Publications by authors named "Liu Mei"

1,159 Publications

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Development of CpG oligodeoxynucleotide TLR9 agonists in anti-cancer therapy.

Expert Rev Anticancer Ther 2021 Apr 8. Epub 2021 Apr 8.

Department of Neurology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, P.R. China.

Introduction: Toll-like receptor-9(TLR9) can recognize the foreign unmethylated CpG DNA, and thus intrigue a strong Th1 response which plays a crucial role in the innate and adaptive immune responses. To date, CpG oligodeoxynucleotide (ODN)-based TLR9 agonists have undergone four generations. Each generations' breakthroughs in immune activation, safety profiles and pharmacokinetic properties were confirmed by both preclinical and clinical studies.

Areas Covered: We reviewed the development and major clinical trials of TLR9 agonists and summarized the optimization strategies of each generation. The applications, limitations and prospects of TLR9 agonists in cancer immunotherapy were discussed were also discussed.

Expert Opinion: Clinical trials of CpG ODN TLR9 agonists as a single agent demonstrated insufficient efficacy to reverse the immunosuppressive status of majority of patients with high tumor burden. Therefore, more efforts are now been carried out in combination with chemotherapy, radiotherapy, immunotherapy maintenance therapy as well as vaccine adjuvant. Importantly, the synergistic and complementary effect of TLR9 agonists and tumor immune checkpoint inhibitor therapy is expected to exert greater potential. On the other hand, the double-edged sword effect of TLR9 activation in tumor and toxic effect reported in combination therapies should be noted and further studies required.
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http://dx.doi.org/10.1080/14737140.2021.1915136DOI Listing
April 2021

L-leucine promotes axonal outgrowth and regeneration via mTOR activation.

FASEB J 2021 May;35(5):e21526

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Discovering safe and effective drugs that promote neuron regeneration is an essential strategy for the recovery of central nervous system injuries. In this study, we found that L-leucine, an essential amino acid obtained from both supplements and food sources, could dramatically boost axonal outgrowth and regeneration. First, the effects of L-leucine on neurons were evaluated by cell apoptosis, survival, and death assays, and the results showed no changes in these processes after treatment. By live cell imaging, L-leucine was found to remarkably increase axonal length and growth velocity after axotomy. We also verified that L-leucine enhanced p-mTOR/p-S6K activation in neurons by testing with an mTOR inhibitor, rapamycin. Thereafter, we investigated the effects of L-leucine on the spinal cord injury in vivo. A mouse model of spinal cord hemi-section was established, and L-leucine was administered by tail intravenous injection. Basso mouse scale values revealed that L-leucine could improve functional recovery after injury. It was also notable that L-leucine treatment promoted axon growth across chondroitin sulfate proteoglycan (CSPG) areas. Furthermore, we used CSPGs as inhibitory environmental cues and clarified that L-leucine significantly enhanced axonal outgrowth and regeneration by promoting p-mTOR and p-S6K activation. Therefore, our study is the first to report that L-leucine promotes axonal regeneration in vitro and in vivo and could be candidate drug for axonal re-growth and nervous functional recovery.
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http://dx.doi.org/10.1096/fj.202001798RRDOI Listing
May 2021

Author Correction: Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is upregulated by HBx.

Sci Rep 2021 Mar 31;11(1):7523. Epub 2021 Mar 31.

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

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http://dx.doi.org/10.1038/s41598-021-87154-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012372PMC
March 2021

The molecular structure and role of CCL2 (MCP-1) and C-C chemokine receptor CCR2 in skeletal biology and diseases.

J Cell Physiol 2021 Mar 30. Epub 2021 Mar 30.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Monocyte chemoattractant protein-1, also called chemokine (C-C motif) ligand 2 (CCL2) or small inducible cytokine A2, is an inflammatory mediator capable of recruiting monocytes, memory T cells, and dendritic cells. CCL2 is a member of the CC chemokine superfamily, which binds to its receptor, C-C motif chemokine receptor-2 (CCR2), for the induction of chemotactic activity and an increase of calcium influx. It exerts multiple effects on a variety of cells, including monocytes, macrophages, osteoclasts, basophils, and endothelial cells, and is involved in a diverse range of diseases. This review discusses the molecular structure and role of CCL2 and CCR2 in skeletal biology and disease. Molecular structure analyses reveal that CCL2 shares a conserved C-C motif; however, it has only limited sequence homology with other CCL family members. Likewise, CCR2, as a member of the G-protein-coupled seven-transmembrane receptor superfamily, shares conserved cysteine residues, but exhibits very limited sequence homology with other CCR family members. In the skeletal system, the expression of CCL2 is regulated by a variety of factors, such as parathyroid hormone/parathyroid hormone-related peptide, interleukin 1b, tumor necrosis factor-α and transforming growth factor-beta, RANKL, and mechanical forces. The interaction of CCL2 and CCR2 activates several signaling cascades, including PI3K/Akt/ERK/NF-κB, PI3K/MAPKs, and JAK/STAT-1/STAT-3. Understanding the role of CCL2 and CCR2 will facilitate the development of novel therapies for skeletal disorders, including rheumatoid arthritis, osteolysis and other inflammatory diseases related to abnormal chemotaxis.
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http://dx.doi.org/10.1002/jcp.30375DOI Listing
March 2021

The Public's Risk Information Seeking and Avoidance in China During Early Stages of the COVID-19 Outbreak.

Front Psychol 2021 12;12:649180. Epub 2021 Mar 12.

