Publications by authors named "Wei Hu"

2,005 Publications

  • Page 1 of 1

Overexpression of miRNA-22-3p attenuates osteoporosis by targeting MAPK14.

Exp Ther Med 2021 Jul 2;22(1):692. Epub 2021 May 2.

Department of Orthopaedics, Chongqing Public Health Medical Center, Chongqing 400036, P.R. China.

Osteoporosis (OP) results from an imbalance between bone formation, which is regulated by osteoblasts, and bone resorption, which is mediated by osteoclasts. MicroRNA-22-3p (miR-22-3p) expression is decreased during the process of osteoclast differentiation and p38α mitogen-activated protein kinase (MAPK)14 promotes the proliferation and differentiation of osteoclast progenitors. However, whether miR-22-3p could target MAPK14 to regulate the progression of OP remains unknown, which was the aim of the present study. CD14 PBMCs were used for the establishment of osteoclastic differentiation . In the present study, reverse transcription quantitative PCR was used to determine the mRNA expression of MAPK14, tartrate resistant acid phosphatase (TRAP), nuclear factor of activated T-cells (NFATC1) and cathepsin K (CTSK). Western blotting was applied to determine the protein expression of MAPK14, TRAP, NFATC1, CTSK, p-p65 and p65. Dual luciferase reporter assay was applied to confirm the relation between miR-22-3p and MAPK14. Cell Counting Kit-8 assay and flow cytometry assays were used to determine the cell proliferation and cell apoptosis, respectively. The results demonstrated that miR-22-3p expression was lower while MAPK14 expression was higher in the serum from patients with OP compared with healthy volunteers. Furthermore, miR-22-3p expression was negatively correlated with MAPK14 expression in patients with OP. In addition, miR-22-3p expression was decreased and MAPK14 expression was increased during the progression of CD14peripheral blood mononuclear cells (PBMCs) osteoclastic differentiation in a time-dependent manner. Furthermore, miR-22-3p inhibited the proliferation and differentiation and promoted the apoptosis of CD14PBMCs by targeting MAPK14. In summary, the findings from the present study suggested that miR-22-3p may serve a potential therapeutic role in patients with OP.
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http://dx.doi.org/10.3892/etm.2021.10124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112124PMC
July 2021

Safety and Tolerability of Burst-Cycling Deep Brain Stimulation for Freezing of Gait in Parkinson's Disease.

Front Hum Neurosci 2021 26;15:651168. Epub 2021 Apr 26.

Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United States.

: Freezing of gait (FOG) is a common symptom in Parkinson's disease (PD) and can be difficult to treat with dopaminergic medications or with deep brain stimulation (DBS). Novel stimulation paradigms have been proposed to address suboptimal responses to conventional DBS programming methods. Burst-cycling deep brain stimulation (BCDBS) delivers current in various frequencies of bursts (e.g., 4, 10, or 15 Hz), while maintaining an intra-burst frequency identical to conventional DBS. : To evaluate the safety and tolerability of BCDBS in PD patients with FOG. : Ten PD subjects with STN or GPi DBS and complaints of FOG were recruited for this single center, single blinded within-subject crossover study. For each subject, we compared 4, 10, and 15 Hz BCDBS to conventional DBS during the PD medication-OFF state. : There were no serious adverse events with BCDBS. It was feasible and straightforward to program BCDBS in the clinic setting. The benefit was comparable to conventional DBS in measures of FOG, functional mobility and in PD motor symptoms. BCDBS had lower battery consumption when compared to conventional DBS. : BCDBS was feasible, safe and well tolerated and it has potential to be a viable future DBS programming strategy.
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http://dx.doi.org/10.3389/fnhum.2021.651168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109241PMC
April 2021

Compromised long-lived memory CD8+ T cells are associated with reduced IL-7 responsiveness in HIV-infected immunological non-responders.

Eur J Immunol 2021 May 11. Epub 2021 May 11.

Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.

Immune deficiency is one of the hallmarks of HIV infection and a major cause of adverse outcomes in people living with HIV (PLWH). Long-lived memory CD8 T cells (LLMCs) are essential executors of long-term protective immunity; however, the generation and maintenance of LLMCs during chronic HIV infection are not well understood. In the present study, we analyzed circulating LLMCs in healthy controls (HCs) and PLWH with different disease statuses, including treatment naïve patients (TNs), complete responders (CRs), and immunological non-responders (INRs). We found that both TNs and INRs showed severely compromised LLMCs compared with HCs and CRs, respectively. The decrease of LLMCs in TNs correlated positively with the reduction of their precursors, namely memory precursor effector T cells (MPECs), which might be associated with elevated pro-inflammatory cytokines. Strikingly, INRs showed an accumulation of MPECs, which exhibited diminished responsiveness to interleukin 7 (IL-7), thereby indicating abrogated differentiation into LLMCs. Moreover, in vitro studies showed that treatment with dexamethasone could improve the IL7-phosphorylated (p)-signal transducer and activator of transcription (STAT5) response by upregulating the expression of the interleukin 7 receptor (IL-7Rα) on MPECs in INRs. These findings provide insights that will encourage the development of novel therapeutics to improve immune function in PLWH. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/eji.202149203DOI Listing
May 2021

Prevalence and factors associated with intestinal schistosomiasis and human fascioliasis among school children in Amhara Regional State, Ethiopia.

Trop Med Health 2021 May 11;49(1):35. Epub 2021 May 11.

Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.

Background: Schistosomiasis and fascioliasis are digenean parasitic infections and are among the neglected tropical diseases that have both medical and veterinary importance. They are found mainly in areas having limited access to safe water supply and improved sanitation.

