Publications by authors named "Jian Wang"

8,927 Publications

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Bone morphogenetic protein 4 inhibits pulmonary fibrosis by modulating cellular senescence and mitophagy in lung fibroblasts.

Eur Respir J 2022 Jul 1. Epub 2022 Jul 1.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China

Accumulation of myofibroblasts is critical to fibrogenesis in idiopathic pulmonary fibrosis (IPF). Senescence and insufficient mitophagy in fibroblasts contribute to their differentiation into myofibroblasts, thereby promoting the development of lung fibrosis. Bone morphogenetic protein 4 (BMP4), a multifunctional growth factor, is essential for the early stage of lung development, however, the role of BMP4 in modulating lung fibrosis remains unknown.This study was to evaluate the role of BMP4 in lung fibrosis using BMP4-haplodeleted mice, BMP4-overexpressed mice, primary lung fibroblasts, and lung samples from patients with IPF.BMP4 expression was down-regulated in IPF lungs and fibroblasts compared to control individuals, negatively correlated with fibrotic genes, and BMP4 decreased with TGF-β1 stimulation in lung fibroblasts in a time- and dose-dependent manner. In mice challenged with bleomycin, BMP4 haploinsufficiency perpetuated activation of lung myofibroblasts and caused accelerated lung function decline, severe fibrosis and mortality. While BMP4 overexpression using AAV9 vectors showed preventative and therapeutic efficacy against lung fibrosis. In vitro, BMP4 attenuated TGF-β1-induced fibroblast-to-myofibroblast differentiation and extracellular matrix (ECM) production by reducing impaired mitophagy and cellular senescence in lung fibroblasts. Whereas Pink1 silencing by shRNA transfection abolished the ability of BMP4 to reverse the TGF-β1-induced myofibroblast differentiation and ECM production, indicating dependence on Pink1-mediated mitophagy. Moreover, the inhibitory effect of BMP4 on fibroblast activation and differentiation was accompanied with an activation of Smad1/5/9 signaling and suppression of TGF-β1-meidtaed Smad2/3 signaling and In conclusion, strategies for enhancing BMP4 signaling may represent an effective treatment for pulmonary fibrosis.
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http://dx.doi.org/10.1183/13993003.02307-2021DOI Listing
July 2022

Comprehensive analysis of transcriptome-wide mA methylome in the lung tissues of mice with acute particulate matter exposure.

Ecotoxicol Environ Saf 2022 Jun 28;241:113810. Epub 2022 Jun 28.

Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200030, China.

Particulate matter (PM) exposure is identified as a critical risk factor for chronic airway diseases, but the biological mechanism of PM-induced lung damage was not fully elucidated. The mA methylation, as the main member of epigenetic modifications, has been found to play an important role in different pulmonary diseases, but its regulatory effect on PM-induced lung damage remains unknown. This study firstly used the methylated RNA immunoprecipitation sequencing (MeRIP-seq) to reveal the mA methylome profiles in the lung tissues of mice with acute PM exposure. Compared with the normal control, a total of 2210 differentially hypermethylated mA peaks within 1879 genes and 1278 differentially hypomethylated mA peaks within 1153 genes were identified in the PM-exposed group. Conjoint analysis of MeRIP-seq and high-throughput sequencing for RNA (RNA-seq) data predicated several potential pathways including MAPK signaling pathway, cell senescence, and cell cycle. Four mA-modified differentially expressed genes (IL-1a, IL-1b, ADAM-8, and HMOX-1) were selected for validation using MeRIP-qPCR. Furthermore, the mA-modified IL-1a promoted PM-induced inflammation via regulating MAPK signaling pathway. These results provide a new insight into the biological mechanism of PM-induced lung damage, and help us to develop new methods to prevent and treat PM-induced adverse health effects.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113810DOI Listing
June 2022

Functional Characterization of UDP-Glycosyltransferases Involved in Anti-viral Lignan Glycosides Biosynthesis in .

Front Plant Sci 2022 14;13:921815. Epub 2022 Jun 14.

School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, China.

is a popular herbal medicine with its noticeable antiviral properties, which are primarily due to its lignan glycosides such as lariciresinol-4--β-D-glucoside and lariciresinol-4,4'-bis--β-D-glucosides (also called clemastanin B). UDP-glucose-dependent glycosyltransferases are the key enzymes involved in the biosynthesis of these antiviral metabolites. In this study, we systematically characterized the UGT72 family gene IiUGT1 and two UGT71B family genes, IiUGT4 and IiUGT71B5a, with similar enzymatic functions. Kinetic analysis showed that IiUGT4 was more efficient than IiUGT1 or IiUGT71B5a for the glycosylation of lariciresinol. Further knock-down and overexpression of these in hairy roots indicates that they play different roles : primarily participates in the biosynthesis of coniferin not pinoresinol diglucoside, and primarily participates in the biosynthesis of pinoresinol diglucoside, while is responsible for the glycosylation of lariciresinol and plays a dominant role in the biosynthesis of lariciresinol glycosides in . Analysis of the molecular docking and site-mutagenesis of IiUGT4 have found that key residues for its catalytic activity are H373, W376, E397, and that F151 could be associated with substrate preference. This study elucidates the biosynthetic route of anti-viral lignan glycosides in , and provides the foundation for the production of anti-viral lignan glycosides synthetic biology under the heterologous model.
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http://dx.doi.org/10.3389/fpls.2022.921815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237620PMC
June 2022

Corrigendum to "Bone marrow mononuclear cells exert long-term neuroprotection in a rat model of ischemic stroke by promoting arteriogenesis and angiogenesis" [Brain Behav. Immun. 34 (2013) 56-66].

