Publications by authors named "Xuelian Zhang"

131 Publications

Peroxiredomin-4 ameliorates lipotoxicity-induced oxidative stress and apoptosis in diabetic cardiomyopathy.

Biomed Pharmacother 2021 Jun 12;141:111780. Epub 2021 Jun 12.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China. Electronic address:

Diabetic cardiomyopathy (DCM), one severe complication in the diabetes, leads to high mortality in the diabetic patients. However, the understanding of molecular mechanisms underlying DCM is far from completion. Herein, we investigated the disease-related differences in the proteomes of DCM based on db/db mice and verified the protective roles of peroxiredoxin-4 (Prdx4) in H9c2 cardiomyocytes treated by palmitic acid (PA). Fasting blood glucose (FBG) and cardiac function was detected in the 6-month-old control and diabetic mice. The hearts were then collected and analyzed by a coupled label-free and mass spectrometry approach. In vivo investigation indicated that body weight and FBG of db/db mice markedly increased, and diabetic heart exhibited obvious cardiac hypertrophy and lipid droplet accumulation, and cardiac dysfunction as is indicated by the increases of left ventricle posterior wall thickness in systole (LVPWd) and diastole (LVPWs), and reduction of fractional shortening (FS). We used proteomic analysis and then detected a grand total of 2636 proteins. 175 differentially expressed proteins (DEPs) were markedly detected in the diabetic heart. Thereinto, Prdx4 was markedly down-regulated in the diabetic heart. In vitro experiments revealed that 250 μM PA significantly inhibited viability of H9c2 cell. PA induced much accumulation of lipid droplet in cardiomyocytes and resulted in an increase of mRNA expressions of lipogenic genes (FASN and SCD1) and cardiac hypertrophic genes. Additionally, protein level of Prdx4 evidently reduced in the PA-treated H9c2 cell. It was further found that shRNA-mediated Prdx4 knockdown exacerbated PA-induced oxidative stress and cardiomyocyte apoptosis, whereas overexpressing Prdx4 in the H9c2 cells noteworthily limited PA-induced ROS generation and cardiomyocytes apoptosis. These data collectively reveal the essential role of abnormal Prdx4 in pathological alteration of DCM, and provide potentially therapeutic target for the prevention of DCM.
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http://dx.doi.org/10.1016/j.biopha.2021.111780DOI Listing
June 2021

FOXO3a regulates lipid accumulation and adipocyte inflammation in adipocytes through autophagy : Role of FOXO3a in obesity.

Inflamm Res 2021 May 23;70(5):591-603. Epub 2021 Apr 23.

Department of Endocrinology, Yangpu Hospital, Tongji University School of Medicine, 450 Tengyue Road, Yangpu, Shanghai, 200090, China.

Background: FOXO3a is a widely studied transcription factor and plays an important role in a variety of biology. The purpose of this study was to explore the role and potential mechanism of FOXO3a on lipid accumulation and adipocyte inflammation in adipocytes through regulation of autophagy.

Methods: The obese mouse model was successfully induced by high-fat diet. SiRNA targeting FOXO3a was transfected into differentiation of 3T3-L1 adipocytes to reduce the expression of FOXO3a. The culture medium of RAW264.7 cells was added to the differentiated 3T3-L1 adipocytes to form a co-culture system. Subsequently, ELISA or AdipoRed assay was performed to measure the expression of triglyceride (TG) and cholesterol (TC) in mouse adipose tissue or differentiation of 3T3-L1 adipocytes. Adipocyte differentiation was detected by Oil Red O-staining. Ad-mCherry-GFP-LC3II was used to detect the level of autophagy in differentiation of 3T3-L1 adipocytes. Western blotting or qRT-PCR was used to detect the expression of FOXO3a, autophagy-related proteins (beclin 1, CEBPβ, PPARγ, ACC1 and KLF4), inflammatory cytokines (TNF-α, IL-1β, IL-6 and MCP1), NF-κB signal pathway-related proteins or adipokines (Adiponectin, AdipoR1 and resistin) in differentiated 3T3-L1 or RAW264.7 cells.

Results: The expression of FOXO3a and autophagy levels were significantly increased in visceral adipose tissue of obese mice and differentiation of 3T3-L1 adipocytes. Downregulation of FOXO3a significantly inhibited the autophagy and lipid accumulation in differentiation of 3T3-L1 adipocytes. In addition, FOXO3a knockdown significantly reduced Lipopolysaccharide (LPS)-induced inflammation and adipokines release in RAW264.7 cells treated with the culture medium of 3T3-L1 adipocytes. These above activity changes could be reversed by autophagy inducer rapamycin.

Conclusion: FOXO3a could promote lipid accumulation and inflammation in differentiated 3T3-L1 adipocytes by targeting autophagy. Our results provide a new theoretical basis for FOXO3a to regulate obesity.
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http://dx.doi.org/10.1007/s00011-021-01463-0DOI Listing
May 2021

Effect of Saponins and Major Anti-Obesity Components on Weight Loss.

Front Pharmacol 2020 25;11:601751. Epub 2021 Mar 25.

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

The prevalence of individuals who are overweight or obese is rising rapidly globally. Currently, majority of drugs used to treat obesity are ineffective or are accompanied by obvious side effects; hence, the options are very limited. Therefore, it is necessary to find more effective and safer anti-obesity drugs. It has been proven and that the active ingredient notoginsenosides isolated from traditional Chinese medicine (Burk.) F. H. Chen exhibits anti-obesity effects. Notoginsenosides can treat obesity by reducing lipid synthesis, inhibiting adipogenesis, promoting white adipose tissue browning, increasing energy consumption, and improving insulin sensitivity. Although notoginsenosides are potential drugs for the treatment of obesity, their effects and mechanisms have not been analyzed in depth. In this review, the anti-obesity potential and mechanism of action of notoginsenosides were analyzed; thus laying emphasis on the timely prevention and treatment of obesity.
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http://dx.doi.org/10.3389/fphar.2020.601751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027240PMC
March 2021

Study for cerebral central network mechanism of acupuncture stimulation quantity based on changes of cerebral functional connection of fMRI.

