Publications by authors named "Ying He"

983 Publications

Selenogenome and AMPK signal insight into the protective effect of dietary selenium on chronic heat stress-induced hepatic metabolic disorder in growing pigs.

J Anim Sci Biotechnol 2021 Jun 12;12(1):68. Epub 2021 Jun 12.

Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.

Background: Chronic heat stress (CHS) disrupts hepatic metabolic homeostasis and jeopardizes product quality of pigs. Selenium (Se) may regulate the metabolic state through affect selenoprotein. Thus, we investigate the protective effect of dietary hydroxy-4-methylselenobutanoic acid (HMSeBA) on CHS induced hepatic metabolic disorder in growing pigs, and the corresponding response of selenoprotein.

Methods: Forty crossbreed growing pigs were randomly assigned to five groups: control group raised in the thermoneutral environment (22 ± 2 °C) with basal diet; four CHS groups raised in hyperthermal condition (33 ± 2 °C) with basal diet and supplied with 0.0, 0.2, 0.4, and 0.6 mg Se/kg HMSeBA, respectively. The trial lasted 28 d. The serum biochemical, hepatic metabolism related enzyme, protein and gene expression and 25 selenoproteins in liver tissue were determined by real-time PCR, ELISA and western blot.

Results: CHS significantly increased the rectal temperature, respiration rate, serum aspartate aminotransferase (AST) and low-density lipoprotein cholesterol (LDL-C) of pigs, up-regulated hepatic heat shock protein 70 (HSP70) and induced lower liver weight, glycogen content, hepatic glucokinase and glutathione peroxidase (GSH-Px). The CHS-induced liver metabolic disorder was associated with the aberrant expression of 6 metabolism-related gene and 11 selenoprotein encoding genes, and decreased the protein abundance of GCK, GPX4 and SELENOS. HMSeBA improved anti-oxidative capacity of liver. 0.4 or 0.6 mg Se/kg HMSeBA supplementation recovered the liver weight, glycogen content and rescue of mRNA abundance of genes related to metabolism and protein levels of GCK. HMSeBA supplementation changed expressions of 15 selenoprotein encoding genes, and enhanced protein expression of GPX1, GPX4 and SELENOS in the liver affected by CHS. CHS alone showed no impact while HMSeBA supplementation increased protein levels of p-AMPKα in the liver.

Conclusions: In summary, HMSeBA supplementation beyond nutrient requirement mitigates CHS-induced hepatic metabolic disorder, recovered the liver glycogen content and the processes that are associated with the activation of AMPK signal and regulation of selenoproteins in the liver of growing pigs.
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http://dx.doi.org/10.1186/s40104-021-00590-2DOI Listing
June 2021

Protein kinase C δ as a neuronal mechanism for headache in a chronic intermittent nitroglycerin model of migraine in mice.

Pain 2021 May 31. Epub 2021 May 31.

Department of Pharmaceutical Sciences and Center for Biomolecular Science, University of Illinois, Chicago, IL 60612 Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin, Texas, USA Department of Neurology & Rehabilitation, University of Illinois, Chicago, IL 60612 Department of Bioengineering, University of Illinois, Chicago, IL 60607.

Abstract: Migraine is one of the most common neurological disorders characterized by recurrent attacks of typically throbbing and unilateral headaches, affecting up to 20 % of the population worldwide. Despite the high prevalence and severity of this primary headache disorder, it remains to be a challenge to fully understand and treat migraine headaches. By characterizing and validating a mouse migraine model, this study aimed to investigate the functional contribution of PKC isoforms in migraine. In this study, we identified the presence of migraine-like ongoing pain in mice after chronic intermittent treatment with nitroglycerin (NTG). The peptide antagonist of calcitonin gene related peptide (CGRP) α-CGRP (8-37), but not topiramate nor sumatriptan, effectively blocked ongoing pain and elicited pain relief-induced CPP in NTG-treated mice. Prominent activation of PKCδ was observed in chronic NTG-treated mice. Functional inhibition of PKCδ significantly attenuated ongoing spontaneous pain in chronic NTG-treated mice. Furthermore, we recapitulated the NTG-triggered migraine behavior in wild-type, but not in PKCδ-null mice. In response to repeated administration of NTG, ongoing spontaneous pain was not developed in mice lacking the specific PKC isoform. This study identified the presence of ongoing pain in mice treated with nitroglycerin, a known human migraine trigger that closely resembles the common manifestation of spontaneous migraine attacks in humans. These findings demonstrated a critical regulatory role of PKCδ in migraine pathophysiology, which may offer new pharmacological targets for anti-migraine treatment.
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http://dx.doi.org/10.1097/j.pain.0000000000002353DOI Listing
May 2021

Ru-Embedded Highly Porous Carbon Nanocubes Derived from Metal-Organic Frameworks for Catalyzing Reversible LiO Formation.

ACS Appl Mater Interfaces 2021 Jun 8. Epub 2021 Jun 8.

Soochow Institute for Energy and Materials Innovations, College of Energy, Soochow University, Suzhou 215006, China.

