Publications by authors named "Xin Gu"

313 Publications

Circular RNA_PDHX Promotes the Proliferation and Invasion of Prostate Cancer by Sponging MiR-378a-3p.

Front Cell Dev Biol 2020 28;8:602707. Epub 2021 Jan 28.

Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The dysregulation of circular RNAs (circRNAs) is implicated in the pathogenesis of prostate cancer (PCa). However, the underlying mechanisms by which hsa_circ_0003768 (circPDHX) contributes to PCa remain elusive. The differentially expressed circRNAs between PCa and normal tissues were identified by Gene Expression Omnibus dataset. The association of circPDHX and miR-378a-3p expression with the clinicopathological parameters and prognosis in patients with PCa was analyzed by fluorescence hybridization and The Cancer Genome Atlas dataset. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays as well as a xenograft tumor model were used to assess the role of circPDHX in PCa cells. circPDHX-specific binding with miR-378a-3p was validated by bioinformatic analysis, luciferase gene reporter, and RNA immunoprecipitation assays. As a result, we found that increased expression of circPDHX was associated with Gleason score ( = 0.001) and pathogenic T stage ( = 0.01) and acted as an independent prognostic factor of poor survival ( = 0.036) in patients with PCa. Knockdown of circPDHX inhibited cell proliferation and invasion and , but ectopic expression of circPDHX reversed these effects. Furthermore, circPDHX could sponge miR-378a-3p to promote cell proliferation, but miR-378a-3p counteracted circPDHX-induced cell proliferation and insulin-like growth factor 1 receptor (IGF1R) expression in PCa cells. In conclusion, our findings demonstrated that circPDHX facilitated the proliferation and invasion of PCa cells by sponging miR-378a-3p.
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http://dx.doi.org/10.3389/fcell.2020.602707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901981PMC
January 2021

Application of magnetic fields to wastewater treatment and its mechanisms: A review.

Sci Total Environ 2021 Jan 30;773:145476. Epub 2021 Jan 30.

School of Civil Engineering, College of Engineering and Informatics, National University of Ireland, Galway, Ireland.

Magnetic field (MF) has been applied widely and successfully as an efficient, low-cost and easy-to-use technique to enhance wastewater treatment (WWT) performance. Although the effects of MF on WWT were revealed and summarized by some works, they are still mysterious and complex. This review summarizes the application of MF in magnetic adsorption-separation of heavy metals and dyes, treatment of domestic wastewater and photo-magnetic coupling technology. Furthermore, the mechanisms of MF-enhanced WWT are critically elaborated from the perspective of magnetic physicochemical and biological effects, such as magnetoresistance, Lorentz force, and intracellular radical pair mechanism. At last, the challenges and opportunities for MF application in WWT are discussed. For overcoming the limitations and taking advantages of MFs in WWT, fundamental research of the mechanisms of the application of MFs should be carried out in the future.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145476DOI Listing
January 2021

Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models.

Stem Cell Res Ther 2021 Jan 25;12(1):87. Epub 2021 Jan 25.

Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201999, China.

Background: Erectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived mesenchymal stem cell (ADSC)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED.

Methods: In this study, ED was induced in Sprague Dawley (SD) rats using chronic intermittent hypoxia (CIH) exposure. CIH-mediated influences were then measured in the corpus cavernous smooth muscle cells (CCSMCs).

Results: Our data showed that miR-301a-3p-enriched exosome treatment significantly recovered erectile function in rats and CCSMCs by promoting autophagy and inhibiting apoptosis. The treatment also significantly recovered the level of alpha smooth muscle actin (α-SMA) in rats and CCSMCs. Bioinformatics predicted that phosphatase and tensin homolog (PTEN) and Toll-like receptor 4 (TLR4) might be targets of miR-301a-3p.

Conclusions: Our results indicate that PTEN-overexpression vectors or TLR4-overexpression vectors reverse the therapeutic effects achieved by miR-301a-3p in CCSMCs indicating that PTEN/hypoxia-inducible factor-1 alpha (HIF-1α) and TLR4 signaling pathways play key roles in the progression of ED. The findings in this study suggest that miR-301a-3p should be considered a new therapeutic target for treating ED associated with OSA.
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http://dx.doi.org/10.1186/s13287-021-02161-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836493PMC
January 2021

Erratum to development and formulation of the classification criteria for osteoarthritis.

Ann Transl Med 2020 Dec;8(23):1630

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

[This corrects the article DOI: 10.21037/atm-20-4673.].
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http://dx.doi.org/10.21037/atm-2020-29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791258PMC
December 2020

Fate of antibiotics and antibiotic resistance genes in home water purification systems.

Water Res 2021 Feb 22;190:116762. Epub 2020 Dec 22.

School of Environmental Science and Engineering, Tianjin University, Weijin Road 92, Tianjin, 300072, China.