Medicine (Baltimore) 2021 Apr;100(14):e25480

Yunnan University of Traditional Chinese Medicine.

Background: Ischemic stroke is a major chronic noninfectious disease that seriously endangers health. Acupuncture is effective for ischemic stroke and less adverse reactions. However, there is not enough clinical trial data and solid evidence could confirm how acupuncture work to cerebral functional connectivity changes, and whether the changes is related to the different stimulation quantity.

Design: This is a multicenter, central-randomized, controlled, double-blind, noninferiority, 2 factors and 3 levels orthogonal clinical trial. A total of 100 participants with ischemic stroke aged from 40 to 80 were randomized into experimental group and control group, the experimental group was divided into 9 groups (A1-A9) according to different factors or levels, and each group have 10 participants. The whole study period is 17 days, including 1 week for baseline observation, 3 days treatment and observation, and 1 week follow-up. Primary outcome is the fMRI based on blood oxygenation level dependent. Secondary outcomes included National Institute of Health Stroke Scale, Modified Barthel Index, Brunnstrom stroke recovery, stroke Chinese medicine symptom. Clinical assessments will be evaluated at before and the 0 hour, 24 hours, 36 hours after treatment, and 1 week follow-up. The primary outcome of the postacupuncture effect were investigated by paired T-test, and the continuous outcome variables will be analyzed with univariate repetitive measurement deviation analysis. Adverse events will be noted and recorded for the safety evaluation.

Conclusion: The purpose of this study was to evaluate the central mechanism of acupuncture stimulation quantity using time and frequency as control conditions. This study will provide reasonable stimulation parameters and strong mechanism evidence of cerebral central network for the use of acupuncture for ischemic stroke.

Chictr Registration Number: ChiCTR1900023169. Registered 15 May 2019.
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http://dx.doi.org/10.1097/MD.0000000000025480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036113PMC
April 2021

The histone variant Sl_H2A.Z regulates carotenoid biosynthesis and gene expression during tomato fruit ripening.

Hortic Res 2021 Apr 1;8(1):85. Epub 2021 Apr 1.

Department of Horticulture, College of Horticulture and Plant Protection, Yangzhou University, 225009, Yangzhou, Jiangsu, China.

The conserved histone variant H2A.Z is essential for transcriptional regulation; defense responses; and various biological processes in plants, such as growth, development, and flowering. However, little is known about how H2A.Z affects the developmental process and ripening of tomato fruits. Here, we utilized the CRISPR/Cas9 gene-editing system to generate a sl_hta9 sl_hta11 double-mutant, designated sl_h2a.z, and found that these two mutations led to a significant reduction in the fresh weight of tomato fruits. Subsequent messenger RNA (mRNA)-seq results showed that dysfunction of Sl_H2A.Z has profound effects on the reprogramming of genome-wide gene expression at different developmental stages of tomato fruits, indicating a ripening-dependent correlation between Sl_H2A.Z and gene expression regulation in tomato fruits. In addition, the expression of three genes, SlPSY1, SlPDS, and SlVDE, encoding the key enzymes in the biosynthesis pathway of carotenoids, was significantly upregulated in the later ripening stages, which was consistent with the increased contents of carotenoids in sl_h2a.z double-mutant fruits. Overall, our study reveals a role of Sl_H2A.Z in the regulation of carotenoids and provides a resource for the study of Sl_H2A.Z-dependent gene expression regulation. Hence, our results provide a link between epigenetic regulation via histone variants and fruit development, suggesting a conceptual framework to understand how histone variants regulate tomato fruit quality.
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http://dx.doi.org/10.1038/s41438-021-00520-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012623PMC
April 2021

High prevalence of extrapulmonary tuberculosis in dairy farms: Evidence for possible gastrointestinal transmission.

PLoS One 2021 30;16(3):e0249341. Epub 2021 Mar 30.

National Animal Tuberculosis Reference Laboratory, Division of Zoonoses Surveillance, China Animal Health and Epidemiology Center, Qingdao, Shandong, China.

Bovine tuberculosis (bTB) caused by Mycobacterium bovis (M. bovis) represents one of major zoonotic diseases among cattle, it also affects the health of human, other domestic animals and wild life populations. Inhalation of infected aerosol droplets is considered as the most frequent route of the infection. This study aims to investigate the current forms of tuberculosis in cattle and identify the possible transmission modes in dairy farms of China. 13,345 cows from eight dairy farms in three provinces were comprehensively diagnosed by a multitude of assays, including SIT, CIT, IFN-γ assay and ELISA. It has been indicated that advanced infection of bTB was found in 752 (5.64%) cattle, suggesting a high prevalence of tuberculosis in these dairy farms. In the necropsy examination of 151 positive cattle, typical bTB lesions were observed in 131 cattle (86.75%), of which, notably, 90.84% lesions appeared in liver, spleen, mesenteric lymph nodes, mammary lymph nodes and other organs, taking up a large proportion among cattle with advanced bTB infection. 71.26% extrapulmonary tuberculosis (EPTB) was related to gastrointestinal system. M. bovis nucleic acid was further found in milk and feces samples and M. bovis was even isolated from milk samples. Phylogenetic analysis based on whole genome sequencing unraveled that six isolates were closely related to M. bovis AF2122/97 originated from UK, whereas four isolates shared close relation to M. bovis 30 from China, respectively. Our data demonstrate that the increase of EPTB transmitted by digestive tract is implicated in the current high prevalence rate of bTB in China, which also provides leads for bTB control in other countries with high prevalence of bTB in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249341PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009431PMC
March 2021

Simultaneous electrochemical aptasensing of patulin and ochratoxin A in apple juice based on gold nanoparticles decorated black phosphorus nanomaterial.

