The digital economy and the green and high-quality development of the industry-a study on the mechanism of action and regional heterogeneity.

Consistently rising carbon emissions in the global economy make it more challenging to meet the goals of the Paris climate agreement. Knowing what factors play a role is essential to help shape strategies to reduce carbon emissions. While there is a wealth of material on how GDP expansion correlates with increases in carbon emissions, little is known about how democracy and renewable energy could improve environmental conditions in developing nations. The purpose of this article was to use fair data to assess the effect of renewable energy and green technology advances on carbon neutrality in 23 provinces across China from 2005 to 2020. The research used the dynamic ordinary least square, the fully modified ordinary least square, and the two-step GMM to determine that digitalization, industrial development, and health expenditures result in lower carbon emissions. Urbanization, tourism, and per capita income in certain Chinese provinces also drove carbon emissions. The study also showed that the impact of these factors on carbon emissions varies depending on the amount of economic growth. Environmental pollution is reduced due to the digitalization of tourist and healthcare costs, industrial development, and urbanization. According to the study's findings, we advise these nations to seek economic growth and invest in health care and renewable energy initiatives.

Comparison of catalytic functions and expression patterns of two pinene synthases from Wurfbainia villosa / 中国中药杂志

Wurfbainia villosa fruit is rich in volatile terpenoids, among which pinene is one of the main components and has anti-inflammatory, antibacterial, anti-tumor, and other pharmacological activities. This research group found that W. villosa fruits were rich in α-pinene by GC-MS, and terpene synthase(WvTPS63, formerly known as AvTPS1) with β-pinene as the main product was cloned and identified, but α-pinene synthase had not been identified. In this study, based on the genome data of W. villosa, we screened and found WvTPS66 with highly similar sequences to WvTPS63, identified enzyme functions of WvTPS66 in vitro, and performed a comparative analysis of sequence, catalytic function, expression pattern, and promoter with WvTPS63. Multiple sequence alignment showed that the amino acid sequences of WvTPS63 and WvTPS66 were highly similar and the conservative motif of terpene synthase was almost identical. In vitro enzymatic experiments on catalytic functions showed that both could produce pinene, and the main product of WvTPS63 was β-pinene, while that of WvTPS66 was α-pinene. Expression pattern analysis showed that WvTS63 was highly expressed in flowers, WvTPS66 was expressed in the whole plant, and the highest expression level was found in the pericarp, which indicated that it might be mainly responsible for the synthesis of α-pinene in fruits. In addition, promoter analysis revealed the presence of multiple regulatory elements related to stress response in the promoter regions of both genes. The findings of this study can provide a reference for the functional study of terpene synthase genes and new genetic elements for pinene biosynthesis.

Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses

Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within bats at the level of individual animals, and hence the frequency of virus co-infection and inter-species transmission. Using an unbiased meta-transcriptomics approach we characterised the mammalian associated viruses present in 149 individual bats sampled from Yunnan province, China. This revealed a high frequency of virus co-infection and species spillover among the animals studied, with 12 viruses shared among different bat species, which in turn facilitates virus recombination and reassortment. Of note, we identified five viral species that are likely to be pathogenic to humans or livestock, including a novel recombinant SARS-like coronavirus that is closely related to both SARS-CoV-2 and SARS-CoV, with only five amino acid differences between its receptor-binding domain sequence and that of the earliest sequences of SARS-CoV-2. Functional analysis predicts that this recombinant coronavirus can utilize the human ACE2 receptor such that it is likely to be of high zoonotic risk. Our study highlights the common occurrence of inter-species transmission and co-infection of bat viruses, as well as their implications for virus emergence.