Department of Agricultural Economics and Management, College of Economics and Management, Huazhong Agricultural University, Wuhan, China.

This study uses the Planned Risk Information Seeking Model (PRISM) to estimate the public's information seeking and avoidance intentions during the COVID-19 outbreak based on an online sample of 1031 Chinese adults and provides support for the applicability of PRISM framework in the situation of a novel high-level risk. The results indicate that information seeking is primarily directed by informational subjective norms (ISN) and perceived seeking control (PSC), while the main predictors of information avoidance include ISN and attitude toward seeking. Because ISN are the strongest predictor of both information seeking and avoidance, the way the public copes with COVID-19 information may be strongly affected by individuals' social environment. Furthermore, a significant relationship between risk perception and affective risk response is identified. Our results also indicate that people who perceive greater knowledge of COVID-19 are more likely to report greater knowledge insufficiency, which results in less information avoidance.
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http://dx.doi.org/10.3389/fpsyg.2021.649180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994604PMC
March 2021

Systematic review and meta-analysis of transgluteal versus prone approach to extracorporeal shockwave lithotripsy for patients with distal ureteral stones.

Asian J Surg 2021 Mar 23. Epub 2021 Mar 23.

Department of Urology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

To explore the effectiveness of transgluteal approach during extracorporeal shockwave lithotripsy (ESWL) for patients with distal ureteral stones compared to the prone approach. A systematic literature search was carried out by two reviewers independently on the basis of three electronic databases up to Aug. 2020. Three randomized controlled trials (RCT) and one cohort studies (CS), with a total of 516 patients, comparing transgluteal approach with prone approach during ESWL for distal ureteral stones were included. The methodological quality of RCT was evaluated by Cochrane collaboration's tools, and the quality of CS and CCS was evaluated by modified Newcatle-Ottawa scale. The weighted mean difference (WMD) and odds ratio (OR) was respectively used to describe results of continuous and dichotomous variables. Pooled data showed that transgluteal approach could significantly improve the rate of stone free after the first treatment [OR = 3.18, 95% confidence interval (CI) 2.19-4.63, p < 0.00001] and the rate of overall stone free (OR = 4.03, 95% CI 2.43-6.69, p < 0.00001). In addition, compared with the prone approach, the transgluteal one could also significantly reduce the rate of ureteroscopy (OR = 0.21, 95% CI 0.12-0.36, p < 0.00001). What's more, complications were rarely reported, which demonstrated a similar safety for two approaches. Our study suggested that, during ESWL for patients with distal ureteral stones, transgluteal approach was a safe and more effective choice than the prone position.
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http://dx.doi.org/10.1016/j.asjsur.2021.02.021DOI Listing
March 2021

SENP2: A Novel Regulatory Mechanism of Brown Adipocyte Differentiation.

Biomed Environ Sci 2020 Nov;33(11):872-876

Hengyang Medical College, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China, Hengyang 421001, Hunan, China.

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http://dx.doi.org/10.3967/bes2020.119DOI Listing
November 2020

Illicium verum and Eucommia ulmoides leaf extracts promote nutrient availability and antioxidant capacity in piglets by upregulating duodenal and jejunal Nrf2/TNF-α.

J Anim Physiol Anim Nutr (Berl) 2021 Mar 26. Epub 2021 Mar 26.

Department of Animal Sciences and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian City, Shandong Province, China.

The effect of Illicium verum extracts (IVE) or Eucommia ulmoides leaf extracts (ELE) on nutrient availability, duodenal and jejunal antioxidant ability of Duroc ×Landrace × Yorkshire (DLY) and Chinese native Licha-black (LCB) piglets was investigated. Ninety-six piglets (48 DLY and 48 LCB respectively) without significant difference in body weight (11.22 ± 0.32 kg) were used in a 2 × 4 factorial design. Animals were randomly allocated to four treatments, and each had four replicates with three DLY and three LCB piglets. Treatments were basal diet (CON) and basal diet with 500 mg/kg IVE, 250 mg/kg ELE and 50 mg/kg chlortetracycline (CHL) respectively. Animals were placed individually for 7-days adaptation following 42-days test. Results showed the significant interaction (p < 0.05) between dietary treatments and pig species in activity of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), content of malondialdehyde (MDA), and α-tumour necrosis factor (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2/TNF-α at mRNA and protein level in duodenum and jejunum of DLY and LCB piglets. The IVE and ELE increased (p < 0.05) activity of GSH-Px and T-SOD, and the Nrf2/TNF-α at mRNA and protein level, however, the decreased (p < 0.05) MDA content, and TNF-α at mRNA and protein level in duodenum and jejunum were observed. The CHL decreased (p < 0.05) activity of GSH-Px and T-SOD, TNF-α and Nrf2 at mRNA and protein level in duodenum, but increased (p < 0.05) MDA content and Nrf2/TNF-α in jejunum. DLY piglets had higher (p < 0.05) nutrient digestibility (organic matter, crude protein and gross energy), availability (biological value and net protein utilization), MDA content, and TNF-α at mRNA and protein level in jejunum, and had lower (p < 0.05) activity of GSH-Px and T-SOD, and Nrf2 and Nrf2/TNF-α at mRNA and protein level in duodenum and jejunum than LCB. In conclusion, the 500 mg/kg IVE and 250 mg/kg ELE improved the nutrient availability, and the improvement of antioxidant capacity is realized by activating the Nrf2/TNF-α of duodenum and jejunum. The CHL had adverse effects on antioxidant ability of DLY and LCB piglets. The results showed that the nutrient digestion and absorption capacity of DLY were stronger than that of LCB piglets, but the antioxidant capacity was lower than that of LCB piglets. Therefore, the IVE and ELE are recommended as a new potential alternative to antibiotics in piglets' diets.
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http://dx.doi.org/10.1111/jpn.13534DOI Listing
March 2021

Right Ventricular Contractility as a Potential Independent Evaluation Parameter in Pulmonary Hypertension.

