Publications by authors named "Zhenguo Liu"

218 Publications

Systemic Inflammation Increases the Susceptibility to Levodopa-Induced Dyskinesia in 6-OHDA Lesioned Rats by Targeting the NR2B-Medicated PKC/MEK/ERK Pathway.

Front Aging Neurosci 2020 1;12:625166. Epub 2021 Feb 1.

Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The long-term administration of levodopa (L-dopa), the gold-standard treatment for Parkinson's disease (PD), is irreparably associated with L-dopa-induced dyskinesia (LID), which dramatically affects the quality of life of patients. However, the underlying molecular mechanisms of how LID exacerbates remain unknown. Neuroinflammation in the striatum plays an active role in LID. These findings prompt an investigation of non-neuronal mechanisms of LID. This study will examine the effects of systemic inflammation in the development and progression of LID. To evaluate the possible influence of systemic inflammation in the appearance of LID, the PD rats received an intraperitoneal (IP) injection of various concentrations of lipopolysaccharides (LPS, 1, 2, and 5 mg/kg) or saline. One day later, these PD rats started to receive daily treatment with L-dopa (6 mg/kg) along with benserazide (6 mg/kg) or saline for 21 days, and dyskinesia was evaluated at several time points. Moreover, the activation of microglia and astrocytes and the molecular changes in NR2B and mGLUR5 signaling pathways were measured. We found that systemic inflammatory stimulation with LPS exacerbated the intensity of abnormal involuntary movements (AIMs) induced by L-dopa treatment in 6-hydroxydopamine (6-OHDA) lesioned rats. The LPS injection activated the gliocytes and increased the levels of proinflammatory cytokines in the striatum in LID rats. The PD rats that received the LPS injection showed the overexpression of p-NR2B and NR2B, as well as activated PKC/MEK/ERK and NF-κB signal pathways in response to the L-dopa administration. On the contrary, clodronate-encapsulated liposomes (Clo-lipo), which could suppress the inflammatory response induced by peripheral LPS injection, improved behavioral dysfunction, inhibited neuroinflammation, prevented NR2B overexpression, and decreased the phosphorylation of PKC/MEK/ERK and NF-κB signaling pathways. This study suggests that systemic inflammation, by exacerbating preexisting neuroinflammation and facilitating NR2B subunit activity, may play a crucial role in the development of LID. The administration of Clo-lipo restores the effects of LPS and decreases the susceptibility to LID in 6-OHDA lesioned rats.
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http://dx.doi.org/10.3389/fnagi.2020.625166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882708PMC
February 2021

A Nomogram to Predict Lifestyle Factors for Recurrence of Large-Vessel Ischemic Stroke.

Risk Manag Healthc Policy 2021 2;14:365-377. Epub 2021 Feb 2.

Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China.

Background: Stroke is the leading cause of morbidity and mortality in China. Recurrent stroke (RS) could occur in a significant portion of patients with ischemic stroke with devastating consequence.

Methods: To investigate the association between lifestyle and the risk of RS in Chinese patients with acute large-vessel ischemic stroke (ALVIS). A total of 258 patients with ALVIS were recruited in the study (median age 63 years, 30.6% female), and followed for a median of 366 days. The primary outcomes were first RS. Cox Regression and Akaike information criterion were used to establish the best-fit nomograms.

Results: During follow-up, 38 of 258 (14.7%) participants had the primary endpoint event. After adjusting for confounding factors in multivariate Cox regression analysis, healthy lifestyles, including bland diet (hazard ratio [HR], 0.365; 95% CI, 0.138-0.965), daily fruit consumption (HR, 0.474; 95% CI, 0.238-0.945), good sleep (HR, 0.364; 95% CI, 0.180-0.739), housework: HR (0.461; 95% CI, 0.200-1.065), and HDL (HR, 0.329; 95% CI, 0.130-0.831) were associated with significantly decreased risk for RS after ALVIS, while smoking was associated with a substantial increase in RS risk (HR, 2.590; 95% CI, 1.340-5.005) and included into the nomogram. A weighted point (from 0 to 100) was given to each risk factor, and the total points could be used to predict the probability of RS for the patient.

Conclusion: The nomogram shows that healthy lifestyles (bland diet, daily fruit consumption, good sleep, cigarette cessation, and housework) were important for reducing RS in patients with ALVIS.
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http://dx.doi.org/10.2147/RMHP.S289761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868708PMC
February 2021

Simultaneous Activation of Erk1/2 and Akt Signaling is Critical for Formononetin-Induced Promotion of Endothelial Function.

Front Pharmacol 2020 11;11:608518. Epub 2021 Jan 11.

Center for Precision Medicine and Division of Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, MO, United States.

Formononetin (FMNT) is a major bioactive compound from (Fisch.) Bunge, and has been widely used to treat conditions related to vascular insufficiency. However, the molecular mechanism for the therapeutic effect has not been well defined. This study aimed to investigate the effect and mechanism of FMNT on endothelial function. The potential targets and signaling pathways of FMNT in the setting of ischemia were predicted using network pharmacology analysis. Human umbilical vein endothelial cells (HUVECs) were used for the studies and C57BL/6 mice were used for experiments. The results of the network pharmacology analysis showed that multiple signaling molecules including MAPK and PI3K-Akt pathways could be involved in the pharmacological actions of FMNT against ischemic diseases. The experimental validation data showed that FMNT significantly promoted the growth, proliferation, migration and tube formation of HUVECs in association with activation of endothelial nitric oxide synthase (eNOS) and promotion of intracellular nitric oxide (NO) production. FMNT also markedly activated Erk1/2 and Akt signaling in HUVECs. The enhanced endothelial function by FMNT was abolished when the cells were pre-treated with eNOS inhibitor. FMNT-induced eNOS/NO activation, endothelial function and angiogenesis was also effectively attenuated when Erk1/2 or Akt signaling pathway was inhibited. In addition, FMNT significantly promoted wound healing in C57BL/6 mice associated with activation of Erk1/2 and Akt signaling. Enhanced wound healing by FMNT in mice was prevented when eNOS-, Erk1/2, or Akt-medicated signaling was inhibited. Moreover, when Akt signaling was inhibited in HUVECs, FMNT was still able to activate Erk1/2 signaling without promotion of endothelial function. Similarly, FMNT could activate Akt signaling with no change in endothelial function when Erk1/2 signaling was attenuated in HUVECs. Conclusively, the present study demonstrated that FMNT significantly enhanced endothelial function and promoted angiogenesis and through activating Erk1/2- and Akt-mediated eNOS/NO signaling pathway. The data also suggested that simultaneous activation of Erk1/2 and Akt signaling was required for FMNT-induced promotion of endothelial function. Results from the present study might provide support and evidence for the application of FMNT during the clinical treatment of conditions related to vascular insufficiency.
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http://dx.doi.org/10.3389/fphar.2020.608518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832036PMC
January 2021

CD34 cells and endothelial progenitor cell subpopulations are associated with cerebral small vessel disease burden.