Knockdown of EDA2R alleviates hyperoxia-induced lung epithelial cell injury by inhibiting NF-KB pathway

Background: Long-term hyperoxia impairs growth of the lungs and contributes to develop-ment of bronchopulmonary dysplasia. Ectodysplasin A (EDA) binds to ectodysplasin A2 recep-tor (EDA2R) and is essential for normal prenatal development. The functioning of EDA2R in bronchopulmonary dysplasia is investigated in this study.Methods: Murine lung epithelial cells (MLE-12) were exposed to hyperoxia to induce cell injury. Cell viability and apoptosis were detected, respectively, by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay and flow cytometry. Inflammation and oxidative stress were evaluated by enzyme-linked immunosorbent serologic assay.Results: Hyperoxia decreased cell viability and promoted cell apoptosis of MLE-12. EDA2R was elevated in hyperoxia-induced MLE-12. Silencing of EDA2R enhanced cell viability and reduced cell apoptosis of hyperoxia-induced MLE-12. Hyperoxia-induced up-regulation of tumor necro-sis factor alpha (TNF-α), Interleukin (IL)-1β, and IL-18 as well as MLE-12 was suppressed by knockdown of EDA2R. Inhibition of EDA2R down-regulated the level of malondialdehyde (MDA), up-regulated superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in hyperoxia-induced MLE-12. Interference of EDA2R attenuated hyperoxia-induced increase in p-p65 in M LE-12.Conclusion: Knockdown of EDA2R exerted anti-inflammatory and antioxidant effects against hyperoxia-induced injury in lung epithelial cells through inhibition of nuclear factor kappa B (NF-κB) pathway (AU)

Analysis of pathogen detection results of neonatal Echovirus 11 infection outbreaks in Guangdong Province in 2019 / 中华微生物学和免疫学杂志

Objective:To analyze the laboratory test results of two outbreaks of neonatal enterovirus infections in Guangdong Province in 2019 and the genetic characteristics of Echo11, aiming to provide reference for the prevention and control of neonatal enterovirus infections.Methods:The pathogenic specimens of neonatal cases suspected of enterovirus infection were collected. Fluorescence quantitative PCR and sequencing were used for enterovirus typing and identification, and virus isolation was carried out for positive specimens.The complete sequences of VP1 of Echo11 were amplified and sequenced and the phylogenetic analysis was performed using the bioinformatics software such as Danstar6, Bioedit7.09 and MEGA6.06.Results:A total of 93 specimens from 36 neonatal cases were collected. After identification, 55 specimens from 24 cases were positive for enterovirus, of which 23 cases were positive for Echo11 and one case was positive for Coxsackievirus B4(CVB4). A total of 29 enterovirus strains were isolated from the specimens of 19 cases, of which 28 were Echo11 from 18 cases, and one was CVB4. Phylogenetic analysis revealed that the nucleotide homology between the 18 strains of Echo11 in this study was 98.2%-100.0%, and the nucleotide homology between the Echo11 strains causing the two neonatal infections was 99.7%-100.0% and 99.8%-100.0%, respectively. Echo11 could be divided into six genotypes as A, B, C, D, E and F, in which genotype A and genotype C were further divided into A1-5 and C1-4, and genotype D could be divided into D1-5. The 18 strains of Echo11 in this study were all subtype D5.Conclusions:In 2019, two outbreaks of neonatal infections in medical institutions in Guangdong Province were caused by Echo11, which belonged to the genotype D5.

Preparation and application of a PDGFRβ-targeted near-infrared fluorescent probe for molecular optical imaging of lung cancer / 中国胸心血管外科临床杂志

