Publications by authors named "Jie Sheng"

174 Publications

Effects of single and combined gestational phthalate exposure on blood pressure, blood glucose and gestational weight gain: A longitudinal analysis.

Environ Int 2021 Oct 11;155:106677. Epub 2021 Jun 11.

MOE Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), No. 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No. 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China; Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address:

Few studies have investigated the association of gestational exposure to phthalate with metabolic risk and have reached inconsistent conclusions. Based on the Ma'anshan Birth Cohort, 3273 women were included in the present study. All participants provided up to three urine samples for 7 phthalate metabolite measurements. The hazard index (HI) was used to evaluate the cumulative risk of multiple phthalate coexposures. The outcomes of interest included hypertensive disorders of pregnancy (HDOP), gestational diabetes mellitus (GDM), and gestational weight gain (GWG). The incidences of HDOP, GDM, and excessive GWG were 5.93%, 13.09%, and 28.95%, respectively. Exposure to a single phthalate metabolite or a specific diester during the first trimester of pregnancy elevated blood pressure (BP) and fasting plasma glucose (FPG) in the third trimester and body weight gain throughout pregnancy. However, inverse relationships were revealed for some phthalate metabolites, which were inconsistent with the results of their diesters. The HI value during the first trimester was positively associated with subsequent BP, FPG, and GWG. In addition, HI during the first trimester increased the risks of GDM [odds ratio (OR) = 1.34, 95% confidence intervals (CIs) = 1.02-1.75)] and excessive GWG (OR = 1.76, 95% CIs = 1.41-2.19) in a linear manner thereafter. Notably, phthalates might directly increase maternal blood glucose and pressure, and these changes were secondary effects of the obesiogenic effects of certain phthalates. In conclusion, exposure to single and multiple phthalates during the first trimester of pregnancy increased the risks of maternal metabolic syndrome components. However, the conflicting findings between phthalates and their metabolites need to be interpreted carefully.
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http://dx.doi.org/10.1016/j.envint.2021.106677DOI Listing
October 2021

A highly conductive Ni(OH) nano-sheet wrapped CuCoS nano-tube electrode with a core-shell structure for high performance supercapacitors.

Dalton Trans 2021 Jun;50(24):8476-8486

School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001, China.

The design of microstructures and the optimum selection of electrode materials have substantial effects on the electrochemical performances of supercapacitors. A core-shell structured [email protected](OH)2 electrode material was designed, with CuCo2S4 nanotubes as the core wrapped by interlaced Ni(OH)2 nano-sheets as the shell. The hydrothermal and electro-deposition processes were adopted to synthesize [email protected](OH)2 materials. The CuCo2S4 nanotubes can both provide specific capacitance and act as a "superhighway" for electrons due to their highly conductive skeleton structure. The Ni(OH)2 nano-sheets will boost the electrochemically active sites and enhance the specific surface area. Meanwhile, the mutually restricted core-shell [email protected](OH)2 electrode could regulate the volume deformation to improve its stability. The [email protected](OH)2 electrode had a maximum specific capacitance of 2668.4 F g-1 at a current density of 1 A g-1 and a superior cycling stability of 90.3% after 10 000 cycles. Moreover, a [email protected](OH)2//active carbon asymmetric supercapacitor with a maximum energy density of 44 W h kg-1 was assembled, suggesting that [email protected](OH)2 is a successful binder-free electrode material for high performance supercapacitors.
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http://dx.doi.org/10.1039/d1dt01075aDOI Listing
June 2021

Nickel-Catalyzed Cross-Coupling of Ethyl Chlorofluoroacetate with Aryl Bromides.

Chem Asian J 2021 Jul 28;16(13):1741-1744. Epub 2021 May 28.

Hefei National Laboratory for Physical Sciences at Microscale and Department of Chemical, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China.

A combinatorial nickel-catalyzed monofluoroalkylation of aryl bromides with the industrial raw regent ethyl chlorofluoroacetate has been developed. The two key factors to successful conversion are the combination of nickel with readily available nitrogen and phosphine ligands and the using of a mixture of different solvents. Mechanistic investigations indicated a new zinc regent might generated in situ and be involved in the reaction process.
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http://dx.doi.org/10.1002/asia.202100348DOI Listing
July 2021

Establishing content validity for a composite activities-specific risk of falls scale:linkage between fear of falling and physical activity.

BMC Geriatr 2021 04 26;21(1):275. Epub 2021 Apr 26.

Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, 201619, China.

Background: Fear of falling (FoF) and physical activity (PA) are important psychological and behavioral factors associated with falls. No instrument quantifies the link between these two factors to evaluate the risk of falls. We aimed to design a scale linking FoF with PA (Composite Activities-specific Risk of Falls Scale, CARFS) for people with various disability levels.

Methods: First, we designed a questionnaire comprising 40 balance-related activities from the International Classification of Functioning, Disability, and Health (ICF) for a pilot survey. Second, participants were interviewed about their activities-specific FoF degree and PA frequency. The participants comprised 30 community-dwelling older adults, hospitalized patients with strokes, and those with spinal cord injuries, each with different disability levels. Third, the content validity of the items was evaluated twice by 12 experienced rehabilitation professionals: one based on experience and the other on the survey responses. Items with a higher than moderate relevance in both evaluations were included in the CARFS. The panel of professionals discussed and voted on the contribution of FoF and PA on the CARF score. Finally, the scale sensitivity in distinguishing disability levels was analyzed to evaluate the population suitability to the CARFS.

Results: The CARFS included 14 activities. A five-point Likert scale was used to quantify degree of FoF (A) and frequency of PA (B). The CARF score (C), which was determined using the eq. C = A+(4-B) + A × B/2, reflected sensitivity to disability levels in most items.

Conclusions: The CARFS has strong content validity for measuring risk of falls in relation to the FoF and PA of people with various disability levels. It has a potential to provide a guide for designing individualized exercise- and behavior-focused fall prevention programs and enable the precise trtrun 0acking of program effectiveness as a multidimensional outcome measure.
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http://dx.doi.org/10.1186/s12877-021-02211-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077745PMC
April 2021

NUCB1 Suppresses Growth and Shows Additive Effects With Gemcitabine in Pancreatic Ductal Adenocarcinoma via the Unfolded Protein Response.

