Publications by authors named "Chong Li"

638 Publications

Discovery and Optimization of a Novel 2-Pyrazolo[3,4-d]pyrimidine Derivative as a Potent Irreversible Pan-Fibroblast Growth Factor Receptor Inhibitor.

J Med Chem 2021 Jun 15. Epub 2021 Jun 15.

The State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, College of Pharmacy, Nankai University, Tianjin 300071, P. R. China.

Fibroblast growth factor receptors (FGFRs) have become promising therapeutic targets in various types of cancers. In fact, several selective irreversible inhibitors capable of covalently reacting with the conserved cysteine of FGFRs are currently being evaluated in clinical trials. In this article, we optimized and discovered a novel lead compound with remarkable inhibitory effects against FGFR (1-3), which is a derivative of 2-pyrazolo[3,4-d]pyrimidine. The irreversible binding to FGFRs was characterized by LC-MS. This compound has been shown to exhibit significant anti-proliferation effects against NCI-H1581 and SNU-16 cancer cell lines both and . Compound has also demonstrated a low toxicity profile and adequate pharmacokinetic properties and is currently under validation as a potential drug candidate.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00174DOI Listing
June 2021

One-step enzyme kinetics measurement in 3D printed microfluidics devices based on a high-performance single vibrating sharp-tip mixer.

Anal Chim Acta 2021 Aug 24;1172:338677. Epub 2021 May 24.

C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, USA. Electronic address:

Measuring enzyme kinetics is of great importance to understand many biological processes and improve biosensing and industrial applications. Conventional methods of measuring enzyme kinetics require to prepare a series of solutions with different substrate concentrations and measure the signal response over time with these solutions, leading to tedious sample preparation steps, high reagents/sample consumption, and difficulties in studying fast enzyme kinetics. Here we report a one-step assay to measure enzyme kinetics using a 3D-printed microfluidic device, which eliminates the steps of preparing and handling multiple solutions thereby simplifying the whole workflow significantly. The assay is enabled by a highly efficient vibrating sharp-tip mixing method that can mix multiple streams of fluids with minimal mixing length (∼300 μm) and time (as low as 3 ms), and a wide range of working flow rates from 1.5 μL/min to 750 μL/min. Owing to the high performance of the mixer, a series of experiments with different substrate concentrations are performed by simply adjusting the flow rates of reagents loaded from three inlets in one experiment run. The Michaelis-Menten kinetics of the horseradish peroxidase (HRP)-catalyzed reaction between HO and amplex red is measured in this system. The calculated Michaelis constant is consistent with the values from literature and conventional analysis methods. Due to the simplicity in fabrication and operation, rapid analysis, low power consumption (1.4-45.0 mW), and high temporal resolution, this method will significantly facilitate enzyme kinetics measurement, and offers great potential for optimizing enzyme based biosensing experiments and probing many biochemical processes.
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http://dx.doi.org/10.1016/j.aca.2021.338677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206521PMC
August 2021

Frontiers in Bladder Cancer Genomic Research.

Front Oncol 2021 20;11:670729. Epub 2021 May 20.

Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Most of the etiology studies of bladder cancer focus on genetic changes, mainly including mutation and activation of oncogenes, mutation and inactivation of tumor suppressor genes, and rearrangement or heterozygous deletion of chromosomes. Moreover, bladder cancer is highly heterogeneous mainly due to abnormal changes in the genome and proteome of tumor cells. Surgery is the main treatment for bladder cancer, but because the recurrence rate is high after surgery and most of the muscle-invasive bladder cancer acquires distant metastasis. Therefore, there is a need to combine with chemotherapy to consolidate the treatment effect. However, there are differences in chemosensitivity among patients. In this article, we review the up-to-date genomic researches on bladder cancer occurrence, development, metastasis, and chemosensitivity in patients, in order to provide some theoretical support for the diagnosis and treatment strategy for bladder cancer.
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http://dx.doi.org/10.3389/fonc.2021.670729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173177PMC
May 2021

Growing in Mixed Stands Increased Leaf Photosynthesis and Physiological Stress Resistance in Moso Bamboo and Mature Chinese Fir Plantations.

Front Plant Sci 2021 20;12:649204. Epub 2021 May 20.

State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Lin'an, China.

Mixed-stand plantations are not always as beneficial for timber production and carbon sequestration as monoculture plantations. Systematic analyses of mixed-stand forests as potential ideal plantations must consider the physiological-ecological performance of these plantations. This study aimed to determine whether mixed moso bamboo ( (Pradelle) Mazel ex J. Houz.) and Chinese fir ( (Lamb.) Hook.) stands exhibited better physiological-ecological performance than monoculture plantations of these species. We analyzed leaf photosynthesis, chlorophyll fluorescence, antioxidant enzyme activities, chlorophyll content and leaf chemistry in a moso bamboo stand, a Chinese fir stand and a mixed stand with both species. The results showed that both species in the mixed stand exhibited significantly higher leaf net photosynthesis rate (Amax), instantaneous carboxylation efficiency (CUE), chlorophyll content, maximum quantum yield of photosynthesis (Fv/Fm), photochemical quenching coefficient (qP), PSII quantum yield [Y(II)], leaf nitrogen content, and antioxidant enzyme activities than those in the monoculture plantations. However, the non-photochemical quenching (NPQ) in Chinese fir and 2-year-old moso bamboo was significantly lower in the mixed stand than in the monocultures. In addition, the water use efficiency (WUE) of Chinese fir was significantly higher in the mixed stand. The results suggest that the increase in leaf net photosynthetic capacity and the improved growth in the mixed stand could be attributed primarily to the (i) more competitive strategies for soil water use, (ii) stronger antioxidant systems, and (iii) higher leaf total nitrogen and chlorophyll contents in the plants. These findings suggest that mixed growth has beneficial effects on the leaf photosynthesis capacity and physiological resistance of moso bamboo and Chinese fir.
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http://dx.doi.org/10.3389/fpls.2021.649204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173113PMC
May 2021

Adiponectin modulates steroid hormone secretion, granulosa cell proliferation and apoptosis via binding its receptors during hens' high laying period.

Poult Sci 2021 Apr 11;100(7):101197. Epub 2021 Apr 11.

College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450046, China; Henan Key laboratory for innovation and utilization of chicken germplasm resources, Zhengzhou, 450046, China.