@#Objective    To prepare platelet-derived growth factor receptor β (PDGFRβ)-targeted near-infrared molecular probe and evaluate its potential in optical molecular imaging of lung cancer. Methods    PDGFRβ-specific affibody Z-tri was recombinantly expressed in Escherichia coli (E. coli) and purified using affinity chromatography. In vitro cell-binding of Z-tri was analyzed by flow cytometry. Cellular distribution of Z-tri in tumor grafts was determined by protein-tracing. The molecular probe CF750-Z-tri was prepared by conjugating near-infrared fluorescent dye CF750 to Z-tri. The optical images of xenografts of lung cancer were obtained by using CF750-Z-tri combined with optical imaging system. Results    PDGFRβ-specific affibody Z-tri was highly expressed in E. coli and purified to homogeneity. Z-tri could bind PDGFRβ-positive cells but not PDGFRβ-negative cells cultured in vitro. In the tumor xenografts of human lung cancer, intravenously injected Z-tri was predominantly distributed on cells overexpressing PDGFRβ. The near infrared fluorescent dye CF750 was efficiently conjugated to Z-tri. Optical images with high contrast of lung cancer xenografts were produced by using the near-infrared fluorescent probe CF750-Z-tri combined with optical imaging system. Conclusion    The near-infrared fluorescent probe CF750-Z-tri can be used for optical imaging of human lung cancer, which takes great potential in optical imaging-guided surgery of lung cancer.

Study on Mechanism of Quercetin in Heart Failure Based on Network Pharmacology and Experimental Validation / 中国实验方剂学杂志

Objective:To predict the therapeutic targets and related signaling pathways of quercetin in the treatment of heart failure （HF） by network pharmacology and molecular docking methods，and further clarify its mechanisms through <italic>in vitro</italic> cell model. Method:The pharmacological targets of quercetin were obtained by SwissTargetPrediction and Targetnet databases； the heart failure related targets were obtained by Online Mendelian Inheritance in Man（OMIM），GeneCards and Therapeutic Target Database（TTD） databases； the protein-protein interaction（PPI） network was analyzed by STRING database（Search Tool for Recurring Instances of Neighbouring Genes），and the PPI network diagram of quercetin for heart failure target was established. Cytoscape 3.7.2 software was used for analyzing and screening the anti-heart failure network nodes of quercetin，and the obtained targets were enriched with gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis by DAVID database. In order to explore the mechanism of quercetin in the treatment of heart failure，we used cell model to verify the function in heart failure treatment. Results:The predicted results showed that there were 23 targets for the treatment of heart failure，such as Matrix Metallopeptidase-9（MMP-9），androgen receptor（AR），coagulation factor 2（F2），insulin like growth factor 1 receptor（IGF1R），epidermal growth factor receptor（EGFR），janus kinase-2（JAK2），cytochrome P450 family 19 subfamily A member 1（CYP19A1），estrogen receptor-1（ESR1），tumor necrosis factor（TNF），protein tyrosine phosphatase receptor type C（PTPRC） and cytochrome P450 family 17 subfamily A member 1（CYP17A1） etc. The results suggest that quercetin may play a role in the treatment of heart failure by intervening in the physiological processes of cardiovascular cell proliferation and metabolism，regulating hypoxia-inducible factor 1 （HIF-1）signaling pathway and steroid hormone biosynthesis. Conclusion:Quercetin has the characteristics of multi-target，multi-channel and multi-channel in the treatment of heart failure. It may play a role in the treatment of heart failure by regulating MMP-9，EGFR and other key genes，participating in the biological process of cardiac and vascular cell proliferation and metabolism.

Effect of Shuangyu Tiaozhi Decoction on HNF1α/PCSK9/LDLR Signaling Pathway in Liver of Hypercholesterolemic Rats / 中国实验方剂学杂志

