Publications by authors named "Hong-wei Wang"

503 Publications

Parallel subgenome structure and divergent expression evolution of allo-tetraploid common carp and goldfish.

Nat Genet 2021 Oct 30;53(10):1493-1503. Epub 2021 Sep 30.

North China University of Science and Technology, Tangshan, China.

How two subgenomes in allo-tetraploids adapt to coexistence and coordinate through structure and expression evolution requires extensive studies. In the present study, we report an improved genome assembly of allo-tetraploid common carp, an updated genome annotation of allo-tetraploid goldfish and the chromosome-scale assemblies of a progenitor-like diploid Puntius tetrazona and an outgroup diploid Paracanthobrama guichenoti. Parallel subgenome structure evolution in the allo-tetraploids was featured with equivalent chromosome components, higher protein identities, similar transposon divergence and contents, homoeologous exchanges, better synteny level, strong sequence compensation and symmetric purifying selection. Furthermore, we observed subgenome expression divergence processes in the allo-tetraploids, including inter-/intrasubgenome trans-splicing events, expression dominance, decreased expression levels, dosage compensation, stronger expression correlation, dynamic functionalization and balancing of differential expression. The potential disorders introduced by different progenitors in the allo-tetraploids were hypothesized to be alleviated by increasing structural homogeneity and performing versatile expression processes. Resequencing three common carp strains revealed two major ecotypes and uncovered candidate genes relevant to growth and survival rate.
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http://dx.doi.org/10.1038/s41588-021-00933-9DOI Listing
October 2021

Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2.

Cell Discov 2020 Sep 29;6(1):68. Epub 2020 Sep 29.

CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the recent pandemic COVID-19, is reported to have originated from bats, with its intermediate host unknown to date. Here, we screened 26 animal counterparts of the human ACE2 (hACE2), the receptor for SARS-CoV-2 and SARS-CoV, and found that the ACE2s from various species, including pets, domestic animals and multiple wild animals, could bind to SARS-CoV-2 receptor binding domain (RBD) and facilitate the transduction of SARS-CoV-2 pseudovirus. Comparing to SARS-CoV-2, SARS-CoV seems to have a slightly wider range in choosing its receptor. We further resolved the cryo-electron microscopy (cryo-EM) structure of the cat ACE2 (cACE2) in complex with the SARS-CoV-2 RBD at a resolution of 3 Å, revealing similar binding mode as hACE2 to the SARS-CoV-2 RBD. These results shed light on pursuing the intermediate host of SARS-CoV-2 and highlight the necessity of monitoring susceptible hosts to prevent further outbreaks.
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http://dx.doi.org/10.1038/s41421-020-00210-9DOI Listing
September 2020

Atomically Thin Bilayer Janus Membranes for Cryo-electron Microscopy.

ACS Nano 2021 Sep 27. Epub 2021 Sep 27.

Center for Nanochemistry, Beijing Science and Engineering Center for Nanocarbons, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Cryo-electron microscopy (cryo-EM) has emerged as a vital tool to reveal the native structure of beam-sensitive biomolecules and materials. Yet high-resolution cryo-EM analysis is still limited by the poorly controlled specimen preparation and urgently demands a robust supporting film material to prepare desirable samples. Here, we developed a bilayer Janus graphene membrane with the top-layer graphene being functionalized to interact with target molecules on the surface, while the bottom layer being kept intact to reinforce its mechanical steadiness. The ultraclean and atomically thin bilayer Janus membrane prepared by our protocol on one hand generates almost no extra noise and on the other hand reduces the specimen motion during cryo-EM imaging, thus allowing the atomic-resolution characterization of surface functional groups. Using such Janus membranes in cryo-EM specimen preparation, we were able to directly image the lithium dendrite and reconstruct macromolecules at near-atomic resolution. Our results demonstrate the bilayer Janus design as a promising supporting material for high-resolution cryo-EM and EM imaging.
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http://dx.doi.org/10.1021/acsnano.1c06233DOI Listing
September 2021

Recurrent colorectal liver metastasis patients could benefit from repeat hepatic resection.

BMC Surg 2021 Aug 16;21(1):327. Epub 2021 Aug 16.

Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, No. 52, Fu-Cheng-Lu Street, Beijing, 100142, People's Republic of China.

Background: Local treatment remains the best option for recurrent colorectal liver metastasis (CRLM). The current study aimed to investigate predictive factors of survival outcomes and select candidates for local treatment for CRLM at first recurrence.

Methods: Data were collected retrospectively from CRLM patients who underwent hepatic resection and developed first recurrence between 2000 and 2019 at our institution.
A nomogram predicting overall survival was established based on a multivariable Cox model of clinicopathologic factors. The predictive accuracy and discriminative ability of the nomogram were determined by the concordance index and calibration curve.

Results: Among 867 patients who underwent curative hepatic resection, 549 patients developed recurrence. Three hundred patients were evaluated and had resectable and liver-limited disease. Among them, repeat liver resection and percutaneous radiofrequency ablation were performed in 88 and 85 patients, respectively. The other 127 patients received only systemic chemotherapy. Multivariable analysis identified primary lymph node positivity, tumor size > 3 cm, early recurrence, RAS gene mutation and no local treatment as independent risk factors for survival outcomes. Integrating these five variables, the nomogram presented a good concordance index of 0.707. Compared with patients who received only systemic chemotherapy, radical local treatment did not significantly improve survival outcomes (median OS: 21 vs. 15 months, p = 0.126) in the high-risk group (total score ≥ 13).

Conclusion: Radical local treatment improved the survival of recurrent CRLM patients. The proposed model facilitates personalized assessments of prognosis for patients who develop first recurrence in the liver.
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http://dx.doi.org/10.1186/s12893-021-01323-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365902PMC
August 2021

Characterizing the interruption-recovery patterns of urban air pollution under the COVID-19 lockdown in China.

Build Environ 2021 Nov 11;205:108231. Epub 2021 Aug 11.

