 0.01], and there was no significant difference in cTnI level before and after PCI [μg/L: 0.00 (0.00, 0.02) vs. 0.00 (0.00, 0.02), P > 0.05]. There were no significant differences in miR-1 and cTnI levels before and after procedure in the CAG group [miR-1 (2): 1.09 (1.00, 1.40) vs. 1.21 (1.00, 1.71), cTnI (μg/L): 0.00 (0.00, 0.02) vs. 0.00 (0.00, 0.02), both P > 0.05]. ROC curve analysis showed that the area under ROC curve (AUC) and 95% confidence interval (95%CI) of miR-1 in the diagnosis of coronary plaque rupture were 0.794 (0.687-0.900), P < 0.01, the sensitivity was 82.8%, the specificity was 68.4%, and the optimal cut-off value was 1.51. The AUC and 95%CI of the difference of miR-1 before and after operation (ΔmiR-1) were 0.704 (0.567-0.842), P = 0.004, the sensitivity was 62.1%, the specificity was 84.2%, and the optimal cut-off value was 0.39. The efficancy of miR-1 and ΔmiR-1 after procedure to diagnose coronary plaque rupture in patients with SCAD was similar (Z = 1.287, P = 0.198). However, baseline miR-1 might not predict whether patients with SCAD need PCI or not (AUC = 0.630, P > 0.05). Multivariate binary Logistic regression analysis showed that increased postoperative miR-1 expression was an independent risk factor for coronary plaque rupture in SCAD patients [odds ratios (OR) = 2.887, 95%CI was 1.044-7.978, P = 0.041].

Conclusions: Circulating miR-1 might have the value for early diagnosis of coronary artery plaque rupture in SCAD patients.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200907-00614DOI Listing
May 2021

Modulation of the transport of valproic acid through the blood-brain barrier in rats by the Gastrodia elata extracts.

J Ethnopharmacol 2021 Jun 1;278:114276. Epub 2021 Jun 1.

Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. Electronic address:

Headings Ethnopharmacological Relevance: Valproic acid (VPA) is primarily used as a medicine for the treatment of seizures. Gastrodia elata (G. elata) extract has been used as an alternative medicine for epilepsy patients. Cotreatment with VPA and G. elata extract is commonly prescribed in Taiwan and mainland China. Nevertheless, the mechanism of the blood-brain barrier (BBB) transportation effect of G. elata extract on VPA has not been characterized.

Aim Of Study: Our hypothesis is that G. elata extract modulates the BBB penetration of VPA through specific transporter transfer.

Materials And Methods: A validated liquid chromatography-tandem mass spectrometry and multiple microdialysis method was developed to simultaneously monitor VPA in the blood and brain of rats. To investigate the mechanism of BBB modulation by the G. elata extract on VPA in the brain, cyclosporin A, a P-glycoprotein (P-gp) inhibitor and organic anion transporting polypeptide (OATP) inhibitor, was coadministered with the G. elata extract and VPA.

Results: The pharmacokinetic results demonstrated that the VPA penetration ratio of the BBB, determined by the area under the concentration curve (AUC) ratio of VPA (AUC/AUC), was approximately 0.36. After treatment with the G. elata extract (1 and 3 g/kg, p.o. for 5 consecutive days), the VPA penetration ratios were significantly enhanced to 1.47 and 1.02, respectively. However, in the experimental group coadministered cyclosporin A, the G. elata extract was unable to enhance the BBB transportation of VPA. Instead, the VPA penetration ratio in the brain was suppressed back to 0.38.

Conclusions: The present study reveals that the enhancement effect of the transporter mechanism of G. elata extract on VPA transport into the brain occurs through the OATP transporter but not the P-gp transporter.
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http://dx.doi.org/10.1016/j.jep.2021.114276DOI Listing
June 2021

Association between D-dimer level and chest CT severity score in patients with SARS-COV-2 pneumonia.

Sci Rep 2021 06 2;11(1):11636. Epub 2021 Jun 2.

Department of Cardiology, West China Hospital, Sichuan University, #37 Guoxue Alley, Chengdu, 610041, People's Republic of China.

The elevated level of D-dimer and its relationship with poor outcomes in SARS-COV-2 pneumonia patients have been demonstrated. In addition to a hypercoagulable state, D-dimer is also a biomarker of inflammation. We investigated the relationship between D-dimer level and chest computed tomography (CT) severity score, which could reflect the severity of inflammation in SARS-COV-2 pneumonia patients. We retrospectively enrolled 86 consecutive SARS-COV-2 pneumonia patients. CT severity scores were computed to quantify the overall lung involvement. The D-dimer level among CT score tertiles and the association of the D-dimer level with CT score were analyzed. Our results showed that the median D-dimer level was 0.70 mg/L (IQR 0.35-1.76). 42 patients (48.8%) had D-dimer levels above the median level. The D-dimer levels were significantly different across CT score tertiles (0.37 mg/l [IQR 0.31-0.87], 0.66 mg/l [IQR 0.39-1.43], 1.83 mg/l [IQR 0.85-4.41], P < 0.001). The natural logarithm of the D-dimer level was significantly associated with the CT score (r = 0.586, P < 0.001). In conclusion, the D-dimer level may be associated with the severity of inflammation of SARS-COV-2 pneumonia prior to coagulopathy/thrombosis. This could be an additional explanation for the mechanism of the relationship between elevated D-dimer level and higher mortality.
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http://dx.doi.org/10.1038/s41598-021-91150-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172878PMC
June 2021

Type II Grass Carp Reovirus Infects Leukocytes but Not Erythrocytes and Thrombocytes in Grass Carp ().

