Publications by authors named "Ping Yuan"

478 Publications

MiR-4310 regulates hepatocellular carcinoma growth and metastasis through lipid synthesis.

Cancer Lett 2021 Jul 22;519:161-171. Epub 2021 Jul 22.

Medical School of Guizhou University, Guiyang, 550025, China; Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, 100850, China. Electronic address:

Hepatocellular carcinoma (HCC), which is characterized by reprogrammed lipid metabolism, is a highly malignant tumor with a high incidence and mortality rate. While lipid metabolism is a promising target for HCC therapy, the regulation of lipid metabolism is not well elucidated. Through CRISPR/Cas9 screening, we show that miR-4310 inhibits lipid synthesis by targeting fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1). In patients with HCC, miR-4310 is significantly downregulated, and its expression is negatively correlated with expressions of FASN and SCD1. Furthermore, low expression of miR-4310 is associated with poor prognosis. By suppressing SCD1-and FASN-mediated lipid synthesis, miR-4310 inhibits HCC cell proliferation, migration, and invasion in vitro and suppresses HCC tumor growth and metastasis in vivo. Our data indicate that miR-4310 plays an important role in HCC tumor growth and metastasis by regulating the FASN- and SCD1-mediated lipid synthesis pathways. Targeting the miR-4310-FASN/SCD pathway may provide a novel strategy for HCC treatment.
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http://dx.doi.org/10.1016/j.canlet.2021.07.029DOI Listing
July 2021

Response of Wheat DREB Transcription Factor to Osmotic Stress Based on DNA Methylation.

Int J Mol Sci 2021 Jul 18;22(14). Epub 2021 Jul 18.

College of Life Sciences, Henan Normal University, Xinxiang 453007, China.

Dehydration-responsive element-binding protein (DREB) plays an important role in response to osmotic stress. In this study, , and are isolated from wheat AK58, yet they belong to different types of DREB transcription factors. Under osmotic stress, the transcript expression of , and has tissue specificity and is generally higher in leaves, but their expression trends are different along with the increase of osmotic stress. Furthermore, some elements related to stresses are found in their promoters, promoters of and are slightly methylated, but 's promoter is moderately methylated. Compared with the control, the level of promoter methylation in is significantly lower under osmotic stress and is also lower at CG site in , yet is significantly higher at CHG and CHH sites in , which is also found at a CHG site in . The status of promoter methylation in , and also undergoes significant changes under osmotic stress; further analysis showed that promoter methylation of is negatively correlated with their expression. Therefore, the results of this research suggest the different functions of , and in response to osmotic stress and demonstrate the effects of promoter methylation on the expression regulation of .
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http://dx.doi.org/10.3390/ijms22147670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307787PMC
July 2021

The role of informal caregivers for patients with glioma: a systematic review and meta-synthesis of qualitative studies.

Ann Transl Med 2021 Jun;9(12):1020

Department of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background: This study aimed to systematically review, appraise, and synthesize the current evidence on the experiences and needs encountered by informal caregiver of patients with glioma throughout the disease trajectory and to provide a set of practical implications for health professionals.

Methods: Seven English databases and four Chinese databases were searched in this systematic review and meta-analysis. Additional manual searches were completed to identify primary studies, with the language limited by English and Chinese. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research was used to appraise the methodological quality of each study.

Results: The systematic review included 16 papers that yielded 71 findings and 6 categories. Finally, 2 synthesized findings were extracted: (I) role transition of caregivers for glioma patients throughout the disease trajectory; (II) support and information need by caregivers of glioma patients. Accordingly, there is a need to recognize the importance of permanent and tailored support for caregivers by providing accurate, practical, and evidence-based information.

Discussion: This is the first attempt to systematically evaluate the breadth and quality of the literature concerning the experiences of caregivers with glioma patients. The results generated from the review may shed some light on problems encountered by glioma patients and their families. A limitation of this review is that in most selected studies, the reflexivity of interviewees is not addressed, which may influence the interpretation of the findings. Moreover, the selected studies were reported in English or Chinese, therefore, caution is needed in interpreting the results.
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http://dx.doi.org/10.21037/atm-21-2761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267327PMC
June 2021

The effect of docosahexaenoic acid on predicting the survival of patients with idiopathic pulmonary arterial hypertension.

Ann Transl Med 2021 Jun;9(12):995

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.

Background: Abnormal lipid metabolism has been reported in patients with idiopathic pulmonary arterial hypertension (IPAH); however, the prognostic value of plasma free fatty acids (FFAs) for these patients is unclear. The present study aimed to determine whether FFA can play a role in predicting the survival of patients with IPAH.

Methods: A total of 69 blood samples from patients with IPAH were subjected to liquid chromatography-mass spectrometry (LC-MS). According to the classification criteria for pulmonary hypertension in the European Society of Cardiology (ESC) guidelines, patients were divided into low-risk, intermediate-risk, and high-risk groups. The FFA expression levels of patients in the three groups were compared, and the indicators with significant differences were selected. Cox regression analysis was performed to examine the associations between survival and different factors. Receiver operator characteristic (ROC) curves were used to assess the predictive effect of plasma lipids in assessing patients' risk of morbidity, including area under the curve (AUC), sensitivity, specificity and the best cutoff value. Kaplan-Meier curves were used to predict survival.

Results: A total of 24 FFA molecules were detected in the patients with IPAH. Among them, FFA (20:4), FFA (20:5), FFA (22:5), FFA (22:6), FFA (24:0) and FFA (30:4) showed significant differences between the low-risk and the intermediate-risk or high-risk patients with IPAH. These six FFAs were significantly correlated with hemodynamic parameters. FFA (22:6), named docosahexaenoic acid (DHA), displayed significant negative correlations with World Health Organization functional classification (WHO FC), mean right atrial pressure (mRAP), and pulmonary vascular resistance (PVR), and significant positive correlations with 6-minute walking distance (6MWD) and cardiac index (CI). Cox regression analyses demonstrated that total bilirubin (TBIL) and DHA were independent risk factors for survival of IPAH. Receiver operating characteristic curve analysis revealed that DHA had a cut-off value of 77.55, which had a sensitivity of 96.7% and a specificity of 62.5% for predicting survival. Kaplan-Meier curve analysis showed that a lower level of DHA predicted a poor outcome in patients with IPAH.

