Publications by authors named "Li Fan"

1,837 Publications

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Highly Efficient Electro-reforming of 5-Hydroxymethylfurfural on Vertically Oriented Nickel Nanosheet/Carbon Hybrid Catalysts: Structure-Function Relationships.

Angew Chem Int Ed Engl 2021 Apr 20. Epub 2021 Apr 20.

Institute of Metal Research, Chinese Academy of Sciences, Catalysis and Materials Division, 72, Wenhua Road, 110016, Shenyang, CHINA.

Ni-promoted electrocatalytic biomass reforming has shown promising prospect in enabling high value-added product synthesis. Here, we developed a novel hybrid catalyst with Ni nanosheet forests anchored on carbon paper. The hybrid catalyst exhibits high efficiency in electrooxidation of HMF to FDCA coupling with H2 production in high purity. The Ni nanosheets have small crystal grain sizes with abundant edges, which is able to deliver an efficient HMF oxidation to FDCA (selectivity >99%) at low potential of 1.36 VRHE with high stability. The post-reaction structure analysis reveals the Ni nanosheets would transfer electrons to carbon and readily turn into NiOx and Ni(OH)x during the reaction. DFT results suggest high valence Ni species would facilitate the chemical adsorption (activation) of HMF revealing the reaction pathway. This work emphasizes the importance of the precise control of Ni activity via atomic structure engineering.
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http://dx.doi.org/10.1002/anie.202102359DOI Listing
April 2021

Effects of the tight junction protein CLDN6 on cell migration and invasion in high-grade meningioma.

World Neurosurg 2021 Apr 13. Epub 2021 Apr 13.

Central Laboratory, The First People's Hospital of Yibin, Yibin 644000, Sichuan, China. Electronic address:

Background: Meningioma is a common tumor of the central nervous system, and malignant meningioma is highly aggressive and frequently recurs after surgical resection. Claudin 6 (CLDN6) is involved in cell proliferation, migration, and invasion and plays a role in maintaining tight junctions (TJs) between cells as well as obstructing the movement of cells to neighboring tissues.

Methods: In this study, we attempted to evaluate the effect of TJ protein CLDN6 expression levels on meningioma invasiveness by using silencing and overexpression constructs in both in vitro and in vivo models. The expression of CLDN6 at the mRNA and protein levels was measured using quantitative RT-PCR and western blot assays.

Results: We found that CLDN6 was expressed at higher levels in normal meningeal tissue/cell samples. Then, vectors with silenced and overexpressed CLDN6 were successfully established, and the expression levels of CLDN6 mRNA and protein in IOMM-Lee and CH157-MN cell lines were downregulated after transfection with siRNA-CLDN6 and upregulated by transfection of the entire CLDN6 sequence vector. An in vitro assay revealed that abrogation of CLDN6 expression added to the capacity of tumor migration and invasion relative to the overexpression of CLDN6. In addition to the in vitro evidence, we observed a significant increase in tumor growth and invasion-associated gene expression, including MMP-2, MMP-9, vimentin and N-cadherin, after silencing CLDN6 expression in vivo.

Conclusions: CLDN6 may play an important role in meningioma migration and invasion, and it may serve as a novel diagnostic/prognostic biomarker as well as a potential therapeutic target.
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http://dx.doi.org/10.1016/j.wneu.2021.04.005DOI Listing
April 2021

Chitosan/alginate/hyaluronic acid polyelectrolyte composite sponges crosslinked with genipin for wound dressing application.

Int J Biol Macromol 2021 Apr 10;182:512-523. Epub 2021 Apr 10.

Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin 300457, PR China; Institute of Medical Support Technology, Academy of Military Sciences, Tianjin 300161, PR China. Electronic address:

Wound dressing composed of polyelectrolyte complexes (PECs), based on chitosan/alginate/hyaluronic acid (CS/ALG/HYA) crosslinked by genipin, was prepared by freeze-dried molding. Genipin as excellent natural biological crosslinker was chose for high biocompatibility and improving mechanical properties of materials. The CS/ALG/HYA sponges (CAHSs) were characterized by FTIR, XRD, DSC and SEM. Porosity, swelling behavior and mechanical properties and in vitro degradation of CAHSs were investigated. The cytotoxicity assay was carried out on HUVEC cells in vitro and the result proves the good biocompatibility of CAHSs. Hemolysis tests indicated that the prepared CAHSs were non-hemolytic material (hemolysis ratio < 5%, no cytotoxicity). PT and aPPT coagulation tests demonstrated that CAHS2 and CAHS3 could both activate the extrinsic and intrinsic coagulation pathway and thus accelerated blood coagulation. Further, in a rat full-thickness wounds model, the CAHS2 sponge significantly facilitates wound closure compared to other groups. CAHSs exhibited adjustable physical, mechanical and biological properties. Thus, the chitosan-based polyelectrolyte composite sponges exhibit great potential as promising wound dressings.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.044DOI Listing
April 2021

A meta-analysis on the relationship of exosomes and the prognosis of lung cancer.

Medicine (Baltimore) 2021 Apr;100(15):e25332

Department of Urology, Affiliated Hospital of Guilin Medical University.

Background: A lot of research evidence shows that exosomes play an indelible role in the prognosis of lung cancer, but there are many disputes. Therefore, we conduct a meta-analysis to further demonstrate.

Methods: A literature retrieval was performed through a search of PubMed, Embase, Web of Science, Cochrane, CKNI, Wanfang, and other databases to locate documents from the literature that satisfied the inclusion criteria. There were four outcome indicators: overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Subgroup analysis was conducted according to sample size, country, detection method, analysis method, and pathological type. Stata 14.0 software was used to evaluate the prognostic value of exosomes in lung cancer.

