Publications by authors named "Xiaohua Li"

499 Publications

Deciphering the Formulation Secret Underlying Chinese Huo-Clearing Herbal Drink.

Front Pharmacol 2021 22;12:654699. Epub 2021 Apr 22.

Laboratory of Drug Discovery and Molecular Engineering, Department of Medicinal Plants, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, China.

Herbal teas or herbal drinks are traditional beverages that are prevalent in many cultures around the world. In Traditional Chinese Medicine, an herbal drink infused with different types of medicinal plants is believed to reduce the 'Shang Huo', or excessive body heat, a status of sub-optimal health. Although it is widely accepted and has a very large market, the underlying science for herbal drinks remains elusive. By studying a group of herbs for drinks, including 'Gan' ( Fisch. Ex DC.), 'Ju' ( (Ramat.) Tzvelev), 'Bu' ( L.), 'Jin' ( Thunb.), 'Xia' ( L.), and 'Ji' ( L.), the long-term jargon is connected with the inflammation of modern immunology through a few pro-inflammatory markers. studies have indicated that cellular inflammation is lowered by Ju and Jin either individually or synergistically with Gan. Among all herbs, only Gan detoxicated cellular toxicity of Bu in a dose dependent manner. The synergistic formulation of Ju and Gan, or Jin and Gan, in a reduction of Shang Huo, was tested . Both combinations exhibited a lower percentage of neutrophils, monocytes, and CD4/CD8 ratio in the blood, as well as inflammatory cytokines. Furthermore, body weight in the combinatory groups was more stable than treatments using single herbs. The combination of old traditional oriental methods with Western science logistics, has resulted in the formulation of different herbs into one concoction for the use of detoxification and synergism.
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http://dx.doi.org/10.3389/fphar.2021.654699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100228PMC
April 2021

The Positive Effect of ZnS in Waste Tire Carbon as Anode for Lithium-Ion Batteries.

Materials (Basel) 2021 Apr 24;14(9). Epub 2021 Apr 24.

Centre for Clean Environment and Energy, Gold Coast Campus, Griffith University, Gold Coast, QLD 4222, Australia.

There is great demand for high-performance, low-cost electrode materials for anodes of lithium-ion batteries (LIBs). Herein, we report the recovery of carbon materials by treating waste tire rubber via a facile one-step carbonization process. Electrochemical studies revealed that the waste tire carbon anode had a higher reversible capacity than that of commercial graphite and shows the positive effect of ZnS in the waste tire carbon. When used as the anode for LIBs, waste tire carbon shows a high specific capacity of 510.6 mAh·g at 100 mA·g with almost 97% capacity retention after 100 cycles. Even at a high rate of 1 A·g, the carbon electrode presents an excellent cyclic capability of 255.1 mAh·g after 3000 cycles. This high-performance carbon material has many potential applications in LIBs and provide an alternative avenue for the recycling of waste tires.
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http://dx.doi.org/10.3390/ma14092178DOI Listing
April 2021

Downregulation of miR‑106b‑3p increases sensitivity to cisplatin in esophageal cancer cells by targeting TGM3.

Mol Med Rep 2021 Jun 26;23(6). Epub 2021 Apr 26.

Radiation Therapy Department, Baoji Central Hospital, Baoji, Shaanxi 721008, P.R. China.

Esophageal cancer (EC) is one of the most malignant and lethal digestive‑related tumors worldwide. However, acquired drug resistance is a major obstacle concerning anticancer chemotherapy. An increasing number of studies have reported that microRNAs (miRNAs/miRs) are implicated in regulating the sensitivity of drug resistance in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the role of miR‑106b‑3p in the sensitivity of cisplatin for ESCC. Initially, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to analyze miR‑106b‑3p and protein‑glutamine γ‑glutamyltransferase E (TGM3) expression levels in ESCC and non‑tumor adjacent tissues. By using bioinformatics software TargetScan, TGM3 was predicted to be a potential downstream target of miR‑106‑3p. Following verification that TGM3 was a downstream target of miR‑106b‑3p by the dual‑luciferase reporter assay, the effects of miR‑106b‑3p transfection on KYSE30 cell viability and apoptosis following treatment with cisplatin were confirmed using Cell Counting Kit‑8 and flow cytometry assays, respectively. The results revealed that miR‑106b‑3p levels were upregulated, whereas TMG3 levels were downregulated in ESCC tissues. Dual‑luciferase reporter assays confirmed that miR‑106b‑3p negatively regulated TGM3 expression by binding to its 3'UTR sequence. It was also shown that inhibition of miR‑106b‑3p could enhance the anti‑proliferative effects, while promoting the apoptotic effects of cisplatin in the KYSE30 cell line by targeting TGM3. In conclusion, the present study demonstrated that downregulation of miR‑106b‑3p may increase the sensitivity of KYSE30 cell to cisplatin by targeting TGM3.
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http://dx.doi.org/10.3892/mmr.2021.12110DOI Listing
June 2021

A tumor-targeted near-infrared fluorescent probe for HNO and its application to the real-time monitoring of HNO release .

Chem Commun (Camb) 2021 Apr 22. Epub 2021 Apr 22.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. and University of Chinese Academy of Sciences, Beijing 100049, China.

Nitroxyl (HNO) is a promising regulator for cancer therapy. Here, we develop a tumor-targeted near-infrared fluorescent probe for HNO and utilize it in the real-time imaging of HNO release in vivo.
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http://dx.doi.org/10.1039/d1cc01462eDOI Listing
April 2021

Comparison of Clinical Features and Outcomes of Medically Attended COVID-19 and Influenza Patients in a Defined Population in the 2020 Respiratory Virus Season.

Front Public Health 2021 23;9:587425. Epub 2021 Mar 23.

Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), which is causing the coronavirus disease-2019 (COVID-19) pandemic, poses a global health threat. However, it is easy to confuse COVID-19 with seasonal influenza in preliminary clinical diagnosis. In this study, the differences between influenza and COVID-19 in epidemiological features, clinical manifestations, comorbidities and pathogen biology were comprehensively compared and analyzed. SARS-CoV-2 causes a higher proportion of pneumonia (90.67 vs. 17.07%) and acute respiratory distress syndrome (12.00 vs. 0%) than influenza A virus. The proportion of leukopenia for influenza patients was 31.71% compared with 12.00% for COVID-19 patients ( = 0.0096). The creatinine and creatine kinase were significantly elevated when there were COVID-19 patients. The basic reproductive number (R) for SARS-CoV-2 is 2.38 compared with 1.28 for seasonal influenza A virus. The mutation rate of SARS-CoV-2 ranges from 1.12 × 10 to 6.25 × 10, while seasonal influenza virus has a lower evolutionary rate (0.60-2.00 × 10). Overall, this study compared the clinical features and outcomes of medically attended COVID-19 and influenza patients. In addition, the S477N and N439K mutations on spike may affect the affinity with receptor ACE2. This study will contribute to COVID-19 control and epidemic surveillance in the future.
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http://dx.doi.org/10.3389/fpubh.2021.587425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021703PMC
April 2021

Circ_GRN Promotes the Proliferation, Migration, and Inflammation of Vascular Smooth Muscle Cells in Atherosclerosis Through miR-214-3p/FOXO1 Axis.

J Cardiovasc Pharmacol 2021 Apr;77(4):470-479

Department of Cardiovasology, Foshan Chancheng Central Hospital, Foshan City, China.

Abstract: Dysfunction of vascular smooth muscle cells (VSMCs) assumes a fundamental part in the pathogenesis of atherosclerosis (AS). Circular RNA granulin precursor (circ_GRN) was identified to promote the proliferation and invasion of human VSMCs (HVSMCs) in an in vitro AS model. However, the underlying mechanisms remain unclear. Levels of circ_GRN, microRNA (miR)-214-3p, and forkhead box protein O1 (FOXO1) were detected using quantitative real-time polymerase chain reaction and Western blot assays. The proliferation, migration, and inflammatory response of HVSMCs were evaluated by using flow cytometry, colony formation, Cell Counting Kit-8, Western blot, transwell assays, and enzyme-linked immunosorbent assay, respectively. The binding interaction between miR-214-3p and circ_GRN or FOXO1 was detected by dual-luciferase reporter assay. In this study, we found that circ_GRN was elevated in the serum of AS and oxidized low-density lipoprotein (ox-LDL)-induced HVSMCs. The in vitro AS model was established by exposing HVSMCs to ox-LDL, and we found circ_GRN knockdown reversed ox-LDL-evoked cell proliferation, migration, and inflammation. In a mechanical study, miR-214-3p directly bound to circ_GRN or FOXO1, and circ_GRN could regulate FOXO1 expression by competitively binding to miR-214-3p. Importantly, we demonstrated that miR-214-3p inhibition attenuated the protective effects of circ_GRN knockdown on ox-LDL-induced HVSMCs; besides that, miR-214-3p overexpression abolished ox-LDL-triggered HVSMC proliferation, migration, and inflammation, which were counteracted by FOXO1 upregulation. In conclusion, circ_GRN promoted the proliferation, migration, and inflammation of HVSMCs through miR-214-3p/FOXO1 axis in ox-LDL-induced AS model in vitro, suggesting the potential involvement in an AS process, which provided a potential candidate for future clinic intervention in AS.
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http://dx.doi.org/10.1097/FJC.0000000000000982DOI Listing
April 2021

Suspended MoS Photodetector Using Patterned Sapphire Substrate.

Small 2021 Apr 4:e2100246. Epub 2021 Apr 4.

Joint Key Laboratory of Ministry of Education, Institute of Applied Physics and Materials Engineering, University of Macau, Taipa, Macau, 999078, China.

The introduction of patterned sapphire substrates (PSS) has been regarded as an effective method to improve the photoelectric performance of 2D layered materials in recent years. Molybdenum disulfide (MoS ), an intriguing transition metal 2D materials with splendid photoresponse owing to a direct-indirect bandgap transition at monolayer, shows promising optoelectronics applications. Here, a large-scale, continuous multilayer MoS film is prepared on a SiO /Si substrate and transferred to flat sapphire substrate and PSS, respectively. An enhanced dynamic distribution of local electric field and concentrated photon excitons across the interface between MoS and patterned sapphire substrates are revealed by the finite-difference time-domain simulation. The photoelectric performance of the MoS /PSS photodetector is improved under the three lasers of 365, 460, and 660 nm. Under the 365 nm laser, the photocurrent increased by 3 times, noise equivalent power (NEP) decreases to 1.77 × 10 W/Hz and specific detectivity (D*) increases to 1.2 × 10 Jones. Meanwhile, the responsivity is increased by 7 times at 460 nm, and the response time of the MoS /PSS photodetector is also shortened under three wavelengths. The work demonstrates an effective method for enhancing the optical properties of photodetectors and enabling simultaneous detection of broad-spectrum emissions.
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http://dx.doi.org/10.1002/smll.202100246DOI Listing
April 2021

Improving the Accuracy of Diabetes Diagnosis Applications through a Hybrid Feature Selection Algorithm.

Neural Process Lett 2021 Mar 27:1-17. Epub 2021 Mar 27.

Department of Computer Engineering, Islamshahr Branch, Islamic Azad University, Islamshahr, Iran.

Artificial intelligence is a future and valuable tool for early disease recognition and support in patient condition monitoring. It can increase the reliability of the cure and decision making by developing useful systems and algorithms. Healthcare workers, especially nurses and physicians, are overworked due to a massive and unexpected increase in the number of patients during the coronavirus pandemic. In such situations, artificial intelligence techniques could be used to diagnose a patient with life-threatening illnesses. In particular, diseases that increase the risk of hospitalization and death in coronavirus patients, such as high blood pressure, heart disease and diabetes, should be diagnosed at an early stage. This article focuses on diagnosing a diabetic patient through data mining techniques. If we are able to diagnose diabetes in the early stages of the disease, we can force patients to stay home and care for their health, so the risk of being infected with the coronavirus would be reduced. The proposed method has three steps: preprocessing, feature selection and classification. Several combinations of Harmony search algorithm, genetic algorithm, and particle swarm optimization algorithm are examined with K-means for feature selection. The combinations have not examined before for diabetes diagnosis applications. K-nearest neighbor is used for classification of the diabetes dataset. Sensitivity, specificity, and accuracy have been measured to evaluate the results. The results achieved indicate that the proposed method with an accuracy of 91.65% outperformed the results of the earlier methods examined in this article.
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http://dx.doi.org/10.1007/s11063-021-10491-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997791PMC
March 2021

Holographic Recording Performance of Acrylate-Based Photopolymer under Different Preparation Conditions for Waveguide Display.