Conclusions: Our study suggested that FFA levels were correlated with disease severity. Lower levels of DHA predict poor survival in patients with IPAH.
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http://dx.doi.org/10.21037/atm-21-2479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267313PMC
June 2021

Soluble ST2 and mixed venous oxygen saturation for prediction of mortality in patients with pulmonary hypertension.

J Thorac Dis 2021 Jun;13(6):3478-3488

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.

Background: Although soluble suppression of tumorigenicity-2 (sST2) has been identified as a clinical biomarker for pulmonary hypertension (PH) by previous studies, the implication of sST2 combined with hemodynamic parameters in PH has not been well studied. This study aimed to evaluate the relationship between sST2 and hemodynamic parameters and to evaluate the predictive value of sST2 for mortality in patients with PH.

Methods: One hundred eighty-four incident patients with PH and 14 healthy controls were retrospectively enrolled by Shanghai Pulmonary Hospital for this retrospective study. After all patients underwent right heart catheterization, blood samples were collected and serum sST2 concentration was assessed by the Presage™ ST2 assay. Kaplan-Meier curve and Cox regression analyses were used to predict survival and the association between survival and different factors such as sST2, SvO.

Results: During a follow-up of 44.9 (IQR 28.5-64.4) months, 65 patients died. The median concentration of sST2 in PH patients was 33.1 ng/mL, which is higher than that in control group (23.1 ng/mL, P=0.005). Furthermore, for PH group, the level of sST2 was higher in non-survivors than that in survivors. Cox regression analyses demonstrated that sST2 and SvO were independent risk factors for survival. In Kaplan-Meier curve analyses, elevated sST2 level and reduced SvO predicted a poor outcome for patients with PH.

Conclusions: Higher sST2 was independently associated with increased mortality, as well as lower SvO in patients with PH. Especially, the combination of higher sST2 and lower SvO had the strongest predictive value of mortality in patients with PH.
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http://dx.doi.org/10.21037/jtd-20-2732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264676PMC
June 2021

Survival in severe pulmonary hypertension due to chronic lung disease: influence of in-hospital platelet distribution width.

Pulm Circ 2021 Jul-Sep;11(3):20458940211026484. Epub 2021 Jun 30.

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Platelet distribution width has been recognized as risk predictors of idiopathic pulmonary arterial hypertension. This study aims to investigate whether in-hospital platelet distribution width would be useful to predict all-cause death in patients with severe pulmonary hypertension due to chronic lung diseases (CLD-PH). Early in-hospital platelet distribution width was measured in 67 severe CLD-PH patients who were confirmed by right heart catheterization and followed up. Event-free survival was estimated using the Kaplan-Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the association between the platelet distribution width level and all-cause death. During median of 2.4 (2.5, 3.7) years of follow-up, 44 patients died. A significant association was noted between in-hospital platelet distribution width level and the adjusted risk of all-cause mortality (hazard ratio: 1.245; 95% confidence interval: 1.117-1.386,  < 0.001). Compared with those with platelet distribution width <16.1%, the hazard ratio for all-cause death increased by 5.278 (95% confidence interval: 2.711-10.276,  < 0.0001) among patients with platelet distribution width ≥16.1%. Higher levels of platelet distribution width were also associated with increased risk of all-cause death. In-hospital platelet distribution width was independently associated with all-cause death in patients with severe CLD-PH. This potentially could be used to estimate the severity of severe CLD-PH.
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http://dx.doi.org/10.1177/20458940211026484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258768PMC
June 2021

Extracellular vesicles derived from lung cancer cells exposed to intermittent hypoxia upregulate programmed death ligand 1 expression in macrophages.

Sleep Breath 2021 Jul 12. Epub 2021 Jul 12.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.

Purpose: Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), compromises immune surveillance through the upregulation of programmed cell death-1 ligand (PD-L1). Tumor-released extracellular vesicles (EVs) have been reported to modulate immunosuppressive activities. We investigated whether or not EVs derived from intermittent hypoxic lung cancer cells can alter the expression of PD-L1 in macrophages.

Methods: The expression of PD-L1monocytes from 40 patients with newly diagnosed non-small-cell lung cancer (NSCLC) and with (n=21) or without (n=19) OSA were detected. Plasma EVs isolated from NSCLC patients with moderate-severe OSA (n=4) and without OSA (n=4) were co-cultured with macrophages. A549 cells were exposed to normoxia or IH (48 cycles of 5 min of 1% O hypoxia, followed by 5 min of normoxia). EVs were isolated from cell supernatant and were co-cultured with macrophages differentiated from THP-1. PD-L1 and hypoxia-inducible factor-1 α (HIF-1α) expressions were measured by flow cytometry, immunofluorescence, and Western blot analysis.

Results: PD-L1monocytes were elevated in NSCLC patients with OSA and increased with the severity of OSA and nocturnal desaturation. PD-L1 macrophages were induced by EVs from NSCLC patients with OSA and positively correlated with HIF-1α expressions. EVs from IH-treated A549 can promote PD-L1 and HIF-1α expression in macrophages and the upregulation of PD-L1 expression was reversed by specific HIF-1α inhibitor.

Conclusion: IH can enhance the function of EVs derived from lung cancer cells to aggravate immunosuppressive status in macrophages. HIF-1α may play an important role in this process.
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http://dx.doi.org/10.1007/s11325-021-02369-1DOI Listing
July 2021

Rational Design of Poly(disulfide)s as a Universal Platform for Delivery of CRISPR-Cas9 Machineries toward Therapeutic Genome Editing.

ACS Cent Sci 2021 Jun 27;7(6):990-1000. Epub 2021 May 27.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

We synthesized a series of poly(disulfide)s by ring-opening polymerization and demonstrated that the copolymerization of monomer 1 containing diethylenetriamine moieties and monomer 2 containing guanidyl ligands could generate an efficient delivery platform for different forms of CRISPR-Cas9-based genome editors, including plasmid, mRNA, and protein. The excellent delivery performance of designed poly(disulfide)s stems from their delicate molecular structures to interact with genome-editing biomacromolecules, unique delivery pathways to mediate the cellular uptake of CRISPR-Cas9 cargoes, and strong ability to escape the endosome. The degradation of poly(disulfide)s by intracellular glutathione not only promotes the timely release of CRISPR-Cas9 machineries into the cytosol but also minimizes the cytotoxicity that nondegradable polymeric carriers often encounter. These merits collectively account for the excellent ability of poly(disulfide)s to mediate different forms of CRISPR-Cas9 for their efficient genome-editing activities in vitro and in vivo.
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http://dx.doi.org/10.1021/acscentsci.0c01648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227594PMC
June 2021

Enhancing Defect Tolerance with Ligands at the Surface of Lead Halide Perovskites.