Biomark Med 2021 Feb 26;15(3):191-200. Epub 2021 Jan 26.

Department of Medicine, Center for Precision Medicine & Division of Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA.

Endothelial dysfunction is considered to be involved in the pathogenesis of cerebral small vessel disease (CSVD). Endothelial progenitor cells are associated with endothelial dysfunction. The present study was designed to investigate the correlation between the populations of circulating CD34-positive cells and endothelial progenitor cells and CSVD burden. A total of 364 patients with confirmed diagnosis of CSVD were included in this prospective study. Multiple ordinal logistic regression analyses showed that subjects with higher CSVD burden had significantly decreased circulating CD34 cell level (odds ratio [OR], 0.42; p = 0.034) and significantly increased levels of circulating CD34CD133CD309 and CD34CD133 cells (OR 1.07, p = 0.031; OR 1.03, p = 0.001, respectively), compared with patients with lower CSVD burden. The findings suggest that the levels of circulating CD34 cells, CD34CD133CD309 cells and CD34CD133 cells may be used as potential biomarkers to monitor the disease progression of CSVD.
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http://dx.doi.org/10.2217/bmm-2020-0350DOI Listing
February 2021

Cardiac Troponin I R193H Mutation Is Associated with Mitochondrial Damage in Cardiomyocytes.

DNA Cell Biol 2021 Feb 18;40(2):184-191. Epub 2021 Jan 18.

Department of Cardiovascular Medicine, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China.

Malfunction of myocardial mitochondria plays a crucial role in the development of cardiovascular disorders, especially hypertrophic and dilated cardiomyopathies. Cardiac troponin I (cTnI) is an important structural protein and essential to contraction and relaxation of cardiomyocytes. Recent studies suggest that mutated cTnIR193H could function as a regulatory molecule for other cell functions. This study was to determine whether mutated cTnI could contribute to mitochondrial dysfunction of cardiomyocytes. Primary cardiomyocytes were transfected with cTnIR193H adenovirus with empty vector as control. Mitochondrial structure and function were evaluated in the cells 72 h after transfection. Transmission electron microscopy examination showed mitochondria in the cardiomyocytes with R193H mutation displayed broken cristae, vacuolation, and mitophagy. Mitochondrial function studies revealed a significant decrease in complex I activity, ATP and reactive oxygen species levels, and oxygen consumption rate compared with controls. Western blot analysis demonstrated that expressions of mitochondria-related genes, including ND5 (ubiquinone oxidoreductase chain 5), LRPPRC (a leucine-rich protein of pentatricopeptide repeat family), and PGC-1α (PPARG co-activator 1 alpha), were significantly downregulated in R193H mutation cardiomyocytes compared with the control. Swelling and broken cristae were observed in the mitochondria of cardiomyocytes from cTnIR193H mutation transgenic mice with decreased mitochondrial function, not from the littermate control mice. The data from the present study demonstrated that mitochondrial structure and function were significantly impaired in cardiomyocytes with cTnIR193H mutation, suggesting that cTnI might be critically involved in maintaining the structural and functional integrity of myocardial mitochondria.
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http://dx.doi.org/10.1089/dna.2020.5828DOI Listing
February 2021

Prognostic Role of ABO Blood Type in Operable Esophageal Cancer: Analysis of 2179 Southern Chinese Patients.

Front Oncol 2020 18;10:586084. Epub 2020 Dec 18.

Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: The prognostic value of ABO blood types is not well clarified for esophageal carcinoma (EC). This study attempted to elucidate the associations between different ABO blood types and disease-free survival (DFS) and overall survival (OS) of EC.

Methods: This study was a retrospective review of the records of 2179 patients with EC who received surgery from December 2000 to December 2008. The prognostic impact of ABO blood group on DFS and OS were estimated using the Kaplan-Meier method and cox proportional hazard models.

Results: Univariate analyses found significant differences in DFS and OS among the four blood types. Multivariate analyses showed ABO blood type independently predicted DFS (=0.001) and OS (=0.002). Furthermore, patients with non-B blood types had a significantly shorter DFS (HR=1.22, 95%CI:1.07-1.38, =0.002) and OS (HR=1.22, 95%CI:1.07-1.38, =0.003) than patients with blood type B, and patients with non-O blood types had a significantly better DFS (HR=0.86, 95%CI:0.77-0.96, =0.006) and OS (HR=0.86, 95%CI:0.77-0.96, =0.007) than patients with blood type O. Subgroup analyses found that blood type B had a better DFS and OS than non-B in patients who were male, younger, early pathological stages and had squamous-cell carcinomas (ESCC). Blood type O had a worse DFS and OS than non-O in patients who were male, younger, and had ESCC (<0.05).

Conclusions: The results demonstrate that ABO blood group is an independent prognostic factor of survival, and that type B predicts a favorable prognosis, whereas type O predicts an unfavorable prognosis for survival in patients with EC, especially those with ESCC.
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http://dx.doi.org/10.3389/fonc.2020.586084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775654PMC
December 2020

Survival after pulmonary metastasectomy for relapsed osteosarcoma.

J Thorac Cardiovasc Surg 2020 Nov 24. Epub 2020 Nov 24.

Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address:

Objectives: The purpose of this study was to evaluate the postrelapse survival of relapsed osteosarcoma with pulmonary metastases in patients who received pulmonary metastasectomy using intent to treat and propensity score analysis.

Methods: Patients with osteosarcoma who relapsed with pulmonary metastases between 2004 and 2018 who were treated in a hospital affiliated with a medical school were included. All the enrolled patients were evaluated as operable with assessment algorithm at the time of diagnosis of pulmonary relapse and intent to treat analysis was done. Multiple propensity score methods (eg, matching, stratification, covariate adjustment, and inverse probability of treatment weighting) were performed to balance confounding bias. Cox proportional hazards regression and the Kaplan-Meier method were used to evaluate patient survival.

Results: A total of 125 patients met the study criteria. Of these, 59 (47.2%) patients received pulmonary metastasectomy combined with chemotherapy and 66 (52.8%) received chemotherapy alone. The 2-year and 5-year postrelapse survival rate of metastasectomy group and nonmetastasectomy group were 68.4% versus 25.0% and 41.0% versus 0%, respectively. The median postrelapse survival was 24.9 versus 13.5 months, respectively. Pulmonary metastasectomy was independently associated with improved survival (hazard ratio, 0.185; 95% confidence interval, 0.103-0.330; P < .001). These results were confirmed by multiple propensity score analyses. Further stratified analysis revealed that the survival advantage associated with metastasectomy was not significant in patients with metastases involving ≥3 lung lobes and patients with very high pretreatment serum alkaline phosphatase (more than twice the upper limit).