Rechargeable lithium-oxygen batteries (LOBs) have attracted increasing attention due to their high energy density but highly rely on the development of efficient oxygen catalysts for reversible LiO deposition/decomposition. Herein, highly porous carbon nanocubes with a specific surface area up to 1600 m g are synthesized and utilized to tightly anchor Ru nanoparticles for using as the oxygen-cathode catalyst in LOBs, achieving a low charge/discharge potential gap of only 0.75 V, a high total discharge capacity of 17,632 mA h g, and a superb cycling performance of 550 cycles at 1000 mA g. Comprehensive ex situ and operando characterizations unravel that the outstanding LOB performance is ascribed to the highly porous catalyst structure embedding rich active sites that synergistically function in reducing overpotentials, suppressing parasitic reactions, accommodating reaction products, and promoting mass and charge transportation.
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http://dx.doi.org/10.1021/acsami.1c06572DOI Listing
June 2021

An enhanced method for nucleic acid detection with CRISPR-Cas12a using phosphorothioate modified primers and optimized gold-nanopaticle strip.

Bioact Mater 2021 Dec 15;6(12):4580-4590. Epub 2021 May 15.

Yaneng Biotech, Co., Ltd, Fosun Pharma, Shenzhen 518100, China.

CRISPR-Cas12a system has been shown promising for nucleic acid diagnostics due to its rapid, portable and accurate features. However, cleavage of the amplicons and primers by the - and -activity of Cas12a hinders the attempts to integrate the amplification and detection into a single reaction. Through phosphorothioate modification of primers, we realized onepot detection with high sensitivity using plasmids of SARS-CoV-2, HPV16 and HPV18. We also identified the activated Cas12a has a much higher affinity to C nucleotide-rich reporter than others. By applying such reporters, the reaction time required for a lateral-flow readout was significantly reduced. Furthermore, to improve the specificity of the strip-based assay, we created a novel reporter and, when combined with a customized gold-nanopaticle strip, the readout was greatly enhanced owing to the elimination of the nonspecific signal. This established system, termed argeting DNA by Cas12a-based ye ight esting in an nepot eaction (TESTOR), was validated using clinical cervical scrape samples for human papillomaviruses (HPVs) detection. Our system represents a general approach to integrating the nucleic acid amplification and detection into a single reaction in CRISPR-Cas systems, highlighting its potential as a rapid, portable and accurate detection platform of nucleic acids.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141609PMC
December 2021

A Dynamic Transcription Factor Signature Along the Colorectal Adenoma-Carcinoma Sequence in Patients With Co-Occurrent Adenoma and Carcinoma.

Front Oncol 2021 21;11:597447. Epub 2021 May 21.

Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Background: Colorectal carcinoma (CRC) often arises from benign adenoma after a stepwise accumulation of genetic alterations. Here, we profiled the dynamic landscapes of transcription factors (TFs) in the mucosa-adenoma-carcinoma progression sequence.

Methods: The transcriptome data of co-occurrent adenoma, carcinoma, and normal mucosa samples were obtained from GSE117606. Identification of differentially expressed TFs (DE-TFs) and subsequent function annotation were conducted in R software. Expression patterns of DE-TFs were clustered by Short Time-series Expression Miner software. Thereafter, modular co-expression analysis, Kaplan-Meier survival analysis, mutation profiling, and gene set enrichment analysis were conducted to investigate TF dynamics in colorectal tumorigenesis. Finally, tissue microarrays, including 51 tumors, 32 adenomas, and 53 normal tissues, were employed to examine the expression of significant candidates by immunohistochemistry staining.

Results: Compared to normal tissues, 20 (in adenoma samples) and 29 (in tumor samples) DE-TFs were identified. During the disease course, 28 expression patterns for DE-TFs and four co-expression modules were clustered. Notably, six DE-TFs, DACH1, GTF2IRD1, MEIS2, NR3C2, SOX9, and SPIB, were identified as having a dynamic signature along the colorectal adenoma-carcinoma sequence. The dynamic signature was of significance in GO enrichment, prognosis, and co-expression analysis. Among the 6-TF signature, the roles of GTF2IRD1, SPIB and NR3C2 in CRC progression are unclear. Immunohistochemistry validation showed that GTF2IRD1 enhanced significantly throughout the mucosa-adenoma-carcinoma sequence, while SPIB and NR3C2 kept decreasing in stroma during the disease course.

Conclusions: Our study provided a dynamic 6-TF signature throughout the course of colorectal mucosa-adenoma-carcinoma. These findings deepened the understanding of colorectal cancer pathogenesis.
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http://dx.doi.org/10.3389/fonc.2021.597447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176860PMC
May 2021

Asymmetric allylic substitution-isomerization to axially chiral enamides hydrogen-bonding assisted central-to-axial chirality transfer.

Chem Sci 2020 Sep 7;11(37):10119-10126. Epub 2020 Sep 7.

School of Chemical Engineering, Nanjing University of Science & Technology Nanjing 210094 China

Axially chiral enamides bearing a N-C axis have been recently studied and were proposed to be valuable chiral building blocks, but a stereoselective synthesis has not been achieved. Here, we report the first enantioselective synthesis of axially chiral enamides a highly efficient, catalytic approach. In this approach, C(sp)-N bond formation is achieved through an iridium-catalyzed asymmetric allylation, and then isomerization of the initial products through an organic base promoted 1,3-H transfer, leading to the enamide products with excellent central-to-axial transfer of chirality. Computational and experimental studies revealed that the 1,3-H transfer occurs a stepwise deprotonation/re-protonation pathway with a chiral ion-pair intermediate. Hydrogen bonding interactions with the enamide carbonyl play a significant role in promoting both the reactivity and stereospecificity of the stepwise 1,3-H transfer. The mild and operationally simple formal -vinylation reaction delivered a series of configurationally stable axially chiral enamides with good to excellent yields and enantioselectivities.
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http://dx.doi.org/10.1039/d0sc02828bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162293PMC
September 2020

Enantioselective Kinetic Resolution/Desymmetrization of -Quinols: A Case Study in Boronic-Acid-Directed Phosphoric Acid Catalysis.

