Publications by authors named "Fang Zhang"

1,614 Publications

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Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression.

Front Microbiol 2021 31;12:722748. Epub 2021 Aug 31.

Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.

Herpes simplex virus type 1 (HSV-1) infection induces various clinical disorders, such as herpes simplex encephalitis (HSE), herpes simplex keratitis (HSK), and genital herpes. In clinical intervention, acyclovir (ACV) is the major therapeutic drug used to suppress HSV-1; however, ACV-resistant strains have gradually increased. In the present study, harringtonine (HT) significantly inhibited infection of HSV-1 as well as two ACV-resistant strains, including HSV-1 blue and HSV-1 153. Time-of-drug addition assay further revealed that HT mainly reduced the early stage of HSV-1 infection. We also demonstrated that HT mainly affected herpes virus entry mediator (HVEM) expression as shown by qPCR, Western Blot, and . Collectively, HT showed antiviral activity against HSV-1 and ACV-resistant strains by targeting HVEM and could be a promising therapeutic candidate for mitigating HSV-1-induced-pathogenesis.
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http://dx.doi.org/10.3389/fmicb.2021.722748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438530PMC
August 2021

Isolation, structural characterization and bioactivities of polysaccharides from Laminaria japonica: A review.

Food Chem 2021 Sep 1;370:131010. Epub 2021 Sep 1.

National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Laminaria japonica is a familiar marine plant and is often used as food due to its abundant carbohydrates, vitamins and minerals. As one of the main types of active substances in L. japonica, polysaccharides are widely used in the food and chemical industries and in medicine and healthcare due to their health benefits, such as immunoregulatory, antioxidant, and antidiabetic effects. However, there has been no systematic summary of the isolation, structural characterization and bioactivities of L. japonica polysaccharides (LJPs). Therefore, the present review includes a survey of extraction and purification methods for these bioactive molecules, along with a dissertation on the structural characterization of the carbohydrate components. Moreover, an overview of the most recent results related to LJP biological activities is provided. This review provides a useful reference for further research, production, and application of LJPs in functional foods and therapeutic agents.
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http://dx.doi.org/10.1016/j.foodchem.2021.131010DOI Listing
September 2021

Trends in high deductible health plan enrolment and spending among commercially insured members with and without chronic conditions: a Natural Experiment for Translation in Diabetes (NEXT-D2) Study.

BMJ Open 2021 Sep 13;11(9):e044198. Epub 2021 Sep 13.

Division of Health Policy and Insurance Research, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.

Objectives: To examine trends in high deductible health plan (HDHP) enrolment among members with diabetes and cardiovascular disease (CVD) compared with healthy members and compare out-of-pocket (OOP) and total spending for members with chronic conditions in HDHPs versus low deductible plans.

Design: Descriptive study with time trends.

Setting: A large national commercial insurance database.

Participants: 1.2 million members with diabetes, 4.5 million members with CVD (without diabetes) and 18 million healthy members (defined by a low comorbidity score) under the age of 65 years and insured between 2005 and 2013.

Outcome Measures: Percentage of members in an HDHP (ie, annual deductible ≥$1000) by year, annual mean OOP and total spending, adjusted for member sociodemographic and employer characteristics.

Results: Enrolment in HDHPs among members in all disease categories increased by 5 percentage points a year and was over 50% by 2013. On average, over the study period, HDHP enrolment among members with diabetes and CVD was 2.84 (95% CI: 2.78 to 2.90) and 2.02 (95% CI: 1.98 to 2.05) percentage points lower, respectively, than among healthy members. HDHP members with diabetes, CVD and low morbidity had higher annual OOP costs ($636 (95% CI: 630 to 642), $539 (95% CI: 537 to 542) and $113 (95% CI: 112 to 113)) and lower total costs (-$529 (95% CI: -597 to -461), -$364 (95% CI: -385 to -342) and -$79 (95% CI: -81 to -76)), respectively, than corresponding low deductible members when averaged over the study period. Members with chronic diseases had yearly OOP expenditures that were five to seven times higher than healthier members.

Conclusion: High HDHP enrolment coupled with the high OOP costs associated with HDHPs may be particularly detrimental to the financial well-being of people with diabetes and CVD, who have more healthcare needs than healthier populations.
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http://dx.doi.org/10.1136/bmjopen-2020-044198DOI Listing
September 2021

Combination of Matching Responsive Stimulations of Hippocampus and Subiculum for Effective Seizure Suppression in Temporal Lobe Epilepsy.

Front Neurol 2021 26;12:638795. Epub 2021 Aug 26.

Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou, China.

Responsive neural stimulation (RNS) is considered a promising neural modulation therapy for refractory epilepsy. Combined stimulation on different targets may hold great promise for improving the efficacy of seizure control since neural activity changed dynamically within associated brain targets in the epileptic network. Three major issues need to be further explored to achieve better efficacy of combined stimulation: (1) which nodes within the epileptogenic network should be chosen as stimulation targets? (2) What stimulus frequency should be delivered to different targets? and (3) Could the efficacy of RNS for seizure control be optimized by combined different stimulation targets together? In our current study, Granger causality (GC) method was applied to analyze epileptogenic networks for finding key targets of RNS. Single target stimulation (100 μA amplitude, 300 μs pulse width, 5s duration, biphasic, charge-balanced) with high frequency (130 Hz, HFS) or low frequency (5 Hz, LFS) was firstly delivered by our lab designed RNS systems to CA3, CA1, subiculum (SUB) of hippocampi, and anterior nucleus of thalamus (ANT). The efficacy of combined stimulation with different groups of frequencies was finally assessed to find out better combined key targets with optimal stimulus frequency. Our results showed that stimulation individually delivered to SUB and CA1 could shorten the average duration of seizures. Different stimulation frequencies impacted the efficacy of seizure control, as HFS delivered to CA1 and LFS delivered to SUB, respectively, were more effective for shortening the average duration of electrographic seizure in Sprague-Dawley rats ( = 3). Moreover, the synchronous stimulation of HFS in CA1 combined with LFS in SUB reduced the duration of discharge significantly in rats ( = 6). The combination of responsive stimulation at different targets may be an inspiration to optimize stimulation therapy for epilepsy.
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http://dx.doi.org/10.3389/fneur.2021.638795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426572PMC
August 2021

Acetate and electricity generation from methane in conductive fiber membrane- microbial fuel cells.

Sci Total Environ 2021 Sep 4;804:150147. Epub 2021 Sep 4.