J Phys Chem Lett 2021 Jul 6;12(27):6299-6304. Epub 2021 Jul 6.

Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.

High defect tolerance has been considered a primary reason for the long charge carrier lifetime and high photoluminescence quantum yield in bulk lead halide perovskites (LHPs). On the other hand, surface defects play a critical role in determining charge carrier dynamics and optical properties, especially for LHP nanocrystals and quantum dots. Understanding the nature of surface defects and developing strategy for their effective passivation are thus of strong interest. Focusing on a prototypical LHP, CsPbBr, our work uses first-principles calculations to reveal that interstitial sites and antisites can have lower formation energies when they form at the surface while simultaneously creating deep trap states within the bandgap. Meanwhile, the formation of halide vacancies is energetically less favorable. On the basis of a new surface defect model, we demonstrate the explicit role of molecular ligands in passivating these defects, which eliminate trap states in favor of shallow states and enhance photoluminescence.
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http://dx.doi.org/10.1021/acs.jpclett.1c01243DOI Listing
July 2021

Comparative Effectiveness of Exercise Training for Patients With Chronic Thromboembolic Pulmonary Hypertension After Pulmonary Endarterectomy: A Systematic Review and Meta-Analysis.

Front Cardiovasc Med 2021 17;8:664984. Epub 2021 Jun 17.

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) still experience reduced exercise capacity despite pulmonary endarterectomy (PEA). Exercise training improves the exercise capacity and quality of life (QoL) in patients with PH, but data on the effects of exercise training on these patients are scarce. The aim of this meta-analysis and systematic review was to evaluate the effectiveness and safety of exercise training in CTEPH after PEA. We searched the relevant literature published before January 2020 for the systematic review and meta-analysis using the PubMed, EMBASE, and Cochrane Library databases. The primary outcome was a change in the 6-min walking distance (6 MWD). We also assessed the effect of exercise on the peak oxygen uptake (VO) or peak VO/kg, oxygen uptake anaerobic threshold, workload, oxygen pulse, hemodynamics, arterial blood gases, oxygen saturation, N-terminal pro-brain-type natriuretic peptide (NT-proBNP), quality of life (QoL) and pulmonary function tests. We included 4 studies with 208 exercise-training participants. In the pooled analysis, short-term exercise training can improve the 6 MWD of 58.89 m (95% CI: 46.26-71.52 m, < 0.0001). There was a significant increase in the peak VO/kg or peak VO after exercise training (3.15 ml/min/kg, 95% CI: 0.82-5.48, = 0.008; 292.69 ml/min, 95% CI: 24.62-560.75, = 0.032, respectively). After exercise training, the maximal workload and O pulse significantly improved. Three months of exercise training increased the right ventricular ejection fraction by 3.53% (95% CI: 6.31-11.94, < 0.00001, = 0) independently of PEA surgery. In addition, NT-proBNP plasma levels significantly improved with exercise training after PEA [weighted mean difference (WMD): -524.79 ng/L, 95% CI: 705.16 to -344.42, < 0.0001, = 0]. The partial pressure of oxygen and pH improved progressively over 12 weeks of exercise training (WMD: 4 mmHg, 95% CI: 1.01-8.33, = 0.01; WMD: 0.03, 95% CI: 0.02-0.04, < 0.0001, respectively). Subscales of the QoL measured by the SF-36 questionnaire had also improved. In addition, exercise training was well-tolerated with a low dropout rate, and no major adverse events occurred during exercise training. Exercise training may be associated with a significant improvement in the exercise capacity and QoL among CTEPH patients after PEA and was proven to be safe. However, more large-scale multicentre studies are needed to confirm the effectiveness and safety of exercise training in CTEPH patients after PEA. CRD42021235275.
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http://dx.doi.org/10.3389/fcvm.2021.664984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245692PMC
June 2021

Impact of Parthanatos on the Increased Risk of Onset and Mortality in Male Patients With Pulmonary Hypertension.

Am J Mens Health 2021 May-Jun;15(3):15579883211029458

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.

There have been no studies as to whether parthanatos, a poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1)-dependent and apoptosis-inducing factor (AIF)-mediated caspase-independent programmed cell death, is present in pulmonary hypertension (PH). Basic studies have, however, been conducted on several of the key molecules in parthanatos, such as PARP-1, AIF, and macrophage migration inhibitory factor (MIF). For this study, we collected blood samples from 88 incident male patients with PH and 50 healthy controls at the Shanghai Pulmonary Hospital. We measured the key factors of parthanatos (PARP-1, PAR, AIF, and MIF) by enzyme-linked immunosorbent assay and performed a logistic regression, Cox proportional hazards analysis, and Kaplan-Meier test to assess the prognostic value of the key molecules in diagnosing and predicting survival. The patients who ultimately died had a significantly poorer clinical status during the study than those who survived. The PARP-1, PAR, AIF, and MIF levels were significantly higher in the patients than in the controls (all < .0001), and the PARP-1, PAR, and AIF levels were higher in the nonsurvivors than in the survivors (all < .0001). PARP-1 and AIF levels served as independent predictors of disease onset and mortality in these patients (all < .005). Patients with PARP-1 levels <11.24 ng/mL or AIF levels <1.459 pg/mL had significantly better survival than those with higher PARP-1 or AIF levels ( < .0001). Circulating levels of PARP-1 and AIF were independent predictors for PH onset and mortality, which indicated that parthanatos might be associated with the pathogenesis of PH.
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http://dx.doi.org/10.1177/15579883211029458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256257PMC
June 2021

LncRNA MAYA promotes iron overload and hepatocyte senescence through inhibition of YAP in non-alcoholic fatty liver disease.

J Cell Mol Med 2021 Jun 30. Epub 2021 Jun 30.

Department of Pharmacology, School of Pharmacy, Wannan Medical College, Wuhu, China.

