Publications by authors named "Wanying Zhang"

77 Publications

Sesamol Attenuates Neuroinflammation by Regulating the AMPK/SIRT1/NF-B Signaling Pathway after Spinal Cord Injury in Mice.

Oxid Med Cell Longev 2022 6;2022:8010670. Epub 2022 Jan 6.

Department of Orthopaedics, Affiliated Pingyang Hospital and School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.

Inflammation is one of the crucial mechanisms mediating spinal cord injury (SCI) progress. Sesamol, a component of sesame oil, has anti-inflammatory activity, but its mechanism in SCI remains unclear. We investigated if the AMPK/SIRT1/NF-B pathway participated in anti-inflammation of sesamol in SCI. Sesamol could inhibit neuronal apoptosis, reduce neuroinflammation, enhance M2 phenotype microglial polarization, and improved motor function recovery in mice after SCI. Furthermore, sesamol increased SIRT1 protein expression and p-AMPK/AMPK ratio, while it downregulated the p-p65/p65 ratio, indicating that sesamol treatment upregulated the AMPK/SIRT1 pathway and inhibited NF-B activation. However, these effects were blocked by compound C which is a specific AMPK inhibitor. Together, the study suggests that sesamol is a potential drug for antineuroinflammation and improving locomotor functional recovery through regulation of the AMPK/SIRT1/NF-B pathway in SCI.
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http://dx.doi.org/10.1155/2022/8010670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758308PMC
January 2022

Application of copper(II)-based chemicals induces CHBr and CHCl emissions from soil and seawater.

Nat Commun 2022 01 10;13(1):47. Epub 2022 Jan 10.

Department of Geography, University of California, Berkeley, CA, 94720, USA.

Methyl bromide (CHBr) and methyl chloride (CHCl) are major carriers of atmospheric bromine and chlorine, respectively, which can catalyze stratospheric ozone depletion. However, in our current understanding, there are missing sources associated with these two species. Here we investigate the effect of copper(II) on CHBr and CHCl production from soil, seawater and model organic compounds: catechol (benzene-1,2-diol) and guaiacol (2-methoxyphenol). We show that copper sulfate (CuSO) enhances CHBr and CHCl production from soil and seawater, and it may be further amplified in conjunction with hydrogen peroxide (HO) or solar radiation. This represents an abiotic production pathway of CHBr and CHCl perturbed by anthropogenic application of copper(II)-based chemicals. Hence, we suggest that the widespread application of copper(II) pesticides in agriculture and the discharge of anthropogenic copper(II) to the oceans may account for part of the missing sources of CHBr and CHCl, and thereby contribute to stratospheric halogen load.
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http://dx.doi.org/10.1038/s41467-021-27779-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748922PMC
January 2022

A novel effector, CsSp1, from Bipolaris sorokiniana, is essential for colonization in wheat and is also involved in triggering host immunity.

Mol Plant Pathol 2022 Feb 6;23(2):218-236. Epub 2021 Nov 6.

Department of Plant Pathology, College of Plant Protection, Henan Agricultural University/Collaborative Innovation Center of Henan Grain Crops/National Key Laboratory of Wheat and Maize Crop Science, Zhengzhou, China.

The hemibiotrophic pathogen Bipolaris sorokiniana causes root rot, leaf blotching, and black embryos in wheat and barley worldwide, resulting in significant yield and quality reductions. However, the mechanism underlying the host-pathogen interactions between B. sorokiniana and wheat or barley remains unknown. The B. sorokiniana genome encodes a large number of uncharacterized putative effector proteins. In this study, we identified a putative secreted protein, CsSp1, with a classic N-terminal signal peptide, that is induced during early infection. A split-marker approach was used to knock out CsSP1 in the Lankao 9-3 strain. Compared with the wild type, the deletion mutant ∆Cssp1 displayed less radial growth on potato dextrose agar plates and produced fewer spores, and complementary transformation completely restored the phenotype of the deletion mutant to that of the wild type. The pathogenicity of the deletion mutant in wheat was attenuated even though appressoria still penetrated the host. Additionally, the infectious hyphae in the deletion mutant became swollen and exhibited reduced growth in plant cells. The signal peptide of CsSp1 was functionally verified through a yeast YTK12 secretion system. Transient expression of CsSp1 in Nicotiana benthamiana inhibited lesion formation caused by Phytophthora capsici. Moreover, CsSp1 localized in the nucleus and cytoplasm of plant cells. In B. sorokiniana-infected wheat leaves, the salicylic acid-regulated genes TaPAL, TaPR1, and TaPR2 were down-regulated in the ∆Cssp1 strain compared with the wild-type strain under the same conditions. Therefore, CsSp1 is a virulence effector and is involved in triggering host immunity.
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http://dx.doi.org/10.1111/mpp.13155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743017PMC
February 2022

The influence of sea animals on selenium distribution in tundra soils and lake sediments in maritime Antarctica.

Chemosphere 2022 Mar 1;291(Pt 1):132748. Epub 2021 Nov 1.

Key Laboratory of Functional Agriculture, Suzhou Research Institute, University of Science and Technology of China, Suzhou, 215123, Jiangsu, China.