Objective:To observe the expression of hepatocyte nuclear factor 1<italic>α</italic> （HNF1<italic>α</italic>）， proprotein convertase subtilisin/kexin type 9 （PCSK9） and low-density lipoprotein cholesterol （LDLR） in hypercholesterolemia rat liver， and investigate the mechanism of Shuangyu Tiaozhi Decoction regulating cholesterol metabolism and attenuating hypercholesterolemia. Method:After providing a high-fat diet for 4 weeks， 40 SD rats were selected， 8 of which were randomly selected as normal group and fed a normal diet， and the remaining 32 rats were fed a high-fat diet. The rats successfully established as hypercholesterolemic model， were randomized into 4 groups： model group， low dose of Shuangyu Tiaozhi decoction group （7.8 g·kg^-1）， high dose of Shuangyu Tiaozhi decoction group （15.6 g·kg^-1）， and simvastatin group （4 mg·kg^-1）， with 8 rats in each group. The drugs were continuously given for 8 weeks. Serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C） were measured. The pathomorphological changes in liver were observed by hematoxylin and eosin （HE） staining. The immunohistochemistry was used to detect PCSK9 and LDLR expression in liver. The mRNA and protein expression levels of HNF1<italic>α</italic>， PCSK9 and LDLR were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Result:Compared with normal group， the TC， TG， LDL-C levels in model group were significantly increased （<italic>P</italic><0.01）， the morphology showed obvious liver steatosis. The mRNA and protein expression of HNF1<italic>α</italic> and PCSK9 were increased （<italic>P</italic><0.05）， the mRNA and protein expression of LDLR was decreased （<italic>P</italic><0.05）. Compared with model group， the serum TC， TG， LDL-C levels were significantly lowered in the Shuangyu Tiaozhi decoction high-dose group （<italic>P</italic><0.01）， the serum TC， LDL-C levels were significantly lowered in the Shuangyu Tiaozhi decoction low-dose group and simvastatin group （<italic>P</italic><0.05，<italic>P</italic><0.01）， while no significant effect was observed on the serum HDL-C levels in each treatment group. The liver steatosis decreased in each treatment group. The mRNA and protein expression of HNF1<italic>α</italic> was obviously decreased in each treatment group （<italic>P</italic><0.05，<italic>P</italic><0.01）， the mRNA and protein expression of PCSK9 was obviously decreased in Shuangyu Tiaozhi decoction low and high-dose groups （<italic>P</italic><0.05，<italic>P</italic><0.01）， the mRNA expression of PCSK9 was significantly increased in the simvastatin group （<italic>P</italic><0.01）， while the protein expression showed a downward trend. The LDLR mRNA levels were significantly increased in each treatment group （<italic>P</italic><0.01）， the LDLR protein expression was significantly increased in Shuangyu Tiaozhi high-dose group （<italic>P</italic><0.01）， and showed an upward trend in Shuangyu Tiaozhi low-dose group and simvastatin group. Results of immunohistochemistry showed PCSK9 expression was weakly positive， the expression of LDLR was strongly positive in each treatment group. The therapeutic effect of Shuangyu Tiaozhi decoction high-dose group was more remarkable than simvastatin group， while there was no obvious difference between the Shuangyu Tiaozhi decoction low-dose group and simvastatin group. Conclusion:Shuangyu Tiaozhi decoction may reduce the blood lipid levels through HNF1<italic>α</italic>/PCSK9/LDLR signaling pathway， play an active role on regulating cholesterol metabolism and alleviating high-fat diet-induced hypercholesterolemia.

Recurrence factors for myelin oligodendrocyte glycoprotein antibody disease in children and the effect of recurrence prevention regimens / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and recurrence factors of myelin oligodendrocyte glycoprotein (MOG) antibody disease in children and the effect of recurrence prevention regimens.@*METHODS@#A retrospective analysis was performed on the medical data of 41 children with MOG antibody disease who were hospitalized in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from December 2014 to September 2020. According to the presence or absence of recurrence, they were divided into a monophasic course group (@*RESULTS@#For these 41 children, acute disseminated encephalomyelitis was the most common initial manifestation and was observed in 23 children (56%). Of the 41 children, 22 (54%) experienced recurrence, with 57 recurrence events in total, among which optic neuritis was the most common event (17/57, 30%). The proportion of children in the recurrence group who were treated with corticosteroids for less than 3 months in the acute phase was higher than that in the monophasic course group (64% @*CONCLUSIONS@#More than half of the children with MOG antibody disease may experience recurrence. Most children with recurrence are treated with corticosteroids for less than 3 months in the acute phase. Rituximab and azathioprine may reduce the risk of recurrence.

