Publications by authors named "Yongjian Liu"

220 Publications

Role and mechanism of TXNIP in ageing-related renal fibrosis.

Mech Ageing Dev 2021 Mar 26;196:111475. Epub 2021 Mar 26.

Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China; Chongqing Clinical Research Center for Geriatrics and Gerontology, Chongqing, 409000, China. Electronic address:

Kidney ageing, which is always accompanied by renal fibrosis, drives the progression of renal fibrosis. Thioredoxin-interacting protein (TXNIP) is an endogenous suppressor of the reactive oxygen species-scavenging protein thioredoxin, which has been implicated in the ageing of some organs and is involved in renal fibrosis. However, the expression of TXNIP in ageing kidneys has not been examined, and the relationship between TXNIP and ageing-related renal fibrosis is unclear. We found that TXNIP expression was upregulated in aged mouse kidneys, and this upregulation was accompanied by ageing-related renal fibrosis phenotypes. We demonstrated that the ageing biomarkers were downregulated in TXNIP-knockout mice, and these effects resulted in the alleviation of renal fibrosis and impairments in kidney function. TXNIP overexpression in tubular cells upregulated senescence markers, promoted a profibrotic response and activated STAT3 signalling, and these parameters were inhibited by the silencing of TXNIP. Similarly, the TXNIP-mediated profibrotic response was significantly suppressed by a STAT3 inhibitor. By coimmunoprecipitation, we verified that TXNIP directly bound to STAT3, which suggested that TXNIP exacerbates renal tubular epithelial fibrosis by activating the STAT3 pathway. In summary, TXNIP plays an important role in age-related renal fibrosis and might be a therapeutic target for preventing ageing-associated renal fibrosis.
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http://dx.doi.org/10.1016/j.mad.2021.111475DOI Listing
March 2021

Chromosome-level genome reference and genome editing of the tea geometrid.

Mol Ecol Resour 2021 Mar 19. Epub 2021 Mar 19.

CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, China.

The tea geometrid is a destructive insect pest on tea plants, which seriously affects tea production in terms of both yield and quality and causes severe economic losses. The tea geometrid also provides an important study system to address the ecological adaptive mechanisms underlying its unique host plant adaptation and protective resemblance. In this study, we fully sequenced and de novo assembled the reference genome of the tea geometrid, Ectropis grisescens, using long sequencing reads. We presented a highly continuous, near-complete genome reference (787.4 Mb; scaffold N50: 26.9 Mb), along with the annotation of 18,746 protein-coding genes and 53.3% repeat contents. Importantly, we successfully placed 97.8% of the assembly in 31 chromosomes based on Hi-C interactions and characterized the sex chromosome based on sex-biased sequencing coverage. Multiple quality-control assays and chromosome-scale synteny with the model species all supported the high quality of the presented genome reference. We focused biological annotations on gene families related to the host plant adaptation and camouflage in the tea geometrid and performed comparisons with other representative lepidopteran species. Important findings include the E. grisescens-specific expansion of CYP6 P450 genes that might be involved in metabolism of tea defensive chemicals and unexpected massive expansion of gustatory receptor gene families that suggests potential polyphagy for this tea pest. Furthermore, we developed an efficient genome editing system based on CRISPR/Cas9 technology and successfully implement mutagenesis of a Hox gene in the tea geometrid. Our study provides key genomic resources both for exploring unique mechanisms underlying the ecological adaptation of tea geometrids and for developing environment-friendly strategies for tea pest management.
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http://dx.doi.org/10.1111/1755-0998.13385DOI Listing
March 2021

CC Chemokine Receptor 5 Targeted Nanoparticles Imaging the Progression and Regression of Atherosclerosis Using Positron Emission Tomography/Computed Tomography.

Mol Pharm 2021 03 16;18(3):1386-1396. Epub 2021 Feb 16.

Mallinckrodt Institute of Radiology, Washington University, St. Louis, Missouri 63110, United States.

