Publications by authors named "Huijie Zhang"

151 Publications

Fate of chlorpyrifos, omethoate, cypermethrin, and deltamethrin during wheat milling and Chinese steamed bread processing.

Food Sci Nutr 2021 Jun 1;9(6):2791-2800. Epub 2021 May 1.

Chinese Academy of Agricultural Sciences / Laboratory of Quality and Safety Risk Assessment for Cereal Products (Beijing) Institute of Crop Sciences Ministry of Agriculture Beijing China.

To investigate the fractioning of chlorpyrifos, omethoate, cypermethrin, and deltamethrin during wheat milling and the fate of four pesticides during Chinese steamed bread (CSB) processing, wheat samples, which were sprayed twice with chlorpyrifos, omethoate, cypermethrin, and deltamethrin at three levels of concentrations during the grain-filling stage, were milled, and wheat flour was processed to CSB. The residues of four pesticides in the milling products, kneaded dough, fermented dough, and CSB were determined with GC-MS/MS. The concentrations of chlorpyrifos, omethoate, cypermethrin, and deltamethrin in bran were 1.46-1.57, 1.85-2.13, 1.27-1.86, and 1.63-2.33 times higher than those in wheat, respectively, while the residues of the four pesticides in shorts decreased approximately 27.97% to 57.02% for chlorpyrifos, 6.22% to 44.77% for cypermethrin, and 13.13% to 61.15% for deltamethrin compared with the residues in wheat ( < .05); however, omethoate levels approximately doubled in the ten-fold treatment group in shorts compared with those in wheat ( < .05). The residues of the four pesticides in flour were significantly lower than those in wheat, ranging from 38.68% to 98.04%. Chlorpyrifos and omethoate levels showed a slight decrease during the kneading and fermentation process, and further decreases of 2.46%-29.51% for chlorpyrifos and 14.22%-71.11% for omethoate were found in CSB; however, most of the groups of cypermethrin and deltamethrin showed various degrees of increases in kneaded and fermented dough and steamed bread compared with flour. The mechanism of this increase is unknown and needs further research.
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http://dx.doi.org/10.1002/fsn3.1523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194911PMC
June 2021

Evaluating the associations of adult heel BMD with birth weight and growth parameters at age 10 in UK biobank cohort.

Bone 2021 Jun 9:116038. Epub 2021 Jun 9.

Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China. Electronic address:

Objective: This study was aimed to evaluate the associations of adult heel bone mineral density (BMD) with birth weight and growth parameters at the age of ten years.

Methods: The analysis data (97178-178,494 subjects) was derived from the UK Biobank cohort. Birth weight, comparative body size and height size at the age of ten years were determined by self-report. The heel BMD was estimated by the Quantitative Ultrasound Index through the calcaneus. Linear regression analysis was applied to test the associations of adult heel BMD with birth weight and growth parameters at the age of ten years, respectively. Age, sex, body mass index and 10 principle components (PC) of population structure were used as covariates in the regression analysis of total samples. In sex-specific analysis, age, body mass index and 10 PC were used as covariates.

Results: We observed significant associations of heel BMD with birth weight (b = -0.02, P = 1.97 × 10), comparative body size (b = 0.02, P = 2.54 × 10) and comparative height size (b = -0.02, P = 5.89 × 10) at the age of ten years in total samples. In females, birth weight (b = -0.04, P = 2.87 × 10) and comparative height size (b = -0.04, P = 2.03 × 10) were statistically associated with adult heel BMD. In males, comparative body size appeared to be associated with adult heel BMD (b = 0.03, P = 1.59 × 10).

Conclusion: Our study results support the predictive effects of birth weight and growth parameters at the age of ten years on adult heel BMD. We also observed sex-specific association between adult heel BMD and growth parameters at the age of ten years.
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http://dx.doi.org/10.1016/j.bone.2021.116038DOI Listing
June 2021

Washed microbiota transplantation in patients with respiratory spreading diseases: Practice recommendations.

Med Microecol 2021 Mar 10;7:100024. Epub 2020 Oct 10.

Department of Gastroenterology, National Clinical Research Center of Infectious Disease, The Third People's Hospital of Shenzhen, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518114, China.

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http://dx.doi.org/10.1016/j.medmic.2020.100024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547313PMC
March 2021

Adiposity Measurements and Metabolic Syndrome Are Linked Through Circulating Neuregulin 4 and Adipsin Levels in Obese Adults.

Front Physiol 2021 4;12:667330. Epub 2021 May 4.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Adiposity and adipokines are associated with metabolic disorders, but little is known regarding that whether adiposity measurements link metabolic syndrome (MetS) through circulating neuregulin 4 (Nrg4) and adipsin levels.

Materials And Methods: A total of 1212 subjects with a waist circumference greater than 90 cm for men or 80 cm for women were enrolled from a Chinese community. Circulating Nrg4 and adipsin levels were measured using commercial kits. Mediation analyses of circulating Nrg4 and adipsin were performed in the study using linear and logistic regression.

Results: Subjects with MetS had higher waist circumference, visceral fat level, and circulating adipsin level, and lower levels of circulating Nrg4 and muscle mass to visceral fat (MVF) ratio (all < 0.05). In multivariable logistic regression analyses, after adjusting for confounding variables, per standard deviation (SD) increase in waist circumference and visceral fat level were significantly associated with increased odds of MetS [OR (95% CI), 1.42 (1.22-1.64); 2.20 (1.62-2.99); respectively]; and per SD reduction in MVF ratio was significantly associated with reduced odds of MetS [OR (95% CI), 0.65 (0.55-0.77)]. In the mediation analyses, both circulating Nrg4 and adipsin levels mediated the association between waist circumference (8.31% and 18.35%, respectively), visceral fat level (7.50% and 9.98%, respectively), and MVF ratio (5.80% and 9.86%, respectively) and MetS after adjustments.

Conclusion: These findings indicate that adiposity measurements and MetS are linked through circulating Nrg4 and adipsin levels in obese adults, suggesting that circulating Nrg4 and adipsin levels might be potential predictors for management of MetS.
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http://dx.doi.org/10.3389/fphys.2021.667330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129583PMC
May 2021

Correction: Transgenic PDGF-BB/sericin hydrogel supports for cell proliferation and osteogenic differentiation.