Conclusions: Pulmonary metastasectomy is associated with improved survival in patients with recurrent osteosarcoma.
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http://dx.doi.org/10.1016/j.jtcvs.2020.10.137DOI Listing
November 2020

Molecular Mechanism of the UDP-Glucuronosyltransferase 2B20-like Gene () in Pesticide Resistance of .

Front Genet 2020 19;11:592595. Epub 2020 Nov 19.

College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.

UDP-glucuronosyltransferases (UGTs), being multifunctional detoxification enzymes, play a major role in the process of resistance to various pesticides in insects. However, the mechanism underlying the molecular regulation of pesticide resistance remains unclear, especially in . In this study, all of the UGTs in (AccUGT) have been identified through the multiple alignment and phylogenetic analysis. Expression of AccUGT genes under different pesticides, and antioxidant genes after silencing of , were detected by qRT-PCR. The resistance of overexpressed to oxidative stress was investigated by an overexpression system. Also, antioxidant-related enzyme activity was detected after silencing of the gene. Expression pattern analysis showed that almost all UGT genes were upregulated under different pesticide treatments. This result indicated that AccUGTs participate in the detoxification process of pesticides. was the major gene because it was more highly induced than the others. Overexpression of in could effectively improve oxidative stress resistance. Specifically, silencing the gene increased oxidative stress by repressing the expression of oxidation-related genes, decreasing antioxidant-related enzyme activity, and increasing malondialdehyde concentration. Taken together, our results indicate that AccUGTs are involved in pesticide resistance, among which, contributes to the detoxification of pesticides by eliminating oxidative stress in . This study explains the molecular basis for the resistance of bees to pesticides and provides an important safeguard for maintaining ecological balance.
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http://dx.doi.org/10.3389/fgene.2020.592595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710801PMC
November 2020

Admission Glucose Levels May Increase the Risk for Early Neurological Deterioration in Females With Acute Ischemic Stroke.

Front Neurol 2020 5;11:548892. Epub 2020 Nov 5.

Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, United States.

Early neurological deterioration (END) is associated with poor outcome for patients with acute ischemic stroke (AIS). Patients with hyperglycemia have increased risk for stroke and tend to have poor outcome with and without diabetes after stroke. The present study aimed to determine if blood glucose was associated with END and if sex difference was present in the development of END in AIS patients. A total of 220 consecutive patients (both males and females) with AIS between 2012 and 2015 were screened for this retrospective study. After exclusion, 213 patients were included for analysis. Propensity-score matching was used for normalization of variables including stroke severity, time from symptom onset to treatment, and treatment methods. END was present in 68 patients (31.9%). Multivariate regression analysis showed that the risk of END was significantly higher in males with AIS than in females ( < 0.001), and admission blood glucose level was independently associated with END ( < 0.001). However, subgroup analysis demonstrated that admission glucose levels were significantly associated with increased risk for END only in females, but not in males ( = 0.008). When the cutoff value of 107.1 mg/dL was used, the admission blood glucose level had a significant predictive value for END prediction with a sensitivity of 100% and a specificity of 53% in female patients. The data demonstrated that sex difference was present for the development of END in AIS patients with an increased risk for males. The present study also showed that admission glucose level could be an important predicting factor for END in female patients with AIS.
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http://dx.doi.org/10.3389/fneur.2020.548892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674944PMC
November 2020

Metabolite Support of Long-Term Storage of Sperm in the Spermatheca of Honeybee () Queens.

Front Physiol 2020 10;11:574856. Epub 2020 Nov 10.

College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.

The polyandrous mating system of honeybees ( L.) has garnered widespread attention. Long-lived honeybee queens only mate early in maturation, and the sperm obtained from the aerial mating is stored in the spermatheca. The maintenance of sperm viability in the spermatheca is an intriguing and complex process. However, the key physiological and biochemical adaptations underlying the long-term storage of sperm remain unclear. Analysis of the metabolite profile could help better understand the biology of the spermatheca and offer insights into the breeding and conservation of honeybees and even pest control strategies. Here, the changes in metabolites in the spermatheca were quantified between virgin queens and new-laying queens (with stored sperm) via liquid chromatography-mass spectrometry. Compared with virgin queens, changes occurred in lipids and lipid-like molecules, including fatty acyls and glycerophospholipids (GPL), prenol lipids, and sterol lipids, during storage of sperm in new-laying honeybee queens. Furthermore, the metabolic pathways that were enriched with the differentially expressed metabolites were identified and included GPL metabolism, biosynthesis of amino acids, and the mTOR signaling pathway. The likely roles of the pathways in the maintenance and protection of sperm are discussed. The study identifies key metabolites and pathways in the complex interplay of substances that contribute to the long-term storage of sperm and ultimately reproductive success of honeybee queens.
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http://dx.doi.org/10.3389/fphys.2020.574856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683436PMC
November 2020

A Modified VATS Procedure for Treating Adult Intralobar Pulmonary Sequestration.

Thorac Cardiovasc Surg 2020 Nov 17. Epub 2020 Nov 17.

Department of Thoracic Surgery, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China.

Video-assisted thoracoscopic surgery (VATS) makes it possible to treat intralobar sequestration (ILS) more minimally invasive compared with conventional open surgery. However, this procedure is challenging to expose and isolate the aberrant arteries of ILS and the risk of bleeding is high. Herein, we developed a modified VATS procedure in which the aberrant vessels are treated in the last step of lobectomy, rather than at the beginning. In this way, we can expose the aberrant vessels easier and reduce the risk of massive blood loss, also simplifying the surgical procedure.
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http://dx.doi.org/10.1055/s-0040-1708870DOI Listing
November 2020

Essen Stroke Risk Score Predicts Carotid Atherosclerosis in Chinese Community Populations.

Risk Manag Healthc Policy 2020 13;13:2115-2123. Epub 2020 Oct 13.

Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA.

Background: Carotid atherosclerosis (CA) is closely related to stroke, and Framingham Risk Score (FRS) has been used for CA risk evaluation. However, FRS could only be used for subjects of up to 74 years old. The present study was to determine if Essen Stroke Risk Score (ESRS) could be used to estimate CA risk in community populations without age limits.

Methods: In the present prospective multi-community screening study, we evaluated the prevalence of CA using high-resolution ultrasound in 521 males and 1039 females (35 to 91 years old). Both FRS and ESRS were calculated for the subjects. Multivariate logistic regression analysis was used to determine the predictive values of FRS and ESRS for CA in these subjects.