Front Cell Dev Biol 2021 29;9:641836. Epub 2021 Mar 29.

Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, Shanghai, China.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient prognosis. A cellular stress response mechanism called the unfolded protein response (UPR) has been implicated in PDAC progression. More recently, nucleobindin 1 (NUCB1), a calcium-binding protein, has been shown to control the UPR but its precise role in PDAC has not been explored. Here, we found that downregulation of NUCB1 was associated with poor prognosis in patients with PDAC. Functionally, NUCB1 overexpression suppressed pancreatic cancer cell proliferation and showed additive effects with gemcitabine (GEM) and . Moreover, by controlling ATF6 activity, NUCB1 overexpression suppressed GEM-induced UPR and autophagy. Last but not least, we uncovered METTL3-mediated mA modification on NUCB1 5'UTR via the reader YTHDF2 as a mechanism for NUCB1 downregulation in PDAC. Taken together, our study revealed crucial functions of NUCB1 in suppressing proliferation and enhancing the effects of gemcitabine in pancreatic cancer cells and identified METTL3-mediated mA modification as a mechanism for NUCB1 downregulation in PDAC.
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http://dx.doi.org/10.3389/fcell.2021.641836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041069PMC
March 2021

Diversity-Oriented Synthesis of Aliphatic Fluorides via Reductive C(sp )-C(sp ) Cross-Coupling Fluoroalkylation.

Angew Chem Int Ed Engl 2021 06 1;60(27):15020-15027. Epub 2021 Jun 1.

Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui, 230026, China.

Monofluorinated alkyl compounds are of great importance in pharmaceuticals, agrochemicals and materials. Herein, we describe a direct nickel-catalyzed monofluoromethylation of unactivated alkyl halides using a low-cost industrial raw material, bromofluoromethane, by demonstrating a general and efficient reductive cross-coupling of two alkyl halides. Results with 1-bromo-1-fluoroalkane also demonstrate the viability of monofluoroalkylation, which further established the first example of reductive C(sp )-C(sp ) cross-coupling fluoroalkylation. These transformations demonstrate high efficiency, mild conditions, and excellent functional-group compatibility, especially for a range of pharmaceuticals and biologically active compounds. Mechanistic studies support a radical pathway. Kinetic studies reveal that the reaction is first-order dependent on catalyst and alkyl bromide whereas the generation of monofluoroalkyl radical is not involved in the rate-determining step. This strategy provides a general and efficient method for the synthesis of aliphatic fluorides.
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http://dx.doi.org/10.1002/anie.202102481DOI Listing
June 2021

DeepDigest: Prediction of Protein Proteolytic Digestion with Deep Learning.

Anal Chem 2021 04 7;93(15):6094-6103. Epub 2021 Apr 7.

CEMS, NCMIS, RCSDS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, P. R. China.

Proteolytic digestion of proteins by one or more proteases is a key step in shotgun proteomics, in which the proteolytic products, i.e., peptides, are taken as the surrogates of their parent proteins for further qualitative or quantitative analysis. The proteases generally cleave proteins at specific amino acid residue sites, but digestion is hardly complete (wide existence of missed cleavage sites). Therefore, it would be of great help to improve the prior experimental design and the posterior data analysis if the digestion behaviors of proteases can be accurately modeled and predicted. At present, systematic studies about the commonly used proteases in proteomics are insufficient, and there is a lack of easy-to-use tools to predict the cleavage sites of different proteases. Here, we propose a novel sequence-based deep learning algorithm-DeepDigest, which integrates convolutional neural networks and long short-term memory networks for protein digestion prediction. DeepDigest can predict the cleavage probability of each potential cleavage site on the protein sequences for eight popular proteases including trypsin, ArgC, chymotrypsin, GluC, LysC, AspN, LysN, and LysargiNase. We compared DeepDigest with three traditional machine learning algorithms, i.e., logistic regression, random forest, and support vector machine. On the eight training data sets, the 10-fold cross-validation accuracies (AUCs) of DeepDigest were 0.956-0.982, significantly higher than those of the three traditional algorithms. On the 11 independent test data sets, DeepDigest achieved AUCs between 0.849 and 0.978, outperforming the other traditional algorithms in most cases. Transfer learning then further improved the prediction accuracy. Besides, some interesting characteristics of different proteases were revealed and discussed. Ultimately, as an application, we used DeepDigest to predict the digestibilities of peptides and demonstrated that peptide digestibility is an informative new feature to discriminate between correct and incorrect peptide identifications.
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http://dx.doi.org/10.1021/acs.analchem.0c04704DOI Listing
April 2021

Moderating effects of plastic packaged food on association of urinary phthalate metabolites with emotional symptoms in Chinese adolescents.

Ecotoxicol Environ Saf 2021 Mar 31;216:112171. Epub 2021 Mar 31.

Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, PR China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, 81 Meishan Road, Hefei 230032, Anhui, PR China. Electronic address:

Previous research reports that diet is the main source of phthalate exposure to adolescents, and phthalate is associated with adolescent mental and behavioral problems. However, no study has explored the moderating effects of eating behavior in this association. This study aimed to analyze the moderating effects of plastic packaged food consumption in the longitudinal association between phthalate metabolite concentration and emotional symptoms in adolescents. This school-based survey was carried out among adolescents in two Chinese provinces. We conducted a baseline and follow-up surveys for 893 freshmen using the purposive sampling method from December 2018 to November 2019. We used food frequency questionnaire to assess eating behavior. The Chinese version of 21-item Depression Anxiety Stress Scales was used to assess emotional symptoms, and high-performance liquid chromatography-tandem mass spectrometry was used to analyze the concentration of six urine phthalate metabolites. The results of latent moderation model indicated that plastic packaged food consumption moderated the association of low molecular weight phthalate (LMWP) with depressive symptoms (β = 0.27, P = 0.002), anxiety symptoms (β = 0.89, P < 0.01), and stress symptoms (β = 0.23, P = 0.019). The moderating effects were significant at the higher scores (β = 0.14-0.35, P < 0.05) and/or the lower scores (β = -0.35 to -0.12, P < 0.05) of plastic packaged food consumption. The results suggest that plastic packaged food consumption to some extent moderates the longitudinal association of phthalate exposure with emotional symptoms in adolescents.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112171DOI Listing
March 2021

Pioneering Iodine-125-Labeled Nanoscale Covalent Organic Frameworks for Brachytherapy.