Biomater Sci 2021 Jun;9(11):4212-4213

Biological Science Research Center, Chongqing Key Laboratory of Sericultural Science, Chongqing Engineering and Technology Research Center for Novel Silk Materials, Southwest University, Chongqing, 400715, People's Republic of China.

Correction for 'Transgenic PDGF-BB/sericin hydrogel supports for cell proliferation and osteogenic differentiation' by Feng Wang et al., Biomater. Sci., 2020, 8, 657-672, DOI: 10.1039/C9BM01478K.
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http://dx.doi.org/10.1039/d1bm90052hDOI Listing
June 2021

Large-scale analysis of 2,152 Ig-seq datasets reveals key features of B cell biology and the antibody repertoire.

Cell Rep 2021 May;35(6):109110

Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai 200433, China. Electronic address:

Antibody repertoire sequencing enables researchers to acquire millions of B cell receptors and investigate these molecules at the single-nucleotide level. This power and resolution in studying humoral responses have led to its wide applications. However, most of these studies were conducted with a limited number of samples. Given the extraordinary diversity, assessment of these key features with a large sample set is demanded. Thus, we collect and systematically analyze 2,152 high-quality heavy-chain antibody repertoires. Our study reveals that 52 core variable genes universally contribute to more than 99% of each individual's repertoire; a distal interspersed preferences characterize V gene recombination; the number of public clones between two repertoires follows a linear model, and the positive selection dominates at RGYW motif in somatic hypermutations. Thus, this population-level analysis resolves some critical features of the antibody repertoire and may have significant value to the large cadre of scientists.
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http://dx.doi.org/10.1016/j.celrep.2021.109110DOI Listing
May 2021

Polydatin Inhibits Cell Viability, Migration, and Invasion Through Suppressing the c-Myc Expression in Human Cervical Cancer.

Front Cell Dev Biol 2021 12;9:587218. Epub 2021 Apr 12.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing, China.

Polydatin, an active ingredient from the roots of , is considered to have protective effects on the cardiovascular system and liver. In this study, we demonstrated that polydatin has antitumor activity against human cervical cancer. Polydatin efficiently inhibited cervical cancer cell proliferation by regulating cell cycle-related proteins including p21, p27, CDK2, CDK4, Cyclin D1, and Cyclin E1. Furthermore, polydatin suppressed cell invasion and migration by regulating epithelial-mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, Snail and Slug. The c-Myc, as a proto-oncogene, is considered to be closely associated with the proliferation and metastasis of tumor cells. After polydatin treatment, the protein expression of c-Myc showed a significant decrease. Based on these data, we overexpressed c-Myc in cervical cancer cells and observed that the overexpression of c-Myc rescued the inhibitory effect of polydatin on cell proliferation and metastasis. These results indicated that polydatin can inhibit cell proliferation and metastasis through suppressing the c-Myc expression in human cervical cancer.
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http://dx.doi.org/10.3389/fcell.2021.587218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072354PMC
April 2021

Age-specific risk factors of severe pneumonia among pediatric patients hospitalized with community-acquired pneumonia.

Ital J Pediatr 2021 Apr 23;47(1):100. Epub 2021 Apr 23.

Department of Pediatrics, Fujian Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China.

Background: Risk factors that predispose the development of severe community-acquired pneumonia (CAP) among pediatric CAP patients of different age ranges are yet to be identified.

Methods: We retrospectively analyzed pediatric in-patients (< 6 years old) diagnosed with CAP in our hospital. We subdivided patients into four age groups (< 6 months, 6 months-1 year, 1-2 years, and 2-6 years). Their medical records, including demographic information, clinical features, laboratory findings, and chest radiographic reports, were reviewed and collected for further analysis. Univariate logistic regression analysis and stepwise regression analysis were applied to identify risk factors associated with severe CAP and ICU admission for overall patients and age-stratified subgroups.

Results: A total of 20,174 cases were initially included. Among them, 3309 (16.40%) cases were identified as severe CAP, and 2824 (14.00%) cases required ICU admission. Potential risk factors for severe CAP and ICU admission identified by univariate analysis included younger age, rural residency, premature birth, low birth weight (LBW), formula feeding, congenital heart disease (CHD), history of pneumonia or neonatal jaundice, patients with other health issues, certain symptoms (manifesting wheezing, dyspnea, cyanosis, but have no cough or fever), abnormal laboratory findings (abnormal levels of white blood cells, albumin, and C-reactive protein and RSV infection), and chest X-ray (odds ratio [OR] > 1 for all). CHD, low albumin, proteinuria, abnormal chest x-ray were independent risks factors across different age groups, whereas birth or feeding history, history of pneumonia, cyanosis or dyspnea on admission, and RSV infection were independent risk factors for only younger kids (< 1 year), and wheezing was an independent risk factor only for older children (2-5 years old).

Conclusions: Risk factors predicting disease severity among children hospitalized with CAP vary with age. Risk factor stratification of pediatric CAP based on age-specific risk factors can better guide clinical practice.

Trial Registration: This study has been registered in China, with the registration number being ChiCTR2000033019 .
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http://dx.doi.org/10.1186/s13052-021-01042-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062938PMC
April 2021

Pesticides in surface waters of tropical river basins draining areas with rice-vegetable rotations in Hainan, China: Occurrence, relation to environmental factors, and risk assessment.

Environ Pollut 2021 Aug 12;283:117100. Epub 2021 Apr 12.

Environment and Plant Protection Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, China; Danzhou Scientific Observing and Experimental Station of Agro-Environment, Ministry of Agriculture and Rural Affairs, Danzhou, 571737, China; National Agricultural Experimental Station for Agricultural Environment, Danzhou, 571737, China; Hainan Engineering Research Center for Non-point Source and Heavy Metal Pollution Control, Danzhou, 571737, China.