Fujian Provincial Key Laboratory of Soil Environmental Health and Regulation, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; Advanced Laboratory for Environmental Research and Technology, USTC-CityU, Suzhou, China; CAS Key Laboratory of Urban Pollutant Conversion, Department of Applied Chemistry, University of Science and Technology of China, Hefei 230026, China. Electronic address:

Microbial conversion of methane to electricity, fuels, and liquid chemicals has attracted much attention. However, due to the low solubility of methane, it is not considered a suitable substrate for microbial fuel cells (MFCs). In this study, a conductive fiber membrane (CFM) module was constructed as the bioanode of methane-driven MFCs, directly delivering methane. After biofilm formation on the CFM surface, a steady voltage output of 0.6 to 0.7 V was recorded, and the CFM-MFCs obtained a maximum power density of 64 ± 2 mW/m. Moreover, methane oxidation produced a high concentration of intermediate acetate (up to 7.1 mM). High-throughput 16S rRNA gene sequencing suggests that the microbial community was significantly changed after electricity generation. Methane-related archaea formed a symbiotic consortium with characterized electroactive bacteria and fermentative bacteria, suggesting a combination of three types of microorganisms for methane conversion into acetate and electricity.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150147DOI Listing
September 2021

A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer.

Front Cell Dev Biol 2021 20;9:712230. Epub 2021 Aug 20.

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Bladder cancer (BC) belongs to one of the most common and highly heterogeneous malignancies. Ferroptosis is a newly discovered regulated cell death (RCD), characterized by accumulation of toxic lipid peroxides, and plays a crucial role in tumor progression. Here, we conducted a comprehensive analysis on the transcriptomics data of ferroptosis-related genes in BC based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. In our study, a 6-gene signature was identified based on the potential prognostic ferroptotic regulatory genes. Furthermore, our signature revealed a good independent prognostic ability in BC. Patients with low-risk score exhibited higher FGFR3 mutation rates while high risk score had a positive association with higher RB1 mutation rates. Meanwhile, higher proportions of macrophages were observed in high BC risk group simultaneously with four methods. Unexpectedly, the risk score showed a significant positive correlation with epithelial-mesenchymal transition (EMT) status. Functional assays indicated that CRYAB and SQLE knockdown was associated with attenuated invasion capacity. Our study revealed a ferroptosis-related risk model for predicting prognostic and BC progression. Our results indicate that targeting ferroptosis may be a therapeutic strategy for BC.
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http://dx.doi.org/10.3389/fcell.2021.712230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417704PMC
August 2021

Out-of-Pocket Spending for Asthma-Related Care Among Commercially Insured Patients, 2004-2016.

J Allergy Clin Immunol Pract 2021 Sep 1. Epub 2021 Sep 1.

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Mass.

Background: Out-of-pocket (OOP) health care costs can cause financial burden and deferred care for many Americans. Little is known about OOP spending for asthma-related care among the commercially insured.

Objectives: To analyze OOP spending for asthma-related care overall, across types of care, and by income.

Methods: Using enrollment, claims, and geocoded census tract data on income from a large US commercial health plan from 2004 to 2016, we measured inflation-adjusted OOP spending for individuals with asthma ages 4 to 64 years (n = 1,986,769). We estimated annual asthma-related OOP spending over time, and average total, asthma-related, asthma type of care, and asthma medication spending by income. We measured trends in median OOP cost per medication. Linear regression models were adjusted for patient covariates and deductible level.

Results: Asthma-related OOP spending decreased over time both for patients enrolled in high-deductible health plans and for those in traditional plans. High-deductible plan enrollment increased from 7% to 54%. Compared with patients living in high-income areas, patients in the lowest-income areas had similar annual total and asthma-related OOP spending, but spent 30% less on controller medications and a higher proportion of their asthma-related OOP spending on inpatient and emergency care (10% vs 3%; P < .001). Asthma-related OOP spending represented a higher proportion of household income for patients in lower-income areas.

Conclusions: Patients with asthma living in the lowest-income areas have greater cost burden, lower spending on controller medications, and greater spending on high-acuity care than higher-income counterparts.
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http://dx.doi.org/10.1016/j.jaip.2021.07.054DOI Listing
September 2021

Fumaric acid and succinic acid treat gestational hypertension by downregulating the expression of KCNMB1 and TET1.

Exp Ther Med 2021 Oct 28;22(4):1072. Epub 2021 Jul 28.

Department of Obstetrics, The First Affliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, P.R. China.

The present study hypothesized that fumaric acid and succinic acid may exhibit therapeutic effects on gestational hypertension. During pregnancy, estrogen upregulates ten-eleven translocation 1 (TET1) expression, which subsequently increases calcium-activated potassium channel subunit β1 (KCNMB1) expression. KCNMB1 is associated with hypertension. Fumaric acid and succinic acid are understood to inhibit TET. Therefore, the present study investigated whether fumaric acid and succinic acid exhibit therapeutic effects on gestational hypertension and whether these effects are mediated by TET1 and KCNMB1. Nω-Nitro-L-arginine methyl ester hydrochloride was injected into rats to establish a gestational hypertension model. Dimethyl fumarate (DMF) and succinic acid were administrated into rats to treat gestational hypertension. Rats were divided into five groups: i) Control; ii) model; iii) DMF; iv) succinic acid; and v) DMF + succinic acid. Blood pressure was monitored by a noninvasive meter and urinary protein was determined using a urinary protein kit. Placenta pathology was examined by hematoxylin-eosin staining. Compared with the control group, urinary protein and blood pressure in the model group increased significantly. The placental cells in the control group were arranged orderly. However, in the model group, decidual cellular edema of placenta and vacuolar degeneration were observed, and the intervascular membrane was markedly thicker with plenty of fibrin deposition. These results indicate successful establishment of a gestational hypertension model. However, compared with the model group, urinary protein, blood pressure, edema, vacuoles and fibrin deposition were markedly reduced in the DMF, succinic acid and DMF + succinic acid groups. mRNA and protein levels of TET1 and KCNMB1 in placenta were evaluated by immunohistochemical analysis, reverse transcription-quantitative polymerase chain reaction and western blotting. The TET1 and KCNMB1 levels in the model group were markedly increased compared with those in the control group. However, compared with the model group, the expression levels were markedly downregulated in the DMF, succinic acid and DMF + succinic acid groups. In conclusion, fumaric acid and succinic acid may treat gestational hypertension by downregulating the expression of KCNMB1 and TET1.
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http://dx.doi.org/10.3892/etm.2021.10506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355717PMC
October 2021

Insights into vertical differences of particle number size distributions in winter in Beijing, China.

Sci Total Environ 2021 Aug 19;802:149695. Epub 2021 Aug 19.