Methods: A cross-sectional study was conducted to determine the prevalence of Schistosoma mansoni and Fasciola species infections and to identify associated risk factors among school children in Amhara Regional State, Ethiopia. Stool specimens were collected from 798 children (419 males, 379 females) and processed using Kato-Katz and formol-ether concentration techniques. A semi-structured questionnaire was used to collect socio-demographic and other exposure information to explore potential risk factors for the infections.

Results: The overall prevalence of S. mansoni and Fasciola species infections was 25.6% (95% confidence interval (CI): 22.5-28.6) and 5.5% (95% CI: 3.9-7.1), respectively. S. mansoni was present in all surveyed schools with the prevalence ranging from 12.8% (16/125; 95% CI = 5.6-20.0) to 39.7% (64/161; 95% CI = 32.2-47.2) while Fasciola species was identified in five schools with the prevalence ranging from 2.5% (4/160; 95% CI = 0.001-4.9) to 9.8% (13/133; 95% CI = 4.7-14.8). The prevalence of S. mansoni infection was significantly associated with swimming in rivers (Adjusted odds ratio (AOR): 1.79, 95% CI, 1.22-2.62; P=0.003), bathing in open freshwater bodies (AOR, 2.02; 95% CI, 1.39-2.94; P<0.001) and engaging in irrigation activities (AOR, 1.69; 95% CI, 1.19-2.39; P=0.004), and was higher in children attending Addis Mender (AOR, 2.56; 95% CI, 1.20-5.46; P=0.015 ) and Harbu schools (AOR, 3.53; 95% CI, 1.64-7.59; P=0.001). Fasciola species infection was significantly associated with consumption of raw vegetables (AOR, 2.47; 95% CI, 1.23-4.97; P=0.011) and drinking water from unimproved sources (AOR, 2.28; 95% CI, 1.11-4.70; P=0.026).

Conclusion: Both intestinal schistosomiasis and human fascioliasis are prevalent in the study area, affecting school children. Behaviors and access to unimproved water and sanitation are among significant risk factors. The findings are instrumental for targeted interventions.
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http://dx.doi.org/10.1186/s41182-021-00326-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111779PMC
May 2021

Discovery and validation of novel protein markers in mucosa of portal hypertensive gastropathy.

BMC Gastroenterol 2021 May 10;21(1):214. Epub 2021 May 10.

Department of Gastroenterology, Shenzhen Hospital of Southern Medical University, Shenzhen, 518000, Guangdong, China.

Background: Portal hypertension induced esophageal and gastric variceal bleeding is the main cause of death among patients of decompensated liver cirrhosis. Therefore, a standardized, biomarker-based test, to make an early-stage non-invasive risk assessment of portal hypertension, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified.

Methods: We conducted a pilot study consisting of 5 portal hypertensive gastropathy (PHG) patients and 5 normal controls, sampling the gastric mucosa of normal controls and PHG patients before and after endoscopic cyanoacrylate injection, using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in gastric mucosa from PHG patients and normal controls. Then we further used parallel reaction monitoring (PRM) to verify the abundance of the targeted protein.

Results: LFQ analyses identified 423 significantly differentially expressed proteins. 17 proteins that significantly elevated in the gastric mucosa of PHG patients were further validated using PRM.

Conclusions: This is the first application of an LFQ-PRM workflow to identify and validate PHG-specific biomarkers in patient gastric mucosa samples. Our findings lay the foundation for comprehending the molecular mechanisms of PHG pathogenesis, and provide potential applications for useful biomarkers in early diagnosis and treatment. Trial registration and ethics approval: Trial registration was completed (ChiCTR2000029840) on February 25, 2020. Ethics Approvals were completed on July 17, 2017 (NYSZYYEC20180003) and February 15, 2020 (NYSZYYEC20200005).
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http://dx.doi.org/10.1186/s12876-021-01787-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111717PMC
May 2021

A new strategy to construct gold nanocluster-based optical probes using luminescence resonance energy transfer.

Chem Commun (Camb) 2021 May 10. Epub 2021 May 10.

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.

Monolayer-protected metal nanoclusters (MPCs) are emerging as intriguing luminescent materials, but the construction of MPC-based optical probes is still scarce because of both the limited photoluminescence efficiency of MPCs and the lack of recognition mechanism. We herein propose a luminescence resonance energy transfer-based strategy to circumvent these problems.
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http://dx.doi.org/10.1039/d1cc01482jDOI Listing
May 2021

Highly Permeable Polyamide Nanofiltration Membrane Mediated by an Upscalable Wet-Laid EVOH Nanofibrous Scaffold.

ACS Appl Mater Interfaces 2021 May 7. Epub 2021 May 7.

Key Laboratory of Textile Fiber and Products, Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Intelligent Textile Materials & Application, Wuhan Textile University, Wuhan 430200, China.