Pesticides are heavily applied in rice-vegetable rotations in tropical China, yet publicly available information on the contamination and risk of currently used pesticides (CUPs) and legacy pesticides (LPs) in surface waters of river basins draining these areas is very limited. Therefore, in two tropical river basins (Nandu River and Wanquan River basins) dominated by rice-vegetable rotations in Hainan, China, pesticides were analyzed in 256 surface water samples in wet and dry seasons. Forty-one pesticides were detected, and total concentrations ranged from not detectable to 24.2 μg/L. Carbendazim and imidacloprid were the two most prevalent CUPs, detected in 59.8% and 17.7%, respectively, of surface water samples at concentrations above 0.1 μg/L. Chlorpyrifos was the main LP, detected in 9.0% of samples at a concentration above 0.05 μg/L. The fungicides difenoconazole and emamectin benzoate, the herbicide butachlor, and the insecticide acetamiprid occurred in ≥12.5% samples at concentrations above 0.1 μg/L. Surface waters typically (85.2%) contained 5 to 15 residues, with an average of nine. Seasonally, the concentrations of the 41 pesticides were in the order January > July > November > September. Spatially, the composition of the main CUPs (not LPs) was significantly different depending on position in the drainage, which also changed with seasons. Crop and pest types and wet and dry seasons were the key factors controlling the spatiotemporal distribution of CUPs and LPs in surface waters. On the basis of evaluations of the exposures to individual pesticides and the dominant combinations with ≥8 pesticides, multiple pesticides were likely a significant risk to aquatic organisms, although noncarcinogenic and carcinogenic risks to humans were low. This study provides valuable data to better understand pesticide occurrence and ecological risks in river basins draining areas with rice-vegetable rotation systems in tropical China.
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http://dx.doi.org/10.1016/j.envpol.2021.117100DOI Listing
August 2021

Association of circulating adipsin with nonalcoholic fatty liver disease in obese adults: a cross-sectional study.

BMC Gastroenterol 2021 Mar 21;21(1):131. Epub 2021 Mar 21.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, 510515, China.

Background: As a secreted adipokine, adipsin has been recently shown to play a pivotal role in metabolic disorders. However, information regarding the association of circulating adipsin with non-alcoholic fatty liver disease (NAFLD) in humans is scant.

Methods: We recruited 1163 obese adult subjects with waist circumference at least 90 cm in men and 80 cm in women from the community. Circulating adipsin levels were measured by enzyme-linked immunosorbent assay.

Results: Circulating adipsin levels of NAFLD subjects was decreased compared to those in non-NAFLD (p < 0.05). The prevalence of NAFLD with lower levels of serum adipsin was significantly higher than those with higher values (57.6% vs. 50.9%, p < 0.05). Circulating adipsin levels were significantly associated with decreasing levels of fasting glucose and postprandial glucose (both p < 0.001 for interaction) in NAFLD subjects but not in non-NAFLD subjects. The risk of NAFLD was significantly decreased by 21.7% [OR (95% CI): 0.783 (0.679-0.902), p < 0.001], adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, HOMA-IR, and body fat mass. Importantly, subjects in the lowest quartile of circulating adipsin were 1.88 times more likely to have NAFLD than those in the highest quartile in multivariable logistic regression analyses. However, such associations with circulating adipsin were not noted for metabolic syndrome, abnormal liver enzyme and significant liver fibrosis.

Conclusions: These results demonstrate that circulating adipsin levels in Chinese obese adults are negatively associated with risk of NAFLD, implying that serum adipsin levels may be a potential protective factor in NAFLD.
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http://dx.doi.org/10.1186/s12876-021-01721-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981882PMC
March 2021

Cancer Cell-Membrane Biomimetic Boron Nitride Nanospheres for Targeted Cancer Therapy.

Int J Nanomedicine 2021 11;16:2123-2136. Epub 2021 Mar 11.

School of Life Sciences, Shanghai University, Shanghai, 200444, People's Republic of China.

Purpose: Nanomaterial-based drug-delivery systems allowing for effective targeted delivery of smallmolecule chemodrugs to tumors have revolutionized cancer therapy. Recently, as novel nanomaterials with outstanding physicochemical properties, boron nitride nanospheres (BNs) have emerged as a promising candidate for drug delivery. However, poor dispersity and lack of tumor targeting severely limit further applications. In this study, cancer cell-membrane biomimetic BNs were designed for targeted anticancer drug delivery.

Methods: Cell membrane extracted from HeLa cells (HM) was used to encapsulate BNs by physical extrusion. Doxorubicin (Dox) was loaded onto HM-BNs as a model drug.

Results: The cell-membrane coating endowed the BNs with excellent dispersibility and cytocompatibility. The drug-release profile showed that the [email protected] responded to acid pH, resulting in rapid Dox release. Enhanced cellular uptake of [email protected] by HeLa cells was revealed because of the homologous targeting of cancer-cell membranes. CCK8 and live/dead assays showed that [email protected] had stronger cytotoxicity against HeLa cells, due to self-selective cellular uptake. Finally, antitumor investigation using the HeLa tumor model demonstrated that [email protected] possessed much more efficient tumor inhibition than free Dox or [email protected]

Conclusion: These findings indicate that the newly developed HM-BNs are promising as an efficient tumor-selective drug-delivery vehicle for tumor therapy.
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http://dx.doi.org/10.2147/IJN.S266948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959002PMC
April 2021

Comparative transcriptomic analysis of cantaloupe melon under cold storage with ozone treatment.

Food Res Int 2021 02 15;140:109993. Epub 2020 Dec 15.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing Key Laboratory of Functional Food from Plant Resources, Beijing 100083, China. Electronic address:

Ozone treatment was found to delay the postharvest cantaloupe melon decay and improve its intrinsic quality during the cold storage. The transcriptomes of cantaloupe peel and pulp in response to ozone treatment were investigated to reveal the mechanisms using a high-throughput RNA sequencing approach. Results showed that 570 and 313 differentially expressed genes were identified in peel and pulp, respectively. According to these identified genes, the gene ontology and pathway enrichment analysis indicated that the ozone treatment could maintain the firmness of the cantaloupe by changing pectin metabolites and reduction of the ethylene production by regulating relevant genes especially in the peel. The total flavonoid content changes in peel and pulp related to the regulation of phenylalanine ammonia lyase, 4-coumarate-CoA ligase and P450 family genes which further leading to the inhibition of phenylalanine metabolic pathway in peel but promotion of secondary metabolism in pulp. The qRT-PCR results were in accordance with our RNA sequencing results which validated the conclusions. The present study for the first time reveals the mechanism of cantaloupe in response to ozone treatment at a transcriptome level which is of importance for cantaloupe storage.
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http://dx.doi.org/10.1016/j.foodres.2020.109993DOI Listing
February 2021

The S100 calcium-binding protein A11 promotes hepatic steatosis through RAGE-mediated AKT-mTOR signaling.