Adiponectin is an important adipocytokine and plays the roles in multiple metabolic processes via binding its receptors - AdipoR1 and AdipoR2, which has also been found to participate in the regulation of the reproductive system of animals, in particular by influencing the secretion of ovarian steroid hormones. To further investigate the expression of adiponectin and its receptors in follicles after in vitro incubation, and their role in the steroid synthesis of laying hens' ovaries, we performed qRT-PCR and ELISA to detect the expressions of AdipoQ, AdipoR1, and AidpoR2, and determined the key genes involved in steroidogenesis and the secretion of estradiol (E2) and progesterone (P4) through the in vitro activation of adiponectin (AipoRon) and overexpression or knockdown of AdipoR1 and AdipoR2. Our results revealed that adiponectin and its receptors wildly exist in follicles and granulosa cells, and AdipoRon (5 and 10 µg/mL) had no effect on granulosa cell proliferation and apoptosis but significantly stimulated the secretion of adiponectin and its receptors in granulosa cells after incubation for 24 h. Furthermore, AdipoRon could significantly stimulate the secretion of P4 and inhibit E2 level compared to those of the control group through modulating the key genes expression of steroidogenesis (CYP19A1, StAR, CYP11A1, FSHR, and LHR). The secretion of E2 was also decreased in granulosa cells by the treatments of overexpression and knockdown of AdipoR1/2, however, there was no difference in terms of the level of P4 and StAR expression between them if there was overexpression or knockdown of AdipoR1/2. In addition, it was shown that the secretion of E2 only exhibits a marked drop if co-processing 10 µg/mL AdipoRon and pGMLV AdipoR2 compared to single treatments. Taken together, the study highlighted the role of adiponectin and its receptors in the regulation of steroid synthesis and secretion in ovarian granulosa cells in laying hens.
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http://dx.doi.org/10.1016/j.psj.2021.101197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182267PMC
April 2021

Antioxidant Effect of Soymilk Fermented by HFY01 on D-Galactose-Induced Premature Aging Mouse Model.

Front Nutr 2021 17;8:667643. Epub 2021 May 17.

First Affiliated Hospital of Gannan Medical University, Ganzhou, China.

The antioxidant effect of soymilk fermented by HFY01 (screened from yak yogurt) was investigated on mice with premature aging induced by D-galactose. antioxidant results showed that HFY01-fermented soymilk (LP-HFY01-DR) had better ability to scavenge the free radicals 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt (ABTS) than unfermented soymilk and -fermented soymilk. Histopathological observation showed that LP-HFY01-DR could protect the skin, spleen and liver, reduce oxidative damage and inflammation. Biochemical results showed that LP-HFY01-DR could effectively upregulate glutathione (), catalase (), superoxide dismutase (), and glutathione peroxidase () levels and decrease malondialdehyde () content in the liver, brain, and serum. Real-time quantitative reverse transcription polymerase chain reaction further showed that LP-HFY01-DR could promote the relative expression levels of the genes encoding for cuprozinc superoxide dismutase (), manganese superoxide dismutase (), , and in the liver, spleen, and skin. High-performance liquid chromatography results revealed daidzin, glycitin, genistin, daidzein, glycitein, and genistein in LP-HFY01-DR. In conclusion, LP-HFY01-DR could improve the antioxidant capacity in mice with premature aging induced by D-galactose.
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http://dx.doi.org/10.3389/fnut.2021.667643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165163PMC
May 2021

Avian Influenza H7N9 Virus Adaptation to Human Hosts.

Viruses 2021 05 10;13(5). Epub 2021 May 10.

Centre for Bioinformatics, School of Data Sciences, Perdana University, Wisma Chase Perdana, Changkat Semantan, Damansara Heights, Kuala Lumpur 50490, Malaysia.

Avian influenza virus A (H7N9), after circulating in avian hosts for decades, was identified as a human pathogen in 2013. Herein, amino acid substitutions possibly essential for human adaptation were identified by comparing the 4706 aligned overlapping nonamer position sequences (1-9, 2-10, etc.) of the reported 2014 and 2017 avian and human H7N9 datasets. The initial set of virus sequences (as of year 2014) exhibited a total of 109 avian-to-human (A2H) signature amino acid substitutions. Each represented the most prevalent substitution at a given avian virus nonamer position that was selectively adapted as the corresponding index (most prevalent sequence) of the human viruses. The majority of these avian substitutions were long-standing in the evolution of H7N9, and only 17 were first detected in 2013 as possibly essential for the initial human adaptation. Strikingly, continued evolution of the avian H7N9 virus has resulted in avian and human protein sequences that are almost identical. This rapid and continued adaptation of the avian H7N9 virus to the human host, with near identity of the avian and human viruses, is associated with increased human infection and a predicted greater risk of human-to-human transmission.
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http://dx.doi.org/10.3390/v13050871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150935PMC
May 2021

Laser-Induced Carbon Electrodes in a Three-Dimensionally Printed Flow Reactor for Detecting Lead Ions.

ACS Omega 2021 May 4;6(19):12470-12479. Epub 2021 May 4.

Department of Chemistry, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024 Liaoning, P.R. China.

Nowadays, heavy metal pollution has attracted wide attention. Many electrochemical methods have been developed to detect heavy metal ions. The electrode surface usually needs to be modified, and the process is complicated. Herein, we demonstrate the fabrication of electrodes by direct laser sintering on commercial polymer films. The prepared porous carbon electrodes can be used directly without any modification. The electrodes were fixed in a 3D-printed flow reactor, which led to very little analyte required during the detection process. The velocities of the analyte under stirring and flowing conditions were simulated numerically. The results prove that flow detection is more conducive to improving detection sensitivity. The limit of detection is about 0.0330 mg/L for Pb. Moreover, the electrode has been proved to have good repeatability and stability.
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http://dx.doi.org/10.1021/acsomega.0c06274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154136PMC
May 2021

A potential probiotic bacterium for antipsychotic-induced metabolic syndrome: mechanisms underpinning how Akkermansia muciniphila subtype improves olanzapine-induced glucose homeostasis in mice.

Psychopharmacology (Berl) 2021 May 27. Epub 2021 May 27.

Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.

Background: Olanzapine (OLZ) is one of the most effective atypical antipsychotics but is associated with severe metabolic side effects, in which the gut microbiota plays an important role. Akkermansia muciniphila (A. muciniphila; Akk), a Gram-negative anaerobic bacterium in the intestine, can potentially improve metabolic syndrome.

Objective: This study investigated the effect and underlying mechanisms of an A. muciniphila subtype (A. muciniphila; Akk) on OLZ-induced metabolic dysfunction in lean and obese mice.