Polymers (Basel) 2021 Mar 18;13(6). Epub 2021 Mar 18.

Joint International Research Laboratory of Information Display and Visualization, School of Electronics and Engineering, Southeast University, Nanjing 210018, China.

This work proposes a green light-sensitive acrylate-based photopolymer. The effects of the preparation conditions for the waveguide applied volume holographic gratings (VHGs) were experimentally investigated. The optimum preparation conditions for holographic recording were revealed. After optimization, the peak of VHG diffraction efficiency reached 99%, the diffractive wavelength bandwidth increased from 13 nm to 22 nm, and the corresponding RIM was 0.06. To prove the wide application prospect of the acrylate-based photopolymer in head-mounted augmented reality (AR) displays, green monochromatic volume holographic waveguides were fabricated. The display results showed that the prototype was able to achieve a 28° diagonal FOV and possessed a system luminance of 300 cd/m.
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http://dx.doi.org/10.3390/polym13060936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078166PMC
March 2021

Flexible Carbon Nanotubes Confined Yolk-Shelled Silicon-Based Anode with Superior Conductivity for Lithium Storage.

Nanomaterials (Basel) 2021 Mar 11;11(3). Epub 2021 Mar 11.

Key Laboratory of Materials Physics, and Anhui Key Laboratory of Nanomaterials and Nanotechnology, Institute of Solid State Physics, Chinese Academy of Sciences, Hefei 230031, China.

The further deployment of silicon-based anode materials is hindered by their poor rate and cycling abilities due to the inferior electrical conductivity and large volumetric changes. Herein, we report a silicon/carbon nanotube (Si/CNT) composite made of an externally grown flexible carbon nanotube (CNT) network to confine inner multiple Silicon (Si) nanoparticles (Si NPs). The in situ generated outer CNTs networks, not only accommodate the large volume changes of inside Si NPs but also to provide fast electronic/ionic diffusion pathways, resulting in a significantly improved cycling stability and rate performance. This Si/CNT composite demonstrated outstanding cycling performance, with 912.8 mAh g maintained after 100 cycles at 100 mA g, and excellent rate ability of 650 mAh g at 1 A g after 1000 cycles. Furthermore, the facial and scalable preparation method created in this work will make this new Si-based anode material promising for practical application in the next generation Li-ion batteries.
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http://dx.doi.org/10.3390/nano11030699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001621PMC
March 2021

High-Performance MoS Photodetectors Prepared Using a Patterned Gallium Nitride Substrate.

ACS Appl Mater Interfaces 2021 Apr 23;13(13):15820-15826. Epub 2021 Mar 23.

College of Materials Science and Engineering, College of Electronics and Information Engineering, Guangdong Research Center for Interfacial Engineering of Functional Materials, Shenzhen University, 3688 Nanhai Avenue, Shenzhen 518060, People Republic of China.

Strain-adjusting the band gap of MoS using patterned substrates to improve the photoelectric performance of MoS has gradually become a research hotspot in recent years. However, there are still difficulties in obtaining high-quality two-dimensional materials and preparing photodetectors on patterned substrates. To overcome this, a continuous multilayer MoS film was transferred to a patterned gallium nitride substrate (PGS) for the fabrication of photodetectors, and density functional theory calculations showed that the band gap of the MoS film increased and that the electron effective mass decreased due to the introduction of PGS. In addition, finite difference time domain simulation showed that the electric field in the MoS area on the PGS is enhanced compared with that on the flat gallium nitride substrate due to the enhanced light scattering effect of the PGS. The photoresponse of the MoS/PGS photodetector at 460 nm was also enhanced, with increasing by 5 times, increasing by 2 times, NEP decreasing to 3.88 × 10 W/Hz, and increasing to 5.6 × 10 Jones. Our research has important guiding significance in adjusting the band gap of MoS and enhancing the photoelectric performance of MoS photodetectors.
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http://dx.doi.org/10.1021/acsami.0c22799DOI Listing
April 2021

Comparative evaluation of cardiovascular risks among nine FDA-approved VEGFR-TKIs in patients with solid tumors: a Bayesian network analysis of randomized controlled trials.

J Cancer Res Clin Oncol 2021 Mar 16. Epub 2021 Mar 16.

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Sichuan, China.

Purpose: The present meta-analysis study was performed to identify the potential cardiotoxicity risks when using Vascular Endothelial Growth Factor Receptor Tyrosine kinase inhibitors (VEGFR-TKIs) as anticancer drugs in patients with solid tumors.

Methods: Pubmed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for the randomized controlled trials. We have included 45 randomized controlled trials (RCTs) associated with nine VEGFR-TKIs Food and Drug Administration (FDA)-approved drugs used to treat patients with solid tumors. To evaluate the trials' risk of bias, Cochrane Risk of Bias Tool was assessed. A direct comparison was assessed by RevMan5.3 software, calculating the odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was tested by the I statistic and Chi-square test for P value. Bayesian network meta-analysis was performed using Stata 15.0 and GeMTC 0.14.3 software, calculated OR along with corresponding 95% credible interval (CrI). The model's convergence was evaluated by the potential scale reduced factor (PSRF). Consistency between direct and indirect comparisons was assessed by the "node-splitting" method.