For energy-saving purposes, the pursuit of ultrahigh permeance nanofiltration membranes without sacrificing selectivity is never-ending in desalination, wastewater treatment, and industrial product separation. Herein, we reported a novel facile route to engineer a highly porous and superhydrophilic nanofibrous substrate to mediate the interfacial polymerization between trimesoyl chloride and piperazine, generating an ultrathin PA active layer (∼13 nm) with a hierarchical crumpled surface. The wet laying process and subsequent plasma treatment endowed a rougher and more hydrophilic surface for ethylene vinyl alcohol copolymer (EVOH) nanofibers in the thin compact nanofibrous scaffold (∼9 μm) with a mean pore size of 210 nm, radically different from the nanofibrous membrane by other methods. Nanofibrous scaffold with these features provide abundant thin-thick alternative continuous water layers between nanofibers and organic phase, facilitating the formation of the abovementioned PA layer. As a result, an ultrahigh permeance of 42.25 L·m h bar and a reasonably high rejection of 95.97% to 1000 ppm NaSO feed solution were obtained, superior to most state-of-the-art NF membranes reported so far. Our work provides an easy and scalable method to fabricate advanced PA NF membranes with outstanding performance, highlighting its great potential in liquid separation.
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http://dx.doi.org/10.1021/acsami.1c02776DOI Listing
May 2021

Tubular decoy receptor 2 as a predictor of prognosis in patients with immunoglobulin A nephropathy.

Clin Kidney J 2021 May 27;14(5):1458-1468. Epub 2021 Jan 27.

Department of Nephrology, Daping Hospital, Army Medical University, Chongqing, China.

Background: Accelerated senescence of renal tubular epithelial cells (RTECs) might contribute to immunoglobulin A nephropathy (IgAN) progression. This study aimed to determine whether the RTEC senescence marker, decoy receptor 2 (DcR2), could predict prognosis in IgAN.

Methods: We included a retrospective cohort of 105 patients with biopsy-proven IgAN. Tubular DcR2 expression was assessed at renal biopsy and the Oxford histological MEST-C score [mesangial hypercellularity (M), endocapillary proliferation (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C)] defined disease severity. IgAN progression was defined as a composite of end-stage renal disease or a 30% decline in the estimated glomerular filtration rate (eGFR), analyzed using Kaplan-Meier and Cox regression analyses.

Results: Tubular DcR2 was overexpressed in IgAN. Numbers of DcR2 and p16 double-positive RTECs increased with increasing severity of tubular atrophy/interstitial fibrosis (T lesion). Patients with ≥25% tubular DcR2 expression experienced worse proteinuria, T lesions and a lower eGFR. Cumulative renal survival was significantly lower in patients with ≥25% DcR2 positivity. Multivariate regression analyses showed that ≥25% tubular DcR2 expression was significantly associated with worse eGFR slopes (the rate of renal function decline; P = 0.003) and the incidence of the composite outcome (P = 0.001) in IgAN. The addition of tubular DcR2 to a model with clinical data at biopsy (mean arterial pressure, proteinuria and eGFR) or MEST-C score significantly improved the 5-year risk prediction of IgAN progression, as confirmed by receiver operating characteristic curve analyses.

Conclusions: Tubular DcR2 expression detected at biopsy was a strong independent predictor for IgAN progression and might have prognostic value in addition to established risk markers.
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http://dx.doi.org/10.1093/ckj/sfaa257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087134PMC
May 2021

Physiological Roles of the Rapidly Activated Delayed Rectifier K Current in Adult Mouse Heart Primary Pacemaker Activity.

Int J Mol Sci 2021 Apr 30;22(9). Epub 2021 Apr 30.

Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, Manchester M13 9PL, UK.

Robust, spontaneous pacemaker activity originating in the sinoatrial node (SAN) of the heart is essential for cardiovascular function. Anatomical, electrophysiological, and molecular methods as well as mathematical modeling approaches have quite thoroughly characterized the transmembrane fluxes of Na, K and Ca that produce SAN action potentials (AP) and 'pacemaker depolarizations' in a number of different in vitro adult mammalian heart preparations. Possible ionic mechanisms that are responsible for SAN primary pacemaker activity are described in terms of: (i) a Ca-regulated mechanism based on a requirement for phasic release of Ca from intracellular stores and activation of an inward current-mediated by Na/Ca exchange; (ii) time- and voltage-dependent activation of Na or Ca currents, as well as a cyclic nucleotide-activated current, I; and/or (iii) a combination of (i) and (ii). Electrophysiological studies of single spontaneously active SAN myocytes in both adult mouse and rabbit hearts consistently reveal significant expression of a rapidly activating time- and voltage-dependent K current, often denoted I, that is selectively expressed in the leading or primary pacemaker region of the adult mouse SAN. The main goal of the present study was to examine by combined experimental and simulation approaches the functional or physiological roles of this K current in the pacemaker activity. Our patch clamp data of mouse SAN myocytes on the effects of a pharmacological blocker, E4031, revealed that a rapidly activating K current is essential for action potential (AP) repolarization, and its deactivation during the pacemaker potential contributes a small but significant component to the pacemaker depolarization. Mathematical simulations using a murine SAN AP model confirm that well known biophysical properties of a delayed rectifier K current can contribute to its role in generating spontaneous myogenic activity.
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http://dx.doi.org/10.3390/ijms22094761DOI Listing
April 2021

High-resolution age-specific mapping of the two-week illness prevalence rate based on the National Health Services Survey and geostatistical analysis: a case study in Guangdong province, China.

Int J Health Geogr 2021 May 3;20(1):20. Epub 2021 May 3.

School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.

Background: The two-week illness prevalence rate is an important and comparable indicator of health service needs. High-spatial-resolution, age-specific risk mapping of this indicator can provide valuable information for health resource allocation. The age-prevalence relationships may be different among areas of the study region, but previous geostatistical models usually ignored the spatial-age interaction.

Methods: We took Guangdong province, the province with the largest population and economy in China, as a study case. We collected two-week illness data and other potential influencing predictors from the fifth National Health Services Survey in 2013 and other open-access databases. Bayesian geostatistical binary regression models were developed with spatial-age structured random effect, based on which, high-resolution, age-specific two-week illness prevalence rates, as well as number of people reporting two-week illness, were estimated. The equality of health resource distribution was further evaluated based on the two-week illness mapping results and the health supply data.