Viruses 2021 05 10;13(5). Epub 2021 May 10.

Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.

Grass carp reovirus (GCRV) causes serious losses to the grass carp industry. At present, infectious tissues of GCRV have been studied, but target cells remain unclear. In this study, peripheral blood cells were isolated, cultured, and infected with GCRV. Using quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot, indirect immunofluorescence, flow cytometry, and transmission electron microscopy observation, a model of GCRV infected blood cells in vitro was established. The experimental results showed GCRV could be detectable in leukocytes only, while erythrocytes and thrombocytes could not. The virus particles in leukocytes are wrapped by empty membrane vesicles that resemble phagocytic vesicles. The empty membrane vesicles of leukocytes are different from virus inclusion bodies in kidney (CIK) cells. Meanwhile, the expression levels of , , , were significantly up-regulated in leukocytes, indicating that GCRV could cause the production of the related immune responses. Therefore, GCRV can infect leukocytes in vitro, but not infect erythrocytes and thrombocytes. Leukocytes are target cells in blood cells of GCRV infections. This study lays a theoretical foundation for the study of the GCRV infection mechanism and anti-GCRV immunity.
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http://dx.doi.org/10.3390/v13050870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150784PMC
May 2021

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses.

Nutr Metab Cardiovasc Dis 2021 Apr 27. Epub 2021 Apr 27.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China. Electronic address:

Background And Aims: Observational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults.

Methods And Results: The China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]).

Conclusions: This study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.
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http://dx.doi.org/10.1016/j.numecd.2021.04.015DOI Listing
April 2021

Development and external validation of a breast cancer absolute risk prediction model in Chinese population.

Breast Cancer Res 2021 May 29;23(1):62. Epub 2021 May 29.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

Backgrounds: In contrast to developed countries, breast cancer in China is characterized by a rapidly escalating incidence rate in the past two decades, lower survival rate, and vast geographic variation. However, there is no validated risk prediction model in China to aid early detection yet.

Methods: A large nationwide prospective cohort, China Kadoorie Biobank (CKB), was used to evaluate relative and attributable risks of invasive breast cancer. A total of 300,824 women free of any prior cancer were recruited during 2004-2008 and followed up to Dec 31, 2016. Cox models were used to identify breast cancer risk factors and build a relative risk model. Absolute risks were calculated by incorporating national age- and residence-specific breast cancer incidence and non-breast cancer mortality rates. We used an independent large prospective cohort, Shanghai Women's Health Study (SWHS), with 73,203 women to externally validate the calibration and discriminating accuracy.

Results: During a median of 10.2 years of follow-up in the CKB, 2287 cases were observed. The final model included age, residence area, education, BMI, height, family history of overall cancer, parity, and age at menarche. The model was well-calibrated in both the CKB and the SWHS, yielding expected/observed (E/O) ratios of 1.01 (95% confidence interval (CI), 0.94-1.09) and 0.94 (95% CI, 0.89-0.99), respectively. After eliminating the effect of age and residence, the model maintained moderate but comparable discriminating accuracy compared with those of some previous externally validated models. The adjusted areas under the receiver operating curve (AUC) were 0.634 (95% CI, 0.608-0.661) and 0.585 (95% CI, 0.564-0.605) in the CKB and the SWHS, respectively.

Conclusions: Based only on non-laboratory predictors, our model has a good calibration and moderate discriminating capacity. The model may serve as a useful tool to raise individuals' awareness and aid risk-stratified screening and prevention strategies.
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http://dx.doi.org/10.1186/s13058-021-01439-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164768PMC
May 2021

Influence of low tumor content on tumor mutational burden estimation by whole-exome sequencing and targeted panel sequencing.

Clin Transl Med 2021 May;11(5):e415

Department of In Vitro Diagnostic Reagent, National Institutes for Food And Drug Control (NIFDC), Beijing, China.

Background: Tumor mutational burden (TMB) is a promising biomarker for stratifying patient subpopulation who would benefit from immune checkpoint blockade (ICB) therapies. Although great efforts have been made for standardizing TMB measurement, mutation calling and TMB quantification can be challenging in samples with low tumor content including liquid biopsies. The effect of varying tumor content on TMB estimation by different assay methods has never been systematically investigated.

Method: We established a series of reference standard DNA samples derived from 11 pairs of tumor-normal matched human cell lines across different cancer types. Each tumor cell line was mixed with its matched normal at 0% (control), 1%, 2%, 5%, and 10% mass-to-mass ratio to mimic the clinical samples with low tumor content. TMB of these reference standards was evaluated by both ∼1000× whole-exome sequencing (wesTMB) and targeted panel sequencing (psTMB) at four different vendors. Both regression and classification analyses of TMB were performed for theoretical investigation and clinical practice purposes.

Results: Linear regression model was established that demonstrated in silico psTMB determined by regions of interest (ROI) as a great representative of wesTMB based on TCGA dataset. It was also true in our reference standard samples as the predicted psTMB interval based on the observed wesTMB captured the intended 90% of the in silico psTMB values. Although ∼1000× deep WES was applied, reference standard samples with less than 5% of tumor proportions are below the assay limit of detection (LoD) of wesTMB quantification. However, predicted wesTMB based on observed psTMB accurately classify (>0.97 AUC) for TMB high and low patient stratification even in samples with 2% of tumor content, which is more clinically relevant, as TMB determination should be a qualitative assay for TMB high and low patient classification. One targeted panel sequencing vendor using an optimized blood psTMB pipeline can further classify TMB status accurately (>0.82 AUC) in samples with only 1% of tumor content.