The biogeochemical behavior of selenium (Se) has been extensively studied in Se-enriched or Se contaminated soils at low and middle latitudes. However, the Se distribution patterns have not been studied in tundra ecosystems of remote Antarctica. Here, the soils/sediments were collected from penguin and seal colonies, their adjacent tundra and lakes, tundra marsh, human-activity areas, normal tundra and the periglacial in maritime Antarctica, and total Se and seven operationally defined Se fractions were analyzed. Overall the regional distribution of Se levels showed high spatial heterogeneity (coefficient of variation, CV = 114%) in tundra soils, with the highest levels in penguin (mean 6.12 ± 2.66 μg g) and seal (mean 2.29 ± 1.43 μg g) colony soils, and the lowest in normal tundra soils and periglacial sediments (<0.5 μg g). The contribution rates of penguins and seals to tundra soil Se levels amounted to 91.7% and 78.0%. The lake sediment Se levels (mean 2.15 ± 0.87 μg g) close to penguin colonies were one order of magnitude higher than those (mean 0.49 ± 0.87 μg g) around normal tundra. Strong positive correlations (p < 0.01) of Se concentrations between lake sediments and adjacent tundra soils, and lower Se: P (<0.001) and S: P (<1) ratios in the lake sediments close to penguin colonies, indicated the infiltration or leaching of penguin guano as the predominant Se source in lake sediment. The Se species in penguin and seal guano were dominated by SeCys (76.6%) and SeMet (73.5%), respectively. The evidence from the predominant proportions of total organic matter-bound Se (Se, 67%-70% of total Se) in penguin or seal colony soils further supported penguin or seal guano had a great influence on the distribution patterns of Se fractions in the tundra. This study confirmed that sea animal activities transported substantial amount Se from ocean to land, and significantly altered the biogeochemical cycle of Se in maritime Antarctica.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132748DOI Listing
March 2022

Broadly neutralizing antibody-derived CAR T cells reduce viral reservoir in individuals infected with HIV-1.

J Clin Invest 2021 10;131(19)

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

BACKGROUNDChimeric antigen receptor (CAR) T cells have emerged as an approach to treat malignant tumors. This strategy has also been proposed for the treatment of HIV-1 infection. We have developed a broadly neutralizing antibody-derived (bNAb-derived) CAR T cell therapy that can exert specific cytotoxic activity against HIV-1-infected cells.METHODSWe conducted an open-label trial of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of bNAb-derived CAR T cell therapy in individuals infected with HIV-1 who were undergoing analytical interruption of antiretroviral therapy (ART).RESULTSA total of 14 participants completed only a single administration of bNAb-derived CAR T cells. CAR T cell therapy administration was safe and well tolerated. Six participants discontinued ART, and viremia rebound occurred in all of them, with a 5.3-week median time. Notably, the cell-associated viral RNA and intact proviruses decreased significantly after CAR T cell treatment. Analyses of HIV-1 variants before or after CAR T cell administration suggested that CAR T cells exerted pressure on rebound viruses, resulting in a selection of viruses with less diversity and mutations against CAR T cell-mediated cytotoxicity.CONCLUSIONNo safety concerns were identified with adoptive transfer of bNAb-derived CAR T cells. They reduced viral reservoir. All the rebounds were due to preexisting or emergence of viral escape mutations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03240328).FUNDINGMinistry of Science and Technology of China, National Natural Science Foundation of China, and Department of Science and Technology of Guangdong Province.
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http://dx.doi.org/10.1172/JCI150211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483761PMC
October 2021

Pleiotropy method reveals genetic overlap between orofacial clefts at multiple novel loci from GWAS of multi-ethnic trios.

PLoS Genet 2021 07 9;17(7):e1009584. Epub 2021 Jul 9.

Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.

Based on epidemiologic and embryologic patterns, nonsyndromic orofacial clefts- the most common craniofacial birth defects in humans- are commonly categorized into cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP), which are traditionally considered to be etiologically distinct. However, some evidence of shared genetic risk in IRF6, GRHL3 and ARHGAP29 regions exists; only FOXE1 has been recognized as significantly associated with both CL/P and CP in genome-wide association studies (GWAS). We used a new statistical approach, PLACO (pleiotropic analysis under composite null), on a combined multi-ethnic GWAS of 2,771 CL/P and 611 CP case-parent trios. At the genome-wide significance threshold of 5 × 10-8, PLACO identified 1 locus in 1q32.2 (IRF6) that appears to increase risk for one OFC subgroup but decrease risk for the other. At a suggestive significance threshold of 10-6, we found 5 more loci with compelling candidate genes having opposite effects on CL/P and CP: 1p36.13 (PAX7), 3q29 (DLG1), 4p13 (LIMCH1), 4q21.1 (SHROOM3) and 17q22 (NOG). Additionally, we replicated the recognized shared locus 9q22.33 (FOXE1), and identified 2 loci in 19p13.12 (RAB8A) and 20q12 (MAFB) that appear to influence risk of both CL/P and CP in the same direction. We found locus-specific effects may vary by racial/ethnic group at these regions of genetic overlap, and failed to find evidence of sex-specific differences. We confirmed shared etiology of the two OFC subtypes comprising CL/P, and additionally found suggestive evidence of differences in their pathogenesis at 2 loci of genetic overlap. Our novel findings include 6 new loci of genetic overlap between CL/P and CP; 3 new loci between pairwise OFC subtypes; and 4 loci not previously implicated in OFCs. Our in-silico validation showed PLACO is robust to subtype-specific effects, and can achieve massive power gains over existing approaches for identifying genetic overlap between disease subtypes. In summary, we found suggestive evidence for new genetic regions and confirmed some recognized OFC genes either exerting shared risk or with opposite effects on risk to OFC subtypes.
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http://dx.doi.org/10.1371/journal.pgen.1009584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270211PMC
July 2021

Multilevel thresholding using a modified ant lion optimizer with opposition-based learning for color image segmentation.

Math Biosci Eng 2021 04;18(4):3092-3143

College of Information Engineering, Sanming University, Sanming 365004, China.