Although recent evidence has shown that hepatocyte senescence plays a crucial role in the pathogenesis and development of non-alcoholic fatty liver disease (NAFLD), the mechanism is still not clear. The purpose of this study was to investigate the signal transduction pathways involved in the senescence of hepatocyte, in order to provide a potential strategy for blocking the process of NAFLD. The results confirmed that hepatocyte senescence occurred in HFD-fed Golden hamsters and PA-treated LO2 cells as manifested by increased levels of senescence marker SA-β-gal, p16 and p21, heterochromatin marker H3K9me3, DNA damage marker γ-H2AX and decreased activity of telomerase. Further studies demonstrated that iron overload could promote the senescence of hepatocyte, whereas the overexpression of Yes-associated protein (YAP) could blunt iron overload and alleviate the senescence of hepatocyte. Of importance, depression of lncRNA MAYA (MAYA) reduced iron overload and cellular senescence via promotion of YAP in PA-treated hepatocytes. These effects were further supported by in vivo experiments. In conclusion, these data suggested that inhibition of MAYA could up-regulate YAP, which might repress hepatocyte senescence through modulating iron overload. In addition, these findings provided a promising option for heading off the development of NAFLD by abrogating hepatocyte senescence.
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http://dx.doi.org/10.1111/jcmm.16764DOI Listing
June 2021

Ladder-shape melting temperature isothermal amplification of nucleic acids.

Biotechniques 2021 Jul 24;71(1):358-369. Epub 2021 Jun 24.

Molecular Characterization of Foodborne Pathogens Research Unit, Eastern Regional Research Center, Agricultural Research Service, US Department of Agriculture, Wyndmoor, PA 19038, USA.

A novel method, termed ladder-shape melting temperature isothermal amplification (LMTIA), was developed in this study. As a proof of concept, one pair of primers or two pairs of nested primers and a thermostable DNA polymerase were employed to amplify the internal transcribed spacer of with the ladder-shape melting temperature curve. Our results demonstrated that the LMTIA assay with nested primers was 50-fold more sensitive than the LAMP assay with the same level of specificity. The LMTIA method has the potential to be used for the prevention and control of emerging epidemics caused by different types of pathogens.
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http://dx.doi.org/10.2144/btn-2020-0173DOI Listing
July 2021

Dysregulated lncRNA TUG1 in different pulmonary artery cells under hypoxia.

Ann Transl Med 2021 May;9(10):879

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.

Background: At present, the role of lncRNAs in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH) is not fully understood. This study aimed to explore differences in the hypoxia-induced expression of lncRNAs and their potential role in multiple pulmonary artery cells.

Methods: LncRNA expression in pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) was analyzed by high-throughput sequencing and compared between normoxic and hypoxic cells. Bioinformatics analysis was conducted to predict their functions.

Results: PASMCs, PMECs, and PCs displayed 275 (140 upregulated), 251 (162 upregulated), and 290 (176 upregulated) different lncRNAs, respectively. Among these, lncRNA TUG1 levels increased in PASMCs and PCs but decreased in PMECs. Bioinformatics analysis indicated that lncRNA TUG1 might target miR-145-5p, thereby affecting SOX4 and BMF expression, and could also regulate miR-129-5p levels to affect CYP1B1 and VCP expression. It could also regulate miR-138-5p levels to affect KCNK3 and RHOC expression.

Conclusions: Hypoxia exposure of vascular cells resulted in differential expression of lncRNAs, especially lncRNA TUG1, which showed significant abnormal expression in all three types of vascular cells under hypoxia. Our results suggested that abnormal expression of lncRNA TUG1 might be involved in the regulation of pulmonary vascular cell function under hypoxia.
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http://dx.doi.org/10.21037/atm-21-2040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184498PMC
May 2021

Neural Stem Cell-Derived Exosomes Regulate Neural Stem Cell Differentiation Through miR-9-Hes1 Axis.

Front Cell Dev Biol 2021 13;9:601600. Epub 2021 May 13.

Center for Translational Neurodegeneration and Regenerative Therapy, Tenth People's Hospital of Tongji University, Shanghai, China.

Exosomes, a key element of the central nervous system microenvironment, mediate intercellular communication via horizontally transferring bioactive molecules. Emerging evidence has implicated exosomes in the regulation of neurogenesis. Recently, we compared the neurogenic potential of exosomes released from primary mouse embryonic neural stem cells (NSCs) and astrocyte-reprogrammed NSCs, and observed diverse neurogenic potential of those two exosome populations . However, the roles of NSC-derived exosomes on NSC differentiation and the underlying mechanisms remain largely unknown. In this study, we firstly demonstrated that NSC-derived exosomes facilitate the differentiation of NSCs and the maturation of both neuronal and glial cells in defined conditions. We then identified miR-9, a pro-neural miRNA, as the most abundantly expressed miRNA in NSC-derived exosomes. The silencing of miR-9 in exosomes abrogates the positive effects of NSC-derived exosomes on the differentiation of NSCs. We further identified as miR-9 downstream target, as the transfection of Hes1 siRNA restored the differentiation promoting potential of NSC-derived exosomes after knocking down exosomal miR-9. Thus, our data indicate that NSC-derived exosomes facilitate the differentiation of NSCs via transferring miR-9, which sheds light on the development of cell-free therapeutic strategies for treating neurodegeneration.
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http://dx.doi.org/10.3389/fcell.2021.601600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155619PMC
May 2021

IIMLP: integrated information-entropy-based method for LncRNA prediction.

BMC Bioinformatics 2021 May 13;22(Suppl 3):243. Epub 2021 May 13.

School of Computer Science and Technology, Harbin Institute of Technology (Shenzhen), Shenzhen, 518055, Guangdong, China.

Background: The prediction of long non-coding RNA (lncRNA) has attracted great attention from researchers, as more and more evidence indicate that various complex human diseases are closely related to lncRNAs. In the era of bio-med big data, in addition to the prediction of lncRNAs by biological experimental methods, many computational methods based on machine learning have been proposed to make better use of the sequence resources of lncRNAs.

Results: We developed the lncRNA prediction method by integrating information-entropy-based features and machine learning algorithms. We calculate generalized topological entropy and generate 6 novel features for lncRNA sequences. By employing these 6 features and other features such as open reading frame, we apply supporting vector machine, XGBoost and random forest algorithms to distinguish human lncRNAs. We compare our method with the one which has more K-mer features and results show that our method has higher area under the curve up to 99.7905%.

Conclusions: We develop an accurate and efficient method which has novel information entropy features to analyze and classify lncRNAs. Our method is also extendable for research on the other functional elements in DNA sequences.
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http://dx.doi.org/10.1186/s12859-020-03884-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117603PMC
May 2021

Mitochondria Targeted O Economizer to Alleviate Tumor Hypoxia for Enhanced Photodynamic Therapy.

Adv Healthc Mater 2021 06 3;10(12):e2100198. Epub 2021 May 3.