Conclusions: We developed a linear model to establish the quantitative correlation between wesTMB and psTMB. A set of DNA reference standards was produced in aid to standardize TMB measurements in samples with low tumor content across different targeted sequencing panels. This study is a significant contribution aiming to harmonize TMB estimation and extend its future application in clinical samples with low tumor content including liquid biopsy.
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http://dx.doi.org/10.1002/ctm2.415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102856PMC
May 2021

Herb-partitioned moxibustion alleviates colonic inflammation in Crohn's disease rats by inhibiting hyperactivation of the NLRP3 inflammasome via regulation of the P2X7R-Pannexin-1 signaling pathway.

PLoS One 2021 27;16(5):e0252334. Epub 2021 May 27.

Yueyang Clinical Medicine School, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Crohn's disease is a chronic inflammatory bowel disease and the NLRP3 inflammasome plays an important role in Crohn's disease. Previous studies have shown that Herb-partitioned moxibustion treating (at Qihai (CV 6) and Tianshu (ST 25)) prevented the excessive activation of the NLRP3 inflammasome and repaired damaged colonic mucosa in Crohn's disease. However, the mechanism by which Herb-partitioned moxibustion (at CV 6 and ST 25) regulates NLRP3 remains unclear. In this study, we treated Crohn's disease rats with herb-partitioned moxibustion (at CV 6 and ST 25) to investigate the mechanism by which Herb-partitioned moxibustion regulates the colonic NLRP3 inflammasome by observing colon length, the colon macroscopic damage indexes, and the expression of ATP, P2X7R, Pannexin-1, NF-κBp65, NLRP3, ASC, caspase-1, IL-1β and IL-18 in the colon in Crohn's disease. Here, this study shows that herb-partitioned moxibustion (at CV 6 and ST 25) can reduce colon macroscopic damage indexes and colon histopathological scores, alleviate colon shortening and block the abnormal activation of the NLRP3 inflammasome by inhibiting the ATP content and the expression of P2X7R, Pannexin-1 and NF-κBp65, thereby reducing the release of the downstream inflammatory cytokine IL-1β and ultimately suppressing colonic inflammation in Crohn's disease rats. This study for the first time identifies the mechanism by which herb-partitioned moxibustion (at CV 6 and ST 25) may inhibit the abnormal activation of the NLRP3 inflammasome by inhibiting the P2X7R-Pannexin-1 signaling pathway in Crohn's disease rats.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252334PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158928PMC
May 2021

Inhibition of catechol--methyltransferase by natural pentacyclic triterpenes: structure-activity relationships and kinetic mechanism.

J Enzyme Inhib Med Chem 2021 Dec;36(1):1079-1087

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Inhibitors of COMT are clinically used for the treatment of Parkinson's disease. Here, we report the first natural pentacyclic triterpenoid-type COMT inhibitors and their structure-activity relationships and inhibition mechanism. The most potent compounds were found to be oleanic acid, betulinic acid and celastrol with IC values of 3.89-5.07 μM, that acted as mixed (uncompetitive plus non-competitive) inhibitors of COMT, representing a new skeleton of COMT inhibitor. Molecular docking suggested that they can specifically recognise and bind with the unique hydrophobic residues surrounding the catechol pocket. Furthermore, oleanic acid and betulinic acid proved to be less disruptive of mitochondrial membrane potential (MMP) compared to tolcapone, thus reducing the risk of liver toxicity. These findings could be used to produce an ideal lead compound and to guide synthetic efforts in generating related derivatives for further preclinical testing.
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http://dx.doi.org/10.1080/14756366.2021.1928112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158265PMC
December 2021

Age-specific associations between habitual snoring and cardiovascular diseases in China: a 10-year cohort study.

Chest 2021 May 21. Epub 2021 May 21.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China. Electronic address:

Background: There is limited convincing evidence of the relationship between habitual snoring and cardiovascular diseases (CVDs).

Research Question: Is habitual snoring associated with total CVD and CVD subtypes in different age groups of Chinese adults?

Study Design And Methods: The China Kadoorie Biobank study enrolled over 0.5 million adults aged 30 to 79 years from 10 regions in China. Snoring status and other baseline characteristics were collected from 2004 to 2008 using an interviewer-administered laptop-based questionnaire. The present analysis included 489,583 participants without stroke or coronary heart disease at baseline. Cox proportional hazards models were used to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of CVDs for habitual snoring versus nonhabitual snoring.

Results: During a median follow-up of 9.6 years, 130,935 participants developed CVDs. Associations between habitual snoring and CVDs varied with age. Among participants aged <50 years at baseline, habitual snoring was associated with an increased risk of total CVD (HR: 1.11, 95% CI: 1.07-1.14) after adjustment for known CVD risk factors including systolic blood pressure. The corresponding HRs (95% CIs) for ischemic heart disease, ischemic stroke, and hemorrhagic stroke were 1.18 (1.12-1.24), 1.12 (1.05-1.19), and 1.05 (0.92-1.19), respectively. However, such associations in adults aged 50∼64 years were much weaker, and no statistically significant association was observed among individuals aged ≥65 years. Age-specific risk estimates were generally similar across sex and obesity subgroups.

Interpretation: Habitual snoring was associated with increased risks of total CVD, ischemic heart disease, ischemic stroke, but not hemorrhagic stroke in Chinese and these associations were mainly limited to those aged<50 years. Clinicians in China are suggested to identify snoring, particularly in younger adults.
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http://dx.doi.org/10.1016/j.chest.2021.04.070DOI Listing
May 2021

Contribution of Different Mechanisms to Ciprofloxacin Resistance in spp.

