Publications by authors named "Xin Gong"

172 Publications

Structural insights into proteolytic activation of the human Dispatched1 transporter for Hedgehog morphogen release.

Nat Commun 2021 Nov 29;12(1):6966. Epub 2021 Nov 29.

Department of Biology, School of Life Sciences, Southern University of Science and Technology, 518055, Shenzhen, Guangdong, China.

The membrane protein Dispatched (Disp), which belongs to the RND family of small molecule transporters, is essential for Hedgehog (Hh) signaling, by catalyzing the extracellular release of palmitate- and cholesterol-modified Hh ligands from producing cells. Disp function requires Furin-mediated proteolytic cleavage of its extracellular domain, but how this activates Disp remains obscure. Here, we employ cryo-electron microscopy to determine atomic structures of human Disp1 (hDisp1), before and after cleavage, and in complex with lipid-modified Sonic hedgehog (Shh) ligand. These structures, together with biochemical data, reveal that proteolytic cleavage opens the extracellular domain of hDisp1, removing steric hindrance to Shh binding. Structure-guided functional experiments demonstrate the role of hDisp1-Shh interactions in ligand release. Our results clarify the mechanisms of hDisp1 activation and Shh morphogen release, and highlight how a unique proteolytic cleavage event enabled acquisition of a protein substrate by a member of a family of small molecule transporters.
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http://dx.doi.org/10.1038/s41467-021-27257-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630017PMC
November 2021

AGPAT2 interaction with CDP-diacylglycerol synthases promotes the flux of fatty acids through the CDP-diacylglycerol pathway.

Nat Commun 2021 Nov 25;12(1):6877. Epub 2021 Nov 25.

School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW, 2052, Australia.

AGPATs (1-acylglycerol-3-phosphate O-acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic acid (PA), a key step in the glycerol-3-phosphate pathway for the synthesis of phospholipids and triacylglycerols. AGPAT2 is the only AGPAT isoform whose loss-of-function mutations cause a severe form of human congenital generalized lipodystrophy. Paradoxically, AGPAT2 deficiency is known to dramatically increase the level of its product, PA. Here, we find that AGPAT2 deficiency impairs the biogenesis and growth of lipid droplets. We show that AGPAT2 deficiency compromises the stability of CDP-diacylglycerol (DAG) synthases (CDSs) and decreases CDS activity in both cell lines and mouse liver. Moreover, AGPAT2 and CDS1/2 can directly interact and form functional complexes, which promote the metabolism of PA along the CDP-DAG pathway of phospholipid synthesis. Our results provide key insights into the regulation of metabolic flux during lipid synthesis and suggest substrate channelling at a major branch point of the glycerol-3-phosphate pathway.
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http://dx.doi.org/10.1038/s41467-021-27279-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616899PMC
November 2021

Application of a feature extraction and normalization method to improve research evaluation across clinical disciplines.

Ann Transl Med 2021 Oct;9(20):1580

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: To deal with the large disparity across disciplines using impact factor, which is widely used in hospitals and has recently come under attack for distorting good scientific practices, we propose a set of systematic methods to improve the equality of research evaluations of various clinical disciplines.

Methods: We used bibliometric information on 18 clinical disciplines from 2016 to 2018. We first sought to clarify disciplinary characteristics with the aim of identifying the characteristic fields for each clinical discipline, and we constructed a keyword database. To minimize the disparity across various clinical disciplines, we used normalized evaluation, referring to the calculation of the normalized coefficient of a specific discipline, to enable a relatively clear evaluation across different disciplines.

Results: Feature extraction was performed, and over 700,000 journals were retrieved each year. Using this information, the journal correlation coefficient was calculated. From 2016 to 2018, oncology had the largest normalized coefficient (0.133, 0.136, 0.146 respectively), which reflects the highest correlation between the characteristic journals of the discipline. The findings showed a clear distinction in journal coverage and journal correlations for different disciplines.

Conclusions: The new evaluation indicator and normalized process measure different features of disciplines, providing a basis for the further balancing of evaluations, and considering differences across disciplines.
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http://dx.doi.org/10.21037/atm-21-5046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576718PMC
October 2021

The multivariable prognostic models for severe complications after heart valve surgery.

BMC Cardiovasc Disord 2021 10 11;21(1):491. Epub 2021 Oct 11.

Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, No.58, Zhongshan Road II, Guangzhou, 510080, China.

Background: To provide multivariable prognostic models for severe complications prediction after heart valve surgery, including low cardiac output syndrome (LCOS), acute kidney injury requiring hemodialysis (AKI-rH) and multiple organ dysfunction syndrome (MODS).

Methods: We developed multivariate logistic regression models to predict severe complications after heart valve surgery using 930 patients collected retrospectively from the first affiliated hospital of Sun Yat-Sen University from January 2014 to December 2015. The validation was conducted using a retrospective dataset of 713 patients from the same hospital from January 2016 to March 2017. We considered two kinds of prognostic models: the PRF models which were built by using the preoperative risk factors only, and the PIRF models which were built by using both of the preoperative and intraoperative risk factors. The least absolute shrinkage selector operator was used for developing the models. We assessed and compared the discriminative abilities for both of the PRF and PIRF models via the receiver operating characteristic (ROC) curve.

Results: Compared with the PRF models, the PIRF modes selected additional intraoperative factors, such as auxiliary cardiopulmonary bypass time and combined tricuspid valve replacement. Area under the ROC curves (AUCs) of PRF models for predicting LCOS, AKI-rH and MODS are 0.565 (0.466, 0.664), 0.688 (0.62, 0.757) and 0.657 (0.563, 0.751), respectively. As a comparison, the AUCs of the PIRF models for predicting LOCS, AKI-rH and MODS are 0.821 (0.747, 0.896), 0.78 (0.717, 0.843) and 0.774 (0.7, 0.847), respectively.

