Publications by authors named "Hongyuan Wang"

151 Publications

Leached phosphorus apportionment and future management strategies across the main soil areas and cropping system types in northern China.

Sci Total Environ 2022 Jan 20;805:150441. Epub 2021 Sep 20.

Key laboratory of Nonpoint Source Pollution Control, Ministry of Agriculture and Rural Affairs of P. R. China, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Excess phosphorus (P) leached from high fertiliser input cropping systems in northern China is having detrimental effects on water quality. Before improved management can be directed at specific soils and cropping system types estimates of P leached loss apportionment and mitigation potentials across the main soil (fluvo-aquic soil, FAS; cinnamon soil, CS; black soil, BS) areas and cropping systems (protected vegetable fields, PVFs; open vegetable fields, OVFs; cereal fields, CFs) are needed. The present study designed and implemented conventional fertilisation and low input system trials at 75 sites inclusive of these main soils and cropping system types in northern China. At all sites, a uniform lysimeter design (to 0.9 m depth) enabled the collection and analysis of leachate samples from 7578 individual events between 2008 and 2018. In addition, site-specific static and dynamic activity data were recorded. Results showed that annual total phosphorus (TP) leached losses across the main soil areas and cropping systems were 4.99 × 10 kg in northern China. A major finding was PVFs contributed to 48.5% of the TP leached losses but only accounted for 5.7% of the total cropping areas. The CFs and OVFs accounted for 40.3% and 11.2% of the TP leached losses, respectively. Across northern China, the TP leached losses in PVFs and OVFs were greatest in FAS areas followed by CS and BS areas. The higher TP leached losses in FAS areas were closely correlated with greater P fertiliser inputs and irrigation practices. From a management perspective in PVFs and OVFs systems, a decrease of P inputs by 10-30% would not negatively affect yields while protecting water quality. The present study highlights the importance of decreasing P inputs in PVFs and OVFs and supporting soil P nutrient advocacy for farmers in China.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150441DOI Listing
January 2022

Effects of perchlorate and exogenous T4 exposures on development, metamorphosis and endochondral ossification in Bufo gargarizans larvae.

Aquat Toxicol 2021 Nov 17;242:106036. Epub 2021 Nov 17.

College of Life Science, Shaanxi Normal University, Xi'an 710119, China. Electronic address:

Several endocrine-disrupting chemicals (EDCs) have been proven to interfere with the physiological function of thyroid hormone (TH), which affected growth and development. However, few studies have investigated the effects of EDCs on TH axis with consequence for skeletal development in amphibians. This study thus examined the potential role of perchlorate and T4 in growth, development and endochondral ossification during metamorphosis of Bufo gargarizans. Our studies showed that NaClO₄ treatment caused weight gain and delayed the developmental stage in B. gargarizans tadpoles, while T4 decreased body size and survival rate, accelerated metamorphic duration and increased the risk of early death. Histological sections suggested that NaClO₄ and T4 treatments caused damages to thyroid tissue, such as decreased thyroid gland size, follicle size, colloid area, the height of follicular epithelial cells and the number of follicles. In addition, the double skeletal staining and RT-qPCR showed that NaClO₄ and T4 treatments inhibited the endochondral ossification by regulating TH synthesis (TRs, Dios) and endochondral ossification-related genes (MMPs, Runxs, VEGFs and VEGFRs) expression levels, which might affect terrestrial locomotion and terrestrial life. Altogether, these thyroid injury and gene expression changes as caused by NaClO₄ and T4 may have an influence on development and endochondral ossification during the metamorphosis of amphibians.
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http://dx.doi.org/10.1016/j.aquatox.2021.106036DOI Listing
November 2021

Automatic underwater polarization imaging without background region or any prior.

Opt Express 2021 Sep;29(20):31283-31295

Previous polarization underwater imaging methods based on the physical scattering model usually require background region included in the image and the prior knowledge, which hinders its practical application. In this paper, we analyze and optimize the physically feasible region and propose an improved method by degenerating intermediate variables, which can realize automatic underwater image recovery without background region or any prior. The proposed method does not need to estimate the intermediate variables in the traditional underwater imaging model and is adaptable to the underwater image with non-uniform illumination, which avoids the poor and unstable image recovery performance caused by inaccurate estimation of intermediate parameters due to the improper identification of the background region. Meanwhile, our method is effective for both images without background region and images in which the background region is hard to be identified. In addition, our method solves the significant variation in recovery results caused by the different selection of background regions and the inconsistency of parameter adjustment. The experimental results of different underwater scenes show that the proposed method can enhance image contrast while preserving image details without introducing considerable noise, and the proposed method is effective for the dense turbid medium.
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http://dx.doi.org/10.1364/OE.434398DOI Listing
September 2021

Shift of lakeshore cropland to buffer zones greatly reduced nitrogen loss from the soil profile caused by the interaction of lake water and shallow groundwater.

Sci Total Environ 2022 Jan 3;803:150093. Epub 2021 Sep 3.

Key Laboratory of Non-point Source Pollution Control, Ministry of Agriculture and Rural Affairs, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

The interaction of lake water (LW) and shallow groundwater (SGW) accelerates nitrogen (N) loss from the soil profile in the lakeshore cropland, and cropland buffer zone (CBZ) significantly inhibits N loss in this area. Here, characteristics of N loss and transformations driven by SGW and LW interactions were explored using microcosmic experiments, and N loss was estimated using in situ monitoring data before and after the construction of the CBZ along the west bank of Erhai Lake. The results indicated that NO-N, dissolved organic N and total dissolved N sustained the main N losses in the soil, and the organic N was responsible for the main N loss in the effluent. The lower total nitrogen (TN) concentrations of SGW in this area, the greater the soil N loss. Moreover, N total loss from the 100 cm soil profile in the control check was 1.8 times that in the simulated SGW treatment. We found that nitrification, denitrification and anammox driven by the microbial community and N functional genes were the key processes leading to N loss. The effluent N (3.64%) and gaseous N (0.32%) loss ratios in the cropland for continuously growing vegetables (CGV) were much higher than that in the CBZ (1.07% of effluent N and 0.25% of gaseous N loss ratios). If a 100 m wide and 48 km long area of lakeshore cropland is CGV, an increase by 47% is projected by 2030 compared with the N loss in 2020. But this region was built as a 100 m wide CBZ or 50 m wide CBZ + 50 m wide CGV after 2019, N loss will be reduced by 87% and 44% in 2030 compared with the N loss in CGV. The results implied that restoring a suitable width of CBZ can significantly reduce N loss.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150093DOI Listing
January 2022

Electrical conductivity and dissolved oxygen as predictors of nitrate concentrations in shallow groundwater in Erhai Lake region.