Results: A total of 2456 patients with lung cancer from 29 studies in 16 articles were included. The expression level of exosomes was closely associated with the OS and DFS of patients, although no statistical difference was observed between exosomes and DSS or PFS. Eighteen studies with 2,110 patients were evaluated to examine the prognostic value of exosomes in lung cancer by exploring the association between exosomes and OS. The results showed that exosomes were strongly associated with worse OS, and the combined hazard ratio (HR) was 2.01 (95% confidence interval [CI]: 1.70-2.39, P = .000). Six studies investigated the association between exosomes and DFS, and showed a pooled HR of 2.48 (95% CI: 1.75-3.53, P = .000).

Conclusion: Our analysis indicated that the expression level of exosomes was closely associated with the OS and DFS of patients with lung cancer, suggesting that exosomes are associated with poor prognosis of lung cancer. Exosomes may be a new biomarker for the prognosis of lung cancer, although a large number of prospective studies are still needed to support this.
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http://dx.doi.org/10.1097/MD.0000000000025332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051998PMC
April 2021

Functionalized Ionic Liquid-Crystal Additive for Perovskite Solar Cells with High Efficiency and Excellent Moisture Stability.

ACS Appl Mater Interfaces 2021 Apr 12. Epub 2021 Apr 12.

Department of Materials Science and Engineering, Nanchang University, 999 Xuefu Avenue, Nanchang 330031, China.

Organic-inorganic hybrid perovskite solar cells (PSCs) have emerged as a promising candidate for next-generation solar cells. However, the limited stability of PSCs hampers their practical applications. In this work, for the first time, a functionalized π-conjugated ionic liquid crystal (ILC), 4'-(,,-trimethyl ammonium bromide hexyloxy)-4-cyanobiphenyl (6CNBP-N), is developed as a novel chemical additive to obtain CHNHPbI (MAPbI) PSCs with high efficiency and excellent moisture stability. This 6CNBP-N ILC possesses the characteristics of ionic liquids and liquid crystals. The inclusion of the 6CNBP-N ILC can effectively improve the quality and stability of perovskite films, reduce the trap-state densities, and promote the carrier transport induced by the cyano group (C≡N), a rod-like π-conjugated biphenyl mesogenic unit and quaternary alkylammonium cations (RN) in 6CNBP-N. Through this functionalized ILC engineering strategy, the power conversion efficiency (PCE) of PSCs is greatly increased from 18.07% for the control PSC to 20.45% for the PSC with 6CNBP-N along with the depressed hysteresis effect and enhanced moisture stability of PSCs. Our work provides a new strategy for designing functionalized additives for high-performance PSCs.
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http://dx.doi.org/10.1021/acsami.1c02728DOI Listing
April 2021

Can peritumoral regions increase the efficiency of machine-learning prediction of pathological invasiveness in lung adenocarcinoma manifesting as ground-glass nodules?

J Thorac Dis 2021 Mar;13(3):1327-1337

Department of Radiology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Background: The peri-tumor microenvironment plays an important role in the occurrence, growth and metastasis of cancer. The aim of this study is to explore the value and application of a CT image-based deep learning model of tumors and peri-tumors in predicting the invasiveness of ground-glass nodules (GGNs).

Methods: Preoperative thin-section chest CT images were reviewed retrospectively in 622 patients with a total of 687 pulmonary GGNs. GGNs are classified according to clinical management strategies as invasive lesions (IAC) and non-invasive lesions (AAH, AIS and MIA). The two volumes of interest (VOIs) identified on CT were the gross tumor volume (GTV) and the gross volume of tumor incorporating peritumoral region (GPTV). Three dimensional (3D) DenseNet was used to model and predict GGN invasiveness, and five-fold cross validation was performed. We used GTV and GPTV as inputs for the comparison model. Prediction performance was evaluated by sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).

Results: The GTV-based model was able to successfully predict GGN invasiveness, with an AUC of 0.921 (95% CI, 0.896-0.937). Using GPTV, the AUC of the model increased to 0.955 (95% CI, 0.939-0.971).

Conclusions: The deep learning method performed well in predicting GGN invasiveness. The predictive ability of the GPTV-based model was more effective than that of the GTV-based model.
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http://dx.doi.org/10.21037/jtd-20-2981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024795PMC
March 2021

Practical value of hierarchical teaching combined with simulation scenario training for operating-room nurses.

Am J Transl Res 2021 15;13(3):1833-1839. Epub 2021 Mar 15.

Operating-Room of The Second Affiliated Hospital of Soochow University Suzhou 215004, Jiangsu, China.

Objective: This study explored the application value of combined training by hierarchical teaching with situational simulations for operating-room (OR) nurses.

Methods: A total of 41 nurses that received pre-job training for the operating room from January 2018 to December 2019 were selected as the research subjects and randomly divided into a control group and a study group. The control group was given the hierarchical nurse-teaching method, while the study group was given combined training with the hierarchical teaching and scenario simulations. In this study, the operating room capability, clinical work ability, results of theoretical assessment and specialized operation, and nurses' satisfaction with the teaching patterns were compared between the two groups.

Results: After training, the scores of the operating-room operations in the study group, such as laying of aseptic towels, surgical hand washing, wearing of surgical gowns and gloves, and the setting up of the operating table, were higher than that in the control group (<0.05). The scores of clinical work abilities in the study group, such as emergency handling ability, standardized operation ability, mastery of professional knowledge, observation and evaluation ability of disease, and clinical thinking ability, were higher than those in the control group (<0.05). The theoretical examination scores and specialized operation scores of nurses in the study group were higher than those in the control group (<0.05). The satisfaction with the degree of teaching methods in the study group was higher than that in the control group (<0.05).

Conclusion: The application of the combined training methods of hierarchical teaching with situational simulations for OR nurses can effectively improve their operational and clinical work ability, deepen their mastery of theoretical knowledge, and enable junior nurses to master the professional skills required in the operating room in a faster way, which is worthy of clinical teaching application.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014425PMC
March 2021

Aptamer assisted CRISPR-Cas12a strategy for small molecule diagnostics.

Biosens Bioelectron 2021 Mar 24;183:113196. Epub 2021 Mar 24.