Multilevel thresholding has important research value in image segmentation and can effectively solve region analysis problems of complex images. In this paper, Otsu and Kapur's entropy are adopted among thresholding segmentation methods. They are used as the objective functions. When the number of threshold increases, the time complexity increases exponentially. In order to overcome this drawback, a modified ant lion optimizer algorithm based on opposition-based learning (MALO) is proposed to determine the optimum threshold values by the maximization of the objective functions. By introducing the opposition-based learning strategy, the search accuracy and convergence performance are increased. In addition to IEEE CEC 2017 benchmark functions validation, 11 state-of-the-art algorithms are selected for comparison. A series of experiments are conducted to evaluate the segmentation performance of the algorithm. The evaluation metrics include: fitness value, peak signal-to-noise ratio, structural similarity index, feature similarity index, and computational time. The experimental data are analyzed and discussed in details. The experimental results significantly demonstrate that the proposed method is superior over others, which can be considered as a powerful and efficient thresholding technique.
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http://dx.doi.org/10.3934/mbe.2021155DOI Listing
April 2021

Artificial dual solid-electrolyte interfaces based on in situ organothiol transformation in lithium sulfur battery.

Nat Commun 2021 May 28;12(1):3031. Epub 2021 May 28.

Materials Science and Engineering Program & Texas Materials Institute, The University of Texas at Austin, Austin, TX, USA.

The interfacial instability of the lithium-metal anode and shuttling of lithium polysulfides in lithium-sulfur (Li-S) batteries hinder the commercial application. Herein, we report a bifunctional electrolyte additive, i.e., 1,3,5-benzenetrithiol (BTT), which is used to construct solid-electrolyte interfaces (SEIs) on both electrodes from in situ organothiol transformation. BTT reacts with lithium metal to form lithium 1,3,5-benzenetrithiolate depositing on the anode surface, enabling reversible lithium deposition/stripping. BTT also reacts with sulfur to form an oligomer/polymer SEI covering the cathode surface, reducing the dissolution and shuttling of lithium polysulfides. The Li-S cell with BTT delivers a specific discharge capacity of 1,239 mAh g (based on sulfur), and high cycling stability of over 300 cycles at 1C rate. A Li-S pouch cell with BTT is also evaluated to prove the concept. This study constructs an ingenious interface reaction based on bond chemistry, aiming to solve the inherent problems of Li-S batteries.
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http://dx.doi.org/10.1038/s41467-021-23155-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163853PMC
May 2021

Erbium Single Atom Composite Photocatalysts for Reduction of CO under Visible Light: CO Molecular Activation and 4f Levels as an Electron Transport Bridge.

Small 2021 Jul 27;17(26):e2102089. Epub 2021 May 27.

Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education, School of Chemistry and Materials Science, Heilongjiang University, Harbin, 150080, China.

It is still challenging to design a stable and efficient catalyst for visible-light CO reduction. Here, Er single atom composite photocatalysts are successfully constructed based on both the special role of Er and the special advantages of Zn GeO /g-C N heterojunction in the photocatalysis reduction of CO . Especially, Zn GeO :Er /g-C N obtained by in situ synthesis is not only more conducive to the tight junction of Zn GeO and g-C N , but also more favorable for g-C N to anchor rare-earth atoms. Under visible-light irradiation, Zn GeO :Er /g-C N shows more than five times enhancement in the catalytic efficiency compared to that of pure g-C N without any sacrificial agent in the photocatalytic reaction system. A series of theoretical and experimental results show that the charge density around Er, Ge, Zn, and O increases compared with Zn GeO :Er , while the charge density around C decreases compared with g-C N . These results show that an efficient way of electron transfer is provided to promote charge separation, and the dual functions of CO molecular activation of Er single atom and 4f levels as electron transport bridge are fully exploited. The pattern of combining single-atom catalysis and heterojunction opens up new methods for enhancing photocatalytic activity.
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http://dx.doi.org/10.1002/smll.202102089DOI Listing
July 2021

Set-valued mode recognition-based Bayesian estimation for nonlinear stochastic systems with unknown sensor mode.

ISA Trans 2021 May 21. Epub 2021 May 21.

Beijing Institute of Nearspace Vehicle's Systems Engineering, Beijing, China. Electronic address:

This paper proposes the problem of joint state estimation and mode recognition for nonlinear stochastic systems with unknown sensor mode. The considered sensor mode is represented by a random finite set, whose elements can be one specific mode or a set of certain modes. A set-valued mode recognition-based Bayesian estimation framework is proposed to propagate the posterior density of the state conditioned on sensor modes and measurements, where the mode is recognized based on the maximum correntropy criterion. Furthermore, a mode-separability metric is proposed to discern the reliability of mode recognition, and utilized to derive two distinct implementation schemes, including state estimation based on separable and inseparable modes. Simulation results of fault detection and target tracking are provided to demonstrate the superiority of the proposed method in terms of state estimation accuracy and mode recognition effectiveness.
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http://dx.doi.org/10.1016/j.isatra.2021.05.023DOI Listing
May 2021

Growth inhibition of Spodoptera frugiperda larvae by camptothecin correlates with alteration of the structures and gene expression profiles of the midgut.

BMC Genomics 2021 May 26;22(1):391. Epub 2021 May 26.

Guangzhou City Key Laboratory of Subtropical Fruit Trees Outbreak Control, Institute for Management of Invasive Alien Species, Zhongkai University of Agriculture and Engineering, 313 Yingdong teaching building, 510225, Guangzhou, PR China.

Background: Spodoptera frugiperda is a serious pest that causes devastating losses to many major crops, including corn, rice, sugarcane, and peanut. Camptothecin (CPT) is a bioactive secondary metabolite of the woody plant Camptotheca acuminata, which has shown high toxicity to various pests. However, the effect of CPT against S. frugiperda remains unknown.

Results: In this study, bioassays have been conducted on the growth inhibition of CPT on S. frugiperda larvae. Histological and cytological changes were examined in the midgut of larvae fed on an artificial diet supplemented with 1.0 and 5.0 µg/g CPT. The potential molecular mechanism was explored by comparative transcriptomic analyses among midgut samples obtained from larvae under different treatments. A total of 915 and 3560 differentially expressed genes (DEGs) were identified from samples treated with 1.0 and 5.0 µg/g CPT, respectively. Among the identified genes were those encoding detoxification-related proteins and components of peritrophic membrane such as mucins and cuticle proteins. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that part of DEGs were involved in DNA replication, digestion, immunity, endocrine system, and metabolism.