Int J Clin Pract 2021 Mar 26:e14183. Epub 2021 Mar 26.

Department of Internal Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.

Background: Pulmonary artery hypertension (PAH) is a common disease with high disability and mortality rates, and can lead to right heart failure. We aimed to evaluate the capability of right ventricular pressure volume coupling parameters, end-systolic elastance (Ees), right ventricular afterload (Ea) and arterial elastance (Ees/Ea) for assessing right ventricular performance during chronic development of PAH.

Methods: Thirty-six PAH patients were enrolled in this study. We reported the cutoff values of the right ventricular pressure volume coupling parameters in the progression of PAH and their relations with other pressure volume loop measurements in both the right and left ventricles.

Results: Ees and normalized Ees (Ees/Ea) calculated from the pressure method performed better than ones from the volume method in correlation with mean pulmonary arterial pressure and mean right arterial pressure. The cutoff sets of Ees and Ees/Ea were capable of grouping pulmonary hypertension patients which were well supported by their significant correlation with several key right ventricular hemodynamic parameters. Additionally, the normalized Ees was able to reflect the changes of left ventricular function during deterioration of PAH.

Conclusion: Ees and Ees/Ea are promising independent reference parameters for assessing ventricular function in progressing PAH patients.
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http://dx.doi.org/10.1111/ijcp.14183DOI Listing
March 2021

Prevalence and Genetic Diversity of Isolated From Retail Pork in Wuhan, China.

Front Microbiol 2021 9;12:620482. Epub 2021 Mar 9.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

is a ubiquitous bacteria and causative agent of zoonotic listeriosis with high mortality. The consumption of contaminated animal-derived foods has been linked with both epidemic and sporadic listeriosis. In this work, a total of 64 isolates from 259 pork samples sold in 11 supermarket chains were identified and characterized by comparative whole-genome analysis. All isolates were delineated into eight clonal complexes (CCs), namely CC2, CC8, CC9, CC11, CC155, CC121, CC204, and CC619, spanning two lineages (I and II) and carrying 3-5 antibiotic-resistant genes (, , , , and ). It is noted that pathogenicity island (LIPI)-1, LIPI-3, and LIPI-4 were distributed in all ST619 isolates from two supermarket chains that were closely related with clinical isolates (<40 SNP). Some of the isolates from different supermarket chains with 0 SNP difference indicated a common pork supply source. Notably, 57.81% of the strains carried types IB, IIA, or IIIB CRISPR-Cas system, CC121 isolates carried both types IB and IIA CRISPR-Cas systems, Cas proteins of CC155 isolates located between two CRISPR loci, each CC has unique organization of Cas proteins as well as CRISPR loci. CRISPR-Cas system-based subtyping improved discrimination of pork-derived isolates. Comparisons at the genome level contributed to understand the genetic diversities and variations among the isolates and provided insights into the genetic makeup and relatedness of these pathogens.
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http://dx.doi.org/10.3389/fmicb.2021.620482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986423PMC
March 2021

Developmental Patterns of Fecal Bile Acids in Healthy Neonates and Children.

Med Sci Monit 2021 Mar 26;27:e928214. Epub 2021 Mar 26.

Department of Pediatrics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China (mainland).

BACKGROUND Normal profiles of FBAs in healthy neonates and children in Kunming city and surrounding areas in China have not been previously determined. The objective of this study was to determine a developmental pattern of fecal bile acids (FBAs) in healthy neonates and children. MATERIAL AND METHODS A cross-sectional study was performed on 238 healthy neonates and children recruited in the First Affiliated Hospital of Kunming Medical University, China from October 2015 to September 2016. Secreted primary and secondary FBAs in fresh feces were quantitated by liquid chromatography mass spectrometry (LC-MS). Amounts of FBAs in feces were compared among various age groups. RESULTS Trace amounts of cholic acid and chenodiol acid of primary FBAs were detectable at day 3 after birth, with a significant increase from day 3 to day 7. The primary FBAs gradually decreased from day 25 to the age of 6 years old. In contrast, a significant amount of glycochenodeoxycholic acid was detected on day 3 but decreased to a trace amount by day 7 and onwards. Primary FBAs appeared to maintain a high level, accounting for 98% of total FBAs, with no significant changes from day 7 to day 25 after birth. They gradually decreased from 90% to 10% from age 6 months to 6 years old. While the secondary FBAs were barely detected in neonates, only accounting for 2% of total FBAs, they were gradually elevated to 90% of total FBAs from age 6 months to 6 years old. CONCLUSIONS The liver can effectively synthesize primary bile acids 7 days after birth, and fecal primary bile acids tend to be stable after the neonate stage. Secondary bile acids continuously increase along with the maturation of intestinal flora, which reaches a relatively stable level at around 3 years old.
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http://dx.doi.org/10.12659/MSM.928214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008968PMC
March 2021

Coagulation dysfunction in patients with AECOPD and its relation to infection and hypercapnia.

J Clin Lab Anal 2021 Mar 25:e23733. Epub 2021 Mar 25.