Anal Bioanal Chem 2021 May 13;413(11):3131-3140. Epub 2021 Mar 13.

College of Food Science and Technology, Northwest University, Xi'an, 710069, Shaanxi, China.

Simultaneous detection of patulin (PAT) and ochratoxin A (OTA) in food products is in great demand, which can prevent toxins from being exposed to human and animal bodies. However, simultaneous detection of multiple targets still faces a challenge. Herein, we developed a novel electrochemical aptasensor for the simultaneous detection of PAT and OTA in apple juice based on gold nanoparticles decorated black phosphorus (AuNPs-BP) nanomaterial. AuNPs-BP function?/work? as a sensing platform for loading much different electrochemical signal molecules functionalized aptamers. In this context, methylene blue functionalized PAT aptamers (Mb-PAT-aptamers) and ferrocene functionalized OTA aptamers (Fc-OTA-aptamers) have been introduced here to fabricate the aptasensor. Fc close to electrode surface showed a strong signal, whereas Mb was far away from electrode surface so exhibited a weak signal in the absence of OTA and PAT. Two kinds of electrochemical signal changes have been recorded dependent on target of OTA and PAT concentrations. So, simultaneous detection of OTA and PAT is achieved. Under the optimum conditions, using this developed biosensor, PAT and OTA can be quantified at a linearity range of 0.01 × 10 μg·mL ~ 0.10 μg·mL. In addition, it also has good selectivity, stability and repeatability. For the practical application, it shows promising performance for the simultaneous detection of PAT and OTA in apple juice.
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http://dx.doi.org/10.1007/s00216-021-03253-3DOI Listing
May 2021

Infection Prevalence and Antibiotic Resistance Levels in and in Gynecological Outpatients of a Tertiary Hospital in China from 2015 to 2018.

Can J Infect Dis Med Microbiol 2021 13;2021:8842267. Epub 2021 Jan 13.

Department of Gynecology, The Fourth People's Hospital of Chongqing, Chongqing 400014, China.

The aim of this study was to estimate the and infection prevalence and antibiotic resistance levels in gynecological outpatients. Clinical characteristics and laboratory data of gynecological outpatients of the Fourth People's Hospital of Chongqing from 2015 to 2018 were retrospectively analyzed. Antibiotic resistance levels in and were defined by a commercial kit for antibiotic susceptibility testing. Univariate analysis and multivariate logistic regression analysis were performed to evaluate risk factors associated with isolation. Comparisons of yearly distributions and resistance rates were assessed by chi-square tests. Fifty-six percent of gynecological outpatients were positive for , and 11.02% were positive for . In the univariate analysis, women aged 30-39 years or with a history of pregnancy or gynecological diseases had an increased risk for isolation, while women who were postmenopausal or had an education level of undergraduate degree or above had a decreased risk of isolation. In the multivariate logistic regression model, an independent risk factor for isolation was a history of gynecological diseases, while a bachelor's degree, master's degree, or above were protective factors against isolation. There were distinctly gradual increases in the positivity rates of and from 2015 to 2018 and an overall increasing trend of resistance to ten antibiotics among and . The top three antibiotics associated with resistance were ofloxacin, sparfloxacin, and levofloxacin. Doxycycline, josamycin, and minocycline were preferred because they had the lowest levels of resistance. Increases in the prevalence of infection and antibiotic resistance in and were observed from 2015 to 2018, clearly confirming the necessity to monitor the standardized administration of antibiotics.
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http://dx.doi.org/10.1155/2021/8842267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817312PMC
January 2021

Identification of three new microsatellites and their effects on body measurement traits in pigs using time of flight-mass spectrometry (TOF-MS).

Anim Biotechnol 2021 Jan 5:1-10. Epub 2021 Jan 5.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.

The body status of livestock affects their physiological function and productive performances. Microsatellites, one of the most used DNA markers, have been found to be associated with pig productive traits. However, their identifications and effects on body measurement traits of the Chinese Qinghai Bamei pig still uncovered. According to our previous sequencing data, in this study, three novel microsatellites were found in this breed. Using time of flight-mass spectrometry (TOF-MS) method, these microsatellites were further identified in a large Bamei pig population. TOF-MS spectra showed that there are three microsatellites loci, named P1, P2 and P3. These microsatellites were linkage equilibrium based on the values of D' and tests. Association results demonstrated that P1 locus was associated with the body length, body height and chest width and the beneficial genotype was 150-/150-bp ( < 0.05); and P2 locus was associated with the body height ( < 0.05), and the 145-/145-bp, 145-/147-bp and 145-/149-bp were claimed as favorable genotypes and 145-bp allele was considered as the favorable allele. These findings suggested that P1 and P2 microsatellites might be considered as the candidate genetic markers to select pigs with superior body sizes, especially in local breed.
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http://dx.doi.org/10.1080/10495398.2020.1865389DOI Listing
January 2021

Weighted gene co-expression network analysis revealed host transcriptional response to H1N1 influenza A virus infection.

J Infect 2021 03 29;82(3):e4-e7. Epub 2020 Dec 29.

College of Life Science and Engineering, Foshan University, No33 Guangyun road, Shishan town, Nanhai District, Foshan 528231, Guangdong, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2020.12.017DOI Listing
March 2021

Rice transcription factor MADS32 regulates floral patterning through interactions with multiple floral homeotic genes.