Conclusions: Our results provide useful information on the molecular basis for the impact of CPT on S. frugiperda and for future studies on potential practical application.
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http://dx.doi.org/10.1186/s12864-021-07726-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157707PMC
May 2021

Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft.

Front Cell Dev Biol 2021 16;9:621018. Epub 2021 Apr 16.

Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, United States.

Two large studies of case-parent trios ascertained through a proband with a non-syndromic orofacial cleft (OFC, which includes cleft lip and palate, cleft lip alone, or cleft palate alone) were used to test for possible gene-environment (G × E) interaction between genome-wide markers (both observed and imputed) and self-reported maternal exposure to smoking, alcohol consumption, and multivitamin supplementation during pregnancy. The parent studies were as follows: GENEVA, which included 1,939 case-parent trios recruited largely through treatment centers in Europe, the United States, and Asia, and 1,443 case-parent trios from the Pittsburgh Orofacial Cleft Study (POFC) also ascertained through a proband with an OFC including three major racial/ethnic groups (European, Asian, and Latin American). Exposure rates to these environmental risk factors (maternal smoking, alcohol consumption, and multivitamin supplementation) varied across studies and among racial/ethnic groups, creating substantial differences in power to detect G × E interaction, but the trio design should minimize spurious results due to population stratification. The GENEVA and POFC studies were analyzed separately, and a meta-analysis was conducted across both studies to test for G × E interaction using the 2 df test of gene and G × E interaction and the 1 df test for G × E interaction alone. The 2 df test confirmed effects for several recognized risk genes, suggesting modest G × E effects. This analysis did reveal suggestive evidence for G × Vitamin interaction for on 1p36 located about 3 Mb from , a recognized risk gene. Several regions gave suggestive evidence of G × E interaction in the 1 df test. For example, for G × Smoking interaction, the 1 df test suggested markers in on 9q31.3 from meta-analysis. Markers near also showed suggestive evidence in the 1 df test for G × Alcohol interaction, and rs41117 near (a.k.a. ) also gave suggestive significance in the meta-analysis of the 1 df test for G × Vitamin interaction. While it remains quite difficult to obtain definitive evidence for G × E interaction in genome-wide studies, perhaps due to small effect sizes of individual genes combined with low exposure rates, this analysis of two large case-parent trio studies argues for considering possible G × E interaction in any comprehensive study of complex and heterogeneous disorders such as OFC.
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http://dx.doi.org/10.3389/fcell.2021.621018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085423PMC
April 2021

NMI Facilitates Influenza A Virus Infection by Promoting Degradation of IRF7 through TRIM21.

Am J Respir Cell Mol Biol 2021 07;65(1):30-40

Department of Infectious Diseases and.

Acute respiratory infections caused by influenza A virus (IAV) spread widely and lead to substantial morbidity and mortality. Host cell induction of type I interferon (IFN-I) plays a fundamental role in eliminating the virus during the innate antiviral response. The potential role of N-myc and STAT interactor (NMI) and its underlying mechanisms of action during IAV infection, however, remain elusive. In this study, we found that the expression of NMI increased after IAV infection. -knockout mice infected with IAV displayed increased survival rate, decreased weight loss, lower viral replication, and attenuated lung inflammation when compared with wild-type mice. Deficiency of NMI promoted the production of IFN-I and IFN-stimulated genes and . Reduced levels of NMI also resulted in an increase of the expression of IFN regulator factor (IRF) 7. Further studies have revealed that NMI could interact with IRF7 after IAV infection, and this interaction involved its NID1 and NID2 domain. In addition, NMI facilitated ubiquitination and proteasome-dependent degradation of IRF7 through recruitment of the E3 ubiquitin ligase TRIM21 (tripartite motif-containing 21) to limit the IAV-triggered innate immunity. Our findings reveal a clearer understanding of the role of NMI in regulating the host innate antiviral response and provide a potential therapeutic target for controlling IAV infection.
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http://dx.doi.org/10.1165/rcmb.2020-0391OCDOI Listing
July 2021

MitoQ protects against hyperpermeability of endothelium barrier in acute lung injury via a Nrf2-dependent mechanism.

Redox Biol 2021 05 6;41:101936. Epub 2021 Mar 6.

Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. Electronic address:

Recently, numerous evidence has revealed that excessive reactive oxygen species (ROS) production and mitochondrial disruption during acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS) will aggravate the inflammatory process. To identify whether antioxidation can be one of the treatment strategies during this progress, we chose mitoQ, a mitochondria-targeted antioxidant that was proved to be effective in reducing ROS generated in mitochondria, as a ROS scavenger to investigate the role of antioxidation in ALI. We demonstrated that overoxidation occurred during the process of ALI, which could be reduced by mitoQ. In the meantime, apoptosis of endothelial cells of ALI mice, accompanied by hyperpermeability of pulmonary vascular and impaired pulmonary function, was partially reversed following an intraperitoneal injection of mitoQ. Moreover, in in vitro study, lipopolysaccharides (LPS) induced excessive ROS production, mitochondrial dysfunction and apoptosis in human pulmonary microvascular endothelial cells (HPMECs), which were rectified by mitoQ. To explore underlying mechanisms, we proceeded RNA-sequencing and found significantly upregulated expression of musculoaponeurotic fibrosarcoma F (MafF) in mitoQ treated group. Additionally, mitoQ inhibited the degradation and increased nuclear translocation of NF-E2-related factor 2 (Nrf2) and upregulated its downstream antioxidant response elements (AREs), such as heme oxygenase (HO)-1 and NAD(P)H:quinone oxidoreductase (NQO)-1. This effect was abolished by transfecting HPMECs with Nrf2 or Maff siRNA. In Nrf2 deficient mice, the protective effects of mitoQ on LPS model of ALI were largely vanished. Taken together, these results provide insights into how antioxidation exerts beneficial effects on ALI via maintaining mitochondrial hemostasis, inhibiting endothelial cells apoptosis, attenuating the endothelial disruption and regulating lung inflammation via Nrf2-MafF/ARE pathway.
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http://dx.doi.org/10.1016/j.redox.2021.101936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005834PMC
May 2021

Novel insights into di‑(2‑ethylhexyl)phthalate activation: Implications for the hypothalamus‑pituitary‑thyroid axis.