Department of Respiratory and Critical Care Medicine, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China.

Background: Patients with chronic obstructive pulmonary disease (COPD) often have coagulation abnormalities. However, the factors that lead to coagulation dysfunction in acute exacerbation of COPD (AECOPD) remain insufficiently explored. This study aimed to investigate the factors affecting coagulation status in patients with COPD and their influence on thrombosis.

Methods: Data of COPD patients, including 135 cases in acute exacerbation stage and 44 cases in stable stage from Nov 2016 to Nov 2019 in our hospital, were collected. Healthy people (n = 135) were enrolled as the controls. The coagulation parameters, blood gas indexes and blood routine examination results were collected and analyzed.

Results: White blood count (WBC), neutrophil count, neutrophil percentage (N%), platelet (PLT), prothrombin time (PT), international normalized ratio (INR), fibrinogen (FIB), and activated partial thromboplastin time (APTT) increased, plasma thrombin time (TT) decreased in AECOPD group compared with the control group. In AECOPD group, PT, APTT, and FIB were positively correlated with neutrophils and C-reaction protein levels. PT was positively correlated with PCO2 and negatively with pH. Thrombosis was observed in five acute exacerbation and three stable stage COPD patients.

Conclusions: Patients with AECOPD presented abnormal coagulation status, which was correlated to infection and hypercapnia and might be potentially the risk factor of thrombosis.
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http://dx.doi.org/10.1002/jcla.23733DOI Listing
March 2021

2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside, a major bioactive component from Polygoni multiflori Radix (Heshouwu) suppresses DSS induced acute colitis in BALb/c mice by modulating gut microbiota.

Biomed Pharmacother 2021 May 23;137:111420. Epub 2021 Feb 23.

School of Agriculture and Biology, Zhongkai University of Agriculture and Engineering, No. 501 Zhongkai Rd, Haizhu District, Guangzhou, Guangdong Province 510225, PR China. Electronic address:

Background: Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD), which is a common idiopathic digestive disease without a specific cure or treatment for improvement. Because Polygoni multiflori Radix has a traditional medicinal use to treat intestinal diseases, and the water extract of this herbal medicine had a positive influence on dextran sulfate sodium (DSS) induced UC model in our study. Meanwhile 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) as the major component of the water extract of Polygoni multiflori Radix with yield of more than 10% exhibited the remarkable anti-inflammatory activity in vivo and in vitro, we predicted that TSG may contribute to benefit intestinal tract presented by the water extract of Polygoni multiflori Radix. Therefore, the present study aims to explore the pharmacological effect of this compound on UC model and its possible mechanism to regulate intestinal function through gut microbiota.

Methods: Ulcerative colitis model was established in BALb/c mice by continuously administrating 3% (w/v) DSS aqueous solution for one week. The disease activity index (DAI), colon length, histopathological examination by H&E and the levels of tight junction proteins (TJP) by immunofluorescence staining were performed in ulcerative colitis model following the protocol. Furthermore, the levels of main inflammatory factors like TNF-α, IL-β, IL-6, and IL-10 were analyzed by the ELIZA kits for the further confirmation of anti-inflammatory activity of TSG on ulcerative colitis model. Finally, 16S rDNA sequencing technology was conducted to explore the composition and relative abundance of gut microbiota of different treatment groups.

Results: TSG treatments effectively increased body weight about 5% of those in DSS group (p < 0.001) as well remarkably reduced the DAI scores to the 50% of those in DSS group (p < 0.001) in the UC model. TSG treatments of either 25 mg/kg (TSG-25) or 100 mg/kg (TSG-100) dosage restored epithelial barrier structure and exhibited obviously intact colon histology with reduced signs of inflammatory cells infiltration, preserved epithelia barrier, restored crypt structure, and increased numbers of goblet cells. TSG treatments could markedly lessen the histopathologic score two or three times than those in DSS group (p < 0.001). Especially for TSG-100 treatment, the fluorescence intensity of ZO-1 and Occludin were nearly back to 80% of those in normal group, and were 1.5 times more than those in the DSS group (p < 0.001). Additionally, direct evidence pointed to TSG as a therapeutically active molecule in the prevention and treatment of UC by significantly reducing the production of these pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6 (p < 0.05-0.001) and increasing the levels of anti-inflammatory cytokine IL-10 (p < 0.05-0.001). Finally, it was found TSG treatments significantly raised the relative abundances of Firmicutes and Bacteroidetes with a dose-dependently and improved the homeostasis of the gut microbiota composition which disrupted by DSS through increasing genus level Lachnospiraceae_NK4A136 and decreasing genus level of Helicobacter, Bacteroides, Parabacteroides.

Conclusion: The present results suggested that TSG treatments had a desirable pharmacological effect on acute colitis induced by DSS in the mice as well showed the possible mechanism relate to improve the intestinal function through balancing the gut microbiota of intestinal flora.
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http://dx.doi.org/10.1016/j.biopha.2021.111420DOI Listing
May 2021

Prevalence and clinical correlates of insomnia symptoms and their association with quality of life in Chinese patients with HBV-related liver disease.

PeerJ 2021 4;9:e10956. Epub 2021 Mar 4.

Beijing YouAn Hospital, Capital Medical University, Beijing, China.

Objective: This study aimed to describe the one-month prevalence of insomnia symptoms (insomnia hereafter) and the demographic and clinical correlates, and its association with quality of life (QOL) in Chinese patients with HBV-related liver disease.