Adv Synth Catal 2020 Jan 6;362(2):295-301. Epub 2019 Sep 6.

Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720 (USA).

A chiral phosphoric acid-catalyzed kinetic resolution and desymmetrization of -quinols operating via oxa-Michael addition was developed and subsequently subjected to mechanistic study. Good to excellent -factors/enantioselectivities were obtained over a broad range of substrates. Kinetic studies were performed, and DFT studies favor a hydrogen bonding activation mode. The mechanistic studies provide insights to previously reported chiral anion phase transfer reactions involving chiral phosphate catalysts in combination with boronic acids.
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http://dx.doi.org/10.1002/adsc.201900816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174618PMC
January 2020

A New Method for Detection African Swine Fever Virus: Time-resolved Fluorescence Immunoassay.

J Fluoresc 2021 Jun 1. Epub 2021 Jun 1.

Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, 510663, China.

African swine fever (ASF) has severely influenced the swine industry of the whole world. Fast and accurate African swine fever virus (ASFV) antigen detection is very important for ASF prevention. This study aims to establish a new detection method for detection ASFV antigen using time-resolved fluorescence immunoassay (TRFIA) in the nose and mouth discharge. A double antibody sandwich TRFIA method was optimized and established. Recombinant P30 recombinant antigen was captured by its antibodies immobilized on 96-well plate, and then banded together with another detection antibodies labeled with Europium(III) (Eu) chelates, finally time-resolved analyzer measured the fluorescence intensity. The performance of this TRFIA (sensitivity, specificity and accuracy) was evaluated using the clinical samples and compared with the nucleic acid testing method. The sensitivity of this TRFIA was 0.015 ng/mL (dynamic range 0.24-500 ng/mL) with high specificity. The recovery ranged from 92.00 to 103.62 %, the inter-assay CVs ranged from 5.50 to 11.96 %, and the intra-assay CVs was between 5.20 and 10.53 %. Additionally, the cutoff value was 0.016. TRFIA took only 45 min to generate results, and its detection capability comparable to the nucleic acid detection. This study developed a TRFIA method that could be used for qualitative/quantitative detection of ASFV antigen in pigs nasal discharge, which has high sensitivity, specificity and accuracy. This TRFIA provides a new method for rapidly screening ASFV infection in pigs industry.
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http://dx.doi.org/10.1007/s10895-021-02754-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169433PMC
June 2021

Ultra-Highly Sensitive Hydrogen Chloride Detection Based on Quartz-Enhanced Photothermal Spectroscopy.

Sensors (Basel) 2021 May 20;21(10). Epub 2021 May 20.

National Key Laboratory of Science and Technology on Tunable Laser, Harbin Institute of Technology, Harbin 150001, China.

Combining the merits of non-contact measurement and high sensitivity, the quartz-enhanced photothermal spectroscopy (QEPTS) technique is suitable for measuring acid gases such as hydrogen chloride (HCl). In this invited paper, we report, for the first time, on an ultra-highly sensitive HCl sensor based on the QEPTS technique. A continuous wave, distributed feedback (CW-DFB) fiber-coupled diode laser with emission wavelength of 1.74 µm was used as the excitation source. A certified mixture of 500 ppm HCl:N was adapted as the analyte. Wavelength modulation spectroscopy was used to simplify the data processing. The wavelength modulation depth was optimized. The relationships between the second harmonic (2) amplitude of HCl-QEPTS signal and the laser power as well as HCl concentration were investigated. An Allan variance analysis was performed to prove that this sensor had good stability and high sensitivity. The proposed HCl-QEPTS sensor can achieve a minimum detection limit (MDL) of ~17 parts per billion (ppb) with an integration time of 130 s. Further improvement of such an HCl-QEPTS sensor performance was proposed.
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http://dx.doi.org/10.3390/s21103563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160860PMC
May 2021

SIK2 kinase synthetic lethality is driven by spindle assembly defects in FANCA-deficient cells.

Mol Oncol 2021 May 31. Epub 2021 May 31.

Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

The Fanconi anemia (FA) pathway safeguards genomic stability through cell cycle regulation and DNA damage repair. The canonical tumor suppressive role of FA proteins in the repair of DNA damage during interphase is well established, but their function in mitosis is incompletely understood. Here we performed a kinome-wide synthetic lethality screen in FANCA-/- fibroblasts, which revealed multiple mitotic kinases as necessary for survival of FANCA-deficient cells. Among these kinases, we identified the depletion of the centrosome kinase SIK2 as synthetic lethal upon loss of FANCA. We found that FANCA co-localizes with SIK2 at multiple mitotic structures and regulates the activity of SIK2 at centrosomes. Furthermore, we found that loss of FANCA exacerbates cell cycle defects induced by pharmacological inhibition of SIK2, including impaired G2-M transition, delayed mitotic progression, and cytokinesis failure. In addition, we showed that inhibition of SIK2 abrogates nocodazole-induced prometaphase arrest, suggesting a novel role for SIK2 in the spindle assembly checkpoint. Together, these findings demonstrate that FANCA-deficient cells are dependent upon SIK2 for survival, supporting a preclinical rationale for targeting of SIK2 in FA-disrupted cancers.
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http://dx.doi.org/10.1002/1878-0261.13027DOI Listing
May 2021

Re-isolation of Wuxiang Virus from Wild Sandflies Collected from Yangquan County, China.

Virol Sin 2021 May 31. Epub 2021 May 31.