Mol Med Rep 2021 04 2;23(4). Epub 2021 Mar 2.

Department of Environmental Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

Di (2‑ethylhexyl) phthalate (DEHP), an environmental pollutant, is widely used as a plasticizer and causes serious pollution in the ecological environment. As previously reported, exposure to DEHP may cause thyroid dysfunction of the hypothalamic‑pituitary‑thyroid (HPT) axis. However, the underlying role of DEHP remains to be elucidated. The present study performed intragastrical administration of DEHP (150, 300 and 600 mg/kg) once a day for 90 consecutive days. DEHP‑stimulated oxidative stress increased the thyroid follicular cavity diameter and caused thyrocyte oedema. Furthermore, DEHP exposure altered mRNA and protein levels. Thus, DEHP may perturb TH homeostasis by affecting biosynthesis, biotransformation, bio‑transportation, receptor levels and metabolism through disruption of the HPT axis and activation of the thyroid‑stimulating hormone (TSH)/TSH receptor signaling pathway. These results identified the formerly unappreciated endocrine‑disrupting activities of phthalates and the molecular mechanisms of DEHP‑induced thyrotoxicity.
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http://dx.doi.org/10.3892/mmr.2021.11930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930932PMC
April 2021

Variational Learning Data Fusion With Unknown Correlation.

IEEE Trans Cybern 2021 Feb 10;PP. Epub 2021 Feb 10.

This article proposes the problem of joint state estimation and correlation identification for data fusion with unknown and time-varying correlation under the Bayesian learning framework. The considered data correlation is represented by the randomly weighted sum of positive semi-definite matrices, where the random weights depict at least three kinds of unknown correlation across single-sensor measurement components, multisensor measurements, and local estimates. Based on the variational Bayesian mechanism, the joint posterior distribution of the state and weights is derived in a closed-form iterative manner, through minimizing the Kullback-Leibler divergence. The three-case simulation shows the superiority of the proposed method in the root-mean-square error of estimation and identification.
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http://dx.doi.org/10.1109/TCYB.2021.3049769DOI Listing
February 2021

Examination of Racial and Ethnic Differences in Deceased Organ Donation Ratio Over Time in the US.

JAMA Surg 2021 04 14;156(4):e207083. Epub 2021 Apr 14.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: Historically, deceased organ donation was lower among Black compared with White populations, motivating efforts to reduce racial disparities. The overarching effect of these efforts in Black and other racial/ethnic groups remains unclear.

Objective: To examine changes in deceased organ donation over time.

Design, Setting, And Participants: This population-based cohort study used data from January 1, 1999, through December 31, 2017, from the Scientific Registry of Transplant Recipients to quantify the number of actual deceased organ donors, and from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Detailed Mortality File to quantify the number of potential donors (individuals who died under conditions consistent with organ donation). Data were analyzed from December 2, 2019, to May 14, 2020.

Exposures: Race and ethnicity of deceased and potential donors.

Main Outcomes And Measures: For each racial/ethnic group and year, a donation ratio was calculated as the number of actual deceased donors divided by the number of potential donors. Direct age and sex standardization was used to allow for group comparisons, and Poisson regression was used to quantify changes in donation ratio over time.

Results: A total of 141 534 deceased donors and 5 268 200 potential donors were included in the analysis. Among Black individuals, the donation ratio increased 2.58-fold from 1999 to 2017 (yearly change in adjusted incidence rate ratio [aIRR], 1.05; 95% CI, 1.05-1.05; P < .001). This increase was significantly greater than the 1.60-fold increase seen in White individuals. Nevertheless, substantial racial differences remained, with Black individuals still donating at only 69% the rate of White individuals in 2017 (P < .001). Among other racial minority populations, changes were less drastic. Deceased organ donation increased 1.80-fold among American Indian/Alaska Native and 1.40-fold among Asian or Pacific Islander populations, with substantial racial differences remaining in 2017 (American Indian/Alaska Native population donation at 28% and Asian/Pacific Islander population donation at 85% the rate of the White population). Deceased organ donation differences between Hispanic/Latino and non-Hispanic/Latino populations increased over time (4% lower in 2017).

Conclusions And Relevance: The findings of this cohort study suggest that differences in deceased organ donation between White and some racial minority populations have attenuated over time. The greatest gains were observed among Black individuals, who have been the primary targets of study and intervention. Despite improvements, substantial differences remain, suggesting that novel approaches are needed to understand and address relatively lower rates of deceased organ donation among all racial minorities.
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http://dx.doi.org/10.1001/jamasurg.2020.7083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876622PMC
April 2021

Significant Overlap of α-Synuclein, Amyloid-β, and Phospho-Tau Pathologies in Neuropathological Diagnosis of Lewy-related Pathology: Evidence from China Human Brain Bank.

J Alzheimers Dis 2021 ;80(1):447-458

Institute of Basic Medical Sciences, Neuroscience Center, National Human Brain Bank for Development and Function, Chinese Academy of Medical Sciences, Beijing, China.

Background: Lewy-related pathology (LRP), primarily comprised of α-synuclein, is a typical neuropathological change that has been identified in many neurodegenerative disorders such as Parkinson's disease (PD), PD with dementia, and dementia with Lewy bodies.

Objective: To investigate the distribution of LRP in the China Human Brain Bank, the co-occurrence of neuropathologic features of Alzheimer's disease (AD) in LRP cases, and LRP-related cognitive dysfunction.