Conclusions: Adding the intraoperative factors can increase the predictive power of the prognostic models for severe complications prediction after heart valve surgery.
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http://dx.doi.org/10.1186/s12872-021-02268-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504034PMC
October 2021

Analysis of Gene Family and Its Function on Cell Lignification in Pears ().

Plants (Basel) 2021 Sep 10;10(9). Epub 2021 Sep 10.

Pear Engineering Research Centre, College of Horticulture, Nanjing Agricultural University, 1 Weigang, Nanjing 210095, China.

Class III peroxidases (PRXs) are plant-specific enzymes that play key roles in the responses to biotic and abiotic stress during plant growth and development. In addition, some peroxidases also play roles in plant lignification. In this study, a total of 114 (designated ) genes were identified in the pear () genome based on systematic analysis. These genes were divided into 12 groups based on their phylogenetic relationships. We performed systematic bioinformatics analysis of the genes, including analysis of gene structures, conserved motifs, phylogenetic relationships, and gene expression patterns during pear fruit growth. The are unevenly distributed on the 17 pear chromosomes and some of them on other scaffolds. Gene duplication event analysis indicated that whole-genome duplication (WGD) and segmental duplication play key roles in gene amplification. Ka/Ks analysis suggested that most duplicated experienced purifying selection, with limited functional divergence during the duplication events. Furthermore, the analysis indicated that those highly expressed genes might play significant roles in the lignification of cells to form stone cells in pear fruit. We examined the expression of those highly expressed genes during fruit growth using quantitative real-time PCR (qRT-PCR), verifying differential expression patterns at different stages of fruit. This study provides useful information for further functional analysis of the gene family in pears.
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http://dx.doi.org/10.3390/plants10091874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470002PMC
September 2021

A vaccine based on the receptor-binding domain of the spike protein expressed in glycoengineered targeting SARS-CoV-2 stimulates neutralizing and protective antibody responses.

Engineering (Beijing) 2021 Jul 13. Epub 2021 Jul 13.

Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China.

In 2020 and 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, caused a global pandemic. Vaccines are expected to reduce the pressure of prevention and control, and have become the most effective strategy to solve the pandemic crisis. SARS-CoV-2 infects the host by binding to the cellular receptor angiotensin converting enzyme 2 (ACE2) via the receptor-binding domain (RBD) of the surface spike (S) glycoprotein. In this study, a candidate vaccine based on a RBD recombinant subunit was prepared by means of a novel glycoengineered yeast expression system with characteristics of glycosylation modification similar to those of mammalian cells. The candidate vaccine effectively stimulated mice to produce high-titer anti-RBD specific antibody. Furthermore, the specific antibody titer and virus-neutralizing antibody (NAb) titer induced by the vaccine were increased significantly by the combination of the double adjuvants Al(OH) and CpG. Our results showed that the virus-NAb lasted for more than 6 months in mice. To summarize, we have obtained a SARS-CoV-2 vaccine based on the RBD of the S glycoprotein expressed in glycoengineered , which stimulates neutralizing and protective antibody responses. A technical route for fucose-free complex-type -glycosylation modified recombinant subunit vaccine preparation has been established.
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http://dx.doi.org/10.1016/j.eng.2021.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378774PMC
July 2021

Genes: Genome-Wide Identification, Evolution, and Their Contribution to Lignin Biosynthesis in Pear ().

Plants (Basel) 2021 Jul 15;10(7). Epub 2021 Jul 15.

Pear Engineering Research Centre, College of Horticulture, Nanjing Agricultural University, 1 Weigang, Nanjing 210095, China.

The synthetic enzyme cinnamyl alcohol dehydrogenase (CAD) is involved in responses to various stresses during plant growth. It regulates the monolignol biosynthesis and catalyzes hydroxyl cinnamaldehyde reduction to the corresponding alcohols. Although the CAD gene families have been explored in some species, little known is in Rosaceae. In this study, we identified 149 genes in (), (), () and (). They were phylogenetically clustered into six subgroups. All CAD genes contained ADH-N and ADH-zinc-N domains and were distributed on chromosomes unevenly. Dispersed and WGD/segmental duplications accounted the highest number of evolutionary events. Eight collinear gene pairs were identified among the four Rosaceae species, and the highest number was recorded in pear as five pairs. The five gene pairs had undergone purifying selection under Ka/Ks analysis. Furthermore, nine genes were identified based on transcriptomic and stone cell content in pear fruit. In qRT-PCR, the expression patterns of , , , and were consistent with variation in stone cell content during pear fruit development. These results will provide valuable information for understanding the relationship between gene expressions and stone cell number in fruit.
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http://dx.doi.org/10.3390/plants10071444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309377PMC
July 2021

First Report of Lotus Seedpod Withering Caused by Fusarium proliferatum on Nelumbo nucifera Plants in China.

Plant Dis 2021 Jul 28. Epub 2021 Jul 28.

Jiangxi Agricultural University, 91595, College of Agronomy, Zhimin Road, Nanchang, China, 330045;