Brain Behav Immun 2022 Jun 27;104:213-214. Epub 2022 Jun 27.

Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bbi.2022.04.025DOI Listing
June 2022

Practice Patterns in Endoscopic Treatment for Gastric Varices: a Chinese Survey.

J Dig Dis 2022 Jun 30. Epub 2022 Jun 30.

Department of Gastroenterology, Zhongshan Hospital, Fudan University,Shanghai, China.

Objectives: Gastric varices (GVs), a common complication of liver cirrhosis, often cause serious consequences. However, the management of GVs remains debated. In this study, we explore the practice patterns of Chinese practitioners in GV treatment and discuss whether these patterns conform to the guidelines in China and around the world.

Methods: Between October 2020 and January 2021, an online questionnaire was sent to doctors from different regions in China via WeChat. We analyzed the data on the practice patterns for endoscopic treatment with and without a multidisciplinary discussion team (MDT) for GVs.

Results: A total of 241 questionnaires from 29 provinces were completed by practitioners. Before endoscopic treatment, 100 (41%) of the practitioners arranged computed tomography angiography (CTA) examination. In an endoscopic tissue adhesive (ETA) treatment, 183 (76%) of the practitioners chose to inject tissue adhesive combined with lauromacrogol. Approximately one-fourth of all practitioners did not prescribe drugs to reduce portal pressure. Only 75 (31%) physicians preferred using early transjugular intrahepatic portosystemic shunt (TIPS) for high-risk patients. Compared to those without MDT clinics, practitioners with MDT clinics more often chose early TIPS for high-risk patients (39.0% vs. 18.9%, P = 0.001).

Conclusion: Many practitioners treat GVs differently in China. Practitioners with MDT clinics can better use assistant means, such as HVPG and CTA, to evaluate the risk and efficacy. We need to design further clinical studies and establish more detailed guidelines to standardize clinical practice for GVs. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1751-2980.13108DOI Listing
June 2022

The De Winter-like electrocardiogram pattern associated with multi-vessel disease.

Ann Noninvasive Electrocardiol 2022 Jun 30:e12984. Epub 2022 Jun 30.

Department of Cardiology, Binzhou Medical University Hospital, Binzhou City, China.

Background: The de Winter ECG pattern was described by upsloping ST-segment depression in leads V1-V6, tall and symmetrical T waves in precordial leads. The ECG pattern is regarded to be associated with occlusion of the left anterior descending (LAD) artery.

Methods: One patient with de Winter ECG pattern was included. The 12-lead ECG of patients with chest pain showed upsloping ST-segment depression up to 3 mm at the J point in leads V2-V6; tall symmetrical T waves in leads V2-V4; 1mm J point elevation in lead aVR; ST-segment depression 1mm in I, aVL leads and inverted T waves in the inferior leads. The ECG was showed the de Winter pattern.

Results: The ECG was showed the de Winter pattern. CAG was performed, which showed the normal left main; 60%-80% LAD stenosis; 50%-60% ostial right coronary artery(RCA) stenosis; and 90% stenosis of the vessel at middle segment. Both proximal and middle RCA vascular lesions were dilated and successfully inserted with drug-eluting stents, respectively.

Conclusion: Our case the ECG was showed horizontal ST depression with tall T waves in leads V2-V4 (maximal ST depression in lead V4) while only ST depression in leads V5-V6, which may result from multivessel disease.
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http://dx.doi.org/10.1111/anec.12984DOI Listing
June 2022

Association Between Sleep Duration and Parkinson's Disease Varied Across Related Orphan Receptor A rs2028122 Genotypes.

Front Neurosci 2022 13;16:902895. Epub 2022 Jun 13.

Shenzhen Mental Health Centre, Shenzhen Kangning Hospital, Shenzhen, China.

Background: The purpose of the study was to examine the association of long and short sleep duration with risk of Parkinson's disease (PD) across RORA rs2028122 genotypes.

Methods: In the present prospective study with a large sized UK Biobank cohort, we performed multivariate logistic regression analyses, generalized additive model, interaction terms, stratification analysis, and mediation analysis to evaluate the association of long and short sleep duration with risk of PD across RORA rs2028122 genotypes.

Results: The GG genotype [1.16 (1.01, 1.33)], a short sleep duration [1.23 (1.10, 1.37)], and a long sleep duration [1.19 (1.03, 1.37)] were identified as the independent risk factors for PD. Sleep duration exhibited a curvilinear U-shaped correlation with the risk of PD; first, the risk of PD gradually decreased as the length of sleep increase, but then, the risk began to increase as the length of sleep increase. Among habitual long sleepers, AG carriers had a higher risk of PD compared with AA carriers [1.67 (1.09, 2.55)]. Among AG carriers, both habitual short [1.28 (1.09, 1.50)] and long [1.38 (1.13, 1.69)] sleepers increased the risk of PD compared with habitual normal sleepers. Among GG carriers, habitual short sleepers have a higher risk of PD [1.26 (1.06, 1.50)] compared with habitual normal sleepers. A mediation model suggested that the rs2028122 genotype partially mediated the causal pathway of sleep duration leading to the development of PD on a positive effect.