Methods: C57BL/6 female mice were fed a high-fat diet to induce obesity or normal chow for 8 weeks before OLZ treatment for 16 weeks. During the treatment period, mice in each group were orally administrated A. muciniphila. Weight gain, glucose and lipid metabolism, and inflammation were evaluated.

Results: A. muciniphila decreased OLZ-related weight gain only at week 16 in lean mice and significantly alleviated OLZ-induced hyperglycemia irrespective of diet. This was accompanied by reduced levels of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK)-key enzymes in hepatic gluconeogenesis-and OLZ-associated insulin resistance. Moreover, OLZ-induced increases in serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were improved by A. muciniphila in both obese and lean mice. OLZ did not increase serum lipid levels or hepatic fat accumulation.

Conclusions: A. muciniphila improves OLZ-related hyperglycemia via regulation of G6Pase and PEPCK levels and insulin resistance. Moreover, A. muciniphila alleviates systemic inflammation caused by OLZ. A. muciniphila is a promising probiotic treatment for OLZ-induced metabolic dysfunction.
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http://dx.doi.org/10.1007/s00213-021-05878-9DOI Listing
May 2021

AddictGene: An integrated knowledge base for differentially expressed genes associated with addictive substance.

Comput Struct Biotechnol J 2021 19;19:2416-2422. Epub 2021 Apr 19.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.

Addiction, a disorder of maladaptive brain plasticity, is associated with changes in numerous gene expressions. Nowadays, high-throughput sequencing data on addictive substance-induced gene expression have become widely available. A resource for comprehensive annotation of genes that show differential expression in response to commonly abused substances is necessary. So, we developed AddictGene by integrating gene expression, gene-gene interaction, gene-drug interaction and epigenetic regulatory annotation for over 70,156 items of differentially expressed genes associated with 7 commonly abused substances, including alcohol, nicotine, cocaine, morphine, heroin, methamphetamine, and amphetamine, across three species (human, mouse, rat). We also collected 1,141 addiction-related experimentally validated genes by techniques such as RT-PCR, northern blot and hybridization. The easy-to-use web interface of AddictGene (http://159.226.67.237/sun/addictgedb/) allows users to search and browse multidimensional data on DEGs of their interest: 1) detailed gene-specific information extracted from the original studies; 2) basic information about the specific gene extracted from NCBI; 3) SNP associated with substance dependence and other psychiatry disorders; 4) expression alteration of specific gene in other psychiatric disorders; 5) expression patterns of interested gene across 31 primary and 54 secondary human tissues; 6) functional annotation of interested gene; 7) epigenetic regulators involved in the alteration of specific genes, including histone modifications and DNA methylation; 8) protein-protein interaction for functional linkage with interested gene; 9) drug-gene interaction for potential druggability. AddictGene offers a valuable repository for researchers to study the molecular mechanisms underlying addiction, and might provide valuable insights into potential therapies for drug abuse and relapse.
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http://dx.doi.org/10.1016/j.csbj.2021.04.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113760PMC
April 2021

MEF2C silencing downregulates NF2 and E-cadherin and enhances Erastin-induced ferroptosis in meningioma.

Neuro Oncol 2021 May 13. Epub 2021 May 13.

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Ferroptosis, a programmed cell death characterized by lipid peroxidation, is implicated in various diseases including cancer. Although cell density-dependent E-cadherin and Merlin/Neurofibromin (NF2) loss can modulate ferroptosis, the role of ferroptosis and its potential link to NF2 status and E-cadherin expression in meningioma remain unknown.

Methods: Relationship between ferroptosis modulators expression and NF2 mutational status was examined in 35 meningiomas (10 NF2 loss and 25 NF2 wildtype). The impact of NF2 and E-cadherin on ferroptosis were examined by LDH release, lipid peroxidation and western blot assays in IOMM-Lee, CH157 and patient-derived meningioma cell models. Luciferase reporter and chromatin immunoprecipitation assays were used to assess the ability of MEF2C (myocyte enhancer factor 2C) to drive expression of NF2 and CDH1 (E-cadherin). Therapeutic efficacy of Erastin-induced ferroptosis was tested in xenograft mouse models.

Results: Meningioma cells with NF2 inactivation were susceptible to Erastin-induced ferroptosis. Meningioma cells grown at higher density increased expression of E-Cadherin, which suppressed Erastin-induced ferroptosis. Maintaining NF2 and E-cadherin inhibited ferroptosis-related lipid peroxidation and meningioma cell death. MEF2C was found to drive the expression of both NF2 and E-cadherin. MEF2C silencing enhanced Erastin-induced ferroptotic meningioma cell death and lipid peroxidation levels in vitro, which was limited by forced expression of MEF2C targets, NF2 and E-Cadherin. In vivo, anti-meningioma effect of Erastin was augmented by MEF2C knockdown and was counteracted by NF2 or E-Cadherin.

Conclusions: NF2 loss and low E-cadherin create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma.
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http://dx.doi.org/10.1093/neuonc/noab114DOI Listing
May 2021

Fluoride exposure decreased neurite formation on cerebral cortical neurons of SD rats in vitro.

Environ Sci Pollut Res Int 2021 May 11. Epub 2021 May 11.

College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.

Fluoride, a geochemical element, can damage the brain and result in dysfunction of the central nervous system. In recent years, fluoride-induced neurotoxicity has become one of research focuses of environmental toxicology. Our previous study showed that fluoride could induce the structural damages of the cerebral cortex and reduce the learning and memory abilities of mice offspring. However, the underlying mechanisms of these effects remain unclear. In this study, primary neurons were isolated from the cerebral cortices of postnatal 1-day SD rats. The primary cultured cerebral cortical neurons were adherent and the cellular network was obvious. Neurons were identified by Nissl's staining and were used for experiments. Different concentrations of sodium fluoride (0.5, 1.0, 1.5, 2.0 and 2.5 mM) were chosen to explore its toxic effects on neuron of SD rats in vitro. Results showed that neuronal morphology was obviously damaged in 2.0 and 2.5 mM, but was not adversely affected in 0.5 and 1 mM. Further studies revealed that the neurites of neuron were shrunken and even became fractured with the increase in NaF dose, which have been detected by scanning electron microscopy (SEM). Meanwhile, TEM showed marginated chromatin, widened nuclear gaps, damaged nuclei and swollen or even absent mitochondria in 1.5, 2 and 2.5 mM group. The cytoskeletal staining was consistent with the above results. The number of neurites of cerebral cortical neuron significantly decreased after fluoride exposure by immunofluorescent assay. In summary, high fluoride (1.5, 2 and 2.5 mM) concentrations exerted a significant toxic effect on the cellular morphologies and neural formation of primary cultured cortical neurons. These findings provide new insights into the roles of NaF in neuronal damage and can contribute to an improved understanding of fluoride-induced neurotoxicity.
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http://dx.doi.org/10.1007/s11356-021-13950-2DOI Listing
May 2021

Targeted Sequencing Analysis of Predominant Histological Subtypes in Resected Stage I Invasive Lung Adenocarcinoma.