MOE Key Laboratory for Industrial Biocatalysis, Institute of Biochemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China; Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084, China. Electronic address:

Molecular diagnostics are vital for the identification, prevention, and treatment of numerous diseases and are of particular demand in point-of-care (POC) settings. Nevertheless, most reported biosensors based on the CRISPR-Cas system have focused on nucleic-acid targets. Here, we report a versatile diagnostic strategy for small molecules called Molecular Radar (Random Molecular Aptamer-Dependent CRISPR-Assist Reporter), The workflow is simple, convenient, and rapid (conducted at 37 °C in under 25 min), indicating the substantial potential of the proposed assay could be adapted into a biosensor for POC settings and on-site molecular diagnostics. This strategy is based on the CRISPR Cas12a-assisted fluorescence reporter system that consists of Cas12a, CRISPR RNA (crRNA), a single-stranded DNA (ssDNA) probe labeled with a fluorophore at the 5' end and a quencher at the 3' end (F-Q probe), and a single-stranded DNA aptamer for the target molecule. In the presence of a target molecule, the aptamer binds to this small molecule with high specificity and affinity, resulting in a decrease of aptamer hybridized to the crRNA-Cas12a duplex. This decrease in activated Cas12a leads to a significant reduction in fluorescence signal. In this study, adenosine-5'-triphosphate (ATP) was selected as model target molecule and an ATP detect method was developed with high specificity and sensitivity with a linear range from 25 to 500 μM and a detection limit of 104 nM. Moreover, the particular characteristics of CRISPR-Cas12a that we report here for the first time have enriched our understanding of Cas12a and provided guidance for further research on CRISPR-Cas12a-based biosensors.
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http://dx.doi.org/10.1016/j.bios.2021.113196DOI Listing
March 2021

Risk factors for incorrect surgical count during surgery: An observational study.

Int J Nurs Pract 2021 Apr 10:e12942. Epub 2021 Apr 10.

Department of Surgery, The First Affiliated Hospital of Soochow University, Suzhou City, China.

Background: Incorrect surgical counts are closely related to retained surgical items, which pose a threat to patients. However, the risk factors for incorrect surgical counts have not been identified yet.

Aim: To identify the risk factors associated with incorrect surgical counts during surgery in a tertiary hospital.

Design: An observational case-control study.

Methods: Seventy cases of incorrect surgical counts were reviewed in this study. Data were collected from January 1, 2014, to April 4, 2019. For each case, we included four randomly selected control cases involving the same surgical procedures by the same surgeon within a 6-month period for comparison. The medical data of these cases were extracted for further statistical analysis.

Results: A higher incidence of incorrect surgical counts was observed among surgical counts performed between 8:00 a.m. to 12:00 a.m., emergency operations, prolonged procedures, and/or after addition of surgical items.

Conclusion: Prolonged surgical procedures, emergency operations, time of occurrence, and addition of surgical items were the risk factors related to incorrect surgical counts during surgery.

Summary Statement: What is already known about the topic? Incorrect surgical count is a perplexing problem during operation. Incorrect surgical count is closely associated with retained surgical items which can cause patient injury. The underlaying risk factors of incorrect surgical count were still unknown. What this paper adds? This was the first case-control study for incorrect surgical counts in China. The present research demonstrated that several risk factors were significantly associated with the occurrence of incorrect surgical counts, including the time period, the type of surgery, and the duration of the procedure. Vigilance should be maintained during an emergency operation or a long procedure to reduce the incidence of incorrect surgical counts. The implications of this paper: It is important for nurses to be aware of the factors that can interfere with correct surgical counts, thereby ensuring vigilance during emergency operations or long procedures. By identifying these risk factors, a more comprehensive safety policy in the operation room can be implemented to reduce incorrect surgical counts. Novel technological adjuncts should be promoted in the operating room gradually to improve overall patient safety.
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http://dx.doi.org/10.1111/ijn.12942DOI Listing
April 2021

Multi-omics Analysis of the Amygdala in a Rat Chronic Unpredictable Mild Stress Model of Depression.

Neuroscience 2021 Apr 6. Epub 2021 Apr 6.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Physical Examination, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Major depressive disorder is a serious and complex mental illness, and multiple brain regions are involved in its pathogenesis. There is increasing evidence that the amygdala is involved in depression; however, the underlying molecular mechanisms remain unclear. In this study, we applied a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomic and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic to study changes in the amygdala in a chronic unpredictable mild stress (CUMS) rat model of depression. Differential analysis identified 42 metabolites and 171 proteins that were differentially expressed in the CUMS and control groups. Integrated analyses revealed two major changes in the amygdala of CUMS rats: (1) perturbations in amino acids and carbohydrate metabolism, transport-/catabolism-related proteins activity, and metabolic enzyme activity; (2) abnormal expression of synaptogenesis and oxidative phosphorylation-associated proteins.
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http://dx.doi.org/10.1016/j.neuroscience.2021.03.031DOI Listing
April 2021

Sample size estimation for modified Poisson analysis of cluster randomized trials with a binary outcome.

Authors:
Fan Li Guangyu Tong

Stat Methods Med Res 2021 Apr 7:962280221990415. Epub 2021 Apr 7.

Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.

The modified Poisson regression coupled with a robust sandwich variance has become a viable alternative to log-binomial regression for estimating the marginal relative risk in cluster randomized trials. However, a corresponding sample size formula for relative risk regression via the modified Poisson model is currently not available for cluster randomized trials. Through analytical derivations, we show that there is no loss of asymptotic efficiency for estimating the marginal relative risk via the modified Poisson regression relative to the log-binomial regression. This finding holds both under the independence working correlation and under the exchangeable working correlation provided a simple modification is used to obtain the consistent intraclass correlation coefficient estimate. Therefore, the sample size formulas developed for log-binomial regression naturally apply to the modified Poisson regression in cluster randomized trials. We further extend the sample size formulas to accommodate variable cluster sizes. An extensive Monte Carlo simulation study is carried out to validate the proposed formulas. We find that the proposed formulas have satisfactory performance across a range of cluster size variability, as long as suitable finite-sample corrections are applied to the sandwich variance estimator and the number of clusters is at least 10. Our findings also suggest that the sample size estimate under the exchangeable working correlation is more robust to cluster size variability, and recommend the use of an exchangeable working correlation over an independence working correlation for both design and analysis. The proposed sample size formulas are illustrated using the Stop Colorectal Cancer (STOP CRC) trial.
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http://dx.doi.org/10.1177/0962280221990415DOI Listing
April 2021

Tumor-derived exosomal long noncoding RNA LINC01133, regulated by Periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-catenin pathway by silencing AXIN2.