Bioconjug Chem 2021 04 28;32(4):755-762. Epub 2021 Mar 28.

State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, 199 Ren'ai Road, Suzhou 215123, China.

Brachytherapy has been clinically used for the treatment of malignant solid tumors. However, the classic therapeutic radioactive I seed must be surgically implanted directly into tumors. To avoid the surgery and prevent irrational radioactive distribution, radioiodine-loaded nanomaterials are ever-developing for brachytherapy. Hence, it is still a notable challenge to obtain an advanced material that simultaneously incorporates features of high radiolabeling rate, short labeling time, good radiolabeling stability, and long tumor retention time. Covalent organic frameworks (COFs), which are crystalline polymers with ordered pores, are widely applied in guest delivery of drugs based on their high porosity and modifiable skeleton. Herein, we developed a functionalized nanoscale PEG-COF-Ag material, which could rapidly capture radioiodine reaching a 94% radiolabeling yield in 30 s. In addition, more than 95% I was maintained after 24 h in PBS (phosphate-buffered saline) as well as in serum and over 90% for nearly 1 week. PEG-COF-Ag-I (I-COF) demonstrated excellent cancer cell killing performance in vitro, and further experiments in vivo revealed a long tumor retention time and effective tumor treatment during the radiotherapy. The results indicate that radioiodine-labeled PEG-COF-Ag could be potentially applied in brachytherapy with a promising therapeutic effect.
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http://dx.doi.org/10.1021/acs.bioconjchem.1c00040DOI Listing
April 2021

The less conserved metal-binding site in human CRISP1 remains sensitive to zinc ions to permit protein oligomerization.

Sci Rep 2021 Mar 9;11(1):5498. Epub 2021 Mar 9.

Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

Cysteine-rich secretory proteins (CRISPs) are a subgroup of the CRISP, antigen 5 and PR-1 (CAP) superfamily that is characterized by the presence of a conserved CAP domain. Two conserved histidines in the CAP domain are proposed to function as a Zn-binding site with unknown function. Human CRISP1 is, however, one of the few family members that lack one of these characteristic histidine residues. The Zn-dependent oligomerization properties of human CRISP1 were investigated using a maltose-binding protein (MBP)-tagging approach in combination with low expression levels in XL-1 Blue bacteria. Moderate yields of soluble recombinant MBP-tagged human CRISP1 (MBP-CRISP1) and the MBP-tagged CAP domain of CRISP1 (MBP-CRISP1) were obtained. Zn specifically induced oligomerization of both MBP-CRISP1 and MBP-CRISP1 in vitro. The conserved His142 in the CAP domain was essential for this Zn dependent oligomerization process, confirming a role of the CAP metal-binding site in the interaction with Zn. Furthermore, MBP-CRISP1 and MBP-CRISP1 oligomers dissociated into monomers upon Zn removal by EDTA. Condensation of proteins is characteristic for maturing sperm in the epididymis and this process was previously found to be Zn-dependent. The Zn-induced oligomerization of human recombinant CRISP1 may shed novel insights into the formation of functional protein complexes involved in mammalian fertilization.
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http://dx.doi.org/10.1038/s41598-021-84926-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943821PMC
March 2021

Rhizoma drynariae total flavonoids inhibit the inflammatory response and matrix degeneration via MAPK pathway in a rat degenerative cervical intervertebral disc model.

Biomed Pharmacother 2021 Jun 16;138:111466. Epub 2021 Mar 16.

School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei 230032, Anhui, China. Electronic address:

Rhizoma drynariae total flavonoids (RDTF) are extracted from Drynaria fortunei J. Sm (D. fortunei), which was a Chinese herb commonly used to treat fractures and bruises. Modern pharmacological studies indicate flavonoids have anti-inflammatory effect in clinical practice. However, its active ingredients and the mechanisms of action are far from clear. The present study aims to determine whether RDTF can protect against intervertebral disc degeneration in a rat cervical intervertebral disc model and investigate the associated molecular mechanisms. Sprague Dawley (SD) rats were randomized into five groups: control group (CG, n = 8), intervertebral disc degeneration group (NG, n = 8), low-dose RDTF-treated group (LG, n = 8), medium-dose RDTF-treated group (MG, n = 8), and high-dose RDTF-treated group (HG, n = 8). Hematoxylin and eosin (HE) staining, immunohistochemistry (IHC), immunofluorescence, ELISA, Western blot and quantitative real time PCR (qRT-PCR) assays were used to investigate inflammatory, catabolic factors and the latent regulatory mechanism of the effects of RDTF on intervertebral disc cells. HE staining showed disc degeneration in all groups except CG, and the function was restored after RDTF treatment. IHC, Western blot, qRT-PCR, immunofluorescence and ELISA results showed that RDTF prevented intervertebral disc degeneration by suppressing mitogen-activated protein kinase (MAPK) pathway, which reduced expression of intracellular matrix metalloproteinases (MMPs), such MMP3, MMP13, and inflammatory factors including interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α). Notably RDTF inhibited extracellular matrix (ECM) degeneration by increasing expression of aggrecan and collagen type II and preventing the upregulation of collagen type I and III. It suggests that RDTF has a potential therapeutic effect on cervical spondylosis.
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http://dx.doi.org/10.1016/j.biopha.2021.111466DOI Listing
June 2021

[Exploration of organoid in breast cancer related research].

Sheng Wu Gong Cheng Xue Bao 2021 Feb;37(2):395-403

Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan 430081, Hubei, China.

Breast cancer is the most common cancer in women. At present, the in vivo model and traditional cell culture are mainly used in breast cancer researches. However, as high as 90% clinical trials are failed for drugs explored by the above two methods, due to the inherent species differences between humans and animals, as well as the differences in the tissue structure between organs and cells. Therefore, organoid three-dimensional culture is emerging. As a new tumor research model, organoid, a three-dimensional cell complex with spatial structure, has broad application prospects, such as precision medicine, organ transplantation, establishment of refractory disease model, gene therapy and drug research and development. Therefore, organoid is considered as one of the ideal carriers for life science research in the future. Breast cancer, a heterogeneous disease with complex phenotypes, has a low survival rate. Breast cancer organoid can reproduce many key features of human breast cancer, thus, the construction of organoid biological library of breast cancer will provide a new platform for studying the occurrence, development, metastasis and drug resistance mechanism of breast cancer. In this review, we systematically introduce the culture conditions of organoids and their application in breast cancer related research, and the application prospect of organoids.
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http://dx.doi.org/10.13345/j.cjb.200285DOI Listing
February 2021

Copper-Catalyzed Trifluoromethylation/Cyclization of Alkynes for Synthesis of Dioxodibenzothiazepines.