J Cancer 2021 2;12(11):3222-3229. Epub 2021 Apr 2.

Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, China.

Lung adenocarcinoma (LADC) is classified into five main histological subtypes with distinct clinicopathologic characteristics: lepidic-predominant adenocarcinoma (LPA), acinar-predominant adenocarcinoma (APA), papillary-predominant adenocarcinoma (PPA), micropapillary-predominant adenocarcinoma (MPA) and solid-predominant adenocarcinoma (SPA). However, the mutational profiles of predominant histological subtypes have not been well defined. In this study, we aimed to reveal the genomic landscape of 5 main histological subtypes. We performed next-generation sequencing (NGS) in a cohort of 86 stage I invasive adenocarcinoma (IAC) patients, using a customized panel including 168 cancer-associated genes. Our analysis identified a total of 302 genomic alterations. Five subtypes showed different mutation profiles with LPA, APA, PPA, MPA and SPA had an average mutation rate of 1.95 (range: 0-5), 2.56 (range: 1-6), 3.5 (range: 1-7), 3.75 (range: 1-8) and 6.05 (range: 2-12), respectively (p=4.17e-06). Driver mutations occurred in 96.55% (83/86) of all patients. EGFR (73.3%), KRAS (9.3%), ALK (4.7%) and MET (4.7%) are the most commonly mutated lung cancer driver genes, TP53 is the top mutated tumor suppressor gene. SPA patients harbored more driver mutations and higher frequency of TP53 than LPA patients. Interestingly, mutations, which has been reported to be associated with high tumor mutation burden and better response to immunotherapy, were only detected from 5 SPA patients (p=0.001). No patients from other four cohorts harbored mutations. We revealed distinctive mutation landscape of the 5 major histological subtypes of LADC, evident by distinctive average mutation rate with SPA and LPA having the highest and lowest average mutation rate, respectively. SPA patients showed higher mutation rate of LRP1B and higher rates for PD-L1 positivity, indicating that SPA patients may have better response to immunotherapy.
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http://dx.doi.org/10.7150/jca.51405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100815PMC
April 2021

Protective Effects of Silymarin Against D-Gal/LPS-Induced Organ Damage and Inflammation in Mice.

Drug Des Devel Ther 2021 4;15:1903-1914. Epub 2021 May 4.

Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing, 400067, People's Republic of China.

Aim: Silymarin contains various flavonoids and exhibits antioxidative, anti-inflammatory, and anticancer effects, in addition to other pharmacological properties. This study explored the alleviating effect of silymarin on multiple-organ damage induced by D-galactose/lipopolysaccharide in Kunming mice.

Methods: Kunming mice were injected intraperitoneally with D-galactose (30 mg/kg·BW)/LPS (3 μg/kg·BW) and then treated using silymarin with different doses (75 mg/kg·bw and 150 mg/kg·bw) via intragastric administration. Changes in organ indexes, pathological changes, liver-function index, biochemical indexes, molecular biological indexes, and genes related to the oxidation and inflammation of main organs were evaluated.

Results: After the mice were treated with silymarin, their body weight showed no significant change, and the liver, kidney, and lung indexes of the treated mice were higher than those of the model group; meanwhile, the corresponding histopathological formation was reduced. Compared with the model group, the silymarin-treated group showed reductions in ALT, AST, and liver function indexes in the mouse serum. Silymarin treatment also increased the SOD, CAT, GSH, GSH-Px, T-AOC, IL-10, and IL-12 levels, as well as reduced the MDA, NO, IL-6, IL-1β, TNF-α, IFN-γ levels in the mouse serum and liver tissues. In addition, quantitative polymerase chain reaction analysis indicated that the mRNA expression levels of , and were higher in the liver tissue of the silymarin-treated mice than in those of the model group; meanwhile, the mRNA expression levels of , and were lower than those in the model group.

Conclusion: Silymarin, which exhibits antioxidative and anti-inflammatory effects, can alleviate the liver, lung, and kidney damage induced by D-galactose/lipopolysaccharide. High-dose (150 mg/kg·bw) silymarin can more effectively inhibit organ damage, compared with low-dose silymarin (75 mg/kg·bw) in Kunming mice.
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http://dx.doi.org/10.2147/DDDT.S305033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106468PMC
May 2021

Why clinical training in China should improve: a cross-sectional study of MD graduates.

BMC Med Educ 2021 May 10;21(1):266. Epub 2021 May 10.

Center for Research and Development of Education, University Medical Center Utrecht, Utrecht, the Netherlands.

Background: China is experiencing major medical education reforms that include establishing national training standards, standards for health professionals, and advanced health delivery system requirements. Graduate medical education (GME) is being piloted as a merger of Doctor of Medicine (MD) with PhD programs to improve academic research and clinical training. However, the academic degree-centred system has led to a preoccupation with research rather than clinical training. Unfortunately, there is a shortage of quality information regarding the clinical training of MD graduates from Chinese medical schools. To fill this gap, this general investigation aims to provide the perspective of recent MD graduates in China for the different subspecialties of clinical training as experienced in different contexts.

Methods: There were 432 MD graduates who participated in an online survey regarding their clinical training. Information collected included overall satisfaction, educational supervision, supervised learning events, curriculum coverage, local teaching, teamwork, educational governance, workload, supportiveness of the environment, feedback, clinical experience, patient safety, handovers, and reporting systems.

Results: Only 37.4% reported satisfaction with the overall clinical training quality; 54.6% rated the informal and bedside quality as "good"; 64.4% reported they knew who provided clinical supervision; but only 35.5% rated the quality of clinical supervision as high; 51.8% reported that they judged senior physicians as "not competent"; 41.9% agreed that the staff treated each other respectfully; 97.4% admitted that they worked beyond the mandatory hours and claimed they were regularly short of sleep; 84.2% raised concerns about patient safety; 45.3% reported that they received regular informal feedback; 48.1% believed that their concerns about education and training would be addressed.