Sci Total Environ 2022 Jan 25;802:149879. Epub 2021 Aug 25.

Key Laboratory of Non-point Source Pollution Control, Ministry of Agriculture and Rural Affairs, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Elevated nitrogen (N) concentration in shallow groundwater is becoming increasingly problematic, putting water resources under pressure. For more effective management of such a resource, more precise predictors of N level in groundwater using smart monitoring networks are needed. However, external factors such as land use type, rainfall, and N loads from multiple sources (residential and agricultural) make it difficult to accurately predict the spatial and temporal variations of N concentration. In order to identify the key factors affecting spatial and temporal N concentration in shallow groundwater and develop a predictive model, 635 groundwater samples from drinking wells in residential areas and agricultural wells in croplands of a typical agricultural watershed in the Erhai Lake Basin, southwest China, in the period from 2018 to 2020, were collected and analyzed. The results showed that the type of land use and seasonal variations significantly affected the N forms and their concentrations in the shallow groundwater, as the ratios of ON and NO-N to TN were 30%-39% and 52%-59% for the two land uses and 25%-44% and 46%-66% for seasonal changes. Their variations were reflected by electrical conductivity (EC) and redox environment. EC and dissolved oxygen (DO) had a positive non-linear relationship with the concentrations of total nitrogen (TN) and nitrate (NO-N). The fitted non-linear quantitative models were established separately to predict TN and NO-N concentrations in groundwater using easily available indictors (EC and DO). The high accuracy and performance of the models were investigated and approved by rRMSE, MAE, and 1:1 line. These findings can provide technical support for the rapid prediction and evaluation of N pollution in shallow groundwater through easily available indicators.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149879DOI Listing
January 2022

Altered temperature affect body condition and endochondral ossification in Bufo gargarizans tadpoles.

J Therm Biol 2021 Jul 4;99:103020. Epub 2021 Jun 4.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, China. Electronic address:

Bufo gargarizans is one kind of economic animals with higher medicinal value in China. In this study, B. gargarizans (Bufo gargarizans) tadpoles were reared at three different water temperature (15, 22 and 29 °C) from Gosner stages 28-46. We investigated the effects of temperature on growth, development, survival, metamorphic duration, size and skeletal ossification at Gosner stage 40, 42, and 46, as well as thyroid tissue reached metamorphic climax (Gs42). Besides, we examined the transcription levels of endochondral ossification-related genes in hind limb at metamorphic climax (Gs42). Our results showed that the growth and development of tadpoles conform to the temperature-size rule (TSR). While warm temperature resulted in the decrease in body size and hind limb length, and shorten larval period, cold temperature led to increase in body size and hind limb length but prolonged larval period. Histological examinations revealed that warm and cold temperatures caused damage to thyroid tissue. Also, warm and cold temperatures inhibited the degree of ossification with the double staining methodology. Additionally, the real-time PCR results suggested that warm and cold temperatures significantly up-regulated Runx2, VEGF and VEGFR mRNA levels, and down-regulated TRβ, MMP9, MMP13 and Runx3 mRNA levels. The up-regulation of Dio2 level and down-regulation of Dio3 level were observed in warm temperature. TRα mRNA level was significantly increased in warm temperature, but decreased in cold temperature. Collectively, these observations demonstrated that warm and cold temperatures affected endochondral ossification in B. gargarizans tadpoles, which might influence their capacity to terrestrial locomotion.
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http://dx.doi.org/10.1016/j.jtherbio.2021.103020DOI Listing
July 2021

Multiple Magnetic Topological Phases in Bulk van der Waals Crystal MnSb_{4}Te_{7}.

Phys Rev Lett 2021 Jun;126(24):246601

School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.

The magnetic van der Waals crystals MnBi_{2}Te_{4}/(Bi_{2}Te_{3})_{n} have drawn significant attention due to their rich topological properties and the tunability by external magnetic field. Although the MnBi_{2}Te_{4}/(Bi_{2}Te_{3})_{n} family have been intensively studied in the past few years, their close relatives, the MnSb_{2}Te_{4}/(Sb_{2}Te_{3})_{n} family, remain much less explored. In this work, combining magnetotransport measurements, angle-resolved photoemission spectroscopy, and first principles calculations, we find that MnSb_{4}Te_{7}, the n=1 member of the MnSb_{2}Te_{4}/(Sb_{2}Te_{3})_{n} family, is a magnetic topological system with versatile topological phases that can be manipulated by both carrier doping and magnetic field. Our calculations unveil that its A-type antiferromagnetic (AFM) ground state stays in a Z_{2} AFM topological insulator phase, which can be converted to an inversion-symmetry-protected axion insulator phase when in the ferromagnetic (FM) state. Moreover, when this system in the FM phase is slightly carrier doped on either the electron or hole side, it becomes a Weyl semimetal with multiple Weyl nodes in the highest valence bands and lowest conduction bands, which are manifested by the measured notable anomalous Hall effect. Our work thus introduces a new magnetic topological material with different topological phases that are highly tunable by carrier doping or magnetic field.
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http://dx.doi.org/10.1103/PhysRevLett.126.246601DOI Listing
June 2021

Influence of octylphenol on gene expression of gonadotropins and their receptors, testicular structure and mating behavior of male Rana chensinensis.