J Exp Bot 2021 03;72(7):2434-2449

Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University-University of Adelaide Joint Centre for Agriculture and Health, State Key Laboratory of Hybrid Rice, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Floral patterning is regulated by intricate networks of floral identity genes. The peculiar MADS32 subfamily genes, absent in eudicots but prevalent in monocots, control floral organ identity. However, how the MADS32 family genes interact with other floral homeotic genes during flower development is mostly unknown. We show here that the rice homeotic transcription factor OsMADS32 regulates floral patterning by interacting synergistically with E class protein OsMADS6 in a dosage-dependent manner. Furthermore, our results indicate important roles for OsMADS32 in defining stamen, pistil, and ovule development through physical and genetic interactions with OsMADS1, OsMADS58, and OsMADS13, and in specifying floral meristem identity with OsMADS6, OsMADS3, and OsMADS58, respectively. Our findings suggest that OsMADS32 is an important factor for floral meristem identity maintenance and that it integrates the action of other MADS-box homeotic proteins to sustain floral organ specification and development in rice. Given that OsMADS32 is an orphan gene and absent in eudicots, our data substantially expand our understanding of flower development in plants.
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http://dx.doi.org/10.1093/jxb/eraa588DOI Listing
March 2021

Targeting Orphan Nuclear Receptors NR4As for Energy Homeostasis and Diabetes.

Front Pharmacol 2020 27;11:587457. Epub 2020 Nov 27.

Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Orphan nuclear receptors are important members of the nuclear receptor family and may regulate cell proliferation, metabolism, differentiation, and apoptosis. NR4As, a subfamily of orphan nuclear receptors, have been reported to play key roles in carbohydrate and lipid metabolism and energy homeostasis. Popularity of obesity has resulted in a series of metabolic diseases such as diabetes and its complications. While imbalance of energy intake and expenditure is the main cause of obesity, the concrete mechanism of obesity has not been fully understood. It has been reported that NR4As have significant regulatory effects on energy homeostasis and diabetes and are expected to become new targets for discovering drugs for metabolic syndrome. A number of studies have demonstrated that abnormalities in metabolism induced by altered levels of NR4As may contribute to numerous diseases, such as chronic inflammation, tumorigenesis, diabetes and its complications, atherosclerosis, and other cardiovascular diseases. However, systematic reviews focusing on the roles of NR4As in mediating energy homeostasis and diabetes remain limited. Therefore, this article reviews the structure and regulation of NR4As and their critical function in energy homeostasis and diabetes, as well as small molecules that may regulate NR4As. Our work is aimed at providing valuable support for the research and development of drugs targeting NR4As for the treatment of obesity and related metabolic diseases.
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http://dx.doi.org/10.3389/fphar.2020.587457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728612PMC
November 2020

Role of the PE/PPE Family in Host-Pathogen Interactions and Prospects for Anti-Tuberculosis Vaccine and Diagnostic Tool Design.

Front Cell Infect Microbiol 2020 26;10:594288. Epub 2020 Nov 26.

State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.

The genes are found in pathogenic, slow-growing and other complex (MTBC) species. These genes are considered key factors in host-pathogen interactions. Although the function of most PE/PPE family proteins remains unclear, accumulating evidence suggests that this family is involved in infection. Here, we review the role of PE/PPE proteins, which are believed to be linked to the ESX system function. Further, we highlight the reported functions of PE/PPE proteins, including their roles in host cell interaction, immune response regulation, and cell fate determination during complex host-pathogen processes. Finally, we propose future directions for PE/PPE protein research and consider how the current knowledge might be applied to design more specific diagnostics and effective vaccines for global tuberculosis control.
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http://dx.doi.org/10.3389/fcimb.2020.594288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726347PMC
June 2021

ESX-1-secreted substrate protein EspC promotes mycobacterial survival through endoplasmic reticulum stress-mediated apoptosis.

Emerg Microbes Infect 2021 Dec;10(1):19-36

State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, People's Republic of China.

EsxA, secreted by the ESAT-6 secretion system 1 (ESX-1) secretion system, is considered the major () virulence determinant. However, the roles of the individual ESX-1 substrates, such as EspC, remain unclear due to their interdependency for secretion with EsxA. Here, we validated that EspC triggered ER stress-mediated apoptosis in macrophages. The EspC-mediated ER stress was involved in pro-inflammatory cytokines generation, intracellular Ca release, and reactive oxygen species accumulation. Mitochondrial transmembrane potential dissipation and mitochondrial outer membrane permeabilization occurred in EspC-treated macrophages, causing apoptosis. Furthermore, ER stress-mediated apoptosis was effectively induced in EspC-overexpressing Mycobacterium smegmatis-infected macrophages and mice. EspC overexpression caused a significant increase in bacterial survival in the macrophages, spleens, and lungs, and accelerated mouse death was observed. Moreover, the increased viability of bacteria in the macrophages was significantly reduced by pretreatment with the apoptosis inhibitor. Overall, our results revealed that EspC is an essential ESX-1 protein for -host interactions and EspC-induced ER stress-mediated apoptosis may be employed by Mtb to establish and spread infection. Given the critical roles of the ESX systems in pathogenesis and immunity, our findings offer new perspectives on the complex host-pathogen interactions and mechanisms underlying ESX-1-mediated pathogenesis.
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http://dx.doi.org/10.1080/22221751.2020.1861913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832037PMC
December 2021

Association Between Cannabinoid Receptor-1 Gene Polymorphism and the Risk of Diabetic Nephropathy Among Patients with Type 2 Diabetes Mellitus.

Pharmgenomics Pers Med 2020 12;13:591-599. Epub 2020 Nov 12.

Department of Statistical Teaching and Research, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.