Effect of interaction between sleep and occupational stress on the prevalence of hypertension in petroleum workers / 中国职业医学

OBJECTIVE: To explore the influence of the interaction among occupational stress, sleep duration and sleep quality on the prevalence of hypertension in petroleum workers. METHODS: A total of 3 040 workers from six oil field bases in Karamay City were selected as study subjects by multi-stage random cluster sampling method. The Chinese version of Pittsburgh Sleep Quality Scale and the revised version of Occupational Stress Scale were used to evaluate their sleep quality and occupational stress status. Binary logistic regression was used to analyze the effect of interaction of occupational stress, sleep duration and sleep quality on hypertension. RESULTS: The prevalence of hypertension in the study subjects was 15.3%(466/3 040), and the detection rates of sleep deprivation, poor sleep quality and high occupational stress were 26.5%, 78.3% and 19.6% respectively. After adjusting for confounding factors such as gender, ethnicity, age, marital status, education level, length of service, professional title, shift work, smoking, alcohol consumption and body mass index, the interaction analysis results showed that the risk of hypertension was higher in the poor sleep quality groups with normal sleep duration, sleep deprivation or longer sleep duration than that in good sleep quality group with normal sleep duration(all P<0.05), respectively. The risk of hypertension was higher in the group with sleep deprivation and high occupational stress than that in the group with normal sleep duration and low occupational stress(P<0.01). In the group with poor sleep quality and high occupational stress the risk of hypertension was higher than that in the group with good sleep quality and low occupational stress(P<0.05). CONCLUSION: The interaction among occupational stress, sleep duration and sleep quality may increase the risk of hypertension in petroleum workers.

Modes of contact and risk of transmission in COVID-19 among close contacts

BackgroundRapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Guangzhou and elsewhere in China. Modes of contact and risk of transmission among close contacts have not been well estimated. MethodsWe included 4950 closes contacts from Guangzhou, and extracted data including modes of contact, laboratory testing, clinical characteristics of confirmed cases and source cases. We used logistic regression analysis to explore the risk factors associated with infection of close contacts. ResultsAmong 4950 closes contacts, the median age was 38.0 years, and males accounted for 50.2% (2484). During quarantine period, 129 cases (2.6%) were diagnosed, with 8 asymptomatic (6.2%), 49 mild (38.0%), and 5 (3.9%) severe to critical cases. The sensitivity of throat swab was 71.32% and 92.19% at first to second PCR test. Among different modes of contact, household contacts were the most dangerous in catching with infection of COVID-19, with an incidence of 10.2%. As the increase of age for close contacts and severity of source cases, the incidence of COVID-19 presented an increasing trend from 1.8% (0-17 years) to 4.2% (60 or over years), and from 0.33% for asymptomatic, 3.3% for mild, to 6.2% for severe and critical source cases, respectively. Manifestation of expectoration in source cases was also highly associated with an increased risk of infection in their close contacts (13.6%). Secondary cases were in general clinically milder and were less likely to have common symptoms than those of source cases. ConclusionsIn conclusion, the proportion of asymptomatic and mild infections account for almost half of the confirmed cases among close contacts. The household contacts were the main transmission mode, and clinically more severe cases were more likely to pass the infection to their close contacts. Generally, the secondary cases were clinically milder than those of source cases.

Research Progress of Regulatory Effect and Mechanism of Flavonoids on Vascular Endothelial Cell Injury / 中国实验方剂学杂志