Center for Intelligent Transportation Systems and Unmanned Aerial Systems Applications Research, State-Key Laboratory of Ocean Engineering, School of Naval Architecture, Ocean and Civil Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

The COVID-19 pandemic provides an opportunity to study the effects of urban lockdown policies on the variation in pollutant concentrations and to characterize the recovery patterns of urban air pollution under the interruption of COVID-19 lockdown policies. In this paper, interruption-recovery models and regression discontinuity design were developed to characterize air pollution interruption-recovery patterns and analyze environmental impacts of the COVID-19 lockdown, using air pollution data from four Chinese metropolises (i.e., Shanghai, Wuhan, Tianjin, and Guangzhou). The results revealed the air pollutant interruption-recovery curve represented by the three lockdown response periods (Level I, Level II and Level III) during COVID-19. The curve decreased during Level I (A 25.3%-48.8% drop in the concentration of NO has been observed in the four metropolises compared with the same period in 2018-2019.), then recovered around reopening, but decreased again during Level III. Moreover, the interruption-recovery curve of the year-on-year air pollution difference suggests a process of first decreasing during Level I and gradually recovering to a new equilibrium during Level III (e.g., the unit cumulative difference of NO mass concentrations in Shanghai was 21.7, 22.5, 11.3 (μg/m) during Level I, II, and III and other metropolises shared similar results). Our findings reveal general trends in the air quality externality of different lockdown policies, hence could provide valuable insights into air pollutant interruption-recovery patterns and clear scientific guides for policymakers to estimate the effect of different lockdown policies on urban air quality.
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http://dx.doi.org/10.1016/j.buildenv.2021.108231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354860PMC
November 2021

Estrogen Deficiency Aggravates Fluoride-Induced Liver Damage and Lipid Metabolism Disorder in Rats.

Biol Trace Elem Res 2021 Aug 15. Epub 2021 Aug 15.

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, 471023, Henan, People's Republic of China.

Estrogen exerts essential role in liver metabolism, and its deficiency is frequently accompanied by a series of metabolic disorder diseases. To investigate the role of estrogen deficiency in fluorine ions (F) induced liver injury, the ovariectomy (OVX) rat models were performed by surgically removing the ovaries, and the rats from OVX and non-OVX models were exposed to differential dose of F (0, 25, 50 and 100 mg/L) in drinking water for 90 days. The liver morphological structure was evaluated by hematoxylin-eosin staining. Proliferation ability of hepatocytes was evaluated by 5-bromo-2-deoxyuridine (BrdU) assay. And distribution of lipid droplets in liver tissue was observed via oil red O staining. In addition, the liver function and lipid metabolism parameters in serum were detected by commercial kits. Results showed that F induced hepatocytes morphological damage and inhibited the proliferation ability of hepatocytes; estrogen deficiency exacerbated these changes. The deposition of lipid droplets in the liver tissue was multiplicative with increased F dose, especially after estrogen deficiency. In addition, F exposure increased (P < 0.05 or P < 0.01) serum aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (γ-GT) activities and total bilirubin (T-bil) level; meanwhile, serum triglyceride (TG) and cholesterol (TC) levels were also elevated (P < 0.05 or P < 0.01). F-induced liver function and lipid metabolism indexes were further increased (P < 0.05 or P < 0.01) in the state of estrogen deficiency. In conclusion, estrogen deficiency aggravated F-induced liver damage and lipid metabolism disorder.
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http://dx.doi.org/10.1007/s12011-021-02857-1DOI Listing
August 2021

[Clinical Significance of Truncated Mutant ΔJBP of TET2 Gene in Patients with Acute Myeloid Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Aug;29(4):1011-1018

Departmenet of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China,E-mail:

Objective: To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML).

Methods: Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion.

Results: Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPA) were more frequency (31.3% vs 0, P=0.009), the complete remission (CR) rate after induction chemotherapy(37.5% vs 81.8%, P=0.008) were lower, the median EFS (5 vs 19 months, P=0.000) and median OS (16 vs 22 months, P=0.041) were shorter. Univariate analysis showed that platelets <50×109/L (P=0.004) and CEBPA (P=0.001) were related to the shorter OS of the patients. Further COX multivariate analysis showed that CEBPA is an independent prognostic factors of OS in TET2ΔJBP patients (P=0.010). In addition, ΔJBP patients with CEBPA showed lower hemoglobin levels (62 vs 75g/L, P=0.030) and lower median OS (9 months vs 18 months, P=0.000) than the patients without CEBPA.

Conclusion: AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPA, which is the independent prognostic factors of OS in AML patients with TET2ΔJBP.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.04.001DOI Listing
August 2021

Three epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants.

Cell Discov 2021 Jul 20;7(1):53. Epub 2021 Jul 20.

Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China.

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations at the receptor-binding domain (RBD) have emerged, and some of them can evade existing neutralizing antibodies. Here, we utilized RenMab, a novel mouse carrying the entire human antibody variable region, for neutralizing antibody discovery. We obtained several potent RBD-blocking antibodies and categorized them into four distinct groups by epitope mapping. We determined the involved residues of the epitope of three representative antibodies by cryo-electron microscopy (Cryo-EM) studies. Moreover, we performed neutralizing experiments with 50 variant strains with single or combined mutations and found that the mixing of three epitope-distinct antibodies almost eliminated the mutant escape. Our study provides a sound basis for the rational design of fully human antibody cocktails against SARS-CoV-2 and pre-emergent coronaviral threats.
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http://dx.doi.org/10.1038/s41421-021-00292-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290868PMC
July 2021

Characterization of genomic alterations in Chinese colorectal cancer patients with liver metastases.

J Transl Med 2021 07 19;19(1):313. Epub 2021 Jul 19.

Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Haidian District, Beijing, China.

Background: The exploration of genomic alterations in Chinese colorectal liver metastasis (CRLM) is limited, and corresponding genetic biomarkers for patient's perioperative management are still lacking. This study aims to understand genome diversification and complexity that developed in CRLM.