Home water purification systems (HWPSs) are utilized worldwide to obtain clean drinking water. However, the reliability of HWPSs in providing safe water is unknown or not well-proven. In this study, the occurrences of antibiotics and antibiotic resistance genes (ARGs) in tap water, effluents, and filters of HWPSs were investigated in twenty-six houses and one laboratory. The levels of antibiotics and ARGs were between less than the limit of detection (LOD) and 7.9 ng/L and between less than LOD and 3.45 × 10 copies/L, respectively, in tap water. HWPSs with fresh filters had a high efficiency in removing antibiotics and ARGs, with removal rates of 91-92% and 0.46-2.43 log, respectively. However, after long-term operation (e.g., more than three months), some HWPSs had low removal rates of antibiotics and ARGs (3-79% and 0.03-0.15 log, respectively) and some HWPSs released antibiotics and ARGs into the effluents leading to higher levels of antibiotics and ARGs in the effluents than those in the influents. Biofilms were observed on many filters of the investigated HWPSs. ARGs were detected on the filters with relative abundances (the ratio of the abundance of ARGs to the abundance of 16S rRNA) of 2.56 × 10-2.89 × 10. High-throughput sequencing analysis showed that Proteobacteria, Acidobacteria, Chloroflexi, and Bacteroidetes were the dominant phyla, and Alphaproteobacteria and Gammaproteobacteria were the dominant classes. The abundances of Cyanobacteria, Patescibacteria, Bacteroidetes, and Proteobacteria were significantly positively correlated with the abundances of ARGs. Microbial growth and enrichment commonly observed in HWPSs can accelerate the exposure risk posed by antibiotics and ARGs to the consumers of water from these appliances.
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http://dx.doi.org/10.1016/j.watres.2020.116762DOI Listing
February 2021

The Influence of Individual Differences on Diverging Behavior at the Weaving Sections of an Urban Expressway.

Int J Environ Res Public Health 2020 12 22;18(1). Epub 2020 Dec 22.

Jiangsu Key Laboratory of Urban ITS, Jiangsu Collaborative Innovation Center of Modern Urban Traffic Technologies, School of Transportation, Southeast University, Nanjing 21189, Jiangsu, China.

Urban expressway weaving sections suffer from a high crash risk in urban transportation systems. Studying driving behavior is an important approach to solve safety and efficiency issues at expressway weaving sections. This study aimed to investigate the influence of drivers' individual differences on diverging behavior at expressway weaving sections. First, a k-means cluster analysis of 650 questionnaires was performed, to classify drivers into three categories: aggressive, conservative and normal. Then, the driving behavior of 45 drivers from the three categories was recorded in a driving simulator and analyzed by an analysis of variance. The results show that different types of drivers have different driving behaviors at weaving sections. Aggressive drivers have a higher mean speed and mean longitudinal deceleration, followed by normal and conservative drivers. Significant differences in the range of lane-change positions were found between 100, 150 and 200 m of weaving length for the same type of drivers, and the duration of weaving for aggressive drivers was significantly smaller than for normal and conservative drivers. A significant correlation was found between lane-change position and weaving duration. These results can help traffic engineers to propose effective control strategies for different types of drivers, to improve the safety of weaving sections.
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http://dx.doi.org/10.3390/ijerph18010025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792952PMC
December 2020

Sustained-Release Method for the Directed Synthesis of ZIF-Derived Ultrafine Co-N-C ORR Catalysts with Embedded Co Quantum Dots.

ACS Appl Mater Interfaces 2020 Dec 18;12(52):57847-57858. Epub 2020 Dec 18.

College of New Energy, China University of Petroleum (East China), Qingdao 266580, P. R. China.

M-N-C catalysts with optimized local and external structures offer great potential for replacing expensive and labile Pt-based catalysts for the oxygen reduction reaction (ORR) in fuel cells. Herein, we report a novel and facile strategy of synthesizing ultrafine ZIF-derived Co-N-C catalysts by precisely controlling the crystallization rate of ZIFs. The employment of meta-soluble Co-doped basic zinc acetate (Co-BZA), which shows a sustained-release effect in solvents, allows for the control of the solubility of Co-BZA in solvents. Detailed investigations suggest that the solubility of Co-BZA in the solvent is the key for governing the grain size of the resulting Zn/Co bimetallic ZIFs. Therefore, the self-assembly process between ligands and metal ions can be regulated by tuning the composition of mixed solvents, thus enabling rational tuning of the grain size of the resulting ZIFs. One-step pyrolysis of the ultrafine Zn/Co bimetallic ZIF precursor leads to Co and N co-doped carbon with an ultrafine grain size (termed UF Co-N-C). The Co centers that are uniformly distributed in the carbon matrix possess a quantum-dot-level grain size. Furthermore, this type of carbon nanohybrid exhibits a hierarchical pore structure, as well as a high surface area. When used as an ORR catalyst, the UF Co-N-C catalyst possesses high ORR activity (with an of 0.9 V) that can rival 20 wt % commercial Pt/C (with an of 0.835 V) in alkaline media. Notably, this catalyst also displays strong ORR performance similar to that of Pt/C in acidic media. The superior durability and methanol tolerance in both alkaline and acidic media for UF Co-N-C compared to Pt/C illustrate its great potential in replacing commercial Pt/C catalysts. The outstanding ORR performance of UF Co-N-C could be attributed to the simultaneous optimization of both external structures and active sites, demonstrating the effectiveness of this strategy in constructing ORR catalysts with controlled structures and desired functionalities.
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http://dx.doi.org/10.1021/acsami.0c16081DOI Listing
December 2020

Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression.