Org Lett 2021 Mar 26;23(6):2194-2198. Epub 2021 Feb 26.

Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China.

A facile and efficient approach for the synthesis of the CF-containing dioxodibenzothiazepines has been developed via copper-catalyzed trifluoromethylation/cyclization of alkynes utilizing a radical relay strategy. This method has demonstrated low catalyst loading, high regiocontrol, and broad scope under mild conditions. Good compatibility for the N-protecting group, gram-scale experiment, and further derivation of product prove the versatility of this transformation.
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http://dx.doi.org/10.1021/acs.orglett.1c00344DOI Listing
March 2021

Fam83D promotes tumorigenesis and gemcitabine resistance of pancreatic adenocarcinoma through the Wnt/β-catenin pathway.

Life Sci 2021 Feb 8:119205. Epub 2021 Feb 8.

Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai 200032, PR China. Electronic address:

Background: Elevated expression of family with sequence similarity 83 member D (Fam83D) has been found in various cancers; however, its role in pancreatic adenocarcinoma (PDAC) remains unclear. The current study was designed to elucidate the roles of Fam83D in pancreatic cancer.

Method: The level of Fam83D was detected in PDAC tissues and adjacent no-tumorous tissues. Effects of Fam83D on proliferation, glycolysis and gemcitabine (GEM) sensitivity of pancreatic cancer cells were examined.

Results: Fam83D was overexpressed in PDAC and associated with clinical stage, metastatic status and survival rates of PDAC patients. Function study showed that Fam83D knockdown (KD) caused inhibited proliferation, suppressed mitochondrial respiration capacity, reduced aerobic glycolysis, and down-regulation of nuclear β-catenin, proto-oncogene C-Myc, and lactate dehydrogenase A (LDHA). Fam83D KD enhanced the sensitivity of PDAC cells to GEM in vitro and in vivo. On the contrary, Fam83D overexpression displayed reverse effects on PDAC cells. Moreover, the Wnt/β-catenin inhibitor abolished the effects of Fam83D overexpression in PDAC cells.

Conclusions: the current data suggest that enhanced Fam83D expression contributes to PDAC progression and the development of chemoresistance through the Wnt/β-catenin signaling.
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http://dx.doi.org/10.1016/j.lfs.2021.119205DOI Listing
February 2021

Diverse Synthesis of Chiral Trifluoromethylated Alkanes via Nickel-Catalyzed Asymmetric Reductive Cross-Coupling Fluoroalkylation.

Angew Chem Int Ed Engl 2021 04 18;60(18):9947-9952. Epub 2021 Mar 18.

Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui, 230026, China.

The trifluoromethyl group represents one of the most functional and widely used fluoroalkyl groups in drug design and screening, while the drug candidates containing chiral trifluoromethyl-bearing carbons are still few due to the lack of efficient methods for the asymmetric introduction of trifluoromethyl group into organic molecules. Herein, we described a nickel-catalyzed asymmetric trifluoroalkylation of aryl iodides, for the first time, by utilizing reductive cross-coupling in enantioselective fluoroalkylation. This novel method has demonstrated high efficiency, mild conditions, and excellent functional group tolerance, especially for substrates containing diverse pharmaceutical and bioactive molecules moieties. This strategy provided an efficient and facile way for diversity-oriented synthesis of chiral trifluoromethylated alkanes.
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http://dx.doi.org/10.1002/anie.202101076DOI Listing
April 2021

Antibiotic exposure and potential risk of depression in the Chinese elderly: a biomonitoring-based population study.

Environ Sci Pollut Res Int 2021 Jun 26;28(21):26794-26806. Epub 2021 Jan 26.

School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China.

Objective: To examine the associations between urinary antibiotics from various sources and depression in the elderly using the biomonitoring method.

Methods: In the current study, we investigated 990 elderly individuals (≥ 60 years old) from a community-based elderly cohort in West Anhui, China. The participants were interviewed by the Geriatric Depression Scale and self-developed questionnaires. A total of 45 antibiotics belonging to nine categories were screened in urine samples by the developed liquid chromatography electrospray tandem mass spectrometry method. Creatinine-corrected concentrations of antibiotics in urines were used to assess their exposure. Logistic regression analysis was employed to test the relationships between exposure to antibiotics and depression.

Results: Compared to the control group, the multinomial logistic regression analyses showed the elderly exposed to higher concentrations of azithromycin (OR = 1.81, 95% CI: 1.09-3.00) and sulfaclozine (OR = 1.54, 95% CI: 1.05-2.28) had increased risks of depression, respectively. After categorizing the detected antibiotics, tetracyclines (OR = 1.48, 95% CI: 1.02-2.16) and veterinary antibiotics (VAs) (OR = 1.53, 95% CI: 1.06-2.20) were positively correlated with increased risks of depression. After stratified by sex, the VAs (OR = 2.04, 95% CI: 1.13-3.71) at higher concentrations were associated with elevated risks of depression in males, while the associations between depression and antibiotic exposures were observed in tetracyclines (OR = 1.74, 95% CI: 1.04-2.85) and all antibiotics (OR = 2.24, 95% CI: 1.01-2.94) at higher levels in females, respectively. Notably, after the stratification by age, the significant associations were mainly present in the subjects under the age of 70.

Conclusions: Our findings reveal that azithromycin, sulfaclozine, tetracyclines, and the VAs were significantly associated with elevated risks of depression in the elderly. Importantly, sex- and age-specific differences were observed in the associations between antibiotic exposures and depression.
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http://dx.doi.org/10.1007/s11356-021-12560-2DOI Listing
June 2021

Patients' Preferences for Artificial Intelligence Applications Versus Clinicians in Disease Diagnosis During the SARS-CoV-2 Pandemic in China: Discrete Choice Experiment.

J Med Internet Res 2021 02 23;23(2):e22841. Epub 2021 Feb 23.

Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China.

Background: Misdiagnosis, arbitrary charges, annoying queues, and clinic waiting times among others are long-standing phenomena in the medical industry across the world. These factors can contribute to patient anxiety about misdiagnosis by clinicians. However, with the increasing growth in use of big data in biomedical and health care communities, the performance of artificial intelligence (Al) techniques of diagnosis is improving and can help avoid medical practice errors, including under the current circumstance of COVID-19.

Objective: This study aims to visualize and measure patients' heterogeneous preferences from various angles of AI diagnosis versus clinicians in the context of the COVID-19 epidemic in China. We also aim to illustrate the different decision-making factors of the latent class of a discrete choice experiment (DCE) and prospects for the application of AI techniques in judgment and management during the pandemic of SARS-CoV-2 and in the future.

Methods: A DCE approach was the main analysis method applied in this paper. Attributes from different dimensions were hypothesized: diagnostic method, outpatient waiting time, diagnosis time, accuracy, follow-up after diagnosis, and diagnostic expense. After that, a questionnaire is formed. With collected data from the DCE questionnaire, we apply Sawtooth software to construct a generalized multinomial logit (GMNL) model, mixed logit model, and latent class model with the data sets. Moreover, we calculate the variables' coefficients, standard error, P value, and odds ratio (OR) and form a utility report to present the importance and weighted percentage of attributes.

Results: A total of 55.8% of the respondents (428 out of 767) opted for AI diagnosis regardless of the description of the clinicians. In the GMNL model, we found that people prefer the 100% accuracy level the most (OR 4.548, 95% CI 4.048-5.110, P<.001). For the latent class model, the most acceptable model consists of 3 latent classes of respondents. The attributes with the most substantial effects and highest percentage weights are the accuracy (39.29% in general) and expense of diagnosis (21.69% in general), especially the preferences for the diagnosis "accuracy" attribute, which is constant across classes. For class 1 and class 3, people prefer the AI + clinicians method (class 1: OR 1.247, 95% CI 1.036-1.463, P<.001; class 3: OR 1.958, 95% CI 1.769-2.167, P<.001). For class 2, people prefer the AI method (OR 1.546, 95% CI 0.883-2.707, P=.37). The OR of levels of attributes increases with the increase of accuracy across all classes.

Conclusions: Latent class analysis was prominent and useful in quantifying preferences for attributes of diagnosis choice. People's preferences for the "accuracy" and "diagnostic expenses" attributes are palpable. AI will have a potential market. However, accuracy and diagnosis expenses need to be taken into consideration.
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http://dx.doi.org/10.2196/22841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903977PMC
February 2021

p53-targeted lncRNA ST7-AS1 acts as a tumour suppressor by interacting with PTBP1 to suppress the Wnt/β-catenin signalling pathway in glioma.

Cancer Lett 2021 Apr 19;503:54-68. Epub 2021 Jan 19.

Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016, China. Electronic address:

Glioma is the most prevalent intracranial tumour, with considerable morbidity. Long non-coding RNAs are important in the biological processes of various cancers. However, little is known about ST7 antisense RNA 1 (ST7-AS1) and its role in glioma progression. ST7-AS1 expression was reduced in glioma tissues and cells in comparison to normal brain tissues. p53 transcriptionally targeted the ST7-AS1 promoter in U251 glioma cells. The targeting significantly inhibited cell migration, invasion, and proliferation, and promoted apoptosis. ST7-AS1 directly bound to and downregulated polypyrimidine tract-binding protein 1 (PTBP1) at the post-transcriptional level. ST7-AS1 overexpression inhibited glioma progression by suppressing Wnt/β-catenin signalling by downregulating PTBP1 expression. Additionally, p53 expression negatively correlated with PTBP1 expression. Glioma progression is regulated by a positive feedback loop involving the p53/ST7-AS1/PTBP1 axis, which might be a promising therapeutic target for glioma treatment.
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http://dx.doi.org/10.1016/j.canlet.2020.12.039DOI Listing
April 2021

Antibiotics biomonitored in urine and obesogenic risk in a community-dwelling elderly population.

Ecotoxicol Environ Saf 2021 Mar 3;210:111863. Epub 2021 Jan 3.

School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University),Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, No 81 Meishan Road, Hefei 230032, Anhui, China; School of Health Management, Anhui Medical University, Hefei 230032, China.

Background: Experimental and epidemiological studies have linked antibiotics use to gut dysbiosis-mediated risk of chronic metabolic diseases. However, whether adiposity is linked to antibiotic exposure in elderly remains inadequately understood.

Objective: To investigate the association between internal exposure of antibiotics and adiposity in elderly by using a biomonitoring method.

Methods: We included 990 participants (≥60 years) from the baseline survey of the Cohort of Elderly Health and Environment Controllable Factors in Lu'an city, China, from June to September 2016. Forty-five antibiotics and two metabolites in urine were monitored through liquid chromatography-electrospray tandem mass spectrometry (HPLC-MS/MS). Creatinine-corrected urinary concentrations were used to assess antibiotic exposure levels. Body mass index (BMI), waist circumference (WC) and body fat percentage (BFP) were used as indicators of adiposity. Multiple linear regression and binary logistic regression analyses were used to analyze the association of antibiotic concentrations with obesity-related indices. Subsequently, a gender-stratified analysis was performed.

Results: Of the included elderly, 50.7% were defined as having overweight/ obesity, 59.8% as having central preobesity/obesity, and 37.5% as having slightly high/high BFP. Linear regression analysis revealed that a 1-unit increase in the logarithmic transformation of norfloxacin concentrations was related with an increase of 0.29 kg/m (95% CI: 0.02-0.04), 0.99 cm (95% CI:0.24-1.75), and 0.69% (95% CI:0.21-1.17) in BMI, WC, and BFP, respectively. Compared with the control group, exposure to doxycycline (tertile 2: odds ratio, 2.06 [95% CI: 1.12-3.76]) and norfloxacin (tertile 2: 2.13 [1.05-4.29]; tertile 3: 2.07 [1.03-4.17]) had BMI-based overweight/obesity risk. Additionally, ciprofloxacin (tertile 2: 2.06 [1.12-3.76]), norfloxacin (tertile 3: 2.95 [1.34-6.49]), and florfenicol (tertile 3: 1.84 [1.07-3.14]) were related to WC-based central preobesity/obesity risk. Norfloxacin (tertile 3: 2.54 [1.23-5.24]) was positively associated with a slightly high/high BFP risk. Gender-stratified analysis demonstrated an increased adiposity risk in women compared with men.