Nelumbo nucifera (Nymphaeaceae family) is a well-known plant in China and with the increasing value of this crop, the planting area of lotus is expanding. In May 2019, an unknown withering lotus seedpod was obtained in Guangchang County of Jiangxi Province (26.79°N, 116.31°E). The disease arose between May and July of each year, resulted in the withering and consequent death of ~10% of lotus seedpods, with the disease being most serious during the rainy season. The initial symptoms of this disease include the shrinking of young lotus seedpods with concomitant yellowing of the epidermal tissue layer. These pods failed to grow normally and could to wither and die within one week, with the withering symptoms gradually spreading to associated stem tissues. To characterize the pathogens responsible for this disease, ten diseases seedpods were collected and cut into pieces of ~5×5 mm, then sterilized with 75% ethanol for 30 s, and treated with 0.1% mercuric chloride for 5 min. After being washed four times under sterilized water, samples were then transferred onto potato dextrose agar (PDA) and incubated for 7 d at 28℃ in the dark. Eight purified isolates yielded large numbers of aerial mycelium that were initially white in color, but then changed to a purple-red color over the course of this incubation period. The average mycelial growth rate was 6.3 mm per day (n=5). On PDA, macroconidia exhibited 3-5 septa and were straight or slightly curved, with a size of 21.6-47.4×2.5-4.6 µm (average: 31.9×3.5 µm, n=50). The microconidia were hyaline, ovoid or ellipse and 4.6-13.5×2.2-4.3 µm in size (average: 8.7×3.1 µm, n=50). The morphological features of these fungi were noted to be in line with those of Fusarium proliferatum (Leslie and Summerell, 2006; Zhao et al., 2019). To confirm the identity of this putative pathogen at the molecular level, the universal ITS4/ITS5 primers (White et al., 1990), the Fusarium specific pair PRO1/PRO2 (Mulè et al., 2004), EF1T/EF2T (O'Donnell et a., 1998) and RPB2F/R (O'Donnell et al., 2010) primers were utilized to amplify the internal transcribed spacer 1 (ITS1)-5.8S rRNA gene-internal transcribed spacer 2 (ITS2), calmodulin, alpha elongation factor genes, and RNA-dependent DNA polymerase II subunit from these isolates. Following alignment of the resultant sequences with GenBank via a BLAST analysis, the sequences (GenBank accession numbers: MW862499, MW762531, MW767988, MW831311, respectively.) showed 100% identities to the corresponding DNA sequences in F. proliferatum (GenBank accession numbers: MW817705, LS423443, MH153750, and MW091308, respectively.). Based upon these morphological and molecular findings, this pathogen was identified as F. proliferatum. Pathogenicity testing was then performed using five plump healthy lotus seedpods. Sterile needles were used to generate wounds (2 mm deep, 1 mm in diameter) a 10 µL suspension of prepared spores (1.0×106 spores/mL) derived from a 7-day-old culture grown on PDA was injected into the wound sites of the lotus seedpod. As a control, give seedpods were additionally wounded and injected as the same as treated with 10 µL of sterile water. The experiments were repeated three times with five biological replicates. All seedpods were then incubated at 28℃ in a growth chamber (12 h light/dark) with 80% relative humidity. After a 3-day incubation period, wounded sites injected with spore suspensions exhibited browning. Following a 5-day incubation period, a mean lesion diameter of 9.8 mm was observed, with white mycelia growing on the wound surface and with evident withering of the internal and external tissues near the wounded site. In contrast, blank control wound sites remained healthy. We were again able to isolate F. proliferatum from the infected lotus seedpods. Finally, eight isolates were obtained were identified as the pathogen based on these morphological and molecular analyses, thus fulfilling Koch's postulates. This is the first report to our knowledge to have described a case of F. proliferatum causing lotus seedpod withering in China, providing a foundation for future research efforts aimed at presenting diseases caused by this pathogen.
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http://dx.doi.org/10.1094/PDIS-06-21-1236-PDNDOI Listing
July 2021

CRISPR-Cereal: a guide RNA design tool integrating regulome and genomic variation for wheat, maize and rice.

Plant Biotechnol J 2021 Nov 14;19(11):2141-2143. Epub 2021 Aug 14.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, China.

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http://dx.doi.org/10.1111/pbi.13675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541771PMC
November 2021

Rh(III)-Catalyzed Divergent Synthesis of Alkynylated Imidazo[1,5-]indoles and α,α-Difluoromethylene Tetrasubstituted Alkenes.

Org Lett 2021 08 19;23(15):5766-5771. Epub 2021 Jul 19.

Jinhua Branch, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Jinhua 321007, China.

Herein, we report the divergent synthesis of alkynylated imidazo[1,5-]indoles and α,α-difluoromethylene tetrasubstituted alkenes through Rh(III)-catalyzed [4 + 1] annulation/alkyne moiety migration and C-H alkenylation/DG migration, respectively. This protocol features tunable product selectivity, excellent chemo-, regio-, and stereoselectivity, broad substrate scope, moderate to high yields, good tolerance of functional groups, and mild redox-neutral conditions.
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http://dx.doi.org/10.1021/acs.orglett.1c01929DOI Listing
August 2021

Physical and Reported Subjective Health Status in 222 Individuals with XY Disorder of Sex Development.

J Endocr Soc 2021 Aug 2;5(8):bvab103. Epub 2021 Jun 2.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for chronic sick children, Department of Pediatric Endocrinology, Berlin, Germany.

Context: Little is known about the physical health of individuals with 46,XY disorders of sex development (DSD).

Objective: To assess physical and reported subjective health of individuals with XY DSD.

Methods: As part of the dsd-LIFE study, patients with an XY DSD condition were analyzed in different diagnosis groups for metabolic parameters, comorbidities, metabolic syndrome, bone outcomes, and reported subjective health. Findings were evaluated by descriptive statistics.

Results: A total of 222 patients with XY DSD were included with a mean age of 28.8 ± 12.2 years, mean height of 175.3 ± 7.7 cm, mean weight of 74.3 ± 20.0 kg, and mean body mass index of 24.1 ± 6.0 kg/m. Obesity rate was not increased when descriptively compared with Eurostat data. Fourteen patients had metabolic syndrome (14/175; 8.0%). In descriptive comparison with data from the DECODE study and World Health Organization, subjects fared better in the categories waist circumference, glucose, triglyceride, cholesterol, and high-density lipoprotein. Of participants with available bone health data, 19/122 (15.6%) patients had a Z-score ≤ -2.0 at lumbar spine indicating lowered bone mineral density (BMD). Mostly gonadectomized individuals with complete androgen insensitivity syndrome (CAIS) and no estrogen therapy had lowered BMD at lumbar spine. Individuals with XY DSD performed poorly in the category subjective health in descriptive comparison with Eurostat data.

Conclusion: Participants reported a lower subjective health status than Eurostat data but their overall metabolic health status was good. Decreased BMD at lumbar spine was especially present in gonadectomized individuals with CAIS and no estrogen therapy.
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http://dx.doi.org/10.1210/jendso/bvab103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271184PMC
August 2021

Premature atrial complexes can predict atrial fibrillation in ischemic stroke patients: A systematic review and meta-analysis.