Methods: A custom-designed IDT capture panel including 620 genes was performed in the Chinese CRLM cohort, which included 396 tumor samples from metastatic liver lesions together with 133 available paired primary tumors.

Results: In this Chinese CRLM cohort, the top-ranked recurrent mutated genes were TP53 (324/396, 82%), APC (302/396, 76%), KRAS (166/396, 42%), SMAD4 (54/396, 14%), FLG (52/396, 13%) and FBXW7 (43/396, 11%). A comparison of CRLM samples derived from left- and right-sided primary lesions confirmed that the difference in survival for patients with different primary tumor sites could be driven by variations in the transforming growth factor β (TGF-β), phosphatidylinositol 3-kinase (PI3K) and RAS signaling pathways. Certain genes had a higher variant rate in samples with metachronous CRLM than in samples with simultaneous metastasis. Overall, the metastasis and primary tumor samples displayed highly consistent genomic alterations, but there were some differences between individually paired metastases and primary tumors, which were mainly caused by copy number variations.

Conclusion: We provide a comprehensive depiction of the genomic alterations in Chinese patients with CRLM, providing a fundamental basis for further personalized therapy applications.
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http://dx.doi.org/10.1186/s12967-021-02986-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287676PMC
July 2021

3D-printed titanium implant combined with interleukin 4 regulates ordered macrophage polarization to promote bone regeneration and angiogenesis.

Bone Joint Res 2021 Jul;10(7):411-424

Institute of Stomatology, Shandong University, Jinan, Shandong, China.

Aims: The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration.

Methods: IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively.

Results: DT plus 30 ng/ml of IL4 (DT + 30 IL4) from day 3 to day 7 significantly (p < 0.01) enhanced macrophage type 2 polarization and BMMSC osteogenesis compared with the other groups. Local injection of IL4 enhanced new bone formation surrounding the DT.

Conclusion: DT + 30 IL4 may switch macrophage polarization at the appropriate timepoints to promote bone regeneration. Cite this article:  2021;10(7):411-424.
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http://dx.doi.org/10.1302/2046-3758.107.BJR-2020-0334.R4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333031PMC
July 2021

The effects of high-intensity interval training, Nordic walking and moderate-to-vigorous intensity continuous training on functional capacity, depression and quality of life in patients with coronary artery disease enrolled in cardiac rehabilitation: A randomized controlled trial (CRX study).

Prog Cardiovasc Dis 2021 Jul 7. Epub 2021 Jul 7.

Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada; School of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada. Electronic address:

Background: Coronary artery disease (CAD) patients undergoing revascularization procedures often experience ongoing, diminished functional capacity, high rates of depression and markedly low quality of life (QoL). In CAD patients, studies have demonstrated that high-intensity interval training (HIIT) is superior to traditional moderate-to-vigorous intensity continuous training (MICT) for improving functional capacity, whereas no differences between Nordic walking (NW) and MICT have been observed. Mental health is equally as important as physical health, yet few studies have examined the impact of HIIT and NW on depression and QoL. The purpose of this randomized controlled trial (RCT) was to compare the effects of 12 weeks of HIIT, NW and MICT on functional capacity in CAD patients. The effects on depression severity, brain-derived neurotrophic factor (BDNF) and QoL were also examined.

Methods: CAD patients who underwent coronary revascularization procedures were randomly assigned to: (1) HIIT (4 × 4-min of high-intensity work periods at 85%-95% peak heart rate [HR]), (2) NW (resting HR [RHR] + 20-40 bpm), or (3) MICT (RHR + 20-40 bpm) twice weekly for 12 weeks. Functional capacity (six-min walk test [6MWT]), depression (Beck Depression Inventory-II [BDI-II]), BDNF (from a blood sample), and general (Short-Form 36 [SF-36]) and disease-specific (HeartQoL) QoL were measured at baseline and follow-up. Linear mixed-effects models for repeated measures were used to test the effects of time, group and time × group interactions.

Results: N = 135 CAD patients (aged 61 ± 7 years; male: 85%) participated. A significant time × group interaction (p = 0.042) showed greater increases in 6MWT distance (m) for NW (77.2 ± 60.9) than HIIT (51.4 ± 47.8) and MICT (48.3 ± 47.3). BDI-II significantly improved (HIIT: -1.4 ± 3.7, NW: -1.6 ± 4.0, MICT: -2.3 ± 6.0 points, main effect of time: p < 0.001) whereas BDNF concentrations did not change (HIIT: -2.5 ± 9.6, NW: -0.4 ± 7.7, MICT: -1.2 ± 6.4 ng/mL, main effect of time: p > 0.05). Significant improvements in SF-36 and HeartQoL values were observed (main effects of time: p < 0.05). HIIT, NW and MICT participants attended 17.7 ± 7.5, 18.3 ± 8.0 and 16.1 ± 7.3 of the 24 exercise sessions, respectively (p = 0.387).

Conclusions: All exercise programmes (HIIT, NW, MICT) were well attended, safe and beneficial in improving physical and mental health for CAD patients. NW was, however, statistically and clinically superior in increasing functional capacity, a predictor of future cardiovascular events.
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http://dx.doi.org/10.1016/j.pcad.2021.07.002DOI Listing
July 2021

High and Tunable Proton Conduction in Six 3D-Substituted Imidazole Dicarboxylate-Based Lanthanide-Organic Frameworks.

Inorg Chem 2021 Jul 1;60(14):10808-10818. Epub 2021 Jul 1.

College of Chemistry and Green Catalysis Centre, Zhengzhou University, Zhengzhou, 450001 Henan, P. R. China.