Results: Ultrasound data showed that CA was present in 56.2% of the participants (total of 1560). Multivariate logistic regression analysis showed that ESRS was associated with CA with odds ratio (OR): 1.34 (95% confidence interval (CI), 1.12-1.60, =0.001). Central obesity (OR: 1.40, CI: 1.07-1.83, =0.015), female (OR: 0.55, CI: 0.39-0.77, <0.001) and age (OR: 2.63, CI: 2.27-3.06, <0.001) were also associated with CA. Based on the estimated area under curve (AUC), FRS (AUC 0.775) was better than ESRS (AUC 0.693) (z statistic 6.774, <0.001) for CA prediction for individuals of ≤74 years old. However, receiver operating characteristic analysis showed ESRS was a good CA predictor for all subjects (AUC of 0.715).

Conclusion: ESRS could be used as an alternative to FRS to predict CA in community population of all age.
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http://dx.doi.org/10.2147/RMHP.S274340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568636PMC
October 2020

Identification of a new P450s gene () and its roles in abiotic stress resistance in the Fabricius.

Bull Entomol Res 2021 Feb 27;111(1):57-65. Epub 2020 Oct 27.

College of Animal Science and Technology, Shandong Agricultural University, Tai'an, Shandong, People's Republic of China.

Cytochrome P450 monooxygenases (P450s) play significant roles in protecting organisms from abiotic stress damage. Here, we report the sequence and characterization of a P450s gene (AccCYP4AV1), isolated from Apis cerana cerana Fabricius. The open reading frame of AccCYP4AV1 is 1506 base pairs long and encodes a predicted protein of 501 amino acids and 57.84 kDa, with an isoelectric point of 8.67. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis indicated that AccCYP4AV1 is more highly expressed in the midgut than in other tissues. In addition, the highest expression occurs in newly emerged adult workers, followed by the first instar of the larval stage. In addition, the expression of the AccCYP4AV1 was upregulated by low temperature (4 °C), ultraviolet radiation, hydrogen peroxide, paraquat, and dichlorvos treatments. In contrast, AccCYP4AV1 transcription was downregulated by other abiotic stress conditions: exposure to increased temperature (44 °C), deltamethrin, cadmium chloride, and mercury (II) chloride. Moreover, when AccCYP4AV1 was knocked-down by RNA interference, the results suggested that multiple antioxidant genes (AccsHSP22.6, AccSOD2, AccTpx1, and AccTpx4) were downregulated and antioxidant genes AccGSTO1 and AccTrx1 were upregulated. The activity levels of peroxidase and catalase were upregulated in the AccCYP4AV1-knocked-down samples, compared with those in the control groups. These findings suggest that the AccCYP4AV1 protein might be involved in the defense against abiotic stress damage.
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http://dx.doi.org/10.1017/S0007485320000644DOI Listing
February 2021

Influence of the COVID-19 Pandemic on Quality of Life of Patients with Parkinson's Disease.

Parkinsons Dis 2020 5;2020:1216568. Epub 2020 Oct 5.

Tongren Hospital, Shanghai Jiao Tong University Medical School, Shanghai 200336, China.

Introduction: This study investigated the influence of lockdown during the 2019 coronavirus disease (COVID-19) pandemic on the quality of life of patients with Parkinson's disease (PD).

Methods: We conducted a questionnaire survey involving 113 patients with PD from Xihu District, Hangzhou, Zhejiang. During the epidemic prevention and control period (February 1 to March 31, 2020), patients enrolled were asked to fill out questionnaires, including the "COVID-19 Questionnaire for PD Patients during the Period of Epidemic Prevention and Control" and "39-item Parkinson's Disease Questionnaire (PDQ-39)." During the phase of gradual release of epidemic prevention and control (April 1 to April 30, 2020), all patients were followed up again, and PDQ-39 questionnaires were completed.

Results: The quality of life for patients during the period of epidemic prevention and control was worse than that after epidemic prevention and control ( < 0.001). The biggest problem that they faced was that they could not receive their doctor's advice or guidance regularly. The quality of life of patients who had difficulty getting doctors' guidance or those who changed their routine medication due to lockdown was even worse. Telemedicine was quite effective and efficient for patients to get doctors' guidance during lockdown.

Conclusions: The inconvenient treatment during the pandemic directly caused the aggravation of patients' symptoms and the decline in their quality of life. It is suggested that social media (such as WeChat or Tencent QQ) are used for regular interactions and follow-up appointments for patients with inconvenient medical treatment.
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http://dx.doi.org/10.1155/2020/1216568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537675PMC
October 2020

Molecular and functional characterization of the novel odorant-binding protein gene AccOBP10 from Apis cerana cerana.

J Biochem 2020 Sep 14. Epub 2020 Sep 14.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, Shandong, P. R. China.

Odorant-binding proteins (OBPs) play an important role in odor perception and transport in insects. However, little is known about whether OBPs perform other functions in insects, particularly in Apis cerana cerana. Within this study, an OBP gene (AccOBP10) was isolated and identified from Apis cerana cerana. Both homology and phylogenetic relationship analyses indicated that the amino acid sequence of AccOBP10 had a high degree of sequence identity with other members of the gene family. Analysis of real-time quantitative PCR (qRT-PCR) showed that AccOBP10 mRNA was expressed at higher levels in the venom gland than in other tissues. The mRNA transcript expression of AccOBP10 was upregulated by low temperature (4 °C), hydrogen peroxide (H2O2), pyridaben, methomyl and imidacloprid but downregulated by heat (42 °C), ultraviolet (UV) light, vitamin C, mercuric chloride (HgCl2), cadmium chloride (CdCl2), paraquat and phoxim. Expression of AccOBP10 under abiotic stress was analyzed by Western blotting, and the results were consistent with those of qRT-PCR. And as a further study of AccOBP10 function, we demonstrated that knockdown of AccOBP10 by RNA interference (RNAi) could slightly increase the expression levels of some stress-related genes. Collectively, these results suggest that AccOBP10 is mainly involved in the response to stress conditions.
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http://dx.doi.org/10.1093/jb/mvaa103DOI Listing
September 2020

Genome-Wide Differential DNA Methylation in Reproductive, Morphological, and Visual System Differences Between Queen Bee and Worker Bee ().

Front Genet 2020 7;11:770. Epub 2020 Aug 7.

Laboratory of Nutrition and Physiology of Honeybees, College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.