Metabolism 2021 04 9;117:154725. Epub 2021 Feb 9.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China. Electronic address:

Rationale: Nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, has become an increasingly severe public health problem. However, the underlying mechanism for the occurrence and development of NAFLD remains largely unknown. S100 calcium-binding protein A11 (S100A11) is a multifunctional protein previously reported to be a poor prognostic indicator of hepatocellular carcinoma, while the role of S100A11 affects NAFLD is still not clear.

Methods: Immunohistochemical staining was performed using human NAFLD and control biopsy specimens. Serum level of S100A11 were analyzed by Elisa assays. The S100A11 over-expressed/ knocked-down model was established in vitro or in vivo. The expression levels of genes related to lipid metabolism in liver tissue were performed by quantitative PCR and western blotting. Hepatic lipid accumulation was determined by biochemical measurements and histochemistry.

Results: We showed that the concentration of serum S100A11 was significantly elevated in NAFLD patients, and expression of S100A11 was remarkedly increased in the livers of NAFLD patients and mouse models. Overexpression of S100A11 in vivo markedly increased liver steatosis, body weight, and serum aspartate aminotransaminase (AST) levels. Mechanistically, our results demonstrated that S100A11 acted as a positive regulator of AKT/mTOR signaling to induce lipid synthesis and aggravate lipid deposition.

Conclusions: These results provide evidence for a novel role of S100A11 that contributes to hepatic steatosis, suggesting that targeting S100A11 may be an alternative approach for the treatment of NAFLD.
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http://dx.doi.org/10.1016/j.metabol.2021.154725DOI Listing
April 2021

An amiRNA screen uncovers redundant CBF and ERF34/35 transcription factors that differentially regulate arsenite and cadmium responses.

Plant Cell Environ 2021 May 25;44(5):1692-1706. Epub 2021 Feb 25.

Division of Biological Sciences, Cell and Developmental Biology Section, University of California, San Diego, California, USA.

Arsenic stress causes rapid transcriptional responses in plants. However, transcriptional regulators of arsenic-induced gene expression in plants remain less well known. To date, forward genetic screens have proven limited for dissecting arsenic response mechanisms. We hypothesized that this may be due to the extensive genetic redundancy present in plant genomes. To overcome this limitation, we pursued a forward genetic screen for arsenite tolerance using a randomized library of plants expressing >2,000 artificial microRNAs (amiRNAs). This library was designed to knock-down diverse combinations of homologous gene family members within sub-clades of transcription factor and transporter gene families. We identified six transformant lines showing an altered response to arsenite in root growth assays. Further characterization of an amiRNA line targeting closely homologous CBF and ERF transcription factors show that the CBF1,2 and 3 transcription factors negatively regulate arsenite sensitivity. Furthermore, the ERF34 and ERF35 transcription factors are required for cadmium resistance. Generation of CRISPR lines, higher-order T-DNA mutants and gene expression analyses, further support our findings. These ERF transcription factors differentially regulate arsenite sensitivity and cadmium tolerance.
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http://dx.doi.org/10.1111/pce.14023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068611PMC
May 2021

FOXA3 induction under endoplasmic reticulum stress contributes to non-alcoholic fatty liver disease.

J Hepatol 2021 Jul 4;75(1):150-162. Epub 2021 Feb 4.

The Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

Background & Aims: Chronic endoplasmic reticulum (ER) stress in the liver has been shown to play a causative role in non-alcoholic fatty liver disease (NAFLD) progression, yet the underlying molecular mechanisms remain to be elucidated. Forkhead box A3 (FOXA3), a member of the FOX family, plays critical roles in metabolic homeostasis, although its possible functions in ER stress and fatty liver progression are unknown.

Methods: Adenoviral delivery, siRNA delivery, and genetic knockout mice were used to crease FOXA3 gain- or loss-of-function models. Tunicamycin (TM) and a high-fat diet (HFD) were used to induce acute or chronic ER stress in mice. Chromatin immunoprecipiation (ChIP)-seq, luciferase assay, and adenoviral-mediated downstream gene manipulations were performed to reveal the transcriptional axis involved. Key axis protein levels in livers from healthy donors and patients with NAFLD were assessed via immunohistochemical staining.

Results: FOXA3 transcription is specifically induced by XBP1s upon ER stress. FOXA3 exacerbates the excessive lipid accumulation caused by the acute ER-inducer TM, whereas FOXA3 deficiency in hepatocytes and mice alleviates it. Importantly, FOXA3 deficiency in mice reduced diet-induced chronic ER stress, fatty liver, and insulin resistance. In addition, FOXA3 suppression via siRNA or adeno-associated virus delivery ameliorated the fatty liver phenotype in HFD-fed and db/db mice. Mechanistically, ChIP-Seq analysis revealed that FOXA3 directly regulates Period1 (Per1) transcription, which in turn promotes the expression of lipogenic genes, including Srebp1c, thus enhancing lipid synthesis. Of pathophysiological significance, FOXA3, PER1, and SREBP1c levels were increased in livers of obese mice and patients with NAFLD.

Conclusion: The present study identified FOXA3 as the bridging molecule that links ER stress and NAFLD progression. Our results highlighted the role of the XBP1s-FOXA3-PER1/Srebp1c transcriptional axis in the development of NAFLD and identified FOXA3 as a potential therapeutic target for fatty liver disease.

Lay Summary: The molecular mechanisms linking endoplasmic reticulum stress to non-alcoholic fatty liver disease (NAFLD) progression remain undefined. Herein, via in vitro and in vivo analysis, we identified Forkhead box A3 (FOXA3) as a key bridging molecule. Of pathophysiological significance, FOXA3 protein levels were increased in livers of obese mice and patients with NAFLD, indicating that FOXA3 could be a potential therapeutic target in fatty liver disease.
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http://dx.doi.org/10.1016/j.jhep.2021.01.042DOI Listing
July 2021

Glycosides of Caulis Lonicerae inhibits the inflammatory proliferation of IL-1β-mediated fibroblast-like synovial cells cocultured with lymphocytes.

Phytother Res 2021 Jan 23. Epub 2021 Jan 23.