Results: In this network meta-analysis, a total of 20,027 patients from 45 randomized controlled trials and associated with nine FDA-approved VEGFR-TKIs (axitinib, cabozantinib, lenvatinib, nintedanib, pazopanib, regorafenib, sorafenib, sunitinib, vandetanib), were enrolled. Findings indicated that lenvatinib had the most significant probability of provoking all grades cardiovascular incident and hypertension, followed by vandetanib, cabozantinib, axitinib, pazopanib, sorafenib, sunitinib, regorafenib and nintedanib. The nine agent's severe cardiovascular and severe hypertension risk was probably similar. The ranking probability of cardiac toxicity shows that vandetanib ranked most likely to have the highest risk for cardiotoxicity among all the VEGFR-TKIs reviewed, followed by pazopanib, axitinib, sorafenib, sunitinib. In contrast, regorafenib and nintedanib did not exhibit an increased risk of cardiac damage.

Conclusions: The association between the nine VEGFR-TKIs with potential cardiotoxicity occurrence was reviewed. Both the regorafenib and nintedanib did not display detectable signs of cardiotoxic damage. In contrast, lenvatinib and vandetanib are ranked to have the most severe cardiotoxicity side impacts. These results may provide information for clinical practice guidelines, implementing strategies in selecting the adequate VEGFR-TKIs, and understanding the cardiovascular toxicity inflicted by the VEGFR-TKIs.

Prospero Identifier: CRD 42,020,167,307.
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http://dx.doi.org/10.1007/s00432-021-03521-wDOI Listing
March 2021

Oxidative Dissolution of Metals in Organic Solvents.

Chem Rev 2021 Apr 16;121(8):4506-4530. Epub 2021 Mar 16.

KU Leuven, Department of Chemistry, Celestijnenlaan 200F, P.O. Box 2404, B-3001 Leuven, Belgium.

Dissolution of metals in organic solvents is relevant to various application fields, such as metal extraction from ores or secondary resources, surface etching or polishing of metals, direct synthesis of organometallic compounds, and separation of metals from other compounds. Organic solvents for dissolution of metals can offer a solution when aqueous systems fail, such as separation of metals from metal oxides, because both the metal and metal oxide could codissolve in aqueous acidic solutions. This review critically discusses organic media (conventional molecular organic solvents, ionic liquids, deep-eutectic solvents and supercritical carbon dioxide) for oxidative dissolution of metals in different application areas. The reaction mechanisms of dissolution processes are discussed for various lixiviant systems which generally consist of oxidizing agents, chelating agents, and solvents. Different oxidizing agents for dissolution of metals are reviewed such as halogens, halogenated organics, donor-acceptor electron-transfer systems, polyhalide ionic liquids, and others. Both chemical and electrochemical processes are included. The review can guide researchers to develop more efficient, economic, and environmentally friendly processes for dissolution of metals in their elemental state.
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http://dx.doi.org/10.1021/acs.chemrev.0c00917DOI Listing
April 2021

Synthesis of 4-Alkylindoles from 2-Alkynylanilines via Dearomatization- and Aromatization-Triggered Alkyl Migration.

Org Lett 2021 Mar 10;23(6):2130-2134. Epub 2021 Mar 10.

Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, China.

A simple method for rapid synthesis of 4-alkylindoles from 2-alkynylanilines was reported. The protocol involves an oxidative dearomatization and an aromatization triggered regioselective alkyl migration. A range of alkyl groups including linear, branched, or cycloalkyl groups can be introduced into the C4 position of indole.
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http://dx.doi.org/10.1021/acs.orglett.1c00280DOI Listing
March 2021

Laparoscopic versus open surgery in the treatment of hepatic hemangioma: A meta-analysis.

Authors:
He Jien Li Xiaohua

Medicine (Baltimore) 2021 Feb;100(8):e24155

Department of Radiotherapy, Baoji Central Hospital, China.

Background: The aim of this study was to systematically evaluate and compare the effectiveness and safety of laparoscopic versus open resection (LR vs OR) in the treatment of hepatic hemangioma.

Methods: We searched PubMed, the Cochrane Library, Web of Science, Medline, EMBASE, and the Chinese Biomedicine Database from January 2000 to April 2020 for studies comparing the outcomes of laparoscopic versus open surgery in hepatic hemangioma treatment.

Results: Based on the preset criteria, 12 randomized clinical trials (RCTs) and 12 observational clinical studies (OCSs) were selected for analysis. Our results showed that laparoscopic surgery was more effective than open surgery in terms of reducing operation time, intraoperative blood loss, postoperative exhaust time, postoperative complications, postoperative bile leak, postoperative intra-abdominal infection, postoperative alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values, postoperative visual analog scale (VAS) scores, and hospitalize length. No significant differences were found between the 2 groups in hepatectomy time, hospitalized cost, intra-abdominal hemorrhage, and the postoperative recurrence of hemangioma.

Conclusion: While similar therapeutic effect was achieved by the compared herein surgical methods, the findings of our analysis revealed that laparoscopic surgery is superior over open surgery in terms of less trauma, faster recovery, less postoperative pain, shorter hospitalize length, and reduced postoperative complications. Therefore, laparoscopic resection of hepatic hemangioma is a safe, effective, and feasible surgical method that is worth considering in clinical applications.
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http://dx.doi.org/10.1097/MD.0000000000024155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909164PMC
February 2021

Glutathione Peroxidase Is Essential for Oxidative Stress Resistance and Efficient Nodulation.

Front Microbiol 2021 9;12:627562. Epub 2021 Feb 9.

Hubei Provincial Engineering and Technology Research Center for Resources and Utilization of Microbiology, College of Life Sciences, South-Central University for Nationalities, Wuhan, China.