Conclusions: This study suggests that the quality of clinical training for MD graduates should be improved. While the overall satisfaction with the teaching quality was acceptable, the quality of many clinical training aspects scored poorly. A major problem seems an undue focus on research in MD/PhD training at the cost of the quality of clinical training, due to career perspectives that undervalue clinical competence. The findings of this study should benefit from a deeper investigation to understand the causes and possible remediation. Suggestions include defining subspecialties and training lengths; monitoring, evaluation, and integration SST with MD degree; providing funds or rewards for academic and clinical training; establishing supervising teams to guide clinical training; and establishing physician scientist task force to help overcome challenges.
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http://dx.doi.org/10.1186/s12909-021-02647-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108351PMC
May 2021

A Programmed Cell-Mimicking Nanoparticle Driven by Potato Alkaloid for Targeted Cancer Chemoimmunotherapy.

Adv Healthc Mater 2021 May 8:e2100311. Epub 2021 May 8.

Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.

Membrane camouflaged-nanoparticles (CM-NPs) have been exploited to inherit desired functionalities from source cells. Despite those advantages, membrane cloak may play a "double-edged sword" role in tumor-targeting therapy, as the intact membrane coating may hinder function-exertion of loaded drugs after reaching predetermined site. Therefore, further optimization of CM-NPs is still needed to enhance their delivery efficiency. Herein, natural product, Solamargine (SM), a cholesterol-affiliative amphiphilic potato alkaloid is first applied as core component of "inner core," to design a cell-mimicking "core-shell" nanoparticle (RBC-SLip) with acid-responsive off-coating properties for tumor-targeted therapy. Owing to red blood cell membrane (RBCm)-derived outer coating, it circulates stably in physiological conditions. While it would undergo an off-coating morphological change in response to acid stimuli in tumor microenvironment (TME), afterwards, the resulting off-coating liposome (SLip) shows active tumor-targeting and endosomal escape abilities, thus contributing to superior antitumor efficacy. In addition, SM also possesses natural TME-modulating ability; therefore, RBC-SLip can synergize with the PD1/PD-L1 blockade immunotherapy when encapsulated with PTX to achieve enhanced chemoimmunotherapy. The off-coating strategy developed by natural products SM, provide a brand-new perspective to optimize CM-NPs, and it also embodies application value of "unification of medicines and excipients" of natural products.
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http://dx.doi.org/10.1002/adhm.202100311DOI Listing
May 2021

The RNA Structurome in the Asexual Blood Stages of Malaria Pathogen .

RNA Biol 2021 May 7. Epub 2021 May 7.

Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, North Carolina 28223.

is a deadly human pathogen responsible for the devastating disease called malaria. In this study, we measured the differential accumulation of RNA secondary structures in coding and noncoding transcripts from the asexual developmental cycle in in human red blood cells. Our comprehensive analysis that combined high-throughput nuclease mapping of RNA structures by duplex RNA-seq, SHAPE-directed RNA structure validation, immunoaffinity purification and characterization of antisense RNAs collectively measured differentially base-paired RNA regions throughout the parasite's asexual RBC cycle. Our mapping data not only aligned to a diverse pool of RNAs with known structures but also enabled us to identify new structural RNA regions in the malaria genome. On average, approximately 71% of the genes with secondary structures are found to be protein coding mRNAs. The mapping pattern of these base-paired RNAs corresponded to all regions of mRNAs, including the 5' UTR, CDS and 3' UTR as well as the start and stop codons. Histone family genes which are known to form secondary structures in their mRNAs and transcripts from genes which are important for transcriptional and post-transcriptional control, such as the unique plant-like transcription factor family, , DNA/RNA binding protein, and proteins important for RBC invasion and malaria cytoadherence also showed strong accumulation of duplex RNA reads in various asexual stages in . Intriguingly, our study determined stage-specific, dynamic relationships between mRNA structural contents and translation efficiency in asexual blood stages, suggesting an essential role of RNA structural changes in malaria gene expression programs.
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http://dx.doi.org/10.1080/15476286.2021.1926747DOI Listing
May 2021

A Pilot Study on the Cutoff Value of Related Brain Metabolite in Chinese Elderly Patients With Mild Cognitive Impairment Using MRS.

Front Aging Neurosci 2021 9;13:617611. Epub 2021 Apr 9.

Department of Rehabilitation, Bao'an Hospital, Southern Medical University, Shenzhen, China.

This cross-sectional study aimed to distinguish patients with mild cognitive impairment (MCI) from patients with normal controls (NCs) by measuring the levels of -acetyl aspartate (NAA), total creatinine (tCr), and choline (Cho) in their hippocampus (HIP) and their posterior cingulate gyrus (PCG) by using proton magnetic resonance spectroscopy (MRS) and to predict the cutoff value on the ratios of metabolites. We further aimed to provide a reference for the diagnosis of MCI in elderly patients in China. About 69 patients who underwent a clinical diagnosis of the MCI group and 67 patients with NCs, the Mini-Mental Status Examination (MMSE) score, the Montreal Cognitive Assessment (MoCA) score, and MRS of the bilateral HIP and bilateral PCG were considered. The ratio of NAA/tCr and Cho/tCr in the bilateral HIP and bilateral PCG was calculated. The relationship between the ratios of metabolites and the scores of MMSE and MoCA was analyzed, and the possible brain metabolite cutoff point for the diagnosis of MCI was evaluated. Compared with the NC group, the scores of MMSE and MoCA in the MCI group decreased significantly ( < 0.05); the ratio of NAA/tCr in the bilateral HIP and bilateral PCG and the ratio of Cho/tCr at the right HIP in the MCI group decreased significantly ( < 0.05); however, there was no significant difference in the ratio of Cho/tCr in the left HIP and bilateral PCG between the two groups ( > 0.05). The correlation coefficient between MMSE/MoCA and the ratio of NAA/tCr was 0.49-0.56 in the bilateral HIP ( < 0.01). The best cutoff value of NAA/creatine (Cr) in the left HIP and the right HIP was 1.195 and 1.19. Sensitivity, specificity, and the Youden index (YDI) in the left HIP and the right HIP were (0.725, 0.803, 0.528) and (0.754, 0.803, 0.557), respectively. The level of metabolites in the HIP and the PCG of patients with MCI and of those with normal subjects has a certain correlation with the score of their MMSE and MoCA. When the value of NAA/tCr in the left HIP and right HIP is <1.19, it suggests that MCI may have occurred. According to this cutoff point, elderly patients with MCI in China could be screened.
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http://dx.doi.org/10.3389/fnagi.2021.617611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063036PMC
April 2021

Association between resilience and burnout of front-line nurses at the peak of the COVID-19 pandemic: Positive and negative affect as mediators in Wuhan.