Conclusions: Our research provided an evidence that exposure to specific types of antibiotics (tetracyclines and fluoroquinolones) probably from the food chain contributed to obesity in elderly. Prospective cohort studies with larger sample size are warrented to explore the causation.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111863DOI Listing
March 2021

Levels and determinants of urinary phthalate metabolites in Chinese community-dwelling older adults.

Sci Total Environ 2021 Mar 24;762:144173. Epub 2020 Dec 24.

School of Public Health, Department of Epidemiology and Health Statistics, Anhui Medical University, Hefei, Anhui 230032, China. Electronic address:

Background: Biomonitoring studies have demonstrated extensive exposure of infants, children, and pregnant women to phthalates, but data on phthalate exposure and their determinants in Chinese older adults remain insufficient. This study aims to assess urinary phthalate metabolite levels, individual and cumulative exposure risk, and their determinants in Chinese community-dwelling older adults.

Methods: A total of 987 individuals aged 60 years or over were included in this study. The urinary levels of seven phthalate metabolites were measured using high-performance liquid chromatography-tandem mass spectrometry. The estimated daily intake (EDI), hazard quotient (HQ), and hazard index (HI) of phthalates were calculated based on urinary metabolite levels. The associations between phthalate metabolite levels and potential determinants were examined using multiple linear regressions.

Results: Detection rates of seven phthalate metabolites from the study population ranged from 63.83% to 99.39%. The highest median concentration was 43.64 μg/L (42.59 μg/g creatinine) for mono-butyl phthalate (MBP). The highest median EDI was 1.55 μg/kg-bw/day for diethyl phthalate (DBP). Nearly 5% of participants had high HI values exceeding 1, mainly attributed to DBP and di-2-ethylhexyl phthalate (DEHP). Furthermore, we found that females, higher body mass index (BMI), smoking, having two or more chronic diseases, and vegetable-based diets were significantly associated with higher levels of parts of phthalate metabolites. More interestingly, higher urine levels of high-molecular-weight (HMW) phthalate metabolites and lower urine levels of low-molecular-weight (LMW) phthalate metabolites were found in rural older adults than in urban older adults.

Conclusions: Chinese community-dwelling older adults are extensively exposed to phthalates, especially to DBP and DEHP. More attention should be paid to urban-rural differences in exposure to HMW and LMW phthalates and to phthalate exposure among older adults with overweight/obesity, females, and individuals who are current heavy smokers, have two or more chronic diseases, and consume vegetable-based diets.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144173DOI Listing
March 2021

Combined ablation-chemotherapy versus chemotherapy alone for pancreatic cancer with liver metastasis: a propensity score matching study.

Expert Rev Gastroenterol Hepatol 2021 Jan 8:1-10. Epub 2021 Jan 8.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

: To retrospectively assess the efficacy of combined ablation-chemotherapy in comparison to that of chemotherapy alone in patients with liver metastasized pancreatic ductal adenocarcinoma (lmPDAC).: In total 104 patients with hepatic oligo metastasized PDAC were identified; among them, 74 patients underwent combined thermal ablation-chemotherapy, and 30 patients underwent chemotherapy alone. Through propensity score matching, 1:1 matching of the combined ablation-chemotherapy group and chemotherapy group was achieved. The primary endpoint of this study was overall survival (OS). Clinical and tumor-related factors affecting OS were also analyzed through univariate and multivariate analyses using the Cox risk model.: For patients treated with combined ablation-chemotherapy, the median OS was 10.77 months, while it was 5.77 months for patients treated with chemotherapy alone (P = 0.011). The survival benefit for patients treated with combined ablation-chemotherapy was still preserved in the matched cohort, with a median OS of 8.17 months compared to 5.77 months in the chemotherapy group. Univariate and multivariate analyses in the matched population also showed treatment with combined ablation-chemotherapy was an independent prognostic factor (P < 0.05).: For patients with liver metastases from pancreatic cancer, the combined use of thermal ablation and systemic chemotherapy offers a chance for a better survival outcome.
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http://dx.doi.org/10.1080/17474124.2021.1869937DOI Listing
January 2021

Comparative Transcriptome Analysis Reveals the Intensive Early Stage Responses of Host Cells to SARS-CoV-2 Infection.

Front Microbiol 2020 25;11:593857. Epub 2020 Nov 25.

Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a widespread outbreak of highly pathogenic coronavirus disease 2019 (COVID-19). It is therefore important and timely to characterize interactions between the virus and host cell at the molecular level to understand its disease pathogenesis. To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection. Our analysis results showed that the rapid growth of the virus was accompanied by an early intensive response of host genes. We also systematically compared the molecular footprints of the host cells in response to SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV). Upon infection, SARS-CoV-2 induced hundreds of up-regulated host genes hallmarked by a significant cytokine production, followed by virus-specific host antiviral responses. While the cytokine and antiviral responses triggered by SARS-CoV and MERS-CoV were only observed during the late stage of infection, the host antiviral responses during the SARS-CoV-2 infection were gradually enhanced lagging behind the production of cytokine. The early rapid host responses were potentially attributed to the high efficiency of SARS-CoV-2 entry into host cells, underscored by evidence of a remarkably up-regulated gene expression of TPRMSS2 soon after infection. Taken together, our findings provide novel molecular insights into the mechanisms underlying the infectivity and pathogenicity of SARS-CoV-2.
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http://dx.doi.org/10.3389/fmicb.2020.593857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723856PMC
November 2020

The Influence of Average Temperature and Relative Humidity on New Cases of COVID-19: Time-Series Analysis.

JMIR Public Health Surveill 2021 01 25;7(1):e20495. Epub 2021 Jan 25.

School of Medicine, Jinan University, Guangzhou, China.

Background: The influence of meteorological factors on the transmission and spread of COVID-19 is of interest and has not been investigated.

Objective: This study aimed to investigate the associations between meteorological factors and the daily number of new cases of COVID-19 in 9 Asian cities.