Conclusion: Our study demonstrated that the association between sleep duration and PD risk varied across different RORA rs2028122 genotypes. Our findings could help individuals to identify their potential risk profile and take timely actions to prevent the PD.
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http://dx.doi.org/10.3389/fnins.2022.902895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235404PMC
June 2022

Platinum(II)-Metallaclip-Based Theranostics for Cell Imaging and Synergetic Chemotherapy-Photodynamic Therapy.

Inorg Chem 2022 Jun 29. Epub 2022 Jun 29.

School of Chemistry and Chemical Engineering, Nantong University, Nantong, Jiangsu 226019, P. R. China.

Supramolecular coordination complexes formed by coordination-induced assembly not only avoid the loss of activity of precursors but also provide an efficient way for controlled release, which can be further used in various fields of biology such as drug delivery, cell imaging, and tumor treatment. In this work, a Pt metallaclip () was prepared from 4-[4-(1,2,2-triphenylvinyl)phenyl]pyridine (), 5,10,15-triphenyl-20-(pyridin-4-yl)porphyrin (), , and glycol-chain-modified isophthalic acid () in an acetone/water mixture through the "coordination-driven self-assembly" method. P and H NMR spectroscopy and high-resolution mass spectrometry were used to characterize the obtained metallaclip . can self-assemble into fluorescent nanostructures in aqueous solution because of the tetraphenylethylene unit and its amphiphilic nature. Importantly, the fluorescent nanoparticles not only can be employed for cell imaging but also can generate singlet oxygen (O) under 660 nm laser irradiation and the release of drug in the tumor issue for cancer therapy. The work may provide a new way for scientists to construct functional biomaterials with multiple applications via molecular self-assembly.
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http://dx.doi.org/10.1021/acs.inorgchem.2c01206DOI Listing
June 2022

The autotetraploid potato genome provides insights into highly heterozygous species.

Plant Biotechnol J 2022 Jun 29. Epub 2022 Jun 29.

Academy of Agriculture and Forestry Sciences, Qinghai University, Xining, China.

Potato (Solanum tuberosum L.) originated in the Andes and evolved its vegetative propagation strategy through short day-dependent tuber development. Herein, we present a high-quality, chromosome-scale reference genome sequence of a tetraploid potato cultivar. The total length of this genome assembly was 2.67 Gb, with scaffold N50 and contig N50 sizes of 46.24 and 2.19 Mb, respectively. In total, 1.69 Gb repetitive sequences were obtained through de novo annotation, and long terminal repeats were the main transposable elements. A total of 126,070 protein-coding genes were annotated, of which 125,077 (99.21%) were located on chromosomes. The 48 chromosomes were classified into four haplotypes. We annotated 31,506 homologous genes, including 5,913 (18.77%) genes with four homologs, 11,103 (35.24%) with three homologs, 12,177 (38.65%) with two homologs, and 2,313 (7.34%) with one homolog. MLH3, MSH6/7 and RFC3, which are the genes involved in the mismatch repair pathway, were found to be significantly expanded in the tetraploid potato genome relative to the diploid potato genome. Genome-wide association analysis revealed that cytochrome P450, flavonoid synthesis, chalcone enzyme, glycosyl hydrolase and glycosyl transferase genes were significantly correlated with the flesh colors of potato tuber in 150 tetraploid potatoes. This study provides valuable insights into the highly heterozygous autotetraploid potato genome and may facilitate the development of tools for potato cultivar breeding and further studies on autotetraploid crops.
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http://dx.doi.org/10.1111/pbi.13883DOI Listing
June 2022

Interactions between the Autonomic Nervous System and the Immune System after Stroke.

Compr Physiol 2022 Jun 29;12(3):3665-3704. Epub 2022 Jun 29.

Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China.

Acute stroke is one of the leading causes of morbidity and mortality worldwide. Stroke-induced immune-inflammatory response occurs in the perilesion areas and the periphery. Although stroke-induced immunosuppression may alleviate brain injury, it hinders brain repair as the immune-inflammatory response plays a bidirectional role after acute stroke. Furthermore, suppression of the systemic immune-inflammatory response increases the risk of life-threatening systemic bacterial infections after acute stroke. Therefore, it is essential to explore the mechanisms that underlie the stroke-induced immune-inflammatory response. Autonomic nervous system (ANS) activation is critical for regulating the local and systemic immune-inflammatory responses and may influence the prognosis of acute stroke. We review the changes in the sympathetic and parasympathetic nervous systems and their influence on the immune-inflammatory response after stroke. Importantly, this article summarizes the mechanisms on how ANS regulates the immune-inflammatory response through neurotransmitters and their receptors in immunocytes and immune organs after stroke. To facilitate translational research, we also discuss the promising therapeutic approaches modulating the activation of the ANS or the immune-inflammatory response to promote neurologic recovery after stroke. © 2022 American Physiological Society. Compr Physiol 12:3665-3704, 2022.
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http://dx.doi.org/10.1002/cphy.c210047DOI Listing
June 2022

Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes.

Cell Discov 2022 Jun 28;8(1):60. Epub 2022 Jun 28.