Six isostructural three-dimensional (3D) Ln(III)-organic frameworks, {[Ln(HMIDC)(μ-CO)(HO)]·4HO} [Ln = Gd (), Eu (), Sm (), Nd (), Pr (), and Ce ()], have been fabricated by using a multifunctional ligand of 2-methyl-1-imidazole-4,5-dicarboxylic acid (HMIDC). Ln-metal-organic frameworks (MOFs) present 3D structures and possess abundant H-bonded networks between imidazole-N atoms and coordinated and free water molecules. All the six Ln-MOFs demonstrate humidity- and temperature-dependent proton conductivity (σ) having the optimal values of 2.01 × 10, 1.40 × 10, 0.93 × 10, 2.25 × 10, 1.11 × 10, and 0.96 × 10 S·cm for , respectively, at 100 °C/98% relative humidity, in the order of Ce () < Pr () < Nd () < Sm () < Eu () < Gd (). In particular, the σ for is 1 order of magnitude higher than that for , and it enhances systematically according to the decreasing order of the ionic radius, indicating that the lanthanide-contraction tactics can effectively regulate the proton conductivity while retaining the proton conduction routes. This will offer valuable guidance for the acquisition of new proton-conducting materials. In addition, the outstanding water stability and electrochemical stability of such Ln-MOFs will afford a solid material basis for future applications.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01522DOI Listing
July 2021

Association between the Polymorphisms of and and Poly-Unsaturated Fatty Acids in Common Carp ().

Animals (Basel) 2021 Jun 15;11(6). Epub 2021 Jun 15.

Key Laboratory of Aquatic Genomics, Ministry of Agriculture and Rural Affairs, and Beijing Key Laboratory of Fishery Biotechnology, Chinese Academy of Fishery Sciences, Beijing 100141, China.

Fatty acid desaturase 2 () is one of the rate-limiting enzymes in PUFAs biosynthesis. Compared with the diploid fish encoding one , the allo-tetraploid common carp, one most important food fish, encodes two fads2 genes ( and ). The associations between the contents of different PUFAs and the polymorphisms of and have not been studied. The contents of 12 PUFAs in common carp individuals were measured, and the polymorphisms in the coding sequences of and were screened. We identified five coding single nucleotide polymorphisms (cSNPs) in and eleven cSNPs in . Using the mixed linear model and analysis of variance, a synonymous cSNP was significantly associated with the content of C20:3n-6. One non-synonymous cSNP (fads2b.751) and one synonymous cSNP (fads2b.1197) were associated with the contents of seven PUFAs and the contents of six PUFAs, respectively. The heterozygous genotypes in both loci were associated with higher contents than the homozygous genotypes. The fads2b.751 genotype explained more phenotype variation than the fads2b.1197 genotype. These two SNPs were distributed in one haplotype block and associated with the contents of five common PUFAs. These results suggested that might be the major gene responding to common carp PUFA contents and that fads.751 might be the main effect SNP. These cSNPs would be potential markers for future selection to improve the PUFA contents in common carp.
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http://dx.doi.org/10.3390/ani11061780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232129PMC
June 2021

En bloc right hemicolectomy with pancreatoduodenectomy for right-sided colon cancer invading duodenum.

BMC Surg 2021 Jun 29;21(1):302. Epub 2021 Jun 29.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital & Institute, Beijing, China.

Background: En bloc right hemicolectomy with pancreatoduodenectomy (RHCPD) is the optimum treatment to achieve the adequate margin of resection (R0) for locally advanced right-sided colon cancer with duodenal invasion. Information regarding the indications and outcomes of this procedure is limited.

Method: In this retrospective study, 2269 patients with right colon cancer underwent radical right colectomy between October 2010 and May 2019, in which 19 patients underwent RHCPD for LARCC were identified. The overall survival (OS), disease-free survival (DFS), operative mortality, postsurgical complications, gene mutational analysis, and prognostic factors were evaluated. Survival was estimated using Kaplan-Meir method.

Results: Of these 19 patients who underwent LARCC, the OS was 88%, 66%, and 58% at 1, 3, and 5 years. The DFS was 72%, 56%, and 56% at 1, 3, and 5 years. The median operative time was 320 min (range: 222-410 min), and the median operative blood loss was 268 mL (range: 100-600 mL). The OS was significantly better among patients with well-differentiated tumor, N0 stage, and high microsatellite instability (MSI) and in patients who received adjuvant chemotherapy. The major postoperative complications occurred in 8 patients (42%), with pancreatic fistula (PF) being the most common. On the basis of the univariate analysis, poorly differentiated tumor, regional lymph node dissemination, MSI status, and no perioperative chemotherapy were the significant predictors of poor survival (P < 0.05).

Conclusions: This study suggests that RHCPD is feasible and can achieve complete tumor clearance with favorable outcome, particularly in patients with lymph node-negative status.
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http://dx.doi.org/10.1186/s12893-021-01286-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243482PMC
June 2021

Case Report: Anlotinib Combined With Sintilimab as Third-Line Treatment in a Metastatic Urothelial Bladder Carcinoma Patient With FGFR3 Mutation.

Front Oncol 2021 24;11:643413. Epub 2021 May 24.

Comprehensive Urogenital Cancer Center, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, China.

We report on a case of metastatic urothelial bladder carcinoma (mUBC) treated with anlotinib combined with sintilimab. A 69-year-old male was diagnosed with non-muscle invasive bladder cancer (NMIBC). He received transurethral resection of bladder tumor (TURBT) and intravesical gemcitabine chemotherapy. After the patients' cancer progressed to mUBC, cisplatin-based chemotherapy (gemcitabine combined with cisplatin, GC) was performed to this patient as first line therapy for four cycles. However, the disease progressed again within 6 months. Local radiotherapy was performed on the metastatic lesions, and after radiotherapy, the patient received anti-PD-1 antibody (sintilimab 200 mg, q3w)combined with Albumin-bound (Nab)-paclitaxel (100 mg, qw) as the second-line therapy, but the patient's cancer was still observed to be progressing. Molecular characterization confirmed the presence of FGFR3 mutations in the patient. Anlotinib was recommended to this patient. After the patient was fully informed and he was aware of off-label use of the drug, then, Nab-paclitaxel was replaced by anlotinib (10 mg D1-14, q3w) and sintilimab infusions were maintained for every 3 weeks. Partial response (PR) was observed through imaging examinations and stable disease (SD) was observed for more than 11 months; the patient's quality of life also improved. This case suggested that anlotinib combined with sintilimab may be a safe and effective choice in the treatment of mUBC in patients with FGFR3 mutations.
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http://dx.doi.org/10.3389/fonc.2021.643413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180869PMC
May 2021