To investigate the effect of flavonoid compounds on vascular endothelial cells. Vascular endothelial cells were located between plasma and vascular tissue, and can complete the metabolic exchange of plasma and interstitial fluid, synthesize and secrete a variety of biologically active substances, so as to ensure the normal contraction and relaxation of blood vessels, and maintain the tension of blood vessels. Besides, it can regulate blood pressure and the balance of blood coagulation and anticoagulation, and maintain normal blood flow and long-term patency of blood vessels. Endothelial cell damage can cause a series of cardiovascular diseases, such as hypertension and coronary heart disease. Flavonoids are widely found in nature. Because these compounds are mostly yellow or light yellow, they contain ketone groups in the molecule, which are called flavones. Flavonoids are widely distributed, mostly in higher plants and ferns. Various flavonoid compounds, such as flavonoids, flavonols, flavanones isoflavones and flavanones, can protect vascular endothelial cells. This article reviews relevant findings published in domestic and foreign journals. It is found that flavonoids have effects in resisting inflammation, reducing blood vessel fragility, improving blood vessel permeability, lowering blood lipids and cholesterol, vasodilating and resisting hemagglutinating, with the same effect as phytoestrogens. They can reduce vascular endothelial cell damage through anti-inflammatory, anti-oxidative stress, stable mitochondrial function, and regulating nitric oxide（NO）. It can be used in clinic to treat diseases, such as insufficient cerebral blood supply, sequelae caused by cerebral hemorrhage, hyperviscosity, cerebral thrombosis, coronary heart disease and angina pectoris.

Progress of residual inflammatory cardiovascular risk / 医学研究生学报

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality in the world. Although the comprehensive control of cardiovascular disease risk factors has achieved remarkable progress in recent years, the incidence of cardiovascular events is still high after the control of traditional risk factors such as low density lipoprotein cholesterol, blood pressure and blood glucose, collectively referred to as cardiovascular residual risk. Inflammation is a central driver of atherosclerosis and the ultimate rupture of plaque, as well as an important cause of residual cardiovascular risk. Therefore, this article reviews the formation, assessment and treatment of residual inflammatory cardiovascular risk.

Mutations in aminoacyl-tRNA synthetase genes: an analysis of 10 cases / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of the diseases associated with aminoacyl-tRNA synthetases (ARS) deficiency.@*METHODS@#A retrospective analysis was performed of the clinical and gene mutation data of 10 children who were diagnosed with ARS gene mutations, based on next-generation sequencing from January 2016 to October 2019.@*RESULTS@#The age of onset ranged from 0 to 9 years among the 10 children. Convulsion was the most common initial symptom (7 children). Clinical manifestations included ataxia and normal or mildly retarded intellectual development (with or without epilepsy; n=4) and onset of epilepsy in childhood with developmental regression later (n=2). Some children experienced disease onset in the neonatal period and had severe epileptic encephalopathy, with myoclonus, generalized tonic-clonic seizure, and convulsive seizure (n=4); 3 had severe delayed development, 2 had feeding difficulty, and 1 had hearing impairment. Mutations were found in five genes: 3 had novel mutations in the AARS2 gene (c.331G>C, c.2682+5G>A, c.2164C>T, and c.761G>A), 2 had known mutations in the DARS2 gene (c.228-16C>A and c.536G>A), 1 had novel mutations in the CARS2 gene (c.1036C>T and c.323T>G), 1 had novel mutations in the RARS2 gene (c.1210A>G and c.622C>T), and 3 had novel mutations in the AARS gene (c.1901T>A, c.229C>T, c.244C>T, c.961G>C, c.2248C>T, and Chr16:70298860-70316687del).@*CONCLUSIONS@#A high heterogeneity is observed in the clinical phenotypes of the diseases associated with the ARS deficiency. A total of 14 novel mutations in 5 genes are reported in this study, which enriches the clinical phenotypes and genotypes of the diseases associated with ARS deficiency.