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

We previously isolated a new species of the genus Phlebovirus from wild sandflies collected from Wuxiang County in central China, which named the Wuxiang virus (WUXV). In this study, we re-isolated the WUXV from wild sandflies collected from two villages in Yangquan County, China in 2019. Four virus isolates that caused cytopathic effects in BHK-21 cells were successfully isolated from sandfly specimens collected from chicken pens and sheep pens. Phylogenetic analyses of the L, M and S gene segments of the viruses revealed that the four virus strains represented the previously isolated WUXV. The minimum infection rate (MIR) of the virus isolated from the sheep pen was 3.21, and the MIR of the virus isolated from the chicken pen was 3.45. The positive rates of Wuxiang virus neutralizing antibodies in serum samples of local healthy people and domestic chickens were 8.7% (4/46) and 100% (4/4), respectively, suggesting that Wuxiang virus can infect human and animal. In view of the fact that Wuxiang virus is infectious to humans and animals and has a relatively wide geographical distribution in China, it is of great public health significance to strengthen the investigation and study on the infection status of Wuxiang virus in humans and animals.
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http://dx.doi.org/10.1007/s12250-021-00398-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165349PMC
May 2021

Quartz tuning fork-based demodulation of an acoustic signal induced by photo-thermo-elastic energy conversion.

Photoacoustics 2021 Jun 15;22:100272. Epub 2021 May 15.

National Key Laboratory of Science and Technology on Tunable Laser, Harbin Institute of Technology, Harbin 150001, China.

A gas sensing method based on quartz-enhanced photothermal spectroscopy (QEPTS) demodulated by quartz tuning fork (QTF) sensing acoustic wave is reported for the first time. Different from traditional QEPTS, the method proposed in this paper utilizes the second QTF to sense acoustic wave produced by the first QTF owing to the vibration resulted from photo-thermo-elastic effect. This indirect demodulation by acoustic wave sensing can avoid QTF being irradiated by laser beam and therefore get less noise and realize better detection sensitivity. Four different sensing configurations are designed and verified. Acetylene (CH) with a volume concentration of 1.95 % is selected as the target gas. A model of sound field produced by the first QTF vibrating is established by finite element method to explain the variation trend of signal and noise in the second QTF. The measured results indicate that this technique had an enhanced signal-to-noise ratio (SNR) of 1.36 times when compared to the traditional QEPTS. Further improvement methods for such technique is proposed.
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http://dx.doi.org/10.1016/j.pacs.2021.100272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144470PMC
June 2021

Construction of Stable Helical Metal-Organic Frameworks with Conformationally Rigid "Concave Ligand".

Chemistry 2021 May 25. Epub 2021 May 25.

Jilin University, College of Chemistry, CHINA.

A helical-shaped metal-organic framework was prepared using conformationally rigid tetratopic benzoic acid ligand with binding units pointing toward each other (concave ligand). To avoid the obvious intramolecular interactions between binding units, matching spacing groups was applied to introduce atropic repulsion, allowing the formation of extended frameworks for the first time. With this new ligand design, a helical-shaped MOF was successfully prepared with significantly improved air and moisture stability, providing a new strategy for ligand design toward porous material constructions.
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http://dx.doi.org/10.1002/chem.202101173DOI Listing
May 2021

The Dynamic Counterbalance of RAC1-YAP/OB-Cadherin Coordinates Tissue Spreading with Stem Cell Fate Patterning.

Adv Sci (Weinh) 2021 05 8;8(10):2004000. Epub 2021 Mar 8.

Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry Peking University School and Hospital of Stomatology Beijing 100081 P. R. China.

Tissue spreading represents a key morphogenetic feature of embryonic development and regenerative medicine. However, how molecular signaling orchestrates the spreading dynamics and cell fate commitment of multicellular tissue remains poorly understood. Here, it is demonstrated that the dynamic counterbalance between RAC1-YAP and OB-cadherin plays a key role in coordinating heterogeneous spreading dynamics with distinct cell fate patterning during collective spreading. The spatiotemporal evolution of individual stem cells in spheroids during collective spreading is mapped. Time-lapse cell migratory trajectory analysis combined with in situ cellular biomechanics detection reveal heterogeneous patterns of collective spreading characteristics, where the cells at the periphery are faster, stiffer, and directional compared to those in the center of the spheroid. Single-cell sequencing shows that the divergent spreading result in distinct cell fate patterning, where differentiation, proliferation, and metabolism are enhanced in peripheral cells. Molecular analysis demonstrates that the increased expression of RAC1-YAP rather than OB-cadherin facilitated cell spreading and induced differentiation, and vice versa. The in vivo wound healing experiment confirms the functional role of RAC1-YAP signaling in tissue spreading. These findings shed light on the mechanism of tissue morphogenesis in the progression of development and provide a practical strategy for desirable regenerative therapies.
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http://dx.doi.org/10.1002/advs.202004000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132063PMC
May 2021

Evaluation of the treatment efficacy of systemic care combined with thymopentin and 2HRZE/4HR for primary tuberculosis.

Authors:
Ying He Wandi Zheng

Am J Transl Res 2021 15;13(4):2891-2898. Epub 2021 Apr 15.

Department of Infectious Diseases, The First People's Hospital of Fuyang Hangzhou Hangzhou 311400, Zhejiang, China.

Objective: To investigate the efficacy of systemic care combined with thymopentin and 2HRZE/4HR in the treatment of primary tuberculosis.