Department of Biochemistry and Department of Orthopaedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

As a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. A long and unstructured C-terminal region of IRS-1 recruits downstream effectors for promoting insulin/IGF signals. However, the underlying molecular basis for this remains elusive. Here, we found that the C-terminus of IRS-1 undergoes liquid-liquid phase separation (LLPS). Both electrostatic and hydrophobic interactions were seen to drive IRS-1 LLPS. Self-association of IRS-1, which was mainly mediated by the 301-600 region, drives IRS-1 LLPS to form insulin/IGF-1 signalosomes. Moreover, tyrosine residues of YXXM motifs, which recruit downstream effectors, also contributed to IRS-1 self-association and LLPS. Impairment of IRS-1 LLPS attenuated its positive effects on insulin/IGF-1 signaling. The metabolic disease-associated G972R mutation impaired the self-association and LLPS of IRS-1. Our findings delineate a mechanism in which LLPS of IRS-1-mediated signalosomes serves as an organizing center for insulin/IGF-1 signaling and implicate the role of aberrant IRS-1 LLPS in metabolic diseases.
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http://dx.doi.org/10.1038/s41421-022-00426-xDOI Listing
June 2022

An implant-supported overdenture for a mandibular defect after tumor resection guided by 3-dimensional finite element analysis: A clinical report.

J Prosthet Dent 2022 Jun 25. Epub 2022 Jun 25.

Associate Professor, State Key Laboratory of Oral Diseases, Department of Prosthodontics, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, PR China. Electronic address:

This clinical report describes the rehabilitation of a mandibular defect after tumor resection with an implant-supported overdenture and the attachment selection as guided by 3-dimensional finite element analysis. Autologous bone grafting was declined by the patient who demanded the restoration of lateral appearance and mastication function. Three implants were placed based on the condition of the bone, and a satisfactory definitive prosthesis was provided that corresponded with the results of the finite element analysis.
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http://dx.doi.org/10.1016/j.prosdent.2022.04.031DOI Listing
June 2022

Comparing the Clinical Outcomes Observed with Rivaroxaban Versus Warfarin for the Management of Obese Patients with Non-valvular Atrial Fibrillation: a Systematic Review and Meta-analysis.

Cardiovasc Drugs Ther 2022 Jun 28. Epub 2022 Jun 28.

Department of Cardiovascular Medicine, The Fourth Hospital of Changsha, Changsha, 410000, Hunan, People's Republic of China.

Background: Atrial fibrillation (AF) is an irregular heart rhythm which is becoming more and more common in this new era. Obesity is a risk factor for cardiovascular events, and obese patients are more at risk for stroke. The Framingham Heart Study demonstrated an increase in the developmental risk of AF by 4% for every unit (kg/m) increase in body mass index (BMI). An anticoagulant is often required for the management of such patients. In this analysis, we aimed to systematically compare the clinical outcomes which were associated with rivaroxaban versus warfarin for the treatment of obese patients with non-valvular AF.

Methods: PubMed, EMBASE, Web of Science, http://www.

Clinicaltrials: gov , Google Scholar, and Cochrane Central were the searched databases. Clinical outcomes including stroke, systemic embolism, and major bleeding were the endpoints. In this study, dichotomous data were analyzed by the RevMan software version 5.4. Risk ratio (RR) with 95% confidence interval (CI) was used for result interpretation.

Results: Ten studies consisting of a total number of 168,081 obese participants were included whereby 81,332 participants were treated with rivaroxaban and 86,749 participants were treated with warfarin. The risks of ischemic (RR: 0.79, 95% CI: 0.74-0.84; P = 0.00001) and hemorrhagic stroke (RR: 0.61, 95% CI: 0.48-0.76; P = 0.0001) as well as systemic embolism (RR: 0.73, 95% CI: 0.62-0.87; P = 0.0004) were significantly lower with rivaroxaban compared to warfarin for the management of these obese patients with non-valvular AF. Rivaroxaban was also associated with a significantly lower risk of major bleeding (RR: 0.75, 95% CI: 0.65-0.87; P = 0.0001).

Conclusion: Based on this analysis, rivaroxaban seemed to be a better option in comparison to warfarin, due to its association with significantly lower risks of stroke and bleeding outcomes in obese patients with non-valvular AF. However, this hypothesis should further be confirmed in larger clinical trials.
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http://dx.doi.org/10.1007/s10557-022-07361-9DOI Listing
June 2022

Light-Addressable Electrochemical Sensors toward Spatially Resolved Biosensing and Imaging Applications.

ACS Sens 2022 Jun 28. Epub 2022 Jun 28.

Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.

The light-addressable electrochemical sensor (LAES) is a recently emerged bioanalysis technique combining electrochemistry with the photoelectric effect in a semiconductor. In an LAES, a semiconductor substrate is illuminated locally to generate charge carriers in a well-defined area, thereby confining the electrochemical process to a target site. Benefiting from the unique light addressability, an LAES can not only detect multiple analytes in parallel within a single sensor plate but also act as a bio(chemical) imaging sensor to visualize the two-dimensional distribution of specific analytes. An LAES usually has three working modes: a potentiometric mode using light-addressable potentiometric sensors (LAPS) and an impedance mode using scanning photoinduced impedance microscopy (SPIM), while an amperometric mode refers to light-addressable electrochemistry (LAE) and photoelectrochemical (PEC) sensing. In this review, we describe the detection principles of each mode of LAESs and the concept of light addressability. In addition, we highlight the recent progress and advance of LAESs in spatial resolution, sensor system design, multiplexed detection, and bio(chemical) imaging applications. An outlook on current research challenges and future prospects is also presented.
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http://dx.doi.org/10.1021/acssensors.2c00940DOI Listing
June 2022

Triphenylamine-containing imine-linked porous organic network for luminescent detection and adsorption of Cr(VI) in water.