Int J Ment Health Nurs 2021 Apr 23. Epub 2021 Apr 23.

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.

The outbreak of coronavirus disease 2019 (COVID-19) is having a dramatic effect on the mental health of healthcare workers (HCWs). Upon the emergence of the COVID-19 pandemic, the Chinese government dispatched about 42 000 HCWs to Wuhan City and Hubei Province to fight this pandemic. This study briefly examines front-line nurses who experienced burnout, with the main objective of investigating the mediating roles of positive and negative affect in the relationship between resilience and burnout in Wuhan hospitals at the peak of the COVID-19 pandemic. A total of 180 front-line nurses voluntarily participated via a social media group. They completed the online questionnaires, including the Maslach Burnout Inventory-General Survey (MBI-GS), the Positive and Negative Affect Schedule (PANAS), the Connor-Davidson Resilience Scale (CD-RISC), demographics, and work-related characteristics. Structural equation modelling (SEM) analysis was used to examine the mediating effect of positive and negative affect on the relationship between resilience and burnout. The total prevalence of burnout was 51.7%, of which 15.0% were severe burnout. These preliminary results revealed that positive and negative affect fully mediated the effects of resilience on burnout, emotional exhaustion, depersonalization, and reduced personal accomplishment of front-line nurses. It is necessary to know the impact of resilience on HCWs with burnout through the positive and negative affect of individual backgrounds and situations, and how policymakers can deploy resilience interventions to support front-line HCWs.
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http://dx.doi.org/10.1111/inm.12847DOI Listing
April 2021

Hydrophilic AIE-Active Tetraarylethenes for Fluorescence Sensing and Super-Resolution Imaging of Amyloid Fibrils from Hen Egg White Lysozyme.

ACS Appl Mater Interfaces 2021 May 22;13(17):19625-19632. Epub 2021 Apr 22.

Wuhan National Laboratory for Optoelectronics, School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

Hen egg white lysozyme (HEWL) is frequently applied as a model protein for research on protein folding, unfolding, and fibrillization identified by featured fluorescent probes. Here, a series of hydrophilic, pH-sensitive tetraarylethene (TAE)-type AIEgens are synthesized via a geminal cross-coupling (GCC) reaction and evaluated for their capabilities of fluorescence sensing and super-resolution localization imaging of HEWL fibrils. With superior optical and sensing properties, the selected TAE-type AIEgen probe is weakly emissive in aqueous media, without dependence on the pH value and buffer concentration, but exhibits "turn-on" fluorescence upon interaction with HEWL amyloid fibrils in a spontaneous and reversible way that just meets the requirement of fluorescence random switching for super-resolution imaging. The selected probe has the strongest fluorescence response to HEWL amyloid fibrils exhibiting a limit of detection of 0.59 nmol/L and enables super-resolution fluorescence imaging of amyloid aggregates with a high resolution of 40 nm.
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http://dx.doi.org/10.1021/acsami.1c01819DOI Listing
May 2021

Nuclear mA reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos.

Protein Cell 2021 Jun 22;12(6):455-474. Epub 2021 Apr 22.

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, China.

N-methyladenosine (mA) on chromosome-associated regulatory RNAs (carRNAs), including repeat RNAs, plays important roles in tuning the chromatin state and transcription, but the intrinsic mechanism remains unclear. Here, we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells (ESCs), which highly depends on the mA-binding ability. Ythdc1 is required for sufficient rRNA synthesis and repression of the 2-cell (2C) transcriptional program in ESCs, which recapitulates the transcriptome regulation by the LINE1 scaffold. Detailed analyses revealed that YTHDC1 recognizes mA on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1. Moreover, the establishment of H3K9me3 on 2C-related retrotransposons is interrupted in Ythdc1-depleted ESCs and inner cell mass (ICM) cells, which consequently increases the transcriptional activities. Our study reveals a role of mA in regulating the RNA scaffold, providing a new model for the RNA-chromatin cross-talk.
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http://dx.doi.org/10.1007/s13238-021-00837-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160034PMC
June 2021

White Tip Silver Needle (Slightly Fermented White Tea) Flavonoids Help Prevent Aging via Antioxidative and Anti-Inflammatory Effects.

Drug Des Devel Ther 2021 31;15:1441-1457. Epub 2021 Mar 31.

Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing, 400067, People's Republic of China.

Aim: White tip silver needle, a slightly fermented white tea, is abundant in flavonoids, and it has great significance in terms of D-galactose/lipopolysaccharide-induced aging in mice.

Methods: We analyzed the antioxidant capacity of white tip silver needle flavonoids (WTSNF) in vitro, assessed the effects of WTSNF on organ indexes, pathological changes, liver function indexes, biochemical indicators, molecular biological indicators, and genes related to oxidation and inflammation.

Results: Ultra-high performance liquid chromatography-tandem mass spectrometry results showed that WTSNF contained baicalin, kaempferol, kaempferide, quercetin, isorhamnetin, lespenephryl, and rutin. WTSNF showed strong scavenging ability for both 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) free radicals. Pathological analysis results showed that WTSNF reduced liver, kidney, and lung damage in mice with induced aging. In the serum and liver tissue, WTSNF effectively increased the antioxidant-related levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione, and total antioxidant capacity and reduced the levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde and nitric oxide. WTSNF also reduced the inflammation-related levels of interleukin-6, interleukin-1 beta, tumor necrosis factor alpha (TNFα), and interferon gamma (IFN-γ) and increased the levels of interleukin-10 and interleukin-12. Furthermore, WTSNF upregulated the mRNA expression levels of cupro-zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, interleukin-10, neuronal nitric oxide synthase, endothelial nitric oxide synthase, nuclear factor erythroid 2-related factor, heme oxygenase 1, NAD(P)H dehydrogenase [quinone] 1, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α), and thioredoxin, while it downregulated the mRNA expression levels of interleukin-6, interleukin-18, interleukin-1 beta, TNFα, IFN-γ, inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB).

Conclusion: WTSNF is a high-quality natural product with antioxidative and anti-inflammatory properties that can inhibits D-galactose/lipopolysaccharide-induced aging in mice.
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http://dx.doi.org/10.2147/DDDT.S304885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020812PMC
March 2021

Mitochondrial DNA copy number of cumulus cells is not linked to embryo implantation in good prognosis IVF patients.