[Quantitative Analysis on Immunophenotype of CD34 Myeloid Precursor Cells in Myelodysplastic Syndrome and Its Correlation with Clinical Features].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):832-839

Department of Hematology, Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China,E-mail:

Objective: To investigate the quantitative expression of immunophenotype of CD34 myeloid precursor cells in myelodysplastic syndrome (MDS) patients and its correlation with clinical characteristics, and understand the effect of quantitative expression of CD7 and CD117 on the prognosis of low-risk MDS patients.

Methods: Multi-parameter flow cytometry (FCM) was used to detect the proportion and mean fluorescence intensity (MFI) of each antigen of bone marrow CD34 myeloid precursor cells in 79 MDS patients. The correlation between the expression level of each immune marker and clinical characteristics was compared. The effects of quantitative expressions of CD7 and CD117 on the overall survival rate of low-risk patients were explored.

Results: Bone marrow blast cell proportion (P<0.01), RBC level (P<0.01), and Hb level (P<0.05) of high-risk MDS patients were higher, while EPO level (P<0.05) was lower than those of low-risk patients. The proportion of CD34 blast cells (P<0.01), the proportion of CD117 (P<0.05) and the MFI of CD7 (P<0.05) were higher in high-risk patients than those in low-risk patients, but the MFI of CD123 was lower (P<0.05). In high-risk MDS patients, CD15/CD34 (MFI) and CD19/CD34 (MFI) positively correlated with the proportion of total T cells (r=0.458; r=0.505), while CD19/CD34 (%) and CD19/CD34 (MFI) negatively correlated with WBC levels (r=-0.469; r=-0.503). In low-risk MDS patients, CD34 (%) positively correlated with bone marrow erythrocyte proportion, PLT level and neutrophil level (r=0.426; r=0.486; r=0.495), but negatively correlated with LDH level (r=-0.421); WT1 expression level was positively correlated with CD10/CD34 (%), CD10/CD34 (MFI) and CD117/CD34 (MFI) (r=0.745; r=0.800; r=0.434), while negatively correlated with CD11b/CD34 (%)(r=-0.457); CD19/CD34 (%) and CD71/CD34 (MFI) negatively correlated with NK cell proportion (r=-0.786; r=-0.514); CD10/CD34 (%) positively correlated with Th/Ts, while CD7/CD34 (MFI) negatively correlated with the proportion of Th cells (r=0.738; r=-0.513); HLADR/CD34 (%) and HLADR/CD34 (MFI) negatively correlated with PLT level (r=-0.461; r=-0.445), while HLADR/CD34 (MFI) positively correlated with bone marrow NAP fraction (r=0.552). The quantitative expression of CD7 and CD117 had no significant effect on the overall survival rate of low-risk MDS patients.

Conclusion: The immunophenotype of CD34 myeloid precursor cell in different risk groups in MDS patients is related to clinical characteristics. Bone marrow cell morphology, clinical and laboratory features and immunophenotype will be of great significance to the diagnosis, clinical classification and prognosis evaluation of MDS patients.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.028DOI Listing
June 2021

Anticoccidial effect of toltrazuril and Radix Sophorae Flavescentis combination: Reduced inflammation and promoted mucosal immunity.

Vet Parasitol 2021 Aug 27;296:109477. Epub 2021 May 27.

College of Animal Science and Technology, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang, Henan, 471023, People's Republic of China.

An anticoccidial model of chicken infected with Eimeria tenella was established to investigate the effect of toltrazuril (Tol) combined with the Radix Sophorae Flavescentis (RSF) on coccidiosis. The anticoccidial index (ACI) was evaluated, and the cecal developmental parameters (i.e., villus height, [VH], crypt depth, [CD], and VH/CD) were determined. The distributions of glycoproteins and goblet cells in the cecal tissue were determined through the Periodic Acid-Schiff (PAS) and Alcian blue PAS staining methods, respectively. The mRNA expression levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, and IL-17 of the cecal tissue were determined through quantitative real-time PCR. The moderate ACI was obtained using the combination of Tol and RSF. Compared with the normal control (NC) group, the infected control (IC) group showed remarkably lower VH and VH/CD at five and seven days postinfection. Compared with the IC group, the IC + RSF and IC + TolRSF groups showed remarkably higher VH and VH/CD at five and seven days postinfection. Compared with the NC group, the IC group contained fewer glycoproteins and goblet cells, but the Tol and RSF treatment promoted more glycoproteins and goblet cells at five and seven days postinfection. The mRNA expression levels of IL-1β, IL-2, IL-4, IL-6, IL-10, and IL-17 in the IC group were upregulated (P < 0.01) compared with those in the NC group. The IC + RSF and IC + TolRSF groups had downregulated mRNA expression levels of IL-1β, IL-6, and IL-17 cytokines (P < 0.01), and upregulated mRNA expression levels of IL-2 and IL-4 cytokines (P < 0.01) compared with the IC group. Results showed that the combination of Tol and RSF exerts anticoccidial effect by reducing inflammation and promoting intestinal mucosal immunity.
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http://dx.doi.org/10.1016/j.vetpar.2021.109477DOI Listing
August 2021

The prognostic impact of resection margin status varies according to the genetic and morphological evaluation (GAME) score for colorectal liver metastasis.

J Surg Oncol 2021 Sep 3;124(4):619-626. Epub 2021 Jun 3.

Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Ministry of Education, Peking University School of Oncology, Beijing, China.