There are many differences in external morphology and internal physiology between the queen bee and worker bee, some of which are relevant to beekeeping production. These include reproductive traits, body size, royal jelly secreting properties, and visual system development, among others. The identification of candidate genes that control the differentiation of these traits is critical for selective honeybee breeding programs. In this study, we compared the genomic methylation of queen bee and worker bee larvae at 3, 4, and 5 days of age by whole-genome bisulfite sequencing, and found that the basic characteristics of genomic methylation in queen and worker larvae were the same. There were approximately 49 million cytosines in the larvae genome, of which about 90,000 were methylated. Methylated CpG sites accounted for 99% of the methylated cytosines, and methylation mainly occurred in exons. However, methylation levels of queen and worker larvae showed different trends with age: the methylation level of queen larvae varied with age in an inverted parabola, while the corresponding trend for worker larvae with resembled an exponential curve with a platform. The methylation level of queen larvae was higher than that of worker larvae at 3 days of age, lower than that of worker larvae at 4 days of age, and similar to that of worker larvae at 5 days old. The top 10 differentially methylated genes (DMGs) and 13 caste-specific methylated genes were listed, and correlations with caste determination were speculated. We additionally screened 38 DMGs between queen larvae and worker larvae involved in specific organ differentiation as well as reproduction, morphology, and vision differentiation during caste determination. These genes are potential molecular markers for selective breeding of to improve fecundity, royal jelly production, body size, and foraging, and represent candidate genes for investigating specialized functional segregation during the process of caste differentiation.
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http://dx.doi.org/10.3389/fgene.2020.00770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438783PMC
August 2020

White matter hyperintensities: a marker for apathy in Parkinson's disease without dementia?

Ann Clin Transl Neurol 2020 09 28;7(9):1692-1701. Epub 2020 Aug 28.

Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kong jiang Road, Shanghai, 200092, People's Republic of China.

Objective: The objective of this study was to assess the relationship between white matter hyperintensities (WMH) and the occurrence and progression of apathy in Parkinson's disease (PD).

Methods: We recruited patients with PD who underwent baseline evaluation, which included apathy assessment and magnetic resonance imaging (MRI) head scans. After 2.5 years of follow-up, we re-evaluated patient apathy symptoms. The severity and location of WMH were assessed with fluid-attenuated inversion recovery (FLAIR) sequences using the Fazekas visual rating scale. Logistic regression and linear regression analyses of baseline WMH characteristics were conducted to explore the potential association between apathy and WMH.

Results: A total of 141 PD patients were recruited. The apathy group had a higher proportion of male patients, advanced disease, and depression, which was coupled with a lower quality of life. Morever, higher WMH severity was significantly associated with apathy. Logistic regression analyses demonstrated that WMH severity was a risk factor for apathy. In addition, linear regression analysis also suggests that apathy severity is positively correlated with baseline WMH Fazekas scales (ϐ = 0.959, P < 0.001). Baseline WMH severity was also a risk factor for apathy progression.

Interpretation: WMH is associated with apathy and could be a promising marker to predict apathy progression in PD.
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http://dx.doi.org/10.1002/acn3.51159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480903PMC
September 2020

Fecal Microbiomes Distinguish Patients With Autoimmune Hepatitis From Healthy Individuals.

Front Cell Infect Microbiol 2020 3;10:342. Epub 2020 Aug 3.

Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

The intestinal microbiome is associated with various autoimmune diseases. Regional difference is the main influencing factor of intestinal microbial difference. This study aimed to identify the differences in fecal microbiome between autoimmune hepatitis (AIH) patients and healthy controls (HCs) in Central China, and to validate the efficacy of fecal microbiome as a diagnostic tool for AIH. We collected 115 fecal samples from AIH patients ( = 37) and HCs ( = 78) in Central China and performed gene sequencing. Fecal microbiomes were characterized and microbial markers for AIH were identified. Fecal microbial diversity showed a downward trend in AIH compared with HCs. Fecal microbial communities significantly differed between both groups. At the phylum level, a abundance was significantly increased, while and were significantly decreased in the AIH patients vs. the HCs. Compared to the HCs, 15 genera, including , and , were enriched, while 19 genera, such as , and , were decreased in the AIH patients. Ten genera, including , and , predominated in the AIH patients. Five microbial biomarkers were deemed optimal diagnostic tools for AIH. The probability of disease was significantly increased in AIH group vs. HCs, achieving 83.25% value of area under the curve. We present the characteristics of AIH patients in Central China for the first time. Five microbial biomarkers, including , and , achieved a high potential distinguishing AIH patients from HCs.
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http://dx.doi.org/10.3389/fcimb.2020.00342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416601PMC
August 2020

Development and Feasibility of a Mobile Health-Supported Comprehensive Intervention Model (CIMmH) for Improving the Quality of Life of Patients With Esophageal Cancer After Esophagectomy: Prospective, Single-Arm, Nonrandomized Pilot Study.

J Med Internet Res 2020 08 18;22(8):e18946. Epub 2020 Aug 18.

Department of Emergency Medicine, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

Background: Patients with esophageal cancer often experience clinically relevant deterioration of quality of life (QOL) after esophagectomy owing to malnutrition, lack of physical exercise, and psychological symptoms.

Objective: This study aimed to evaluate the feasibility, safety, and efficacy of a comprehensive intervention model using a mobile health system (CIMmH) in patients with esophageal cancer after esophagectomy.

Methods: Twenty patients with esophageal cancer undergoing the modified McKeown surgical procedure were invited to join the CIMmH program with both online and offline components for 12 weeks. The participants were assessed before surgery and again at 1 and 3 months after esophagectomy. QOL, depressive symptoms, anxiety, stress, nutrition, and physical fitness were measured.

Results: Of the 20 patients, 16 (80%) completed the program. One month after esophagectomy, patients showed significant deterioration in overall QOL (P=.02), eating (P=.005), reflux (P=.04), and trouble with talking (P<.001). At the 3-month follow-up, except for pain (P=.02), difficulty with eating (P=.03), dry mouth (P=.04), and trouble with talking (P=.003), all other QOL dimensions returned to the preoperative level. There were significant reductions in weight (P<.001) and BMI (P=.02) throughout the study, and no significant changes were observed for physical fitness measured by change in the 6-minute walk distance between baseline and the 1-month follow-up (P=.22) or between baseline and the 3-month follow-up (P=.52). Depressive symptoms significantly increased 1 month after surgery (P<.001), while other psychological measures did not show relevant changes. Although there were declines in many measures 1 month after surgery, these were much improved at the 3-month follow-up, and the recovery was more profound and faster than with traditional rehabilitation programs.

Conclusions: The CIMmH was feasible and safe and demonstrated encouraging efficacy testing with a control group for enhancing recovery after surgery among patients with esophageal cancer in China.