Methods: LRP neuropathological diagnosis was performed in 180 postmortem brains. AD neuropathological diagnosis was then performed in the 21 neuropathologically-diagnosed LRP cases. Antemortem cognitive functioning evaluation (Everyday Cognitive, ECog) was assessed for brain donors by the immediate kin of the donor within 24 hours after death.

Results: 12% (21 in 180) postmortem brains were neuropathologically diagnosed as LRP cases. 86% (18 in 21) aged above 80, 81% (17 in 21) LRP cases combined with AD neuropathology, and 62% (13 in 21) combined with both the intermediate or high-level amyloid-β and phospho-tau pathologies. ECog scores showed significant differences between the groups of LRP brainstem-predominant type and LRP diffuse neocortical type, and between groups of AD and the combined LRP (diffuse neocortical type)-AD.

Conclusion: The overlap of neocortical α-synuclein, amyloid-β, phospho-tau, and neuritic plaques in LRP suggested the potential interplay among the common characteristics of proteinopathies in the late stage of neuropathological development of LRP in human brains. The anatomic progression of LRP, the process of α-synuclein spreading from the brainstem to limbic and neocortical regions, might aggravate the deterioration of cognitive function in addition to that effect of AD.
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http://dx.doi.org/10.3233/JAD-201548DOI Listing
September 2021

Brain pharmacokinetics of anti-transferrin receptor antibody affinity variants in rats determined using microdialysis.

MAbs 2021 Jan-Dec;13(1):1874121

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo , Buffalo, NY, USA.

Receptor-mediated transcytosis (RMT) is used to enhance the delivery of monoclonal antibodies (mAb) into the central nervous system (CNS). While the binding to endogenous receptors on the brain capillary endothelial cells (BCECs) may facilitate the uptake of mAbs in the brain, a strong affinity for the receptor may hinder the efficiency of transcytosis. To quantitatively investigate the effect of binding affinity on the pharmacokinetics (PK) of anti-transferrin receptor (TfR) mAbs in different regions of the rat brain, we conducted a microdialysis study to directly measure the concentration of free mAbs at different sites of interest. Our results confirmed that bivalent anti-TfR mAb with an optimal dissociation constant (K) value (76 nM) among four affinity variants can have up to 10-fold higher transcytosed free mAb exposure in the brain interstitial fluid (bISF) compared to lower and higher affinity mAbs (5 and 174 nM). This bell-shaped relationship between K values and the increased brain exposure of mAbs was also visible when using whole-brain PK data. However, we found that mAb concentrations in postvascular brain supernatant (obtained after capillary depletion) were almost always higher than the concentrations measured in bISF using microdialysis. We also observed that the increase in mAb area under the concentration curve in CSF compartments was less significant, which highlights the challenge in using CSF measurement as a surrogate for estimating the efficiency of RMT delivery. Our results also suggest that the determination of mAb concentrations in the brain using microdialysis may be necessary to accurately measure the PK of CNS-targeted antibodies at the site-of-actions in the brain.
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http://dx.doi.org/10.1080/19420862.2021.1874121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849817PMC
October 2021

Configuration Analysis of Influencing Factors of Technical Efficiency Based on DEA and fsQCA: Evidence from China's Medical and Health Institutions.

Risk Manag Healthc Policy 2021 8;14:49-65. Epub 2021 Jan 8.

King's Business School, King's College London, London, UK.

Purpose: This paper aims to measure the technical efficiency of China's medical and health institutions from 2012 to 2017 and outline the path to achieve high-quality development.

Methods: The DEA-Malmquist was used to evaluate the total factor productivity of medical and health institutions in 31 provinces. A fuzzy set Qualitative Comparative Analysis (fsQCA) was used for configuration analysis of determinants affecting technical efficiency.

Results: The average total factor productivity (TFP) of those institutions was 0.965, namely TFP declined averagely by 3.5% annually. The efficiency change and the technical change were 0.998 and 0.967, respectively. The realization paths of high technical efficiency are composed of high fatality rate and high financial allocation-led, high population density and high GDP-led. Low dependency ratio and low financial allocation-led, low fatality rate and low financial allocation-led are the main reasons for low technical efficiency.

Conclusion: Due to advanced medical technology and economic development, major cities like Beijing, Shanghai, and Guangdong have attracted a large number of high-level health personnel, achieving long-term and stable health business growth. Hubei, Anhui, and Sichuan also have made rapid development of health care through appropriate financial subsidies and policy supports. The technical changes in Qinghai, Yunnan, and Inner Mongolia are higher than the national average, but the operation and management level of the medical and health institutions is relatively weak. Henan, Jiangxi, and Heilongjiang have a prominent performance in the efficiency change, but the technical change is weaker than the national average.
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http://dx.doi.org/10.2147/RMHP.S282178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802899PMC
January 2021

Clinical characteristics and infectivity of asymptomatic carriers of SARS-CoV-2 (Review).

Exp Ther Med 2021 Feb 3;21(2):115. Epub 2020 Dec 3.

Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China.

Since December 2019, the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. At present, confirmed patients are the main source of infection, while a number of studies have indicated that asymptomatic carriers also have the ability to spread the virus. As of September 29, 2020, as the first country to report coronavirus disease 2019 (COVID-19), China has 375 asymptomatic infections according to the National Health Commission of China. Asymptomatic carriers have become the current focus of global epidemic prevention and control efforts. The present review article provides a brief introduction on the clinical characteristics and infectivity of asymptomatic carriers, and makes suggestions for the identification of asymptomatic carriers.
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http://dx.doi.org/10.3892/etm.2020.9547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739853PMC
February 2021

Extended conjugation of ESIPT-type dopants in nematic liquid crystalline phase for enhancing fluorescence efficiency and anisotropy.

Phys Chem Chem Phys 2020 Dec;22(48):28393-28400

Department of Molecular Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan.