Background: Surgical margin status remains a controversial factor in predicting the outcome of colorectal liver metastases (CRLM) resection. Our study aims to evaluate the effects of surgical margins on oncologic outcomes with regard to the genetic and morphological evaluation (GAME) score.

Methods: R1 resection was defined as having a less than 1 mm margin width. Patients who underwent surgery for CRLM from January 2005 to December 2018 were recruited. The patients were divided into two risk subgroups, namely, the low or medium risk (GAME 0-3) and high-risk (GAME score 4 or more) groups. The effects of margin status on overall survival (OS) and recurrence-free survival rate (RFS) were examined.

Results: In total, 661 patients were recruited, among which 159 (24.1%) had R1 resection. Before hepatectomy, 514 patients showed a low or medium risk (R1 resection: n = 124), while 147 patients demonstrated a high risk (R1 resection: n = 35). In the whole cohort, multivariable analysis did show that R1 resection was associated with worse RFS and OS. While further research only found that in the low or medium risk group, R1 resection was related to poor OS and RFS. Meanwhile, in the high risk group, no significant difference was found in the median OS and RFS among patients with R0 or R1 resection.

Conclusion: The prognostic role of margin status varied according to the GAME score. Margin clearance only improved survival rates in patients with low or medium GAME score. In contrast, R1 resection demonstrated similar oncologic outcomes with R0 resection in patients with high GAME score.
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http://dx.doi.org/10.1002/jso.26557DOI Listing
September 2021

Root endophyte-enhanced peanut-rhizobia interaction is associated with regulation of root exudates.

Microbiol Res 2021 Sep 14;250:126765. Epub 2021 May 14.

Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Industrialization of Microbial Resources, College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu Province, 210023, China. Electronic address:

Root exudates play a crucial role in the symbiosis between leguminous plants and rhizobia. Our previous studies have shown that a fungal endophyte Phomopsis liquidambaris promotes peanut-rhizobia nodulation and nitrogen fixation, but the underlying mechanism are largely unknown. Here, we explore the role of peanut root exudates in Ph. liquidambaris-mediated nodulation enhancement. We first collected root exudates from Ph. liquidambaris-inoculated and un-inoculated peanuts and determined their effects on rhizobial growth, biofilm formation, chemotaxis, nodC gene expression, and peanut nodulation. Our results found a positive effect of Ph. liquidambaris-inoculated root exudates on these characteristics of rhizobia. Next, we compared the root exudates profile of Ph. liquidambaris-inoculated and un-inoculated plants and found that Ph. liquidambaris altered the concentrations of phenolic acids, flavonoids, organic acids and amino acids in root exudates. Furthermore, the rhizobial chemotaxis, growth and biofilm formation in response to the changed compounds at different concentrations showed that all of the test compounds induced rhizobial chemotactic behavior, and organic acids (citric acid and oxalic acid) and amino acid (glutamate, glycine and glutamine) at higher concentrations increased rhizobial growth and biofilm formation. Collectively, our results suggest that root exudates alterations contribute to Ph. liquidambaris-mediated peanut-rhizobia nodulation enhancement.
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http://dx.doi.org/10.1016/j.micres.2021.126765DOI Listing
September 2021

Molecular basis of cross-species ACE2 interactions with SARS-CoV-2-like viruses of pangolin origin.

EMBO J 2021 08 8;40(16):e107786. Epub 2021 Jun 8.

College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.

Pangolins have been suggested as potential reservoir of zoonotic viruses, including SARS-CoV-2 causing the global COVID-19 outbreak. Here, we study the binding of two SARS-CoV-2-like viruses isolated from pangolins, GX/P2V/2017 and GD/1/2019, to human angiotensin-converting enzyme 2 (hACE2), the receptor of SARS-CoV-2. We find that the spike protein receptor-binding domain (RBD) of pangolin CoVs binds to hACE2 as efficiently as the SARS-CoV-2 RBD in vitro. Furthermore, incorporation of pangolin CoV RBDs allows entry of pseudotyped VSV particles into hACE2-expressing cells. A screen for binding of pangolin CoV RBDs to ACE2 orthologs from various species suggests a broader host range than that of SARS-CoV-2. Additionally, cryo-EM structures of GX/P2V/2017 and GD/1/2019 RBDs in complex with hACE2 show their molecular binding in modes similar to SARS-CoV-2 RBD. Introducing the Q498H substitution found in pangolin CoVs into the SARS-CoV-2 RBD expands its binding capacity to ACE2 homologs of mouse, rat, and European hedgehog. These findings suggest that these two pangolin CoVs may infect humans, highlighting the necessity of further surveillance of pangolin CoVs.
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http://dx.doi.org/10.15252/embj.2021107786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209949PMC
August 2021

Quantification of JAK2V617F mutation load by droplet digital PCR can aid in diagnosis of myeloproliferative neoplasms.

Int J Lab Hematol 2021 Aug 11;43(4):645-650. Epub 2021 May 11.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Introduction: This study developed a method for quantifying the JAK2V617F mutation load in patients with myeloproliferative neoplasm (MPN) using droplet digital PCR (ddPCR), which provides a new laboratory method for diagnosing polycythemia vera (PV), essential thrombocythemia (ET), and pre-primary myelofibrosis (pre-PMF).

Methods: Patients with MPN who had JAK2V617F mutations from March 2013 to August 2019 were enrolled in this study. JAK2V617F mutation loads were quantified using ddPCR technology.

Results: The study examined 225 patients, including 135 with ET, 58 with PV, and 32 with PMF. JAK2V617F mutation loads significantly differed (P < .001) between the ET and PV groups and between the ET and PMF groups. Bone marrow biopsies were reclassified in accordance with the 2016 World Health Organization diagnostic criteria, which revealed 132 patients with MPN: 62 with ET, 35 with PV, 17 with pre-PMF, and 18 with overt-PMF. JAK2V617F mutation loads significantly differed (P < .001) between the ET and PV groups and between the ET and pre-PMF groups. The cutoff value between the ET and pre-PMF groups was 49.9.