Front Microbiol 2021 6;12:663731. Epub 2021 May 6.

Guangdong Key Laboratory of Veterinary Drug Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

Development of fluoroquinolone resistance can involve several mechanisms that include chromosomal mutations in genes ( and ) encoding the target bacterial topoisomerase enzymes, increased expression of the AcrAB-TolC efflux system, and acquisition of transmissible quinolone-resistance genes. In this study, 176 isolates from animals with a broad range of ciprofloxacin MICs were collected to analyze the contribution of these different mechanisms to different phenotypes. All isolates were classified according to their ciprofloxacin susceptibility pattern into five groups as follows: highly resistant (HR), resistant (R), intermediate (I), reduced susceptibility (RS), and susceptible (S). We found that the ParC T57S substitution was common in strains exhibiting lowest MICs of ciprofloxacin while increased MICs depended on the type of GyrA mutation. The ParC T57S substitution appeared to incur little cost to bacterial fitness on its own. The presence of PMQR genes represented an route for resistance development in the absence of target-site mutations. Switching of the plasmid-mediated quinolone resistance (PMQR) gene location from a plasmid to the chromosome was observed and resulted in decreased ciprofloxacin susceptibility; this also correlated with increased fitness and a stable resistance phenotype. The overexpression of AcrAB-TolC played an important role in isolates with small decreases in susceptibility and expression was upregulated by MarA more often than by RamA. This study increases our understanding of the relative importance of several resistance mechanisms in the development of fluoroquinolone resistance in from the food chain.
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http://dx.doi.org/10.3389/fmicb.2021.663731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137344PMC
May 2021

A Disulfide Switch Providing Absolute Handedness Control in Double Helices via Conversion from the Antiparallel to Parallel Helical Pattern.

Chemistry 2021 May 20. Epub 2021 May 20.

Huazhong University of Science&Technology, School of Chemistry and chemical engineering, Luoyu Road 1037, 430074, Wuhan, CHINA.

A strategy to reversibly switch the parallel/antiparallel helical conformation of aromatic double helices through the formation/breakage of a disulfide bond is presented. Single-crystal X-ray structures, NMR, and circular dichroism spectroscopy demonstrate that the double helices with terminal thiol groups favor an antiparallel helical arrangement both in the solid state and in solution, while the P / M bias of helicity induced by chiral segments from another extremity of the sequence is weak in this structural motif. The antiparallel helices can be rearranged to parallel helices through the disulfide connection of the sequences. This in turn enhances the bias of helical handedness and results in absolute chirality control of the double helices. The handedness mediated process can be governed by the oxidation-reduction cycle, thereby switching the structural arrangement and the enhancement of chiral bias. In addition, we find that the sequences can dimerize into an intermolecular double helix with the disulfide connection. And the helical handedness is also fully controlled due to the head-to-head structural motif.
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http://dx.doi.org/10.1002/chem.202101221DOI Listing
May 2021

The correlation between neonatal vitamin D levels and the risk of childhood asthma attacks.

Transl Pediatr 2021 Apr;10(4):914-920

Department of Neonatology, Haikou Hospital of The Maternal And Child Health, Haikou, China.

Background: To explore the correlation between neonatal vitamin D levels and the risk of asthma in children aged 3-9 years.

Methods: A total of 1,534 subjects were selected, and clinical and laboratory test data of all subjects were collected at birth, including 25-hydroxyvitamin D3 [25(OH)D3] levels, gender, season of birth, birth weight; whether delivery was premature, cesarean section, or primipara; and parental details including maternal age, ethnicity, level of education, history of smoking, and history of maternal or paternal asthma. The level of 25(OH)D3 was used as a continuous variable to analyze its correlation with the risk of asthma using the Cox proportional regression model. In addition, subjects were divided into four groups according to their 25(OH)D3 quartiles, and the first quantile group was used as a reference to analyze the risk of asthma in the other groups. Further subgroup analysis was conducted according to the patients' gender and birth season.

Results: Among the 1,534 subjects included, there were 107 cases in the asthma-affected group and 1,427 cases in the normal control group. Compared with the control group, the level of 25(OH)D3 in the asthma group was significantly lower (P=0.03), the mother's education level was lower (P=0.002), but the preterm birth rate, cesarean section rate, and parental asthma prevalence rate were significantly higher (all P<0.05). When the neonatal 25(OH)D3 was divided into quartiles to perform a categorical variable analysis, we found that compared with the first quantile (Q1, 0.0-25.1 mmol/L), the risk of asthma in Q4 was reduced by 50% (HR=0.50, 95% CI: 0.38-0.76). The second quantile group (Q2) and the third quantile group (Q3) showed no significant difference in the risk of disease compared with Q1 but showed a trend of decreasing risk as the quantile group increased (the trend P values were both <0.05). This correlation was still valid when a stratified analysis was made based on gender and birth season.

Conclusions: There is a significant correlation between a reduced vitamin D level in newborns and the subsequent risk of asthma in children aged 3-9 years. Moreover, the level of vitamin D is an independent risk factor for childhood asthma.
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http://dx.doi.org/10.21037/tp-21-92DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107849PMC
April 2021

Predictive Model of Ursodeoxycholic Acid Treatment Response in Primary Biliary Cholangitis.

J Clin Transl Hepatol 2021 Apr 4;9(2):187-193. Epub 2021 Mar 4.