Background: The cannabinoid receptor 1 (CNR1) gene polymorphism is reportedly associated with components of metabolic syndrome and coronary artery diseases in patients with type 2 diabetes mellitus (T2DM). We investigated whether the common variant rs10493353 polymorphism is associated with diabetic nephropathy (DN) in T2DM patients.

Patients And Methods: T2DM patients with DN were enrolled as a case group, and patients with only T2DM as a control group. Demographic data and biochemical parameters were collected. The polymerase chain reaction-based restriction fragment length polymorphism technique was used for genotyping. The odds ratio and 90% confidence interval were calculated to assess the association between genotypes and the risk of DN.

Results: In total, 320 T2DM patients and 320 DN patients were enrolled. Compared with T2DM patients, the DN patients have a significantly larger body mass index (BMI), longer duration of disease, and higher proportions of smokers, drinkers, and hypertension. The risk of DN was significantly decreased by genotypes AA (OR=0.39, 95% CI=0.23-0.67) and GA (OR=0.53, 95% CI=0.37-0.75) vs GG (codominant model), GA/AA vs GG (OR=0.49, 95% CI=0.35-0.67; dominant model), AA vs GG/GA (OR=0.47, 95% CI=0.28-0.80; recessive model), and the A allele (OR=0.52, 95% CI=0.40-0.68; allele model). Multiple logistic regressions still show significant levels. Negative interactions were found between gene and clinical parameters, including drinking, smoking, BMI, and hypertension.

Conclusion: The A allele of CNR1 gene rs10493353 may be a protective factor for DN in T2DM patients. The risk factors of DN can affect the protective role of A allele in the progression of DN.
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http://dx.doi.org/10.2147/PGPM.S278897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669503PMC
November 2020

Corrigendum: Ginsenoside Re Attenuates High Glucose-Induced RF/6A Injury Regulating PI3K/AKT Inhibited HIF-1a/VEGF Signaling Pathway.

Front Pharmacol 2020 23;11:1312. Epub 2020 Oct 23.

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

[This corrects the article DOI: 10.3389/fphar.2020.00695.].
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http://dx.doi.org/10.3389/fphar.2020.01312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645230PMC
October 2020

A compound heterozygous mutation of the alkaline phosphatase ALPL gene causes hypophosphatasia in a Han Chinese family.

Exp Ther Med 2020 Dec 6;20(6):152. Epub 2020 Oct 6.

Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Hypophosphatasia (HPP) is a rare hereditary systemic disease that is characterized by defective bone and/or dental mineralization, and is caused by mutations in the alkaline phosphatase gene (ALPL). The present study investigated the ALPL mutation in a Chinese Han family with HPP and studied the pathogenesis of the mutations of the ALPL gene. DNA was extracted from peripheral venous blood of the family members. Sanger sequencing was used to screen the mutations. Associations between pathogenesis for both mutations were analyzed by bioinformatics, subcellular localization, measurement of enzyme activity and western blotting. Sanger sequencing revealed the compound heterozygous mutations c.203C>T (p.T68M) and c.571G>A (p.E191K). The mutations were located at exon 4 and 6 of the ALPL gene and were predicted by Polyphen-2 analysis to be harmful. Protein analysis indicated a decrease in mature protein production and lower enzyme activity in 293T cells transfected with plasmids carrying the mutations. The ALPL gene was cloned into the pcDNA3.1(+) vector and mutant plasmids ALPL-pT68M and ALPL-pE191K were constructed. Immunofluorescence observed in cells transfected with the ALPL-pE191K mutant plasmid was mainly located in the cell membrane. However, staining in the cytoplasm was increased compared with the wild type, and almost no fluorescence was identified in 293T cells transfected with the ALPL-pT68M mutant plasmid. The present findings demonstrated that the compound heterozygous c.571G>A and c.203C>T mutations may contribute to childhood HPP by resulting in mislocalization, decreased protein expression and loss of enzyme activity in a Han Chinese family. The results of the current study may provide insights into the potential molecular mechanism of HPP.
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http://dx.doi.org/10.3892/etm.2020.9281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571384PMC
December 2020

Genetic characterization of a novel genotype H9N2 avian influenza virus from chicken in South China.

J Infect 2020 11 19;81(5):816-846. Epub 2020 Sep 19.

College of Life Science and Engineering, Foshan University, No. 33 guangyun road, Shishan town, Nanhai district, Foshan 528231, Guangdong, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2020.09.011DOI Listing
November 2020

Goat sperm associated antigen 17 protein gene (SPAG17): Small and large fragment genetic variation detection, association analysis, and mRNA expression in gonads.

Genomics 2020 11 16;112(6):5115-5121. Epub 2020 Sep 16.

College of Animal Science and Technology, Northwest A&F University, Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Yangling, Shaanxi, China. Electronic address:

Transcriptome sequencing analyses have suggested that sperm associated antigen 17 protein gene (SPAG17) may play important regulating roles in litter size. In this study, the expression profiles and genetic variations of the SPAG17 were studied in Shaanbei White Cashmere (SBWC) goats (n=1567). SPAG17 was highly expressed in testis and ovary of SBWC goats. At different developmental stages, it also continued to be highly expressed in testis. In addition, two variations of SPAG17, one indel locus and one copy number variation locus, were significantly associated with first-born litter size. Joint analysis results suggested that two polymorphic loci of the SPAG17 gene may regulate host gene expression in goat ovary and testis. Overall, the results indicated the important role of SPAG17 in the reproductive process of goats.
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http://dx.doi.org/10.1016/j.ygeno.2020.09.029DOI Listing
November 2020

Dietary restriction and/or exercise training impairs spermatogenesis in normal rats.

Appl Physiol Nutr Metab 2021 Mar 9;46(3):229-237. Epub 2020 Sep 9.

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.