State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing 100029, China; Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China. Electronic address:

Particle number size distribution (PNSD) is of importance for understanding the mechanisms of particle growth, haze formation and climate impacts. However, the measurements of PNSD aloft in megacities are very limited. Here we report the first simultaneous winter measurements of size-resolved particle number concentrations along with collocated gaseous species and aerosol composition at ground level and 260 m in Beijing. Our study showed that the vertical differences of particle number concentrations between ground level and aloft varied significantly as a function of particle size throughout the study. Further analysis illustrated the impacts of boundary dynamics and meteorological conditions on the vertical differences of PNSD. In particular, the temperature and relative humidity inversions were one of the most important factors by decoupling the boundary layer into different sources and processes. Positive matrix factorization analysis identified six sources of PNSD at both ground level and city aloft. The local source emissions dominantly contributed to Aitken-mode particles, and showed the largest vertical gradients in the city. Comparatively, the regional particles were highly correlated between ground level and city aloft, and the vertical differences were relatively stable throughout the day. Our results point towards a complex vertical evolution of PNSD due to the changes in boundary layer dynamics, meteorological conditions, sources, and processes in megacities.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149695DOI Listing
August 2021

The kinetics of E- and P-selectin-induced intermediate activation of integrin αLβ2 on neutrophil.

J Cell Sci 2021 Aug 26. Epub 2021 Aug 26.

Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0363, USA.

Selectins and integrins are key players of the adhesion and signaling cascade that recruits leukocytes to inflamed tissues. Selectin binding induces β2-integrin binding to slow rolling. A micropipette was used to characterize neutrophil adhesion to E-selectin and intercellular adhesion molecule (ICAM)-1 at room temperature. The time-dependent adhesion frequency displayed two-stage kinetics with an E-selectin-mediated fast increase to a low plateau followed by a slow increase to a high plateau mediated by intermediate-affinity binding of integrin αLβ2 to ICAM-1. The αLβ2 activation required ≥5s contact to E-selectin and spleen tyrosine kinase activity. A multi-zone channel was used to analyze αLβ2 activation by P-selectin in separate zones of receptors or antibodies, finding an inverse relationship between the rolling velocity on ICAM-1 and P-selectin dose, and a P-selectin dose-dependent change from bent to extended conformations with a closed headpiece that was faster at 37oC than room temperature. Activation of αLβ2 exhibited different levels of cooperativity and persistent times depending on the strength and duration of selectin stimulation. These results define the precise timing and kinetics of intermediate activation of αLβ2 by E- and P-selectins.
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http://dx.doi.org/10.1242/jcs.258046DOI Listing
August 2021

The Optimal Second-Line Systemic Treatment Model for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: A Bayesian Network Meta-Analysis.

Front Immunol 2021 2;12:719650. Epub 2021 Aug 2.

Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.

Background: The optimal second-line systemic treatment model for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains controversial. A Bayesian network meta-analysis (NMA) was performed to address this issue with regard to efficacy and toxicity.

Methods: By searching MEDLINE ( PubMed), Embase, the Cochrane Central Register of Controlled Trials and Web of Science, we extracted eligible studies. Efficacy, represented as overall survival (OS) and progression-free survival (PFS), and overall toxicity, represented as ≥ grade 3 severe acute events (sAE), were assessed to compare the following 7 treatment models through an NMA: standard-of-care therapy (SoC), single targeted therapy different from SoC (ST), double targeted therapy (DT), targeted therapy combined with chemotherapy (T+C), single immune checkpoint inhibitor therapy (SI), double immune checkpoint inhibitor therapy (DI) and single chemotherapy different from SoC (SC). Rank probabilities according to the values of the surface under the cumulative ranking curve (SUCRA) were separately determined for efficacy and toxicity.

Results: In total, 5285 patients from 24 eligible studies were ultimately screened, with 5184, 4532 and 4026 involved in the NMA of OS, PFS and sAE, respectively. All qualifying studies were absent from first-line immune checkpoint inhibitor therapy. In terms of OS, SI was superior to the other treatments, followed by DI, ST, T+C, SoC, DT and SC. Other than SI and SC, all treatments tended to be consistent, with hazard ratios (HRs) close to 1 between groups. For PFS, ST ranked first, while DT ranked last. For the toxicity profiles, compared with the other models, SI resulted in the lowest incidences of sAE, with statistical significance over SoC (odds ratio [OR] 0.31, 95% credible interval [CrI] 0.11 to 0.90), ST (OR 0.23, 95% CrI 0.06 to 0.86) and DT (OR 0.11, 95% CrI 0.02 to 0.53), while DT was the worst. When the SUCRA values of OS and sAE were combined, a cluster plot illustrated the superiority of SI, which demonstrated the best OS and tolerability toward sAE.

Conclusion: For R/M HNSCC patients without immune checkpoint inhibitors in the first-line setting, SI may serve as the optimal second-line systemic treatment model, demonstrating the best OS and least sAE.
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http://dx.doi.org/10.3389/fimmu.2021.719650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367750PMC
August 2021

Identification of sensitive indicators in immune response for leprosy affected patients: An observational clinical study of safety and immunogenicity of influenza vaccine.

Medicine (Baltimore) 2021 Aug;100(31):e26744

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract: Cured leprosy patients have special physical conditions, which could pose challenges for safety and immunogenicity after immunization. We performed an observational clinical study aimed to identify the safety and immunogenicity of influenza vaccine in cured leprosy patients. A total of 65 participants from a leprosarium were recruited into leprosy cured group or control group, and received a 0.5 ml dose of the inactivated split-virion trivalent influenza vaccine and a follow-up 28 days proactive observation of any adverse events. Hemagglutination and hemagglutination inhibition test was performed to evaluate serum antibody titer, flow cytometry was conducted to screen of cytokines level. The total rate of reactogenicity was 0.0% [0/41] in leprosy cured group and 37.5% [9/24] in control group. The seroconversion rate for H1N1 was difference between leprosy cured group and control group (41.83% vs 79.17%, P = .0082), but not for H3N2 (34.25% vs 50.00%, P = .4468). At day 0, leprosy cured group have relatively high concentration of interleukin-6, interleukin-10, tumor necrosis factor, interferon-γ, and interleukin-17 compared to control group. The interleukin-2 concentration increased 2 weeks after vaccination compared to pre-vaccination in leprosy cured group, but declined in control group (0.92 pg/ml vs -0.02 pg/ml, P = .0147). Leprosy cured group showed a more rapid down-regulation of interleukin-6 when influenza virus was challenged compared to control group (-144.38 pg/ml vs -11.52 pg/ml, P < .0001). Subgroup analysis revealed that the immunization administration declined interleukin-17 concentration in Tuberculoid type subgroup, but not in Lepromatous type subgroup or control group. Clinically cured leprosy patients are relatively safe for influenza vaccine. Leprosy cured patient have immune deficit in producing antibody. Interleukin-6 and interleukin-17 were 2 sensitive indicators in immune response for leprosy affected patients. The identification of indicators might be help management of leprosy and used as predictive markers in leprosy early symptom monitoring.
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http://dx.doi.org/10.1097/MD.0000000000026744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341344PMC
August 2021

Characterization of Shallow Whole-Metagenome Shotgun Sequencing as a High-Accuracy and Low-Cost Method by Complicated Mock Microbiomes.