Glutathione (GSH) plays a key role in regulating the cellular Redox Homeostasis, and appears to be essential for initiation and development of root nodules. Glutathione peroxidase (Gpx) catalyzes the reduction of HO and organic hydroperoxides by oxidation of GSH to oxidized GSH (GSSG), which in turn is reduced by glutathione reductase (GR). However, it has not been determined whether the Gpx or GR is required during symbiotic interactions with pea. To characterize the role of glutathione-dependent enzymes in the symbiotic process, single and double mutants were made in (encoding glutathione peroxidase) and (encoding glutathione reductase) genes. All the mutations did not affect the rhizobial growth, but they increased the sensitivity of strains to HO. Mutant in GpxA had no effect on intracellular GSH levels, but can increase the expression of the catalase genes. The mutant can induce the formation of normal nodules, while the single and double mutants exhibited a nodulation phenotype coupled to more than 50% reduction in the nitrogen fixation capacity, these defects in nodulation were characterized by the formation of ineffective nodules. In addition, the and double mutant was severely impaired in rhizosphere colonization and competition. Quantitative proteomics using the TMT labeling method was applied to study the differential expression of proteins in bacteroids isolated from pea root nodules. A total of 27 differentially expressed proteins were identified in these root bacteroids including twenty down-regulated and seven up-regulated proteins. By sorting the down-regulated proteins, eight are transporter proteins, seven are dehydrogenase, deoxygenase, oxidase, and hydrolase. Moreover, three down-regulating proteins are directly involved in nodule process.
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http://dx.doi.org/10.3389/fmicb.2021.627562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900000PMC
February 2021

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas.

Cancer Biol Med 2021 Feb;18(1):283-297

State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Medical University of PLA, Xi'an 710032, China.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.

Methods: A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m.

Results: Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069-1.430; and HR: 1.600, 95% CI: 1.350-1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054-1.434; and HR: 1.658, 95% CI: 1.389-1.979, respectively). Patients with both NLR ≥ 3 and underweight ( neither) had much worse OS (HR: 2.445, 95% CI: 1.853-3.225) and RFS (HR: 2.405, 95% CI: 1.802-3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy.

Conclusions: Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877168PMC
February 2021

Water-Soluble Near-Infrared Fluorescent Probes for Specific Detection of Monoamine Oxidase A in Living Biosystems.

Anal Chem 2021 03 23;93(9):4285-4290. Epub 2021 Feb 23.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

Monoamine oxidase (MAO) has two isomers (A and B), and the analysis of each one in biological samples is of great potential in studying MAO-related diseases. However, specific detection and imaging of MAO-A in cells and are still a great challenge at present due to the relative lack of suitable near-infrared (NIR) fluorescent probes. In this work, two new NIR fluorescent probes, Rma-1 and Rma-2, have been developed for the analysis of MAO-A in living biosystems. The probes were designed by conjugating the specific structure of the MAO-A inhibitor to hemicyanine (an NIR fluorophore) directly or through a self-immolative linker. Both probes are water-soluble and showed selective and sensitive NIR (708 nm) responses toward MAO-A rather than MAO-B, of which probe Rma-1 with a self-immolative linker exhibited superior analytical performance with a detection limit of 4.5 ng/mL and 13-fold specificity for MAO-A over MAO-B. Further, probe Rma-1 has been successfully utilized to image the MAO-A activity in cells, zebrafish, and tumor-bearing mice, showing a promising prospect for MAO-A study in carcinoma.
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http://dx.doi.org/10.1021/acs.analchem.0c05283DOI Listing
March 2021

Phytoexclusion of heavy metals using low heavy metal accumulating cultivars: A green technology.

J Hazard Mater 2021 Jul 13;413:125427. Epub 2021 Feb 13.

Key Laboratory of Land Surface Pattern and Simulation, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101, China.

Heavy metal (HM) pollution of farmland is a serious problem worldwide and consumption of HM-contaminated food products poses significant public health risks. Phytoexclusion using low HM accumulating cultivars (LACs) is a promising and practical technology to mitigate the risk of HM contamination of agricultural products grown in polluted soils, and does not alter cultivation practices, is easy to apply, and is economical. This review provides an overview of the major scientific advances accomplished in the field of LACs worldwide. The LACs concept and identification criteria are presented, and the known LACs among currently cultivated grain crops and vegetables are re-evaluated. The low HM accumulation by LACs is affected by crop ecophysiological features and soil physicochemical characteristics. Taking low Cd accumulating cultivars as an example, it is known that they can efficiently exclude Cd from entering their edible parts in three ways: 1) decrease in root Cd uptake by reducing organic acids secretion in the rhizosphere and transport protein production; 2) restriction of Cd translocation from roots to shoots via enhanced Cd retention in the cell wall and Cd sequestration in vacuoles; and 3) reduction in Cd translocation from shoots to grains by limiting Cd redirection and remobilization mediated through nodes. We propose an LAC application strategy focused on LACs and optimized to work with other agronomic measures according to the classification of HM risk level for LACs, providing a cost-effective and practical solution for safe utilization of large areas of farmland polluted with low to moderate levels of HMs.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125427DOI Listing
July 2021

Increase of tyrosinase activity at the wound site in zebrafish imaged by a new fluorescent probe.

Chem Commun (Camb) 2021 Mar;57(22):2764-2767

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. and University of Chinese Academy of Sciences, Beijing 100049, China.

Tyrosinase plays a pivotal role in the hyperpigmentation of wounds. Here, we develop a new fluorescent probe and with it, we reveal an increase of tyrosinase activity at the wound site in zebrafish.
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http://dx.doi.org/10.1039/d0cc08134eDOI Listing
March 2021

Inhibition of laser induced rats choroidal neovascularization by intravitreous injection of sEphB4-HSA.

Ann Transl Med 2021 Jan;9(1):18

Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.

Background: Choroidal neovascularization (CNV) is a leading cause of central vision loss complicated with age-related macular degeneration. Although intravitreal anti-VEGF therapy is widely used in wet age-related macular degeneration, optimal treatment regimens for the disease are still under investigation. EphrinB2 and EphB4 regulate angiogenesis, and interruption of EphB4/ephrinB2 has been demonstrated to inhibit angiogenesis. In the current study, we studied the effects of soluble EphB4 (sEphB4) on laser induced CNV in a rat model by intravitreous injection and the underlying mechanism.

Methods: Male rats (Brown-Norway) were used in the study. CNV was induced by laser and the sEphB4 was injected intravitreous after laser at days 3 and 7. The CNV lesions were evaluated by three methods: fluorescein angiography (FA) , CNV volume by confocal analysis of choroidal flat-mounts and H&E staining. The expression of fibronectin (FN), VEGFR-2, phospho-VEGFR-2 (pVEGFR-2), the double labeling of EphB4 with FN was analyzed by immunofluorescence. The interaction of FN with EphB4 and the effects of intraocular injection of sEphB4 on the inhibition of pVEGFR-2 were determined by western blot.