Environ Toxicol Pharmacol 2021 Oct 18;87:103694. Epub 2021 Jun 18.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, China. Electronic address:

In the present study, responses of the Chinese brown frog (Rana chensinensis) to exposure to different doses and duration of Octyphenol (OP) which degraded from alkylphenol ethoxylates (APEs) were characterized during the adult periods. The effects of OP on growth, development and reproduction and the expression of genes in gonad were investigated. The expression levels of fshβ, lhβ, fshr and lhr had significant differences as the exposure time increased. The pathological and morphological changes were also observed in the OP treatments. Furthermore, the number of TUNEL positive cells and the TUNEL index was elevated after exposed to OP. Besides that, OP treatment could influence its mating behavior and reduce the fertilization rates. Taken together, these results indicated that OP disrupt sex steroid signaling, normal development of spermatogenesis, courtship behavior of male frogs and decline fertilization rate in R. chensinensis.
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http://dx.doi.org/10.1016/j.etap.2021.103694DOI Listing
October 2021

Molecular Dynamics Simulation of Ion Adsorption and Ligand Exchange on an Orthoclase Surface.

ACS Omega 2021 Jun 4;6(23):14952-14962. Epub 2021 Jun 4.

School of Chemical and Environmental Engineering, China University of Mining and Technology (Beijing), Beijing 100083, China.

Orthoclase (K-feldspar) is one of the natural inorganic materials, which shows remarkable potential toward removing heavy metal ions from aqueous solutions. Understanding the interactions of the orthoclase and metal ions is important in the treatment of saline wastewater. In this paper, molecular dynamics simulations were used to prove the adsorption of different ions onto orthoclase. The adsorption isotherms show that orthoclase has remarkable efficiency in the removal of cations at low ion concentrations. Aluminol groups are the preferential adsorption sites of cations due to higher negative charges. The adsorption types and adsorption sites are influenced by the valence, radius, and hydration stability of ions. Monovalent cations can be adsorbed in the cavities, whereas divalent cations cannot. The hydrated cation may form an outer-sphere complex or an inner-sphere complex in association with the loss of hydration water. Na, K, and Ca ions mainly undergo inner-sphere adsorption and Mg ions prefer outer-sphere adsorption. On the basis of simulation results, the mechanism of ion removal in the presence of orthoclase is demonstrated at a molecular level.
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http://dx.doi.org/10.1021/acsomega.1c00826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209803PMC
June 2021

Comparison of in vitro biocompatibility and antibacterial activity of two calcium silicate-based materials.

J Mater Sci Mater Med 2021 Apr 26;32(5):52. Epub 2021 Apr 26.

Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, 100050, China.

This study is aimed at comparing and evaluating the biocompatibility and antibacterial activities of mineral trioxide aggregate (MTA) and iRoot BP Plus as novel retro-filling materials. Discs of both materials were prepared and incubated for 72 h to obtain material extracts in medium. Flow cytometry and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay were used to assess the rate of apoptosis and proliferation of human periodontal ligament stem cells (hPDLSCs) when exposed to eluates of both materials. The expression levels of alkaline phosphatase, collagen type I, osteocalcin, Runt-related transcription factor-2, and Osterix were tested for evaluating the osteogenic differentiation of hPDLSCs. The antibacterial activities of both materials were compared by the direct contact test. The hPDLSCs stimulated by MTA or iRoot BP Plus eluates showed significantly higher cell viability than that of the control group with no eluates. No significant differences were observed among the percentages of necrotic and apoptotic cells stimulated by MTA and iRoot BP Plus eluates and the control group. The expression of all osteogenic differentiation markers of hPDLSCs in both experimental groups were significantly higher than those of the control group, while the increment values in MTA group were significantly higher than those of the iRoot BP Plus group. The antibacterial activity against Enterococcus faecalis showed no significant difference between MTA and iRoot BP Plus. Therefore, both materials may be suitable for retro-filling applications.
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http://dx.doi.org/10.1007/s10856-021-06523-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076131PMC
April 2021

Distributed stochastic model predictive control for systems with stochastic multiplicative uncertainty and chance constraints.

ISA Trans 2021 Mar 31. Epub 2021 Mar 31.

Department of Automation, Shanghai Jiao Tong University, Key Laboratory of System Control and Information Processing, Ministry of Education of China, Shanghai, 200240, China.

The rapid development of technology and economy has led to the development of chemical processes, large-scale manufacturing equipment, and transportation networks, with their increasing complexity. These large systems are usually composed of many interacting and coupling subsystems. Moreover, the propagation and perturbation of uncertainty make the control design of such systems to be a thorny problem. In this study, for a complex system composed of multiple subsystems suffering from multiplicative uncertainty, not only the individual constraints of each subsystem but also the coupling constraints among them are considered. All the constraints with the probabilistic form are used to characterize the stochastic natures of uncertainty. This paper first establishes a centralized model predictive control scheme by integrating overall system dynamics and chance constraints as a whole. To deal with the chance constraint, based on the concept of multi-step probabilistic invariant set, a condition formulated by a series of linear matrix inequality is designed to guarantee the chance constraint. Stochastic stability can also be guaranteed by the virtue of nonnegative supermartingale property. In this way, instead of solving a non-convex and intractable chance-constrained optimization problem at each moment, a semidefinite programming problem is established so as to be realized online in a rolling manner. Furthermore, to reduce the computational burdens and amount of communication under the centralized framework, a distributed stochastic model predictive control based on a sequential update scheme is designed, where only one subsystem is required to update its plan by executing optimization problem at each time instant. The closed-loop stability in stochastic sense and recursive feasibility are ensured. A numerical example is employed to illustrate the efficacy and validity of the presented algorithm in this study.
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http://dx.doi.org/10.1016/j.isatra.2021.03.038DOI Listing
March 2021

Effects of ClpP protease on biofilm formation of Enterococcus faecalis.