The Fifth Affiliated Hospital, Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, P. R. China.

Photodynamic therapy (PDT) often suffers from the exacerbated tumor hypoxia and the heterogeneous distribution of photosensitizers, leading to an inefficient ROS productivity and availability. In this work, a mitochondria targeted O economizer (designated as Mito-OxE) is developed to improve PDT efficiency by alleviating tumor hypoxia and enhancing the subcellular localization of photosensitizers. Specifically, the photosensitizer of protoporphyrin IX (PpIX) is modified with the hydrophilic polyethylene glycol and the lipophilic cation of triphenylphosphine (TPP) to fabricate the biocompatible mitochondria targeted photosensitizers (designated as Mito-PSs). And Mito-OxE is prepared by using Mito-PSs to load the mitochondrial oxidative phosphorylation inhibitors of atovaquone (ATO). Benefiting from the targeting capability of TPP, Mito-OxE can selectively accumulate in mitochondria after cellular uptake. Subsequently, the mitochondrial respiration would be suppressed to with the participation of ATO, resulting in a local hypoxia mitigation for enhanced PDT. Compared with Mito-PSs, Mito-OxE maximizes the therapeutic effect against hypoxic tumors under light irradiation. This design of mitochondria targeted O economizer would advance the development of targeted drug delivery system for effective PDT regardless of hypoxic microenvironment.
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http://dx.doi.org/10.1002/adhm.202100198DOI Listing
June 2021

The predictive value of Holter monitoring in the risk of obstructive sleep apnea.

J Thorac Dis 2021 Mar;13(3):1872-1881

Department of Sleep Center, Department of Pulmonary and Critical Care Medicine, Guangdong Provincial People's Hospital/Guangdong Academy of Medical Sciences/Guangdong Provincial Geriatrics Institute/Medical College, South China University of Technology, Guangzhou, China.

Background: Patients with obstructive sleep apnea (OSA) often present with cardiovascular symptoms. Holter monitors were reported to predict sleep apnea, though were rarely used in everyday clinical practice. In this study, by comparing Holter monitoring to polysomnography (PSG), we try to find out an operable way for clinicians to use Holter to predict OSA risk.

Methods: Patients (n=63) suspected of OSA underwent Holter monitoring with concurrent PSG at a sleep center. Respiration and heart rate variability (HRV) indices were calculated from the Holter and compared with PSG indices.

Results: The sensitivity of the Holter-derived respiratory waveform for OSA was 90.0%, and the specificity was 82.6%. The time domain indices including standard deviation of all NN intervals during 24 hours, mean of standard deviation of the averages of NN intervals in all 5-minute segments, square root of the mean squared differences of successive NN intervals, percentage of beat-to-beat NN interval differences that were more than 50 milliseconds, and the frequency domain index of high frequency decreased in participants with OSA and correlated with the PSG derived indices including apnea-hypopnea index (AHI), oxygen reduction index (ODI) and nadir SaO. Logistic regression showed that standard deviation of all NN intervals during 24 hours and gender could predict the risk of OSA (P<0.001), with a sensitivity for diagnosing moderate to severe OSA of 87.5% and could accurately distinguish the risk of OSA in 77.8% of patients. Males with standard deviation of all NN intervals during 24 hours ≤177 ms or females with standard deviation of all NN intervals during 24 hours ≤80.9 ms were considered to be at high risk for OSA.

Conclusions: Commercial and common parameters from Holter monitoring could predict the risk of OSA with high sensitivity. Therefore, the risk of OSA may be assessed using the Holter examination to improve the diagnosis and treatment rate of OSA.
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http://dx.doi.org/10.21037/jtd-20-3078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024822PMC
March 2021

Clinical and Prognostic Analysis of Autoantibody-Associated CNS Demyelinating Disorders in Children in Southwest China.

Front Neurol 2021 26;12:642664. Epub 2021 Mar 26.

Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China.

To analyze the positive and recurrence rates of different autoantibody-associated demyelination disorders in children in Southwest China, and describe the clinical, radiological, and prognostic features of the myelin oligodendrocyte glycoprotein antibody (MOG-ab) and aquaporin-4 antibody (AQP4-ab) associated disease. This study also summarizes steroid maintenance therapy approaches for MOG-ab-positive children. A total of 160 children presenting with acquired demyelinating syndromes (ADS) between January 2016 and December 2019 were tested for MOG-ab and AQP4-ab. Clinical data, MRI scans, and survival analyses were compared between MOG-ab-positive and AQP4-ab-positive children. Evolution of serologic status and treatment response to immunosuppressants were collected in MOG-ab-positive children. Of the 160 included children, the MOG-ab positivity rate (47.4%) was significantly higher than the AQP4-ab (5%) positivity rate. The recurrence rate for AQP4-ab disease (71.4%) was higher than that of MOG-ab disease (30.1%). For 135 children with both MOG-ab and AQP4-ab tested, the median age at onset was 7 (interquartile range [IQR] 5-10) years, and the median follow-up period was 19 (IQR 13-27.5) months. MOG-ab-positive children more frequently presented with acute disseminated encephalomyelitis, had deep gray matter lesions on MRI, had a better clinical and radiological recovery, and were less likely to have sustained disability than AQP4-ab-positive children. In MOG-ab-positive and AQP4-ab-positive children, maintenance therapy was a protective factor for recurrence, but presenting optic neuritis was a predictor of earlier relapse. A high Expanded Disability Status Scale score at onset was associated with sustained disability. Steroid maintenance therapy longer than 6 months after the initial attack was associated with a lower risk of a second relapse in MOG-ab-positive children. On serial serum MOG antibody analysis, clinical relapse occurred in 34.6% of children with persistent seropositivity, but none of the children who converted to seronegative status experienced relapse. The MOG antibody is more common in children with ADS than the AQP4 antibody. MOG-ab-positive children are characterized by distinct clinical and radiological features. Although some MOG-ab-positive children experience relapsing courses or have persistently seropositive status, they still predict a better outcome than AQP4-ab-positive children.
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http://dx.doi.org/10.3389/fneur.2021.642664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033000PMC
March 2021

Plasma exosomal miR-596: a novel biomarker predicts survival in patients with idiopathic pulmonary artery hypertension.

J Int Med Res 2021 Mar;49(3):3000605211002379

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.

Objective: To determine if plasma exosomal microRNAs (miRNAs) can predict survival in patients with idiopathic pulmonary arterial hypertension (IPAH).