Trial Registration: Chinese Clinical Trial Registry (ChiCTR-IPR-1800019900); http://www.chictr.org.cn/showprojen.aspx?proj=32811.
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http://dx.doi.org/10.2196/18946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463393PMC
August 2020

Transcriptomic and metabolomic landscape of the molecular effects of glyphosate commercial formulation on Apis mellifera ligustica and Apis cerana cerana.

Sci Total Environ 2020 Nov 12;744:140819. Epub 2020 Jul 12.

College of Animal Science and Technology, Shandong Agricultural University, Taian, Shandong 271018, PR China. Electronic address:

Understanding the causes of the decline in bee population has attracted intensive attention worldwide. The indiscriminate use of agrochemicals is a persistent problem due to their physiological and behavioural damage to bees. Glyphosate and its commercial formulation stand out due to their wide use in agricultural areas and non-crop areas, such as parks, railroads, roadsides, industrial sites, and recreational and residential areas, but the mode of action of glyphosate on bees at the molecular level remains largely unelucidated. Here, we found that the numbers of differentially expressed genes and metabolites under glyphosate commercial formulation (GCF) stress were significantly higher in Apis cerana cerana than in Apis mellifera ligustica. Despite these differences, the number of differentially expressed transcripts increased following an increase in the GCF treatment time in both A. cerana cerana and A. mellifera ligustica. GCF exerted adverse impacts on the immune system, digestive system, nervous system, amino acid metabolism, carbohydrate metabolism, growth and development of both bee species by influencing their key genes and metabolites to some extent. The expression of many genes involved in immunity, agrochemical detoxification and resistance, such as antimicrobial peptides, cuticle proteins and cytochrome P450 families, was upregulated by GCF in both bee species. Collectively, our results indicate that both A. cerana cerana and A. mellifera ligustica strive to mitigate the pernicious effects caused by GCF by regulating detoxification and immune systems. Moreover, A. cerana cerana might be better able to withstand the toxic effects of GCF with lower fitness costs than A. mellifera ligustica. Our work will contribute to elucidating the deleterious physiological and behavioural impacts of GCF on bees.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140819DOI Listing
November 2020

Undetectable circulating tumor DNA levels correlate with low risk of recurrence/metastasis in postoperative pathologic stage I lung adenocarcinoma patients.

Lung Cancer 2020 08 20;146:327-334. Epub 2020 Jun 20.

Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address:

Objectives: The application of circulating tumor DNA (ctDNA) monitoring after resection in pathologic(p) stage I lung adenocarcinoma (LUAD) patients remains controversial and it is of great clinical interest to decipher the difference of genetic features between ground-glass opacity (GGO) and solid nodules (non-GGO) subgroups. We aim to assess the utility of ctDNA in tracking early recurrence or metastasis following surgery and reveal the genetic differences between GGO and non-GGO.

Materials And Methods: Tumor tissues and matched postoperative plasma samples were collected from a total of 82 (p)stage I LUAD patients. Comprehensive genomic profiling was performed using capture-based hybrid next generation sequencing by targeting 422 cancer relevant genes.

Results: EGFR and TP53 represent commonly mutated genes in this cohort of (p)stage I lung adenocarcinoma, followed by alterations in ALK, PIK3CA, STK11 and MYC. For a median follow-up period of 22.83 months after surgery, 65 out of 67 ctDNA-negative patients remained progression-free, while 3 out of 15 ctDNA-positive patients progressed [P = 0.040; positive predictive value = 0.20, 95 % confidence interval (CI), 0.04-0.48; negative predictive value = 0.97, 95 % CI, 0.9-1]. With time-dependent Cox regression analysis, we observed that ctDNA positivity significantly correlated with increased probability of early tumor recurrence or metastasis (P = 0.02, HR=8.5). Further comparison between GGO and non-GGO subgroups indicated the frequency of TP53 mutations in non-GGO was markedly higher than that in GGO (47 % vs 21 %, P < 0.05). Pathway analysis showed the epigenetic regulation pathway was more frequently affected in GGO subgroup, while impaired apoptosis/cell cycle pathway was more enriched in non-GGO LUADs.

Conclusions: Our longitudinal ctDNA monitoring data showed that undetectable ctDNA may predict low risk of tumor recurrence or metastasis in postoperative (p)stage I LUAD patients, while it requires further investigation on how robust the positive ctDNA results could predict tumor relapse in these patients.

Clinical Registration Number: NCT03172156.
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http://dx.doi.org/10.1016/j.lungcan.2020.06.009DOI Listing
August 2020

Bioinspired One Cell Culture Isolates Highly Tumorigenic and Metastatic Cancer Stem Cells Capable of Multilineage Differentiation.

Adv Sci (Weinh) 2020 Jun 28;7(11):2000259. Epub 2020 Apr 28.

Fischell Department of Bioengineering University of Maryland College Park MD 20742 USA.

Cancer stem cells (CSCs) are rare cancer cells that are postulated to be responsible for cancer relapse and metastasis. However, CSCs are difficult to isolate and poorly understood. Here, a bioinspired approach for label-free isolation and culture of CSCs, by microencapsulating one cancer cell in the nanoliter-scale hydrogel core of each prehatching embryo-like core-shell microcapsule, is reported. Only a small percentage of the individually microencapsulated cancer cells can proliferate into a cell colony. Gene and protein expression analyses indicate high stemness of the cells in the colonies. Importantly, the colony cells are capable of cross-tissue multilineage (e.g., endothelial, cardiac, neural, and osteogenic) differentiation, which is not observed for "CSCs" isolated using other contemporary approaches. Further studies demonstrate the colony cells are highly tumorigenic, metastatic, and drug resistant. These data show the colony cells obtained with the bioinspired one-cell-culture approach are truly CSCs. Significantly, multiple pathways are identified to upregulate in the CSCs and enrichment of genes related to the pathways is correlated with significantly decreased survival of breast cancer patients. Collectively, this study may provide a valuable method for isolating and culturing CSCs, to facilitate the understanding of cancer biology and etiology and the development of effective CSC-targeted cancer therapies.
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http://dx.doi.org/10.1002/advs.202000259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284220PMC
June 2020

N-acetylcysteine differentially regulates the populations of bone marrow and circulating endothelial progenitor cells in mice with limb ischemia.

Eur J Pharmacol 2020 Aug 31;881:173233. Epub 2020 May 31.