Oncogene 2021 Apr 6. Epub 2021 Apr 6.

Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.
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http://dx.doi.org/10.1038/s41388-021-01762-0DOI Listing
April 2021

Identification of Novel Sensitive and Reliable Serovar-Specific Targets for PCR Detection of Serovars Hadar and Albany by Pan-Genome Analysis.

Front Microbiol 2021 16;12:605984. Epub 2021 Mar 16.

Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.

The accurate and rapid classification of serovars is an essential focus for the identification of isolates involved in disease in humans and animals. The purpose of current research was to identify novel sensitive and reliable serovar-specific targets and to develop PCR method for C2 serogroups (O:8 epitopes) in food samples to facilitate timely treatment. A total of 575 genomic sequences of 16 target serovars belonging to serogroup C2 and 150 genomic sequences of non-target serovars were analysed by pan-genome analysis. As a result, four and three specific genes were found for serovars Albany and Hadar, respectively. Primer sets for PCR targeting these serovar-specific genes were designed and evaluated based on their specificity; the results showed high specificity (100%). The sensitivity of the specific PCR was 2.8 × 10-10 CFU/mL and 2.3 × 10-10 CFU/mL for serovars Albany and Hadar, respectively, and the detection limits were 1.04 × 10-10 CFU/g and 1.16 × 10-10 CFU/g in artificially contaminated raw pork samples. Furthermore, the potential functions of these serovar-specific genes were analysed; all of the genes were functionally unknown, except for one specific serovar Albany gene known to be a encoded secreted protein and one specific gene for serovars Hadar and Albany that is a encoded membrane protein. Thus, these findings demonstrate that pan-genome analysis is a precious method for mining new high-quality serovar-targets for PCR assays or other molecular methods that are highly sensitive and can be used for rapid detection of serovars.
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http://dx.doi.org/10.3389/fmicb.2021.605984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011537PMC
March 2021

[Clinical Characteristics and Survival Analysis of Patients with IgD Multiple Myeloma].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Apr;29(2):547-552

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.

Objective: To explore the clinical features, prognosis and survival of patients with IgD multiple myeloma (MM).

Methods: The clinical data of 20 patients with IgD MM was analyzed retrospectively. The prognostic factors and survival analysis was carried out. We summarized their clinical characteristics. The survival analysis was carried out by Kaplan-Meier method, and the prognostic factor were analyzed by using log-rank test for single factor analysis of observation index. Variables of P<0.15 in single factor analysis were enrolled in multifactor cox regression analysis.

Results: IgD MM patients accounted for 4.3% of all MM patients in the same period, among which 80% were male, the median age of patients was 57.5(35-77) years old, 90% of the patients belongs to λ light chain type. At the time of diagnosis, 18 patients (90%) were in DS-Ⅲ stages, while 10 patients were in ISS-Ⅲ stage. The first clinical manifestations were fatigue, bone pain, kidney function impairment, anemia (Hb<100 g/L) in 14 cases (70%), 12 cases (60%) with osteolytic bone destruction≥3, combined with renal impairment in 8 cases (40%), and elevated blood calcium in 11 cases (51.4%). In only 5 patients the ratio of albumin to globntin was inverted, hypoalbuminemia accounted for 40%, and globulin increase accounted for only 15%. FISH results showed that the positive rate of 1q21 amplification (50%) was the highest, and it was easy to occur at the same time as other cytogenetic abnormalities. Extramedullary infiltration occurred in 4 cases (20%). The analysis of prognostic factors showed that only the increase of lactate dehydrogenase (LDH) level was an independent poor prognostic factor for IgD MM patients. Extramedullary infiltration and various cytogenetic abnormalities were found in 2 IgD MM patients with primary drug resistance, suggesting that extramedullary infiltration and various cytogenetic abnormalities may be prognostic factors, but the difference was not statistically significant, Which maybe related to the small sample size. All 20 patients were treated with bortezomib-containing regimen, of which 19 patients were evaluated, 17 patients (89.4%) showed effective, including CR+VGPR (52.6%), PR (31.5%), MR (5.3%), 2 patients primary drug resistance. The median PFS and OS was 9.5 and 10.5 months, respectively.

Conclusion: IgD MM is a rare and invasive disease. Increased LDH is an independent prognostic factor. Bortizomib-containing regimen can improve the prognosis of IgD MM patients.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.02.038DOI Listing
April 2021

Incorporation of In Situ Synthesized Nano-Copper Modified Phenol-Formaldehyde Resin to Improve the Mechanical Properties of Chinese Fir: A Preliminary Study.

Polymers (Basel) 2021 Mar 12;13(6). Epub 2021 Mar 12.

International Center for Bamboo and Rattan, Beijing 100102, China.