Methods: Pearson correlation and generalized additive modeling (GAM) were performed to assess the relationships between daily new COVID-19 cases and meteorological factors (daily average temperature and relative humidity) with the most updated data currently available.

Results: The Pearson correlation showed that daily new confirmed cases of COVID-19 were more correlated with the average temperature than with relative humidity. Daily new confirmed cases were negatively correlated with the average temperature in Beijing (r=-0.565, P<.001), Shanghai (r=-0.47, P<.001), and Guangzhou (r=-0.53, P<.001). In Japan, however, a positive correlation was observed (r=0.416, P<.001). In most of the cities (Shanghai, Guangzhou, Hong Kong, Seoul, Tokyo, and Kuala Lumpur), GAM analysis showed the number of daily new confirmed cases to be positively associated with both average temperature and relative humidity, especially using lagged 3D modeling where the positive influence of temperature on daily new confirmed cases was discerned in 5 cities (exceptions: Beijing, Wuhan, Korea, and Malaysia). Moreover, the sensitivity analysis showed, by incorporating the city grade and public health measures into the model, that higher temperatures can increase daily new case numbers (beta=0.073, Z=11.594, P<.001) in the lagged 3-day model.

Conclusions: The findings suggest that increased temperature yield increases in daily new cases of COVID-19. Hence, large-scale public health measures and expanded regional research are still required until a vaccine becomes widely available and herd immunity is established.
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http://dx.doi.org/10.2196/20495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836910PMC
January 2021

The association of marital status with cognitive function and the role of gender in Chinese community-dwelling older adults: a cross-sectional study.

Aging Clin Exp Res 2021 Aug 6;33(8):2273-2281. Epub 2020 Nov 6.

Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Meishan Road 81, Hefei, 230032, Anhui, China.

Background: Evidence of the association between marital status and cognitive function in Chinese older adults is limited.

Aims: To examine the relationship between marital status and cognitive function and to explore the role of gender amongst older adults from three Chinese communities.

Methods: A total of 1376 participants aged 60 years or over were included in this cross-sectional study. Cognitive function was assessed using the Chinese version of the mini-mental state examination (MMSE). Marital status and other variables were collected using a standardized questionnaire. Multiple linear regression models were used to examine associations between marital statuses and cognitive function amongst the target population. The moderating role of gender in these potential associations has also been explored.

Results: In univariate linear regression models, compared to being married, both being widowed (β [95% CI]: -1.46[-2.78 to - 0.13]) and being single (β [95% CI]: - 4.88[-6.43 to - 3.38]) were associated with lower MMSE scores. After adjustment for confounding factors, the significant association of being widowed with MMSE scores disappeared (β [95% CI: - 0.08[- 1.04 to 0.86]), but the association of being single with MMSE scores still existed (β [95% CI]: - 1.87[- 3.17 to - 0.58]). Furthermore, the association of being single with MMSE scores was statistically significant in men (β [95% CI]: - 5.25[- 7.17 to - 3.33]) but not in women (β [95% CI: 0.88[- 0.87 to 2.64]).

Discussion And Conclusions: Being single was associated with poorer cognitive function compared with their married counterparts in older Chinese men but not in women. More preventive measurements should be implemented for single men to reduce or delay cognitive decline. This is particularly important in the context of an aging population in China.
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http://dx.doi.org/10.1007/s40520-020-01743-5DOI Listing
August 2021

Genetic and antigenic heterogeneity of GI-1/Massachusetts lineage infectious bronchitis virus variants recently isolated in China.

Poult Sci 2020 Nov 1;99(11):5440-5451. Epub 2020 Sep 1.

Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin 150001, the People's Republic of China. Electronic address:

Four GI-1/Massachusetts-type (GI-1/Mass-type) infectious bronchitis virus (IBV) strains were isolated and the complete genomes of these isolates, coupled with the Mass-type live-attenuated vaccine H120 and the Mass-type pathogenic M41 strains, were sequenced in the present study. Our results show that isolates LJL/140820 and I0306/17 may be derived from the Ma5 (another Mass-type live-attenuated vaccine strain) and H120 vaccine strains, respectively. The I1124/16 strain was found to be a M41 variant that likely resulted from nucleotide accumulated mutations in the genome. Consistently, the results of the virus neutralization test showed that isolate I1124/16 was antigenically related but slight different from the M41. Our results from the protection experiments pointed out that chickens immunized with H120 failed to eliminate viral shedding after infection with the isolate I1124/16, which was different from that of M41; this result was consistent to the field observation and further implicated that the variant IBV isolate I1124/16 was antigenic different from the M41 strain. Furthermore, the I1124/16 was found to have comparable but slightly lower pathogenicity with the M41 strain. More studies based on the reverse genetic techniques are needed to elucidate the amino acids in the S1 subunit of spike protein contributing to the altered antigenicity of the isolate I1124/16. In addition, an IBV isolate, LJL/130609, was found to be originated from recombination events between the I1124/16- and Connecticut-like strains. Our results from the virus neutralization test also showed that isolates LJL/130609 and I1124/16 were antigenic closely related. Hence, there are at least 3 different genetic evolution patterns for the circulation of the GI-1/Mass-type IBV field strains in China. The differences of vaccines used, the field conditions and genetic pressures between different flocks, likely account for the emergence, evolution patterns, and characteristics of the Mass-type IBV strains.
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http://dx.doi.org/10.1016/j.psj.2020.08.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462518PMC
November 2020

Low levels of arsenic exposure during pregnancy and maternal and neonatal thyroid hormone parameters: The determinants for these associations.

Environ Int 2020 12 6;145:106114. Epub 2020 Oct 6.

Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; MOE Key Laboratory of Population Health Across Life Cycle, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, No 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address:

Background: The potential maternal and neonatal thyrotoxicity associated with exposure to arsenic during pregnancy is very limited and unclear.

Objectives: This study aimed to examine the associations between arsenic exposure levels in maternal and cord serum and maternal and neonatal thyroid hormone parameters in a prospective birth cohort study.