Methods: The clinical data of 93 patients with primary tuberculosis were retrospectively collected and divided into two groups based on the intervention method. Group A (n=46) was treated only with 2HRZE/4HR, and group B (n=47) was treated with the 2HRZE/4HR combined with thymopentin. Meanwhile, both groups received systematic care. The lesion absorption rate, sputum conversion rate (SCR), T lymphocyte subpopulation count, immunoglobulin level, lung function index, changes in sputum supernatant levels of cytokines before and after treatment, and the occurrence of adverse reactions were compared.

Results: Group B exhibited higher complete absorption rate of foci and lower basic absorption rate than group A ( < 0.05). The SCRs of group B after 2, 4 and 6 months of intervention were higher than those of group A ( < 0.05). Compared with group A, group B had lower CD8 level and higher CD4 and CD3 levels ( < 0.05). Group B also had higher levels of IgA, IgG, and IgM than group A after intervention ( < 0.05). Group B had higher levels of FEV1, PEF, and FVC than group A after intervention ( < 0.05). In contrast to group A, group B had lower IL-4 levels and higher TNF-γ levels ( < 0.05). The incidence rate of adverse events in group B was not significantly different from that in group A ( > 0.05).

Conclusion: Systemic care combined with 2HRZE/4HR was effective for treatment of primary tuberculosis, which is beneficial for improving the immunity, SCR, and the inflammatory status, with low incidence of adverse events and a high safety level.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129341PMC
April 2021

Installing CRISPR-Cas12a sensors in a portable glucose meter for point-of-care detection of analytes.

Analyst 2021 May 15;146(10):3114-3120. Epub 2021 Apr 15.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.

Integrating CRISPR-Cas12a sensors with a portable glucose meter (PGM) was developed based on the target-induced activation of the collateral cleavage activity of Cas12a. Considering the portability, low cost and facile incorporation of the PGM system with suitable Cas12a sensors to recognize many targets, the CRISPR/Cas12a-PGM system demonstrated here paves a way to further broaden the POC applications of CRISPR-based diagnostics.
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http://dx.doi.org/10.1039/d1an00008jDOI Listing
May 2021

Trace gas sensing based on single-quartz-enhanced photoacoustic-photothermal dual spectroscopy.

Opt Lett 2021 May;46(10):2449-2452

A single-quartz-enhanced dual spectroscopy (S-QEDS)-based trace gas sensor is reported for the first time, to the best of our knowledge. In S-QEDS, a quartz tuning fork (QTF) was utilized to detect the photoacoustic and photothermal signals simultaneously and added the two signals together. The S-QEDS technique not only improved the detection performance but also avoided the issue of resonant frequency mismatching of QTFs for the multi-QTFs-based sensor systems. Water vapor (${\rm H}_2{\rm O}$) was selected as the target gas to investigate the S-QEDS sensor performance. The photoacoustic, photothermal, and composited signals were measured, respectively, under the same conditions. The experimental results verified the ideal adding of the photoacoustic and photothermal signals by using a single QTF in this S-QEDS sensor system.
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http://dx.doi.org/10.1364/OL.423801DOI Listing
May 2021

Ultrasonographic features of an intravascular lobular capillary hemangioma originating in the basilic vein: Case report and literature review.

J Clin Ultrasound 2021 May 12. Epub 2021 May 12.

Department of Ultrasound Medicine, West China Hospital, Sichuan University, Chengdu, China.

Intravascular lobular capillary hemangioma (ILCH) is a rare variant of pyogenic granuloma, which develops within the lumen of a blood vessel. Here, we report the case of a 38-year-old male presenting with a mobile, incompressible, nonpulsatile nodule in the superficial fascia of the forearm. A first ultrasonographic examination diagnosed the mass as intravascular thrombosis with partial recanalization. Three months later, a second ultrasonographic examination concluded to the existence of an intravascular tumor, which finally turned out at pathological examination to be ILCH. Here, we report the ultrasonographic features of ILCH and the differential diagnosis between ILCH and other intravascular masses like thrombus.
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http://dx.doi.org/10.1002/jcu.23017DOI Listing
May 2021

GmPTF1 modifies root architecture responses to phosphate starvation primarily through regulating GmEXPB2 expression in soybean.

Plant J 2021 May 7. Epub 2021 May 7.

Root Biology Center, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

Though root architecture modifications may be critically important for improving phosphorus (P) efficiency in crops, the regulatory mechanisms triggering these changes remain unclear. In this study, we demonstrate that genotypic variation in GmEXPB2 expression is strongly correlated with root elongation and P acquisition efficiency, and enhancing its transcription significantly improves soybean yield in the field. Promoter deletion analysis was performed using 5' truncation fragments (P1-P6) of GmEXPB2 fused with the GUS gene in soybean transgenic hairy roots, which revealed that the P1 segment containing three E-box elements significantly enhances induction of gene expression in response to phosphate (Pi) starvation. Further experimentation demonstrated that GmPTF1, a basic-helix-loop-helix transcription factor, is the regulatory factor responsible for the induction of GmEXPB2 expression in response to Pi starvation. In short, Pi starvation induced expression of GmPTF1, with the GmPTF1 product directly binding to the E-box motif in the P1 region of the GmEXPB2 promoter. Plus, both GmPTF1 and GmEXPB2 highly expressed in lateral roots, and were significantly enhanced by P deficiency. Further work with soybean stable transgenic plants through RNA sequencing analysis showed that altering GmPTF1 expression significantly impacted the transcription of a series of cell wall genes, including GmEXPB2, and thereby affected root growth, biomass and P uptake. Taken together, this work identifies a novel regulatory factor, GmPTF1, involved in changing soybean root architecture partially through regulation of the expression of GmEXPB2 by binding the E-box motif in its promoter region.
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http://dx.doi.org/10.1111/tpj.15307DOI Listing
May 2021

Physiological and transcriptional responses of Phalaris arundinacea under waterlogging conditions.