Front Microbiol 2021 30;12:678319. Epub 2021 Jul 30.

Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Characterization of the bacterial composition and functional repertoires of microbiome samples is the most common application of metagenomics. Although deep whole-metagenome shotgun sequencing (WMS) provides high taxonomic resolution, it is generally cost-prohibitive for large longitudinal investigations. Until now, 16S rRNA gene amplicon sequencing (16S) has been the most widely used approach and usually cooperates with WMS to achieve cost-efficiency. However, the accuracy of 16S results and its consistency with WMS data have not been fully elaborated, especially by complicated microbiomes with defined compositional information. Here, we constructed two complex artificial microbiomes, which comprised more than 60 human gut bacterial species with even or varied abundance. Utilizing real fecal samples and mock communities, we provided solid evidence demonstrating that 16S results were of poor consistency with WMS data, and its accuracy was not satisfactory. In contrast, shallow whole-metagenome shotgun sequencing (shallow WMS, S-WMS) with a sequencing depth of 1 Gb provided outputs that highly resembled WMS data at both genus and species levels and presented much higher accuracy taxonomic assignments and functional predictions than 16S, thereby representing a better and cost-efficient alternative to 16S for large-scale microbiome studies.
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http://dx.doi.org/10.3389/fmicb.2021.678319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361837PMC
July 2021

Performance and mechanisms of fly ash for graphene oxide removal from aqueous solution.

Environ Sci Pollut Res Int 2021 Aug 14. Epub 2021 Aug 14.

School of Civil Engineering, Shaoxing University, Shaoxing, 312000, Zhejiang, China.

The potential wide use of graphene oxide in various fields results in the possibility of its dispersion throughout natural water systems, with a negative impact on organisms and ecosystems. This study evaluated the removal of graphene oxide (GO) from water by fly ash (FA). The effects of various conditions (including the initial concentration of graphene oxide, the pH of the initial solution, the amount of absorbent, and temperature) on the removal rate of GO were investigated in detail. The results show that the maximum removal rate of graphene oxide by fly ash is 93%; the isotherm adsorption process conforms to a Langmuir model; the adsorption reaction is a spontaneous exothermic process. Under optimal conditions, the pH of the solution was adjusted to 6, the amount of fly ash was 5 mg, the initial concentration of GO was 60 mg·L, and the temperature was 303 K. Using X-ray diffraction (XRD), Raman spectroscopy (Raman), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), transmission electron microscopy (TEM), Zeta potential and X-ray electron spectroscopy (XPS), the adsorption mechanism was characterized. The experimental results demonstrate that fly ash is a good material for GO removal from aqueous solution.
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http://dx.doi.org/10.1007/s11356-021-15769-3DOI Listing
August 2021

Analytical and Clinical Performance of a Liquid Chromatography-Tandem Mass Spectrometry Method for Measuring Gastrin Subtypes G34 and G17 in Serum.

Clin Chem 2021 Sep;67(9):1220-1229

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

Background: Two major forms of gastrin, gastrin-17 (G17) and gastrin-34 (G34), exist in blood. However, conventional immunoassay methods can only quantify total gastrin or G17 alone. Here, we aimed to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify G17 and G34 simultaneously.

Methods: Serum samples were prepared by anion-exchange solid-phase extraction. The analytical performance of the LC-MS/MS method was validated and the method was compared to chemiluminescence immunoassay (CLIA) and radioimmunoassay (RIA). The G17 and G34 concentrations in 245 serum samples from healthy controls, individuals with gastrinoma, and individuals with other diseases were analyzed.

Results: The total runtime of the LC-MS/MS method was 6 min. No substantial matrix effect was observed with internal standard correction. The intraassay coefficients of variation (CVs) for G17 and G34 were 4.0%-14.2% and 4.4%-10.4%, respectively, and total CVs were 5.2%-14.1% and 4.6%-12.4%, respectively. The correlation coefficient between LC-MS/MS and CLIA was 0.87, and between LC-MS/MS and RIA was 0.84. The G17+G34 concentrations for 87.5% of individuals with gastrinoma were higher than the 95th percentile of healthy controls (18.1 pg/mL), whereas the concentrations for individuals with other diseases and gastrinoma overlapped. Based on the Youden indices calculated for G17+G34, G34, and G17, the most specific biomarker was G17 (96.9% clinical specificity at 209.8 pg/mL) for gastrinoma.

Conclusions: This method should aid in the diagnosis of diseases associated with increased gastrin concentrations.
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http://dx.doi.org/10.1093/clinchem/hvab097DOI Listing
September 2021

ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells.

Cell Commun Signal 2021 Aug 11;19(1):85. Epub 2021 Aug 11.

Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, No. 63 Xinjian South Road, Taiyuan, 030001, Shanxi, China.

Background: Vitamin D receptor (VDR) plays a vital protective role in oral and colonic epithelial cells. Albeit we know that VDR expression is reduced in the mucosal epithelial layers of autoimmune diseases, the mechanism by which VDR is decreased remains elusive.

Methods: VDR and zinc finger protein 36 (ZFP36) levels in human samples and cell lines were detected by real-time PCR, western blot and immunostaining. Luciferase report assay was used to test cis-elements in VDR gene promoter, real-time PCR was applied to measure mRNA decay and western blot was performed to evaluate protein degradation. RNA affinity chromatography assay was used to test protein-mRNA interaction. Co-immunoprecipitation was used to detect protein-protein interaction. The role of ZFP36 in AU-rich elements (AREs) in the 3' untranslated region (UTR) of VDR mRNA was also measured by luciferase report assay.