Chemokines and chemokine receptors play an important role in the initiation and progression of atherosclerosis by mediating the trafficking of inflammatory cells. Chemokine receptor 5 (CCR5) has major implications in promoting the development of plaques to advanced stage and related vulnerability. CCR5 antagonist has demonstrated the effective inhibition of atherosclerotic progression in mice, making it a potential biomarker for atherosclerosis management. To accurately determine CCR5 , we synthesized CCR5 targeted Comb nanoparticles through a modular design and construction strategy with control over the physiochemical properties and functionalization of CCR5 targeting peptide d-Ala-peptide T-amide (DAPTA-Comb). pharmacokinetic evaluation through Cu radiolabeling showed extended blood circulation of Cu-DAPTA-Combs conjugated with 10%, 25%, and 40% DAPTA. The different organ distribution profiles of the three nanoparticles demonstrated the effect of DAPTA on not only physicochemical properties but also targeting efficiency. positron emission tomography/computed tomography (PET/CT) imaging in an apolipoprotein E knockout mouse atherosclerosis model (ApoE) showed that the three Cu-DAPTA-Combs could sensitively and specifically detect CCR5 along the progression of atherosclerotic lesions. In an ApoE-encoding adenoviral vector (AAV) induced plaque regression ApoE mouse model, decreased monocyte recruitment, CD68+ macrophages, CCR5 expression, and plaque size were all associated with reduced PET signals, which not only further confirmed the targeting efficiency of Cu-DAPTA-Combs but also highlighted the potential of these targeted nanoparticles for atherosclerosis imaging. Moreover, the up-regulation of CCR5 and colocalization with CD68+ macrophages in the necrotic core of human plaque specimens warrant further investigation for atherosclerosis prognosis.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c01183DOI Listing
March 2021

A combination of NLR and sST2 is associated with adverse cardiovascular events in patients with myocardial injury induced by moderate to severe acute carbon monoxide poisoning.

Clin Cardiol 2021 Mar 26;44(3):401-406. Epub 2021 Jan 26.

Department of Emergency Medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University, Hengshui, China.

Background: Indicators of adverse cardiovascular events in patients with acute carbon monoxide (CO) poisoning-induced myocardial injury have not yet been elucidated.

Hypothesis: This study aimed at determining the risk factors for adverse cardiovascular events in patients with acute CO poisoning-induced myocardial injury.

Methods: We enrolled patients with moderate-to-severe acute CO poisoning-induced myocardial injury. Based on the occurrence of adverse cardiovascular events, the patients were assigned into event and non-event group. Binary logistic regression analysis was performed to analyze the potential risk factors for cardiovascular adverse events.

Results: A total of 413 eligible patients were enrolled. Among them, 61 (14.8%) patients presented adverse cardiovascular events and were assigned to the event group while 352 patients were assigned to the non-event group. Univariate analysis revealed that cTnI, Lac, and NLR levels at admission and sST2 at day 3 in the event group were significantly higher compared to those in the non-event group. Subsequent multivariate analysis revealed that sST2 at day 3 and NLR at admission were independent risk factors for adverse cardiovascular events in patients with acute CO poisoning-induced myocardial injury. Finally, the sensitivity, specificity, and AUC of sST2 at day 3 combined with NLR for event prediction were 79.5%, 82.8%, and 0.858, respectively.

Conclusion: A combination of sST2 at day 3 and NLR is a potential predictor for the occurrence of adverse cardiovascular events in patients with acute CO poisoning-induced myocardial injury. Therefore, cardiovascular risk stratification should be taken into consideration, especially in patients with acute CO poisoning-induced myocardial injury.
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http://dx.doi.org/10.1002/clc.23550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943905PMC
March 2021

Radiolabeling of Gold Nanocages for Potential Applications in Tracking, Diagnosis, and Image-Guided Therapy.

Adv Healthc Mater 2021 Jan 20:e2002031. Epub 2021 Jan 20.

The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332, USA.

Gold nanocages (AuNCs) have emerged as a novel class of multifunctional nanomaterials with an array of applications in nanomedicine, including drug delivery, controlled release, as well as disease diagnosis and treatment. Labeling AuNCs with radionuclides not only offers additional therapeutic capabilities but also makes it easy to analyze their biodistribution, monitor their uptake by the tissue or organ of interest, and optimize their performance in both diagnosis and treatment. Here, an introduction to the chemical synthesis and optical properties of AuNCs is provided in the beginning. The methods developed for their radiolabeling are then showcased, followed by the use of radiolabeled AuNCs in tracking and quantifying their pharmacokinetics, including biodistribution, tumor uptake, and intratumoral distribution. Finally, their potential applications in targeted imaging and image-guided therapy are discussed.
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http://dx.doi.org/10.1002/adhm.202002031DOI Listing
January 2021

CC Chemokine Receptor 2-Targeting Copper Nanoparticles for Positron Emission Tomography-Guided Delivery of Gemcitabine for Pancreatic Ductal Adenocarcinoma.