Int J Mol Med 2021 Jan 11;47(1):137-150. Epub 2020 Nov 11.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

Overproduction of pro‑inflammatory cytokines in the aged, which is called inflammaging, leads to the deterioration of periodontitis. Toll‑like receptor 4 (TLR4) plays a role in the regulation of cellular senescence, and its expression increases with age. However, there has been limited research into the molecular mechanisms underlying the onset of periodontal inflammaging, and the interplay between TLR4 and inflammaging. In the present study, wild‑type and TLR4 gene knockout mice were used to investigate the activation of the TLR4 pathway in mouse periodontitis and the expression of the nucleotide‑binding and oligomerization domain‑like receptor 3 (NLRP3) inflammasome, an upstream immune checkpoint during the development of inflammaging. Activation of TLR4 in a mouse model of periodontitis enhanced the expression of a senescence‑associated secretory phenotype (SASP), which boosted the inflammaging process. Conversely, TLR4 activation downregulated the expression of B cell‑specific Moloney murine leukemia virus integration site 1 (Bmi‑1) and promoted the priming of NLRP3 inflammasome, both of which are regulators of SASP. Treating gingival fibroblasts with Bmi‑1 inhibitor PTC209, it was demonstrated that TLR4 activated the NLRP3 pathway and the inflammaging process by suppressing Bmi‑1. In addition, there was a significant reduction in the expression of Bmi‑1 expression in the gingiva of patients with periodontitis compared with healthy controls. In conclusion, the present study demonstrated that TLR4 acted by inhibiting Bmi‑1 to enhance the NLRP3 pathway and SASP factors. This cascade of reactions may contribute to the senescence of the periodontium.
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http://dx.doi.org/10.3892/ijmm.2020.4787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723510PMC
January 2021

Guidelines for the diagnosis and treatment of osteoarthritis in China (2019 edition).

Ann Transl Med 2020 Oct;8(19):1213

Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Osteoarthritis (OA) is a degenerative disease of middle-aged and elderly people, contributed a higher burden of disease in China and the world. In 2017, under the support of the Rheumatology and Immunology Expert Committee of the Cross-Strait Medical and Health Exchange Association. The objective was to develop an evidence-based diagnosis and treatment guideline for OA in China based on emerging new evidence. The guideline was registered at International Practice Guidelines Registry Platform (IPGRP-2018CN028). The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence and the strength of recommendations, and the RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was followed to report the guideline. The guideline provides recommendations for the OA diagnosis, disease risks monitoring and evaluate, treatment purpose and physical, medical and surgical interventions. This guideline is intended to serve as a tool for Chinese clinicians for the best decisions-making on diagnosis and treatment of OA.
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http://dx.doi.org/10.21037/atm-20-4665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607097PMC
October 2020

Development and formulation of the classification criteria for osteoarthritis.

Ann Transl Med 2020 Sep;8(17):1068

Department of Rheumatology, Peking Union Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Background: The classification criteria of osteoarthritis (OA) is lack of the support of relevant research evidence and there is no standardized protocol for detailed steps of the development or clinical verification of classification criteria has yet been established. This study aims to describe the development process of the Categorization of Osteoarthritis CHecklist (COACH), which is designed to choose the precise treatment option for patients with OA.

Methods: A multidisciplinary panel was established to gather opinions. We conducted questionnaire survey and literature review to generate and COACH Panel members were invited to review the drafted classification criteria and optimize classification criteria. The final list of items was discussed and reached the agreement by the core group of the panel.

Results: Thirty-six experts participated in COACH Panel including rheumatologist (80.6%; 29/36), orthopedist (13.9%; 5/36), methodologist (2.8%; 1/36) and rehabilitation physician (2.8%; 1/36) for classification factors generating and optimizing. The main body of the final classification criteria consists of six types of OA pathogenesis, eight types of medical findings (which can be grouped into two categories), and six types of the location. The final criteria include load-based type, structure-based type, inflammation-based type, metabolic-based type, systemic factor based type and mixed type.

Conclusions: COACH can better help clinicians quickly classify OA patients and help to choose the best treatment option from the aspects of types, findings and locations. What's more, the classification criteria are also helpful to promote the basic medical research and targeted prevention of OA.
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http://dx.doi.org/10.21037/atm-20-4673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575945PMC
September 2020

Four new species of in the clade from northern China.

MycoKeys 2020 8;73:109-132. Epub 2020 Oct 8.

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 3 Park 1, Beichen West Road, Chaoyang District, Beijing 100101, China Chinese Academy of Sciences Beijing China.

The clade of comprises many species, which are associated with a wide variety of substrates. In this study, four new species of , namely , , , and , were encountered from a fruiting body and compost of , soil, and vermicompost. Their colony and mycelial morphology, including features of asexual states, were described. For each species, their DNA sequences were obtained from three loci, the internal transcribed spacer (ITS) regions of the ribosomal DNA, the gene encoding the second largest nuclear RNA polymerase subunit (RPB2), the translation elongation factor 1-α encoding gene (TEF1-α). The analysis combining sequences of the three gene regions distinguished four new species in the clade of . Among them, and clustered with , from which these new species differ in having shorter phialides and smaller conidia. Additionally, differs from in forming phialides with inequilateral to a strongly-curved apex, cultural characteristics, and slow growth on PDA. is closely related to , but it differs from the latter by producing phialides in verticillate whorls and smaller conidia. is the sister species of but is distinguished from by producing shorter and narrower phialides, smaller conidia, and by forming concentric zones on agar plates. This study updates our knowledge of species diversity of .
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http://dx.doi.org/10.3897/mycokeys.73.51424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561617PMC
October 2020

Adsorption Site Selective Occupation Strategy within a Metal-Organic Framework for Highly Efficient Sieving Acetylene from Carbon Dioxide.

Angew Chem Int Ed Engl 2021 Feb 4;60(9):4570-4574. Epub 2021 Jan 4.

State Key Laboratory of Heavy Oil Processing, College of Chemical Engineering, China University of Petroleum (East China), Qingdao, 266580, P. R. China.