Organic compounds capable of excited-state intramolecular proton transfer (ESIPT) show fluorescence with a large Stokes shift and serve as solid-state emitters, luminescent dopants, and fluorescence-based sensing materials. Fluorescence of ESIPT molecules is usually increased in the solid state, but is weak in solvents due to the accelerated non-radiative decays by rotational motions of a part of the molecular core in these environments. Here we report, using a representative ESIPT motif 2-(2-hydroxyphenyl)benzothiazole (HBT), the extended-conjugation strategy of keeping sufficient fluorescence efficiency both in the solid state and in organic media. The introduction of an alkyl-terminated phenylene-ethynylene group into the HBT molecule dramatically enhances the fluorescence quantum yield from 0.01 to 0.20 in toluene and from 0.07 to 0.32 in a representative room-temperature nematic liquid crystal, 4-pentyl-4'-cyano biphenyl (5CB). The newly-synthesized CnP-C[triple bond, length as m-dash]C-HBT (n = 5 or 8) serves as a fluorescent dopant in 5CB and exhibits anisotropic fluorescence with the order parameter of 0.48, where the luminescence is controlled by the applied electric-field. The enhanced emission efficiency is rationalized by the larger height of energy barrier for the ESIPT process due to the introduction of phenylene-ethynylene groups.
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http://dx.doi.org/10.1039/d0cp05415aDOI Listing
December 2020

Ginsenoside Rh2 represses autophagy to promote cervical cancer cell apoptosis during starvation.

Chin Med 2020 Nov 12;15(1):118. Epub 2020 Nov 12.

Jilin Ginseng Academy, Changchun University of Chinese Medicine, Boshuo Road 1035, Changchun, 130117, Jilin, People's Republic of China.

Background: Cancer cells through autophagy-mediated recycling to meet the metabolic demands of growth and proliferation. The steroidal saponin 20(S)-ginsenoside Rh2 effectively inhibits the growth and survival of a variety of tumor cell lines and animal models, but the effects of Rh2 on autophagy remain elusive.

Methods: Cell viability was measured by CCK-8 (cell counting kit-8) assays. Apoptosis, ROS generation and mitochondrial membrane potential were analyzed by flow cytometry. Western blot analyses were used to determine changes in protein levels. Morphology of apoptotic cells and autophagosome accumulation were analyzed by DAPI staining and transmission electron microscopy. Autophagy induction was monitored by acidic vesicular organelle staining, EGFP-LC3 and mRFP-GFP-LC3 transfection. Atg7 siRNA and autophagy regulator was used to assess the effect of autophagy on apoptosis induced by G-Rh2.

Results: In this study, we found that low concentration G-Rh2 attenuated cancer cell growth and induced apoptosis upon serum-free starvation. Caspase 3 inhibitors failed to block apoptosis in G-Rh2-treated cells, indicating a caspase-independent mechanism. G-Rh2-treated cells in serum-deprived conditions showed impaired mitochondrial function, increased release and nuclear translocation of apoptosis-inducing factor, but little changes in the mitochondrial and cytoplasmic distributions of cytochrome C. Annexin A2 overexpression in 293T cells inhibited G-Rh2-induced apoptosis under serum-starved conditions. Meanwhile, G-Rh2 reduced lysosomal activity and inhibited the fusion of autophagosome and lysosome, leading to a block of autophagic flux. Knockdown Atg7 significantly inhibited autophagy and triggered AIF-induced apoptosis in serm free condition. The autophagy inducer significantly decreased the apoptosis levels of G-Rh2-treated cells in serum-free conditions.

Conclusions: Under nutrient deficient conditions, G-Rh2 represses autophagy in cervical cancer cells and enhanced apoptosis through an apoptosis-inducing factor mediated pathway.
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http://dx.doi.org/10.1186/s13020-020-00396-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661217PMC
November 2020

Herbal formula Renshenwuweizi decoction induces p53-mediated cell cycle arrest and apoptosis in A549 cells.

J Tradit Chin Med 2020 10;40(5):766-773

Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China.

Objective: To investigate the effect of Renshenwuweizi decoction (RSWWZ decoction) on the growth of non-small cell lung cancer cells in vitro.

Methods: A549 non-small cell lung cancer cells were divided into two groups: control and RSWWZ decoction treatment groups. Cell Counting Kit-8 was used to measure the inhibitory effect of RSWWZ decoction on the growth of A549 cells. 4', 6-diamidino-2-phenylindole staining and Annexin V-fluorescein isothiocyanate/propidium iodide double staining were used to investigate apoptosis in A549 cells following RSWWZ decoction treatment, and the mitochondrial membrane potential of treated cells was detected with Rhodamine 123. Cell cycle progression was analyzed by flow cytometry. The mRNA levels of p53, Bax, B-cell lymphoma-2 (Bcl-2) and p21 were measured by quantitative real-time reverse transcription polymerase chain reaction. The protein expressions of p53, Bax, Bcl-2, p21, cyclin-dependent kinases 2 (CDK2), and cyclin A were detected by Western blot.

Results: RSWWZ decoction reduced the viability of A549 cells in a dose-dependent manner by inducing apoptosis and decreased mitochondrial membrane potential. RSWWZ decoction increased p53 and Bax expression and decreased Bcl-2 expression in a dose-dependent manner. RSWWZ decoction also induced an S-phase cell cycle arrest by increasing p21 and decreasing cyclin A and CDK2 expression.

Conclusion: In vitro experiments revealed that the Renshenwuweizi decoction-induced decrease in A549 cell proliferation was achieved by inducing apoptosis and S-phase cell cycle arrest via the p53 pathway. These findings provide the experimental basis for Renshenwuweizi decoction treatment of lung cancer.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2020.05.006DOI Listing
October 2020

Recovered COVID-19 patients with recurrent viral RNA exhibit lower levels of anti-RBD antibodies.