Methods: The study enrolled patients with IPAH that underwent right heart catheterization. Plasma was collected and exosomal miRNAs were extracted. Exosomes were evaluated using transmission electron microscopy, Western blot analysis and particle size distribution analysis. MiRNAs were evaluated using a miRNA microarray and validated using real-time polymerase chain reaction.

Results: This study included 12 patients with IPAH in the study group and 48 patients with IPAH in the validation group. The mean ± SD follow-up duration was 60.3 ± 35.4 months in the overall cohort. The levels of miR-596 were higher in the nonsurvivors compared with the survivors. The levels of miR-596 significantly correlated with survival time, mean right atrial pressure, pulmonary vascular resistance (PVR) and cardiac index. High levels of miR-596 and PVR were significantly associated with poor overall survival. Multivariate analysis demonstrated that exosomal miR-596 (hazard ratio [HR] = 2.119; 95% confidence interval [CI] 1.402, 3.203) and PVR (HR = 1.146; 95% CI 1.010, 1.300) were independent predictors of survival.

Conclusions: High levels of plasma exosomal miR-596 were significantly associated with disease severity and poor prognosis of patients with IPAH.
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http://dx.doi.org/10.1177/03000605211002379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020249PMC
March 2021

Resilience, coping style, and COVID-19 stress: effects on the quality of life in frontline health care workers.

Psychol Health Med 2021 Mar 29:1-13. Epub 2021 Mar 29.

Shandong Public Health Clinical Center, Cheeloo College of Medicine, Shandong University, Jinan, China.

The aims of the study were to assess the contribution of resilience, coping style, and COVID-19 stress on the quality of life (QOL) in frontline health care workers (HCWs). The study was a cross-sectional surveyperformed among 309 HCWs in a tertiaryhospital during the outbreak of COVID-19 in China. Data were collected through an anonymous, self-rated questionnaire, including demographic data, a 10-item COVID-19 stress questionnaire, Generic QOL Inventory-74, Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire. Hierarchical regression was used to analyse the relationship between the study variables and the QOL. Among the 309 participants, resilience and active coping were positively correlated with the QOL (P<0.001), whereas, working in confirmed case wards, COVID-19 stress, and passive coping were negatively correlated with the QOL (P<0.001). Resilience and the active coping were negatively correlated with COVID-19 stress (P<0.001). Resilience, coping style,and COVID-19 stressaccounted for 32%, 13%, and 8% of the variance in predicting the Global QOL, respectively. In conclusion, working in confirmed COVID-19 case wards and COVID-19 stress impaired the QOL in HCWs. Psychological intervention to improve the resilience and coping style, and reduce COVID-19 stress are important in improving the QOL and mental health of HCWs.
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http://dx.doi.org/10.1080/13548506.2021.1905860DOI Listing
March 2021

Emerging roles of extracellular vesicles in COVID-19, a double-edged sword?

Immunology 2021 08 4;163(4):416-430. Epub 2021 May 4.

Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.

The sudden outbreak of SARS-CoV-2-infected disease (COVID-19), initiated from Wuhan, China, has rapidly grown into a global pandemic. Emerging evidence has implicated extracellular vesicles (EVs), a key intercellular communicator, in the pathogenesis and treatment of COVID-19. In the pathogenesis of COVID-19, cells that express ACE2 and CD9 can transfer these viral receptors to other cells via EVs, making recipient cells more susceptible for SARS-CoV-2 infection. Once infected, cells release EVs packaged with viral particles that further facilitate viral spreading and immune evasion, aggravating COVID-19 and its complications. In contrast, EVs derived from stem cells, especially mesenchymal stromal/stem cells, alleviate severe inflammation (cytokine storm) and repair damaged lung cells in COVID-19 by delivery of anti-inflammatory molecules. These therapeutic beneficial EVs can also be engineered into drug delivery platforms or vaccines to fight against COVID-19. Therefore, EVs from diverse sources exhibit distinct effects in regulating viral infection, immune response, and tissue damage/repair, functioning as a double-edged sword in COVID-19. Here, we summarize the recent progress in understanding the pathological roles of EVs in COVID-19. A comprehensive discussion of the therapeutic effects/potentials of EVs is also provided.
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http://dx.doi.org/10.1111/imm.13329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251486PMC
August 2021

High-order superlattices by rolling up van der Waals heterostructures.

Nature 2021 03 17;591(7850):385-390. Epub 2021 Mar 17.

Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.

Two-dimensional (2D) materials and the associated van der Waals (vdW) heterostructures have provided great flexibility for integrating distinct atomic layers beyond the traditional limits of lattice-matching requirements, through layer-by-layer mechanical restacking or sequential synthesis. However, the 2D vdW heterostructures explored so far have been usually limited to relatively simple heterostructures with a small number of blocks. The preparation of high-order vdW superlattices with larger number of alternating units is exponentially more difficult, owing to the limited yield and material damage associated with each sequential restacking or synthesis step. Here we report a straightforward approach to realizing high-order vdW superlattices by rolling up vdW heterostructures. We show that a capillary-force-driven rolling-up process can be used to delaminate synthetic SnS/WSe vdW heterostructures from the growth substrate and produce SnS/WSe roll-ups with alternating monolayers of WSe and SnS, thus forming high-order SnS/WSe vdW superlattices. The formation of these superlattices modulates the electronic band structure and the dimensionality, resulting in a transition of the transport characteristics from semiconducting to metallic, from 2D to one-dimensional (1D), with an angle-dependent linear magnetoresistance. This strategy can be extended to create diverse 2D/2D vdW superlattices, more complex 2D/2D/2D vdW superlattices, and beyond-2D materials, including three-dimensional (3D) thin-film materials and 1D nanowires, to generate mixed-dimensional vdW superlattices, such as 3D/2D, 3D/2D/2D, 1D/2D and 1D/3D/2D vdW superlattices. This study demonstrates a general approach to producing high-order vdW superlattices with widely variable material compositions, dimensions, chirality and topology, and defines a rich material platform for both fundamental studies and technological applications.
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http://dx.doi.org/10.1038/s41586-021-03338-0DOI Listing
March 2021

Single-Cell RNA Sequencing Uncovers Paracrine Functions of the Epicardial-Derived Cells in Arrhythmogenic Cardiomyopathy.

Circulation 2021 Jun 17;143(22):2169-2187. Epub 2021 Mar 17.

Center for Cardiovascular Genetics, Institute of Molecular Medicine and Department of Medicine (P.Y., S.M.C., L.R., S.F., P.G., A.J.M.).