Pacing Clin Electrophysiol 2021 Sep 12;44(9):1599-1606. Epub 2021 Jul 12.

Department of Cardiology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.

Background And Purpose: Several studies have explored premature atrial complexes (PACs) as high-risk factors for atrial fibrillation (AF) in ischemic stroke patients; however, the results were controversial. The aim of this systematic review and meta-analysis was to examine whether PACs can predict AF in ischemic stroke patients.

Methods: We comprehensively searched the published literature in PubMed, Embase, and Wiley-Cochrane library databases from inception through August 18, 2020. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed by the fixed-effect model or the random-effect model based on heterogeneity.

Results: We identified 12 eligible studies including 2340 stroke patients with a mean age of 65.9 years. PACs were highly associated with AF occurrence in stroke (pooled OR: 4.16, 95% CI: 3.06-5.65) and cryptogenic stroke patients (pooled OR: 3.72, 95% CI: 2.66-5.20). Subgroup analysis showed PAC presence and frequent PACs were correlated with stroke in AF patients (pooled OR: 3.72, 95% CI: 1.65-8.36 and pooled OR: 5.12, 95% CI: 3.12-8.41, respectively). Frequent PACs were identified as the risks for asymptomatic AF (OR: 6.18, 95% CI: 3.23-11.83) and future AF occurrence (OR: 3.71, 95% CI: 2.62-5.26) in stroke patients. The definition of frequent PACs was inconsistent, and was >70 beats/24 h based on Holter monitoring.

Conclusions: PACs confer high risks for asymptomatic AF and future AF occurrence in stroke patients.
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http://dx.doi.org/10.1111/pace.14302DOI Listing
September 2021

Structural basis of substrate recognition and translocation by human ABCA4.

Nat Commun 2021 06 22;12(1):3853. Epub 2021 Jun 22.

Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China.

Human ATP-binding cassette (ABC) subfamily A (ABCA) transporters mediate the transport of various lipid compounds across the membrane. Mutations in human ABCA transporters have been described to cause severe hereditary disorders associated with impaired lipid transport. However, little is known about the mechanistic details of substrate recognition and translocation by ABCA transporters. Here, we present three cryo-EM structures of human ABCA4, a retina-specific ABCA transporter, in distinct functional states at resolutions of 3.3-3.4 Å. In the nucleotide-free state, the two transmembrane domains (TMDs) exhibit a lateral-opening conformation, allowing the lateral entry of substrate from the lipid bilayer. The N-retinylidene-phosphatidylethanolamine (NRPE), the physiological lipid substrate of ABCA4, is sandwiched between the two TMDs in the luminal leaflet and is further stabilized by an extended loop from extracellular domain 1. In the ATP-bound state, the two TMDs display a closed conformation, which precludes the substrate binding. Our study provides a molecular basis to understand the mechanism of ABCA4-mediated NRPE recognition and translocation, and suggests a common 'lateral access and extrusion' mechanism for ABCA-mediated lipid transport.
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http://dx.doi.org/10.1038/s41467-021-24194-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219669PMC
June 2021

MoS-Decorated/Integrated Carbon Fiber: Phase Engineering Well-Regulated Microwave Absorber.

Nanomicro Lett 2021 Apr 27;13(1):114. Epub 2021 Apr 27.

MOE Key Laboratory of Material Physics and Chemistry Under Extraodinary Conditions School of Chemistry and Chemical Engineering, Ministry of Education, Northwestern Polytechnical University, Xi'an, 710072, People's Republic of China.

Phase engineering is an important strategy to modulate the electronic structure of molybdenum disulfide (MoS). MoS-based composites are usually used for the electromagnetic wave (EMW) absorber, but the effect of different phases on the EMW absorbing performance, such as 1T and 2H phase, is still not studied. In this work, micro-1T/2H MoS is achieved via a facile one-step hydrothermal route, in which the 1T phase is induced by the intercalation of guest molecules and ions. The EMW absorption mechanism of single MoS is revealed by presenting a comparative study between 1T/2H MoS and 2H MoS. As a result, 1T/2H MoS with the matrix loading of 15% exhibits excellent microwave absorption property than 2H MoS. Furthermore, taking the advantage of 1T/2H MoS, a flexible EMW absorbers that ultrathin 1T/2H MoS grown on the carbon fiber also performs outstanding performance only with the matrix loading of 5%. This work offers necessary reference to improve microwave absorption performance by phase engineering and design a new type of flexible electromagnetic wave absorption material to apply for the portable microwave absorption electronic devices.
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http://dx.doi.org/10.1007/s40820-021-00646-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079512PMC
April 2021

Preschoolers' Approaches to Learning and Family-school Connections During COVID-19: An Empirical Study Based on a Wuhan Sample.

Early Child Educ J 2021 May 30:1-11. Epub 2021 May 30.

Wuhan University, Wuhan, Hubei China.

The concept, approaches to learning (ATL), is an important dimension of children's school readiness, which reflects children's enthusiasm and engagement in learning settings. Due to coronavirus disease 2019 (COVID-19), when preschools were shut down for months and children's social interactions were greatly limited, preschoolers' ATL might be negatively affected. However, strengthened family-school connections might have the potential to reduce the adverse effects of the pandemic. Based on a sample of 340 preschoolers from 30 classes of 6 preschools in Wuhan, China, we explored the association between family-preschool connections and preschoolers' ATL scores. The findings showed that the preschoolers' ATL were statistically and positively associated with parental attendance at the online parent-teacher meetings initiated by the preschools (standardized coefficient = 0.15). Policy implications regarding the enhancement of family-preschool connections are discussed.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10643-021-01217-x.
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http://dx.doi.org/10.1007/s10643-021-01217-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164827PMC
May 2021

Options for Care of Elderly Inpatients With Chronic Diseases: Analysis of Distribution and Factors Influencing Use of Care in Shanghai, China.