Research progress on anti-atherosclerosis effect and mechanism of flavonoids compounds mediated by macrophages / 中国中药杂志

Flavonoids are important active ingredients of traditional Chinese medicine, mainly with cardiovascular, anti-liver injury, antioxidant, antispasmodic, and estrogen-like effects. These compounds have obvious effects on the cardiovascular and cerebrovascular diseases. Macrophage-derived foam cells are the key medium in the process of atherosclerosis(AS). In plaque, allserum lipids, serum lipoproteins, and various pro-or anti-inflammatory stimulating factors, chemokines, and small bioactive molecules can significantly affect the macrophage phenotype and induce stronger pro-inflammatory or anti-inflammatory properties. Studies have shown that some flavonoids can be used for macrophages through different pathways and mechanisms, playing an anti-atherosclerosis effect to different degrees, including promotion of cholesterol efflux from macrophages, anti-foaming of macrophages, inhibition of secretion of inflammatory factors, and antioxidant modified low density lipoprotein(ox-LDL)-induced apoptosis of macrophages. Related gene regulation inclu-ded ATP-binding cassette transporter A1(ABCA1), ATP-binding cassette transporter G1(ABCG1), Toll-like receptor(TLR), and scavenger receptor(SR). In this article, we would review the recent research progress of flavonoids on anti-atherosclerosis effect me-diated by macrophage. It is expected to provide new treatment strategies for AS-related cardiovascular and cerebrovascular diseases, and provide research ideas and development directions for the use of related natural medicines and design of new products.

On the necessity of an integrative approach to understand protein structural dynamics / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Proteins are dynamic, fluctuating between multiple conformational states. Protein dynamics, spanning orders of magnitude in time and space, allow proteins to perform specific functions. Moreover, under certain conditions, proteins can morph into a different set of conformations. Thus, a complete understanding of protein structural dynamics can provide mechanistic insights into protein function. Here, we review the latest developments in methods used to determine protein ensemble structures and to characterize protein dynamics. Techniques including X-ray crystallography, cryogenic electron microscopy, and small angle scattering can provide structural information on specific conformational states or on the averaged shape of the protein, whereas techniques including nuclear magnetic resonance, fluorescence resonance energy transfer (FRET), and chemical cross-linking coupled with mass spectrometry provide information on the fluctuation of the distances between protein domains, residues, and atoms for the multiple conformational states of the protein. In particular, FRET measurements at the single-molecule level allow rapid resolution of protein conformational states, where information is otherwise obscured in bulk measurements. Taken together, the different techniques complement each other and their integrated use can offer a clear picture of protein structure and dynamics.

Diagnosis of intellectual disability/global developmental delay via genetic analysis in a central region of China / 中华医学杂志(英文版)

BACKGROUND@#Advanced technology has become a valuable tool in etiological studies of intellectual disability/global developmental delay (ID/GDD). The present study investigated the role of genetic analysis to confirm the etiology in ID/GDD patients where the cause of the disease was uncertain in central China.@*METHODS@#We evaluated 1051 ID/GDD children aged 6 months to 18 years from March 2009 to April 2017. Data concerning basic clinical manifestations were collected, and the method of etiology confirmation was recorded. Genome-wide copy number variations (CNVs) detection and high-throughput sequencing of exons in the targeted regions was performed to identify genetically-based etiologies. We compared the incidence of different methods used to confirm ID/GDD etiology among groups with differing degrees of ID/GDD using the Chi-square or Fisher exact probability test.@*RESULTS@#We recruited 1051 children with mild (367, 34.9%), moderate (301, 28.6%), severe (310, 29.5%), and profoundly severe (73, 6.9%) ID/GDD. The main causes of ID/GDD in the children assessed were perinatal factors, such as acquired brain injury, as well as single gene imbalance and chromosomal gene mutation. We identified karyotype and/or CNVs variation in 46/96 (47.9%) of cases in severe ID/GDD patients, which was significantly higher than those with mild and moderate ID/GDD of 34/96 (35.4%) and 15/96 (15.6%), respectively. A total of 331/536 (61.8%) patients with clear etiology have undergone genetic analysis while 262/515 (50.9%) patients with unclear etiology have undergone genetic analysis (χ = 12.645, P < 0.001). Gene structure variation via karyotype analysis and CNV detection increased the proportion of children with confirmed etiology from 51.0% to 56.3%, and second-generation high-throughput sequencing dramatically increased this to 78.9%. Ten novel mutations were detected, recessive mutations in X-linked genes (ATPase copper transporting alpha and bromodomain and WD repeat domain containing 3) and dominant de novo heterozygous mutations in X-linked genes (cyclin-dependent kinase like 5, protocadherin 19, IQ motif and Sec7 domain 2, and methyl-CpG binding protein 2) were reported in the study.@*CONCLUSIONS@#The present study indicates that genetic analysis is an effective method to increase the proportion of confirmed etiology in ID/GDD children and is highly recommended, especially in ID/GDD children with uncertain etiology.