Background: Arrhythmogenic cardiomyopathy (ACM) manifests with sudden death, arrhythmias, heart failure, apoptosis, and myocardial fibro-adipogenesis. The phenotype typically starts at the epicardium and advances transmurally. Mutations in genes encoding desmosome proteins, including DSP (desmoplakin), are major causes of ACM.

Methods: To delineate contributions of the epicardium to the pathogenesis of ACM, the allele was conditionally deleted in the epicardial cells in mice upon expression of tamoxifen-inducible Cre from the locus. Wild type (WT) and were crossed to Rosa26 (R26) dual reporter mice to tag the epicardial-derived cells with the EGFP (enhanced green fluorescent protein) reporter protein. Tagged epicardial-derived cells from adult :R26 and : R26 mouse hearts were isolated by fluorescence-activated cell staining and sequenced by single-cell RNA sequencing.

Results: WT1 (Wilms tumor 1) expression was progressively restricted postnatally and was exclusive to the epicardium by postnatal day 21. Expression of was reduced in the epicardial cells but not in cardiac myocytes in the mice. The mice exhibited premature death, cardiac dysfunction, arrhythmias, myocardial fibro-adipogenesis, and apoptosis. Single-cell RNA sequencing of ≈18 000 EGFP-tagged epicardial-derived cells identified genotype-independent clusters of endothelial cells, fibroblasts, epithelial cells, and a very small cluster of cardiac myocytes, which were confirmed on coimmunofluorescence staining of the myocardial sections. Differentially expressed genes between the paired clusters in the 2 genotypes predicted activation of the inflammatory and mitotic pathways-including the TGFβ1 (transforming growth factor β1) and fibroblast growth factors-in the epicardial-derived fibroblast and epithelial clusters, but predicted their suppression in the endothelial cell cluster. The findings were corroborated by analysis of gene expression in the pooled RNA-sequencing data, which identified predominant dysregulation of genes involved in epithelial-mesenchymal transition, and dysregulation of 146 genes encoding the secreted proteins (secretome), including genes in the TGFβ1 pathway. Activation of the TGFβ1 and its colocalization with fibrosis in the :R26 mouse heart was validated by complementary methods.

Conclusions: Epicardial-derived cardiac fibroblasts and epithelial cells express paracrine factors, including TGFβ1 and fibroblast growth factors, which mediate epithelial-mesenchymal transition, and contribute to the pathogenesis of myocardial fibrosis, apoptosis, arrhythmias, and cardiac dysfunction in a mouse model of ACM. The findings uncover contributions of the epicardial-derived cells to the pathogenesis of ACM.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169643PMC
June 2021

Health-related quality of life among survivors in minority area 2 years after Jiuzhaigou earthquake: A cross-sectional study.

Medicine (Baltimore) 2021 Mar;100(10):e25089

Institute of Hospital Management, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Abstract: To investigate the health-related quality of life (HRQoL) and related factors, the symptoms of posttraumatic stress disorder (PTSD) among earthquake survivors in minority area 2 years after Jiuzhaigou earthquake.Two years after the Jiuzhaigou earthquake, a cross-sectional survey was conducted by a multi-stage sampling approach. HRQoL was measured by the short form 12 (SF-12), PTSD was measured by the PTSD Check List-Civilian Version (PCL-C), and social support was measured by the Multidimensional Scale of Perceived Social Support. Descriptive statistics, t-tests, ANOVA and multiple linear regression analysis were used for data analysis.Of the 561 participants, the mean scores on the physical component summary (PCS) and mental component summary (MCS) were 46.36 ± 12.79 and 55.03 ± 8.73, and 5.73% reported the symptoms of PTSD. Lower PCS and MCS after an earthquake were associated with elderly age, physical illness, and low level of social support (P < .05). Meanwhile, PTSD was significantly associated with MCS.These findings showed that physical disease and psychological symptoms can adversely affect the HRQoL of survivors. Moreover, providing higher social support to survivors should be considered as a way to improve the HRQoL outcomes of survivors.
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http://dx.doi.org/10.1097/MD.0000000000025089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969211PMC
March 2021

The predictive value of minute ventilation versus carbon dioxide production in pulmonary hypertension associated with left heart disease.

Ann Transl Med 2021 Feb;9(4):351

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Background: The aim of the present study was to investigate the role of key cardiopulmonary exercise testing (CPET) parameters in the identification of pre-capillary components in patients with pulmonary hypertension associated with left heart disease (PH-LHD), and to evaluate their correlations with hemodynamic parameters.

Methods: Ninety patients with PH-LHD underwent right-heart catheterization, echocardiography, and CPET. The differences in related indexes between a combined post- and pre-capillary PH (Cpc-PH) group (n=47) and an isolated post-capillary PH (Ipc-PH) group (n=43) were compared. Correlation analysis was performed. Logistic regression and receiver operator characteristic (ROC) analyses were performed to assess the ability of CPET variables to distinguish patients with Cpc-PH from those with Ipc-PH.

Results: The hemodynamics, hyperventilation and right ventricular function of Cpc-pH group were worse than those of Ipc-pH group. The parameters related to minute ventilation versus carbon dioxide production (VE/VCO) played a significant role in the differentiation of Cpc-PH and Ipc-PH, and had a moderate positive correlation with pulmonary vascular resistance (PVR). Univariate and multivariate logistic analyses showed that lowest percentage of VE/VCO in predicted value (VE/VCO%pred) was the single best predictor of Cpc-PH, and the area under ROC curve also confirmed that lowest VE/VCO%pred (≥137%) could serve as a novel diagnostic marker for Cpc-PH. On the basis of this lowest VE/VCO%pred threshold, patients were divided into two groups. Most hemodynamic parameters were worse in patients with a lowest VE/VCO%pred ≥137%.

Conclusions: VE/VCO-related parameters are powerful prognosticators for the presence of pre-capillary components in patients with PH-LHD, especially lowest VE/VCO%pred.
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http://dx.doi.org/10.21037/atm-21-366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944330PMC
February 2021

Microneedle-assisted genome editing: A transdermal strategy of targeting by CRISPR-Cas9 for synergistic therapy of inflammatory skin disorders.