Results: We identify ZFP36 can bind with the AREs in the 3'UTR of VDR mRNA, leading to mRNA degradation in oral and colonic epithelial cells under inflammatory circumstance. Either ZFP36 protein or AREs of VDR mRNA mutation abolishes this protein-mRNA binding process. After the key amino acid's mutation, ZFP36 fails to decrease VDR mRNA expression. We also find that VDR physically binds with Y box-binding protein 1 (YBX-1) to block YBX-1's nuclear translocation and ameliorate cell death in the presence of inflammation.

Conclusion: These findings provide insights into the cause of VDR decrease in oral and colonic epithelial cells under inflammatory condition and explain how VDR maintains cell viability in these cells. Video abstract.
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http://dx.doi.org/10.1186/s12964-021-00765-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355874PMC
August 2021

Trends in Consumption of Ultraprocessed Foods Among US Youths Aged 2-19 Years, 1999-2018.

JAMA 2021 08;326(6):519-530

Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts.

Importance: The childhood obesity rate has been steadily rising among US youths during the past 2 decades. Increasing evidence links consumption of ultraprocessed foods to excessive calorie consumption and weight gain, but trends in the consumption of ultraprocessed foods among US youths have not been well characterized.

Objective: To characterize trends in the consumption of ultraprocessed foods among US youths.

Design, Setting, And Participants: Serial cross-sectional analysis using 24-hour dietary recall data from a nationally representative sample of US youths aged 2-19 years (n = 33 795) from 10 cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999-2000 to 2017-2018.

Exposures: Secular time.

Main Outcomes And Measures: Percentage of total energy consumed from ultraprocessed foods as defined by NOVA, an established food classification system that categorizes food according to the degree of food processing.

Results: Dietary intake from youths were analyzed (weighted mean age, 10.7 years; 49.1% were girls). From 1999 to 2018, the estimated percentage of total energy from consumption of ultraprocessed foods increased from 61.4% to 67.0% (difference, 5.6% [95% CI, 3.5% to 7.7%]; P < .001 for trend), whereas the percentage of total energy from consumption of unprocessed or minimally processed foods decreased from 28.8% to 23.5% (difference, -5.3% [95% CI, -7.5% to -3.2%]; P < .001 for trend). Among the subgroups of ultraprocessed foods, the estimated percentage of energy from consumption of ready-to-heat and -eat mixed dishes increased from 2.2% to 11.2% (difference, 8.9% [95% CI, 7.7% to 10.2%]) and from consumption of sweet snacks and sweets increased from 10.7% to 12.9% (difference, 2.3% [95% CI, 1.0% to 3.6%]), but the estimated percentage of energy decreased for sugar-sweetened beverages from 10.8% to 5.3% (difference, -5.5% [95% CI, -6.5% to -4.5%]) and for processed fats and oils, condiments, and sauces from 7.1% to 4.0% (difference, -3.1% [95% CI, -3.7% to -2.6%]) (all P < .05 for trend). There was a significantly larger increase in the estimated percentage of energy from consumption of ultraprocessed foods among non-Hispanic Black youths (from 62.2% to 72.5%; difference, 10.3% [95% CI, 6.8% to 13.8%]) and Mexican American youths (from 55.8% to 63.5%; difference, 7.6% [95% CI, 4.4% to 10.9%]) than the increase among non-Hispanic White youths (from 63.4% to 68.6%; difference, 5.2% [95% CI, 2.1% to 8.3%]) (P = .04 for trends).

Conclusions And Relevance: Based on the NHANES cycles from 1999 to 2018, the estimated proportion of energy intake from consumption of ultraprocessed foods has increased among youths in the US and has consistently comprised the majority of their total energy intake.
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http://dx.doi.org/10.1001/jama.2021.10238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356071PMC
August 2021

MMP1 regulated by NEAT1/miR-361-5p axis facilitates the proliferation and migration of cutaneous squamous cell carcinoma via the activation of Wnt pathway.

Cancer Biol Ther 2021 Jun 7;22(5-6):381-391. Epub 2021 Aug 7.

Department of Burn and Plastic Surgery, Shenzhen Longhua District Central Hospital, No. 187 Guanlan Avenue, Longhua District, Shenzhen, 518110, Guangdong, China.

Cutaneous squamous cell carcinoma (CSCC) is one of the most malignant tumors worldwide. It has been validated that matrix metallopeptidase 1 (MMP1) expression was obviously up-regulated in CSCC tissues. However, its specific role in CSCC is still unclear. RT-qPCR analysis and western blot assays were used to measure the mRNA and protein expressions, respectively. MTT and colony formation assays were conducted to assess proliferative ability. Transwell assays were adopted to evaluate migratory and invasive abilities. Flow cytometry and caspase-3/8/9 activity assays were carried out to evaluate cell apoptosis. Relevant mechanism experiments were finally performed to delineate molecular relationship among genes. We found that the expression of MMP1 was up-regulated in CSCC cells, and knockdown of MMP1 suppressed cell proliferation and invasion in CSCC. Subsequently, miR-361-5p was validated to target MMP1. Moreover, miR-361-5p was proved to be sponged by nuclear paraspeckle assembly transcript 1 (NEAT1) in CSCC. We further demonstrated that NEAT1 could activate Wnt pathway to affect cell proliferation and invasion. Finally, miR-361-5p inhibition rescued the suppressing effects of NEAT1 depletion on cell proliferation, invasion as well as Wnt pathway in CSCC. In summary, MMP1 regulated by NEAT1/miR-361-5p axis facilitated CSCC malignant behaviors via Wnt pathway activation.
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http://dx.doi.org/10.1080/15384047.2021.1941583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386739PMC
June 2021

Single cell RNA sequencing (scRNA-Seq) deciphering pathological alterations in streptozotocin-induced diabetic retinas.

Exp Eye Res 2021 Sep 6;210:108718. Epub 2021 Aug 6.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, 200080, Shanghai, China; National Clinical Research Center for Eye Diseases, 200080, Shanghai, China; Shanghai Key Laboratory of Fundus Diseases, 200080, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, 200080, Shanghai, China; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, 200080, Shanghai, China. Electronic address:

Diabetic retinopathy (DR) is an irreversible and progressive diabetic complication leading to visual impairment, even blindness. Due to the delicate and complicated structure of the retina, the pathology of DR has not been completely elucidated yet. We constructed a transcriptome atlas of >14,000 single cells from healthy and streptozotocin (STZ)-induced diabetic murine retinas to decipher pathological alterations of DR. We found four stress-inducible genes Cirbp, Rmb3, Mt1 and Mt2 commonly induced in most types of retinal cells. Bipolar cells were little affected on both number and gene expression. Diabetes increased expression of inflammatory factor genes in retinal microglia, and stimulated expression of immediate early genes (IEGs) in retinal astrocytes. A large number of genes were deregulated in diabetic vascular endothelial cells (ECs), and the differentially expressed genes were paired to the pathways functioning in metabolism, shear stress and vascular permeability. These pathways were mapped by more deregulated genes in a subpopulation of ECs specifically presented in diabetic retinas (diabetic retinal ECs, DRECs). Moreover, several inflammation pathways were activated in DRECs, and the most significant one is the IL-17 signaling pathway. According to the EC markers, DRECs were mainly capillary ECs, confirmed by immunofluorescent staining of S100a9, a target gene of the IL-17 signaling pathway. This study deciphered pathological alterations of DR, and provided clues for potential targets for DR therapy.
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http://dx.doi.org/10.1016/j.exer.2021.108718DOI Listing
September 2021

Clinical evaluation and animal experimental study of different mass concentrations of pingyangmycin in the local injection treatment of lip venous malformation.