Conclusion: JAK2V617F mutation loads provide an additional basis for diagnosis of ET, PV, and PMF, particularly regarding differentiation between ET and pre-PMF.
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http://dx.doi.org/10.1111/ijlh.13560DOI Listing
August 2021

Mutated DNA Damage Repair Pathways Are Prognostic and Chemosensitivity Markers for Resected Colorectal Cancer Liver Metastases.

Front Oncol 2021 31;11:643375. Epub 2021 Mar 31.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital, Beijing, China.

Deficiency of the DNA damage repair (DDR) signaling pathways is potentially responsible for genetic instability and oncogenesis in tumors, including colorectal cancer. However, the correlations of mutated DDR signaling pathways to the prognosis of colorectal cancer liver metastasis (CRLM) after resection and other clinical applications have not been fully investigated. Here, to test the potential correlation of mutated DDR pathways with survival and pre-operative chemotherapy responses, tumor tissues from 146 patients with CRLM were collected for next-generation sequencing with a 620-gene panel, including 68 genes in 7 DDR pathways, and clinical data were collected accordingly. The analyses revealed that 137 of 146 (93.8%) patients had at least one mutation in the DDR pathways. Mutations in BER, FA, HRR and MMR pathways were significantly correlated with worse overall survival than the wild-types (P < 0.05), and co-mutated DDR pathways showed even more significant correlations (P < 0.01). The number of mutated DDR pathways was also proved an independent stratifying factor of overall survival by Cox multivariable analysis with other clinical factors and biomarkers (hazard ratio = 9.14; 95% confidence interval, 1.21-68.9; P = 0.032). Additionally, mutated FA and MMR pathways were positively and negatively correlated with the response of oxaliplatin-based pre-operative chemotherapy (P = 0.0095 and 0.048, respectively). Mutated DDR signaling pathways can predict pre-operative chemotherapy response and post-operative survival in CRLM patients.
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http://dx.doi.org/10.3389/fonc.2021.643375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045762PMC
March 2021

iTRAQ-based quantitative proteomic analysis of low molybdenum inducing thymus atrophy and participating in immune deficiency-related diseases.

Ecotoxicol Environ Saf 2021 Apr 13;216:112200. Epub 2021 Apr 13.

Henan Key Laboratory of Environmental and Animal Product Safety Henan University of Science and Technology, Luoyang 471003, Henan, China. Electronic address:

Molybdenum is a trace element with extremely uneven distribution in the environment. It constitutes the active sites of molybdenum enzymes that can catalyze redox reactions in almost all organisms. In this study, a mouse model with a low molybdenum diet was established to investigate the differential protein expressions in the thymus and the mechanism of molybdenum regulating thymocyte development. Results showed that the thymus evidently atrophied, and the weight and organ index of the thymus substantially decreased under the condition of low molybdenum (P < 0.01). A total of 274 differentially expressed proteins (DEPs) were screened through isobaric tag for relative and absolute quantification; amongst them, ribosomal proteins (38) were the most abundant. Bioinformatics analysis revealed that DEPs were mainly involved in protein metabolism (18%), nucleus (15%) and nucleic acid binding activity (17%), corresponding to biological process, cellular component and molecular function, respectively. Moreover, DEPs induced by low molybdenum were enriched in 94 pathways, of which typical maps including ribosome, oxidative phosphorylation and systemic lupus erythematosus. Flow cytometry analysis indicated the prominent imbalances of CD4 and CD8 cell ratios (P < 0.05, P < 0.01), suggesting the disordered development of T cell subsets. Overall, low molybdenum resulted in thymus atrophy by interfering with ribosomal protein expression and protein metabolism. This study provides a data platform for revealing the linkage between molybdenum and thymus-dependent immunity.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112200DOI Listing
April 2021

Islet transplantation ameliorates diabetes-induced testicular interstitial fibrosis and is associated with inhibition of TGF-β1/Smad2 pathway in a rat model of type 1 diabetes.

Mol Med Rep 2021 05 24;23(5). Epub 2021 Mar 24.

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Islet transplantation (IT) is considered the most effective endocrine replacement therapy for diabetes mellitus (DM). Studies have demonstrated that IT can repair testicular structural injury caused by inflammatory and oxidative stress in a diabetic rat model. However, highly effective exogenous antioxidant and anti-inflammatory drugs can achieve this effect. Testicular interstitial fibrosis caused by long-term hyperglycemia is however difficult to reverse or recover. Thus far, there are no effective drugs that prevent or relieve testicular interstitial fibrosis. Therefore, it is necessary to explore the potential benefit of IT on testicular interstitial fibrosis induced by DM and its underlying molecular mechanisms. In the present study, Wistar rats were used to establish a DM model by intraperitoneal injection of streptozotocin. The diabetic models then underwent IT or received insulin treatment after 12 weeks. IT was more effective than insulin treatment in ameliorating diabetic-induced testicular interstitial fibrosis, Leydig cells apoptosis, testosterone deficiency and poor sperm motility. IT and insulin treatment both significantly inhibited the upregulation of TGF-β1 and phosphorylated Smad2 in DM, with IT being more effective than insulin. The present study's findings proved that IT effectively protects diabetic-induced testicular interstitial fibrosis probably by inhibiting the TGF-β1/Smad2 signaling pathway, which offers hope in male patients with DM complicating with testicular interstitial fibrosis.
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http://dx.doi.org/10.3892/mmr.2021.12015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985996PMC
May 2021

Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies.

Cell Res 2021 05 17;31(5):517-525. Epub 2021 Mar 17.

Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou, Zhejiang, 310024, China.

Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit.
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http://dx.doi.org/10.1038/s41422-021-00487-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966918PMC
May 2021

Impact of the COVID-19 lockdown on roadside traffic-related air pollution in Shanghai, China.

Build Environ 2021 May 18;194:107718. Epub 2021 Feb 18.