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background And Aims: Although ursodeoxycholic acid (UDCA) treatment in primary biliary cholangitis is effective in many patients, there are still many people who respond poorly to it. Identifying and intervening these patients early is important. Therefore, exploring the risk factors and proposing a predictor index to predict the UDCA treatment nonresponse earlier among primary biliary cholangitis patients were the aims of this research.

Methods: A total of 135 primary biliary cholangitis patients treated with UDCA (13-15 mg/kg/d) were enrolled in this retrospective study. The response to treatment was evaluated based on Paris I criteria. The univariate and logistic multivariate regression analyses were adopted to determine the independent risk factors and propose a predictor index. Receiver operating characteristic curve was used to evaluate the predictive ability of the predictor index.

Results: Total bilirubin, albumin, globulin, immunoglobin M, and aspartate aminotransferase-to-platelet ratio index were the five independent risk factors associating with early biochemical nonresponse to UDCA treatment. Based on these factors, we established a predictor index with the predictive value being 0.886 (sensitivity: 82.80%, specificity: 84.40%).

Conclusions: We developed a predictor index that had an accurate prediction of the early biochemical nonresponse to UDCA treatment, which is expected to provide valuable information for the high-risk group before treatment begins.
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http://dx.doi.org/10.14218/JCTH.2020.00127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111104PMC
April 2021

Serial circulating tumor DNA identification associated with the efficacy and prognosis of neoadjuvant chemotherapy in breast cancer.

Breast Cancer Res Treat 2021 May 18. Epub 2021 May 18.

Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifu Garden, Dongcheng District, Beijing, 100010, China.

Background: Circulating tumor DNA (ctDNA) provides a promising noninvasive alternative to evaluate the efficacy of neoadjuvant chemotherapy (NCT) in breast cancer.

Methods: Herein, we collected 63 tissue (aspiration biopsies and resected tissues) and 206 blood samples (baseline, during chemotherapy (Chemo), after chemotherapy (Post-Chemo), after operation (Post-Op), during follow-up) from 32 patients, and preformed targeted deep sequencing with a customed 1021-gene panel.

Results: As the results, TP53 (43.8%) and PIK3CA (40.6%) were the most common mutant genes in the primary tumors. At least one tumor-derived mutation was detected in the following number of blood samples: 21, baseline; 3, Chemo; 9, Post-Chemo; and 5, Post-Op. Four patients with pathologic complete response had no tissue mutation in Chemo and Post-Chemo blood. Compared to patients with mutation-positive Chemo or Post-Chemo blood, the counterparts showed a superior primary tumor decrease (median, 86.5% versus 54.6%) and lymph involvement (median, 1 versus 3.5). All five patients with mutation-positive Post-Op developed distant metastases during follow-up, and the sensitivity of detecting clinically relapsed patients was 71.4% (5/7). The median DFS was 9.8 months for patients with mutation-positive Post-Op but not reached for the others (HR 23.53; 95% CI, 1.904-290.9; p < 0.0001).

Conclusions: Our study shows that sequential monitoring of blood ctDNA was an effective method for evaluating NCT efficacy and patient recurrence. Integrating ctDNA profiling into the management of LABC patients might improve clinical outcome.

Trial Registration: This prospective study recruited LABC patients at Peking Union Medical College Hospital (ClinicalTrials.gov Identifier: NCT02797652).
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http://dx.doi.org/10.1007/s10549-021-06247-yDOI Listing
May 2021

In situ preparation of g-CN/polyaniline hybrid composites with enhanced visible-light photocatalytic performance.

J Environ Sci (China) 2021 Jun 24;104:317-325. Epub 2020 Dec 24.

School of Environment, Key Laboratory for Yellow River and Huai River Water Environmental and Pollution Control, Ministry of Education, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University, Xinxiang 453007, China. Electronic address:

The graphic carbon nitride/polyaniline (g-CN/PANI) hybrid composites were successfully synthesized by a facile in situ polymerization process under ice water bath. The photocatalytic activities of the g-CN/PANI composites were evaluated by using oxytetracycline (OTC) as model pollutants. The optimal g-CN/PANI composite (5%PANI: the g-CN/PANI hybrid with 5 wt.% of PANI) showed an enhancement degradation rate of 5-fold compared to that of conventional g-CN under simulated-sunlight irradiation. In addition, the 5%PANI demonstrate significantly photocatalytic evolution H rate (163.2 μmol/(g⋅hr)) under the visible light irradiation. Furthermore, based on the results of optical performance and electrochemical testing, a possible mechanism was proposed, indicating that the incorporation of PANI into the traditional g-CN can effectively tune the electronic structures, improve the photo-generated electrons-holes separation and enhance extensive absorption of visible light. Such a g-CN/PANI hybrid nanocomposites could be envisaged to possess great potentials in practical wastewater treatment and water splitting.
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http://dx.doi.org/10.1016/j.jes.2020.08.024DOI Listing
June 2021

Image reconstruction with the chaotic fiber laser in scattering media.

Appl Opt 2021 May;60(13):4004-4012

The reconstruction of the size, position, optical properties, and structure of the object in scattering media was realized with a chaotic fiber laser. The light from the chaotic fiber laser was split into two parts. One part was used as the detection signal to detect the object, and the other was used as the reference signal; then, the two signals were cross correlated. The attenuation of light in scattering media was attributed to scattering and absorption. The theoretical model of the peak value of cross correlation of the chaotic signals as projection data were established by the attenuation law, and the filtered back-projection algorithms were used to realize the image reconstruction. The mean squared error, the normalized mean squared error, the peak signal-to-noise ratio, and the structural similarity index of the reconstructed image were analyzed. The results show that the high resolution of the reconstructed image benefits from the high signal-to-noise ratio with the chaotic fiber laser based on a delta-like cross-correlation function.
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http://dx.doi.org/10.1364/AO.420441DOI Listing
May 2021

Benchmark C H /CO Separation in an Ultra-Microporous Metal-Organic Framework via Copper(I)-Alkynyl Chemistry.