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Caulis Lonicerae, the dried stem of Lonicera japonica, has been confirmed to have antiinflammatory and antioxidant therapeutic effects. In the present study, we aimed to evaluate the functional mechanism of glycosides extracted from Caulis Lonicerae on the inflammatory proliferation of interleukin-1 beta (IL-1β)-mediated fibroblast-like synoviocytes (FLSs) from rats. Rat FLSs (RSC-364) co-cultured with lymphocytes induced by IL-1β were used as a cell model. Glycosides in a freeze-dried powder of aqueous extract from Caulis Lonicerae were identified using high-performance liquid chromatography-electrospray ionization/mass spectrometry. After treatment with glycosides, the inflammatory proliferation of FLS, induced by IL-1β, decreased significantly. Flow cytometry analysis showed that treatment with glycosides restored the abnormal balance of T cells by intervening in the proliferation and differentiation of helper T (Th) cells. Glycosides also inhibited the activation of Janus kinase signal transducer and activator of transcription (JAK-STAT) and nuclear factor (NF)-κB signaling pathways by suppressing the protein expression of key molecules in these pathways. Therefore, we concluded that the glycosides of Caulis Lonicerae can intervene in the differentiation of Th cells, suppressing the activation of JAK-STAT and NF-κB signaling pathways, contributing to the inhibitory effect on inflammatory proliferation of FLS co-cultured with lymphocytes induced by pro-inflammatory cytokines.
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http://dx.doi.org/10.1002/ptr.7026DOI Listing
January 2021

Risk factors associated with wheezing in severe pediatric community-acquired pneumonia: a retrospective study.

Minerva Pediatr 2021 Jan 13. Epub 2021 Jan 13.

Department of Pediatrics, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China -

Background: Wheezing is a common clinical manifestation in children with pneumonia. However, the risk factors associated with the development of wheezing pneumonia and its clinical features are not fully characterized, especially in children with severe pneumonia.

Methods: We retrospectively recruited 1434 pediatric patients diagnosed with severe pneumonia between April 2012 and September 2019 in Fujian Maternity and Child Health Hospital. The medical records regarding demographic information, clinical manifestations, radiographic/laboratory findings, and complications were collected. Based on the presence or absence of wheezing symptoms and signs, subjects were divided into wheezing cohort (n=684) and non-wheezing cohort (n=750), and their clinical data were compared. Multivariate cox regression analysis was performed to identify independent risk factors of wheezing.

Results: Demographic features including gender, weigh, onset season, birth weight, full-term birth or not, history of pneumonia were significantly associated with the occurrence of wheezing in severe CAP (P<0.05). Specifically, male gender, onset seasons in autumn/winter, and absence of a history of pneumonia were identified as independent risk factors of wheezing in multivariate analysis (P<0.05). As for clinical features, wheezing cohort differed from the non-wheezing one in terms of clinical manifestation (higher incidence of cough and breathless, but lower incidence of fever), laboratory finding (higher levels of red blood cells, hemoglobin, and albumin and lower levels of total or indirect bilirubin and creatine), pathogen detection (higher incidence of respiratory syncytial viral infection), and clinical complications (lesser risk of sepsis and hydrothorax) (P<0.05).

Conclusions: Severe CAP with wheezing is a special clinical entity of severe pneumonia in children, which has specific risk factors and differ from non-wheezing pneumonia in terms of clinical features and etiologic pathogens.
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http://dx.doi.org/10.23736/S0026-4946.20.06065-XDOI Listing
January 2021

Obesity-induced upregulation of microRNA-183-5p promotes hepatic triglyceride accumulation by targeting the B-cell translocation gene 1.

Life Sci 2021 Mar 7;268:119011. Epub 2021 Jan 7.

Key Laboratory of Functional and Clinical Translational Medicine, Department of General Medicine, Xiamen Medical College, Xiamen, China. Electronic address:

Aims: Obesity is recognized as a risk factor for many metabolic disorders, particularly nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism is still poorly understood. Several lines of evidence indicate that microRNA (miRNA) is a key regulator of lipid metabolism. In this study, we investigated the role of miR-183-5p in the development of NAFLD.

Methods: The expression levels of miR-183-5p and B-cell translocation gene 1 (Btg1) were determined by quantitative real-time PCR and histological analysis in livers of obese mice and cell models induced with palmitic acid (PA), respectively. AML12 cells were treated with PA in the presence or absence of miR-183-5p mimics or inhibitor. Moreover, a Luciferase reporter assay was used to determine whether Btg1 is the direct target of miR-183-5p. Protein levels of BTG1 were estimated using western blotting.

Key Findings: Expression of miR-183-5p was increased in the livers of three murine models and also in the AML12 cell model. Overexpression of miR-183-5p in the cell model and mice led to hepatic triglyceride (TG) accumulation and upregulation of lipogenic genes, whereas inhibition of miR-183-5p in the cell model improved hepatic TG accumulation. Mechanistically, we further identified Btg1 as a direct target gene of miR-183-5p.

Significance: Our findings revealed that miR-183-5p affected the regulation of hepatic TG homeostasis, which may provide a potential therapeutic target for hepatosteatosis.
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http://dx.doi.org/10.1016/j.lfs.2020.119011DOI Listing
March 2021

Simultaneous voltammetric determination of epinephrine and acetaminophen using a highly sensitive CoAl-OOH/reduced graphene oxide sensor in pharmaceutical samples and biological fluids.

Mater Sci Eng C Mater Biol Appl 2021 Feb 28;119:111557. Epub 2020 Sep 28.

Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, PR China; School of Materials Science and Engineering, Henan Normal University, Xinxiang 453007, PR China. Electronic address:

For this study, three novel types of sensors comprised of CoAl-layered double oxyhydroxide (CoAl-LDH), CoAl-LDH/reduced graphene oxide (rGO), and CoAl-OOH/rGO nanosheets were successfully fabricated on glassy carbon electrodes (GCEs) and employed for the electrochemical detection of epinephrine (EP) and acetaminophen (AC). Interestingly, we found that the CoAl-OOH/rGO/GCE was more suitable for the determination of EP and AC in contrast to the CoAl-LDH and CoAl-OOH/rGO sensors. Differential pulse voltammetry results revealed that the CoAl-OOH/rGO/GCE delivered excellent electrocatalytic activity. The sensitivities and detection limits for the simultaneous measurement of EP and AC were 12.2 μA μM cm, 0.023 μM L, and 4.87 μA μM cm, 0.058 μM L, respectively. Especially, the as-obtained CoAl-OOH/rGO/GCE was successfully utilized for the detection in pharmaceutical samples and biological fluids with satisfactory results. Owing to its outstanding electrocatalytic activity and superior sensitivity, the CoAl-OOH/rGO/GCE could be beneficial to construct a promising electrochemical sensor for the detection of EP and AC.
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http://dx.doi.org/10.1016/j.msec.2020.111557DOI Listing
February 2021

One-pot preparation of a multi-functional enzymatically generated gelatin hydrogel with controllable antibacterial and hemorheological properties.