Dalton Trans 2022 Jun 28. Epub 2022 Jun 28.

School of Chemistry and Materials Science & Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou 221116, China.

In this study, an imine-linked luminescent porous organic network (PON) has been successfully synthesized by the Schiff-base condensation reaction between 1,2-diphenylethylenediamine and tris(4-formylphenyl)amine. It exhibits strong fluorescence in an aqueous dispersion and can be applied as a luminescent probe for Cr(VI) (CrO and CrO) with high selectivity and sensitivity (LOD for CrO and CrO were below 0.35 μM and 0.4 μM, respectively) in a turn-off manner. The possible luminescence sensing mechanism and the adsorption capacity of Cr(VI) are also discussed in detail.
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http://dx.doi.org/10.1039/d2dt01046aDOI Listing
June 2022

The latent period of coronavirus disease 2019 with SARS-CoV-2 B.1.617.2 Delta variant of concern in the postvaccination era.

Immun Inflamm Dis 2022 Jul;10(7):e664

Department of Acute Infectious Disease Control and Prevention, Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China.

Introduction: Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have resulted in new challenges for epidemic prevention and control worldwide. However, little is known about the latent period of coronavirus disease by the SARS-CoV-2 Delta variant of concern (VOC) in the postvaccination era.

Methods: The epidemiology and clinical data of cases with confirmed SARS-CoV-2 Delta VOC infection were retrospective collected. Dates of the first positive PCR test were collected to estimate the distribution of latent period.

Results: Of the 40 patients, 16 were male (40%). The median age of patients was 47.5 years. The median latent period of patients was 6.0 days (interquartile range [IQR], 4.0-9.0 days) and the longest latent period was 13.0 days after exposure. The latent periods were longer in male patients compared to female patients (median, 8.5 days vs. 5.0 days, p = .041). The median latent period was comparable among fully vaccinated cases (6.5 days), no vaccinated cases (7.5 days), and partially vaccinated cases (5.5 days).

Conclusions: The median latent period of SARS-CoV-2 Delta VOC infection was 6.0 days. The latent period between vaccinated and non-vaccinated patients was not significantly different. The 14-day quarantine program is sufficient to prevent the transmission of COVID-19 by Delta VOC in the postvaccination era.
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http://dx.doi.org/10.1002/iid3.664DOI Listing
July 2022

Clinical Presentation and Outcomes of Acute Disseminated Encephalomyelitis in Adults Worldwide: Systematic Review and Meta-Analysis.

Front Immunol 2022 9;13:870867. Epub 2022 Jun 9.

Department of Neurology, the Second People's Hospital of Chengdu, Chengdu, China.

Background: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disorder that is often misdiagnosed. To improve early diagnosis, we performed a systematic review and meta-analysis of clinical features, outcomes for ADEM in adults.

Methods: The PubMed, Embase, Web of Science and Cochrane Library databases were searched for studies reporting the clinical features of adults with ADEM between January 1990 and May 2021. A random-effects meta-analysis model was used to pool data on clinical features and functional outcomes.

Results: Twelve studies examining 437 adults with ADEM met the inclusion criteria. Overall, the clinical features and diagnostic findings observed in more than two-thirds of the patients were white matter lesions [87.1%, 95% confidence interval (CI)=75-95.6], polyfocal onset (80.5%, 95% CI=50.5-98.9) and pyramidal signs (68.7%, 95% CI =40.0-91.9). The mortality rate was 7.8% (95% CI = 3.3-13.5), and the risk of residual deficits was 47.5% (95% CI = 31.8-63.4).

Conclusions: Adults with ADEM had worse outcomes than children. Clinicians should maintain high clinical suspicion for patients presenting with certain clinical features and diagnostic findings.
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http://dx.doi.org/10.3389/fimmu.2022.870867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218070PMC
June 2022

Mechanistic analysis for the origin of diverse diterpenes in .

Acta Pharm Sin B 2022 Jun 22;12(6):2923-2933. Epub 2022 Feb 22.

Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.

is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in .
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http://dx.doi.org/10.1016/j.apsb.2022.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214345PMC
June 2022

Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells.

Acta Pharm Sin B 2022 Jun 4;12(6):2905-2922. Epub 2022 Mar 4.

Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound exhibited potent antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound mitigated TGF-1-induced epithelial-mesenchymal transition (EMT).
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http://dx.doi.org/10.1016/j.apsb.2022.02.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214071PMC
June 2022

Surveillance and response systems driving malaria elimination in the mountain areas of Hainan Province.

Adv Parasitol 2022 18;116:69-113. Epub 2022 Mar 18.