J Appl Oral Sci 2021 1;29:e20200733. Epub 2021 Mar 1.

Department of Endodontics, School of Stomatology, Capital Medical University.

Objectives: Enterococcus faecalis (E. faecalis), one of the main pathogens responsible for refractory periapical periodontitis and nosocomial infections, exhibits markedly higher pathogenicity in biofilms. Studies have shown that caseinolytic protease P (ClpP) is involved in biofilm formation. However, to date, few studies have investigated the role of ClpP in the survival of E. faecalis, and in enhancing biofilm formation. Therefore, we investigated the role of ClpP in the formation of E. faecalis biofilms.

Methodology: In our study, we used homologous recombination to construct clpP deleted and clpP complement strains of E. faecalis ATCC 29212. A viable colony counting method was used to analyze the growth patterns of E. faecalis. Crystal violet staining (CV) and confocal scanning laser microscopy (CLSM) were used to characterize biofilm mass formation and scanning electron microscopy (SEM) was used to observe the biofilm microstructure. Data was statistically analyzed via Student's t-test or one-way analysis of variance (ANOVA).

Results: The results exhibited altered growth patterns for the clpP deletion strains and depleted polysaccharide matrix, resulting in reduced biofilm formation capacity compared to the standard strains. Moreover, ClpP was observed to increase biofilm formation in E. faecalis.

Conclusion: Our study shows that ClpP can increase biofilm formation in E. faecalis and emphasizes the importance of ClpP as a potential target against E. faecalis.
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http://dx.doi.org/10.1590/1678-7757-2020-0733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934281PMC
March 2021

Effects of temperature on growth, development and the leptin signaling pathway of Bufo gargarizans.

J Therm Biol 2021 Feb 29;96:102822. Epub 2020 Dec 29.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, China. Electronic address:

Climate change is one of the most important causes of the decline in amphibians. Changes in temperature have an important effect on the growth and development and energy metabolism of amphibians. The aim of this study is to unravel the effects of temperature on the leptin signaling pathway of Bufo gargarizans and its molecular mechanisms. Our results showed that high temperature accelerated the development rate of tadpoles, but reduced body size and mass, while low temperature deferred the development of tadpoles, but increased size and mass. Both high temperature and low temperature exposure caused pathological damage of the liver in B. gargarizans. The results of RT-qPCR revealed that the high temperature treatment significantly upregulated the transcript levels of genes related to thyroid hormone (DIO2 (D2), Thyroid Hormone Receptor-α (TRα)) and the leptin signaling pathway (Leptin Receptor (LepR), Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), Tyrosine kinase 2 (TYK2), Signal Transducer And Activator Of Transcription 3 (STAT3), Signal Transducer And Activator Of Transcription 3.1 (STAT3.1), and Signal Transducer And Activator Of Transcription 6 (STAT6)), while there was a decrease of mRNA expression of these genes (TRα, Thyroid Hormone Receptor-Beta (TRβ), LepR, JAK1, and TYK2) in the liver of tadpoles exposed to high temperature compared with the intermediate temperature treatment. Therefore, our results suggested that temperature extremes might interfere with the thyroid and leptin signaling pathways and affect the growth and development of B. gargarizans. Furthermore, tissue injury of the liver could occur due to exposure to temperature extremes. This work promotes public awareness of environmental protection and species conservation needs, also provides valuable experimental data and a theoretical basis for the protection of amphibians.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102822DOI Listing
February 2021

Mutation of daf-2 extends lifespan via tissue-specific effectors that suppress distinct life-limiting pathologies.

Aging Cell 2021 03 20;20(3):e13324. Epub 2021 Feb 20.

Research Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, UK.

In aging Caenorhabditis elegans, as in higher organisms, there is more than one cause of death. C. elegans exhibit early death with a swollen, infected pharynx (P death), and later death with pharyngeal atrophy (p death). Interventions that alter lifespan can differentially affect frequency and timing of each type of death, generating complex survival curve shapes. Here, we use mortality deconvolution analysis to investigate how reduction of insulin/IGF-1 signaling (IIS), which increases lifespan (the Age phenotype), affects different forms of death. All daf-2 insulin/IGF-1 receptor mutants exhibit increased lifespan in the p subpopulation (p Age), while pleiotropic class 2 daf-2 mutants show an additional marked reduction in P death frequency. The latter is promoted by pharyngeal expression of the IIS-regulated DAF-16 FOXO transcription factor, and at higher temperature by reduced pharyngeal pumping rate. Pharyngeal DAF-16 also promotes p Age in class 2 daf-2 mutants, revealing a previously unknown role for the pharynx in the regulation of aging. Necropsy analysis of daf-2 interactions with the daf-12 steroid receptor implies that previously described opposing effects of daf-12 on daf-2 longevity are attributable to internal hatching of larvae, rather than complex interactions between insulin/IGF-1 and steroid signaling. These findings support the view that wild-type IIS acts through multiple distinct mechanisms which promote different life-limiting pathologies, each of which contribute to late-life mortality. This study further demonstrates the utility of mortality deconvolution analysis to better understand the genetics of lifespan.
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http://dx.doi.org/10.1111/acel.13324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963334PMC
March 2021

Copper-induced sublethal effects in Bufo gargarizans tadpoles: growth, intestinal histology and microbial alternations.

Ecotoxicology 2021 Apr 15;30(3):502-513. Epub 2021 Feb 15.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, People's Republic of China.