Reprod Biomed Online 2021 May 21;42(5):901-908. Epub 2021 Feb 21.

Chongqing Reproductive Medical Center, Chongqing Maternity Hospital, Jintang Street No. 64, Yuzhong District, Chongqing 400013, China; Chongqing Key Laboratory of Human Embryo Engineering, Chongqing Maternity Hospital, Jintang Street No. 64, Yuzhong District, Chongqing 400013, China. Electronic address:

Research Question: Could the mitochondrial DNA (mtDNA) copy number of cumulus cells be used as a biomarker of the potential of embryo implantation in good prognosis IVF patients?

Design: A prospective cohort study on good prognosis IVF patients from a large reproductive medicine centre. A total of 392 embryos from 61 cycles (including 31 implanted and 30 non-implanted cycles) were enrolled in the study. The corresponding cumulus cell mtDNA copy number of embryos was tested by real-time quantitative polymerase chain reaction. The corresponding cumulus cell mtDNA copy numbers were compared between implanted and non-implanted embryos and also compared between high quality and poor quality embryos. Then, a mitochondrial function assay including mitochondrial membrane potentials, concentration of reactive oxygen species (ROS) and ATP content of the corresponding cumulus cells were compared between high quality and poor quality embryos to verify the above experimental findings.

Results: For the same population, the mean cumulus cell mtDNA copy numbers for implanted and non-implanted embryos were 255.61 ± 81.02 and 254.50 ± 73.29 (P = 0.47), and those for high quality and poor quality embryos were 266.02 ± 98.56 and 295.71 ± 70.64 (P = 0.99), respectively. There was no significant difference in cumulus cell mtDNA copy number between implanted and non-implanted embryos or between high quality and poor quality embryos. The mitochondrial membrane potential, ROS levels and ATP content of the corresponding cumulus cells did not differ significantly between high quality and poor quality groups.

Conclusions: Measurement of cumulus cell mtDNA copy number might not provide any advantage to embryo prioritization in good prognosis IVF patients. Any suggested link between cumulus cell mtDNA copy number and embryo implantation requires further validation.
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http://dx.doi.org/10.1016/j.rbmo.2021.01.002DOI Listing
May 2021

Correction to: Identification of highly conserved, serotype-specific dengue virus sequences: implications for vaccine design.

BMC Genomics 2021 Mar 26;22(1):219. Epub 2021 Mar 26.

Centre for Bioinformatics, School of Data Sciences, Perdana University, Jalan MAEPS Perdana, 43400, Serdang, Selangor Darul Ehsan, Malaysia.

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http://dx.doi.org/10.1186/s12864-021-07444-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995763PMC
March 2021

Grating-enabled high-speed high-efficiency surface-illuminated silicon photodiodes.

Opt Express 2021 Feb;29(3):3458-3464

High-speed, high-efficiency silicon photodetectors play important roles in the optical communication links that are used increasingly in data centers to handle the increasing volumes of data traffic and higher bandwidths required as use of big data and cloud computing continues to grow exponentially. Monolithic integration of the optical components with signal processing electronics on a single silicon chip is of paramount importance in the drive to reduce costs and improve performance. Here we report grating-enhanced light absorption in a silicon photodiode. The absorption efficiency is determined theoretically to be as high as 77% at 850 nm for the optimal structure, which has a thin intrinsic absorption layer with a thickness of 220 nm. The fabricated devices demonstrate a high bandwidth of 11.3 GHz and improved radio-frequency output power of more than 14 dB, thus making them suitable for use in data center optical communications.
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http://dx.doi.org/10.1364/OE.412412DOI Listing
February 2021

The Impact of Antarctic Ice Microalgae Polysaccharides on D-Galactose-Induced Oxidative Damage in Mice.

Front Nutr 2021 9;8:651088. Epub 2021 Mar 9.

Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing, China.

Antarctic ice microalgae ( sp.) are a polysaccharide-rich natural marine resource. In this study, we evaluated the impact of Antarctic ice microalgae polysaccharides (AIMP) on D-galactose-induced oxidation in mice. We conducted biological and biochemical tests on tissue and serum samples from mice treated with AIMP. We found that AIMP administration was associated with improved thymus, brain, heart, liver, spleen, and kidney index values. We also found that AIMP treatment inhibited the reduced aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, superoxide dismutase, glutathione peroxidase, and glutathione levels as well as the increased serum, splenic, and hepatic nitric oxide and malondialdehyde levels arising from oxidation in these animals. Pathological examination revealed that AIMP also inhibited D-galactose-induced oxidative damage to the spleen, liver, and skin of these animals. AIMP was additionally found to promote the upregulation of neuronal nitric oxide synthase, endothelial nitric oxide synthase, cuprozinc-superoxide dismutase, manganese superoxide dismutase, catalase, heme oxygenase-1, nuclear factor erythroid 2-related factor 2, γ-glutamylcysteine synthetase, and NAD(P)H dehydrogenase [quinone] 1 as well as the downregulation of inducible nitric oxide synthase in these animals. High-performance liquid chromatography analysis revealed AIMP to be composed of five monosaccharides (mannitol, ribose, anhydrous glucose, xylose, and fucose). Together, these results suggest that AIMP can effectively inhibit oxidative damage more readily than vitamin C in mice with D-galactose-induced oxidative damage, which underscores the value of developing AIMP derivatives for food purposes.
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http://dx.doi.org/10.3389/fnut.2021.651088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985059PMC
March 2021

Performance of a Point of Care Test for Detecting IgM and IgG Antibodies Against SARS-CoV-2 and Seroprevalence in Blood Donors and Health Care Workers in Panama.

Front Med (Lausanne) 2021 2;8:616106. Epub 2021 Mar 2.