Method: A total of 689 patients with HBV-related liver disease in Beijing, China formed the study sample. Three forms of insomnia including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS) and early morning awakening (EMA) were assessed using standardized questions. QOL was measured using the Medical Outcomes Study Short Form 12 (SF-12).

Results: The one-month prevalence of at least one type of insomnia was 69.5%, while DIS, DMS and EMA were 60.4%, 54.7% and 50.9%, respectively. Only 4.8% of patients suffering from insomnia received treatment. Multiple logistic regression analyses revealed that pre-existing medical conditions were positively associated with DIS and EMA; patients with more severe depressive symptoms were more likely to have DIS, DMS and EMA; local residents were less likely to have DIS; and those who were married and older were more likely to have DMS. Insomnia was not independently associated with QOL.

Conclusions: Insomnia is common in Chinese patients with HBV-related liver disease with a very low rate of treatment. Greater attention should be given to identify and treat insomnia in this patient population.
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http://dx.doi.org/10.7717/peerj.10956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937339PMC
March 2021

Complete Genome Sequence of Stenotrophomonas maltophilia Siphophage Salva.

Microbiol Resour Announc 2021 Mar 11;10(10). Epub 2021 Mar 11.

Center for Phage Technology, Texas A&M University, College Station, Texas, USA

is a Gram-negative pathogen causing severe and often refractory illnesses such as pneumonia and bacteremia. We present the genome of phage Salva, a novel phage that is not closely related to any phages currently deposited in GenBank. The genome is 60,789 bp, containing 102 putative protein-coding genes.
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http://dx.doi.org/10.1128/MRA.00083-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953286PMC
March 2021

COVID-19 SignSym: a fast adaptation of a general clinical NLP tool to identify and normalize COVID-19 signs and symptoms to OMOP common data model.

J Am Med Inform Assoc 2021 Mar 1. Epub 2021 Mar 1.

Melax Technologies, Inc, Houston, Texas, USA.

The COVID-19 pandemic swept across the world rapidly, infecting millions of people. An efficient tool that can accurately recognize important clinical concepts of COVID-19 from free text in electronic health records (EHRs) will be valuable to accelerate COVID-19 clinical research. To this end, this study aims at adapting the existing CLAMP natural language processing tool to quickly build COVID-19 SignSym, which can extract COVID-19 signs/symptoms and their 8 attributes (body location, severity, temporal expression, subject, condition, uncertainty, negation, and course) from clinical text. The extracted information is also mapped to standard concepts in the Observational Medical Outcomes Partnership common data model. A hybrid approach of combining deep learning-based models, curated lexicons, and pattern-based rules was applied to quickly build the COVID-19 SignSym from CLAMP, with optimized performance. Our extensive evaluation using 3 external sites with clinical notes of COVID-19 patients, as well as the online medical dialogues of COVID-19, shows COVID-19 SignSym can achieve high performance across data sources. The workflow used for this study can be generalized to other use cases, where existing clinical natural language processing tools need to be customized for specific information needs within a short time. COVID-19 SignSym is freely accessible to the research community as a downloadable package (https://clamp.uth.edu/covid/nlp.php) and has been used by 16 healthcare organizations to support clinical research of COVID-19.
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http://dx.doi.org/10.1093/jamia/ocab015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989301PMC
March 2021

Mechanical/Electrical Characterization of ZnO Nanomaterial Based on AFM/Nanomanipulator Embedded in SEM.

Micromachines (Basel) 2021 Feb 28;12(3). Epub 2021 Feb 28.

Shanghai Key Laboratory of Intelligent Manufacturing and Robotics, School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200072, China.

ZnO nanomaterials have been widely used in micro/nano devices and structure due to special mechanical/electrical properties, and its characterization is still deficient and challenging. In this paper, ZnO nanomaterials, including nanorod and nanowire are characterized by atomic force microscope (AFM) and nanomanipulator embedded in scanning electron microscope (SEM) respectively, which can manipulate and observe simultaneously, and is efficient and cost effective. Surface morphology and mechanical properties were observed by AFM. Results showed that the average Young's modulus of ZnO nanorods is 1.40 MPa and the average spring rate is 0.08 N/m. Electrical properties were characterized with nanomanipulator, which showed that the ZnO nanomaterial have cut-off characteristics and good schottky contact with the tungsten probes. A two-probe strategy was proposed for piezoelectric property measurement, which is easy to operate and adaptable to multiple nanomaterials. Experiments showed maximum voltage of a single ZnO nanowire is around 0.74 mV. Experiment criteria for ZnO manipulation and characterization were also studied, such as acceleration voltage, operation duration, sample preparation. Our work provides useful references for nanomaterial characterization and also theoretical basis for nanomaterials application.
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http://dx.doi.org/10.3390/mi12030248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997223PMC
February 2021

Recurrent neural network with noise rejection for cyclic motion generation of robotic manipulators.

Neural Netw 2021 Feb 17;138:164-178. Epub 2021 Feb 17.

School of Information Science and Engineering, Lanzhou University, Lanzhou 730000, China. Electronic address:

Recurrent neural network (RNN), as a kind of neural network with outstanding computing capability, improvability, and hardware realizability, has been widely used in various fields, especially in robotics. In this paper, an RNN with noise rejection is deliberately constructed to remedy the issue of joint-angle drift frequently occurring during the cyclic motion generation (CMG) of a manipulator in a noisy environment. Different from general RNNs, the proposed RNN possesses inherent noise immunity, especially for time-varying polynomial noises. Besides, proofs on the convergence of the proposed RNN in the absence and presence of noises are given. Furthermore, we carry out simulations on manipulators PUMA 560 and UR5 to demonstrate the reliability of the proposed RNN in remedying joint-angle drift, and comparison simulations under different noisy conditions further verify its superiority. In addition, experiments are conducted on manipulator FRANKA Panda to elucidate the realizability of the proposed RNN.
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http://dx.doi.org/10.1016/j.neunet.2021.02.002DOI Listing
February 2021

Making novel staple foods the norm: perspectives from adult consumers with and without diabetes.