Results: The FA leakage and CNV volume were significantly inhibited by the injection of the sEphB4. Further, histology analysis showed that CNV lesion was significantly smaller in the rats with sEphB4 injection than rats with placebo application. The expressions of pVEGFR-2 and FN in the CNV lesions were reduced compared with controls.

Conclusions: Our study suggests that the inhibition of CNV by sEphB4 may be through suppression of VEGFR-2 phosphorylation and the expression of FN. sEphB4 may be a new potential therapeutic strategy of CNV.
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http://dx.doi.org/10.21037/atm-20-3810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859820PMC
January 2021

Ischemic Conditioning Ameliorated Hypertension and Vascular Remodeling of Spontaneously Hypertensive Rat via Inflammatory Regulation.

Aging Dis 2021 Feb 1;12(1):116-131. Epub 2021 Feb 1.

1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 10053, China.

Vascular remodeling is an initial step in the development of hypertension. Limb remote ischemic conditioning (LRIC) is a physiological treatment that induces endogenous protective effect during acute ischemic injury. However, the impact of long-term LRIC on hypertension, a chronic disease, is unknown. In this study, we aimed to investigate the LRIC effect on blood pressure and vascular remodeling in spontaneously hypertensive rat (SHR) model and patients with prehypertension and early-stage hypertension. LRIC of rats was performed once a day for 6-weeks. Blood pressure, vascular remodeling (cross-sectional area, extracellular deposition, and smooth muscle cell area), inflammation (inflammatory factors, and inflammatory cells) were compared among normotensive Wistar-Kyoto rats (WKY), WKY RIC group, SHR control group, and SHR RIC. Long-term LRCI treatment (twice a day for 4-weeks) was performed on patients with prehypertension or early-stage hypertension. Blood pressure and pulse wave velocity (PWV) were analyzed before and after LRIC treatment. LRIC treatment decreased blood pressure in SHR (n = 9-10). LRIC ameliorated vascular remodeling by decreasing cross-sectional area, suppressing deposition of the extracellular matrix, and hypertrophy of smooth muscle cell in conduit artery and small resistance artery (n = 7). LRIC decreased proinflammatory factors while increasing the anti-inflammatory factors in the circulation (n = 5). LRIC decreased circulating monocyte and natural killer T-cell levels (n = 5). Furthermore, LRIC treatment decreased blood pressure and improved vascular stiffness in patients (n = 20). In conclusion, long term LRIC could decrease blood pressure and ameliorate vascular remodeling via inflammation regulation. LRIC could be a preventive treatment for people with blood pressure elevation or prehypertension.
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http://dx.doi.org/10.14336/AD.2020.0320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801289PMC
February 2021

Bola3 Regulates Beige Adipocyte Thermogenesis Maintaining Mitochondrial Homeostasis and Lipolysis.

Front Endocrinol (Lausanne) 2020 11;11:592154. Epub 2021 Jan 11.

Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Mitochondrial iron-sulfur (Fe-S) cluster is an important cofactor for the maturation of Fe-S proteins, which are ubiquitously involved in energy metabolism; however, factors facilitating this process in beige fat have not been established. Here, we identified BolA family member 3 (Bola3), as one of 17 mitochondrial Fe-S cluster assembly genes, was the most significant induced gene in the browning program of white adipose tissue. Using lentiviral-delivered shRNA , we determined that Bola3 deficiency inhibited thermogenesis activity without affecting lipogenesis in differentiated beige adipocytes. The inhibition effect of Bola3 knockdown might be through impairing mitochondrial homeostasis and lipolysis. This was evidenced by the decreased expression of mitochondria related genes and respiratory chain complexes, attenuated mitochondrial formation, reduced mitochondrial maximal respiration and inhibited isoproterenol-stimulated lipolysis. Furthermore, BOLA3 mRNA levels were higher in human deep neck brown fat than in the paired subcutaneous white fat, and were positively correlated with thermogenesis related genes (UCP1, CIDEA, PRDM16, PPARG, COX7A1, and LIPE) expression in human omental adipose depots. This study demonstrates that Bola3 is associated with adipose tissue oxidative capacity both in mice and human, and it plays an indispensable role in beige adipocyte thermogenesis maintaining mitochondrial homeostasis and adrenergic signaling-induced lipolysis.
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http://dx.doi.org/10.3389/fendo.2020.592154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829353PMC
January 2021

Nanofibrous bicomponent scaffolds for the dual delivery of NGF and GDNF: controlled release of growth factors and their biological effects.

J Mater Sci Mater Med 2021 Jan 20;32(1). Epub 2021 Jan 20.

Oncology Center, Hubei University of Medicine, Shiyan, 442000, P. R. China.

Electrospun fibrous scaffolds capable of providing dual growth factor delivery in a controlled manner have distinctive advantages for tissue engineering. In this study, we have investigated the formation, structure, and characteristics/properties of fibrous bicomponent scaffolds for the dual delivery of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) for peripheral nerve tissue regeneration. GDNF and NGF were incorporated into core-shell structured poly(lactic-co-glycolic acid) (PLGA) and poly (D,L-lactic acid) (PDLLA) nanofibers, respectively, through emulsion electrospinning. Using dual-source dual-power electrospinning, bicomponent scaffolds composed of GDNF/PLGA fibers and NGF/PDLLA fibers with different fiber component ratios were produced. The structure, properties, and in vitro release behavior of mono- and bicomponent scaffolds were systematically investigated. Concurrent and sustained release of GDNF and NGF from bicomponent scaffolds was achieved and their release profiles could be tuned. In vitro biological investigations were conducted. Rat pheochromocytoma cells were found to attach, spread, and proliferate on all scaffolds. The release of growth factors from scaffolds could induce much improved neurite outgrowth and neural differentiation. GDNF and NGF released from GDNF/PLGA scaffolds and NGF/PDLLA scaffolds, respectively, could induce dose-dependent neural differentiation separately. GDNF and NGF released from bicomponent scaffolds exerted a synergistic effect on promoting neural differentiation.
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http://dx.doi.org/10.1007/s10856-020-06479-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817556PMC
January 2021

Upregulation of miR-1269 Contributes to the Progression of Esophageal Squamous Cell Cancer Cells and Is Associated With Poor Prognosis.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033820985858

Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.