Front Public Health 2021 29;9:631189. Epub 2021 Apr 29.

School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, China.

China's ability to provide sufficient healthcare for an elderly population with chronic diseases has become a challenge because of poor utilization of different levels of medical institutions. We aimed to explore the characteristics and factors influencing patient choices and the resulting utilization of different levels of public medical institutions among elderly inpatients with chronic diseases. Data were collected from the Information Center of the Health and Family Planning Commission of Pudong New Area in Shanghai from 2013 to 2016. A cross-sectional study using multinomial logistic regression analysis was performed to find the factors influencing use of care. Records of patients were identified from electronic health records from public medical institutions. There were 95,445 elderly inpatients with chronic diseases in public medical institutions, 17.78% in community health centers, 68.44% in secondary hospitals, and 13.78% in tertiary hospitals. Compared with those over 80 years old, the 60-69 age group showed a preference for secondary hospitals (OR = 2.980, < 0.001) and tertiary hospitals (OR = 4.497, < 0.001), a trend also observed in the 70-79 age group (OR = 1.353, < 0.001; OR = 1.673, < 0.001). Compared with those using urban employee basic medical insurance, inpatients using urban resident basic medical insurance were less likely to visit secondary hospitals than community health centers (OR = 0.237, < 0.001) or tertiary hospitals (OR = 0.293, < 0.001). Compared with those inpatients who were married, inpatients who were widowed were less likely to go to secondary hospitals (OR = 0.391, < 0.001) or tertiary hospitals (OR = 0.045, < 0.001) than community health centers. The utilization of different levels of medical institutions by elderly people is not well-suited to the respective functions of these medical institutions. Most care services should be provided by community health centers, but our findings indicate that elderly people are more inclined to seek inpatient care at secondary hospitals and tertiary hospitals with some variation based on the patients' sex, age, medical insurance, expenses, and expected length of stay.
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http://dx.doi.org/10.3389/fpubh.2021.631189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116524PMC
May 2021

Reduced plasma level of basic fibroblast growth factor is associated with incomplete device endothelialization at six months following left atrial appendage closure.

BMC Cardiovasc Disord 2021 05 16;21(1):242. Epub 2021 May 16.

Department of Cardiology, Shanghai East Hospital, Shanghai, Tongji University School of Medicine, No. 150 Ji Mo Rd, Shanghai, 200120, People's Republic of China.

Objectives: To investigate whether inflammatory and growth factors (IGFs) were associated with incomplete device endothelialization (IDE) at 6 months after successful left atrial appendage closure (LAAC).

Background: IDE after LAAC is correlated with device-related thrombus (DRT) formation and subsequent thromboembolic events. However, biomarkers for early detection of IDE remain lacking.

Methods: Plasma levels of IGFs including basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), stromal cell derived factor (SDF)-1a, transforming growth factor (TGF)-β, vascular growth factor receptor-1 (VEGF-R) and von Willebrand factor (vWF) were determined using ELISA kits in 55 consecutive patients with atrial fibrillation (AF) at 6 months after LAAC with Watchman devices. The status of device endothelialization was assessed by transesophageal echocardiography and cardiac CT.

Results: IDE and complete device endothelialization(CDE)were detected in 38 and 17 patients, respectively. Among the six IGFs, only plasma level of bFGF was significantly lower in patients with IDE compared to those with CDE (303.49 ± 246.84 vs. 556.31 ± 197.84 pg/ml, p < 0.001). C-statistics of plasma bFGF for discriminating patients with IDE from those with CDE was 0.785 (95 % CI: 0.663-0.907, p < 0.001), with a cut-off value of 440.52pg/ml (sensitivity 0.765; specificity 0.789). Multivariate logistic regression model showed that lower bFGF was an independent factor for IDE (OR: 11.752, 95 % CI: 2.869-48.144, P = 0.001). bFGF improved the classification of patients (NRI: 0.677,95 % CI: 0.320-1.033, p = 0.004).

Conclusions: Reduced plasma bFGF level confers an increased risk for IDE after LAAC. Further prospective studies are warranted to examine if bFGF could serve as a biomarker for IDE post LAAC.
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http://dx.doi.org/10.1186/s12872-021-02059-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126129PMC
May 2021

PbCSE1 promotes lignification during stone cell development in pear (Pyrus bretschneideri) fruit.

Sci Rep 2021 05 3;11(1):9450. Epub 2021 May 3.

Pear Engineering Research Centre, College of Horticulture, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.

Pear [Pyrus bretschneideri cv. Dangshan Su] fruit quality is not always satisfactory owing to the presence of stone cells, and lignin is the main component of stone cells in pear fruits. Caffeoyl shikimate esterase (CSE) is a key enzyme in the lignin biosynthesis. Although CSE-like genes have been isolated from a variety of plant species, their orthologs are not characterized in pear. In this study, the CSE gene family (PbCSE) from P. bretschneideri was identified. According to the physiological data and quantitative RT-PCR (qRT-PCR), PbCSE1 was associated with lignin deposition and stone cell formation. The overexpression of PbCSE1 increased the lignin content in pear fruits. Relative to wild-type (WT) Arabidopsis, the overexpression of PbCSE1 delayed growth, increased the lignin deposition and lignin content in stems. Simultaneously, the expression of lignin biosynthetic genes were also increased in pear fruits and Arabidopsis. These results demonstrated that PbCSE1 plays an important role in cell lignification and will provide a potential molecular strategy to improve the quality of pear fruits.
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http://dx.doi.org/10.1038/s41598-021-88825-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093294PMC
May 2021

PbMC1a/1b regulates lignification during stone cell development in pear (Pyrus bretschneideri) fruit.

Hortic Res 2020 May 1;7(1):59. Epub 2020 May 1.

College of Horticulture, Nanjing Agricultural University, Nanjing, China.