J Plant Physiol 2021 Jun 18;261:153428. Epub 2021 Apr 18.

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University, Chengdu, 610065 Sichuan, China. Electronic address:

As a high-yielding forage grass, Phalaris arundinacea widely distributed in the Qinghai-Tibet Plateau region of China. To explore physiological and molecular response mechanism of Phalaris arundinacea under waterlogging, we analyzed the biomass and physiological indexes of three locally grown strains under the submerged condition of 10 cm. The material Z0611 showed the strongest waterlogging resistance while the YS showed the weakest performance. Transcriptome sequencing analysis demonstrated that the YS and Z0611 had 17010 and 7566 differently expression genes (DEGs), respectively, which were mainly concentrated in the metabolic process, cell, ribosome, phenylpropanoid biosynthesis pathway in GO and KEGG databases. We also identified a large number of genes involved in carbohydrate metabolism, hormone signaling regulation, transcription factors, antioxidant system, and ethylene signaling. Our research may provide a scientific basis for the restoration of wetland environment on the Qinghai-Tibet Plateau, and lay a foundation for further exploration of the waterlogging resistance genes of Phalaris arundinacea and breeding of new strains resistant with waterlogging stress.
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http://dx.doi.org/10.1016/j.jplph.2021.153428DOI Listing
June 2021

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.

JAMA Psychiatry 2021 May 5. Epub 2021 May 5.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.

Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).

Design, Setting, And Participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.

Main Outcomes And Measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).

Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001).

Conclusions And Relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.0638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100913PMC
May 2021

Identifying the functions of two biomarkers in human oligodendrocyte progenitor cell development.

J Transl Med 2021 05 1;19(1):188. Epub 2021 May 1.

The Second Clinical College, Southern Medical University, Guangzhou, 510515, China.

Background: Human oligodendrocyte precursor cells (hOPCs) are an important source of myelinating cells for cell transplantation to treat demyelinating diseases. Myelin oligodendrocytes develop from migratory and proliferative hOPCs. It is well known that NG2 and A2B5 are important biological markers of hOPCs. However, the functional differences between the cell populations represented by these two biomarkers have not been well studied in depth.

Objective: To study the difference between NG2 and A2B5 cells in the development of human oligodendrocyte progenitor cells.

Methods: Using cell sorting technology, we obtained NG2+/-, A2B5+/- cells. Further research was then conducted via in vitro cell proliferation and migration assays, single-cell sequencing, mRNA sequencing, and cell transplantation into shiverer mice.

Results: The proportion of PDGFR-α + cells in the negative cell population was higher than that in the positive cell population. The migration ability of the NG2+/-, A2B5+/- cells was inversely proportional to their myelination ability. The migration, proliferation, and myelination capacities of the negative cell population were stronger than those of the positive cell population. The ability of cell migration and proliferation of the four groups of cells from high to low was: A2B5- > NG2- > NG2+ > A2B5+. The content of PDGFR-α+ cells and the ability of cell differentiation from high to low was: NG2- > A2B5- > A2B5+ > NG2+.

Conclusion: In summary, NG2+  and A2B5+ cells have poor myelination ability due to low levels of PDGFR-α+ cells. Therefore, hOPCs with a higher content of PDGFR-α+ cells may have a better effect in the cell transplantation treatment of demyelinating diseases.
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http://dx.doi.org/10.1186/s12967-021-02857-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088696PMC
May 2021

Design, synthesis and evaluation of cinnamic acid hybrids as multi-target-directed agents for the treatment of Alzheimer's disease.

Bioorg Chem 2021 Jul 9;112:104879. Epub 2021 Apr 9.

College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China. Electronic address:

Herein, combining 1,2,3,4-tetrahydroisoquinoline and benzylpiperidine groups into cinnamic acid derivatives, a series of novel cinnamic acid hybrids was rationally designed, synthesized and evaluated by the multi-target-directed ligands (MTDLs) strategy. Hybrid 4e was the most promising one among these hybrids with a reversible huBuChE inhibitor (IC = 2.5 μM) and good MAO-B inhibition activity (IC = 1.3 μM) and antioxidant potency (ORAC = 0.4 eq). Moreover, compound 4e significantly inhibited self-mediated Aβ aggregation (65.2% inhibition rate). Compound 4e exhibited remarkable anti-inflammatory propery and neuroprotective effect. Furthermore, compound 4e displayed favourable blood-brain barrier penetration via parallel artificial membrane permeation assay (PAMPA). The obtained results also revealed that compound 4e significantly improved dyskinesia recovery rate and response efficiency on AD model zebrafish. Further, 4e did not show obvious acute toxicity at dose up to 1500 mg/kg in vivo and improved scopolamine-induced memory impairment. Importantly, compound 4e showed good stability in both artificial gastric fluid and artificial intestinal fluid. Therefore, compound 4e presented a promising multi-targeted active molecule for treating AD.
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http://dx.doi.org/10.1016/j.bioorg.2021.104879DOI Listing
July 2021

Synchronized research on endothelial dysfunction and microcirculation structure in dorsal skin of rats with type 2 diabetes mellitus.

Med Biol Eng Comput 2021 May 29;59(5):1151-1166. Epub 2021 Apr 29.

Anhui Medical University, Hefei, China.