Center for Precision Medicine and Division of Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, MO, USA. Electronic address:

Endothelial progenitor cells (EPCs) are important to tissue repair and regeneration especially after ischemic injury, and very heterogeneous in phenotypes and biological features. Reactive oxygen species are involved in regulating EPC number and function. N-acetylcysteine (NAC) inhibits ischemia-induced reactive oxygen species formation and promotes ischemic limb recovery. This study was to evaluate the effect of NAC on EPC subpopulations in bone marrow (BM) and blood in mice with limb ischemia. Limb ischemia was induced by femoral artery ligation in male C57BL/6 mice with or without NAC treatment. EPC subpopulations, intracellular reactive oxygen species production, cell proliferation and apoptosis in BM and blood cells were analyzed at baseline, day 3 (acute ischemia) and 21 (chronic) after ligation. c-Kit+/CD31+, Sca-1+/Flk-1+, CD34+/CD133+, and CD34+/Flk-1+ were used to define EPC subpopulations. Limb blood flow, function, muscle structure, and capillary density were evaluated with laser Doppler perfusion imaging, treadmill test, and immunohistochemistry, respectively, at day 3, 7, 14 and 21 post ischemia. Reactive oxygen species production in circulating and BM mononuclear cells and EPCs populations were significantly increased in BM and blood in mice with acute and chronic ischemia. NAC treatment effectively blocked ischemia-induced reactive oxygen species production in circulating and BM mononuclear cells, and selectively increased EPC population in circulation, not BM, with preserved proliferation in mice with chronic ischemia, and enhanced limb blood flow and function recovery, while preventing acute ischemia-induced increase in BM and circulating EPCs. These data demonstrated that NAC selectively enhanced circulating EPC population in mice with chronic limb ischemia.
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http://dx.doi.org/10.1016/j.ejphar.2020.173233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483875PMC
August 2020

Development of a deep learning model for classifying thymoma as Masaoka-Koga stage I or II via preoperative CT images.

Ann Transl Med 2020 Mar;8(6):287

Department of Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

Background: Accurate thymoma staging via computed tomography (CT) images is difficult even for experienced thoracic doctors. Here we developed a preoperative staging tool differentiating Masaoka-Koga (MK) stage I patients from stage II patients using CT images.

Methods: CT images of 174 thymoma patients were retrospectively selected. Two chest radiologists independently assessed the images. Variables with statistical differences in univariate analysis were adjusted for age, sex, and smoking history in multivariate logical regression to determine independent predictors of the thymoma stage. We established a deep learning (DL) 3D-DenseNet model to distinguish the MK stage I and stage II thymomas. Furthermore, we compared two different methods to label the regions of interest (ROI) in CT images.

Results: In routine CT images, there were statistical differences (P<0.05) in contour, necrosis, cystic components, and the degree of enhancement between stage I and II disease. Multivariate logical regression showed that only the degree of enhancement was an independent predictor of the thymoma stage. The area under the receiver operating characteristic curve (AUC) of routine CT images for classifying thymoma as MK stage I or II was low (AUC =0.639). The AUC of the 3D-DenseNet model showed better performance with a higher AUC (0.773). ROIs outlined by segmentation labels performed better (AUC =0.773) than those outlined by bounding box labels (AUC =0.722).

Conclusions: Our DL 3D-DenseNet may aid thymoma stage classification, which may ultimately guide surgical treatment and improve outcomes. Compared with conventional methods, this approach provides improved staging accuracy. Moreover, ROIs labeled by segmentation is more recommendable when the sample size is limited.
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http://dx.doi.org/10.21037/atm.2020.02.183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186715PMC
March 2020

High-fat diet selectively decreases bone marrow lin /CD117 cell population in aging mice through increased ROS production.

J Tissue Eng Regen Med 2020 06 12;14(6):884-892. Epub 2020 May 12.

Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA.

Bone marrow (BM) stem cells (BMSCs) are an important source for cell therapy. The outcome of cell therapy could be ultimately associated with the number and function of donor BMSCs. The present study was to evaluate the effect of long-term high-fat diet (HFD) on the population of BMSCs and the role of reactive oxygen species (ROS) in aging mice. Forty-week-old male C57BL/6 mice were fed with HFD for 3 months with regular diet as control. Experiments were repeated when ROS production was reduced in mice treated with N-acetylcysteine (NAC) or using mice overexpressing antioxidant enzyme network (AON) of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase. BM and blood cells were analyzed with flowcytometry for lineage negative (lin ) and Sca-1 , or lin /CD117 , or lin /CD133 cells. Lin /CD117 cell population was significantly decreased with increased intracellular ROS and apoptosis and decreased proliferation in BM, not in blood, in HFD-treated mice without change for Sca-1 or CD133 cell populations in BM or blood. NAC treatment or AON overexpression effectively prevented HFD-induced intracellular ROS production and reduction of BM lin /CD117 population. These data suggested that long-term HFD selectively decreased BM lin /CD117 cell population in aging mice through increased ROS production.
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http://dx.doi.org/10.1002/term.3047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372732PMC
June 2020

Bacterial and fungal infections in COVID-19 patients: A matter of concern.

Infect Control Hosp Epidemiol 2020 09 22;41(9):1124-1125. Epub 2020 Apr 22.

Xiangya Hospital, Central South University, Changsha, China.

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http://dx.doi.org/10.1017/ice.2020.156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184139PMC
September 2020

CARD9 promotes autophagy in cardiomyocytes in myocardial ischemia/reperfusion injury via interacting with Rubicon directly.

Basic Res Cardiol 2020 04 4;115(3):29. Epub 2020 Apr 4.

Department of Pathophysiology, Sepsis Translational Medicine Key Lab of Hunan Province, Xiangya School of Medicine, Central South University, Changsha, 410000, Hunan, China.

Autophagy in cardiomyocyte is involved in myocardial ischemia/reperfusion (M-I/R) injury. Caspase recruitment domain-containing protein 9 (CARD9) plays a critical role in cardiovascular diseases (CVDs) such as hypertension and cardiac fibrosis. However, its role in autophagy following M-I/R injury is yet to be fully elucidated. Here, we found that CARD9 expression increased in M-I/R mouse hearts, and in H9c2 or neonatal rat ventricular myocytes (NRVMs) in response to hypoxia/reoxygenation (H/R) or HO. CARD9 mice exhibited a significant cardiac dysfunction following M-I/R injury (30 min of left ascending coronary (LAD) ischemia and 12 h of reperfusion) compared to wild-type (WT) mice. CARD9 deletion impaired autophagy during M-I/R in vivo and in vitro, evidenced by decrease of microtubule-associated protein 1 light chain 3 (LC3) lipidation and p62 accumulation. Conversely, CARD9 overexpression increased autophagic flux as indicated by enhanced expression of LC3 II/LC3 I and a reduction in p62. The protective effect of CARD9 on cardiomyocytes against H/R-induced oxidative stress was abolished by treatment with autophagy inhibitors, 3-methyladenine (3-MA) or Bafilomycin A1(BafA1). CARD9 interacted with RUN domain Beclin-1-interacting cysteine-rich-containing (Rubicon), a negative regulator of autophagy, and enhanced UV-irradiation-resistance-associated gene (UVRAG)-Beclin1-phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3) interaction and UVRAG-Vps16-mediated Rab7 activation to promote autophagosome formation, maturation, and endocytosis. Ablation of Rubicon by siRNA effectively prevented the detrimental effect of CARD9 knockdown on cardiomyocytes. These results suggest that CARD9 has protective effects on the myocardium against M-I/R injury by activating autophagy and restoring autophagic flux in vivo and in vitro.
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http://dx.doi.org/10.1007/s00395-020-0790-6DOI Listing
April 2020

Wearing-off Identification in Parkinson's Disease: The shapd-woq Study.