Appetite 2021 Mar 2;162:105189. Epub 2021 Mar 2.

Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, 12 Science Drive 2, 117549, Singapore. Electronic address:

Novel staple foods are staple foods that are modified with the purpose of improving their nutritional properties. However, consumers' acceptance towards novel staple foods remains to be evaluated, especially in Asian populations where staple foods like white rice are a major source of energy. The objective of this study was to explore consumers' attitudes and perceptions towards novel staple foods in a multi-ethnic Asian population. We conducted 11 focus group discussions, with 37 healthy participants and 22 participants with diabetes recruited through newspaper, email and poster advertisement and in-person recruitment at a clinic. Thematic analysis using the general inductive approach was performed. We found that participants' conceptual understanding of the modification process affected their acceptance towards novel staple foods. Plant-based modifications were considered natural and acceptable while genetic modification and use of chemicals were unnatural and undesirable. Participants expected novel staple foods to be more expensive and less tasty and this was largely due to their perceptions and experiences with healthy eating. Participants with diabetes or family history of diabetes were generally more willing to compromise taste and cost for healthier staple foods, and this appeared to be driven by concerns about diabetes and its related co-morbidities. The appearance of food was an important influence on participants' initial impression of the food, which appeared to be mediated by taste expectations. Participants' trust of novel staple foods was largely influenced by their trust in food industry, governmental authorities and nutrition science that was mediated through pathways of information and food safety.
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http://dx.doi.org/10.1016/j.appet.2021.105189DOI Listing
March 2021

RhoA/Rock activation represents a new mechanism for inactivating Wnt/β-catenin signaling in the aging-associated bone loss.

Cell Regen 2021 Mar 3;10(1). Epub 2021 Mar 3.

Department of Pharmacology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, China.

The Wnt/β-catenin signaling pathway appears to be particularly important for bone homeostasis, whereas nuclear accumulation of β-catenin requires the activation of Rac1, a member of the Rho small GTPase family. The aim of the present study was to investigate the role of RhoA/Rho kinase (Rock)-mediated Wnt/β-catenin signaling in the regulation of aging-associated bone loss. We find that Lrp5/6-dependent and Lrp5/6-independent RhoA/Rock activation by Wnt3a activates Jak1/2 to directly phosphorylate Gsk3β at Tyr216, resulting in Gsk3β activation and subsequent β-catenin destabilization. In line with these molecular events, RhoA loss- or gain-of-function in mouse embryonic limb bud ectoderms interacts genetically with Dkk1 gain-of-function to rescue the severe limb truncation phenotypes or to phenocopy the deletion of β-catenin, respectively. Likewise, RhoA loss-of-function in pre-osteoblasts robustly increases bone formation while gain-of-function decreases it. Importantly, high RhoA/Rock activity closely correlates with Jak and Gsk3β activities but inversely correlates with β-catenin signaling activity in bone marrow mesenchymal stromal cells from elderly male humans and mice, whereas systemic inhibition of Rock therefore activates the β-catenin signaling to antagonize aging-associated bone loss. Taken together, these results identify RhoA/Rock-dependent Gsk3β activation and subsequent β-catenin destabilization as a hitherto uncharacterized mechanism controlling limb outgrowth and bone homeostasis.
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http://dx.doi.org/10.1186/s13619-020-00071-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925793PMC
March 2021

Microtubule Severing Protein Fignl2 Contributes to Endothelial and Neuronal Branching in Zebrafish Development.

Front Cell Dev Biol 2020 18;8:593234. Epub 2021 Jan 18.

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Previously, () and its family members () and () were found to be highly expressed during zebrafish brain development, suggesting their functions in the nervous system. In this study, we report the effects of loss-of-function of these genes on development. We designed and identified single-guide RNAs targeted to generate , and mutants and then observed the overall morphological and behavioral changes. Our findings showed that while and null mutants displayed no significant defects, null zebrafish mutants displayed pericardial edema, reduced heart rate, and smaller eyes; null mutants responded to the light-darkness shift with a lower swimming velocity. mRNAs were identified in vascular endothelial cells by hybridization and re-analysis of an online dataset of single-cell RNAseq results. Finally, we used morpholino oligonucleotides to confirm that knockdown resulted in severe heart edema, which was caused by abnormal vascular branching. The zebrafish morphants also showed longer axonal length and more branches of caudal primary neurons. Taken together, we summarize that Fignl2 functions on cellular branches in endothelial cells and neurons. This study reported for the first time that the microtubule-severing protein Fignl2 contributes to cell branching during development.
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http://dx.doi.org/10.3389/fcell.2020.593234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873885PMC
January 2021

Point-of-care diagnostics for infectious diseases: From methods to devices.

Nano Today 2021 Apr 6;37:101092. Epub 2021 Feb 6.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, PR China.