Programmed cell death (PCD) and secondary cell wall (SCW) thickening in pear fruit are accompanied by the deposition of cellulose and lignin to form stone cells. Metacaspase is an important protease for development, tissue renewal and PCD. The understanding of the molecular mechanism whereby pear (Pyrus) metacaspase promotes PCD and cell wall lignification is still limited. In this study, the Metacaspases gene family (PbMCs) from P. bretschneideri was identified. PbMC1a/1b was associated with lignin deposition and stone cell formation by physiological data, semiquantitative real-time polymerase chain reaction (RT-PCR) and quantitative RT-PCR (qRT-PCR). Relative to wild-type (WT) Arabidopsis, the overexpression of PbMC1a/1b increased lignin deposition and delayed growth, thickened the cell walls of vessels, xylary fibers and interfascicular fibers, and increased the expression of lignin biosynthetic genes. Yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BiFC) and GST pull-down assays indicated that the PbMC1a/1b protein physically interacted with PbRD21. Simultaneously, the transient expression of PbMC1a/1b and PbRD21 led to significant changes in the expression of genes and lignin contents in pear fruits and flesh calli. These results indicate that PbMC1a/1b plays an important role in cell wall lignification, possibly by interacting with PbRD21 to increase the mRNA levels of some lignin synthesis-associated genes and promote the formation of stone cells in pear fruit.
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http://dx.doi.org/10.1038/s41438-020-0280-xDOI Listing
May 2020

The diagnostic value of EBV-DNA and EBV-related antibodies detection for nasopharyngeal carcinoma: a meta-analysis.

Cancer Cell Int 2021 Mar 10;21(1):164. Epub 2021 Mar 10.

State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, #151 Yanjiangxi Road, Guangzhou, 510120, Guangdong, People's Republic of China.

Background: Numerous individual studies have investigated the diagnostic value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection for nasopharyngeal carcinoma (NPC), but the conclusions remain controversial. This meta-analysis aimed to determine the value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection in the diagnosis of NPC.

Methods: PROSPERO registration number: CRD42019145532. PubMed, EMBASE, Cochrane Library, and Chinese data libraries (Wanfang, CNKI, and CBM) were searched up to January 2019. The pooled sensitivity, specificity, and positive likelihood, negative likelihood, and diagnostic odds ratios were conducted in this meta-analysis. Summary receiver operating characteristic curves evaluated the test-performance global summary. Publication bias was examined by Deek's funnel plot asymmetry test.

Results: Forty-seven studies with 8382 NPC patients (NPC group) and 15,089 individuals without NPC (Control group) were included in this meta-analysis. The sensitivity, specificity, positive likelihood (+ LR), negative likelihood (-LR), DOR and AUC of EBV-DNA in diagnosis of NPC were: 0.76 (95% CI 0.73-0.77), 0.96 (95% CI 0.95-0.97), 14.66 (95% CI 9.97-21.55), 0.19 (95% CI 0.13-0.28), 84 (95% CI 50.45-139.88), 0.96 (SE: 0.001), and 0.55 (95% CI 0.54-0.57), 0.96 (95% CI 0.96-0.97), 12.91 (95% CI 9.55-17.45), 0.35 (95% CI 0.29-0.43), 39.57 (95% CI 26.44-59.23), 0.94 (SE: 0.002) for the EA-IgA, and 0.85 (95% CI 0.84-0.85), 0.89 (95% CI 0.88-0.89), 6.73 (95% CI5.38-8.43), 0.17 (95% CI 0.12-0.23), 43.03 (95% CI 31.51-58.76), 0.93 (SE: 0.007) for the VCA-IgA, and 0.86 (95% CI 0.85-0.88), 0.87 (95% CI 0.88-0.90), 7.55 (95% CI 5.79-9.87), 0.16 (95% CI 0.13-0.19), 50.95 (95% CI 34.35-75.57), 0.94 (SE: 0.008) for the EBNA1-IgA, and 0.70 (95% CI 0.69-0.71), 0.94 (95% CI 0.94-0.95), 9.84 (95% CI 8.40-11.54), 0.25 (95% CI 0.21-0.31), 40.59 (95% CI 32.09-51.35), 0.95 (SE: 0.005) for the Rta-IgG. The EBV-DNA had larger AUC compared with other EBV-based antibodies (P < 0.05), while the difference between EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG was not statistically significant (P > 0.05).

Conclusions: EBV-DNA, VCA-IgA, EBNA1-IgA and Rta-IgG detection have high accuracy in early diagnosis NPC. In addition, EBV-DNA detection has the higher diagnosis accuracy in NPC. On the other hand, EA-IgA is suitable for the diagnosis but not NPC screening.
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http://dx.doi.org/10.1186/s12935-021-01862-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944913PMC
March 2021

Acceleration of fully computed hologram stereogram using lookup table and wavefront recording plane methods.

Appl Opt 2021 Mar;60(7):1814-1820

Lookup table (LUT) and wavefront recording plane (WRP) methods are proposed to accelerate the computation of fully computed hologram stereograms (HSs). In the LUT method, we precalculate large and complete spherical wave phases with varying depths, and each complex amplitude distribution segment of the object point can be obtained quickly by cropping a specific and small part of the precalculated spherical wave phases. Then, each hologram element (hogel) can be calculated by superposing all the related segments. In addition, setting a WRP near the 3D scene can further accelerate computation and reduce storage space. Because the proposed methods only replace the complex calculation using referencing LUT, they are accurate and have no limitation on the size of hogel compared with some methods of paraxial approximation. Simulations and optical experiments verify that the proposed methods can reconstruct quality 3D images with reduced computational load.
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http://dx.doi.org/10.1364/AO.415289DOI Listing
March 2021

Structural insights into the assembly and substrate selectivity of human SPT-ORMDL3 complex.

Nat Struct Mol Biol 2021 03 8;28(3):249-257. Epub 2021 Feb 8.

Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China.