Front Neurol 2020 13;11:116. Epub 2020 Mar 13.

Department of Neurology, Xinhua Hospital, Affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, China.

To clarify the frequency of wearing-off phenomenon (WO) and the validity of the Chinese version of the 9-item wearing-off questionnaire (CWOQ-9) in WO identification in this large population. Parkinson's patients treated with antiparkinsonian medications were consecutively recruited into this observational, cross-sectional investigation. Patients completed the CWOQ-9 prior to the independent clinician assessment. A total of 1,385 patients were included in the analysis. The mean age was 69.7 ± 9.5 years and the mean disease duration was 5.8 ± 4.7 years. Clinicians identified WO in 763 patients, with an overall prevalence of 55.1%. In patients within 1 year of disease duration, clinicians diagnosed WO in eight patients, with a percentage of 12.9%. With the disease progression, the WO frequency gradually increased to 76.2% in patients with 10-15 years of disease duration. Then, it slowly decreased at a longer disease duration. The occurrence of WO was closely associated with the disease duration, H&Y staging, and levodopa daily dose. CWOQ-9 identified 1,071 patients (1071/1398, 77.33%) that had WO-related symptoms. The mean CWOQ-9 score was 3.4 ± 1.6. CWOQ-9 corresponded with clinician assessments of WO in 734 of 763 cases; clinicians disagreed with the CWOQ-9 considering the presence of WO in 337 of 1,071 cases. The sensitivity and specificity of CWOQ-9 were 96.2 and 45.8%, respectively. WO occurred frequently at the early and middle stage of PD. CWOQ-9 was qualified as a pre-visiting screening tool for clinicians to better identify WO.
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http://dx.doi.org/10.3389/fneur.2020.00116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083219PMC
March 2020

The different dietary sugars modulate the composition of the gut microbiota in honeybee during overwintering.

BMC Microbiol 2020 03 17;20(1):61. Epub 2020 Mar 17.

College of Animal Science and Technology, Shandong Agricultural University, Tai'an, 271018, Shandong, China.

Background: The health of honeybee colonies is critical for bee products and agricultural production, and colony health is closely associated with the bacteria in the guts of honeybees. Although colony loss in winter is now the primary restriction in beekeeping, the effects of different sugars as winter food on the health of honeybee colonies are not well understood. Therefore, in this study, the influence of different sugar diets on honeybee gut bacteria during overwintering was examined.

Results: The bacterial communities in honeybee midguts and hindguts before winter and after bees were fed honey, sucrose, and high-fructose syrup as winter-food were determined by targeting the V3-V4 region of 16S rDNA using the Illumina MiSeq platform. The dominant microbiota in honeybee guts were the phyla Proteobacteria (63.17%), Firmicutes (17.61%; Lactobacillus, 15.91%), Actinobacteria (4.06%; Bifidobacterium, 3.34%), and Bacteroidetes (1.72%). The dominant taxa were conserved and not affected by season, type of overwintering sugar, or spatial position in the gut. However, the relative abundance of the dominant taxa was affected by those factors. In the midgut, microbial diversity of the sucrose group was higher than that of the honey and high-fructose syrup groups, but in the hindgut, microbial diversity of the honey and high-fructose groups was higher than that in the sucrose group. Sucrose increased the relative abundance of Actinobacteria (Bifidobacteriales Bifidobacteriaceae) and Alphaproteobacteria (Rhizobiales and Mitochondria) of honeybee midgut, and honey enriched the Bacteroidetes and Gammaproteobacteria (Pasteurellales) in honeybee hindgut. High-fructose syrup increased the relative abundance of Betaproteobacteria (Neisseriales: Neisseriaceae) of the midgut.

Conclusion: The type of sugar used as winter food affected the relative abundance of the dominant bacterial communities in honeybee guts, not the taxa, which could affect the health and safety of honeybee colonies during overwintering. The presence of the supernal Alphaproteobacteria, Bifidobacteriales, and Lactobacillaceae in the gut of honeybees fed sucrose and cheaper than honey both indicate that sucrose is very suitable as the overwintering food for honeybees.
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http://dx.doi.org/10.1186/s12866-020-01726-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076957PMC
March 2020

Infection Impairs Endothelial Function Through an Exosome-Mediated Mechanism.

J Am Heart Assoc 2020 03 15;9(6):e014120. Epub 2020 Mar 15.

Departments of Gastroenterology Third Xiangya Hospital, Central South University Changsha China.

Background Epidemiological studies have suggested an association between () infection and atherosclerosis through undefined mechanisms. Endothelial dysfunction is critical to the development of atherosclerosis and related cardiovascular diseases. The present study was designed to test the hypothesis that infection impaires endothelial function through exosome-mediated mechanisms. Methods and Results Young male and female patients (18-35 years old) with and without infection were recruited to minimize the chance of potential risk factors for endothelial dysfunction for the study. Endothelium-dependent flow-mediated vasodilatation of the brachial artery was evaluated in the patients and control subjects. Mouse infection models with CagA from a gastric ulcer patient were created to determine if infection-induced endothelial dysfunction could be reproduced in animal models. infection significantly decreased endothelium-dependent flow-mediated vasodilatation in young patients and significantly attenuated acetylcholine-induced endothelium-dependent aortic relaxation without change in nitroglycerin-induced endothelium-independent vascular relaxation in mice. eradication significantly improved endothelium-dependent vasodilation in both patients and mice with infection. Exosomes from conditioned media of human gastric epithelial cells cultured with CagA or serum exosomes from patients and mice with infection significantly decreased endothelial functions with decreased migration, tube formation, and proliferation in vitro. Inhibition of exosome secretion with GW4869 effectively preserved endothelial function in mice with infection. Conclusions infection impaired endothelial function in patients and mice through exosome-medicated mechanisms. The findings indicated that infection might be a novel risk factor for cardiovascular diseases.
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http://dx.doi.org/10.1161/JAHA.119.014120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335532PMC
March 2020