Int J Biol Macromol 2021 Jan 9;168:143-151. Epub 2020 Dec 9.

College of Bioresources Chemical and Materials Engineering, Institute of Biomass & Functional Materials, Shaanxi University of Science & Technology, Weiyang District, Xi'an 710021, Shaanxi, China; The Youth Innovation Team of Shaanxi Universities, Xi'an 710021, Shaanxi, China; National Demonstration Center for Experimental Light Chemistry Engineering Education, Shaanxi University of Science & Technology, Xi'an 710021, Shaanxi, China.

The creation of multi-functional bio-hydrogels with tunable properties that meet in vivo demands is significant but remains challenging. Inspired by host-guest chemistry, a novel multi-functional gelatin-based bio-hydrogel with tunable antibacterial and hemorheological properties (TAH-GEL) is synthesized via an in situ one-pot strategy. TAH-GEL not only exhibits excellent mechanical properties but also shows promising self-healing and bio-compatibility features. For the first time, this biomaterial presents controllable antibacterial and hemorheological properties by controlling the TAH-GEL polypseudorotaxane motif. The resulting bio-hydrogel is easy to prepare and delivers superior performance, making it a powerful tool for bio-applications, such as hemostatic materials.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.213DOI Listing
January 2021

Thermoresponsive Hemostatic Hydrogel with a Biomimetic Nanostructure Constructed from Aggregated Collagen Nanofibers.

Biomacromolecules 2021 02 9;22(2):319-329. Epub 2020 Dec 9.

BMI Center for Biomass Materials and Nanointerfaces, School of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan 610065, China.

Uncontrollable bleeding poses considerable fatality risks by large-volume blood losses. Current emergency antibleeding handlings including either compression with gauze or "passive" blood transfusion are thus far from ideal, while most recently developed hemostatic agents still share common limitations without considering the subsequent tissue repairing and antibacterial activity after treatment. Herein, we introduce a novel bioinspired aggregated collagen nanofiber-based biocompatible and efficient hemostatic hydrogel material (TS-Gel-Ag-col) prepared by the integration of multifunctional compounds of muco-mimetic poloxamer, polyvinylpyrrolidone, and dencichine/chitosan dialdehyde synergistic crosslinked aggregated collagen nanofibers decorated with silver nanoparticles. Comprehensive material characterization and and studies of TS-Gel-Ag-col demonstrate that these materials possess effective antihemorrhagic and antibacterial wound protection effects. Moreover, TS-Gel-Ag-col can facilitate the tissue repairing of skin wounds by promoting revascularization. TS-Gel-Ag-col holds great promise for next-generation collagen-based absorbable hemostatic materials and for the development of smart artificial skins.
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http://dx.doi.org/10.1021/acs.biomac.0c01167DOI Listing
February 2021

Paroxetine combined with fluorouracil plays a therapeutic role in mouse models of colorectal cancer with depression through inhibiting IL-22 expression to regulate the MAPK signaling pathway.

Exp Ther Med 2020 Dec 22;20(6):240. Epub 2020 Oct 22.

Department of Psychiatry, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

The objective of the present study was to observe the therapeutic effect of paroxetine combined with fluorouracil on mice with colorectal cancer (CRC) complicated with depression and to explore its mechanism of action. Using chronic mild stress and xenograft tumor methods to model CRC complicated with depression, 60 BALB/c mice were randomly divided into control, tumor model, tumor depression model, tumor depression antidepressant, tumor depression chemotherapy and tumor depression antidepressant plus chemotherapeutic drug groups. Changes in mouse sucrose preference and forced swimming tests were tracked. Changes in tumor volume and weight were compared, the tumor inhibition rate was calculated, Ki-67 expression in tumor tissues was detected using immunohistochemistry and IL-22 levels in peripheral blood were detected using ELISAs. Additionally, protein expression levels of IL-22, Bcl-2, Bax, caspase-3, p38, phosphorylated (p)-p38, ERK, p-ERK, JNK and p-JNK in tumor tissue were detected using western blotting. Following treatment with paroxetine and chemotherapy drugs, the sucrose preference index was increased, autonomic behavior dysfunction was alleviated and tumor growth was significantly inhibited. Furthermore, the expression levels of Ki-67 and apoptosis-related proteins, Bax and caspase-3, increased in tumor tissues, anti-apoptosis protein Bcl2 expression levels decreased significantly, IL-22 levels in the blood and tumor tissues were reduced and p-p38, p-ERK and p-JNK proteins were significantly reduced. It was concluded that paroxetine combined with chemotherapy drugs improved depressive behavior and promoted the survival state in a mouse model of CRC and depression, possibly through inhibiting IL-22 expression to regulate the activity of the MAPK signaling pathway.
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http://dx.doi.org/10.3892/etm.2020.9370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7651781PMC
December 2020

The Nuclear Orphan Receptor NR2F6 Promotes Hepatic Steatosis through Upregulation of Fatty Acid Transporter CD36.

Adv Sci (Weinh) 2020 Nov 21;7(21):2002273. Epub 2020 Sep 21.

The Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education Department of Endocrinology and Metabolism Fudan Institute for Metabolic Diseases Zhongshan Hospital Fudan University Shanghai 230032 P. R. China.

Nuclear receptors (NRs) are a superfamily of transcription factors which sense hormonal signals or nutrients to regulate various biological events, including development, reproduction, and metabolism. Here, this study identifies nuclear receptor subfamily 2, group F, member 6 (NR2F6), as an important regulator of hepatic triglyceride (TG) homeostasis and causal factor in the development of non-alcoholic fatty liver disease (NAFLD). Adeno-associated virus (AAV)-mediated overexpression of NR2F6 in the liver promotes TG accumulation in lean mice, while hepatic-specific suppression of NR2F6 improves obesity-associated hepatosteatosis, insulin resistance, and methionine and choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH). Mechanistically, the fatty acid translocase CD36 is identified as a transcriptional target of NR2F6 to mediate its steatotic role. NR2F6 is able to bind directly onto the CD36 promoter region in hepatocytes and increases the enrichment of nuclear receptor coactivator 1 (SRC-1) and histone acetylation at its promoter. Of pathophysiological significance, NR2F6 is significantly upregulated in the livers of obese mice and NAFLD patients. Moreover, treatment with metformin decreases NR2F6 expression in obese mice, resulting in suppression of CD36 and reduced hepatic TG contents. Therefore, these results provide evidence for an unpredicted role of NR2F6 that contributes to liver steatosis and suggest that NR2F6 antagonists may present a therapeutic strategy for reversing or treating NAFLD/NASH pathogenesis.
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http://dx.doi.org/10.1002/advs.202002273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610302PMC
November 2020

Elevated Serum Tsukushi Levels in Patients With Hyperthyroidism.