Background: MicroRNA-1269 (miR-1269) has been identified upregulated in several cancers, as well as in esophageal cancer. In the present study, we investigated the clinical prognostic significance and potential functional role of miR-1269 in esophageal squamous cell carcinoma (ESCC).

Methods: A total of 107 ESCC patients who underwent surgical resection were enrolled in this study. miR-1269 expression was measured using quantitative real-time PCR (qRT-PCR). Kaplan-Meier method and multivariate Cox regression analysis were used to explore the prognostic significance of miR-1269. CCK-8 assays and Transwell assays were used to investigate the effects of miR-1269 on cell proliferation, migration, and invasion. The direct association between miR-1269 and SOX6 was evaluated using a dual-luciferase reporter assay.

Results: The expression of miR-1269 was significantly upregulated in ESCC tissues and cell lines compared with adjacent normal tissues and esophageal epithelial cell line, respectively. What's more, the upregulation of miR-1269 was associated with positive lymph node metastasis and advanced TNM stage. ESCC patients with high miR-1269 expression had shorter overall survival than those with low miR-1269 expression levels. Compared with the control group, overexpression of miR-1269 promoted cell proliferation, migration, and invasion, while knockdown of miR-1269 inhibited cell proliferation, migration, and invasion. SOX6 was a direct target of miR-1269.

Conclusion: These results suggest that miR-1269 plays an important role in the progression of ESCC by targeting SOX6 and may be a potential prognostic biomarker and the miR-1269/SOX6 axis may be a therapeutic target for the patient with ESCC.
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http://dx.doi.org/10.1177/1533033820985858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097309PMC
January 2021

Utilization of Self-Diagnosis Health Chatbots in Real-World Settings: Case Study.

J Med Internet Res 2021 01 6;23(1):e19928. Epub 2021 Jan 6.

The Institute of Software, Chinese Academy of Sciences, Beijing, China.

Background: Artificial intelligence (AI)-driven chatbots are increasingly being used in health care, but most chatbots are designed for a specific population and evaluated in controlled settings. There is little research documenting how health consumers (eg, patients and caregivers) use chatbots for self-diagnosis purposes in real-world scenarios.

Objective: The aim of this research was to understand how health chatbots are used in a real-world context, what issues and barriers exist in their usage, and how the user experience of this novel technology can be improved.

Methods: We employed a data-driven approach to analyze the system log of a widely deployed self-diagnosis chatbot in China. Our data set consisted of 47,684 consultation sessions initiated by 16,519 users over 6 months. The log data included a variety of information, including users' nonidentifiable demographic information, consultation details, diagnostic reports, and user feedback. We conducted both statistical analysis and content analysis on this heterogeneous data set.

Results: The chatbot users spanned all age groups, including middle-aged and older adults. Users consulted the chatbot on a wide range of medical conditions, including those that often entail considerable privacy and social stigma issues. Furthermore, we distilled 2 prominent issues in the use of the chatbot: (1) a considerable number of users dropped out in the middle of their consultation sessions, and (2) some users pretended to have health concerns and used the chatbot for nontherapeutic purposes. Finally, we identified a set of user concerns regarding the use of the chatbot, including insufficient actionable information and perceived inaccurate diagnostic suggestions.

Conclusions: Although health chatbots are considered to be convenient tools for enhancing patient-centered care, there are issues and barriers impeding the optimal use of this novel technology. Designers and developers should employ user-centered approaches to address the issues and user concerns to achieve the best uptake and utilization. We conclude the paper by discussing several design implications, including making the chatbots more informative, easy-to-use, and trustworthy, as well as improving the onboarding experience to enhance user engagement.
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http://dx.doi.org/10.2196/19928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817366PMC
January 2021

Utilization of Self-Diagnosis Health Chatbots in Real-World Settings: Case Study.

J Med Internet Res 2021 01 6;23(1):e19928. Epub 2021 Jan 6.

The Institute of Software, Chinese Academy of Sciences, Beijing, China.

Background: Artificial intelligence (AI)-driven chatbots are increasingly being used in health care, but most chatbots are designed for a specific population and evaluated in controlled settings. There is little research documenting how health consumers (eg, patients and caregivers) use chatbots for self-diagnosis purposes in real-world scenarios.

Objective: The aim of this research was to understand how health chatbots are used in a real-world context, what issues and barriers exist in their usage, and how the user experience of this novel technology can be improved.

Methods: We employed a data-driven approach to analyze the system log of a widely deployed self-diagnosis chatbot in China. Our data set consisted of 47,684 consultation sessions initiated by 16,519 users over 6 months. The log data included a variety of information, including users' nonidentifiable demographic information, consultation details, diagnostic reports, and user feedback. We conducted both statistical analysis and content analysis on this heterogeneous data set.

Results: The chatbot users spanned all age groups, including middle-aged and older adults. Users consulted the chatbot on a wide range of medical conditions, including those that often entail considerable privacy and social stigma issues. Furthermore, we distilled 2 prominent issues in the use of the chatbot: (1) a considerable number of users dropped out in the middle of their consultation sessions, and (2) some users pretended to have health concerns and used the chatbot for nontherapeutic purposes. Finally, we identified a set of user concerns regarding the use of the chatbot, including insufficient actionable information and perceived inaccurate diagnostic suggestions.

Conclusions: Although health chatbots are considered to be convenient tools for enhancing patient-centered care, there are issues and barriers impeding the optimal use of this novel technology. Designers and developers should employ user-centered approaches to address the issues and user concerns to achieve the best uptake and utilization. We conclude the paper by discussing several design implications, including making the chatbots more informative, easy-to-use, and trustworthy, as well as improving the onboarding experience to enhance user engagement.
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http://dx.doi.org/10.2196/19928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817366PMC
January 2021

Screening and Identifying Cisplatin-Related Gene Mutations in Lung Squamous Cell Carcinoma.