Angew Chem Int Ed Engl 2021 May 12. Epub 2021 May 12.

State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, School of Materials Science and Engineering, Zhejiang University, Zheda Road #38, Hangzhou, 310027, China.

Separation of acetylene from carbon dioxide remains a daunting challenge because of their very similar molecular sizes and physical properties. We herein report the first example of using copper(I)-alkynyl chemistry within an ultra-microporous MOF (Cu @UiO-66-(COOH) ) to achieve ultrahigh C H /CO separation selectivity. The anchored Cu ions on the pore surfaces can specifically and strongly interact with C H molecule through copper(I)-alkynyl π-complexation and thus rapidly adsorb large amount of C H at low-pressure region, while effectively reduce CO uptake due to the small pore sizes. This material thus exhibits the record high C H /CO selectivity of 185 at ambient conditions, significantly higher than the previous benchmark ZJU-74a (36.5) and ATC-Cu (53.6). Theoretical calculations reveal that the unique π-complexation between Cu and C H mainly contributes to the ultra-strong C H binding affinity and record selectivity. The exceptional separation performance was evidenced by breakthrough experiments for C H /CO gas mixtures. This work suggests a new perspective to functionalizing MOFs with copper(I)-alkynyl chemistry for highly selective separation of C H over CO .
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http://dx.doi.org/10.1002/anie.202102810DOI Listing
May 2021

Stroke risk prediction using machine learning: a prospective cohort study of 0.5 million Chinese adults.

J Am Med Inform Assoc 2021 May 9. Epub 2021 May 9.

Department of Engineering Science, University of Oxford, Oxford, UK.

Objective: To compare Cox models, machine learning (ML), and ensemble models combining both approaches, for prediction of stroke risk in a prospective study of Chinese adults.

Materials And Methods: We evaluated models for stroke risk at varying intervals of follow-up (<9 years, 0-3 years, 3-6 years, 6-9 years) in 503 842 adults without prior history of stroke recruited from 10 areas in China in 2004-2008. Inputs included sociodemographic factors, diet, medical history, physical activity, and physical measurements. We compared discrimination and calibration of Cox regression, logistic regression, support vector machines, random survival forests, gradient boosted trees (GBT), and multilayer perceptrons, benchmarking performance against the 2017 Framingham Stroke Risk Profile. We then developed an ensemble approach to identify individuals at high risk of stroke (>10% predicted 9-yr stroke risk) by selectively applying either a GBT or Cox model based on individual-level characteristics.

Results: For 9-yr stroke risk prediction, GBT provided the best discrimination (AUROC: 0.833 in men, 0.836 in women) and calibration, with consistent results in each interval of follow-up. The ensemble approach yielded incrementally higher accuracy (men: 76%, women: 80%), specificity (men: 76%, women: 81%), and positive predictive value (men: 26%, women: 24%) compared to any of the single-model approaches.

Discussion And Conclusion: Among several approaches, an ensemble model combining both GBT and Cox models achieved the best performance for identifying individuals at high risk of stroke in a contemporary study of Chinese adults. The results highlight the potential value of expanding the use of ML in clinical practice.
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http://dx.doi.org/10.1093/jamia/ocab068DOI Listing
May 2021

Albumin-Based LL37 Peptide Nanoparticles as a Sustained Release System against Lung Infection.

ACS Biomater Sci Eng 2021 05 31;7(5):1817-1826. Epub 2020 Aug 31.

Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.

(PA) has emerged as a pressing challenge to pulmonary infection and lung damage. The LL37 peptide is an efficient antimicrobial agent against PA strains, but its application is limited because of fast clearance , biosafety concerns, and low bioavailability. Thus, an albumin-based nanodrug delivery system with reduction sensitivity was developed by forming intermolecular disulfide bonds to increase LL37 performance against PA. Cationic LL37 can be efficiently encapsulated via electrostatic interactions to exert improved antimicrobial effects. The LL37 peptide exhibits greater than 48 h of sustained released from LL37 peptide nanoparticles (LL37 PNP), and prolonged antimicrobial effects were noted as the incubation time increased. Levels of inflammatory cytokines secreted by peritoneal macrophages, including TNF-α and IL-6, were reduced significantly after LL37 PNP treatment following PA stimulation, indicating that LL37 PNP inhibits PA growth and exerts anti-inflammatory effects . In a murine model of acute PA lung infection, LL37 PNP significantly reduced TNF-α and IL-1β expression and alleviated lung damage. The accelerated clearance of PA indicates that LL37 PNP could improve PA lung infection and the subsequent inflammation response more efficiently compared with free LL37 peptide. In conclusion, this excellent biocompatible LL37 delivery strategy may serve as an alternative approach for the application of new types of clinical treatment in future.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01084DOI Listing
May 2021

Metabolic risk factors, genetic predisposition, and risk of severe liver disease in Chinese: a prospective study of 0.5 million people.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, China.

Background: Metabolic risk factors have been shown to be associated with severe liver disease (SLD) in Chinese populations. However, there is limited evidence on the combined impact of these factors, or the genetic variants associated with SLD.