Phenol-formaldehyde (PF) resin, modified using nano-copper with varying contents (0 wt%, 1 wt%, 3 wt%), was manufactured to improve the mechanical properties of Chinese fir. The morphology, chemical, micromechanical and micromechanical properties of the samples were determined by transmission electron microscopy (TEM), atomic force microscopy (AFM), environmental scanning electron microscopy (ESEM), Fourier transform infrared spectroscopy (FTIR), nanoindentation (NI) and traditional mechanical testing. The TEM and AFM results indicated that the in situ synthesized nano-copper particles were well-dispersed, and spherical, with a diameter of about 70 nm in PF resin. From the FTIR chemical changes detected by FTIR inferred that the nano-copper modified PF resin penetrated into the Chinese fir cell walls and interacted with the acetyl groups of hemicellulose by forming a crosslinked structure. Accordingly, the micro-mechanical properties of the Chinese fir cell walls were enhanced after treatment with nano-copper modified PF resin. The filling of the PF-1-Cu resin (1 wt% nano-copper) in the wood resulted in 13.7% and 22.2% increases in the elastic modulus (MOE) and hardness, respectively, of the cell walls. Besides, the impact toughness and compressive strength of the Chinese fir impregnated with PF-1-Cu resin were 21.8% and 8.2% higher than that of the PF-0-Cu resin. Therefore, in situ synthesized nano-copper-modified PF resin is a powerful treatment method for Chinese fir due to improved diffusive properties and reinforcement of the mechanical properties.
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http://dx.doi.org/10.3390/polym13060876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002211PMC
March 2021

Effector and regulator: Diverse functions of C. elegans C-type lectin-like domain proteins.

PLoS Pathog 2021 Apr 1;17(4):e1009454. Epub 2021 Apr 1.

Department of Evolutionary Ecology and Genetics, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.

In C. elegans, 283 clec genes encode a highly diverse family of C-type lectin-like domain (CTLD) proteins. Since vertebrate CTLD proteins have characterized functions in defense responses against pathogens and since expression of C. elegans clec genes is pathogen-dependent, it is generally assumed that clec genes function in C. elegans immune defenses. However, little is known about the relative contribution and exact function of CLEC proteins in C. elegans immunity. Here, we focused on the C. elegans clec gene clec-4, whose expression is highly upregulated by pathogen infection, and its paralogs clec-41 and clec-42. We found that, while mutation of clec-4 resulted in enhanced resistance to the Gram-positive pathogen Bacillus thuringiensis MYBt18247 (Bt247), inactivation of clec-41 and clec-42 by RNAi enhanced susceptibility to Bt247. Further analyses revealed that enhanced resistance of clec-4 mutants to Bt247 was due to an increase in feeding cessation on the pathogen and consequently a decrease in pathogen load. Moreover, clec-4 mutants exhibited feeding deficits also on non-pathogenic bacteria that were in part reflected in the clec-4 gene expression profile, which overlapped with gene sets affected by starvation or mutation in nutrient sensing pathways. However, loss of CLEC-4 function only mildly affected life-history traits such as fertility, indicating that clec-4 mutants are not subjected to dietary restriction. While CLEC-4 function appears to be associated with the regulation of feeding behavior, we show that CLEC-41 and CLEC-42 proteins likely function as bona fide immune effector proteins that have bacterial binding and antimicrobial capacities. Together, our results exemplify functional diversification within clec gene paralogs.
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http://dx.doi.org/10.1371/journal.ppat.1009454DOI Listing
April 2021

Longitudinal dynamics of antibody responses in recovered COVID-19 patients.

Signal Transduct Target Ther 2021 03 31;6(1):137. Epub 2021 Mar 31.

Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China.

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http://dx.doi.org/10.1038/s41392-021-00559-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009921PMC
March 2021

Androgen receptor splice variant 7 detected by immunohistochemical is an independent poor prognostic marker in men receiving adjuvant androgen-deprivation therapy after radical prostatectomy.

Biomark Res 2021 Mar 31;9(1):23. Epub 2021 Mar 31.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP).

Methods: We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort.

Results: In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020).

Conclusion: The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.
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http://dx.doi.org/10.1186/s40364-021-00276-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011087PMC
March 2021

Short versus long biliopancreatic limb in Roux-en-Y gastric bypass surgery for treatment of type 2 diabetes mellitus.

Wideochir Inne Tech Maloinwazyjne 2021 Mar 14;16(1):129-138. Epub 2020 Oct 14.

Department of General Surgery, Daping Hospital, Army Medical University, Chongqing, China.

Introduction: Although laparoscopic Roux-en-Y gastric bypass (RYGB) is still widely accepted as a valid procedure in the treatment of obesity and type 2 diabetes mellitus (T2DM), there continues to be a significant controversy about how long the Roux and biliopancreatic limb should be bypassed for optimum results.

Aim: To assess the effect of a longer biliopancreatic limb (BPL) length on glycemic control after RYGB in T2DM patients.

Material And Methods: Eighty-four patients with uncontrolled T2DM who underwent RYGB between May 2010 and April 2017 were collected from the prospectively designed database. Forty patients (S-BPL group) received BPL lengths ≤ 50 cm, including 30 cm (n = 1), 40 cm (n = 1), and 50 cm (n = 38). Forty-four patients (L-BPL group) received 100 cm BPL. Anthropometry, serum glucose and lipid metabolic parameters were measured at baseline and 1, 3, 6, 12, 24 and 36 months after surgery.

Results: Comparing the two groups, there were no significant differences in anthropometric and biochemical measures, except the weight and body mass index, which were higher in the S-BPL group (85.91 ±20.32 vs. 76.25 ±16.99, p = 0.038; 31.87 ±6.61 vs. 28.7 ±4.29, p = 0.005) compared to the L-BPL group. The body weight, glucose and lipid metabolic parameters decreased over time and then remained essentially stable from the first year in both groups. Two years after surgery, the remission (HbA% ≤ 6%) of T2DM was 31.2% in the S-BPL group and 37.5% in the L-BPL group (p = 0.685).

Conclusions: With consistent total small bowel bypass (AL + BPL) lengths, lengthening of the BPL from 30 to 100 cm did not affect the post-RYGB glycemic control and weight loss.
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http://dx.doi.org/10.5114/wiitm.2020.99997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991953PMC
March 2021

Comparison of Thulium Laser Resection of Bladder Tumors and Conventional Transurethral Resection of Bladder Tumors for Non-Muscle-Invasive Bladder Cancer.