Hainan Provincial Center for Disease Control & Prevention, Haikou, Hainan, PR China. Electronic address:

Hainan Province is in a tropical area of China and previously experienced serious P. falciparum and P. vivax malaria epidemics. After nearly 70 consecutive years of malaria prevention and control, malaria in Hainan has gradually been eliminated. To achieve the elimination of malaria, Hainan enacted six stages: investigative research and pilot prevention and control, large-scale antimalaria measures, adjustment of strategies for prevention and control, joint prevention and control measures, global funding of routine malaria control, and malaria elimination. Different strategies for malaria control were adopted at different stages. Malaria was most prevalent in the mountainous areas of central and southern Hainan, which contain a high-risk population (the forest goers) and two highly effective malaria vectors (An. dirus and An. minimus). Forest goers have been a high-risk population for malaria in Hainan since their identification in the 1990s. This paper summarizes malaria monitoring in forest goers and the response of forest goers to malaria control and elimination, distilling specific malaria control and elimination measures via case studies in Hainan Province. Two case studies in the malaria control stage demonstrated different measures for outbreaks and sporadic cases in forest goers. In view of the malaria outbreak in Sanya during the elimination stage, three-layered strategies (TLSs) were implemented to control outbreaks and improve control measures. Moreover, this paper also illustrates specific management measures to prevent malaria retransmission from sporadic imported malaria cases during the elimination phase. Hainan finally eliminated malaria in 2020. However, the risk of malaria retransmission is still high due to the prevalence of effective malaria vectors in Hainan, and forest goers are still a high-risk population for malaria retransmission.
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http://dx.doi.org/10.1016/bs.apar.2022.01.001DOI Listing
June 2022

Non-typhoidal salmonella invasive infections in China.

Lancet Infect Dis 2022 Jul;22(7):939

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(22)00347-4DOI Listing
July 2022

Adjuvant-Protein Conjugate Vaccine with Built-In TLR7 Agonist on S1 Induces Potent Immunity against SARS-CoV-2 and Variants of Concern.

ACS Infect Dis 2022 Jun 24. Epub 2022 Jun 24.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, College of Chemistry, Central China Normal University, Wuhan 430079, China.

With the global pandemic of the new coronavirus disease (COVID-19), a safe, effective, and affordable mass-produced vaccine remains the current focus of research. Herein, we designed an adjuvant-protein conjugate vaccine candidate, in which the TLR7 agonist (TLR7a) was conjugated to S1 subunit of SARS-CoV-2 spike protein, and systematically compared the effect of different numbers of built-in TLR7a on the immune activity for the first time. As the number of built-in TLR7a increased, a bell-shaped reaction was observed in three TLR7a-S1 conjugates, with TLR7a(10)-S1 (with around 10 built-in adjuvant molecules on one S1 protein) eliciting a more potent immune response than TLR7a(2)-S1 and TLR7a(18)-S1. This adjuvant-protein conjugate strategy allows the built-in adjuvant to provide cluster effects and prevents systemic toxicity and facilitates the co-delivery of adjuvant and antigen. Vaccination of mice with TLR7a(10)-S1 triggered a potent humoral and cellular immunity and a balanced Th1/Th2 immune response. Meanwhile, the vaccine induces effective neutralizing antibodies against SARS-CoV-2 and all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). It is expected that the adjuvant-protein conjugate strategy has great potential to construct a potent recombinant protein vaccine candidate against various types of diseases.
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http://dx.doi.org/10.1021/acsinfecdis.2c00259DOI Listing
June 2022

Clinical characteristics and survival of children with hypertrophic cardiomyopathy in China: A multicentre retrospective cohort study.

EClinicalMedicine 2022 Jul 27;49:101466. Epub 2022 May 27.

Department of Cardiology, Shanghai Children's Medical Centre, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

Background: Few data on paediatric hypertrophic cardiomyopathy (HCM) are available in developing countries. A multicentre, retrospective, cohort study was conducted to profile the clinical characteristics and survival of children with HCM in China.

Methods: We collected longitudinal data on children with HCM aged 0-18 years at three participating institutions between January 1, 2010 and December 31, 2019. Patients were identified by searching for the diagnosis using ICD-10 codes from the electronic medical records database. HCM was diagnosed morphologically with echocardiography or cardiovascular magnetic resonance imaging. The exclusion criteria were secondary aetiologies of myocardial hypertrophy. The primary outcomes were all-cause death or heart transplantation. The Kaplan-Meier method was used to estimate the survival rate of different groups.

Findings: A total of 564 children were recruited, with a median age at diagnosis of 1.0 year (interquartile range, IQR: 0.4-8.0 years), followed for a median of 2.6 years (1977 patient-years, IQR:0.5, 5.9 years). The underlying aetiology was sarcomeric (382, 67.7%), inborn errors of metabolism (IEMs) (108, 19.2%), and RASopathies (74, 13.1%). A total of 149 patients (26.4%) died and no patients underwent heart transplantation during follow-up. The survival probability was 71.1% (95% confidence interval [CI], 66.3%-75.3%) at 5 years. Patients with IEMs or those diagnosed during infancy had the poorest outcomes, with an estimated 5-year survival rate of 16.9% (95% CI, 7.7%-29.1%) and 56.0% (95% CI, 48.8%-62.5%), respectively. Heart failure was the leading cause of death in the cohort (90/149, 60.4%), while sudden cardiac death was the leading cause in patients with sarcomeric HCM (32/66, 48.5%).

Interpretation: There is a high proportion of patients with IEM and a low proportion of patients with neuromuscular disease in children with HCM in China. Overall, mortality remains high in China, especially in patients with IEMs and those diagnosed during infancy.

Funding: National Natural Science Fund of China (81770380, 81974029), China Project of Shanghai Municipal Science and Technology Commission (20MC1920400, 21Y31900301).
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http://dx.doi.org/10.1016/j.eclinm.2022.101466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157015PMC
July 2022

DC Surface Flashover Characteristics of Polyimide Containing Polyhedral Oligomeric Silsesquioxane (POSS) in the Main Chains under Vacuum.

Polymers (Basel) 2022 Jun 16;14(12). Epub 2022 Jun 16.