Ann Transl Med 2021 Jun;9(11):929

Department of Otorhinolaryngology Head and Neck Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

Background: This study investigated the clinical efficacy of different mass concentrations of pingyangmycin in the local injection treatment of lip venous malformation. An animal experimental study of the histopathological effects of different mass concentrations of pingyangmycin on the normal lip tissue of rabbits was also conducted.

Methods: (I) We retrospectively analysed 98 out-patients with lip venous malformation in the Stomatological Hospital and the Fourth Affiliated Hospital of China Medical University from January 2008 to June 2013. The 98 cases were treated by local injection of different mass concentrations (8 mg/3 mL and 8 mg/5 mL) of pingyangmycin for the different sites of the lips. The clinical efficacy was observed, and adverse reactions were recorded. (II) 60 healthy male rabbits were randomly divided into three groups: a 8 mg/5 mL pingyangmycin group, a 8 mg/3 mL pingyangmycin group, and a control group. The right upper lips of the experimental groups were injected with 1ml pingyangmycin (8 mg/5 mL) and 1ml pingyangmycin (8 mg/3 mL) respectively, and the control group was injected with the same volume of normal saline. The thickness of the right upper lip of rabbits in the experimental groups and the control group was measured on the 21st, 28th, 35th, and 60th days after the first injection. Histopathological changes at the injection site were observed by light microscope and transmission electron microscope.

Results: Venous malformations involving the skin tissues of the lips (pingyangmycin 8 mg/3 mL) had an effective rate of 93.62%, and those involving the labial mucosa tissues (pingyangmycin 8 mg/5 mL) had an effective rate of 98.04%. In the animal experiment, there were statistically significant differences in the thickness of the injection site among the 8 mg/3 mL group, 8 mg/5 mL group, and the control group at different time points (P<0.01).

Conclusions: The local injection of pingyangmycin in the treatment of lip venous malformations was efficient, safe and reliable. In the process of clinical application, attention should be paid when the concentration is 8 mg/3 mL to avoid local tissue atrophy and other complications.
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http://dx.doi.org/10.21037/atm-21-2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263871PMC
June 2021

PIWI-interacting RNAs are aberrantly expressed and may serve as novel biomarkers for diagnosis of lung adenocarcinoma.

Thorac Cancer 2021 Sep 3;12(18):2468-2477. Epub 2021 Aug 3.

Department of Respiratory and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.

Background: Lung adenocarcinoma (LUAD) is the main subtype of primary lung cancer and is a leading cause of cancer-related death worldwide. PIWI-interacting RNAs (piRNAs) are a type of small non-coding RNAs that may play crucial roles in cancer progression and serve as biomarkers for tumor detection. This study aimed to explore the expression profiles and diagnostic values of piRNAs in LUAD.

Methods: Small RNA sequencing was performed to investigate tissue piRNA profiles of LUAD. The expression of selected upregulated piRNAs were detected in tissues and serum exosome samples by quantitative real-time polymerase chain reaction (qRT-PCR). Serum exosomes were identified by transmission electron microscope, nanoparticle tracking analysis, and western blot analysis. Receiver operating characteristic (ROC) curve was adopted to quantify the diagnostic potentials of piRNAs in LUAD. Finally, a piRNA panel was developed by multivariate logistic regression model.

Results: We identified that 76 piRNAs were overexpressed and 9 piRNAs were underexpressed in LUAD tissues compared with adjacent non-tumor tissues. Among the top 10 overexpressed piRNAs, 4 piRNAs (piR-hsa-26925, piR-hsa-5444, piR-hsa-30636, and piR-hsa-8757) were verified by qRT-PCR to be significantly upregulated in LUAD tissues. Moreover, piR-hsa-26925 and piR-hsa-5444 had a significantly higher level in serum exosome samples of LUAD patients than those of healthy controls. We finally established a 2-piRNA panel composed of piR-hsa-26925 and piR-hsa-5444, which showed higher diagnostic performance for LUAD with an AUC of 0.833.

Conclusions: Our finding revealed the abnormally expressed piRNAs in LUAD, and serum exosomal piR-hsa-26925 and piR-hsa-5444 could serve as potential biomarkers for LUAD diagnosis.
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http://dx.doi.org/10.1111/1759-7714.14094DOI Listing
September 2021

Exploring the Mechanism of Georgi Efficacy against Oral Squamous Cell Carcinoma Based on Network Pharmacology and Molecular Docking Analysis.

Evid Based Complement Alternat Med 2021 13;2021:5597586. Epub 2021 Jul 13.

Stomatology Hospital, Shanxi Medical University, Taiyuan 030001, China.

Background: Georgi (SBG) has been widely shown to induce apoptosis and inhibit invasion and migration of various cancer cells. Increased evidence shows that SBG may be useful to treat oral squamous cell carcinoma (OSCC). However, the biological activity and possible mechanisms of SBG in the treatment of OSCC have not been fully elucidated. This study aimed to clarify the bioactive component and multitarget mechanisms of SBG against OSCC using network pharmacology and molecular docking.

Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to predict the active components in SBG, and putative molecular targets of SBG were identified using the Swiss Target Prediction database. OSCC-related targets were screened by GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). Then, we established protein-protein interaction (PPI), compound-target-disease (C-T-D), and compound-target-pathway (C-T-P) networks by Cytoscape to identify the main components, core targets, and pharmacological pathways of SBG against OSCC via applying data mining techniques and topological parameters. Metascape database was utilized for Gene Ontology (GO) and pathway enrichment analysis. The potential interaction of the main components with core targets was revealed by molecular docking simulation, and for the correlation between core targets and OSCC prognosis analysis, the Kaplan-Meier Plotter online database was used.