Results: The map across all age groups revealed that the highest risk was concentrated in the central (i.e., Pearl River Delta) and northern regions of the province. These areas had a two-week illness prevalence > 25.0%, compared with 10.0-20.0% in other areas. Age-specific maps revealed significant differences in prevalence between age groups, and the age-prevalence relationships also differed across locations. In most areas, the prevalence rates decrease from age 0 to age 20, and then increase gradually. Overall, the estimated age- and population-adjusted prevalence was 16.5% [95% Bayesian credible interval (BCI): 14.5-18.6%], and the estimated total number of people reporting illness within the two-week period was 17.5 million (95% BCI: 15.5-19.8 million) in Guangdong Province. The Lorenz curve and the Gini coefficient (resulted in 0.3526) showed a moderate level of inequality in health resource distribution.

Conclusions: We developed a Bayesian geostatistical modeling framework with spatial-age structured effect to produce age-specific, high-resolution maps of the two-week illness prevalence rate and the numbers of people reporting two-week illness in Guangdong province. The methodology developed in this study can be generalized to other global regions with available relevant survey data. The mapping results will support plans for health resource allocation.
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http://dx.doi.org/10.1186/s12942-021-00273-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094611PMC
May 2021

Separation of Follicular Cells and Oocytes in Ovarian Follicles of Zebrafish.

J Vis Exp 2021 Apr 18(170). Epub 2021 Apr 18.

College of Life Sciences, Northwest Normal University;

Zebrafish has become an ideal model to study the ovarian development of vertebrates. The follicle is the basic unit of the ovary, which consists of oocytes and surrounding follicular cells. It is vital to separate both follicular cells and oocytes for various research purposes such as for primary culture of follicular cells, analysis of gene expression, oocyte maturation and in vitro fertilization, etc. The conventional method uses forceps to separate both compartments, which is laborious, time consuming and has high damage to the oocyte. Here, we have established a simple method to separate both compartments using a pulled glass capillary. Under a stereomicroscope, oocytes and follicular cells can be easily separated by pipetting in a pulled fine glass capillary (the diameter depends on the follicle diameter). Compared with the conventional method, this new method has high efficiency in separating both oocytes and follicular cells and has low damage to the oocytes. More importantly, this method can be applied to early-stage follicles including at the pre-vitellogenesis stage. Thus, this simple method can be used to separate follicular cells and oocytes of zebrafish.
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http://dx.doi.org/10.3791/62027DOI Listing
April 2021

NAV2 positively modulates inflammatory response of fibroblast-like synoviocytes through activating Wnt/β-catenin signaling pathway in rheumatoid arthritis.

Clin Transl Med 2021 Apr;11(4):e376

State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau, China.

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http://dx.doi.org/10.1002/ctm2.376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087903PMC
April 2021

Left ventricular geometry transition in hypertensive patients with heart failure with preserved ejection fraction.

ESC Heart Fail 2021 May 1. Epub 2021 May 1.

Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China.

Aims: Heart failure with preserved ejection fraction (HFpEF) develops in response to hypertensive left ventricular (LV) hypertrophy and is associated with increased cardiovascular events. Although the progression to systolic heart failure is a known consequence of LV hypertrophy and HFpEF, few data are available on the LV geometry change and frequency of deterioration to systolic dysfunction in this population.

Methods And Results: We evaluated the baseline and follow-up characteristics in 680 patients with LV hypertrophy and HFpEF in this prospective cohort study. The primary endpoint was 5 year all-cause mortality. The changes of LV geometry and heart failure transition were analysed. Systolic dysfunction [left ventricular ejection fraction (LVEF) < 50%] occurred in 182 patients (26.8%) during a 5 year follow-up. Patients with LVEF deterioration were associated with a lower survival rate. Beta-blocker prescription was a protective factor for preserved LVEF. And concentric LV geometry shifted to eccentric hypertrophy was uncommon (10.6%) during a 5 year follow-up.

Conclusions: A quarter of patients with hypertensive LV hypertrophy and HFpEF progresses to systolic dysfunction during a 5 year follow-up, which was accompanied by poor clinical outcomes. And beta-blocker therapy might play a protective role for preserved LVEF in this population.
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http://dx.doi.org/10.1002/ehf2.13349DOI Listing
May 2021

Blockade of TRPM7 Alleviates Chondrocyte Apoptosis and Articular Cartilage Damage in the Adjuvant Arthritis Rat Model Through Regulation of the Indian Hedgehog Signaling Pathway.

Front Pharmacol 2021 13;12:655551. Epub 2021 Apr 13.

Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, China.