Beijing Institute of Control Engineering, Beijing 102206, China.

Polyimide, which is widely used to insulate power equipment operating in a vacuum environment, is prone to insulation failure due to surface flashover. Using POSS to modify it is an effective solution. This paper focuses on the study of DC surface flashover characteristics in vacuum of POSS/polyimide composite film, by introducing 1%, 3%, 5% equivalent mole content of POSS into polyimide, and conducting a surface flashover characteristics test in vacuum together with pure polyimide. The physical and chemical properties of the composite films were tested utilizing Fourier transform infrared spectroscopy and ultraviolet-visible spectroscopy. Combined with resistivity, SEM, and other test techniques, the influence mechanism of POSS molecular modification on DC surface flashover characteristics of polyimide films in vacuum was initially revealed. The results showed that after the introduction of POSS, the overall functional group structure of polyimide remained unchanged, the intermolecular charge transfer complexation was inhibited, and the transmittance of the film increased. The thermal conductivity and thermogravimetric temperature of the film are improved to a certain extent, and the mechanical properties are slightly decreased. With the increase of the introduced POSS content, the dielectric strength of the composite film is also enhanced. The surface flashover voltage of the composite film with a POSS content of 5% is 17.5 kV in vacuum, which is 30.5% higher than that of the pure film. Further analysis shows that the introduction of POSS will reduce the resistivity of the composite film, accelerate the dissipation of surface charges, and increase the flashover voltage. In addition, POSS forms a uniformly distributed Si-O-Si cage-like structure through molecular modification. When the surface of the film is damaged, SiOx inorganic flocculent particles are generated, which can not only scatter electrons, but also shallow the depth of trap energy level and accelerate the dissipation rate of surface charge, thus increasing the flashover voltage.
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http://dx.doi.org/10.3390/polym14122453DOI Listing
June 2022

Investigation of the Specification Degradation Mechanism of CMOS Power Amplifier under Thermal Shock Test.

Micromachines (Basel) 2022 May 24;13(6). Epub 2022 May 24.

School of Microelectronics, Tianjin University, Tianjin 300072, China.

To investigate the critical specifications of a power amplifier (PA) under rapidly changing temperature conditions, we fabricated and tested a 0.3-1.1 GHz complementary metal-oxide-semiconductor (CMOS) PA under thermal shock tests. The results show that high- and low-temperature shocks can accelerate the degradation of critical specifications of PAs and that the critical specifications of PAs degrade with the increasing number of shocks. The main reason for the degradation of critical specifications of PAs with increasing thermal shock tests is the mismatch of thermal expansion coefficients of printed circuit boards (PCB) with FR-4 as a substrate. The results of this paper can provide a reference for the development of temperature-robust PAs design guidelines for the implementation of temperature-robust PAs using low-cost silicon technology.
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http://dx.doi.org/10.3390/mi13060815DOI Listing
May 2022

Study of the Reliability of Field Test Methods for Physical Fitness in Children Aged 2-3 Years.

Int J Environ Res Public Health 2022 Jun 20;19(12). Epub 2022 Jun 20.

School of Public Health, Fudan University, Shanghai 200032, China.

Physical fitness measures overall physical health. It is the ability of the body to work effectively and stay healthy during leisure and emergencies. Given the progressive integration of 2-3-year-olds into preschool, physical fitness testing of these children has become increasingly important. We aimed to develop and test the reliability of an appropriate field test method for physical fitness in 2-3-year-olds children. One hundred and three children (44 boys and 59 girls) volunteered for this study. Their height and weight were tested, and the same tester conducted the test twice for handgrip strength, 3 m balance walking, stair climbing, 5 m run, and kicking a ball at one-minute intervals. Pearson correlation coefficient and intraclass correlation coefficient (ICC) were used for reliability testing. The reliability of this field test method for physical fitness was high in the repetitive tests of Chinese 2-3-year-olds for the four items of handgrip strength, 3 m balance walking, stair climbing and 5 m run, and the reliability was moderate for the kicking the ball item. This study indicates that these field-based physical fitness test methods have good reliability and are simple, feasible, safe, and easy to be accepted and understood by 2-3-year-old children; thus, it may be used as a reference for professionals in China and abroad.
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http://dx.doi.org/10.3390/ijerph19127522DOI Listing
June 2022

Effect of miR-101 on the Proliferation and Apoptosis of Goat Hair Follicle Stem Cells.

Genes (Basel) 2022 Jun 9;13(6). Epub 2022 Jun 9.

Key Laboratory for Animal Genetics & Molecular Breeding of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.

The Yangtze River Delta white goat is a rare goat species capable of producing high-quality brush hair. Dual specificity protein phosphatase 1 () may play a role in the formation of high-quality brush hair, as evidenced by our previous research. We investigated the potential mechanisms that regulate the proliferation and apoptosis of goat hair follicle stem cells. We particularly focused on the relationship between and miR-101, which directly targets predicted and screened through bioinformatics websites. Then, fluorescence assays, flow cytometry, RT-qPCR, and Western blotting were used to investigate the effects of miR-101 on the proliferation and apoptosis of hair follicle stem cells. We found that miR-101 overexpression significantly decreased ( < 0.01) apoptosis and promoted the proliferation of hair follicle stem cells. Furthermore, the overexpression of miR-101 increased ( < 0.05) the mRNA and protein expression levels of the proliferation-related gene () and anti-apoptotic gene (), and it decreased ( < 0.05) the mRNA and protein expression levels of the apoptotic gene (). In conclusion, miR-101 can promote the proliferation of and inhibit the apoptosis of hair follicle stem cells by targeting , which provides a theoretical basis for further elucidating the molecular mechanism that regulates the production of high-quality brush hair of Yangtze River Delta white goats.
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http://dx.doi.org/10.3390/genes13061035DOI Listing
June 2022

Development of a Fully Automated Graf Standard Plane and Angle Evaluation Method for Infant Hip Ultrasound Scans.