The aim of this study was to explore changes in the microvascular tone as measured by laser Doppler flowmetry (LDF) and the microcirculation structure of the dorsal skin of rats with type 2 diabetes mellitus. The diabetic rat model was induced by a diet of high-sugar and high-lipid fodder combined with the injection of streptozotocin into the abdominal cavity. Depending on the interval between the development of diabetes and the experiments, the diabetic rats were subdivided into three groups. The evaluation of microvascular tone was based on the amplitude responses of the LDF signal fluctuations in the appropriate frequency range in the dorsal skin of the rats during a thermal test (at 42 °C). The nitric oxide (NO) level in plasma was also used as a marker of endothelial dysfunction. Changes in the microcirculation structure in the diabetic rats were estimated by measuring the microvascular density in the choke vessels of the dorsal skin of the rats. The experimental results with respect to red blood cell (RBC)-related parameters showed decreased hematocrit and hemoglobin levels and increased standard deviation of the width of the RBC distribution in three diabetic rats. The increasing fluctuation amplitudes diminished in the endothelial frequency range in response to the thermal test and this was accompanied by abnormal NO levels in plasma of the diabetic groups as compared with healthy rats. A significant reduction in the microvascular density of the choke vessels of the dorsal skin was found only in the diabetic group at the most advanced stage of diabetes in this experiment. Thus, we suggest that endothelial dysfunction occurs in diabetic rats and changes in the microcirculation structure of the dorsal skin occur in a later stage of diabetes development. A. Photograph of measurement method by using a LDF probe and heating device in the dorsal skin of the rat. B. Dorsal skin LDF signals of a healthy rat during the thermal stimuli test. (a) Blood flow signal record for the test. Wavelet filtration of blood flow signal in (b) myogenic range, (c) neurogenic range, and (d) endothelial range.
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http://dx.doi.org/10.1007/s11517-021-02363-5DOI Listing
May 2021

HLA-A2.1-restricted ECM1-derived epitope LA through DC cross-activation priming CD8 T and NK cells: a novel therapeutic tumour vaccine.

J Hematol Oncol 2021 Apr 28;14(1):71. Epub 2021 Apr 28.

Department of Pharmacology, School of Pharmacy, China Medical University, No. 13, Beihai Road, Dadong District, Shenyang, Liaoning Province, China.

Background: CD8 T cell-mediated adaptive cellular immunity and natural killer (NK) cell-mediated innate immunity both play important roles in tumour immunity. This study aimed to develop therapeutic tumour vaccines based on double-activation of CD8 T and NK cells.

Methods: The immune Epitope database, Molecular Operating Environment software, and enzyme-linked immunosorbent assay were used for epitope identification. Flow cytometry, confocal microscopy, UPLC-QTOF-MS, and RNA-seq were utilized for evaluating immunity of PBMC-derived DCs, CD8 T or NK cells and related pathways. HLA-A2.1 transgenic mice combined with immunologically reconstituted tumour-bearing mice were used to examine the antitumour effect and safety of epitope vaccines.

Results: We identified novel HLA-A2.1-restricted extracellular matrix protein 1(ECM1)-derived immunodominant epitopes in which LA induced a potent immune response. We also found that LA-loaded DCs upregulated the frequency of CD3/CD8 T cells, CD45RO/CD69 activated memory T cells, and CD3/CD16/CD56 NK cells. We demonstrated cytotoxic granule release of LA/DC-CTLs or LA/DC-NK cells and cytotoxicity against tumour cells and microtissue blocks via the predominant IFN-γ/perforin/granzyme B cell death pathway. Further investigating the mechanism of LA-mediated CD8 T activation, we found that LA could be internalized into DCs through phagocytosis and then formed a LA-MHC-I complex presented onto the DC surface for recognition of the T cell receptor to upregulate Zap70 phosphorylation levels to further activate CD8 T cells by DC-CTL interactions. In addition, LA-mediated DC-NK crosstalk through stimulation of the TLR4-p38 MAPK pathway increased MICA/B expression on DCs to interact with NKG2D for NK activation. Promisingly, LA could activate CD8 T cells and NK cells simultaneously via interacting with DCs to suppress tumours in vivo. Moreover, the safety of LA was confirmed.

Conclusions: LA-induced immune antitumour activity through DC cross-activation with CD8 T and NK cells, which demonstrated proof-of-concept evidence for the capability and safety of a novel therapeutic tumour vaccine.
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http://dx.doi.org/10.1186/s13045-021-01081-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082934PMC
April 2021

Correction: Health Care Cybersecurity Challenges and Solutions Under the Climate of COVID-19: Scoping Review.

J Med Internet Res 2021 Apr 28;23(4):e29877. Epub 2021 Apr 28.

School of Computer Science and Electronic Engineering, University of Essex, Colchester, United Kingdom.

[This corrects the article DOI: 10.2196/21747.].
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http://dx.doi.org/10.2196/29877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116988PMC
April 2021

Metagenomic sequencing reveals viral abundance and diversity in mosquitoes from the Shaanxi-Gansu-Ningxia region, China.

PLoS Negl Trop Dis 2021 Apr 26;15(4):e0009381. Epub 2021 Apr 26.

Chinese Center for Disease Control and Prevention -Wuhan Institute of Virology, Chinese Academy of Sciences Joint Research Center for Emerging Infectious Diseases and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People's Republic of China.

Background: Mosquitoes host and transmit numerous arthropod-borne viruses (arboviruses) that cause disease in both humans and animals. Effective surveillance of virome profiles in mosquitoes is vital to the prevention and control of mosquito-borne diseases in northwestern China, where epidemics occur frequently.