Front Endocrinol (Lausanne) 2020 29;11:580097. Epub 2020 Sep 29.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Tsukushi (TSK) is a secreted hepatokine recently identified as playing an important role in modulating glucose and lipid metabolism, and systemic energy homeostasis. However, information is not available regarding the association between circulating TSK and hyperthyroidism in humans. We measured serum TSK levels in 180 patients with hyperthyroidism and 82 healthy controls recruited from the clinic. Of them, 46 hyperthyroid patients received thionamide treatment for 3 months. Hyperthyroid patients had higher levels of circulating TSK than healthy controls [186.67 (133.63-280.59) ng/ml vs. 97.27 (77.87-146.96) ng/ml, < 0.001]. Subjects with higher level of serum free triiodothyronine (T3) and free thyroxine (T4) had higher levels of circulating TSK. In addition, serum TSK levels markedly declined with the improvement of thyroid function after thionamide treatment. In multivariable linear regression analyses, circulating TSK concentrations were significantly associated with serum free T3, free T4, thyroid stimulating hormone, thyrotropin receptor antibody, total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), high-density lipoprotein cholesterol (HDL-cholesterol), and basal metabolic rate (all < 0.01), adjusting for age, gender, smoking, and body mass index (BMI). Importantly, circulating TSK was significantly associated with risks of hyperthyroidism in multivariable logistic regression analyses, adjusting for age, gender, smoking, BMI, fasting glucose, LDL-cholesterol, and insulin resistance (HOMA-IR) [OR (95% CI), 1.012(1.005-1.019), = 0.001]. These findings indicate that circulating TSK concentrations are independently associated with hyperthyroidism, suggesting that circulating TSK may be a predictive factor of hyperthyroidism and can be used for therapeutic monitoring.
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http://dx.doi.org/10.3389/fendo.2020.580097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553082PMC
June 2021

Electron transport, light energy conversion and proteomic responses of periphyton in photosynthesis under exposure to AgNPs.

J Hazard Mater 2021 01 2;401:123809. Epub 2020 Sep 2.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, 71 East Beijing Road, Nanjing, 210008, China; Zigui Three Gorges Reservoir Ecosystem, Observation and Research Station of Ministry of Water Resources of the People's Republic of China, Yichang, 443605, China. Electronic address:

Silver nanoparticles (AgNPs) including a mix of intact nanoparticle-Ag and 'free' Ag pose high risks to benthic photoautotrophs, but the photosynthetic responses of benthic microbial aggregates to AgNPs still remain largely unknown. Here, periphyton and Nostoc were used to elucidate the photosynthetic responses of benthic algae community to intact nanoparticle-Ag and Ag. During exposure, both intact nanoparticle-Ag and Ag imposed negative effects on photosynthesis of benthic algae, but via different pathways. Specifically, Ag had stronger effects on damaging the oxygen-evolving complex (OEC) and thylakoid membrane than intact nanoparticle-Ag. Ag also suppressed electron transfer from Q to Q, and impaired phycobilisome. Intact nanoparticle-Ag inhibited the expression of PsbD and PsbL in PSII, but prompted the ROS scavenging capacity. In response to the stress of AgNPs, the benthic algae increased light energy absorption to maintain the electron transport efficiency, and up-regulated PSI reaction center protein (PsaA) to compensate the degraded PSII. These results reveal how intact nanoparticle-Ag and Ag influence electron transport, energy conversion and protein expression in the photosynthesis of periphyton, and provide deep insights into the responses of benthic photoautotrophs to different components of AgNPs.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123809DOI Listing
January 2021

Exenatide and Renal Outcomes in Patients with Type 2 Diabetes and Diabetic Kidney Disease.

Am J Nephrol 2020 23;51(10):806-814. Epub 2020 Sep 23.

Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China,

Background: Cardiovascular outcomes in clinical trials with type 2 diabetes mellitus (T2DM) patients have shown that glucagon-like peptide-1 receptor agonist can have a beneficial effect on the kidney. This trial aimed to assess the effects of exenatide on renal outcomes in patients with T2DM and diabetic kidney disease (DKD).

Methods: We performed a randomized parallel study encompassing 4 general hospitals. T2DM patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and macroalbuminuria, defined as 24-h urinary albumin excretion rate (UAER) >0.3 g/24 h were randomized 1:1 to receive exenatide twice daily plus insulin glargine (intervention group) or insulin lispro plus glargine (control group) for 24 weeks. The primary outcome was the UAER percentage change from the baseline after 24 weeks of intervention. The rates of hypoglycemia, adverse events (AEs), and change in eGFR during the follow-up were measured as safety outcomes.

Results: Between March 2016 and April 2019, 92 patients were randomized and took at least 1 dose of the study drug. The mean age of the participants was 56 years. At baseline, the median UAER was 1,512.0 mg/24 h and mean eGFR was 70.4 mL/min/1.73 m2. After 24 weeks of treatment, the UAER percentage change was significantly lower in the intervention group than in the control group (p = 0.0255). Moreover, the body weight declined by 1.3 kg in the intervention group (the difference between the 2 groups was 2.7 kg, p = 0.0001). Compared to the control group, a lower frequency of hypoglycemia and more gastrointestinal AEs were observed in the intervention group.

Conclusion: Exenatide plus insulin glargine treatment for 24 weeks resulted in a reduction of albuminuria in T2DM patients with DKD.
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http://dx.doi.org/10.1159/000510255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677996PMC
September 2020

Circular RNA circNFATC3 acts as a miR-9-5p sponge to promote cervical cancer development by upregulating SDC2.