On the necessity of an integrative approach to understand protein structural dynamics / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Proteins are dynamic, fluctuating between multiple conformational states. Protein dynamics, spanning orders of magnitude in time and space, allow proteins to perform specific functions. Moreover, under certain conditions, proteins can morph into a different set of conformations. Thus, a complete understanding of protein structural dynamics can provide mechanistic insights into protein function. Here, we review the latest developments in methods used to determine protein ensemble structures and to characterize protein dynamics. Techniques including X-ray crystallography, cryogenic electron microscopy, and small angle scattering can provide structural information on specific conformational states or on the averaged shape of the protein, whereas techniques including nuclear magnetic resonance, fluorescence resonance energy transfer (FRET), and chemical cross-linking coupled with mass spectrometry provide information on the fluctuation of the distances between protein domains, residues, and atoms for the multiple conformational states of the protein. In particular, FRET measurements at the single-molecule level allow rapid resolution of protein conformational states, where information is otherwise obscured in bulk measurements. Taken together, the different techniques complement each other and their integrated use can offer a clear picture of protein structure and dynamics.

TGF-β1/Smad signaling pathway in tissue fibrosis:research advances / 国际药学研究杂志

Transforming growth factor-β1(TGF-β1)is an important factor in tissue fibrosis. TGF-β1 directly ac- tivates Smad signaling which triggers the overexpression of profibrotic genes. A large number of studies have shown that the dysregulation of TGF-β1/Smad pathway is an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulators that promote TGF-β1-mediated tissue fibrosis,whereas Smad7 acts as a nega- tive feedback regulator of the TGF-β1/Smad pathway,blocking TGF-β1-mediated fibrosis. In addition,the recent re- searches have shown that microRNA(miRNA)can regulate the TGF-β1/Smad signaling pathway,and affect the process of tissue fibrosis. This article reviews the role of TGF-β1/Smad signaling pathway in renal,hepatic,pulmonary and myo- cardial fibrosis,as well as the regulation of TGF-β1/Smad signaling pathway by miRNA.

Oral microbiological diversity in patients with salivary adenoid cystic carcinoma / 华西口腔医学杂志

OBJECTIVE@#The aim of this study was to identify the differences in microbial diversity and community in patients with salivary adenoid cystic carcinoma (SACC).@*METHODS@#Saliva was collected from 13 patients with SACC confirmed by histopathological diagnosis and 10 healthy control subjects. Total metagenomic DNA was extracted. The DNA amplicons of the V3-V4 hypervariable regions of the 16S rRNA gene were generated and subjected to high-throughput sequencing. Microbial diversity and community structure were analyzed with Mothur software.@*RESULTS@#A total of 16 genera of dominant bacteria in the SACC group were found, including Streptococcus (36.68%), Neisseria (8.55%), Prevotella_7 (7.53%), and Veillonella (6.37%), whereas 15 dominant bacteria in the control group were found, including Streptococcus (18.41%), Neisseria (18.20%), Prevotella_7 (8.89%), Porphyromonas (6.20%), Fusobacterium (5.86%) and Veillonella (5.82%). The statistically different phyla between the two groups were Firmicutes, Proteobacteria and Fusobacterium (P<0.05). The statistically different genera between the two groups were Streptococcus, Neisseria and Porphyromonas (P<0.05), and Capnocytophaga was only detected in patients with SACC.@*CONCLUSIONS@#Significant differences were observed in the oral microorganisms between the two groups.