Copper (Cu) is one of the environmental contaminations which can pose significant risks for organisms. The current study explores the effects of Cu exposure on the growth, intestinal histology and microbial ecology in Bufo gargarizans. The results revealed that 0.5-1 μM Cu exposure induced growth retardation (including reduction of total body length and wet weight) and intestinal histological injury (including disordered enterocyte, changes in the villi and vacuoles) of tadpoles. Also, high-throughput sequencing analysis showed that Cu exposure caused changes in richness, diversity and structure of intestinal microbiota. Moreover, the composition of intestinal microbiota was altered in tadpoles exposed to different concentrations of Cu. At the phylum level, we observed the abundance of proteobacteria was increased, while the abundance of fusobacteria was decreased in the intestinal microbiota of tadpoles exposed to 1 μM Cu. At the genus level, a reduced abundance of kluyvera and aeromonas was observed in the intestinal microbiota of tadpoles under the exposure of 0-0.5 μM Cu. Finally, functional predictions revealed that tadpoles exposed to copper may be at a higher risk of developing metabolic disorders or diseases. Above all, our results will develop a comprehensive view of the Cu exposure in amphibians and will yield a new consideration for sublethal effects of Cu on aquatic organisms.
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http://dx.doi.org/10.1007/s10646-021-02356-yDOI Listing
April 2021

Impacts of earthworm introduction and cadmium on microbial communities composition and function in soil.

Environ Toxicol Pharmacol 2021 Apr 2;83:103606. Epub 2021 Feb 2.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, China. Electronic address:

Heavy metal contamination of soil has become a public concern. Earthworms are key players in the functioning and service of soil ecosystems, with comprehension of their introduction in the polluted soil offering new insights into the protection of soil resources. In the present study, we evaluated the effects of earthworm (Eisenia fetida) introduction and Cd (0, 10, 30, and 60 mg kg of Cd) exposure upon soil microbial community using 16S rRNA gene amplicon sequencing. Our research demonstrated that Gemmatimonadetes and Deinococcus-Thermus upregulated significantly, while Chryseolinea showed an obvious decreasing trend after earthworm introduction. In Cd contaminated soil, many genera exhibited a greater presence of Cd-dependent bacteria, namely Cd-tolerant bacteria such as Altererythrobacter and Luteimonas, and a decrease of sensitive bacteria, such as Amaricoccus and Haliangium. Moreover, functional prediction analysis of soil microbiota indicated that earthworm introduction and Cd exposure changed functional pathways of soil microorganisms. The results obtained in this study are beneficial for understanding soil microbial community impacted by earthworm, and for exploring Cd resistant or tolerant bacteria, with potentially significant findings for soil biodiversity and Cd bioremediation.
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http://dx.doi.org/10.1016/j.etap.2021.103606DOI Listing
April 2021

Intestinal response characteristic and potential microbial dysbiosis in digestive tract of Bufo gargarizans after exposure to cadmium and lead, alone or combined.

Chemosphere 2021 May 2;271:129511. Epub 2021 Jan 2.

School of Environmental Science and Engineering, Chang'an University, Xi'an, 710054, People's Republic of China; Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Xi'an, 710062, People's Republic of China. Electronic address:

The gastrointestinal tract is the largest immune organ in the body and meanwhile, accommodates a large number of microorganisms. Heavy metals could disturb the intestinal homeostasis and change the gut microbial composition. However, the information regarding the links between dysbiosis of gut microbiota and imbalance of host intestinal homeostasis induced by the mixture of heavy metals is insufficient. The present study investigates the effects of Cd/Pb, both single and combination exposure, on the growth performance, intestinal histology, digestive enzymes activity, oxidative stress and immune parameters, and intestinal microbiota in Bufo gargarizans tadpoles. Our results revealed that co-exposure of Cd-Pb induced more severe impacts not only on the host, but the intestinal microbiota. On the one hand, co-exposure of Cd-Pb significantly induced growth retardation, intestinal histological injury, decreased activities of digestive enzymes. On the other hand, Cd and Pb exposure, especially in mixed form, changed the diversity and richness, structure of microbiota. Also, the intestinal microbial composition was altered by Cd/Pb exposure (alone and combination) both at the different levels. Proteobacteria, act as front-line responder, was significantly increased in tadpoles under the exposure of metals. Finally, the functional prediction revealed that the disorders of metabolism and immune responses of intestinal microbiota was increased in tadpoles exposed to Cd/Pb (especially the mixture of Cd and Pb). Our research complements the understanding of links between changes in host fitness loss and intestinal microbiota and will add a new dimension of knowledge to the ecological risks of mixed heavy metals in amphibian.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129511DOI Listing
May 2021

Gallic acid-gold nanoparticles enhance radiation-induced cell death of human glioma U251 cells.

IUBMB Life 2021 02 28;73(2):398-407. Epub 2020 Dec 28.

Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Glioblastoma multiforme (GBM) is among the most common adult brain tumors with invariably fatal character. Following the limited conventional therapies, almost all patients, however, presented with symptoms at the time of recurrence. It is dire to develop novel therapeutic strategies to improve the current treatment of GBM. Gallic acid is a well-established antioxidant, presenting a promising new selective anti-cancer drug, while gold nanoparticles (GNPs) can be developed as versatile nontoxic carriers for anti-cancer drug delivery. Here, we prepared gallic acid-GNPs (GA-GNPs) by loading gallic acid onto GNPs, reduction products of tetrachloroauric acid by sodium citrate, through physical and agitation adsorption. GA-GNPs, rather than GNPs alone, significantly inhibited the survival of U251 GBM cells, as well as enhanced radiation-induced cell death. Moreover, GA-GNPs plus radiation arrested the cell cycle of U251 at the S and G2/M phases and triggered apoptotic cell death, which is supported by increased BAX protein levels and decreased expression of BCL-2. Thus, GA-GNPs have great potential in the combination with radiation therapy in future studies for GBM treatment.
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http://dx.doi.org/10.1002/iub.2436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898864PMC
February 2021

Effects of sodium perchlorate and exogenous L-thyroxine on growth, development and leptin signaling pathway of Bufo gargarizans tadpoles during metamorphosis.

Ecotoxicol Environ Saf 2020 Dec 29;206:111410. Epub 2020 Sep 29.