The separation of acetylene and carbon dioxide is an essential but challenging process owing to the similar molecular sizes and physical properties of the two gas molecules. Notably, these molecules usually exhibit different orientations in the pore channel. We report an adsorption site selective occupation strategy by taking advantage of differences in orientation to sieve the C H from CO in a judiciously designed amine-functionalized metal-organic framework, termed CPL-1-NH . In this material, the incorporation of amino groups not only occupies the adsorption sites of CO molecules and shields the interaction of uncoordinated oxygen atom and CO molecules resulting in a negligible adsorption amount and a decrease in enthalpy of adsorption but also strengthened the binding affinity toward C H molecules. This material thus shows an extremely high amount of C H at low pressure and a remarkably high C H /CO IAST selectivity (119) at 1 bar and 298 K.
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http://dx.doi.org/10.1002/anie.202013965DOI Listing
February 2021

A new specimen for syphilis diagnosis: Evidence by high loads of Treponema pallidum DNA in saliva.

Clin Infect Dis 2020 Oct 25. Epub 2020 Oct 25.

STD Institute, Shanghai Skin Disease Hospital, Shanghai, P. R. China.

Background: DNA from many pathogens can be detected in saliva. However, the presence and quantity of Treponema pallidum DNA in syphilis patients in saliva is unknown.

Methods: A total of 234 syphilis patients with different stages and 30 volunteers were enrolled. Paired saliva and plasma samples were collected from all the participants. Consecutive saliva samples from 9 patients were collected every 4 hours following treatment. Treponema pallidum DNA in samples was determined by nested PCR and droplet digital PCR targeting polA and Tpp47.

Results: Treponema pallidum DNA detection rates in saliva and plasma were 31.0% (9/29) and 51.7% (15/29) in primary syphilis(p=0.11), 87.5% (63/72) and 61.1% (44/72) in secondary syphilis(p<0.001), 25.6%(21/82) and 8.5%(7/82) in latent syphilis (p=0.004), 21.6%(11/51) and 5.9%(3/51) in symptomatic neurosyphilis (p=0.021), respectively. The loads of Tpp47 and polA in saliva were median 627 copies/ml (range, 0-101200 copies/ml) and median 726 copies/ml (range, 0-117260 copies/ml) for syphilis patients, respectively. In plasma, however, the loads of Tpp47 and polA were very low: median 0 copies/ml (range, 0-149.6 copies/ml) and median 0 copies/ml (range, 0-176 copies/ml), respectively. The loads of Treponema pallidum DNA in saliva during treatment were fluctuating downward, and the clearance time was positively correlated with the loads of Treponema pallidum DNA before treatment.

Conclusions: The collection of saliva is noninvasive and convenient. The high loads of Treponema pallidum DNA in saliva and the reduction after treatment indicated that saliva can be not only a diagnostic fluid for syphilis, but also an indicator of therapeutic effectiveness.
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http://dx.doi.org/10.1093/cid/ciaa1613DOI Listing
October 2020

Deep abiotic weathering of pyrite.

Science 2020 10;370(6515)

Department of Geosciences, The Pennsylvania State University, University Park, PA 16802, USA.

Pyrite is a ubiquitous iron sulfide mineral that is oxidized by trace oxygen. The mineral has been largely absent from global sediments since the rise in oxygen concentration in Earth's early atmosphere. We analyzed weathering in shale, the most common rock exposed at Earth's surface, with chemical and microscopic analysis. By looking across scales from 10 to 10 meters, we determined the factors that control pyrite oxidation. Under the atmosphere today, pyrite oxidation is rate-limited by diffusion of oxygen to the grain surface and regulated by large-scale erosion and clast-scale fracturing. We determined that neither iron- nor sulfur-oxidizing microorganisms control global pyrite weathering fluxes despite their ability to catalyze the reaction. This multiscale picture emphasizes that fracturing and erosion are as important as atmospheric oxygen in limiting pyrite reactivity over Earth's history.
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http://dx.doi.org/10.1126/science.abb8092DOI Listing
October 2020

Metastasis of esophageal squamous cell carcinoma to the thyroid gland with widespread nodal involvement: A case report.

World J Clin Cases 2020 Oct;8(19):4588-4594

Department of Thyroid and Breast Surgery, The Affiliated People's Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China.

Background: Esophageal cancer is one of the most common causes of cancer-related death. Some patients with esophageal cancer have distant metastases at the time of diagnosis, but metastasis to the thyroid gland (MTG) and multifocal thyroid lesions alone are extremely rare.

Case Summary: In this case report, we present a case of a 69-year-old male with esophageal MTG. The patient visited our hospital for a routine body check-up, which revealed multifocal nodules in his thyroid lobes and enlarged cervical lymph nodes. A fine needle aspiration biopsy showed malignancies in both thyroid lesions and lymph nodes. The patient was initially diagnosed with primary bilateral thyroid cancer that spread to his lymph nodes, and a total thyroidectomy was performed. The histology showed MTG and therefore, a diagnostic work-up was implemented to determine the primary tumor. A fluorine-18-deoxyglucose positron emission tomography scan showed that the lower part of the esophagus and the lymph nodes in the neck, chest, and abdomen were involved. An esophagogastroscopy and corresponding pathology revealed distal esophageal squamous cell carcinoma. The esophageal MTG diagnosis was confirmed with pathological immunohistochemistry.

Conclusion: This case report highlights the difficulty in diagnosing esophageal MTG. Patients may have no malignancy history and be asymptomatic. Further diagnostic procedures are necessary after MTG is confirmed by cytology or histology, and the final diagnosis should be made according to the identification of the primary malignancy combined with pathological immunohistochemistry findings.
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http://dx.doi.org/10.12998/wjcc.v8.i19.4588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559652PMC
October 2020

Hypoxia contributes to galectin-3 expression in renal carcinoma cells.

Eur J Pharmacol 2021 Jan 13;890:173637. Epub 2020 Oct 13.