Urol Int 2021 Mar 30:1-6. Epub 2021 Mar 30.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Introduction: The thulium laser resection of bladder tumors (TmLRBT) was increasingly used in the treatment of non-muscle-invasive bladder cancer (NMIBC) recently, and here we report the relevant outcomes of our institution to evaluate its efficacy and safety.

Methods: We retrospectively collected the data of NMIBC patients who underwent either TmLRBT or transurethral resection of bladder tumor (TURBT). The baseline characteristics and perioperative outcomes were compared in these 2 groups.

Results: The TmLRBT had a higher rate of detrusor identification than TURBT (97.4 vs. 87.6%, p = 0.001). After screening, 134 patients who underwent TmLRBT and 152 patients who received TURBT were enrolled in the analysis, and their baseline characteristics were similar. During the TURBT, 24 (15.8%) obturator nerve reflexes and 9 (5.9%) bladder perforations occurred, while none happened during the TmLRBT. After surgery, TmLRBT patients had fewer postoperative gross hematuria (38.1 vs. 96.7%, p < 0.001) and postoperative irrigation (27.6 vs. 92.7%, p < 0.001), and its irrigation duration was significantly shorter (2.3 vs. 3.3 day, p < 0.001). During the follow-up, no significant difference in the recurrence rate was detected (p = 0.315).

Conclusions: TmLRBT is a safer technique than conventional TURBT in the treatment of NMIBC, and it could offer better specimens for pathologic assessment while the cancer control was not compromised.
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http://dx.doi.org/10.1159/000514042DOI Listing
March 2021

CRISPR/Cas9-based Discovery of Maize Transcription Factors Regulating Male Sterility and Their Functional Conservation in Plants.

Plant Biotechnol J 2021 Mar 27. Epub 2021 Mar 27.

Zhongzhi International Institute of Agricultural Biosciences, Biology and Agriculture Research Center of USTB, University of Science and Technology Beijing (USTB), Beijing, 100024, China.

Identifying genic male-sterility (GMS) genes and elucidating their roles are important to unveil plant male reproduction and promote their application in crop breeding. However, compared with Arabidopsis and rice, relatively fewer maize GMS genes have been discovered and little is known about their regulatory pathways underlying anther and pollen development. Here, by sequencing and analyzing anther transcriptomes at 11 developmental stages in maize B73, Zheng58 and M6007 inbred lines, 1,100 transcription factor (TF) genes were identified to be stably differentially expressed among different developmental stages. Among them, 14 maize TF genes (9 types belonging to five TF families) were selected and performed CRISPR/Cas9-mediated gene mutagenesis, and then 12 genes in eight types including ZmbHLH51, ZmbHLH122, ZmTGA9-1/-2/-3, ZmTGA10, ZmMYB84, ZmMYB33-1/-2, ZmPHD11 and ZmLBD10/27, were identified as maize new GMS genes by using DNA sequencing, phenotypic and cytological analyses. Notably, ZmTGA9-1/-2/-3 triple-gene mutants and ZmMYB33-1/-2 double-gene mutants displayed complete male sterility, but their double- or single-gene mutants showed male fertility. Similarly, ZmLBD10/27 double-gene mutant displayed partial male sterility with 32.18% of aborted pollen grains. In addition, ZmbHLH51 was transcriptionally activated by ZmbHLH122 and their proteins were physically interacted. Molecular markers co-segregating with these GMS mutations were developed to facilitate their application in maize breeding. Finally, all 14-type maize GMS TF genes identified here and reported previously were compared on functional conservation and diversification among maize, rice and Arabidopsis. These findings enrich GMS gene and mutant resources for deeply understanding the regulatory network underlying male fertility and for creating male-sterility lines in maize.
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http://dx.doi.org/10.1111/pbi.13590DOI Listing
March 2021

Molecular dynamic simulation: Structural insights of multi-stranded curdlan in aqueous solution.

Carbohydr Polym 2021 Jun 22;261:117844. Epub 2021 Feb 22.

State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, PR China.

In this work, by using molecular dynamic simulation we provide microscale structure information which helps to reveal the molecular mechanisms concerning the multi-chain conformational behavior of short curdlan. Through simulations starting with different conformations of curldan dodecasaccharides, it is found that the right-handed triple helix is thermodynamically the most stable conformation in aqueous solutions, which is well maintained and stabilized by an inter-strand hydrogen bonding network of the C hydroxyls. Unlike any predicted forms, the inter-strand hydrogen bonds exhibit a left-handed double helix pattern with preferred global orientations. Temperature REMD results suggest that the formation of triple helix is temperature sensitive, but the already formed triple helix is not. Investigation of curdlan with numbers of repeating units from 3 to 12 captures a critical value of 6, which in a way elucidates the relationship between the formation of triple helix and the chain length.
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http://dx.doi.org/10.1016/j.carbpol.2021.117844DOI Listing
June 2021

Japanese Encephalitis in China in the Period of 1950-2018: From Discovery to Control.

Biomed Environ Sci 2021 Mar;34(3):175-183

Department of Arbovirus, NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China;State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

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http://dx.doi.org/10.3967/bes2021.024DOI Listing
March 2021

Deposition of Atomically Thin Pt Shells on Amorphous Palladium Phosphide Cores for Enhancing the Electrocatalytic Durability.

ACS Nano 2021 Mar 23. Epub 2021 Mar 23.

Frontier Institute of Science and Technology and State Key Laboratory of Multiphase Flow in Power Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.