National and Local Joint Engineering Research Center of Ecological Treatment Technology for Urban Water Pollution, Wenzhou University, 325035, Wenzhou, China; College of Life and Environmental Science, Wenzhou University, 325035, Wenzhou, China. Electronic address:

Sodium perchlorate (NaClO) and exogenous L-thyroxine (T4), two kinds of endocrine-disrupting chemicals (EDCs), mainly affect the circulating thyroid hormones, which regulate the initiation and rate of metamorphosis in amphibian. The aim of this study is to evaluate the potential role of EDCs in regulating the development of tadpoles and leptin signaling pathway of liver during the metamorphosis of Bufo gargarizans. There was completely opposite result of average development stage of tadpoles and morphological parameters between the NaClO and T4 exposure groups. Histological analysis revealed that NaClO and T4 exposure both caused liver injury, such as the decreased size of hepatocytes, atrophy of nucleus, increased melanomacrophage centres and disappearance of hepatocyte membranes. In addition, the results of RT-qPCR revealed that NaClO treatment significantly inhibited the transcript levels of genes related to thyroid hormone (D2, TRα and TRβ) and leptin signaling pathway (LepR, JAK1, JAK2, and TYK2), while there was an increase of mRNA expression of these genes in the liver of tadpoles administrated with T4 compared with control. This work lays an important foundation for assessing the risk of EDCs in relation to amphibian development during metamorphosis.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111410DOI Listing
December 2020

LncRNA THRIL is upregulated in sepsis and sponges miR-19a to upregulate TNF-α in human bronchial epithelial cells.

J Inflamm (Lond) 2020 10;17:31. Epub 2020 Sep 10.

Department of Respiratory and Critical Care Medicine, Inner Mongolia Baogang Hospital (The Third Affiliated Hospital of Inner Mongolia Medical University), Baotou, 014032 Inner Mongolia China.

Background: Long non-coding RNAs (lncRNAs) have been demonstrated to play critical roles in various diseases. Our bioinformatics analysis showed that lncRNA TNFα and heterogenous nuclear ribonucleoprotein L (hnRNPL) related immunoregulatory LincRNA (THRIL) may interact with miR-19a, which targets TNF-α. This study aimed to explore the role of THRIL, an enhancer of LPS-induced inflammatory, in sepsis.

Methods: Research subjects of the present study included 66 sepsis patients and 66 healthy volunteers. The expression levels of THRIL, miR-19a and TNF-α in plasma samples from these participants were determined by RT-qPCR. The interaction between THRIL and miR-19a was explored by performing overexpression experiments in human bronchial epithelial cells (HBEpCs). The roles of THRIL, miR-19a and TNF-α in regulating the apoptosis of HBEpCs were analyzed by cell apoptosis assay.

Results: We found that THRIL was upregulated in sepsis patients. THRIL is predicted to interact with miR-19a, and the interaction was confirmed by dual-luciferase activity assay. However, THRIL and miR-19a did not affect the expression of each other. Instead, overexpression of THRIL resulted in the increased expression levels of TNF-α, a downstream target of miR-19a in HBEpCs. In HBEpCs, LPS treatment induced the overexpression of THRIL. Cell apoptosis analysis showed that overexpression of THRIL and TNF-α promoted the apoptosis of HBEpCs induced by LPS, while overexpression of miR-19a played an opposite role. Overexpression of THRIL attenuated the effects of overexpression of miR-19a.

Conclusion: Therefore, THRIL is upregulated in sepsis and may sponge miR-19a to upregulate TNF-α, thereby promoting lung cell apoptosis.
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http://dx.doi.org/10.1186/s12950-020-00259-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488348PMC
September 2020

Mitochondrial Signature in Human Monocytes and Resistance to Infection in During Fumarate-Induced Innate Immune Training.

Front Immunol 2020 5;11:1715. Epub 2020 Aug 5.

Laboratorio de Inmunorregulación, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.

Monocytes can develop immunological memory, a functional characteristic widely recognized as innate immune training, to distinguish it from memory in adaptive immune cells. Upon a secondary immune challenge, either homologous or heterologous, trained monocytes/macrophages exhibit a more robust production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, than untrained monocytes. , β-glucan, and BCG are all inducers of monocyte training and recent metabolic profiling analyses have revealed that training induction is dependent on glycolysis, glutaminolysis, and the cholesterol synthesis pathway, along with fumarate accumulation; interestingly, fumarate itself can induce training. Since fumarate is produced by the tricarboxylic acid (TCA) cycle within mitochondria, we asked whether extra-mitochondrial fumarate has an effect on mitochondrial function. Results showed that the addition of fumarate to monocytes induces mitochondrial Ca uptake, fusion, and increased membrane potential (Δψm), while mitochondrial cristae became closer to each other, suggesting that immediate (from minutes to hours) mitochondrial activation plays a role in the induction phase of innate immune training of monocytes. To establish whether fumarate induces similar mitochondrial changes in a multicellular organism, effects of fumarate supplementation were tested in the nematode worm . This induced mitochondrial fusion in both muscle and intestinal cells and also increased resistance to infection of the pharynx with . Together, these findings contribute to defining a mitochondrial signature associated with the induction of innate immune training by fumarate treatment, and to the understanding of whole organism infection resistance.
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http://dx.doi.org/10.3389/fimmu.2020.01715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419614PMC
April 2021

Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial.

JAMA 2020 09;324(11):1048-1057

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Importance: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown.

Objective: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment.

Design, Setting, And Participants: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020.

Interventions: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d.

Main Outcomes And Measures: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group.

Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care.

Conclusions And Relevance: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance.

Trial Registration: ClinicalTrials.gov Identifier: NCT04292730.
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http://dx.doi.org/10.1001/jama.2020.16349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442954PMC
September 2020

How long-term excessive manure application affects soil phosphorous species and risk of phosphorous loss in fluvo-aquic soil.

Environ Pollut 2020 Nov 2;266(Pt 2):115304. Epub 2020 Aug 2.

Key Laboratory of Nonpoint Source Pollution Control, Ministry of Agriculture and Rural Affairs/Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, 100081, PR China.