Diagnostics (Basel) 2022 Jun 9;12(6). Epub 2022 Jun 9.

Shenzhen Mindray Bio-Medical Electronics Co., Ltd., Shenzhen 518057, China.

Background: Graf's method is currently the most commonly used ultrasound-based technique for the diagnosis of developmental dysplasia of the hip (DDH). However, the efficiency and accuracy of diagnosis are highly affected by the sonographers' qualification and the time and effort expended, which has a significant intra- and inter-observer variability.

Methods: Aiming to minimize the manual intervention in the diagnosis process, we developed a deep learning-based computer-aided framework for the DDH diagnosis, which can perform fully automated standard plane detection and angle measurement for Graf type I and type II hips. The proposed framework is composed of three modules: an anatomical structure detection module, a standard plane scoring module, and an angle measurement module. This framework can be applied to two common clinical scenarios. The first is the static mode, measurement and classification are performed directly based on the given standard plane. The second is the dynamic mode, where a standard plane from ultrasound video is first determined, and measurement and classification are then completed. To the best of our knowledge, our proposed framework is the first CAD method that can automatically perform the entire measurement process of Graf's method.

Results: In our experiments, 1051 US images and 289 US videos of Graf type I and type II hips were used to evaluate the performance of the proposed framework. In static mode, the mean absolute error of α, β angles are 1.71° and 2.40°, and the classification accuracy is 94.71%. In dynamic mode, the mean absolute error of α, β angles are 1.97° and 2.53°, the classification accuracy is 89.51%, and the running speed is 31 fps.

Conclusions: Experimental results demonstrate that our fully automated framework can accurately perform standard plane detection and angle measurement of an infant's hip at a fast speed, showing great potential for clinical application.
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http://dx.doi.org/10.3390/diagnostics12061423DOI Listing
June 2022

Formation of lysozyme-caseinate heteroprotein complexes for encapsulation of lysozyme by spray-drying: Effect of mass ratio and temperature.

Int J Biol Macromol 2022 Jun 21;215:312-320. Epub 2022 Jun 21.

Univ. Lyon, University Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, 43 Bd 11 Novembre 1918, 69622 Villeurbanne, France. Electronic address:

The formation of heteroprotein complexes obtained by the interactions between sodium caseinate (CAS) and lysozyme (LYS) at pH 7 was investigated by using turbidimetric analysis, particle size distribution, and zeta potential at different CAS/LYS ratios. Moreover, isothermal titration calorimetry (ITC) was used to determine the type and magnitude of the energies involved in the CAS/LYS complexation process and evaluated the thermodynamic behavior of their complexation. Results revealed that the structure of CAS/LYS complexes drastically changed when CAS/LYS ratio increased to 1.0 and the structuring stages were characterized by exothermic signals and were controlled by favorable enthalpy changes due to electrostatic interactions between both proteins. In addition, the interaction between two proteins was temperature-dependent and mainly entropy-driven, which was verified by molecular dynamics (MD) simulations, and the hydrophobic interactions and hydrogen bonding were shown to play an important role in CAS/LYS interactions. Furthermore, CAS/LYS complexes showed minimum LYS enzymatic activity at CAS/LYS ratio 1.0. Though spray-drying of CAS/LYS complexes with ratio 1.0, the LYS activity in reconstituted solution was recovered >80 % of initial activity after calcium chloride addition. The present study provides useful information about CAS/LYS complexation and binding processes, which could facilitate their application in antimicrobial edible food packaging.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.06.123DOI Listing
June 2022

Modeling and Structural Optimization of MSF-RO Desalination System.

Membranes (Basel) 2022 May 24;12(6). Epub 2022 May 24.

School of Automation, Hangzhou Dianzi University, Hangzhou 310018, China.

Based on the mathematical modeling and operational optimization studies of reverse osmosis (RO) and multistage flash (MSF) desalination, the structural optimization of the hybrid process was specially studied in this work with the consideration of reducing comprehensive expenses under given operational conditions. Firstly, according to the process mechanism and flowchart of the RO and MSF seawater desalination technologies, seven hybrid structures with different feed conditions were designed, and their connection equations were established for numerical calculation. Then, in order to evaluate the economic performance of the hybrid systems with different structures, the hourly average operational cost equations of RO and MSF processes were established and formulated as the comprehensive evaluation indicators. Next, with a given water production requirement, simulation calculations of the hybrid system with seven different structures were performed. The results show that the hybrid system with the fourth structure has the lowest operational cost of 4.6834 CNY/m, and at the same time it has the lowest blowdown. However, if we take GOR or production water temperature as the target, the optimal structure of the hybrid system is the fifth or the seventh option. The obtained results are helpful in structural optimization of the hybrid system with aspects of operational cost reduction, maximum GOR, or minimizing the wastewater discharge.
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http://dx.doi.org/10.3390/membranes12060545DOI Listing
May 2022
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