Human serine palmitoyltransferase (SPT) complex catalyzes the initial and rate-limiting step in the de novo biosynthesis of all sphingolipids. ORMDLs regulate SPT function, with human ORMDL3 being related to asthma. Here we report three high-resolution cryo-EM structures: the human SPT complex, composed of SPTLC1, SPTLC2 and SPTssa; the SPT-ORMDL3 complex; and the SPT-ORMDL3 complex bound to two substrates, PLP-L-serine (PLS) and a non-reactive palmitoyl-CoA analogue. SPTLC1 and SPTLC2 form a dimer of heterodimers as the catalytic core. SPTssa participates in acyl-CoA coordination, thereby stimulating the SPT activity and regulating the substrate selectivity. ORMDL3 is located in the center of the complex, serving to stabilize the SPT assembly. Our structural and biochemical analyses provide a molecular basis for the assembly and substrate selectivity of the SPT and SPT-ORMDL3 complexes, and lay a foundation for mechanistic understanding of sphingolipid homeostasis and for related therapeutic drug development.
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http://dx.doi.org/10.1038/s41594-020-00553-7DOI Listing
March 2021

A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.

Science 2021 03 14;371(6533). Epub 2021 Jan 14.

Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.

The sterol regulatory element-binding protein (SREBP) pathway controls cellular homeostasis of sterols. The key players in this pathway, Scap and Insig-1 and -2, are membrane-embedded sterol sensors. The 25-hydroxycholesterol (25HC)-dependent association of Scap and Insig acts as the master switch for the SREBP pathway. Here, we present cryo-electron microscopy analysis of the human Scap and Insig-2 complex in the presence of 25HC, with the transmembrane (TM) domains determined at an average resolution of 3.7 angstrom. The sterol-sensing domain in Scap and all six TMs in Insig-2 were resolved. A 25HC molecule is sandwiched between the S4 to S6 segments in Scap and TMs 3 and 4 in Insig-2 in the luminal leaflet of the membrane. Unwinding of the middle of the Scap-S4 segment is crucial for 25HC binding and Insig association.
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http://dx.doi.org/10.1126/science.abb2224DOI Listing
March 2021

Additive-Controlled Divergent Synthesis of Tetrasubstituted 1,3-Enynes and Alkynylated 3-Pyrrolo[1,2-]indol-3-ones via Rhodium Catalysis.

Org Lett 2021 02 8;23(3):727-733. Epub 2021 Jan 8.

Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, P. R. China.

Herein, we report the additive-controlled divergent synthesis of tetrasubstituted 1,3-enynes and alkynylated 3-pyrrolo[1,2-]indol-3-ones through rhodium-catalyzed C-H alkenylation/DG migration and [3+2] annulation, respectively. This protocol features rare directing group migration in 1,3-diyne-involved C-H activation, excellent regio- and stereoselectivity, excellent monofunctionalization over difunctionalization, broad substrate scope, moderate to high yields, good functional group compatibility, and mild redox-neutral conditions.
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http://dx.doi.org/10.1021/acs.orglett.0c03950DOI Listing
February 2021

Near-Infrared Fluorescent Probes with Rotatable Polyacetylene Chains for the Detection of Amyloid-β Plaques.

J Phys Chem B 2021 01 8;125(2):497-506. Epub 2021 Jan 8.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

The plaques of accumulated β-amyloid (Aβ) in the parenchymal brain are accepted as an important biomarker for the early diagnosis of Alzheimer's disease (AD). Many near-infrared (NIR) probes, which were based on the D-π-A structure and bridged by conjugated double bonds, had been reported and displayed a high affinity to Aβ plaques. Considering the isomerization caused by the polyethylene chain, however, the conjugated polyacetylene chain is a better choice for developing new NIR Aβ probes. Hence, in this report, a new series of NIR probes with naphthyl or phenyl rings and different numbers of conjugated triple bonds were designed, synthesized, and evaluated as NIR probes for Aβ plaques. Upon interaction with Aβ aggregates, these probes displayed a significant increase in fluorescence intensity (45- to 360-fold) and a high to moderate affinity (6.05-56.62 nM). Among them, probe displayed excellent fluorescent properties with a 183-fold increase in fluorescence intensity and an emission maximum at 650 nm after incubated with Aβ aggregates. Furthermore, had a high affinity to Aβ aggregates ( = 12.96 nM) and could efficiently detect the Aβ plaques in brain sections from both transgenic mice and AD patients . In summary, this work may lead to a new direction in the development of novel NIR probes for the detection of Aβ plaques.
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http://dx.doi.org/10.1021/acs.jpcb.0c08845DOI Listing
January 2021

Necessary and Sufficient Conditions of Formation-Containment Control of High-Order Multiagent Systems With Observer-Type Protocols.

IEEE Trans Cybern 2021 Feb 4;PP. Epub 2021 Feb 4.

The analysis and design problems of formation-containment control for high-order linear time-invariant (LTI) multiagent systems (MASs) on directed graphs with observer-based output-feedback protocols are given in this work. To expand the feasibility of state formation configuration, two well-structured compensation signals are introduced for the leaders and followers in the protocols, respectively. Benefitting from the compensation signal of followers, the decoupling between formation control of leaders and containment control of followers is achieved. Thus, a necessary and sufficient condition is first established such that the formation-containment control for high-order LTI MASs can be achieved. Moreover, a heuristic iterative algorithm is developed to compute the controller gains, observer gains, as well as the compensation signals. Finally, two numerical examples are implemented to illustrate the time-varying formation-containment control of high-order MASs, which shows the validity and practicability of the theoretical results and algorithm.
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http://dx.doi.org/10.1109/TCYB.2020.3037133DOI Listing
February 2021

Identification of hub genes associated with the pathogenesis of diffuse large B-cell lymphoma subtype one characterized by host response via integrated bioinformatic analyses.

PeerJ 2020 20;8:e10269. Epub 2020 Nov 20.