The excessive application of manure has caused a high load of phosphorus (P) in the North China Plain. Having an understanding of how manure application affects soil P changes and its transport between different soil layers is crucial to reasonably apply manure P and reduce the associated loss. Based on our 28-year field experiments, the compositions and changes of P species and the risk of P loss under excessive manure treatments were investigated, i.e., no fertilizer (CK), mineral fertilizer NPK (NPK), NPK plus 22.5 t ha yr swine manure (LMNPK), and NPK plus 33.75 t ha yr swine manure (HMNPK). Manure application increased the content of orthophosphate and myo-inositol hexaphosphate (myo-IHP), especially the orthophosphate content exceeded 95%. The amount of orthophosphate in manure and the conversion of organic P to inorganic P in soil were the main reasons for the increased soil orthophosphate. Compared with NPK treatment, soil microbial biomass phosphorus and alkaline phosphatase activity in LMNPK and HMNPK treatments significantly increased. Compared with NPK treatment, a high manure application rate under HMNPK treatment could increase the abundance of organic P-mineralization gene phoD by 60.0% and decrease the abundance of inorganic P-solubilization gene pqqC by 45.9%. Due to the continuous additional manure application, soil P stocks significantly increased under LMNPK and HMNPK treatments. Furthermore, part of the P has been leached to the 60-80 cm soil layer. Segmented regression analysis indicated that CaCl-P increased sharply when Olsen-P was higher than 25.1 mg kg, however the content of Olsen-P did not exceed this value until 10 years after consecutive excessive manure application. In order to improve soil P availability and decrease the risk of P loss, the manure application rate should vary over time based on soil physicochemical conditions, plants requirements, and P stocks from previous years.
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http://dx.doi.org/10.1016/j.envpol.2020.115304DOI Listing
November 2020

4-hydroxy-2(3H)-benzoxazolone alleviates acetaminophen-induced hepatic injury by inhibiting NF-κB and activating Nrf2/HO-1 signaling pathways.

Am J Transl Res 2020 15;12(5):2169-2180. Epub 2020 May 15.

Department of Pharmacology, Guangxi Medical University Nanning 530021, China.

The purpose of this study is to evaluate the protective effect of 4-hydroxy-2(3H)-benzoxazolone from (HBAI) on acute liver injury induced by acetaminophen in mice and its mechanism. Mice were continuously treated with HBAI (200, 100, 50 mg/kg) once a day for 10 days. After that, the mice were fasted for 8 hours, followed by intraperitoneal injection of acetaminophen (300 mg/kg). The results showed that HBAI pretreatment significantly reduced acetaminophen-induced liver tissue congestion, hepatocyte apoptosis and necrosis, and inflammatory cell infiltration. HBAI could effectively reduce the levels of serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, reactive oxygen species and malondialdehyde. Interestingly, the activities of liver catalase, superoxide dismutase, glutathione and glutathione reductase were enhanced by HBAI pretreatment. Moreover, HBAI pretreatment alleviated acetaminophen-induced hepatocyte apoptosis by regulating the expression of Bcl-2 family proteins and the mitochondrial function. Further study showed that HBAI pretreatment effectively promoted the expression of Nrf2 and its signal downstream HO-1, NQO1, GCLC, GCLM, and MGST-1, suggesting the activation of the Nrf2/HO-1 signaling pathway. Meanwhile, HBAI attenuated the phosphorylation of NF-κBp65, IKKα/β, and IκBα, as well as the expression of NF-κBp50, which indicated that HBAI blocked the signal transduction of NF-κB pathway. In conclusion, HBAI protects against acetaminophen-induced acute liver injury by inhibiting the NF-κB and activating Nrf2/HO-1 signaling pathways.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269977PMC
May 2020

Response Patterns of Biomarkers as Tools to Identify Toxic Effects of Cadmium and Lead on Bufo gargarizans Embryo.

Bull Environ Contam Toxicol 2020 Jul 30;105(1):41-50. Epub 2020 May 30.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, China.

Molecular biomarkers play an increasing crucial role in evaluating and predicting toxicity of metals. Expressions patterns of genes related to oxidative stress, apoptosis, immune and inflammation response in the Bufo gargarizans embryo exhibited a development dependent manner. The genes related to oxidative stress (HSP, GPx and SOD) are the first response in the development of embryo, followed by the apoptosis (Bax, BCLAF1 and TRAIL) and inflammation and immune response (SOCS3, IL-27 and IL-17D), respectively. Then, we have verified the HSP, Bax and SOCS3 IL-27 (expressed highest in their respective processes) exhibited the most significant changes in Cd-Pb mixed group compared with control. In addition, we found exposure of Cd-Pb mixed metals causes greater adverse effects than Cd, Pb alone on development and morphology of embryo. Overall, our results provide a useful tool to use the sensitive molecular biomarkers as indicators of developmental toxicity in amphibian embryo.
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http://dx.doi.org/10.1007/s00128-020-02884-zDOI Listing
July 2020

Temperature compensation of optical alternating magnetic field sensor via a novel method for on-line measuring.

Opt Express 2020 Apr;28(9):13682-13693

The variation of environment temperature is a crucial problem for optical magnetic field sensors based on the magneto-optical crystal. In this paper, we propose a novel temperature compensation method for optical alternating magnetic field measuring by analyzing the demodulation principle and establishing the temperature compensation model, which can implement the functions of temperature compensation and on-line measuring simultaneously. Both the temperature and the alternating magnetic field flux density can be obtained only by adding two magnet rings on the magnetic field sensor. The experimental phenomenon agrees well with the temperature characteristics of the magneto-optical crystal and the theoretical compensation model. The experimental results demonstrate that this sensor has excellent stability whose max relative fluctuation is only 0.7402% in the range of 0-4 mT under a constant temperature. In the temperature compensation experiment of 0 °C, 20 °C and 40 °C, the sensor shows strong temperature robustness that the max absolute and relative errors are 0.07 mT and 3.50%, respectively. Meanwhile, compensation efficiency reaches 83.968%, which can effectively avoid temperature crosstalk to a large extent. Additionally, it has a better compensation performance whose max absolute and relative errors are 0.15 mT and 1.66% in the broader range of 0-16 mT when the actual temperature is accurately known.
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http://dx.doi.org/10.1364/OE.388407DOI Listing
April 2020

Nitrate exposure induces intestinal microbiota dysbiosis and metabolism disorder in Bufo gargarizans tadpoles.