Cell Oncol (Dordr) 2021 Feb 9;44(1):93-107. Epub 2020 Sep 9.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang City, 110004, China.

Purpose: Circular RNAs (circRNAs) constitute a class of regulatory RNAs that are thought to play important roles in tumor initiation and progression. Several studies have reported that circRNAs may be involved in various biological processes via networks of competing endogenous RNAs (ceRNAs). However, the regulatory roles and underlying mechanisms of circRNAs in cervical cancer (CC) still largely remain to be resolved.

Methods: CircNFATC3 (hsa_circ_0005615) expression was assessed in CC cell lines (SiHa, H8) using circRNA microarray analysis, whereas qRT-PCR was used to detect circNFATC3 and miR-9-5p expression in primary human CC tissues and cell lines. The tumor promoting role of circNFATC3 was verified in CC cells using a series of functional assays, and interactions between circNFATC3, miR-9-5p and syndecan-2 (SDC2) were investigated using dual-luciferase reporter assays. SDC2 protein expression was detected using Western blotting and immunohistochemistry. The tumor promoting role of circNFATC3 was confirmed in vivo using a CC xenograft model.

Results: We found that circNFATC3 expression was upregulated in primary CC tissues and positively correlated with CC tumor size and stromal invasion. In addition, we found that exogenous circNFATC3 overexpression enhanced the proliferation, migration and invasion of HeLa cells, while its knockdown reduced the malignancy of SiHa cells. We also found that circNFATC3 may act directly as a miR-9-5p sponge to regulate SDC2 expression and its downstream signaling pathways, thereby enhancing CC development.

Conclusion: Our data indicate that circNFATC3 sponges miR-9-5p to regulate SDC2 expression and, thereby, to promote CC tumor development.
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http://dx.doi.org/10.1007/s13402-020-00555-zDOI Listing
February 2021

Silk as templates for hydroxyapatite biomineralization: A comparative study of Bombyx mori and Antheraea pernyi silkworm silks.

Int J Biol Macromol 2020 Dec 20;164:2842-2850. Epub 2020 Aug 20.

Hubei Key Laboratory of Advanced Textile Materials & Application, School of Materials Science and Engineering, Wuhan Textile University, Wuhan 430200, China. Electronic address:

Silk is extensively investigated in bone tissue engineering due to its extraordinary mechanical properties and ability to regulate biomineralization. Protein templates regulate biomineralization process through chemical interaction with ions. However, the effect of structural differences in silk fibroin on biomineralization has not been studied in detail. In this study, Antheraea pernyi silk fibroin (ASF) and Bombyx mori silk fibroin (BSF) fibers were used as templates to study the effect of silk species on biomineralization. The results showed that silk fibroin could induce the formation of calcium-deficient hydroxyapatite in simulated body fluid (SBF), and the SBF treatment resulted in the formation of silk I crystals. Compared with BSF, ASF exhibited a higher ability to induce mineralization, which may depend on the differences in hydrophilic amorphous fractions between ASF and BSF. The amorphous fractions of ASF contain more acidic amino acids, which can provide more nucleation sites in the initial stage of mineralization, resulting in faster mineralization process and more mineral deposits. This study decodes the key role of silk fibroin fractions on biomineralization, and provides deeper insights for the study of silk fibroin as biomineralization template and bone repair materials.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.08.142DOI Listing
December 2020

Rational Design and Evaluation of 6-(Pyrimidin-2-ylamino)-3,4-dihydroquinoxalin-2(1)-ones as Polypharmacological Inhibitors of BET and Kinases.

J Med Chem 2020 09 26;63(17):9787-9802. Epub 2020 Aug 26.

Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.

Cancer exhibits diverse heterogeneity with a complicated molecular basis that usually harbors genetic and epigenetic abnormality, which poses a big challenge for single-target agents. In the current work, we proposed a hybrid strategy by incorporating pharmacophores that bind to the acetylated lysine binding pocket of BET proteins with a typical kinase hinge binder to generate novel polypharmacological inhibitors of BET and kinases. Through elaborating the core structure of 6-(pyrimidin-2-ylamino)-3,4-dihydroquinoxalin-2(1)-one, we demonstrated that this rational design can produce high potent inhibitors of CDK9 and BET proteins. In this series, compound was identified as the potential lead compound with balanced activities of BRD4 (IC = 12.7 nM) and CDK9 (IC = 22.4 nM), as well as good antiproliferative activities on a small cancer cell panel. Together, the current study provided a new method for the discovery of bromodomain and kinase dual inhibitors rather than only being discovered by serendipity.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00962DOI Listing
September 2020

Response of male reproductive function to environmental heavy metal pollution in a free-living passerine bird, Passer montanus.

Sci Total Environ 2020 Dec 1;747:141402. Epub 2020 Aug 1.

Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou, PR China. Electronic address:

Heavy metals affect male reproductive function by impairing reproductive organs, disturbing reproductive hormone levels or directly affecting sperm quality. However, little attention has been given to the effect of environmental heavy metals on reproductive function in wild male birds. The present study investigated the alterations of reproductive function in male tree sparrows (Passer montanus) exposed to environments contaminated by heavy metals in terms of testis parameters, reproductive hormone levels and sperm movement characteristics. Two plots, Baiyin (BY, mainly polluted by copper, zinc, lead and cadmium) and Liujiaxia (LJX, a relatively unpolluted area) were selected as sampling sites. The results showed that tree sparrows from BY (1) accumulated higher levels of cadmium in the testes, (2) showed lower superoxide dismutase (SOD) activity and malondialdehyde level, with higher total antioxidant capacity and apoptosis level in the testes, (3) showed higher plasma levels of estrogen, follicle stimulating hormone and luteinizing hormone (LH), and (4) had better sperm movement performance. Additionally, we found that testis size, SOD activity in testes and LH levels were decisive factors in sperm movement performance in tree sparrows. Heavy metal concentrations in testes negatively correlated with testis size, SOD activity in testes, and estrogen levels in tree sparrows. The present study indicates that heavy metals accumulating in testes of tree sparrows adversely affected some key indicators of male reproductive function. However, testicular function, reproductive hormone levels and sperm quality showed adaptive responses that tended to partially compensate for the negative effects in the heavy metal polluted area. This study further indicated that the regulation of testicular function and reproductive hormone levels was the main factor for better sperm quality in tree sparrows exposed to environments contaminated by heavy metals.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141402DOI Listing
December 2020