Sci Adv 2021 Mar 10;7(11). Epub 2021 Mar 10.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

We report a dissolvable microneedle (MN) patch that can mediate transdermal codelivery of CRISPR-Cas9-based genome-editing agents and glucocorticoids for the effective treatment of inflammatory skin disorders (ISDs). The MN is loaded with polymer-encapsulated Cas9 ribonucleoprotein (RNP) targeting and dexamethasone (Dex)-containing polymeric nanoparticles. Upon insertion into the skin, the MN can be dissolved quickly to release two types of nanoformulations, which are subsequently internalized by keratinocytes and surrounding immune cells to exert their therapeutic effects in the inflammatory subcutaneous layers. Thus, the MN-enabled transdermal codelivery of Cas9 RNP nanocomplexes and Dex nanoparticles result in the disruption of subcutaneous intracellular NLRP3 inflammasomes, which is demonstrated to be critical to alleviate skin inflammations and contributes to glucocorticoid therapy in mouse models of ISDs, including psoriasis and atopic dermatitis. Our study offers innovative insights into the rational design of transdermal delivery systems and defines an effective therapeutic option for the treatment of ISDs.
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http://dx.doi.org/10.1126/sciadv.abe2888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946375PMC
March 2021

Lin28 Inhibits the Differentiation from Mouse Embryonic Stem Cells to Glial Lineage Cells through Upregulation of Yap1.

Stem Cells Int 2021 22;2021:6674283. Epub 2021 Feb 22.

Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China.

The RNA-binding protein Lin28 regulates neurogliogenesis in mammals, independently of the let-7 microRNA. However, the detailed regulatory mechanism remains obscured. Here, we established Lin28a or Lin28b overexpression mouse embryonic stem cells (ESCs) and found that these cells expressed similar levels of the core pluripotent factors, such as Oct4 and Sox2, and increased Yap1 but decreased lineage-specific markers compared to the control ESCs. Further differentiation of these ESCs to neuronal and glial lineage cells revealed that Lin28a/b overexpression did not affect the expression of neuronal marker III-tubulin, but dramatically inhibited the glial lineage markers, such as Gfap and Mbp. Interestingly, overexpression of Yap1 in mouse ESCs phenocopied Lin28a/b overexpression ESCs by showing defect in glial cell differentiation. Inhibition of Yap1/Tead-mediated transcription with verteporfin partially rescued the differentiation defect of Lin28a/b overexpression ESCs. Mechanistically, we demonstrated that Lin28 can directly bind to mRNA, and the induction of Yap1 by Lin28a in mESCs is independent of Let7. Taken together, our results unravel a novel Lin28-Yap1 regulatory axis during mESC to glial lineage cell differentiation, which may shed light on glial cell generation .
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http://dx.doi.org/10.1155/2021/6674283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920735PMC
February 2021

[Associations between Takeaway Food Nutrients and Nutritional Literacy of Takeaway Platform Practitioners in Chengdu].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Feb;43(1):77-81

Department of Epidemiology and Health Statistics,West China Fourth Hospital and West China, School of Public Health,Sichuan University,Chengdu 610041,China.

Objective To investigate the nutritional literacy levels of the takeaway platform practitioners in Chengdu,the takeaway food nutrients,and the correlation between them.Methods We employed a multi-stage random sampling method to investigate the nutritional literacy levels of 100 takeaway platform restaurants in the main urban area of Chengdu and examined the nutritional components of hot set meals in each restaurant.A questionnaire survey was conducted on the nutritional literacy levels of chefs and food matching staff.The correlations of nutrient energy supply rationality with nutritional literacy level and set meal price were then analyzed.Results The total pass rate of nutrition knowledge of chefs/food matching staff was 61.0%.Only 2.0% of the set meals had reasonable total energy supply.The set meals with reasonable energy supply of available carbohydrate,protein,and fat accounted for 3.0%,62.0%,and 21.0%,and those with over energy supply accounted for 97.0%,26.0%,and 73.0%,respectively.The rest set meals provided insufficient energy.There was a positive correlation between the nutritional literacy level and the rationality of protein energy supply(r=0.414,P=0.003).Conclusions The nutritional literacy levels of chefs/food matching staff of takeaway food restaurants in Chengdu are moderate.The hot set meals on the takeaway platform have the problem of excess energy supply.The nutrition knowledge of chefs/food matching staff cannot effectively satisfy rational nutrition matching.The nutritional literacy levels of chefs/food matching staff showed no significant correlation with the rationality of nutrient energy supply.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12530DOI Listing
February 2021

[Nutritional Knowledge and Skills of Fast-food Takeout Practitioners in Chengdu City].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Feb;43(1):69-76

Department of Epidemiology and Health Statistics,West China School of Public Health and West China, Fourth Hospital,Sichuan University,Chengdu 610041,China.

Objective To investigate the current status of nutritional knowledge and skills of fast-food takeout practitioners in Chengdu City,so as to provide evidence for nutritional literacy education among takeout practitioners.Methods A questionnaire survey was conducted among 832 employees of fast-food takeout restaurants in Chengdu from April to September in 2019 through a multi-stage random sampling strategy.Results The awareness rate of nutritional knowledge of fast-food takeout practitioners in Chengdu was 77.28%,and the correct rates of answers to daily oil intake for adults,daily drinking water for adults and daily salt intake for adults in the Dietary Guidelines for Chinese Residents were respectively 17.43%,22.60% and 25.36%.In addition,the proportion of practitioners with the ability to estimate the recommended intake of food for a meal,the ability to estimate condiments intake and the ability to interpret nutrition labels were 8.77%,8.77% and 15.02%,respectively.The awareness rate of nutritional knowledge was the lowest(71.47%)in the practitioners aged≤25 and the highest(84.53%)in those aged 26-39,and the difference was statistically significant(χ =14.419,P=0.001).High awareness rate of nutritional knowledge was found in the practitioners of Han ethnic group(78.45%)compared with those of ethnic minorities(57.14%)(χ =10.346,P=0.001).Besides,the practitioners with a high degree of education showed high awareness rate of nutritional knowledge( [Formula: see text]=36.514,P<0.001),and the correct rate of chefs(17.86%)was higher than that(12.82%)of food matching staff(χ =4.068,P=0.044).Conclusions The fast-food takeout practitioners in Chengdu generally have good nutritional knowledge while have some knowledge gaps.At the same time,the nutrition-related skills of takeout practitioners are not good.We should focus on strengthening the training of takeout restaurant employees for the Dietary Guidelines for Chinese Residents and nutrition labeling-related knowledge,carry out targeted nutritional knowledge training,and comprehensively strengthen the training of nutrition-related skills.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12622DOI Listing
February 2021
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