Environ Pollut 2020 Sep 3;264:114712. Epub 2020 May 3.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, China. Electronic address:

Excess nitrate has been reported to be associated with many adverse effects in humans and experimental animals. However, there is a paucity of information of the effects of nitrate on intestinal microbial community. In this study, the effects of nitrate on development, intestinal microbial community, and metabolites of Bufo gargarizans tadpoles were investigated. B. gargarizans were exposed to control, 5, 20 and 100 mg/L nitrate-nitrogen (NO-N) from eggs to Gosner stage 38. Our data showed that the body size of tadpoles significantly decreased in the 20 and 100 mg/L NO-N treatment group when compared to control tadpoles. Exposure to 20 and 100 mg/L NO-N also caused indistinct cell boundaries and nuclear pyknosis of mucosal epithelial cells in intestine of tadpoles. In addition, exposure to NO-N significantly altered the intestinal microbiota diversity and structure. The facultative anaerobic Proteobacteria occupy the niche of the obligately anaerobic Bacteroidetes and Fusobacteria under the pressure of NO-N exposure. According to the results of functional prediction, NO-N exposure affected the fatty acid metabolism pathway and amino acid metabolism pathway. The whole-body fatty acid components were found to be changed after exposure to 100 mg/L NO-N. Therefore, we concluded that exposure to 20 and 100 mg/L NO-N could induce deficient nutrient absorption in intestine, resulting in malnutrition of B. gargarizans tadpoles. High levels of NO-N could also change the intestinal microbial communities, causing dysregulation of fatty acid metabolism and amino acid metabolism in B. gargarizans tadpoles.
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http://dx.doi.org/10.1016/j.envpol.2020.114712DOI Listing
September 2020

Plastic pollution in croplands threatens long-term food security.

Glob Chang Biol 2020 06 12;26(6):3356-3367. Epub 2020 Apr 12.

Hunan Academy of Agricultural Sciences, Changsha, P.R. China.

Plastic pollution is a global concern given its prevalence in aquatic and terrestrial ecosystems. Studies have been conducted on the distribution and impact of plastic pollution in marine ecosystems, but little is known on terrestrial ecosystems. Plastic mulch has been widely used to increase crop yields worldwide, yet the impact of plastic residues in cropland soils to soil health and crop production in the long term remained unclear. In this paper, using a global meta-analysis, we found that the use of plastic mulch can indeed increase crop yields on average by 25%-42% in the immediate season due to the increase of soil temperature (+8%) and moisture (+17%). However, the unabated accumulation of film residues in the field negatively impacts its physicochemical properties linked to healthy soil and threatens food production in the long term. It has multiple negative impacts on plant growth including crop yield (at the mean rate of -3% for every additional 100 kg/ha of film residue), plant height (-2%) and root weight (-5%), and soil properties including soil water evaporation capacity (-2%), soil water infiltration rate (-8%), soil organic matter (-0.8%) and soil available phosphorus (-5%) based on meta-regression. Using a nationwide field survey of China, the largest user of plastic mulch worldwide, we found that plastic residue accumulation in cropland soils has reached 550,800 tonnes, with an estimated 6%-10% reduction in cotton yield in some polluted sites based on current level of plastic residue content. Immediate actions should be taken to ensure the recovery of plastic film mulch and limit further increase in film residue loading to maintain the sustainability of these croplands.
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http://dx.doi.org/10.1111/gcb.15043DOI Listing
June 2020

4-hydroxybenzo[d]oxazol-2(3H)-one ameliorates LPS/D-GalN-induced acute liver injury by inhibiting TLR4/NF-κB and MAPK signaling pathways in mice.

Int Immunopharmacol 2020 Jun 6;83:106445. Epub 2020 Apr 6.

Department of Pharmacology, Guangxi Medical University, Nanning 530021, China. Electronic address:

The purpose of this study was to synthesize 4-hydroxybenzo[d]oxazol-2(3H)-one (HBO) and to investigate its protective effects on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury. HBO (CHON) was synthesized based on 2-nitro-resorcinol and identified by physicochemical analysis. In the animal experiment, mice were pretreated with HBO (50, 100, 200 mg/kg) for 10 days. At the end of pretreatment, the animals were injected with LPS (10 µg/kg)/D-GalN (700 mg/kg). The results showed that HBO significantly alleviated liver injury induced by LPS/D-GalN in mice. It remarkably decreased inflammatory response by reducing the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Moreover, HBO notably attenuated hepatocyte apoptosis by inhibiting the release of Cytochrome C (Cyt C) from mitochondria into the cytoplasm and regulating the expression of B-cell lymphoma-2 (Bcl-2) family. Furthermore, the result showed that HBO inhibited the expressions of nuclear factor kappa-B p50 (NF-κBp50), toll-like receptor 4 (TLR4), and myeloid differentiation factor 88 (MyD88), as well as the phosphorylation of inhibitor of nuclear factor kappa-B (IκB), inhibitor of nuclear factor kappa-B kinase-α/β (IKK-α/β), nuclear factor kappa-B p65 (NF-κBp65), suggesting that HBO had a certain influence on the TLR4/NF-κB pathway. In addition, the mitogen-activated protein kinase (MAPK) signaling pathway was also affected by HBO, as evidenced by the decrease in the phosphorylation levels of extracellular regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). In conclusion, our study suggested that HBO could protect against LPS/D-GalN-induced liver injury, moreover, treatment with HBO appeared to be capable of further regulating the TLR4/NF-κB and MAPK signaling pathways.
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http://dx.doi.org/10.1016/j.intimp.2020.106445DOI Listing
June 2020
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