ACS Nano 2021 01 6;15(1):1186-1198. Epub 2021 Jan 6.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, United States.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with dire prognosis due to aggressive biology, lack of effective tools for diagnosis at an early stage, and limited treatment options. Detection of PDAC using conventional radiographic imaging is limited by the dense, hypovascular stromal component and relatively scarce neoplastic cells within the tumor microenvironment (TME). The CC motif chemokine 2 (CCL2) and its cognate receptor CCR2 (CCL2/CCR2) axis are critical in fostering and maintaining this kind of TME by recruiting immunosuppressive myeloid cells such as the tumor-associated macrophages, thereby presenting an opportunity to exploit this axis for both diagnostic and therapeutic purposes. We engineered CCR2-targeting ultrasmall copper nanoparticles (Cu@CuO) as nanovehicles not only for targeted positron emission tomography imaging by intrinsic radiolabeling with Cu but also for loading and delivery of the chemotherapy drug gemcitabine to PDAC. This Cu-radiolabeled nanovehicle allowed sensitive and accurate detection of PDAC malignancy in autochthonous genetically engineered mouse models. The ultrasmall Cu@CuO showed efficient renal clearance, favorable pharmacokinetics, and minimal toxicity. Systemic administration of gemcitabine-loaded Cu@CuO effectively suppressed the progression of PDAC tumors in a syngeneic xenograft mouse model and prolonged survival. These CCR2-targeted ultrasmall nanoparticles offer a promising image-guided therapeutic agent and show great potential for translation.
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http://dx.doi.org/10.1021/acsnano.0c08185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846978PMC
January 2021

Phylogenetic Analysis of Sequences in the HIV Database Revealed Multiple Potential Circulating Recombinant Forms in China.

AIDS Res Hum Retroviruses 2021 Feb 1. Epub 2021 Feb 1.

Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

HIV recombination contributes greatly to its diversity and produces many circulating recombinant forms (CRFs) and unique recombinant forms (URFs). In China, 24 CRFs have been reported to date, and CRFs cause more than 80% of HIV infections. However, the prevalence of CRFs might still be underestimated, as a high level of onward transmission of URFs has been reported. In this study, we analyzed all Chinese region (2,253-3,252) sequences in the HIV Database to evaluate potential new CRFs in China. HIV-1 genotypes were verified by the Context-based Modeling for Expeditious Typing (COMET) tool. Maximum-likelihood (ML) trees were constructed based on sequences with unassigned genotypes. Cluster Picker 1.2.1 was used to identify transmission clusters. Meanwhile, a jumping-profile hidden Markov model (jpHMM) was used to perform recombination breakpoint analysis. Beast 1.7.5 was used to estimate the time of the most recent common ancestor of new CRFs. In the HIV databases, CRF01_AE was the most prevalent genetic form in China, accounting for 39.69% of all national infections, followed by CRF07_BC (20.47%), subtype B (17.50%), CRF08_BC (6.60%), subtype C (6.28%), CRF55_01B (2.06%), and other CRFs (1.77%). The URFs were responsible for 5.31% of all infections nationwide. Among URFs, genomes comprising BC, 01BC, 01B, and 01C were dominant. Finally, 17 potential CRFs and 1 novel CRF were identified. BEAST analysis indicates that novel CRF originated around in 2009. The data highlight that more CRFs have been spreading in China. HIV-1 sequences that are commonly used to explore drug resistance are helpful for the surveillance of epidemics of different HIV-1 genotypes.
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http://dx.doi.org/10.1089/AID.2020.0190DOI Listing
February 2021

Dietary Supplementation of Astaxanthin Improved the Growth Performance, Antioxidant Ability and Immune Response of Juvenile Largemouth Bass () Fed High-Fat Diet.

Mar Drugs 2020 Dec 15;18(12). Epub 2020 Dec 15.

Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.

High-fat diet (HFD) usually induces oxidative stress and astaxanthin is regarded as an excellent anti-oxidant. An 8-week feeding trial was conducted to investigate the effects of dietary astaxanthin supplementation on growth performance, lipid metabolism, antioxidant ability, and immune response of juvenile largemouth bass () fed HFD. Four diets were formulated: the control diet (10.87% lipid, C), high-fat diet (18.08% lipid, HF), and HF diet supplemented with 75 and 150 mg kg astaxanthin (HFA1 and HFA2, respectively). Dietary supplementation of astaxanthin improved the growth of fish fed HFD, also decreased hepatosomatic index and intraperitoneal fat ratio of fish fed HFD, while having no effect on body fat. Malondialdehyde content and superoxide dismutase activity were increased in fish fed HFD, astaxanthin supplementation in HFD decreased the oxidative stress of fish. The supplementation of astaxanthin in HFD also reduced the mRNA levels of , , , and . These results suggested that dietary astaxanthin supplementation in HFD improved the growth performance, antioxidant ability and immune response of largemouth bass.
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http://dx.doi.org/10.3390/md18120642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765211PMC
December 2020

CXCR4-Binding Positron Emission Tomography Tracers Link Monocyte Recruitment and Endothelial Injury in Murine Atherosclerosis.

Arterioscler Thromb Vasc Biol 2020 Dec 17:ATVBAHA120315053. Epub 2020 Dec 17.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis. (O.B., L.-H.H., A.E., G.J.R.).

Objective: vMIP-II (viral macrophage inflammatory protein 2)/vCCL2 binds to multiple chemokine receptors, and vMIP-II-based positron emission tomography tracer (Cu-DOTA-vMIP-II: vMIP-II tracer) accumulates at atherosclerotic lesions in mice. Given that it would be expected to react with multiple chemokine receptors on monocytes and macrophages, we wondered if its accumulation in atherosclerosis lesion-bearing mice might correlate with overall macrophage burden or, alternatively, the pace of monocyte recruitment. Approach and Results: We employed a mouse model of atherosclerosis regression involving adenoassociated virus 8 vector encoding murine Apoe (AAV-mApoE) treatment of mice where the pace of monocyte recruitment slows before macrophage burden subsequently declines. Accumulation of Cu-DOTA-vMIP-II at plaque sites was strong but declined with AAV--induced decline in monocyte recruitment, before macrophage burden reduced. Monocyte depletion indicated that monocytes and macrophages themselves were not the only target of the Cu-DOTA-vMIP-II tracer. Using fluorescence-tagged vMIP-II tracer, competitive receptor blocking with CXCR4 antagonists, endothelial-specific Cre-mediated deletion of CXCR4, CXCR4-specific tracer Cu-DOTA-FC131, and CXCR4 staining during disease progression and regression, we show endothelial cell expression of CXCR4 is a key target of Cu-DOTA-vMIP-II imaging. Expression of CXCR4 was low in nonplaque areas but strongly detected on endothelium of progressing plaques, especially on proliferating endothelium, where vascular permeability was increased and monocyte recruitment was the strongest.

Conclusions: Endothelial injury status of plaques is marked by CXCR4 expression and that this injury correlates with the tendency of such plaques to recruit monocytes. Furthermore, our findings suggest positron emission tomography tracers that mark CXCR4 can be used translationally to monitor the state of plaque injury and monocyte recruitment.
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http://dx.doi.org/10.1161/ATVBAHA.120.315053DOI Listing
December 2020

Near Full-Length Genomic Characterization of 16 HIV-1 CRF01_AE Primary Isolates from Guangxi, China.

AIDS Res Hum Retroviruses 2021 Jan 25. Epub 2021 Jan 25.

Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

Isolation and culture of human immunodeficiency virus (HIV) are an important basis for acquired immune deficiency syndrome (AIDS) etiology, immunology, drug screening, clinical treatment, and vaccine research. CRF01_AE is one of the predominant strains of HIV-1 in China. However, there are few HIV-1 CRF01_AE isolates that have been reported. In this study, 16 HIV-1 CRF01_AE strains from Guangxi, China, were isolated, and the near full-length genomes were reverse transcribed and amplified in two halves with the 1 kb overlapping region. The polymerase chain reaction products were sequenced directly. The phylogenetic analysis results showed that all of the 16 isolated strains were CRF01_AE recombinant form, and two clusters were set up in the phylogenetic tree. The tropic prediction of 16 strains showed that 2 isolates were CCR5 tropic, and the others are CXCR4 tropic. Eight of the isolated strains are drug resistant according to the genetic prediction. These 16 near full-length characterized CRF01_AE isolates obtained in this study will provide valuable genomic and phenotypic information on HIV-1 strains circulating in China for related researches.
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http://dx.doi.org/10.1089/AID.2020.0277DOI Listing
January 2021

Disentangling effects of river inflow and marine diffusion in shaping the planktonic communities in a heavily polluted estuary.

Environ Pollut 2020 Dec 9;267:115414. Epub 2020 Sep 9.

National Marine Environmental Monitoring Center, Dalian, 116023, China.

Estuarine ecosystems are important in terms of biodiversity processes because there are intense interactions between the river and sea environments. Phytoplankton and zooplankton have been shown to be ecological indicators of the water quality status in estuary ecosystems. Therefore, a comprehensive evaluation of the effects that multiple pressures have on the phytoplankton and zooplankton communities in estuarine ecosystems is essential. In this study, water samples from 29 stations were collected from the Liaohe Estuary over three different seasons, and biotic factors (i.e., phytoplankton and zooplankton) were obtained and compared. The results showed that there were significant temporal and spatial variations in the phytoplankton and zooplankton communities from the Liaohe Estuary. The correlation analyses showed that water temperature was the most important factor regulating the variation in phytoplankton communities, whereas the main driving force for the zooplankton was nutrient concentrations. Large amounts of nutrients entered the estuary in spring and summer due to intensive human activities in the Liaohe River basin. The inflows by the Liaohe River introduced some phytoplankton and zooplankton into the estuary, such as Coscinodicus asteromphalus, Chaetoceros decipiens, and Schmacheria poplesia. The impacts of Liaohe inflows on the estuary region gradually decreased as the distance from the inlet increased and this change was mediated by marine diffusion. The results from this study will improve knowledge about planktonic communities in estuarine ecosystems and provide a theoretical foundation for estuary environmental management.
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http://dx.doi.org/10.1016/j.envpol.2020.115414DOI Listing
December 2020

Interactions between dietary lipid levels and chronic exposure of legal aquaculture dose of sulfamethoxazole in juvenile largemouth bass Micropterus salmoides.

Aquat Toxicol 2020 Dec 4;229:105670. Epub 2020 Nov 4.

Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.

Antibiotics have been widely used (mainly mixed with feed) in aquaculture, while few studies have evaluated the interactions between feed composition and antibiotics. Sulfamethoxazole (SMX) is a fat-soluble antibiotic, an eight weeks feeding trial was conducted to investigate the interactions between dietary lipid levels and chronic exposure of legal aquaculture dose of sulfamethoxazole in juvenile largemouth bass Micropterus salmoides, and evaluated the possible human health risk. Six practical diets were formulated to three levels of crude lipid (11, 14.5, 18 %) and two levels of SMX (0 and 0.3 %), namely low fat (LF), moderate fat (MF), high fat (HF), low fat and SMX (LFS), moderate fat and SMX (MFS), high fat and SMX (HFS), respectively. Each diet was assigned to three tanks (20 fish per tank, average weight 30.65 ± 0.02 g). Growth and organ indices were increased by SMX. Higher malformation rate and lower hypoxia stress resistance were found in fish exposed to SMX than those not exposed. Cholesterol and bile acid synthesis related gene expressions were down-regulated by SMX exposure. Oxidative stress, inflammation and apoptosis were increased in fish exposed to SMX. Significant interactions between dietary lipid levels and SMX on renal immune response of fish were observed. Remarkable damage of intestinal histology was observed in fish fed the diet HFS. In addition, dietary SMX exposure increased pathogen susceptibility of largemouth bass and induced dysbiosis of gut microbiota. The concentrations of SMX in muscle of fish fed diets containing SMX were higher than those fed other diets, and close to the maximum residue limit (MRL) in China and international organizations. Although chronic legal aquaculture dose of dietary SMX also increased the target hazard quotient (THQ) and estimated daily intake (EDI), there is no health risk in adults and children consuming fish filet.
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http://dx.doi.org/10.1016/j.aquatox.2020.105670DOI Listing
December 2020

Delineating the Role of Macrophages in Cardiovascular Disease: How Specific Do We Need to Be?