Department of Urology Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China. Electronic address:

Galectin-3 is supposed as a prognostic factor and therapeutic target for many cancers. In a previous study, we have reported that galectin-3 was related to the development of renal cell cancer and served a therapeutic target for renal cell carcinoma (RCC). However, the mechanisms underlying the regulation of galectin-3 in RCC are still not known. In this study, we detected the expression of galectin-3 and hypoxia-inducible factor 1 (HIF-1) α in RCC using immunohistochemistry, and then conducted in vitro experiments to verify the regulation of galectin-3 by hypoxia in RCC. Our results showed that the expression of galectin-3 and HIF-1α were remarkably high in RCC tissues compared with those in the paracancerous tissues. Interestingly, hypoxia significantly promoted cytoplasmic and nuclear HIF-1α and galectin-3 expression in renal carcinoma cell lines, but not in renal tubular epithelial cell (HK-2). Renal carcinoma cell line (Caki-1), but not HK-2 showed significant increase of luciferase reporter activity of galectin-3 encoding the fragment from the site of -845 to +50 upon hypoxic insult. Moreover, HIF-1α overexpression vector promoted, while HIF-1α silencing vector reduced luciferase reporter activity of galectin-3 in Caki-1 and HK-2 cells in both normal and hypoxia conditions. A direct interaction of HIF-1α with Gal-3 promoter was also verified by electrophoretic mobility shift assay and chromatin immunoprecipitation. Together, our data indicated that hypoxia was critical for galectin-3 expression in RCC in a HIF-1α-dependent manner.
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http://dx.doi.org/10.1016/j.ejphar.2020.173637DOI Listing
January 2021

Low-Frequency Repetitive Transcranial Magnetic Stimulation over Right Dorsolateral Prefrontal Cortex in Parkinson's Disease.

Parkinsons Dis 2020 14;2020:7295414. Epub 2020 Sep 14.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic tool for Parkinson's disease (PD), and many stimulation targets have been implicated. We aim to explore whether low-frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) improves motor and nonmotor symptoms of individuals with PD.

Methods: We conducted a randomized, single-blind, sham-controlled parallel trial to compare the effect of 10 consecutive daily sessions of 1 Hz rTMS over right DLPFC on individuals with idiopathic PD between active and sham rTMS group. Primary outcomes were changes in Unified Parkinson's Disease Rating Scale (UPDRS) part III and Nonmotor Symptom Questionnaire (NMSQ). Secondary outcomes were changes in UPDRS total score, Hamilton Rating Scale for Depression (HRSD), Pittsburgh Sleep Quality Index (PSQI), and Montreal Cognitive Assessment (MoCA). Assessments were completed at baseline, after treatment, and at 1 month, 3 months, and 6 months after treatment.

Results: A total of 33 participants with PD were randomized. All participants completed the study and no severe adverse effect was noticed. Compared to baseline, active rTMS showed significant improvements in UPDRS part III and NMSQ at 1 month. Change of scores on UPDRS part III, HRSD, and PSQI persisted for 3 months after rTMS intervention. The beneficial effect on cognitive performance assessed by MoCA was maintained for at least 6 months in the follow-up. No significant changes were observed in the group with sham rTMS.

Conclusions: Low-frequency rTMS of right DLPFC could be a potential selection in managing motor and nonmotor symptoms in PD.
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http://dx.doi.org/10.1155/2020/7295414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509565PMC
September 2020

Deep learning-based lumbosacral reconstruction for difficulty prediction of percutaneous endoscopic transforaminal discectomy at L5/S1 level: A retrospective cohort study.

Int J Surg 2020 Oct 1;82:162-169. Epub 2020 Sep 1.

Department of Orthopaedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Spinal Pain Research Institute, Tongji University School of Medicine, Shanghai, China. Electronic address:

Background: Deep learning has been validated as a promising technique for automatic segmentation and rapid three-dimensional (3D) reconstruction of lumbosacral structures on CT. Simulated foraminoplasty of percutaneous endoscopic transforaminal discectomy (PETD) through the Kambin triangle may benefit viability assessment of PETD at L5/S1 level.

Material And Methods: Medical records and radiographic data of patients with L5/S1 lumbar disc herniation (LDH) who received a single-level PETD from March 2013 to February 2018 were retrospectively collected and analyzed. Deep learning was adopted to achieve semantic segmentation of lumbosacral structures (nerve, bone, disc) on CT, and the segmented masks on reconstructed 3D models. Two observers measured the area of the Kambin triangle on 6 selected deep learning-derived 3D (DL-3D) models and ground truth-derived 3D (GT-3D) models, and intraclass correlation coefficient (ICC) was calculated to assess the test-retest and interobserver reliability. Foraminoplasty of PETD was simulated on L5/S1 lumbosacral 3D models. Patients with extended foraminoplasty or stuck canula occurs on simulations were predicted as PETD-difficult cases (Group A). The remaining patients were regarded as PETD-normal cases (Group B). Clinical information and outcomes were compared between the two groups.

Results: Deep learning-derived 3D models of lumbosacral structures (nerves, bones, and disc) from thin-layer CT were reliable. The area of the Kambin triangle was 161.27 ± 40.10 mm on DL-3D models and 153.57 ± 32.37 mm on GT-3D models (p = 0.206). Reliability test revealed strong test-retest reliability (ICC between 0.947 and 0.971) and interobserver reliability of multiple measurements (ICC between 0.866 and 0.961). The average operation time was 99.62 ± 17.39 min in Group A and 88.93 ± 21.87 min in Group B (P = 0.025). No significant differences in patient-reported outcomes or complications were observed between the two groups (P > 0.05).