Dietary restriction and/or exercise has been shown to have multiple benefits for health. However, its effects on reproductive health and the mechanisms by which it regulates reproductive function remain unclear. Here, to evaluate its effects on spermatogenesis and sperm function, rats were divided into 4 groups: ad libitum-fed sedentary control, dietary restriction (DR), exercise training (ET), and dietary restriction plus exercise training (DR+ET) groups. Results indicated that body weight, epididymal fat pad weight, and sperm counts were significantly reduced in the DR, ET, and DR+ET groups. Moreover, sperm motility and capacitation-associated protein tyrosine phosphorylation were suppressed in the DR and DR+ET groups, but not the ET group. Microarray analysis revealed that the number of downregulated genes was higher than that of upregulated genes in the DR and/or ET groups. About half of the downregulated genes are common after exercise training and/or diet restriction. Gene ontology analysis showed that downregulated genes in the DR, ET, and DR+ET groups affected spermatogenesis through overlapping pathways, including glucocorticoid, corticosteroid, extracellular structure organization, and estradiol responses. Our findings suggest that diet restriction and/or exercise training may present potential risks to male reproductive dysfunction by disrupting normal gene expression patterns in the testis. Dietary restriction and/or exercise can lead to the damage of spermatogenesis as well as sperm maturation. Sperm functional changes are more sensitive to dietary restriction than exercise training. Dietary restriction and exercise impair spermatogenesis through overlapping biological pathways in the testis.
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http://dx.doi.org/10.1139/apnm-2020-0477DOI Listing
March 2021

Uptake, accumulation, and translocation mechanisms of steroid estrogens in plants.

Sci Total Environ 2021 Jan 25;753:141979. Epub 2020 Aug 25.

Beijing Soil and Fertilizer Extension Service Station, Beijing 100029, China.

Applying sewage sludge or animal manure onto agricultural land can result in estrogen pollution, which increases the risk of human exposure to steroid estrogens (SEs) via the food chain. However, the uptake and accumulation mechanism of SEs by plants is still unclear. In this study, the uptake, accumulation, and translocation of 17β-E2, a representative SE, were investigated through a series of wheat hydroponic experiments. Various inhibitors were applied to explore the uptake pathways of 17β-E2 by wheat. In addition, the effects of exposure concentrations, coexisting 17α-ethynylestradiol (EE2) and plant properties on the uptake of 17β-E2 were examined. The results indicated that the accumulation of 17β-E2 in wheat roots mainly resulted from adsorption and active uptake that involved aquaporins and anion channels transport. The chlorophyll and protein contents of plants were positively correlated with the uptake of 17β-E2, whereas competitive inhibition occurred when 17β-E2 and EE2 coexisted in the same solution. Nevertheless, the results of a split-root experiment showed that 17β-E2 absorbed by wheat could further migrate in plant via long-distance transport and ultimately was discharged from plants, suggesting that 17β-E2 was still at risk of being released even though it had been absorbed by plants. These results could provide valuable insights into the risk assessment and risk control of the uptake of SEs by plants.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141979DOI Listing
January 2021

Chlorpyrifos inhibits sperm maturation and induces a decrease in mouse male fertility.

Environ Res 2020 09 21;188:109785. Epub 2020 Jun 21.

College of Animal Science and Technology, Northwest A&F University, Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Yangling, Shaanxi, China. Electronic address:

Background: Pesticides, especially organophosphorus pesticides such as chlorpyrifos (CPF), play an important role in modern agriculture. Studies have shown that pesticide residues are an important cause of male reproductive injury in mammal.

Aim: The aim of this study was to evaluate the reproductive damage caused by CPF in male mice and investigate the underlying mechanisms.

Methods: In vivo, C57BL/6 mice (6-8 weeks old) were treated with CPF for 14, 70, and 80 days by intraperitoneal injection, intragastric administration, and dietary supplementation, respectively. Then, sperm from the cauda epididymidis was cultured in vitro to confirm the deleterious effects of CPF.

Results: The in vivo results indicated that, after treatment with CPF by dietary supplementation and intraperitoneal injection, the expression of reproduction-related genes in the mouse testes was altered, although the mice were fertile and the testes presented no morphological abnormalities. Notably, mating experiments revealed that the fertility of male mice was decreased following CPF administration by gavage. Sperm motility within the cauda epididymidis declined significantly after CPF treatment, which was accompanied by a decrease in sperm density, upregulation of relative reactive oxygen species (ROS) levels, and downregulation of glutathione reductase activity. In vitro incubation experiments showed that sperm rapidly lost their capacity for linear movement; the relative ROS levels also increased significantly, while the mitochondrial membrane potential (MMP) showed a significant decrease. However, the integrity of the plasma membrane was not affected by CPF administration.

Conclusions: The above data indicated that exposure to CPF reduces sperm motility by disrupting mitochondrial function and increasing the level of oxidative stress during sperm maturation, thereby reducing the fecundity of male mice.
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http://dx.doi.org/10.1016/j.envres.2020.109785DOI Listing
September 2020

Molecular characterization and phylogenetic analysis of fowl adenovirus serotype-4 from Guangdong Province, China.

Vet World 2020 May 24;13(5):981-986. Epub 2020 May 24.

Department of Microbiology, College of Life Science and Engineering, Foshan University, Foshan 528231, Guangdong Province, China.

Aim: Our aim in this study was to isolate potentially novel strains of fowl adenovirus serotype-4 (FAdV-4) that is currently circulating in broiler chicken flocks in Guangdong Province, China, and to compare nucleotide and amino acid (AA) sequences of their respective genes.

Materials And Methods: The experiment was carried out on poultry farms experiencing outbreaks of FAdV-4-associated hydropericardium syndrome (HPS). Tissue samples from the hearts and livers of deceased chickens were screened for FAdV-4 infection using gene-specific polymerase chain reaction (PCR).