Articular cartilage damage with subsequent impairment of joint function is a common feature of articular diseases, in particular, rheumatoid arthritis and osteoarthritis. While articular cartilage injury mediated by chondrocyte apoptosis is a known major pathological feature of arthritis, the specific mechanisms remain unclear at present. Transient receptor potential melastatin-like seven channel (TRPM7) is reported to play an important regulatory role in apoptosis. This study focused on the effects of TRPM7 on arthritic chondrocyte injury and its underlying mechanisms of action. Sodium nitroprusside (SNP)-induced rat primary chondrocyte apoptosis and rat adjuvant arthritis (AA) were used as and models, respectively. Blockage of TRPM7 with 2-APB or specific siRNA resulted in increased chondrocyte viability and reduced toxicity of SNP. Moreover, treatment with 2-APB enhanced the Bcl-2/Bax ratio and reduced cleaved PARP and IL-6, MMP-13 and ADAMTS-5 expression in SNP-treated chondrocytes. Activation of Indian Hedgehog with purmorphamine reversed the protective effects of 2-APB on SNP-induced chondrocyte apoptosis. Blockage of TRPM7 with 2-APB relieved the clinical signs of AA in the rat model and reduced the arthritis score and paw swelling. Similar to findings in SNP-treated chondrocytes, 2-APB treatment increased the Bcl-2/Bax ratio and suppressed cleaved PARP, IL-6, MMP-13, ADAMTS-5, TRPM7, and Indian hedgehog expression in articular cartilage of AA rats. Our collective findings suggest that blockade of TRPM7 could effectively reduce chondrocyte apoptosis and articular cartilage damage in rats with adjuvant arthritis through regulation of the Indian Hedgehog signaling pathway.
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http://dx.doi.org/10.3389/fphar.2021.655551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076952PMC
April 2021

Retraction: Yang, B. et al. Nitrogen Doped Intercalation TiO/TiN/TiCT Nanocomposite Electrodes with Enhanced Pseudocapacitance. 2020, , 345.

Nanomaterials (Basel) 2021 Apr 6;11(4). Epub 2021 Apr 6.

St. Alban-Anlage 66, 4052 Basel, Switzerland.

This article [1] has been retracted at the request of the authors due to data errors [...].
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http://dx.doi.org/10.3390/nano11040936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067478PMC
April 2021

Recent advances in porous nanostructures for cancer theranostics.

Nano Today 2021 Jun 8;38. Epub 2021 Apr 8.

Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey, 07030, United States.

Porous nanomaterials with high surface area, tunable porosity, and large mesopores have recently received particular attention in cancer therapy and imaging. Introduction of additional pores to nanostructures not only endows the tunability of optoelectronic and optical features optimal for tumor treatment, but also modulates the loading capacity and controlled release of therapeutic agents. In recognition, increasing efforts have been made to fabricate various porous nanomaterials and explore their potentials in oncology applications. Thus, a systematic and comprehensive summary is necessary to overview the recent progress, especially in last ten years, on the development of various mesoporous nanomaterials for cancer treatment as theranostic agents. While outlining their individual synthetic mechanisms after a brief introduction of the structures and properties of porous nanomaterials, the current review highlighted the representative applications of three main categories of porous nanostructures (organic, inorganic, and organic-inorganic nanomaterials). In each category, the synthesis, representative examples, and interactions with tumors were further detailed. The review was concluded with deliberations on the key challenges and future outlooks of porous nanostructures in cancer theranostics.
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http://dx.doi.org/10.1016/j.nantod.2021.101146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059603PMC
June 2021

Evaluating the Biological Potential of Prodigiosin from Serratia Marcescens KH-001 Against Asian Citrus Psyllid.

J Econ Entomol 2021 Apr 22. Epub 2021 Apr 22.

National Navel Orange Engineering Research Center, College of Life Sciences, Gannan Normal University, Ganzhou, China.

The insecticides of microbial origin may be promising biocontrol agents to control pests. In this study, a major metabolite was extracted and purified from Serratia marcescens KH-001 and identified as prodigiosin with a molecule weight of 324.2094, and our primary aim was to evaluate the effects of prodigiosin against Diaphorina citri Kuwayama (Hemiptera: Liviidae) in the laboratory and in the field. Toxicity of purified prodigiosin to nymphs increased with increasing temperature from 25 to 35°C. The laboratory experiment results observed inhibition effects of purified prodigiosin at LC50 on oviposition and egg hatch of D. citri at 30°C. Furthermore, adults that fed on citrus leaves treated with LC20 and LC50 solution of purified prodigiosin at 30°C excreted less honeydew (28-35%) compared with controls, suggesting moderate antifeedant activity of prodigiosin. The results of field experiment showed that 10% prodigiosin emulsifiable concentrate exhibited better control efficacy (70-100%) at three concentrations (100, 200, and 500 mg/liter) in July and August than in October. These data indicate that prodigiosin will be a highly effective compound for the control of D. citri depending on the prevailing temperature conditions and may become a commercially available product to be widely used in citrus orchards.
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http://dx.doi.org/10.1093/jee/toab041DOI Listing
April 2021

Orphan nuclear receptor TLX promotes immunosuppression via its transcriptional activation of PD-L1 in glioma.

J Immunother Cancer 2021 Apr;9(4)

Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China

Background: High-grade gliomas are rapidly progressing tumors of the central nervous system, and are associated with poor prognosis and highly immunosuppressive microenvironments. Meanwhile, a better understanding of PD-L1, a major prognostic biomarker for checkpoint immune therapy, regulation may provide insights for developing novel immunotherapeutic strategies for treating gliomas. In the present study, we elucidate the functional significance of the orphan nuclear receptor TLX in human glioma, and its functional role in immune suppression through regulation of PD-L1/PD-1 axis.

Methods: TLX and PD-L1 expression patterns, and their association with clinicopathological parameters and immune phenotypes of glioma were analysed using CIBERSORT algorithm and single-sample gene-set enrichment analysis from The Cancer Genome Atlas (n=695) and Chinese Glioma Genome Atlas (n=1018) databases. Protein expression and cellular localization of TLX, PD-L1, and PD-1, as well as the prevalence of cytotoxic tumor-infiltrating lymphocytes (TILs), and tumor-associated macrophages (TAMs), in the glioma immune microenvironment were analyzed via tissue microarray by immunohistochemistry and multiplex immunofluorescence. Glioma allografts and xenografts with TLX manipulation (knockdown/knockout or reverse agonist) were inoculated subcutaneously, or orthotopically into the brains of immunodeficient and immunocompetent mice to assess tumor growth by imaging, and the immune microenvironment by flow cytometry. PD-L1 transcriptional regulation by TLX was analyzed by chromatin immunoprecipitation and luciferase reporter assays.