Conclusion: Deep learning achieved accurate and rapid segmentations of lumbosacral structures on CT, and deep learning-based 3D reconstructions were efficacious and reliable. Foraminoplasty simulation with deep learning-based lumbosacral reconstructions may benefit surgical difficulty prediction of PETD at L5/S1 level.
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http://dx.doi.org/10.1016/j.ijsu.2020.08.036DOI Listing
October 2020

Bayesian One-Sided Variable Selection.

Multivariate Behav Res 2020 Sep 1:1-15. Epub 2020 Sep 1.

Department of Methodology and Statistics, Tilburg University.

This paper presents a novel Bayesian variable selection approach that accounts for the sign of the regression coefficients based on multivariate one-sided tests. We propose a truncated prior to specify a prior distribution of coefficients with anticipated signs in a given model. Informative priors for the direction of the effects can be incorporated into prior model probabilities. The best subset of variables is selected by comparing the posterior probabilities of the possible models. The new Bayesian one-sided variable selection procedure has higher chance to include relevant variables and therefore select the best model, if the anticipated direction is accurate. For a large number of candidate variables, we present an adaptation of a Bayesian model search method for the one-sided variable selection problem to ensure fast computation. In addition, a fully Bayesian approach is used to adjust the prior inclusion probability of each one-sided model to correct for multiplicity. The performance of the proposed method is investigated using several simulation studies and two real data examples.
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http://dx.doi.org/10.1080/00273171.2020.1813067DOI Listing
September 2020

A hemicyanine-based "turn-on" fluorescent probe for the selective detection of Cu ions and imaging in living cells.

Anal Methods 2020 Sep 25;12(34):4181-4184. Epub 2020 Aug 25.

Henan Engineering Research Center of Industrial Recirculating Water Treatment, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004, P. R. China.

A novel hemicyanine-based fluorescent probe was developed for the fast, selective, and reversible detection of Cu ions with "turn-on" fluorescence response in the aqueous solution. The sensing mode was demonstrated through fluorescence, UV-vis, HRMS, H NMR, and DFT calculations. The probe was successfully used for the imaging of Cu ions in living cells.
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http://dx.doi.org/10.1039/d0ay01461cDOI Listing
September 2020

Cdc13 is predominant over Stn1 and Ten1 in preventing chromosome end fusions.

Elife 2020 08 5;9. Epub 2020 Aug 5.

The State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai, China.

Telomeres define the natural ends of eukaryotic chromosomes and are crucial for chromosomal stability. The budding yeast Cdc13, Stn1 and Ten1 proteins form a heterotrimeric complex, and the inactivation of any of its subunits leads to a uniformly lethal phenotype due to telomere deprotection. Although Cdc13, Stn1 and Ten1 seem to belong to an epistasis group, it remains unclear whether they function differently in telomere protection. Here, we employed the single-linear-chromosome yeast SY14, and surprisingly found that the deletion of leads to telomere erosion and intrachromosome end-to-end fusion, which depends on Rad52 but not Yku. Interestingly, the emergence frequency of survivors in the SY14 Δ mutant was ~29 fold higher than that in either the Δ or Δ mutant, demonstrating a predominant role of Cdc13 in inhibiting telomere fusion. Chromosomal fusion readily occurred in the telomerase-null SY14 strain, further verifying the default role of intact telomeres in inhibiting chromosome fusion.
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http://dx.doi.org/10.7554/eLife.53144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406354PMC
August 2020

Seismic refraction tracks porosity generation and possible CO production at depth under a headwater catchment.

Proc Natl Acad Sci U S A 2020 08 27;117(32):18991-18997. Epub 2020 Jul 27.

Department of Geosciences, Pennsylvania State University, University Park, PA 16802;

In weathered bedrock aquifers, groundwater is stored in pores and fractures that open as rocks are exhumed and minerals interact with meteoric fluids. Little is known about this storage because geochemical and geophysical observations are limited to pits, boreholes, or outcrops or to inferences based on indirect measurements between these sites. We trained a rock physics model to borehole observations in a well-constrained ridge and valley landscape and then interpreted spatial variations in seismic refraction velocities. We discovered that P-wave velocities track where a porosity-generating reaction initiates in shale in three boreholes across the landscape. Specifically, velocities of 2.7 ± 0.2 km/s correspond with growth of porosity from dissolution of chlorite, the most reactive of the abundant minerals in the shale. In addition, sonic velocities are consistent with the presence of gas bubbles beneath the water table under valley and ridge. We attribute this gas largely to CO produced by 1) microbial respiration in soils as meteoric waters recharge into the subsurface and 2) the coupled carbonate dissolution and pyrite oxidation at depth in the rock. Bubbles may nucleate below the water table because waters depressurize as they flow from ridge to valley and because pores have dilated as the deep rock has been exhumed by erosion. Many of these observations are likely to also describe the weathering and flow path patterns in other headwater landscapes. Such combined geophysical and geochemical observations will help constrain models predicting flow, storage, and reaction of groundwater in bedrock systems.
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http://dx.doi.org/10.1073/pnas.2003451117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431088PMC
August 2020

Understanding the marginal distributions and correlations of link travel speeds in road networks.

Sci Rep 2020 07 16;10(1):11821. Epub 2020 Jul 16.

Business School, Sichuan University, Chengdu, 610065, China.