As an excellent electrocatalyst, platinum (Pt) is often deposited as a thin layer on a nanoscale substrate to achieve high utilization efficiency. However, the practical application of the as-designed catalysts has been substantially restricted by the poor durability arising from the leaching of cores. Herein, by employing amorphous palladium phosphide (a-Pd-P) as substrates, we develop a class of leaching-free, ultrastable core-shell Pt catalysts with well-controlled shell thicknesses and surface structures for fuel cell electrocatalysis. When a submonolayer of Pt is deposited on the 6 nm nanocubes, the resulting Pd@a-Pd-P@Pt core-shell catalyst can deliver a mass activity as high as 4.08 A/mg and 1.37 A/mg toward the oxygen reduction reaction at 0.9 V the reversible hydrogen electrode and undergoes 50 000 potential cycles with only ∼9% activity loss and negligible structural deformation. As elucidated by the DFT calculations, the superior durability of the catalysts originates from the high corrosion resistance of the disordered a-Pd-P substrates and the strong interfacial Pt-P interactions between the Pt shell and amorphous Pd-P layer.
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http://dx.doi.org/10.1021/acsnano.1c00602DOI Listing
March 2021

LINC01614 promotes osteosarcoma progression via miR-520a-3p/SNX3 axis.

Cell Signal 2021 Mar 20;83:109985. Epub 2021 Mar 20.

The Key Laboratory of Zoonosis Research, Chinese Ministry of Education, College of Basic Medical Science, Jilin University, Changchun 130021, China. Electronic address:

Long noncoding RNAs (lncRNAs) have been reported as essential regulators in osteosarcoma (OS), the most malignant bone tumor usually observed in children and adolescents. In the present study, we detected differentially expressed lncRNAs among OS tissues through RNA-sequencing. Then through bioinformatics analysis, we constructed the aberrant lncRNAs regulatory networks, and detected the key-lncRNAs. We identified LINC01614 was most significantly up-regulated among OS tissues, which was positively correlated with the worse prognosis. Through related in vitro experiments, we confirmed that knockdown of LINC01614 could inhibit the proliferation, invasion, and metastasis activities of OS cells. Furthermore, we identified LINC01614 may promote the proliferation and invasion activities of OS cells, via binding miR-520a-3p and increase the expression of SNX3. In conclusion, we identified lncRNAs participate in various malignant behaviors in OS. We also proved that LINC01614 could function as competing endogenous RNAs and promote the proliferation, and invasion of OS cells through miR-520a-3p/SNX3 axis, and thus acts as a novel prognostic marker for OS in clinic.
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http://dx.doi.org/10.1016/j.cellsig.2021.109985DOI Listing
March 2021

Stronger secondary pollution processes despite decrease in gaseous precursors: A comparative analysis of summer 2020 and 2019 in Beijing.

Environ Pollut 2021 Mar 10;279:116923. Epub 2021 Mar 10.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, State Environmental Protection Key Laboratory of Sources and Control of Air Pollution Complex, Beijing Key Laboratory of Indoor Air Quality Evaluation and Control, Tsinghua University, Beijing, 100084, China.

To control the spread of COVID-19, China implemented a series of lockdowns, limiting various offline interactions. This provided an opportunity to study the response of air quality to emissions control. By comparing the characteristics of pollution in the summers of 2019 and 2020, we found a significant decrease in gaseous pollutants in 2020. However, particle pollution in the summer of 2020 was more severe; PM levels increased from 35.8 to 44.7 μg m, and PM increased from 51.4 to 69.0 μg m from 2019 to 2020. The higher PM was caused by two sandstorm events on May 11 and June 3, 2020, while the higher PM was the result of enhanced secondary formation processes indicated by the higher sulfate oxidation rate (SOR) and nitrate oxidation rate (NOR) in 2020. Higher SOR and NOR were attributed mainly to higher relative humidity and stronger oxidizing capacity. Analysis of PM distribution showed that severe haze occurred when particles within Bin2 (size ranging 1-2.5 μm) dominated. SO and SO remained stable under different periods at 0.5 and 0.8, respectively, indicating that SO existed mainly in smaller particles. Decreases in NO and increases in NO from clean to polluted conditions, similar to the variations in PM distribution, suggest that NO played a role in the worsening of pollution. O concentrations were higher in 2020 (108.6 μg m) than in 2019 (96.8 μg m). Marked decreases in fresh NO alleviated the titration of O. Furthermore, the oxidation reaction of NO that produces NO was dominant over the photochemical reaction of NO that produces O, making NO less important for O pollution. In comparison, a lower VOC/NO ratio (less than 10) meant that Beijing is a VOC-limited area; this indicates that in order to alleviate O pollution in Beijing, emissions of VOCs should be controlled.
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http://dx.doi.org/10.1016/j.envpol.2021.116923DOI Listing
March 2021

Sample size and power considerations for cluster randomized trials with count outcomes subject to right truncation.

Authors:
Fan Li Guangyu Tong

Biom J 2021 Mar 10. Epub 2021 Mar 10.

Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.

Cluster randomized trials (CRTs) are widely used in epidemiological and public health studies assessing population-level effect of group-based interventions. One important application of CRTs is the control of vector-borne disease, such as malaria. However, a particular challenge for designing these trials is that the primary outcome involves counts of episodes that are subject to right truncation. While sample size formulas have been developed for CRTs with clustered counts, they are not directly applicable when the counts are right truncated. To address this limitation, we discuss two marginal modeling approaches for the analysis of CRTs with truncated counts and develop two corresponding closed-form sample size formulas to facilitate the design of such trials. The proposed sample size formulas allow investigators to explore the power under a large number of scenarios without computationally intensive simulations. The proposed formulas are validated in extensive simulations. We further explore the implication of right truncation on power and apply the proposed formulas to illustrate the power calculation for a malaria control CRT where the primary outcome is subject to right truncation.
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http://dx.doi.org/10.1002/bimj.202000230DOI Listing
March 2021

PHD3 mediates denervation skeletal muscle atrophy through Nf-κB signal pathway.

FASEB J 2021 Apr;35(4):e21444

Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry and Guangdong Province Key Laboratory of Animal Nutritional Regulation, College of Animal Science, South China Agricultural University, Guangzhou, China.