Cell Mol Immunol 2020 10 16;17(10):1098-1100. Epub 2020 Sep 16.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

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http://dx.doi.org/10.1038/s41423-020-00528-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493297PMC
October 2020

Methyl Chloride and Methyl Bromide Production and Consumption in Coastal Antarctic Tundra Soils Subject to Sea Animal Activities.

Environ Sci Technol 2020 10 8;54(20):13354-13363. Epub 2020 Oct 8.

Department of Geography, University of California Berkeley, Berkeley, California 94720, United States.

Methyl chloride (CHCl) and methyl bromide (CHBr) are the predominant carriers of natural chlorine and bromine from the troposphere to the stratosphere, which can catalyze the destruction of stratospheric ozone. Here, penguin colony soils (PCS) and the adjacent tundra soils (i.e., penguin-lacking colony soils, PLS), seal colony soils (SCS), tundra marsh soils (TMS), and normal upland tundra soils (UTS) in coastal Antarctica were collected and incubated for the first time to confirm that these soils were CHCl and CHBr sources or sinks. Overall, tundra soil acted as a net sink for CHCl and CHBr with potential flux ranges from -18.1 to -2.8 pmol g d and -1.32 to -0.24 pmol g d, respectively. The deposition of penguin guano or seal excrement into tundra soils facilitated the simultaneous production of CHCl and CHBr and resulted in a smaller sink in PCS, SCS, and PLS. Laboratory-based thermal treatments and anaerobic incubation experiments suggested that the consumption of CHCl and CHBr was predominantly mediated by microbes while the production was abiotic and O independent. Temperature gradient incubations revealed that increasing soil temperature promoted the consumption of CHCl and CHBr in UTS, suggesting that the regional sink may increase with Antarctic warming, depending on changes in soil moisture and abiotic production rates.
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http://dx.doi.org/10.1021/acs.est.0c04257DOI Listing
October 2020

TFE3, a potential therapeutic target for Spinal Cord Injury via augmenting autophagy flux and alleviating ER stress.

Theranostics 2020 23;10(20):9280-9302. Epub 2020 Jul 23.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Increasing evidence suggests that spinal cord injury (SCI)-induced defects in autophagic flux may contribute to an impaired ability for neurological repair following injury. Transcription factor E3 (TFE3) plays a crucial role in oxidative metabolism, lysosomal homeostasis, and autophagy induction. Here, we investigated the role of TFE3 in modulating autophagy following SCI and explored its impact on neurological recovery. Histological analysis via HE, Nissl and Mason staining, survival rate analysis, and behavioral testing via BMS and footprint analysis were used to determine functional recovery after SCI. Quantitative real-time polymerase chain reaction, Western blotting, immunofluorescence, TUNEL staining, enzyme-linked immunosorbent assays, and immunoprecipitation were applied to examine levels of autophagy flux, ER-stress-induced apoptosis, oxidative stress, and AMPK related signaling pathways. studies using PC12 cells were performed to discern the relationship between ROS accumulation and autophagy flux blockade. Our results showed that in SCI, defects in autophagy flux contributes to ER stress, leading to neuronal death. Furthermore, SCI enhances the production of reactive oxygen species (ROS) that induce lysosomal dysfunction to impair autophagy flux. We also showed that TFE3 levels are inversely correlated with ROS levels, and increased TFE3 levels can lead to improved outcomes. Finally, we showed that activation of TFE3 after SCI is partly regulated by AMPK-mTOR and AMPK-SKP2-CARM1 signaling pathways. TFE3 is an important regulator in ROS-mediated autophagy dysfunction following SCI, and TFE3 may serve as a promising target for developing treatments for SCI.
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http://dx.doi.org/10.7150/thno.46566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415792PMC
May 2021

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action.

Am J Transplant 2021 05 8;21(5):1754-1764. Epub 2020 Aug 8.

Department of Surgery, University of Cape Town, Cape Town, South Africa.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.
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http://dx.doi.org/10.1111/ajt.16205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073960PMC
May 2021

Fecal Microbiota Transplantation (FMT) Alleviates Experimental Colitis in Mice by Gut Microbiota Regulation.

J Microbiol Biotechnol 2020 Aug;30(8):1132-1141

Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin 150001, P.R. China.

Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera , , , and were upregulated but , and were reduced after FMT administration. Furthermore, FMT administration elevated the concentrations of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.
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http://dx.doi.org/10.4014/jmb.2002.02044DOI Listing
August 2020

Contribution of Alzheimer's disease neuropathologic change to the cognitive dysfunction in human brains with Lewy body-related pathology.

Neurobiol Aging 2020 07 4;91:56-65. Epub 2020 Mar 4.

Institute of Basic Medical Sciences, Neuroscience Center, National Human Brain Bank for Development and Function, Chinese Academy of Medical Sciences, Beijing, China; Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Peking Union Medical College, Beijing, China; Joint Laboratory of Anesthesia and Pain, Peking Union Medical College, Beijing, China. Electronic address:

This study investigated the clinicopathological relationship between cognitive dysfunction and Lewy body-related pathology (LRP), and the role of Alzheimer's disease neuropathologic change (ADNC) in affecting this relationship in the Chinese population. A total of 127 brains with antemortem cognition assessment were collected. The postmortem neuropathological classification of LRP and staging of ADNC were evaluated. Pairwise correlation and ordered logistic regression analysis showed that LRP had a moderate correlation with Global Everyday Cognition scores. The proportion of the people with intermediate and high levels of comorbid ADNC increased with the deterioration of LRP. The fit of the cognition prediction model improved when we incorporated both LRP and ADNC into the model compared with LRP alone. Our study indicated that comorbid ADNC can variably present in patients with Lewy body disease. A combination of LRP and concurrent ADNC improves the prediction of cognitive dysfunction compared with LRP alone. These findings may suggest the potential benefit of combined therapeutic approaches targeting concurrent pathological pathways for the Lewy body diseases in the Chinese population.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.02.022DOI Listing
July 2020
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