Link travel speeds in road networks are essential data for a variety of research problems in logistics, transportation, and traffic management. Real-world link travel speeds are stochastic, and highly dependent on speeds in previous time periods and neighboring road links. To understand how link travel speeds vary over space and time, we uncover their distributions, their space- and/or time-dependent correlations, as well as partial correlations, based on link travel speed datasets from an urban road network and a freeway network. We find that more than 90% (57%) of travel speeds are normally distributed in the urban road (freeway) network, and that correlations generally decrease with increased distance in time and space. We also investigate if and how different types of road links affect marginal distributions and correlations. The results show that different road link types produce quite similar marginal distributions and correlations. Finally, we study marginal distributions and correlations in a freeway network. Except that the marginal distribution and time correlation are different from the urban road network, others are similar.
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http://dx.doi.org/10.1038/s41598-020-68810-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366716PMC
July 2020

Administration of secretome from human placental stem cell-conditioned media improves recovery of erectile function in the pelvic neurovascular injury model.

J Tissue Eng Regen Med 2020 10 31;14(10):1394-1402. Epub 2020 Jul 31.

Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA.

Human placental stem cells (PSCs) enhance histological and functional recovery in a rodent erectile dysfunction (ED) model. We tested the hypothesis that bioactive factors secreted by PSC (i.e., the secretome) mediate functional recovery and that acellular-conditioned media (CM) from PSC culture (PSC-CM) could be used independently to facilitate functional and histological recovery. To identify factors relative to efficacy of PSC, a comparison of CM from PSC and three additional human stem cell populations was performed. CM from human PSC, amniotic fluid stem cells (AFSCs), adipose-derived stem cells (ADSC), and human umbilical vein endothelial cells (HUVECs) was assayed using a semi-quantitative human cytokine antibody array. Male rats, after surgically created ED by neurovascular injury, were randomly divided into four groups: vehicle control (phosphate-buffered saline [PBS]), PSC, PSC-CM, and serum-free media control (SFM) as control. Functional data on intracorporal and mean arterial pressure were obtained, and histological architecture was examined 6 weeks after single injection. PSCs were found to secrete at least 27 cytokines and growth factors at a significantly higher level than the other three cell types. Either single injection of PSC-CM or PSC significantly improved erectile functional recovery and histological architecture compared with SFM or PBS. Injection of the secretome isolated from human PSC improves erectile functional recovery and histological structure in a rat model of neurovascular injury-induced ED. Further characterization of the unique protein expression within the PSC-CM may help to identify the potential for a novel injectable cell-free therapeutic for applicable patients.
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http://dx.doi.org/10.1002/term.3105DOI Listing
October 2020

Comparative transcriptome analysis of two Cercospora sojina strains reveals differences in virulence under nitrogen starvation stress.

BMC Microbiol 2020 06 16;20(1):166. Epub 2020 Jun 16.

Jiamusi Branch of Heilongjiang Academy of Agricultural Sciences, Jiamusi, China.

Background: Cercospora sojina is a fungal pathogen that causes frogeye leaf spot in soybean-producing regions, leading to severe yield losses worldwide. It exhibits variations in virulence due to race differentiation between strains. However, the candidate virulence-related genes are unknown because the infection process is slow, making it difficult to collect transcriptome samples.

Results: In this study, virulence-related differentially expressed genes (DEGs) were obtained from the highly virulent Race 15 strain and mildly virulent Race1 strain under nitrogen starvation stress, which mimics the physiology of the pathogen during infection. Weighted gene co-expression network analysis (WGCNA) was then used to find co-expressed gene modules and assess the relationship between gene networks and phenotypes. Upon comparison of the transcriptomic differences in virulence between the strains, a total of 378 and 124 DEGs were upregulated, while 294 and 220 were downregulated in Race 1 and Race 15, respectively. Annotation of these DEGs revealed that many were associated with virulence differences, including scytalone dehydratase, 1,3,8-trihydroxynaphthalene reductase, and β-1,3-glucanase. In addition, two modules highly correlated with the highly virulent strain Race 15 and 36 virulence-related DEGs were found to contain mostly β-1,4-glucanase, β-1,4-xylanas, and cellobiose dehydrogenase.

Conclusions: These important nitrogen starvation-responsive DEGs are frequently involved in the synthesis of melanin, polyphosphate storage in the vacuole, lignocellulose degradation, and cellulose degradation during fungal development and differentiation. Transcriptome analysis indicated unique gene expression patterns, providing further insight into pathogenesis.
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http://dx.doi.org/10.1186/s12866-020-01853-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298872PMC
June 2020

Virological investigation of genetic variation of enterovirus type 71 in hand, foot and mouth disease.

Exp Ther Med 2020 Jul 7;20(1):543-549. Epub 2020 May 7.

Department of Laboratory, Kunming Yanan Hospital, Kunming, Yunnan 650051, P.R. China.

The aim of the present study was to analyze the sequence of the VP1 gene in enterovirus 71 (EV71) isolates and to explore their genetic evolution, so as to provide a scientific basis for the clinical prevention and treatment of hand, foot and mouth disease. The fecal samples of 590 patients with suspected hand, foot and mouth disease treated at Yan'an Hospital (Kunming, China) between January 2015 and December 2016 were collected and EV71 nucleic acid was detected by fluorescence PCR. The viral RNA of EV71-positive samples was extracted, the VP1 gene was amplified by PCR and the products were sequenced. The VP1 gene sequence was analyzed using DNAMAN and MEGA (version 4.0) software and homologous modeling was performed using Pymol software. A total of 50 EV71-positive samples were identified and the detection rate was 8.47% (50/590 cases). All of the 50 EV71 strains were of the C4 subtype. The genetic distance between the strains detected in the present study and EV71 strains detected in Beijing, Anhui and Malaysia was 0.01-0.03, while that between the strains detected in the present study and Australian strains was 2.11. Homologous modeling indicated that the amino acid sequence of the VP1 gene of the detected strains had a H144Y mutation. There was no significant genetic variation in the EV71 strain within the 2-year period. In conclusion, the EV71 strains detected in the present study was similar to that detected in Beijing, Anhui and Malaysia but different to that from Australia. A point mutation was present in the amino acid sequence of the VP1 gene.
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http://dx.doi.org/10.3892/etm.2020.8728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281934PMC
July 2020

Polyporus Polysaccharide Ameliorates Bleomycin-Induced Pulmonary Fibrosis by Suppressing Myofibroblast Differentiation TGF-β/Smad2/3 Pathway.