Results: TLX and PD-L1 expression was positively associated with macrophage-mediated immunosuppressive phenotypes in gliomas. TLX showed significant upregulation and positive correlation with PD-L1. Meanwhile, suppression of TLX significantly inhibited growth of glioma allografts and xenografts (p<0.05), rescued the antitumoral immune response, significantly decreased the PD-L1, and glioma-associated macrophage population, and increased cytotoxic lymphocyte infiltration (p<0.05). Mechanistically, TLX binds directly to CD274 (PD-L1) gene promoter and activates CD274 transcription.

Conclusions: TLX contributes to glioma malignancy and immunosuppression through transcriptional activation of PD-L1 ligands that bind to PD-1 expressed on both TILs and TAMs. Thus, targeting the druggable TLX may have potential therapeutic significance in glioma immune therapy.
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http://dx.doi.org/10.1136/jitc-2020-001937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055120PMC
April 2021

Downregulation of hsa_circ_0004543 Activates oxLDL-Induced Vascular Endothelial Cell Proliferation and Angiogenesis.

Front Genet 2021 24;12:632164. Epub 2021 Mar 24.

Department of Cardiology, Minhang Hospital, Fudan University, Shanghai, China.

Circular RNAs (circRNAs) are novel non-coding RNAs, which show abnormal expression in several diseases, such as atherosclerosis (AS). The purpose of the present study was to reveal the association between hsa_circ_0004543 and AS. In the present study, hsa_circ_0004543 was overexpressed in human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (oxLDL). Inhibition of hsa_circ_0004543 expression facilitated the proliferation, migration, and invasion of HUVECs and significantly reduced their apoptotic rate following treatment with oxLDL. Furthermore, silencing of hsa_circ_0004543 activated the PI3K/AKT/NOS3 pathway in oxLDL-induced HUVECs. Collectively, these results demonstrated that hsa_circ_0004543 may play a vital role in the development of AS and affect the proliferation of HUVECs, providing a potential target for treating endothelial cell damage in AS.
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http://dx.doi.org/10.3389/fgene.2021.632164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024642PMC
March 2021

Effects of histone H4 hyperacetylation on inhibiting MMP2 and MMP9 in human amniotic epithelial cells and in premature rupture of fetal membranes.

Exp Ther Med 2021 May 22;21(5):515. Epub 2021 Mar 22.

School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063021, P.R. China.

Histone modification is closely associated with several diseases. The aim of the current study was to investigate the associations among histone acetylation, matrix metalloproteinases (MMPs) and premature rupture of membranes (PROM) during pregnancy. A total of 180 puerperants were divided into three groups: i) Preterm-PROM (PPROM), ii) term-PROM (TPROM) and iii) full-term labor (FTL). Enzyme-linked immunosorbent assay (ELISA) kits and western blotting were used to determine the protein concentrations of MMP2, MMP9, histone deacetylase (HDAC)1, HDAC2 and HDAC6, and the protein levels of histone H4 lysine (H4K)5 and H4K8 acetylation, respectively, in three types of fetal membranes. Additionally, human amniotic epithelial cells were used to determine the effects of the HDAC inhibitors droxinostat and chidamide on cell viability, histone acetylation and the levels of MMP2, MMP9, HDAC1, HDAC2 and HDAC6 , using the Cell Counting Kit-8 assay, western blotting and ELISA, respectively. Furthermore, the effects of droxinostat and chidamide on the invasion and migration abilities of human amniotic epithelial cells were investigated using transwell assays. In fetal membranes, the activities of MMP2 and MMP9 increased in PPROM, but decreased in TPROM. Further, the expression of HDAC1 was decreased and histone hyperacetylation was increased in both PPROM and TRPOM. experiments revealed that 5 µM droxinostat and 0.5 µM chidamide selectively decreased the level of HDAC and induced acetylation of H4K5 and H4K8. Additionally, the aforementioned HDAC inhibitors reduced human amniotic epithelial cell viability, invasion and migration, and decreased the expression levels of MMP2 and MMP9. The current study revealed a high expression level of MMP2 and MMP9 in PPROM compared with TPROM and FL tissue, which was in accordance with previously published studies. Furthermore, the tests performed in the current study revealed the effect of histone H4 hyperacetylation on inhibiting MMP2 and MMP9 levels was similar to that observed in TPROM. The results obtained in the current study may be used as a theoretical guide for clinical treatment of premature rupture of membranes.
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http://dx.doi.org/10.3892/etm.2021.9946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014974PMC
May 2021

Validation of posttraumatic stress disorder (PTSD) and complex PTSD in Chinese children as per the ICD-11 proposals using the International trauma questionnaire.

Eur J Psychotraumatol 2021 Mar 11;12(1):1888525. Epub 2021 Mar 11.

Center for Behavioral Health & School of Social Development and Public Policy, Beijing Normal University, Beijing, P.R.China.