Results: New virus isolates were used to infect 7-day-old chicks, which went onto reproduce typical HPS signs. The hypervariable region of the FAdV-4 gene was PCR-amplified and sequenced. The nucleotide and deduced AA sequence identities were 99.8-99.9% and 99.5-99.8%, respectively, among the four novel isolates. In addition, the new isolates were 97-100% and 96.4-99.9% identical to the nucleotide and deduced AA sequences, respectively, of FAdV-4 genes available in the National Center for Biotechnology Information GenBank database. Phylogenetic analyses, based on the gene sequence, revealed that the new isolates, clustered with FAdV-C; the FAdV-A, FAdV-B, FAdV-D, and FAdV-E viruses, were more distantly related.

Conclusion: New FAdV-4 isolates from Guangdong Province are similar to those identified in other regions of the world. This information provides critical insight into HPS epidemiology and provides a perspective for monitoring outbreaks and developing strategies for disease prevention.
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http://dx.doi.org/10.14202/vetworld.2020.981-986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311883PMC
May 2020

Ginsenoside Re Attenuates High Glucose-Induced RF/6A Injury Regulating PI3K/AKT Inhibited HIF-1α/VEGF Signaling Pathway.

Front Pharmacol 2020 21;11:695. Epub 2020 May 21.

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

Hyperglycaemia-induced retinal microvascular endothelial cell apoptosis is a critical and principle event in diabetic retinopathy (DR), which involves a series of complex processes such as mitochondrial dysfunction and oxidative stress. Ginsenoside Re (Re), a key ingredients of ginseng, is considered to have various pharmacologic functions, such as antioxidative, inhibition of inflammation and anti-apoptotic properties. However, the effects of Re in DR and the related mechanisms of endothelial cell injury induced by high glucose (HG) exposure remain unclear. The present study was designed to investigate and evaluate the ability of Re to ameliorate HG-induced retinal endothelial RF/6A cell injury and the potential mechanisms involved in the hypoxia-inducible factor-1-alpha (HIF-1α)/vascular endothelial growth factor (VEGF) signaling regulated by phosphoinositide 3-kinase (PI3K)/AKT pathway. Our results showed that preincubation with Re exerted cytoprotective effects by reversing the HG-induced decrease in RF/6A cell viability, downregulation of apoptosis rate and inhibition of oxidative-related enzymes, thereby reducing the excess intracellular reactive oxygen species (ROS) and HG-triggered RF/6A cell injury. In addition, Western blot analysis results showed ginsenoside Re significantly increased HIF-1α expression in the cytoplasm but decreased its expression in the nucleus, suggesting that it reduced the translocation of HIF-1α from the cytoplasm to the nucleus, and downregulated VEGF level. Moreover, this effect is involved in the activation of the PI3K/Akt pathway. LY294002, a PI3K inhibitor, was used to block the Akt pathway. Afterwards, the effects of Re on the regulation of apoptotic related proteins, VEGF and HIF-1α nuclear transcription was partially reversed. These findings suggested the exerting protective effects of ginsenoside Re were associated with regulating of PI3K/AKT and HIF-1α/VEGF signaling pathway, which indicates that ginsenoside Re may ameliorates HG-induced retinal angiogenesis and suggests the potential for the development of Re as a therapeutic for DR.
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http://dx.doi.org/10.3389/fphar.2020.00695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253708PMC
May 2020

Amorphous-Carbon-Supported Ultrasmall TiB Nanoparticles With High Catalytic Activity for Reversible Hydrogen Storage in NaAlH.

Front Chem 2020 15;8:419. Epub 2020 May 15.

State Key Laboratory of Silicon Materials and School of Materials Science and Engineering, Zhejiang University, Hangzhou, China.

In this paper, we report amorphous-carbon-supported TiB nanoparticles having sizes of 2-4 nm ([email protected]) as highly active catalysts for hydrogen storage in NaAlH. [email protected] was synthesized by a simple calcination at 550°C with CpTiCl and MgB (molar ratio of 1:1) as precursors. The addition of 7 wt% [email protected] reduced the onset dehydrogenation temperature of NaAlH by 100 to 75°C. A practically available hydrogen capacity of 5.04 wt% could be desorbed at 140°C within 60 min, and completely hydrogenated at 100°C within 25 min under a hydrogen pressure of 100 bar. Notably, the hydrogen capacity was almost unchanged after 20 cycles, which shows the stable cyclability, considerably higher than those of structures catalyzed by Ti halides or TiO. The stable catalytic function was closely related to the -formed Ti-Al alloy, which considerably facilitated the dissociation and recombination of H-H and Al-H bondings.
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http://dx.doi.org/10.3389/fchem.2020.00419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243354PMC
May 2020

The Interference Pattern of Plasmonic and Photonic Modes Manipulated by Slit Width.

Nanomaterials (Basel) 2020 Apr 11;10(4). Epub 2020 Apr 11.

Shandong Provincial Engineering and Technical Center of Light Manipulations & Shandong Provincial Key Laboratory of Optics and Photonic Device, College of Physics and Electronics, Shandong Normal University, Jinan 250014, China.

We demonstrate that the interference pattern of the plasmonic and photonic modes can be controlled by changing the slit width of a square slit structure. Based on the analyses of the plasmonic and photonic modes of slits with different widths, we theoretically derived the expressions of wavefield generated by a square slit. A far-field scattered imaging system is utilized to collect the intensity distribution experimentally. Various interference patterns, including stripes, square-like lattice array, and diamond-like lattice array, have been observed by adjusting the slit widths. In addition, the results were validated by performing finite-difference time-domain simulations, which are consistent with the theoretical and experimental results.
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http://dx.doi.org/10.3390/nano10040730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221913PMC
April 2020

Atorvastatin promotes AMPK signaling to protect against high fat diet-induced non-alcoholic fatty liver in golden hamsters.