Methods: Mosquitoes were collected in the Shaanxi-Gansu-Ningxia region (Shaanxi Province, Gansu Province, and Ningxia Hui Autonomous Region) of China from June to August 2019. Morphological methods were used for taxonomic identification of mosquito species. High-throughput sequencing and metagenomic analysis were used to characterize mosquito viromes.

Results: A total of 22,959 mosquitoes were collected, including Culex pipiens (45.7%), Culex tritaeniorhynchus (40.6%), Anopheles sinensis (8.4%), Aedes (5.2%), and Armigeres subalbatus (0.1%). In total, 3,014,183 (0.95% of clean reads) viral sequences were identified and assigned to 116 viral species (including pathogens such as Japanese encephalitis virus and Getah virus) in 31 viral families, including Flaviviridae, Togaviridae, Phasmaviridae, Phenuiviridae, and some unclassified viruses. Mosquitoes collected in July (86 species in 26 families) showed greater viral diversity than those from June and August. Culex pipiens (69 species in 25 families) and Culex tritaeniorhynchus (73 species in 24 families) carried more viral species than Anopheles sinensis (50 species in 19 families) or Aedes (38 species in 20 families) mosquitoes.

Conclusion: Viral diversity and abundance were affected by mosquito species and collection time. The present study elucidates the virome compositions of various mosquito species in northwestern China, improving the understanding of virus transmission dynamics for comparison with those of disease outbreaks.
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http://dx.doi.org/10.1371/journal.pntd.0009381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101993PMC
April 2021

Palitantin derivatives from the Antarctic fungus sp. 3-1.

J Asian Nat Prod Res 2021 Apr 23:1-7. Epub 2021 Apr 23.

Department of Marine Biomedicine and Polar Medicine, Naval Medical Center of PLA, Second Military Medical University, Shanghai 200433, China.

Two new polyketides, palitantins B and C ( and ), along with one known related compound (+)-palitantin () were obtained from the culture of the Antarctic fungus sp. 3-1. The structures of the new compounds were elucidated by detailed analysis of HRESIMS, NMR, CD, and ECD data. Compound showed potent PTP1B inhibitory activity with an IC value of 7.9 M (ursolic acid as positive control, IC = 8.3 M).
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http://dx.doi.org/10.1080/10286020.2021.1915995DOI Listing
April 2021

Isolation and Characterization of Wuxiang Virus from Sandflies Collected in Yangquan County, Shanxi Province, China.

Vector Borne Zoonotic Dis 2021 Jun 23;21(6):446-457. Epub 2021 Apr 23.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

In this study, we isolated a group of viruses that can cause a cytopathic effect in BHK-21 cells from sandfly specimens collected in Yangquan County, Shanxi Province, central China. The representative virus strain is SXYQ1860 and, with increased viral injection, the suckling mice became ill and died, with viral titers continually increasing. The results of molecular genetic evolution analysis of the three gene segments of the virus, L, M, and S, indicate that the newly isolated viruses from Yangquan County are the same as the Wuxiang virus (WUXV) previously isolated from sandflies collected in Wuxiang county, China. This is the first time that the WUXV was also isolated outside Wuxiang County. Therefore, strengthening the surveillance of neglected sandflies and the viruses they transmit to help prevent and control arboviruses and the associated diseases is essential for public health.
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http://dx.doi.org/10.1089/vbz.2020.2699DOI Listing
June 2021

miR-20a-5p inhibits endometrial cancer progression by targeting janus kinase 1.

Oncol Lett 2021 May 30;21(5):427. Epub 2021 Mar 30.

Emergency Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, P.R. China.

Endometrial cancer (EC) is a multi-factorial disease of which pathogenesis has not been fully elucidated. The function and underlying mechanism of microRNA-20a-5p (miR-20a-5p) in EC remain poorly understood. The present study aimed to analyze the association between miR-20a-5p expression and the clinicopathological characteristics of patients with EC. Whether miR-20a-5p could inhibit EC progression by targeting janus kinase 1 (Jak1) was subsequently investigated. To do so, human EC tissues and paracancerous tissues were collected from 47 patients with EC. miR-20a-5p and Jak1 mRNA and protein expression was determined by reverse transcription quantitative PCR and western blotting, respectively. Cell proliferation, invasive ability and adhesion were investigated by MTT, Matrigel invasion and cell adhesion assays, respectively. Dual luciferase reporter assay was used to verify whether miR-20a-5p could directly target Jak1. The results demonstrated that miR-20a-5p was downregulated and that Jak1 was upregulated in EC tissues compared with paracancerous tissues. In addition, miR-20a-5p expression and Jak1 expression level were negatively correlated in EC tissues. miR-20a-5p expression was also significantly associated with the depth of myometrial invasion, FIGO stage, histologic grade and lymph node metastasis in patients with EC. Furthermore, Jak1 was identified as a new direct target of miR-20a-5p, and Jak1 overexpression was demonstrated to reverse the effects of miR-20a-5p-mimic on EC cell proliferation, invasive ability and adhesion. Taken together, the results from this study revealed for the first time that miR-20a-5p expression was significantly associated with the clinicopathological characteristics of patients with EC. These findings suggested that miR-20a-5p may act as a tumor suppressor in EC, in part through decreasing Jak1 expression. miR-20a-5p and Jak1 may therefore serve as potential therapeutic targets in EC.
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http://dx.doi.org/10.3892/ol.2021.12688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025135PMC
May 2021