Department of Pathology and Physiology, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Background: Host response diffuse large B-cell lymphoma (HR DLBCL) shares features of histologically defined T-cell/histiocyte-rich B-cell lymphoma, including fewer genetic abnormalities, frequent splenic and bone marrow involvement, and younger age at presentation. HR DLBCL is inherently less responsive to the standard treatment for DLBCL. Moreover, the mechanism of infiltration of HR DLBCL with preexisting abundant T-cells and dendritic cells is unknown, and their associated underlying immune responses incompletely defined. Here, hub genes and pathogenesis associated with HR DLBCL were explored to reveal molecular mechanisms and treatment targets.

Methods: Differentially expressed genes were identified in three datasets (GSE25638, GSE44337, GSE56315). The expression profile of the genes in the GSE53786 dataset was used to constructed a co-expression network. Protein-protein interactions analysis in the modules of interest identified candidate hub genes. Then screening of real hub genes was carried out by survival analysis within the GSE53786 and GSE10846 datasets. Expression of hub genes was validated in the Gene expression profiling interactive analysis, Oncomine databases and human tissue specimens. Functional enrichment analysis and Gene set enrichment analysis were utilized to investigate the potential mechanisms. Tumor Immune Estimation Resource and The Cancer Genome Atlas were used to mine the association of the hub gene with tumor immunity, potential upstream regulators were predicted using bioinformatics tools.

Results: A total of 274 common differentially expressed genes were identified. Within the key module, we identified CXCL10 as a real hub gene. The validation of upregulated expression level of CXCL10 was consistent with our study. CXCL10 might have a regulatory effect on tumor immunity. The predicted miRNA (hsa-mir-6849-3p) and transcription factor (IRF9) might regulate gene expression in the hub module.
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http://dx.doi.org/10.7717/peerj.10269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682441PMC
November 2020

Disease composition and epidemiological characteristics of primary care visits in Pudong New Area, Shanghai: a longitudinal study, 2016-2018.

BMJ Open 2020 11 17;10(11):e040878. Epub 2020 Nov 17.

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Objectives: This study aims to analyse the disease composition of primary care visits rather than specialist visits, the former of which had scarcely been studied. We adopted specific disease classification (International Statistical Classification of Diseases and Related Health Problems, 10th Revision), disease system and communicable/non-communicable/injury disease classification, and variations of sex and age were also analysed.

Setting: We extracted data from all community health service centres (CHSCs) and community health service stations in Pudong, Shanghai, from 2016 to 2018 using the electronic health record systems of the Pudong health information centre.

Participants: Our data included all 46 720 972 primary care visits from 2016 to 2018 in CHSCs in Pudong.

Results: We found that the top five diseases in primary care visits continued to be primary hypertension, problems related to medical facilities, chronic ischaemic heart disease, unspecified diabetes mellitus and acute upper respiratory infection. Lipoprotein metabolism disorder visits continued to increase over the study years. The numbers and proportions of patients with hypertension and unspecified diabetes were higher among men than women, and other cerebrovascular diseases were higher among women than men. The top five disease systems were circulatory system diseases, respiratory system diseases, endocrine/nutritional/metabolic diseases, factors influencing health status and digestive system diseases. The rankings of respiratory system and endocrine/nutritional/metabolic diseases rose over time. Non-communicable diseases (NCDs) accounted for approximately 90% of the primary care visits-a much higher percentage than other causes. The top five NCDs in primary care visits were cardiovascular and circulatory diseases, musculoskeletal disorders, diabetes, digestive diseases and urogenital diseases. Compared with women, men suffered from cardiovascular diseases at an earlier age.

Conclusions: Different from specialist visits, common diseases, especially NCDs, were the main disease composition of current primary healthcare visits while the former focused on intractable diseases such as tumours, indicating that primary healthcare had played the role of gatekeeper of the healthcare system.
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http://dx.doi.org/10.1136/bmjopen-2020-040878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674101PMC
November 2020

Structural insights into the photoactivation of Arabidopsis CRY2.

Nat Plants 2020 12 16;6(12):1432-1438. Epub 2020 Nov 16.

National Key Laboratory of Crop Genetic Improvement and National Centre of Plant Gene Research, Huazhong Agricultural University, Wuhan, China.

The blue-light receptor cryptochrome (CRY) in plants undergoes oligomerization to transduce blue-light signals after irradiation, but the corresponding molecular mechanism remains poorly understood. Here, we report the cryogenic electron microscopy structure of a blue-light-activated CRY2 tetramer at a resolution of 3.1 Å, which shows how the CRY2 tetramer assembles. Our study provides insights into blue-light-mediated activation of CRY2 and a theoretical basis for developing regulators of CRYs for optogenetic manipulation.
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http://dx.doi.org/10.1038/s41477-020-00800-1DOI Listing
December 2020

Recombinant H7 hemagglutinin expressed in glycoengineered Pichia pastoris forms nanoparticles that protect mice from challenge with H7N9 influenza virus.

Vaccine 2020 11 31;38(50):7938-7948. Epub 2020 Oct 31.

Department of Microorganism Engineering, Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing 100071, China. Electronic address:

Cases of H7N9 human infection caused by an avian-origin H7N9 virus emerged in eastern China in 2013, leading to the urgent requirement of developing an effective vaccine to reduce its pandemic potential. In this report, the full-length recombinant H7 protein (rH7) of A/Hangzhou/1/2013 (H7N9) virus was expressed by a glycoengineered Pichia pastoris system. The rH7 protein underwent complex glycosylation modifications and polymerized to nanoparticles of 30-50 nm in diameter. Recombinant H7 (1.9 µg) elicited a > 1:40 hemagglutination inhibition titer, and 3.75 µg rH7 protected 100% of the mice in the mice challenge model with 10-fold 50% lethal dose of the A/Shanghai/2/2013 (H7N9) rat lung-adapted strain. In conclusion, rH7 produced by the glycoengineered P. pastoris can be used for vaccination against the H7N9 virus, and provides an effective platform for the rapid production of future influenza vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2020.10.061DOI Listing
November 2020
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