The current widespread of COVID-19 all over the world, which is caused by SARS-CoV-2 virus, has again emphasized the importance of development of point-of-care (POC) diagnostics for timely prevention and control of the pandemic. Compared with labor- and time-consuming traditional diagnostic methods, POC diagnostics exhibit several advantages such as faster diagnostic speed, better sensitivity and specificity, lower cost, higher efficiency and ability of on-site detection. To achieve POC diagnostics, developing POC detection methods and correlated POC devices is the key and should be given top priority. The fast development of microfluidics, micro electro-mechanical systems (MEMS) technology, nanotechnology and materials science, have benefited the production of a series of portable, miniaturized, low cost and highly integrated POC devices for POC diagnostics of various infectious diseases. In this review, various POC detection methods for the diagnosis of infectious diseases, including electrochemical biosensors, fluorescence biosensors, surface-enhanced Raman scattering (SERS)-based biosensors, colorimetric biosensors, chemiluminiscence biosensors, surface plasmon resonance (SPR)-based biosensors, and magnetic biosensors, were first summarized. Then, recent progresses in the development of POC devices including lab-on-a-chip (LOC) devices, lab-on-a-disc (LOAD) devices, microfluidic paper-based analytical devices (PADs), lateral flow devices, miniaturized PCR devices, and isothermal nucleic acid amplification (INAA) devices, were systematically discussed. Finally, the challenges and future perspectives for the design and development of POC detection methods and correlated devices were presented. The ultimate goal of this review is to provide new insights and directions for the future development of POC diagnostics for the management of infectious diseases and contribute to the prevention and control of infectious pandemics like COVID-19.
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http://dx.doi.org/10.1016/j.nantod.2021.101092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864790PMC
April 2021

Inducing secondary metabolite production of Aspergillus sydowii through microbial co-culture with Bacillus subtilis.

Microb Cell Fact 2021 Feb 12;20(1):42. Epub 2021 Feb 12.

School of Bioengineering, Dalian University of Technology, DalianLiaoning, 116024, China.

Background: The co-culture strategy which mimics natural ecology by constructing an artificial microbial community is a useful tool to activate the biosynthetic gene clusters to generate new metabolites. However, the conventional method to study the co-culture is to isolate and purify compounds separated by HPLC, which is inefficient and time-consuming. Furthermore, the overall changes in the metabolite profile cannot be well characterized.

Results: A new approach which integrates computational programs, MS-DIAL, MS-FINDER and web-based tools including GNPS and MetaboAnalyst, was developed to analyze and identify the metabolites of the co-culture of Aspergillus sydowii and Bacillus subtilis. A total of 25 newly biosynthesized metabolites were detected only in co-culture. The structures of the newly synthesized metabolites were elucidated, four of which were identified as novel compounds by the new approach. The accuracy of the new approach was confirmed by purification and NMR data analysis of 7 newly biosynthesized metabolites. The bioassay of newly synthesized metabolites showed that four of the compounds exhibited different degrees of PTP1b inhibitory activity, and compound N2 had the strongest inhibition activity with an IC value of 7.967 μM.

Conclusions: Co-culture led to global changes of the metabolite profile and is an effective way to induce the biosynthesis of novel natural products. The new approach in this study is one of the effective and relatively accurate methods to characterize the changes of metabolite profiles and to identify novel compounds in co-culture systems.
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http://dx.doi.org/10.1186/s12934-021-01527-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881642PMC
February 2021

Complete Genome Sequence of Burkholderia cenocepacia Phage Magia.

Microbiol Resour Announc 2021 Feb 11;10(6). Epub 2021 Feb 11.

Center for Phage Technology, Texas A&M University, College Station, Texas, USA

is a Gram-negative bacterium that is implicated in respiratory infections. The 44,942-bp genome of Magia, a phage infecting , does not appear to have strong overall similarity to other known phages. The Magia genome encodes a Cro-like transcriptional regulator, a C2-like immunity repressor, and an integrase, suggesting that it is a temperate phage.
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http://dx.doi.org/10.1128/MRA.01473-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883833PMC
February 2021

Complete Genome Sequence of Burkholderia cenocepacia Phage Mica.

Microbiol Resour Announc 2021 Feb 11;10(6). Epub 2021 Feb 11.

Center for Phage Technology, Texas A&M University, College Station, Texas, USA

is a multidrug-resistant Gram-negative pathogen known to colonize patients with chronic granulomatous disease and cystic fibrosis. Here, we describe phage Mica, which is predicted to be a lysogenic myophage based on the similarity of its structural proteins to phage P2 and phage KL3.
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http://dx.doi.org/10.1128/MRA.01407-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883832PMC
February 2021

Clinical characteristics of inpatients with coronavirus disease 2019 (COVID-19) in Sichuan province.

BMC Infect Dis 2021 Feb 8;21(1):155. Epub 2021 Feb 8.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.

Background: The outbreak of COVID-19 has resulted in serious concerns in China and abroad. To investigate clinical features of confirmed and suspected patients with COVID-19 in west China, and to examine differences between severe versus non-severe patients.

Methods: Patients admitted for COVID-19 between January 21 and February 11 from fifteen hospitals in Sichuan Province, China were included. Experienced clinicians trained with methods abstracted data from medical records using pre-defined, pilot-tested forms. Clinical characteristics between severe and non-severe patients were compared.