Skeletal muscle is the largest organ of the body, the development of skeletal muscle is very important for the health of the animal body. Prolyl hydroxylases (PHDs) are the classical regulator of the hypoxia inducible factor (HIF) signal pathway, many researchers found that PHDs are involved in the muscle fiber type transformation, muscle regeneration, and myocyte differentiation. However, whether PHDs can impact the protein turnover of skeletal muscle is poorly understood. In this study, we constructed denervated muscle atrophy mouse model and found PHD3 was highly expressed in the atrophic muscles and there was a significant correlation between the expression level of PHD3 and skeletal muscle weight which was distinct from PHD1 and PHD2. Then, the similar results were getting from the different weight muscles of normal mice. To further verify the relationship between PHD3 and skeletal muscle protein turnover, we established a PHD3 interference model by injecting PHD3 sgRNA virus into tibialis anterior muscle (TA) muscle of MCK-Cre-cas9 mice and transfecting PHD3 shRNA lentivirus into primary satellite cells. It was found that the Knock-out of PHD3 in vivo led to a significant increase in muscle weight and muscle fiber area (P < .05). Besides, the activity of protein synthesis signal pathway increased significantly, while the protein degradation pathway was inhibited evidently (P < .05). In vitro, the results of 5-ethynyl-2'-deoxyuridine (EdU) and tetramethylrhodamine ethyl ester (TMRE) fluorescence detection showed that PHD3 interference could lead to a decrease in cell proliferation and an increase of cell apoptosis. After the differentiation of satellite cells, the production of puromycin in the interference group was higher than that in the control group, and the content of 3-methylhistidine in the interference group was lower than that in the control group (P < .05) which is consistent with the change of protein turnover signal pathway in the cell. Mechanistically, there is an interaction between PHD3, NF-κB, and IKBα which was detected by immunoprecipitation. With the interfering of PHD3, the expression of the inflammatory signal pathway also significantly decreased (P < .05). These results suggest that PHD3 may affect protein turnover in muscle tissue by mediating inflammatory signal pathway. Finally, we knocked out PHD3 in denervated muscle atrophy mice and LPS-induced myotubes atrophy model. Then, we found that the decrease of PHD3 protein level could alleviate the muscle weight and muscle fiber reduction induced by denervation in mice. Meanwhile, the protein level of the inflammatory signal pathway and the content of 3-methylhistidine in denervated atrophic muscle were also significantly reduced (P < .05). In vitro, PHD3 knock-out could alleviate the decrease of myotube diameter induced by LPS, and the expression of protein synthesis pathway was also significantly increased (P < .05). On the contrary, the expression level of protein degradation and inflammatory signal pathway was significantly decreased (P < .05). Through these series of studies, we found that the increased expression of PHD3 in denervated muscle might be an important regulator in inducing muscle atrophy, and this process is likely to be mediated by the inflammatory NF-κB signal pathway.
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http://dx.doi.org/10.1096/fj.202002049RDOI Listing
April 2021

Hypoxanthine Induces Muscular ATP Depletion and Fatigue via UCP2.

Front Physiol 2021 3;12:647743. Epub 2021 Mar 3.

Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry and Guangdong Province Key Laboratory of Animal Nutritional Regulation, College of Animal Science, South China Agricultural University, Guangzhou, China.

Hypoxanthine (Hx), an intermediate metabolite of the purine metabolism pathway which is dramatically increased in blood and skeletal muscle during muscle contraction and metabolism, is characterized as a marker of exercise exhaustion. However, the physiological effects of Hx on skeletal muscle remain unknown. Herein, we demonstrate that chronic treatment with Hx through dietary supplementation resulted in skeletal muscle fatigue and impaired the exercise performance of mice without affecting their growth and skeletal muscle development. Hx increased the uncoupling protein 2 (UCP2) expression in the skeletal muscle, which led to decreased energy substrate storage and enhanced glycolysis. These effects could also be verified in acute treatment with Hx through intraperitoneal injection. In addition, muscular specifically knockout of UCP2 through intra-muscle tissue injection of adenovirus-associated virus reversed the effects of Hx. In conclusion, we identified a novel role of Hx in the skeletal muscular fatigue mediated by UCP2-dependent mitochondrial uncoupling. This finding may shed light on the pathological mechanism of clinical muscle dysfunctions due to abnormal metabolism, such as muscle fatigue and weakness.
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http://dx.doi.org/10.3389/fphys.2021.647743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966526PMC
March 2021

Hereditary transthyretin amyloidosis in mainland China: a unicentric retrospective study.

Ann Clin Transl Neurol 2021 Apr 19;8(4):831-841. Epub 2021 Mar 19.

Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.

Objective: This study aims to report the genotypes and phenotypes of hereditary transthyretin amyloidosis (ATTR) in a large Chinese cohort, yet the clinical and genetic profiles of ATTR remain elusive in mainland China.

Methods: Fifty-four patients with molecularly confirmed ATTR from 39 unrelated families were identified by sequencing the TTR gene. Sural nerve biopsies were performed in 40 of these cases. The clinical and electrophysiological data were retrospectively collected and analyzed.

Results: The male/female ratio was 42:12. The average age of patients at the onset of the disease was 47.8 ± 13.0 years. The late-onset type occurred in 29 cases (53.7%). Twenty-two probands (56.4%) had a family history with ATTR. The initial symptoms were limb paresthesia in 33 cases (61.1%), autonomic dysfunction in 15 cases (27.8%), and blurred vision in 6 cases (11.1%). A total of 22 different TTR mutations were identified, including Val30Met (25.6%) in 10 families in North China and Ala97Ser in 4 families (10.3%) in South China. Electrophysiological studies revealed general sensorimotor axonal polyneuropathy in 33/44 cases (75.0%), mixed neuropathy with axonal and demyelinating impairment features in 9/44 cases (20.5%) and isolated carpal tunnel syndrome in two cases. Sural nerve biopsies revealed positive Congo red staining in 16/40 cases (40.0%).

Conclusion: Chinese patients with ATTR exhibited heterogeneous TTR genotypes and clinical phenotypes. Val30Met remains the most common mutation type in mainland China.
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http://dx.doi.org/10.1002/acn3.51328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045954PMC
April 2021