Exp Ther Med 2020 Mar 22;19(3):2133-2142. Epub 2020 Jan 22.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, P.R. China.

Non-alcoholic fatty liver disease (NAFLD) is characterized by diffuse fatty acid degeneration and excess fat accumulation in the liver. Notably, the currently available medications used to treat NAFLD remain limited. The aim of the present study was to investigate the protective role of atorvastatin (Ato) against NAFLD in golden hamsters fed a high fat diet (HFD) and in HepG2 cells treated with palmitate, and identify the underlying molecular mechanism. Ato (3 mg/kg) was administered orally every day for 8 weeks to the hamsters during HFD administration. Hamsters in the model group developed hepatic steatosis with high serum levels of triglyceride, cholesterol, insulin and C-reactive protein, which were effectively reduced by treatment with Ato. Additionally, the relative liver weight of hamsters treated with Ato was markedly lower compared with that of the model group. Hematoxylin and eosin, and oil red O staining indicated that the livers of the animals in the model group exhibited large and numerous lipid droplets, which were markedly decreased after Ato treatment. Western blot analysis indicated that Ato inhibited fat accumulation in the liver through the AMP-activated protein kinase (AMPK)-dependent activation of peroxisome proliferator activated receptor α (PPARα), peroxisome proliferator-activated receptor-γ coactivator 1 α and their target genes. Furthermore, , Ato inhibited PA-induced lipid accumulation in HepG2 cells. This inhibitory effect was attenuated following Compound C treatment, indicating that AMPK may be a potential target of Ato. In conclusion, the increase in AMPK-mediated PPARα and its target genes may represent a novel molecular mechanism by which Ato prevents NAFLD.
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http://dx.doi.org/10.3892/etm.2020.8465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027324PMC
March 2020

Correction: Zhou, P., et al. Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy. , 2019, , 213.

Cells 2020 Feb 17;9(2). Epub 2020 Feb 17.

Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.

The authors wish to make the following corrections to this paper [...].
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http://dx.doi.org/10.3390/cells9020450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072801PMC
February 2020

Molecular evidence of the spotted fever group Rickettsiae in ticks from Yunnan Province, Southwest China.

Exp Appl Acarol 2020 Mar 10;80(3):339-348. Epub 2020 Jan 10.

School of Life Sciences and Engineering, Foshan University, Foshan, Guangdong Province, China.

Ixodid ticks transmit many obligate intracellular Rickettsial species. Several previous studies have identified Rickettsia species in the northeastern and southern part of China, but few reports on the prevalence of infection of spotted fever group Rickettsiae (SFGR) in ticks in southwest China are available. Here, we investigated SFGR in 394 adult ticks of five species including Dermacentor nuttalli, Dermacentor silvarum, Haemaphysalis longicornis, Ixodes sinensis and Ixodes persulcatus, collected in the border region between China and Burma in Yunnan Province. PCR was used to detect the presence of the citrate synthase (gltA) gene of Rickettsia species. SFGR was found in 12.1% (15/124) of I. persulcatus ticks, which was significantly higher than the 7.2% (7/97) positive D. nuttalli, 5.4% (3/56) D. silvarum, 5.6% (4/72) H. longicornis and 4.4 (2/45) I. sinensis. A portion of the gltA and ompA gene data subjected to phylogenetic analysis revealed that the detected SFGR clustered into two species, Rickettsia raoultii and the new Rickettsia species Candidatus Rickettsia jingxinensis. Detection of both Rickettsia spp. in this region indicates a potential public health threat posed by SFGR infection in Yunnan Province.
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http://dx.doi.org/10.1007/s10493-020-00467-5DOI Listing
March 2020

Effects of freeze-thaw cycles on distribution and speciation of heavy metals in pig manure.

Environ Sci Pollut Res Int 2020 Mar 2;27(8):8082-8090. Epub 2020 Jan 2.

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing, 100875, China.

To understand the potential environmental influence of animal manure under freeze-thaw cycles, pig manure was used to conduct a simulation experiment to explore the effects of freeze-thaw cycles on heavy metal distribution and form transformation. Thirty cycles of freezing and thawing were performed alternately by freezing at - 18 ± 2 °C for 24 h and thawing at 20 ± 2 °C for 24 h. By a serial wet sieving procedure, manure samples were separated into different sizes of 1000, 250, 75, 38, and < 38 μm. Solid samples were collected from the dry matter at each stage of sieve; then the washing waters were collected as liquid samples accordingly. The concentrations of heavy metals in solid/liquid samples and their five forms were analyzed. It showed that the concentrations of heavy metals in the solid and liquid samples gradually increased because of organic matter degradation during freezing and thawing cycles. The distribution of heavy metals on particles of different sizes was also affected by the degradation and breakup of pig manure; the metals showed a tendency to aggregate in small particles (< 38 μm). Among them, the percentage of Cu and Zn on < 38 μm particles increased by 162.3% and 554.1%, respectively. After several freeze-thaw cycles, the concentrations of EXCH-X (metals of exchangeable form) increased significantly, those of CARB-X (carbonate-bound form) and Fe/Mn-X (Fe/Mn oxide-bound form) decreased accordingly. These form transformations may be largely influenced by the enhancement of dissolved organic matter (DOM) and the reduction of pH value. Therefore, frequent freeze-thaw cycles may promote the mobility and bioavailability of heavy metals in pig manure. The results are significant for understanding the pollution risk of pig manure in the freeze-thaw regions.
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http://dx.doi.org/10.1007/s11356-019-07518-4DOI Listing
March 2020