Results: Of the 169 patients included, 147 were laboratory-confirmed, 22 were suspected. For confirmed cases, the most common symptoms from onset to admission were cough (70·7%), fever (70·5%) and sputum (33·3%), and the most common chest CT patterns were patchy or stripes shadowing (78·0%); throughout the course of disease, 19·0% had no fever, and 12·4% had no radiologic abnormality; twelve (8·2%) received mechanical ventilation, four (2·7%) were transferred to ICU, and no death occurred. Compared to non-severe cases, severe ones were more likely to have underlying comorbidities (62·5% vs 26·2%, P = 0·001), to present with cough (92·0% vs 66·4%, P = 0·02), sputum (60·0% vs 27·9%, P = 0·004) and shortness of breath (40·0% vs 8·2%, P <  0·0001), and to have more frequent lymphopenia (79·2% vs 43·7%, P = 0·003) and eosinopenia (84·2% vs 57·0%, P = 0·046).

Conclusions: The symptoms of patients in west China were relatively mild, and an appreciable proportion of infected cases had no fever, warranting special attention.
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http://dx.doi.org/10.1186/s12879-021-05825-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868861PMC
February 2021

Antagonistic Effects of Delia antiqua (Diptera: Anthomyiidae)-Associated Bacteria Against Four Phytopathogens.

J Econ Entomol 2021 Feb 6. Epub 2021 Feb 6.

Shandong Provincial Key Laboratory of Applied Microbiology, Ecology Institute, Qilu University of Technology (Shandong Academy of Sciences), Ji'nan, China.

Recent studies have revealed multiple roles of insect-associated microbes such as lignin degradation, entomopathogen inhibition, and antibiotic production. These functions improve insect host fitness, and provide a novel source of discovering beneficial microbes for industrial and agricultural production. Previously published research found that in the symbiosis formed by the dipteran pest Delia antiqua (Meigen) (Diptera: Anthomyiidae) and its associated bacteria, the bacteria showed effective inhibition of one fungal entomopathogen, Beauveria bassiana. The antifungal activity of those associated bacteria indicates their potential to be used as biocontrol agents for fungal phytopathogens. In this study, we first isolated and identified bacteria associated with D. antiqua using a culture-dependent method. Second, we tested the antifungal activity of these bacteria against four phytopathogens including Fusarium moniliforme, Botryosphaeria dothidea, and two Fusarium oxysporum strains using the dual-culture method. In total, 74 species belonging to 30 genera, 23 families, eight classes, and four phyla were isolated and identified. Among those bacteria, Ochrobactrum anthropi, Morganella morganii, Arthrobacter sp. 3, and Acinetobacter guillouiae showed significant volatile inhibition activity against F. moniliforme, B. dothidea, and both F. oxysporum, respectively. Moreover, bacteria including Rhodococcus equi, Leucobacter aridicollis, Paenibacillus sp. 3, and Lampropedia sp. showed significant contact inhibition activity against F. moniliforme, B. dothidea, and both F. oxysporum. Our work provides a new source for discovering biocontrol agents against phytopathogens.
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http://dx.doi.org/10.1093/jee/toab002DOI Listing
February 2021

Early physical rehabilitation vs standard care for intracerebral hemorrhage stroke: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jan;100(3):e24219

Department of Rehabilitation Medicine, Second Hospital of Lanzhou University, Lanzhou, China.

Background: The intracerebral hemorrhagic stroke (ICH) is associated with high mortality and severe disability in survivors, which causing about 42% of the disability-adjusted life years lost and 50% of all stroke patients dead within 1 year. Although early functional training is recommended to facility rehabilitation after the stroke, the benefit and safety are still controversial.

Introduction: This systematic review aims to investigate whether early physical rehabilitation could have a beneficial effect for the patients with ICH compared with standard rehabilitation care.

Methods And Analysis: Pubmed, Embase, and Cochrane library will be searched to include randomized control trials which investigate the rehabilitation effective of the early mobilization for patients with ICH compared with routine nursing or standard care. Rev-Man version 5.3 will be used to perform all calculations related to the meta-analysis. Dichotomous data will be calculated in terms of a fixed or random effect model and expressed by the relative risk (RR) with 95% confidence interval (CI). The Cochrane collaborations tool in the following aspects was used to assess the risk of bias (ROB) in included studies. The inconsistency index (I2) and Chi-Squared will be applied for heterogeneity detection between clinical trials. A value of P < .05 will be considered statistically significant.

Conclusion: This study will explore the role of early physical rehabilitation and provide insight for clinicals to improve rehabilitation results of ICH.

Registration Number: INPLASY2020110068.
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http://dx.doi.org/10.1097/MD.0000000000024219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837980PMC
January 2021

Complete Genome Sequence of Burkholderia gladioli Phage Maja.

Microbiol Resour Announc 2021 Feb 4;10(5). Epub 2021 Feb 4.

Center for Phage Technology, Texas A&M University, College Station, Texas, USA

is a Gram-negative bacterium associated with cystic fibrosis infections. Here, we describe the genome sequence of phage Maja. Maja is most related to another phage, BcepF1, and may be a temperate phage, despite the absence of repressor or integrase homologs in its genome sequence.
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http://dx.doi.org/10.1128/MRA.01430-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862960PMC
February 2021

Complete Genome Sequence of Klebsiella aerogenes Myophage Metamorpho.

Microbiol Resour Announc 2021 Feb 4;10(5). Epub 2021 Feb 4.

Center for Phage Technology, Texas A&M University, College Station, Texas, USA

The bacterium is an opportunistic pathogen that often infects hospitalized patients and those who are immunocompromised. in some cases can become resistant to antibiotic treatment. Being a potential therapeutic, Metamorpho is a T4-like myophage targeting .
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http://dx.doi.org/10.1128/MRA.01420-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862958PMC
February 2021