Results: There were 25 active compounds in SBG and 86 genes targeted by OSCC. A total of 141 signaling pathways were identified, and it was found that the PI3K-Akt signaling pathway may occupy core status in the anti-OSCC system. GO analysis revealed that the primary biological processes were related to apoptosis, proliferation, and migration. Molecular docking results confirmed that core targets of OSCC had a high affinity with the main compounds of SBG.

Conclusion: Our study demonstrated multicomponent, multitarget, and multipathway characteristics of SBG in the treatment of OSCC and provided a foundation for further drug development research.
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http://dx.doi.org/10.1155/2021/5597586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292061PMC
July 2021

Occurrence, distribution, and prediction of iron and manganese in groundwater of opencast mines: an example from Inner Mongolia, China.

Environ Monit Assess 2021 Jul 31;193(8):544. Epub 2021 Jul 31.

School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, People's Republic of China.

Based on the geological and hydrologic data, the generation, enrichment, and transportation of iron (Fe) and manganese (Mn) ions in Yimin open-pit mining area were investigated using water quality analysis of groundwater samples, Statistical Product and Service Solutions (SPSS) principal component analysis, and geostatistics analysis by Geographic Information System (GIS). The water quality test results showed that the groundwater of this area was mainly the Na-Ca-HCO type, and the content of Fe and Mn ions significantly exceeded the national standard. The groundwater in the mining area was strongly affected by human activity, deep groundwater mixing effect, and water-rock interaction associated with mining activities. It was also found that Fe and Mn in the research area had a large variation in spatial distribution. On the whole, Fe and Mn ion concentrations found in the groundwater to the north of the research area were higher than those in the south area, with the mining area as the dividing line. The removing of non-mineral layer and the draining of gushing water in the mining area resulted in the formation of a water funnel and the strengthening of an effect between each aquifer. The change of hydrogeological and redox conditions in the mining area promoted the dissolution of Fe and Mn in soil and stratum and migration in groundwater.
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http://dx.doi.org/10.1007/s10661-021-09262-0DOI Listing
July 2021

Clinical potentials of ginseng polysaccharide for treating gestational diabetes mellitus.

World J Clin Cases 2021 Jul;9(19):4959-4979

First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang 550002, Guizhou Province, China.

Gestational diabetes mellitus (GDM) is the most common glucose metabolism complication or cause of potential impaired glucose tolerance that can occur either before or during pregnancy and lactation. The prevalence of GDM and its related complications in young women is increasing, and this condition may cause serious outcomes and health hazards to the foetus. However, traditional oral hypoglycaemic drugs have potential safety hazards; therefore, it is urgent to develop new, safe, effective, and easily administered agents and remedies. Ginseng polysaccharide (GPS), which is isolated from (P.) C. A. Meyer, exhibits notably promising biological activities and effects; specifically, it has been shown to lower blood glucose with mild, safe, and nontoxic characteristics, and it can also improve human bodily functions. Hence, we hypothesise that GPS might be used as an additional therapy and candidate agent for treating GDM. This review innovatively summarizes the available reports and evidence from basic studies to analyze the potential for and feasibility of using GPS as a new therapeutic agent for treating GDM. Additionally, for the first time, this review provides a rationale for the use of GPS. Our summarized results show that GPS may be developed as a novel antidiabetic drug and a remedy for use in preventing and treating GDM, with great application prospects.
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http://dx.doi.org/10.12998/wjcc.v9.i19.4959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283579PMC
July 2021

Rapid Secondary Recrystallization of the Goss Texture in FeGa Sheets Using Nanosized NbC Particles.

Materials (Basel) 2021 Jul 8;14(14). Epub 2021 Jul 8.

Key Laboratory for Anisotropy and Texture of Materials, Ministry of Education, Northeastern University, Shenyang 110819, China.

Herein, a simple and efficient method is proposed for fabricating FeGa alloy thin sheets with a high magnetostriction coefficient. Sharp Goss texture ({110}<001>) was successfully produced in the sheets by rapid secondary recrystallization induced by nanosized NbC particles at low temperatures. Numerous NbC precipitates (size ~90 nm) were obtained after hot rolling, intermediate annealing, and primary recrystallization annealing. The relatively higher quantity of nanosized NbC precipitates with 0.22 mol% resulted in finer and uniform grains (~10 μm) through thickness after primary recrystallization annealing. There was a slow coarsening of the NbC precipitates, from 104 nm to 130 nm, as the temperature rose from 850 °C to 900 °C in a pure nitrogen atmosphere, as well as a primary recrystallization textured by strong γ fibers with a peak at {111} <112> favoring the development of secondary recrystallization of Goss texture at a temperature of 850 °C. Matching of the appropriate inhibitor characteristics and primary recrystallization texture guaranteed rapid secondary recrystallization at temperatures lower than 950 °C. A high magnetostriction coefficient of 304 ppm was achieved for the FeGa sheet after rapid secondary recrystallization.
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http://dx.doi.org/10.3390/ma14143818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306011PMC
July 2021

Programmed cell death-ligand 1 expression predicts poor treatment response and prognostic value in esophageal squamous cell carcinoma patients without esophagectomy.

Aging (Albany NY) 2021 07 22;13(14):18827-18838. Epub 2021 Jul 22.

Department of Radiation Oncology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 26400, Shandong, China.

Research on association between programmed cell death ligand 1 (PD-L1) expression in cancer cells and prognosis of esophageal squamous cell carcinoma (ESCC) has been controversial and has focused on patients with surgical resection. We aimed to investigate impact of PD-L1 on treatment response and prognostic value in ESCC and analyze which subset of patients may benefit from immunotherapy. The PD-L1 expression was evaluated by immunohistochemical analysis in all patients. Stratification analysis was performed according to whether surgery was performed. There were no significant correlations between PD-L1 expression with 3-year overall survival (OS) and progression-free survival (PFS) in 81 ESCC patients. Then stratification analysis was performed. Among these 44 patients without surgery, disease control rate (DCR) in negative PD-L1 expression group (78%) was significantly better than those (42%) in positive PD-L1 expression group ( = 0.032). There were no significant correlations between PD-L1 expression with 3-year OS and PFS in 37 ESCC patients receiving surgery. However, in 44 ESCC patients without surgery, the Kaplan-Meier method showed that 3-year OS and PFS in negative PD-L1 expression group were significantly better than those in positive PD-L1 expression group. In Cox univariate and multivariate model, PD-L1 was an independent prognosticator for inferior OS ( = 0.011; = 0.017). Our research revealed prognostic role of PD-L1 expression in cancer cells may be variable in different treatment methods. Consequently, PD-L1 may serve as an independent prognostic factor and provide a theoretical basis for combining conventional therapy with immunotherapy targeting PD-L1 to achieve better treatment outcome in ESCC patients without esophagectomy.
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http://dx.doi.org/10.18632/aging.203326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351667PMC
July 2021

Analysis of gut microbiota alteration and application as an auxiliary prognostic marker for sepsis in children: a pilot study.