Objectives: We examined the associations of combined metabolic risk factors with risks of SLD, both overall and by genetic predisposition to SLD.

Methods: The study population involved 486,828 participants of the prospective China Kadoorie Biobank aged 30-79 years from 10 diverse areas in China without a history of cancer or liver disease at baseline. Cox regression was used to estimate adjusted HRs for SLD associated with combined metabolic risk factors (central adiposity, physical inactivity, and diabetes) by stratum of genetic risk [assessed separately by a PNPLA3 variant (rs738409) and a BMI genetic risk score].

Results: During ∼10 years of follow-up, 3279 incident cases of SLD were recorded. The overall mean BMI was 23.8 kg/m2 (SD, 3.4 kg/m2), and 5.9% participants had diabetes. Compared with those with 3 metabolic factors, participants with 2, 1, and 0 metabolic factors had 31% (HR, 0.69; 95% CI: 0.65-0.73), 43% (HR, 0.57; 95% CI: 0.53-0.60), and 52% (HR, 0.48; 95% CI: 0.42-0.56) lower risks of SLD, respectively. For both BMI and nonalcoholic fatty liver disease variants, participants with fewer metabolic factors had a lower risk of SLD, lower levels of gamma-glutamyl transferase, and lower fatty liver index scores, in participants with low and high genetic risks (P value for interaction > 0.05).

Conclusions: In relatively lean Chinese adults, individuals with fewer metabolic risk factors had a lower relative risk of SLD and a more favorable profile of liver biomarkers across all strata of genetic risk.
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http://dx.doi.org/10.1093/ajcn/nqab099DOI Listing
May 2021

Phytoremediation of potentially toxic elements in a polluted industrial soil using Poinsettia.

Physiol Mol Biol Plants 2021 Apr 27;27(4):675-686. Epub 2021 Mar 27.

Central South University of Forestry and Technology, Changsha, China.

Potentially toxic elements (PTEs) pollution has become a serious environmental threat, particularly in developing countries such as China. In response, there is a growing interest in phytoremediation studies to identify plant species as designated hyperaccumulators of PTEs in polluted soils. Poinsettia was selected as a candidate species for phytoremediation of six PTEs (Zn, Pb, Hg, Cr, As, Cu) in this study. A pot cultivation experiment (randomized incomplete block experimental design with 5 treatments and 4 blocks) was conducted using contaminated soils gathered from an industrial area in southcentral China. The bioaccumulation factor (BAF), translocation factor (TF), and bioconcentration factor were analyzed to determine the phytoremediation potential of poinsettia potted in different ratios of polluted soils. One-way ANOVA with post-hoc Tukey's test showed that poinsettia had significant uptake of Zn, Pb, Cu (BAF < 1 and TF < 1,  < 0.05) and Hg (BAF < 1 and TF > 1,  < 0.05). Poinsettias can therefore effectively accumulate Zn, Pb, and Cu in their lateral roots while extracting and transferring Hg into their leaves. Moreover, poinsettia exhibited tolerance towards As and Cr. Interestingly, it was also observed that PTEs can inhibit the height of potted poinsettia at a certain concentration.
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http://dx.doi.org/10.1007/s12298-021-00980-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055735PMC
April 2021

Cross-Sectional Study of the Effects of Job Burnout on Immune Function in 105 Female Oncology Nurses at a Tertiary Oncology Hospital.

Med Sci Monit 2021 May 4;27:e929711. Epub 2021 May 4.

Nursing Department, Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China (mainland).

BACKGROUND Nurses who work in hospitals experience a high level of burnout and the relationship between immune variables and burnout syndrome has yet to be elucidated. The aim of the present study was to investigate the effects of job burnout on immune function in female oncology nurses in a tertiary oncology hospital in Guangxi, China. The aspects of the human immune system evaluated were humoral and cellular immunity and complement components 3 (C3) and 4 (C4). MATERIAL AND METHODS We administered the Maslach Burnout Inventory-General Survey (MBI-GS), which includes scales for emotional exhaustion, depersonalization (DP), and personal accomplishment (PA), to measure variables related to immune function in 105 female nurses in a tertiary oncology hospital in Guangxi, China. Levels of humoral immunity and C3 and C4 were detected with immune turbidimetry. Cellular immunity was assessed with indirect immunofluorescence. RESULTS A Spearman rank correlation analysis revealed that levels of C3, C4, and CD4- and CD8-positive T cells were significantly associated with burnout symptoms (P<0.05, P<0.01, and P<0.05, respectively). Furthermore, there was a correlation between demographic data and humoral and cellular immunity (both P<0.05). Multivariable linear regression analysis showed that C4 levels were closely related to DP (P<0.05) and that CD4 and CD8 levels were closely related to PA (P<0.01). CONCLUSIONS These results suggest that DP and PA have an impact on immune function, and that timely psychological and behavioral interventions can be used to reduce the degree of job burnout among nurses and regulate their immunity, thus enabling them to better serve patients.
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http://dx.doi.org/10.12659/MSM.929711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106256PMC
May 2021

Insights into the functional divergence of the haloacid dehalogenase superfamily from phosphomonoesterase to inorganic pyrophosphatase.

Arch Biochem Biophys 2021 Jul 30;705:108896. Epub 2021 Apr 30.