Servicio de Hematología. Complejo Hospitalario Metropolitano Dr. Arnulfo Arias Madrid, Caja de Seguro Social, Panama City, Panama.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has reached 28 million cases worldwide in 1 year. The serological detection of antibodies against the virus will play a pivotal role in complementing molecular tests to improve diagnostic accuracy, contact tracing, vaccine efficacy testing, and seroprevalence surveillance. Here, we aimed first to evaluate a lateral flow assay's ability to identify specific IgM and IgG antibodies against SARS-CoV-2 and second, to report the seroprevalence estimates of these antibodies among health care workers and healthy volunteer blood donors in Panama. We recruited study participants between April 30th and July 7th, 2020. For the test validation and performance evaluation, we analyzed serum samples from participants with clinical symptoms and confirmed positive RT-PCR for SARS-CoV-2, and a set of pre-pandemic serum samples. We used two by two table analysis to determine the test positive and negative percentage agreement as well as the Kappa agreement value with a 95% confidence interval. Then, we used the lateral flow assay to determine seroprevalence among serum samples from COVID-19 patients, potentially exposed health care workers, and healthy volunteer donors. Our results show this assay reached a positive percent agreement of 97.2% (95% CI 84.2-100.0%) for detecting both IgM and IgG. The assay showed a Kappa of 0.898 (95%CI 0.811-0.985) and 0.918 (95% CI 0.839-0.997) for IgM and IgG, respectively. The evaluation of serum samples from hospitalized COVID-19 patients indicates a correlation between test sensitivity and the number of days since symptom onset; the highest positive percent agreement [87% (95% CI 67.0-96.3%)] was observed at ≥15 days post-symptom onset (PSO). We found an overall antibody seroprevalence of 11.6% (95% CI 8.5-15.8%) among both health care workers and healthy blood donors. Our findings suggest this lateral flow assay could contribute significantly to implementing seroprevalence testing in locations with active community transmission of SARS-CoV-2.
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http://dx.doi.org/10.3389/fmed.2021.616106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968482PMC
March 2021

Immunogenic Cell Death (ICD) of Murine H22 Cells Induced by Lentinan.

Nutr Cancer 2021 Mar 15:1-10. Epub 2021 Mar 15.

College of Biological Science and Engineering, Hebei University of Science and Technology, Shijiazhuang, China.

Lentinan can lead to apoptosis of tumor cells and improve immune function. However, limited research focused on the immunogenic death regulation mechanism of lentinan on mouse H22 cells. The study aimed to explore the effect of Lentinan on the expression of immunogenic death-related proteins in mice H22 cells. MTT method was used to detect and evaluate the effect of 200-1000 μg/mL lentinan on the survival rate of H22 cells after 24 h, 48 h, and 72 h, respectively. Flow cytometry was employed to collect the apoptotic rate of lentinan at different concentrations (200-800μg/mL) on H22 cells for 48 h, and obtain the apoptotic rate of 600 μg/mL lentinan at different times (12-72 h). The effect of Lentinan on the expression of H22 Immunogenic Cell Death proteins was analyzed by ELISA and HPLC-MS afterward. Results suggest that lentinan cytotoxic and pro-apoptotic have a concentration-dependent manner with the H22 cells. Moreover, the rate of apoptosis increased significantly ( < 0.05) in 24 h. Lentinan can induce the expression of Calreticulin(CRT), High mobility protein 1(HMGB1), ATP and Heat shock protein 70 (HSP70) .Therefore, the antitumor effect of lentinan may be related to the regulation of immunogenic death-related protein expression, which was beneficial to the future development of liver cancer vaccines.
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http://dx.doi.org/10.1080/01635581.2021.1897632DOI Listing
March 2021

Association of Hydrogen Sulfide with Femoral Bone Mineral Density in Osteoporosis Patients: A Preliminary Study.

Med Sci Monit 2021 Mar 14;27:e929389. Epub 2021 Mar 14.

Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China (mainland).

BACKGROUND Accumulated evidence has suggested that hydrogen sulfide (H₂S) has a role in bone formation and bone tissue regeneration. However, it is unknown whether the H₂S content is associated with bone mineral density (BMD) in patients with osteopenia/osteoporosis. MATERIAL AND METHODS In the present study, we aimed to explore the changes of serum H₂S in osteopenia and osteoporosis patients. We analyzed femur expression of cystathionine ß synthase (CBS), cystathionine γ lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), which are key enzymes for generating H₂S. RESULTS Sixteen (16%) patients had osteopenia, 9 (9%) had osteoporosis, and 75 (75%) had normal BMD. In comparison with patients with normal BMD (controls), the serum levels of H₂S were unexpectedly increased in patients with osteopenia and osteoporosis. This increase was much higher in patients with osteoporosis than in those with osteopenia. Serum H₂S levels were negatively correlated with femoral BMD, but not lumbar BMD. Interestingly, the expression of CBS and CSE were downregulated in femur tissues in patients with osteoporosis, whereas the expression of 3-MST remained unchanged. Serum phosphorus levels, alkaline phosphatase, hemoglobin, and triglycerides were found to be closely associated with CBS and CSE scores in femur tissues. CONCLUSIONS Serum H₂S levels and femur CBS and CSE expression may be involved in osteoporosis pathogenesis.
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http://dx.doi.org/10.12659/MSM.929389DOI Listing
March 2021

Vessel flow void sign and hyperintense vessel sign on FLAIR images distinguish between MELAS and AIS.

Mitochondrion 2021 May 11;58:131-134. Epub 2021 Mar 11.

Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Objective: This study aimed to evaluate the sensitivity and specificity of the vessel signs, including the Vessel Flow Void Sign (VFVS) and the Hyperintense Vessel Sign (HVS) in Fluid Attenuated Inversion Recovery (FLAIR) images during the differentiation of Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) in Acute Ischemic Stroke (AIS).

Methods: Magnetic Resonance Imaging (MRI) scans of 13 MELAS and 20 AIS patients were obtained during the acute stage of the diseases (median time to scan <1 day from symptom onset). To evaluate VFVS and HVS on the FLAIR images, Logistic Regression was used to analyze their correlation with MELAS. Then, a new scale of scoring, involving two aspects (VFVS and HVS) on FLAIR images was established. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of the developed criterion.

Results: FLAIR images from 12 of the 13 MELAS patients exhibited VFVS while none exhibited HVS. Moreover, FLAIR images from 3 of the 20 AIS patients exhibited VFVS while 17 exhibited HVS. Logistic Regression showed that VFVS and the absence of HVS (NoHVS) were independent MELAS predictors. If there were VFVS, the patient scored 2 points, while there were NoHVS, the patient scored 1 point. Patients with >1.5 scores were prone to be MELAS, while patients with <1.5 scores were prone to be AIS. Sensitivity was found to be 92.3%, specificity was 85%, with an AUC of 0.94.

Conclusion: We have established a new scoring criterion, with a high sensitivity and specificity, for differentiating between MELAS and AIS in patients during the acute stage.
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http://dx.doi.org/10.1016/j.mito.2021.02.015DOI Listing
May 2021