International Center for Adaptation Planning and Design, College of Design, Construction and Planning, University of Florida, PO Box 115706, Gainesville, FL, 32611-5706, USA.

The outbreak of COVID-19 has significantly inhibited global economic growth and impacted the environment. Some evidence suggests that lockdown strategies have significantly reduced traffic-related air pollution (TRAP) in regions across the world. However, the impact of COVID-19 on TRAP on roadside is still not clearly understood. In this study, we assessed the influence of the COVID-19 lockdown on the levels of traffic-related air pollutants in Shanghai. The pollution data from two types of monitoring stations-roadside stations and non-roadside stations were compared and evaluated. The results show that NO, PM, PM, and SO had reduced by ~30-40% at each station during the COVID-19 pandemic in contrast to 2018-2019. CO showed a moderate decline of 28.8% at roadside stations and 16.4% at non-roadside stations. In contrast, O concentrations increased by 30.2% at roadside stations and 5.7% at non-roadside stations. This result could be resulted from the declined NOx emissions from vehicles, which lowered O titration. Full lockdown measures resulted in the highest reduction of primary pollutants by 34-48% in roadside stations and 18-50% in non-roadside stations. The increase in O levels was also the most significant during full lockdown by 64% in roadside stations and 33% in non-roadside stations due to the largest decrease in NO precursors, which promote O formation. Additionally, Spearman's rank correlation coefficients between NO and other pollutants significantly decreased, while the values between NO and O increased at roadside stations.
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http://dx.doi.org/10.1016/j.buildenv.2021.107718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891056PMC
May 2021

An unusual case of secondary syphilis misdiagnosed as allergic dermatitis for 2 years.

Clin Case Rep 2020 Dec 13;8(12):2610-2612. Epub 2020 Aug 13.

Department of Dermatology The Third Affiliated Hospital of Soochow University Changzhou China.

Dermatologists should be aware that the clinical manifestations of syphilis are very complex and changeable. Unilaterally distributed skin lesions and painless lip ulcers may also be the clinical manifestations of secondary syphilis.
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http://dx.doi.org/10.1002/ccr3.3229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752569PMC
December 2020

Roadside Air Quality Forecasting in Shanghai with a Novel Sequence-to-Sequence Model.

Int J Environ Res Public Health 2020 12 17;17(24). Epub 2020 Dec 17.

Shanghai Environmental Monitoring Center, Shanghai 200235, China.

The establishment of an effective roadside air quality forecasting model provides important information for proper traffic management to mitigate severe pollution, and for alerting resident's outdoor plans to minimize exposure. Current deterministic models rely on numerical simulation and the tuning of parameters, and empirical models present powerful learning ability but have not fully considered the temporal periodicity of air pollutants. In order to take the periodicity of pollutants into empirical air quality forecasting models, this study evaluates the temporal variations of air pollutants and develops a novel sequence to sequence model with weekly periodicity to forecast air quality. Two-year observation data from Shanghai roadside air quality monitoring stations are employed to support analyzing and modeling. The results conclude that the fine particulate matter (PM) and carbon monoxide (CO) concentrations show obvious daily and weekly variations, and the temporal patterns are nearly consistent with the periodicity of traffic flow in Shanghai. Compared with PM, the CO concentrations are more affected by traffic variation. The proposed model outperforms the baseline model in terms of accuracy, and presents a higher linear consistency in PM prediction and lower errors in CO prediction. This study could assist environmental researchers to further improve the technologies for urban air quality forecasting, and serve as tools for supporting policymakers to implement related traffic management and emission control policies.
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http://dx.doi.org/10.3390/ijerph17249471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766230PMC
December 2020

Osteoprotegerin, interleukin and hepatocyte growth factor for prediction of diabetes and hypertension in the third trimester of pregnancy.

World J Clin Cases 2020 Nov;8(22):5529-5534

Department of Obstetrics, The Second Affiliated Hospital of Hainan Medical College, Haikou 570311, Hainan Province, China.

Background: Gestational diabetes mellitus (GDM) raises the risk of high blood pressure and may cause a series of life-threatening complications in pregnant women. Screening and management of GDM and gestational hypertension (GH) in pregnancy helps to control and reduce these risks and prevent adverse effects on mothers and their fetuses. Currently, the majority criteria used for screening of diabetes mellitus is oral glucose tolerance tests, and blood pressure test is usually used for the screening and diagnosis of hypertension. However, these criteria might not anticipate or detect all GDM or GH cases. Therefore, new specific predictive and diagnostic tools should be evaluated for this population. This study selected three biomarkers of osteoprotegerin (OPG), interleukin (IL) and hepatocyte growth factor (HGF) for GDM and GH predication and diagnosis.

Aim: To explore the feasibility of changes in placental and serum OPG, IL and HGF as tools for prediction and diagnosis of diabetes and hypertension in pregnant women.

Methods: From January 2018 to January 2019, 44 pregnant women with GDM and GH were selected as an observation group, and 44 healthy pregnant women were selected as a control group in the same period. Serum OPG, IL and HGF were compared between the two groups.

Results: The levels of OPG and HGF in the observation group were lower than in the control group, and the level of IL-1β was higher in the observation group than in the control group (all < 0.05). Furthermore, OPG and HGF were negatively associated with gestational diabetes and gestational hypertension, while IL-1β was positively associated with GDM complicated with GH (all < 0.05).

Conclusion: The evaluation of serum OPG, HGF and IL-1β levels in patients with coexistent gestational diabetes complicated with hypertension can predict the degree of disease and play an important role in the follow-up treatment and prognosis prediction.
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http://dx.doi.org/10.12998/wjcc.v8.i22.5529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716305PMC
November 2020

Cross-species recognition of SARS-CoV-2 to bat ACE2.

Proc Natl Acad Sci U S A 2021 01;118(1)

Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China;

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2-related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.
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http://dx.doi.org/10.1073/pnas.2020216118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817217PMC
January 2021
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