Pharmgenomics Pers Med 2020 18;13:757-766. Epub 2020 Dec 18.

Department of Oncology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 611731, People's Republic of China.

Introduction: Platinum-based chemotherapy is the cornerstone of treatment for patients with LUSC, but cisplatin resistance greatly restricts its clinical application. Therefore, it is particularly important to screen the predominant LUSC population using biomarkers.

Methods: Data for 15 LUSC cell lines were downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) Project database to screen for mutations related to cisplatin susceptibility. We conducted whole-exome sequencing (WES) of tumors from 58 LUSC patients from Sichuan Provincial People's Hospital of University of Electronic Science and Technology. Subsequently, the clinical prognostic value of these mutations was verified by using The Cancer Genome Atlas (TCGA)-LUSC cohort and our cohort (n=58).

Results: Based on the cisplatin sensitivity data of GDSC-LUSC and survival analysis of TCGA-LUSC and Local-LUSC cohorts, we found that only mutation of IGF2R was associated with cisplatin sensitivity, better overall survival [OS; P=0.04, HR (95% CI): 0.42 (0.23-0.78)] and progression-free survival [PFS; P =0.016, HR (95% CI): 0.26 (0.12-0.59)]. However, there were no significant differences in the frequencies of gene mutations between the IGF2R-mutant (IGF2R-MT) and IGF2R-wild-type (IGF2R-WT) groups. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) indicated enhanced intracellular detoxification and decreased abnormal signaling activity to reverse cisplatin tolerance in the IGF2R-MT group.

Conclusion: The results suggest that IGF2R mutations are a potential biomarker for screening LUSC patients suitable for cisplatin treatment.
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http://dx.doi.org/10.2147/PGPM.S264545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755377PMC
December 2020

The critical role of mA methylation in the pathogenesis of Graves' ophthalmopathy.

Eye Vis (Lond) 2020 Dec 1;7(1):55. Epub 2020 Dec 1.

Department of Ophthalmology, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, Xizhimen South Street 11, Xi Cheng District, Beijing, 100044, China.

Purpose: To investigate the role of N6-methyladenosine (mA) RNA modification in the pathogenesis of Graves' ophthalmopathy (GO).

Methods: Surgically excised extraocular muscles from 7 patients with GO and 5 subjects without GO were used. The global mA levels in the specimens were determined using an mA RNA methylation quantification kit. RNA sequencing (RNA-seq) was used to analyze the molecules involved in the regulation of mA RNA methylation and the differential expression of mRNAs between the two groups (4 eyes, respectively). The expression of mA RNA modification genes was evaluated by real-time PCR. The functional implications of the gene alterations between the GO and control specimens were determined by Gene Ontology analysis.

Results: The mA level was significantly increased in the specimens of GO patients compared to the control specimens (P < 0.05). The expression of mA methylation regulators, such as WT1 associated protein (WTAP), alkylation repair homolog protein 5 (ALKBH5), E74 like ETS transcription factor 3 (ELF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTHDF3 and YTH domain containing 2 (YTHDC2), was significantly upregulated (P < 0.05). Gene Ontology enrichment analysis showed that the most highly upregulated genes and biological pathways were related to the immune response and inflammatory processes such as lymphocyte activation, leukocyte differentiation, cytokine production and cytokine-mediated signaling pathways.

Conclusions: Our results suggest that mA methylation may play a critical role in the pathogenesis of GO and that targeting genes that regulate mA methylation may provide a new therapeutic approach for GO.
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http://dx.doi.org/10.1186/s40662-020-00221-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708247PMC
December 2020

Antioxidant ability of glutaredoxins and their role in symbiotic nitrogen fixation in bv. 3841.

Appl Environ Microbiol 2020 Dec 4. Epub 2020 Dec 4.

Hubei Provincial Engineering and Technology Research Center for Resources and Utilization of Microbiology, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, Hubei, China.

Glutaredoxins (Grx) are redoxin family proteins that reduce disulfides and mixed disulfides between glutathione and proteins. bv. 3841 contains three genes coding for glutaredoxins: () codes for a dithiolic glutaredoxin, () codes for a monothiol glutaredoxin, while () codes for a glutaredoxin-like NrdH protein. We generated mutants interrupted in one, two, or three glutaredoxin genes. These mutants had no obvious differences in growth phenotypes from the wild type RL3841. However, while a mutant of did not affect the antioxidant or symbiotic capacities of , derived or mutants decreased antioxidant and nitrogen fixation capacities. Furthermore, mutants were severely impaired in rhizosphere colonization, and formed smaller nodules with defects of bacteroid differentiation, whereas nodules induced by mutants contained abnormally thick cortices and prematurely senescent bacteroids. The triple mutant had the greatest defect in antioxidant and symbiotic capacities of and quantitative proteomics revealed it had 56 up-regulated and 81 down-regulated proteins relative to wildtype. Of these proteins, twenty-eight are involved in transporter activity, twenty are related to stress response and virulence, and sixteen are involved in amino acid metabolism. Overall, glutaredoxins behave as antioxidant proteins mediating root nodule symbiosis. Glutaredoxin catalyzes glutathionylation/deglutathionylation reactions, protects SH-groups from oxidation and restores functionally active thiols. Three glutaredoxins exist in and their properties were investigated in free-living bacteria and during nitrogen-fixing symbiosis. All the glutaredoxins were necessary for oxidative stress defense. Dithiol GrxA affects nodulation and nitrogen fixation of bacteroids by altering deglutathionylation reactions, monothiol GrxB is involved in symbiotic nitrogen fixation by regulating Fe-S cluster biogenesis, and GrxC may participate in symbiosis by an unknown mechanism. Proteome analysis provides clues to explain the differences between the triple mutant and wild-type nodules.
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http://dx.doi.org/10.1128/AEM.01956-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851698PMC
December 2020