Methods: The study including 2089 mother-neonate pairs was based upon Ma'an Shan birth cohort study in China. The exposure variables including maternal serum arsenic levels in the first, second and third trimester and average arsenic exposure level during pregnancy and cord serum arsenic level. Maternal serum TSH and FT4 levels in the first, second and third trimester and cord serum TSH and FT4 levels were determined using the electrochemiluminescence immunoassay with Cobas Elecsys 411. Linear mixed models were used to examine associations between arsenic exposure variables during pregnancy and maternal thyroid hormone parameters, and multiple linear regression analyses were used to examine associations between arsenic exposure during pregnancy and neonatal thyroid hormone parameters. Bayesian kernal machine regression (BKMR) analyses based on a kernel function were also used to examine the effects of exposure to metal mixtures (arsenic, mercury, cadmium and selenium).

Results: The geometric means of arsenic exposure levels across 3 trimesters were 1.74 μg/L, 1.81 μg/L and 1.99 μg/L, respectively, and 1.90 μg/L in cord serum; the geometric means of maternal FT4 levels across 3 trimesters were 16.91 pmol/L, 11.91 pmol/L and 13.16 pmol/L, respectively, and 16.10 pmol/L in cord serum; the geometric means of maternal TSH levels across 3 trimesters were 1.27 μIU/mL, 2.32 μIU/mL and 2.08 μIU/mL, respectively, and 8.47 μIU/mL in cord serum. Maternal serum arsenic levels in the first, seond, third trimester and average arsenic exposure level during pregnancy were all not associated with maternal thyroid hormone parameters after adjustment for all the covariates, the adjusted β (95% CI) were -0.002 (-0.10 to 0.09), 0.05 (-0.05 to 0.16), -0.09 (-0.17 to 0.003) and -0.05 (-0.22 to 0.11) for maternal FT4, respectively; and -0.005 (-0.04 to 0.03), -0.003 (-0.04 to 0.03), -0.004 (-0.03 to 0.02) and -0.01 (-0.06 to 0.04) for maternal lnTSH, respectively. Maternal serum arsenic levels in the first, second trimester and average arsenic exposure level during pregnancy were all inversely associated with neonatal FT4 level after adjustment for all the confounders, the adjusted β (95% CI) were -0.19 (-0.31 to -0.07), -0.14 (-0.26 to -0.01), -0.22 (-0.42 to -0.02), respectively; and cord serum arsenic level was positively related with neonatal TSH level, the adjusted β (95% CI) were 0.04 (0.001 to 0.08). The adverse joint toxic effect of the four metals in maternal serum in the first trimester and in cord serum on neonatal thyroid hormone parameters were also found.

Conclusions: In this study, exposure to low levels of arsenic during pregnancy could directly affect neonatal thyroid hormone parameters without being mediated by maternal effect of exposure, and maternal serum arsenic levels in the first, second trimester and average arsenic exposure level during pregnancy and cord serum arsenic level may be risk factors affecting neonatal thyroid hormones. These findings indicate that neonates are more sensitive to the thyrotoxicity of arsenic exposure even at low levels. In addition, the adverse joint toxic effect of metal mixtures is also worthy of attention.
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http://dx.doi.org/10.1016/j.envint.2020.106114DOI Listing
December 2020

Quantitative evaluation of PTPN22 copy number variation by digital droplet PCR and association with type 2 diabetes risk.

Endocr J 2021 Feb 17;68(2):153-162. Epub 2020 Sep 17.

Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei 430081, China.

Type 2 diabetes (T2D) is a chronic endocrine disorder with rapidly increasing prevalence worldwide. Genetic instability leading to metabolic dysfunction plays an important role in T2D susceptibility and progression. Structural alteration in genome, that is, copy number variation (CNV) is emerging as the inherent marker for disease identification. Previous genomic CNV array revealed that protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene was overlapped with a CNV region, however, whether this CNV affected T2D risk remains to be further elucidated. In this study, we first identified divergent distributions of the PTPN22 copy number (CN) between T2D patients and healthy controls in Chinese population (p < 0.01). Risk assessment analysis revealed that the CN gain (OR = 3.28, p < 0.001) was the promising risk factor for T2D. Also, significantly positive correlations of the PTPN22 CNV with fasting plasma glucose and glycated hemoglobin were demonstrated in T2D patients. Statistical association analysis investigated that the T2D individuals carrying CN gain showed higher plasma glucose and lower insulin levels than those carrying CN normal and loss at 60 min/120 min/180 min during an OGTT test. In addition, the PTPN22 CNV had an effect on total cholesterol, and the CN gain presented higher values than the other two CN types. These results suggested that the CN gain types of the PTPN22 gene accompany with the glycometabolism dysregulation, and finally predispose their carriers to T2D; therefore, the PTPN22 CNV may be a promising biomarker for predicting T2D risk, or a clinical target for T2D diagnosis and therapy.
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http://dx.doi.org/10.1507/endocrj.EJ20-0239DOI Listing
February 2021

Oral delivery of anti-TNF antibody shielded by natural polyphenol-mediated supramolecular assembly for inflammatory bowel disease therapy.

Theranostics 2020 29;10(23):10808-10822. Epub 2020 Aug 29.

NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine. Wuxi 214063, China.

Anti-tumor necrosis factor (TNF) therapy is a very effective way to treat inflammatory bowel disease. However, systemic exposure to anti-TNF-α antibodies through current clinical systemic administration can cause serious adverse effects in many patients. Here, we report a facile prepared self-assembled supramolecular nanoparticle based on natural polyphenol tannic acid and poly(ethylene glycol) containing polymer for oral antibody delivery. This supramolecular nanoparticle was fabricated within minutes in aqueous solution and easily scaled up to gram level due to their pH-dependent reversible assembly. DSS-induced colitis model was prepared to evaluate the ability of inflammatory colon targeting ability and therapeutic efficacy of this antibody-loaded nanoparticles. This polyphenol-based nanoparticle can be aqueous assembly without organic solvent and thus scaled up easily. The oral administration of antibody loaded nanoparticle achieved high accumulation in the inflamed colon and low systemic exposure. The novel formulation of anti-TNF-α antibodies administrated orally achieved high efficacy in the treatment of colitis mice compared with free antibodies administered orally. The average weight, colon length, and inflammatory factors in colon and serum of colitis mice after the treatment of novel formulation of anti-TNF-α antibodies even reached the similar level to healthy controls. This polyphenol-based supramolecular nanoparticle is a promising platform for oral delivery of antibodies for the treatment of inflammatory bowel diseases, which may have promising clinical translation prospects.
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http://dx.doi.org/10.7150/thno.47601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482796PMC
May 2021
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