: Given that the validity of applying complex posttraumatic stress disorder (CPTSD) in nonclinical children remains unclear. : The current study aimed to explore the factor structure, discriminant validity, and risk factors of ICD-11 posttraumatic stress disorder (PTSD) and CPTSD using the International Trauma Questionnaire. : A total of 3478 trauma-exposed Chinese children aged 9-12 years were included in this study. All participants were assessed for PTSD and CPTSD using the International Trauma Questionnaire (ITQ). Confirmatory factor analysis (CFA) was conducted to explore the factor structure of CPTSD in a sample of Chinese children. Latent class analysis (LCA) was employed to evaluate the discriminant validity of CPTSD symptoms. Multinomial logistic regression analyses determined associations between the different classes and traumatic events. : The CFA results showed that the first-order six-factor model was identified as the best-fitting model in Chinese children aged 9-12 years. Four different classes, CPTSD symptoms, PTSD symptoms, disturbances in self-organization (DSO) symptoms, and a low symptom class were found by LCA. Both prolonged interpersonal trauma and other types of trauma were risk factors for the CPTSD class and the PTSD class. : The results of this study partially support the factorial validity and strongly support the discriminant validity of the ICD-11 proposals for PTSD and CPTSD in Chinese children, supporting the conceptualization of PTSD and CPTSD as sibling diagnoses based on the ICD-11. However, findings suggest the need for careful consideration of identified trauma types in the ICD-11 proposals.
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http://dx.doi.org/10.1080/20008198.2021.1888525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968872PMC
March 2021

A Critical Role of Peptidylprolyl Isomerase A Pseudogene 22/microRNA-197-3p/Peptidylprolyl Isomerase A Axis in Hepatocellular Carcinoma.

Front Genet 2021 15;12:604461. Epub 2021 Mar 15.

Department of Infectious Diseases, Huashan Hospital, Shanghai, China.

The burden of hepatocellular carcinoma (HCC) worldwide is increasing over time, while the underlying molecular mechanism of HCC development is still under exploration. Pseudogenes are classified as a special type of long non-coding RNAs (lncRNAs), and they played a vital role in regulating tumor-associated gene expression. Here, we report that a pseudogene peptidylprolyl isomerase A pseudogene 22 (PPIAP22) and its parental gene peptidylprolyl isomerase A (PPIA) were upregulated in HCC and were associated with the clinical outcomes of HCC. Further investigation revealed that PPIAP22 might upregulate the expression of PPIA through sponging microRNA (miR)-197-3p, behaving as competing endogenous RNA (ceRNA). PPIA could participate in the development of HCC by regulating mRNA metabolic process and tumor immunity based on the functional enrichment analysis. We also found a strong correlation between the expression levels of PPIA and the immune cell infiltration or the expression of chemokines, especially macrophage, C-C motif chemokine ligand 15 (CCL15), and C-X-C motif chemokine ligand 12 (CXCL12). Our findings demonstrate that the PPIAP22/miR-197-3p/PPIA axis plays a vital role in the progression of HCC by increasing the malignancy of tumor cells and regulating the immune cell infiltration, especially macrophage, through CCL15-CCR1 or CXCL12-CXCR4/CXCR7 pathways.
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http://dx.doi.org/10.3389/fgene.2021.604461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006304PMC
March 2021

Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance.

Brief Bioinform 2021 Mar 30. Epub 2021 Mar 30.

Chinese University of Hong Kong and a researcher at the CUHK-Shenzhen Research Institute, China.

Tumor suppressor genes (TSGs) exhibit distinct evolutionary features. We speculated that TSG promoters could have evolved specific features that facilitate their tumor-suppressing functions. We found that the promoter CpG dinucleotide frequencies of TSGs are significantly higher than that of non-cancer genes across vertebrate genomes, and positively correlated with gene expression across tissue types. The promoter CpG dinucleotide frequencies of all genes gradually increase with gene age, for which young TSGs have been subject to a stronger evolutionary pressure. Transcription-related features, namely chromatin accessibility, methylation and ZNF263-, SP1-, E2F4- and SP2-binding elements, are associated with gene expression. Moreover, higher promoter CpG dinucleotide frequencies and chromatin accessibility are positively associated with the ability of TSGs to resist downregulation during tumorigenesis. These results were successfully validated with independent datasets. In conclusion, TSGs evolved specific promoter features that optimized cancer resistance through achieving high expression in normal tissues and resistance to downregulation during tumorigenesis.
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http://dx.doi.org/10.1093/bib/bbab040DOI Listing
March 2021

Serum Uric Acid Levels Predict Mortality Risk in Male Amyotrophic Lateral Sclerosis Patients.

Front Neurol 2021 11;12:602663. Epub 2021 Mar 11.

Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.

To explore the associations between serum uric acid levels with survival in male and female ALS patients. A longitudinal cohort study was carried out including 313 sporadic and 16 familial ALS patients with repeated serum uric acid measurements. Multivariate Cox regression models were used to evaluate the survival-related factors. There were 207 male and 122 female, and the mean age of onset was 55.7 ± 11.2 years old. The male patients had significantly higher baseline uric acid levels than that in female patients (342.4 ± 91.4 vs. 279.3 ± 71.4 μmol/L; < 0.0001). The uric acid levels were inversely associated with the decline rate of ALSFRS-R per month (ΔALSFRS-R). After multivariate Cox regression analysis, a survival advantage was found in male, but not female, with higher serum uric acid levels. In males, a shorter diagnostic delay (≤10 m), lower BMI at baseline (≤18.70 kg/m), faster disease progression (ΔALSFRS-R > 0.63), and lower baseline uric acid levels (≤292 μmol/L, HR: 1.936; 95% CI: 1.334-2.810) were associated with a shorter survival. During follow-up, the serum uric acid levels were not significantly altered over time. There is an inverse correlation between baseline serum uric acid levels and risk of death, prominently in male ALS patients.
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http://dx.doi.org/10.3389/fneur.2021.602663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991582PMC
March 2021

Embedding atomic cobalt into graphene lattices to activate room-temperature ferromagnetism.