Biomedical Research Center, College of Life Science and Engineering, Northwest Minzu University, Lanzhou, 730030, PR China. Electronic address:

The evolution of enzyme catalytic structures and mechanisms has drawn increasing attention. In this study, we investigate the functional divergence from phosphomonoesterase to inorganic pyrophosphatase in the haloacid dehalogenase (HAD) superfamily. In this study, a series of models was constructed, and calculations were performed by using density functional theory with the B3LYP functional. The calculations suggest that in most HAD members, the active-site structure is unstable due to the binding of the substrate inorganic pyrophosphate (PPi), and reactions involving PPi cannot be catalyzed. In BT2127, which is a unique member of the HAD superfamily, the Mg-coordinating residues Asn172 and Glu47 play a role in stabilizing the active-site structure to adapt to the substrate PPi by providing much stronger coordination interactions with the Mg ion. The calculation results suggest that Asn172 and Glu47 are crucial in the evolution of the inorganic pyrophosphatase activity in the HAD superfamily. Our study provides definitive chemical insight into the functional divergence of the HAD superfamily, and helps in understanding the evolution of enzyme catalytic structures and mechanisms.
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http://dx.doi.org/10.1016/j.abb.2021.108896DOI Listing
July 2021

The Differentiation in Image Post-processing and 3D Reconstruction During Evaluation of Carotid Plaques From MR and CT Data Sources.

Front Physiol 2021 16;12:645438. Epub 2021 Apr 16.

Department of Radiology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, China.

Carotid plaque morphology and tissue composition help assess risk stratification of stroke events. Many post-processing image techniques based on CT and MR images have been widely used in related research, such as image segmentation, 3D reconstruction, and computer fluid dynamics. However, the criteria for the 3D numerical model of carotid plaque established by CT and MR angiographic image data remain open to questioning. We accurately duplicated the geometry and simulated it using computer software to make a 3D numerical model. The initial images were obtained by CTA and TOF-MRA. MIMICS (Materialize's interactive medical image control system) software was used to process the images to generate three-dimensional solid models of blood vessels and plaques. The subsequent output was exported to the ANSYS software to generate finite element simulation results for the further hemodynamic study. The 3D models of carotid plaque of TOF-MRA and CTA were simulated by using computer software. CTA has a high-density resolution for carotid plaque, the boundary of the CTA image is obvious, and the main component of which is a calcified tissue. However, the density resolution of TOF-MRA for the carotid plaque and carotid artery was not as good as that of CTA. The results show that there is a large deviation between the TOF-MRA and CTA 3D model of plaque in the carotid artery due to the unclear recognition of plaque boundary during 3D reconstruction, and this can further affect the simulation results of hemodynamics. In this study, two-dimensional images and three-dimensional models of carotid plaques obtained by two angiographic techniques were compared. The potential of these two imaging methods in clinical diagnosis and fluid dynamics of carotid plaque was evaluated, and the selectivity of image post-processing analysis to original medical image acquisition was revealed.
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http://dx.doi.org/10.3389/fphys.2021.645438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085352PMC
April 2021

Discovery and characterization of flavonoids in vine tea as catechol-O-methyltransferase inhibitors.

Fitoterapia 2021 Apr 28;152:104913. Epub 2021 Apr 28.

School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Vine tea has been used as a traditionally functional herbal tea in China for centuries, which exhibits paramount potential for chronic metabolic diseases. Herein, the inhibitory potential of vine tea toward human catechol-O-methyltransferase (hCOMT) was investigated. A practical bioactivity-guided fractionation combined with chemical profiling strategy was developed to identify the naturally occurring hCOMT inhibitors. Five flavonoids in vine tea displayed moderate to strong inhibition on hCOMT with IC values ranging from 0.96 μM to 42.47 μM, in which myricetin was the critically potent constituent against hCOMT. Inhibition kinetics assays and molecular docking simulations showed that myricetin could bind to the active site of COMT and inhibited COMT-catalyzed 3-BTD methylation in a mixed manner. Collectively, our findings not only suggested that the strong hCOMT inhibition of vine tea has guiding significance in the drug exposure of catechol drugs, but also identified a promising lead compound for developing more efficacious hCOMT inhibitors.
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http://dx.doi.org/10.1016/j.fitote.2021.104913DOI Listing
April 2021

Emerging resistance mechanisms for 4 types of common anti-MRSA antibiotics in Staphylococcus aureus: A comprehensive review.

Microb Pathog 2021 Jul 27;156:104915. Epub 2021 Apr 27.

Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China. Electronic address:

Staphylococcus aureus is one of the leading hospital-associated and community-associated pathogens, which has caused a global public health concern. The emergence of methicillin-resistant S. aureus (MRSA) along with the widespread use of different classes of antibiotics has become a significant therapeutic challenge. Antibiotic resistance is a disturbing problem that poses a threat to humans. Treatment options for S. aureus resistant to β-lactam antibiotics include glycopeptide antibiotic, cyclic lipopeptide antibiotic, cephalosporins and oxazolidinone antibiotic. The most representative types of these antibiotics are vancomycin, daptomycin, ceftaroline and linezolid. The frequent use of the first-line drug vancomycin for MRSA treatment has increased the number of resistant strains, namely vancomycin intermediate resistant S. aureus (VISA) and vancomycin resistant S. aureus (VRSA). A systematic literature review of relevant published studies in PubMed before 2020 was conducted. In recent years, there have been some reports on the relevant resistant mechanisms of vancomycin, daptomycin, ceftaroline and linezolid. In this review, we have summarized the antibiotic molecular modes of action and different gene mutants at the whole-genome level, which will aid in further development on new drugs for effective MRSA treatment based on describing different resistance mechanisms of classic antibiotics.
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http://dx.doi.org/10.1016/j.micpath.2021.104915DOI Listing
July 2021