Transl Pediatr 2021 Jun;10(6):1647-1657

The Laboratory of Pediatric Infectious Diseases, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Emerging evidence suggests that gut microbiota dysbiosis plays a role in sepsis. Recent advances in sequencing technology enable the characterization of the gut microbiota and can provide clues for the pathogenesis of sepsis, which may help develop biomarkers for diagnosis or prognosis prediction in children with sepsis.

Methods: The gut microbiota from 25 children with sepsis and 15 age- and sex-matched healthy controls were extracted and sequenced by high-throughput Illumina Hiseq, targeting the 16S rDNA genes. The differences of gut microbiota between the two groups were analyzed to assess if the gut microbiota can be used as an auxiliary prognostic marker for sepsis.

Results: The diversity of gut microbiota in children with sepsis was significantly lower than that of healthy controls (P<0.001). The overall community structure of gut microbiota was also altered considerably. On the genus level, children with sepsis had more opportunistic pathogens, such as and , while fewer beneficial bacterial, such as , , , , and , were detected. Further analysis of the association between the gut microbiota and clinical features revealed that the pathogens from bacteria culture correlated to the dominant bacteria genus detected in the intestinal flora. Furthermore, the gut microbiota diversity was negatively associated with the antibiotic therapy duration, but did not correlate with type of antibiotics used. Finally, gut microbiota disturbance was correlated with increased mortality rate.

Conclusions: Overall, we confirmed that gut microbiota disturbance occurred in the children with sepsis, and changes in the fecal microbiota were closely related to clinical characteristics. Elucidation of such dysbiosis could improve our understanding of sepsis pathogenesis and help develop microbiota-based diagnosis, monitoring, and therapy for sepsis.
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http://dx.doi.org/10.21037/tp-21-51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261590PMC
June 2021

Expression patterns and prognostic value of RUNX genes in kidney cancer.

Sci Rep 2021 Jul 22;11(1):14934. Epub 2021 Jul 22.

Department of Anesthesia, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.

Kidney cancer is the third most common malignancy of the urinary system, of which, kidney renal clear cell carcinoma (KIRC) accounts for the vast majority. Runt-related transcription factors (RUNX) are involved in multiple cellular functions. However, the diverse expression patterns and prognostic values of RUNX genes in kidney cancer remained to be elucidated. In our study, we mined the DNA methylation, transcriptional and survival data of RUNX genes in patients with different kinds of kidney cancer through Oncomine, Gene Expression Profiling Interactive Analysis, UALCAN, Kaplan-Meier Plotter, cBioPortal and LinkedOmics. We found that RUNX1 and RUNX3 were upregulated in KIRC tissues compared with those in normal tissues. The survival analysis results indicated a high transcription level of RUNX1 was associated with poor overall survival (OS) in KIRC patients. Furthermore, KIRC tumor tissues had significantly lower levels of RUNX1 promoter methylation than that in paracancerous tissues, with decreased DNA methylation of RUNX1 notably associated with poor OS in KIRC. In conclusion, our results revealed that RUNX1 may be a potential therapeutic target for treating KIRC, and RUNX1 promoter methylation level shows promise as a novel diagnostic and prognostic biomarker, which laid a foundation for further study.
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http://dx.doi.org/10.1038/s41598-021-94294-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298387PMC
July 2021

Preventive and Therapeutic Effects of a Novel JAK Inhibitor SHR0302 in Acute Graft-Versus-Host Disease.

Cell Transplant 2021 Jan-Dec;30:9636897211033778

Department of Hematology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Acute graft-versus-host disease (aGVHD) is one of the most common complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Janus kinase (JAK) inhibitors are considered as reliable and promising agents for patients with aGVHD. The prophylactic and therapeutic effects of SHR0302, a novel JAK inhibitor, were evaluated in aGVHD mouse models. The overall survival (OS), progression-free survival (PFS), bodyweight of mice, GVHD scores were observed and recorded. The bone marrow and spleen samples of diseased model mice or peripheral blood of patients were analyzed. SHR0302 could prevent and reverse aGVHD in mouse models with preserving graft-versus-tumor effect. Functionally, SHR0302 improved the OS and PFS, restored bodyweight, reduced GVHD scores, and reduced immune cells infiltrated in target tissues. SHR0302 treatment also enhanced the hematopoietic reconstruction compared to the control group. Mechanistically, our results suggested that SHR0302 could inhibit the activation of T cells and modulate the differentiation of helper T (Th) cells by reducing Th1 and increasing regulatory T (Treg) cells. In addition, SHR0302 decreased the expression of chemokine receptor CXCR3 on donor T cells and the secretion of cytokines or chemokines including interleukin (IL)-6, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), CXCL10, etc. thereby destroying the IFN-γ/CXCR3/CXCL10 axis which promotes the progression of GVHD. Besides, SHR0302 decreased the phosphorylation of JAK and its downstream STATs, AKT and ERK1/2, which ultimately regulated the activation, proliferation, and differentiation of lymphocytes. Experiments on primary cells from aGVHD patients also confirmed the results. In summary, our results indicated that JAK inhibitor SHR0302 might be used as a novel agent for patients with aGVHD.
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http://dx.doi.org/10.1177/09636897211033778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287347PMC
July 2021

An amorphous WC thin film enabled high-efficiency N reduction electrocatalysis under ambient conditions.

Chem Commun (Camb) 2021 Aug;57(63):7806-7809

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China.

Ambient electrochemical N2 reduction offers a promising alternative to the energy-intensive Haber-Bosch process towards renewable NH3 synthesis in aqueous media but needs efficient electrocatalysts to enable the N2 reduction reaction (NRR). Herein, we propose that an amorphous WC thin film magnetron sputtered onto a graphite foil behaves as a superb NRR electrocatalyst for ambient NH3 production with excellent selectivity. In 0.5 M LiClO4, it attains a large NH3 yield of 43.37 μg h-1 mg-1cat. and a high faradaic efficiency of 21.65% at -0.10 V vs. reversible hydrogen electrode. Impressively, this catalyst also shows excellent selectivity and strong durability for NH3 formation.
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http://dx.doi.org/10.1039/d1cc03139bDOI Listing
August 2021
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