Front Pharmacol 2020 26;11:767. Epub 2020 May 26.

Division of Rheumatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Pulmonary fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc) with no effective medication. Polyporus polysaccharide (PPS), extracted from Chinese herbs, has immune regulation, anticancer, antioxidant and antiinflammatory activities. This study aims to investigate antifibrotic effects of PPS. We show that PPS markedly ameliorates bleomycin-induced lung fibrosis in mice. Myofibroblasts are the effector cells responsible for excessive deposition of extracellular matrix (ECM) proteins in fibrotic diseases. evidence reveals that PPS exerts potent antifibrotic effects by inhibiting fibroblast-to-myofibroblast transition, suppressing ECM deposition, and repressing lung fibroblast proliferation and migration. We also find that PPS inhibits TGF-β1-induced Smad2/3 activating. This study is the first to demonstrate an antifibrotic role of PPS in lungs, thus warranting further therapeutic evaluation.
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http://dx.doi.org/10.3389/fphar.2020.00767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264095PMC
May 2020

Application of Transition-Metal Catalysis, Biocatalysis, and Flow Chemistry as State-of-the-Art Technologies in the Synthesis of LCZ696.

J Org Chem 2020 06 15;85(11):6844-6853. Epub 2020 May 15.

Chemical & Analytical Development, Novartis Pharma AG, 4056 Basel, Switzerland.

LCZ696 is a novel treatment for patients suffering from heart failure that combines the two active pharmaceutical ingredients sacubitril and valsartan in a single chemical compound. While valsartan is an established drug substance, a new manufacturing process suitable for large-scale commercial production had to be developed for sacubitril. The use of chemocatalysis, biocatalysis, and flow chemistry as state-of-the-art technologies allowed to efficiently build up the structure of sacubitril and achieve the defined performance targets.
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http://dx.doi.org/10.1021/acs.joc.0c00473DOI Listing
June 2020

Is selective nerve root block necessary for learning percutaneous endoscopic lumbar discectomy: a comparative study using a cumulative summation test for learning curve.

Int Orthop 2020 07 4;44(7):1367-1374. Epub 2020 May 4.

Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, People's Republic of China.

Purpose: The aim of this study was to investigate the effect of lumbar spine selective nerve root block (SNRB) experience on the learning efficiency of percutaneous endoscopic lumbar discectomy (PELD) for junior trainees.

Methods: A total of 480 patients undergoing single-level PELD performed by eight junior trainees were included. The trainees were divided into two groups based on whether they had previous SNRB experience (group A, yes; group B, no). Surgical proficiency was defined as total operation time less than 65 minutes and cumulative radiation exposure time no more than 40 seconds. The learning curve was analyzed by cumulative summation (CUSUM) test. Clinical evaluations included Macnab classification, visual analog scale (VAS)-low back score, VAS-leg score, and Oswestry Disability Index (ODI). Follow-up information at 12 months was also obtained.

Results: Integral number of cases before achieving an acceptable surgical level in group A (47.75 ± 2.50 cases) was significantly smaller than that in group B (56.50 ± 1.29 cases, p < 0.05), along with less accumulated failure (18.75 ± 0.96 cases vs. 25.50 ± 1.75 cases, p < 0.05). The two groups were comparable in clinical outcomes. Forty-seven cases of complications were observed, with 17 in group A and 30 in group B (p < 0.05).

Conclusion: Previous experience of SNRB improved the performance of PELD with shorter operation time and less radiation exposure. SNRB practice may reduce the complication rate without a significant effect on the recurrence of symptoms and reoperation.
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http://dx.doi.org/10.1007/s00264-020-04558-1DOI Listing
July 2020

Mandarin lexical tone recognition in bimodal cochlear implant users.

Int J Audiol 2020 07 17;59(7):548-555. Epub 2020 Apr 17.

Beijing Tongren Hospital, Beijing Institute of Otolaryngology, Capital Medical University, Beijing, China.

To assess the recognition of lexical tones in Mandarin-speaking bimodal cochlear implant (CI) subjects. Lexical tone recognition in quiet and noise (SNR= +5 dB) was measured with electric stimulation (CI alone) or bimodal stimulation (CI + hearing aid (HA)). The recognition and confusion rates of the four tones (T1, T2, T3 and T4) were analysed. Spearman correlation analysis was performed to examine the relationship between hearing levels in the contralateral ear and bimodal benefits. Twenty native Mandarin-speaking bimodal CI users, with ages ranging from 16-49 years. Relative to the CI alone, mean tone recognition with the CI + HA improved significantly from 84.1-92.1% correct in quiet (+8 points) and from 57.9-73.1% correct in noise (+15.2 points). Tone confusions between T2 and T3 were the most prominent in all test conditions, and T4 tended to be labelled as T3 in noise. There was no significant correlation between the bimodal benefits for tone recognition and the unaided or HA-aided pure-tone thresholds at 0.25 kHz. Listeners with CI + HA exhibited significantly better tone recognition than with CI alone. The bimodal advantage for tone recognition was greater in noise than in quiet, perhaps due to a ceiling effect in quiet.
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http://dx.doi.org/10.1080/14992027.2020.1719437DOI Listing
July 2020