Nat Commun 2021 Mar 25;12(1):1854. Epub 2021 Mar 25.

National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, P. R. China.

Graphene is extremely promising for next-generation spintronics applications; however, realizing graphene-based room-temperature magnets remains a great challenge. Here, we demonstrate that robust room-temperature ferromagnetism with T up to ∼400 K and saturation magnetization of 0.11 emu g (300 K) can be achieved in graphene by embedding isolated Co atoms with the aid of coordinated N atoms. Extensive structural characterizations show that square-planar Co-N moieties were formed in the graphene lattices, where atomically dispersed Co atoms provide local magnetic moments. Detailed electronic structure calculations reveal that the hybridization between the d electrons of Co atoms and delocalized p electrons of N/C atoms enhances the conduction-electron mediated long-range magnetic coupling. This work provides an effective means to induce room-temperature ferromagnetism in graphene and may open possibilities for developing graphene-based spintronics devices.
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http://dx.doi.org/10.1038/s41467-021-22122-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994802PMC
March 2021

Acute Kidney Injury following Cardiopulmonary Bypass: A Challenging Picture.

Oxid Med Cell Longev 2021 9;2021:8873581. Epub 2021 Mar 9.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, 229 Taibai North Road, Xi'an 710069, China.

Recent studies have recognized several risk factors for cardiopulmonary bypass- (CPB-) associated acute kidney injury (AKI). However, the lack of early biomarkers for AKI prevents practitioners from intervening in a timely manner. We reviewed the literature with the aim of improving our understanding of the risk factors for CPB-associated AKI, which may increase our ability to prevent or improve this condition. Some novel early biomarkers for AKI have been introduced. In particular, a combinational use of these biomarkers would be helpful to improve clinical outcomes. Furthermore, we discuss several interventions that are aimed at managing CPB-associated AKI, may increase the effect of renal replacement therapy (RRT), and may contribute to preventing CPB-associated AKI. Collectively, the conclusions of this paper are limited by the availability of clinical trial evidence and conflicting definitions of AKI. A guideline is urgently needed for CPB-associated AKI.
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http://dx.doi.org/10.1155/2021/8873581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963912PMC
March 2021

rs4148323 A Allele is Associated With Increased 2-Hydroxy Atorvastatin Formation and Higher Death Risk in Chinese Patients With Coronary Artery Disease.

Front Pharmacol 2021 8;12:586973. Epub 2021 Mar 8.

Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

It is widely accepted that genetic polymorphisms impact atorvastatin (ATV) metabolism, clinical efficacy, and adverse events. The objectives of this study were to identify novel genetic variants influencing ATV metabolism and outcomes in Chinese patients with coronary artery disease (CAD). A total of 1079 CAD patients were enrolled and followed for 5 years. DNA from the blood and human liver tissue samples were genotyped using either Global Screening Array-24 v1.0 BeadChip or HumanOmniZhongHua-8 BeadChip. Concentrations of ATV and its metabolites in plasma and liver samples were determined using a verified ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method. The patients carrying A allele for the rs4148323 polymorphism () showed an increase in 2-hydroxy ATV/ATV ratio ( = 1.69E-07, false discovery rate [FDR] = 8.66E-03) relative to the value in individuals without the variant allele. The result was further validated by an independent cohort comprising an additional 222 CAD patients ( = 1.08E-07). Moreover, the rs4148323 A allele was associated with an increased risk of death (hazard ratio [HR] 1.774; 95% confidence interval [CI], 1.031-3.052; = 0.0198). In conclusion, our results suggested that the rs4148323 A allele was associated with increased 2-hydroxy ATV formation and was a significant death risk factor in Chinese patients with CAD.
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http://dx.doi.org/10.3389/fphar.2021.586973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982952PMC
March 2021

Comparative Study of Three Minimally Invasive Surgical Approaches For the Treatment of L5/S1 Lumbar Intervertebral Disc Herniation.

Turk Neurosurg 2020 May 13. Epub 2020 May 13.

tianjin union medical center.

Aim: To compare the efficacy and safety of minimally endoscopic discectomy (MED), percutaneous endoscopic transforaminal endoscopic discectomy (PETD) and percutaneous endoscopic interlaminar endoscopic discectomy (PEID) in the treatment of L5/S1 lumbar disc herniation (LDH).

Material And Methods: From May 2012 to January 2017, 317 patients with L5/S1 LDH were treated with MED, PETD or PEID. Pre- and postoperative pain was measured using a visual analog scale (VAS; 0 -10), and functional status was assessed using the Oswestry Disability Index (ODI; 0 - 100%). Clinical outcomes, SF-36 scores and CK levels were compared between the 3 groups.

Results: There were 177 females and 140 males; the ages ranged from 22 to 74 years; and the course of disease was 15 to 85 days, with an average of 42.8 days.The postoperative bed rest time and average hospital stay in the MED group were higher than in the other two groups, and the differences were statistically significant.There was no significant difference in the results evaluated by the MacNab criteria. There were no significant differences in the levels of CK between the three groups before and after surgery (p 0.05).

Conclusion: Three minimally invasive surgeries for the treatment of L5/S1 LDH achieved satisfactory clinical outcomes; however, each procedure has its own advantages, disadvantages and indications. Surgeons need to choose the most appropriate surgery according to the individual condition of the patient to achieve the best therapeutic effect.
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http://dx.doi.org/10.5137/1019-5149.JTN.29539-20.2DOI Listing
May 2020