Circ Cardiovasc Imaging 2020 10 20;13(10):e011605. Epub 2020 Oct 20.

Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.

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http://dx.doi.org/10.1161/CIRCIMAGING.120.011605DOI Listing
October 2020

Low Dietary Fish Meal Induced Endoplasmic Reticulum Stress and Impaired Phospholipids Metabolism in Juvenile Pacific White Shrimp, .

Front Physiol 2020 18;11:1024. Epub 2020 Aug 18.

Laboratory of Aquatic Animal Nutrition and Feed, Fisheries College, Guangdong Ocean University, Zhanjiang, China.

This study mainly evaluated the low dietary fish-meal (FM) on growth performance, immune competence and metabolomics response of juvenile Pacific white shrimp, reared at low salinity (7‰). Five experimental diets with graded levels (25, 20, 15, 10, and 5%) of FM were formulated. Weight gain, feed utilization and survival were decreased with the decreasing FM levels. When dietary FM decreased, glucose, cholesterol, total bile acids, and triglyceride in hemolymph decreased. Fatty acid synthesis was promoted and fatty acid lipolysis was reduced in hepatopancreas of shrimp fed low dietary FM. Endoplasmic reticulum (ER) stress related genes expression in hepatopancreas were down-regulated and in intestine were upregulated by low dietary FM. β expression in intestine increased with the dietary FM levels, while mRNA levels of in hepatopancreas showed the opposite tendency. Hematoxylin and eosin (H&E) stain and transmission electron microscope analysis of intestinal samples indicated that low FM diets induced intestinal morphological damage, ER swollen and chromatin condensation. UPLC-Q/TOF-MS analysis indicated that degree of unsaturation of the fatty acid chains of phospholipids in hemolymph decreased with the decreasing dietary FM levels. Lysophospholipids and bile acids metabolism were disturbed by high levels of FM sparing in diet. These results indicated when dietary FM contents decreased, ER stress of shrimp was induced. The decreased unsaturated degree of phospholipids, decreased contents of lysophospholipids, altered lipid metabolism and ER stress may responsible for the impaired growth performance and health of shrimp fed a low FM diet.
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http://dx.doi.org/10.3389/fphys.2020.01024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462021PMC
August 2020

Identification of a novel HIV-1 second-generation Circulating Recombinant Form CRF109_0107 in China.

J Infect 2020 11 16;81(5):816-846. Epub 2020 Sep 16.

Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dongda Street, Fengtai District, Beijing 100071, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2020.09.007DOI Listing
November 2020

Thioredoxin-interacting protein: a critical link between autophagy disorders and pancreatic β-cell dysfunction.

Endocrine 2020 12 6;70(3):526-537. Epub 2020 Sep 6.

Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, 400010, Chongqing, China.

Thioredoxin-interacting protein (TXNIP) is a known important regulatory protein of islet β-cell biology and function, but the detailed mechanism is not clear. Autophagy plays a pivotal role in maintaining cellular homoeostasis. This study aimed to elucidate the influence of TXNIP on the autophagy of β-cell. In this study, C57BL/6 mice and TXNIP mice were fed with a standard diet (SD) or a high-fat and high-sugar diet (HFSD), and then we analysed biochemical and autophagy related indexes in the mice. We infected MIN6 cells with LV-TXNIP and siRNA TXNIP, then the cells were treated with free fatty acid (FFA), autophagic activator rapamycin (RAP), inhibitors of autophagy chloroquine (CQ) and bafilomycin A1(BAF), finally, we examined the changes of autophagy in MIN6 cells. The results showed that HFSD led to β-cell dysfunction and autophagy dysregulation, which was improved by TXNIP knockout in mice. In vitro experiments, TXNIP gene silencing enhanced LC3B-I conversion to LC3B-II, reduced the protein level of P62, decreased autophagosome accumulation induced by FFA treatment, increased the glucose-stimulated insulin secretion (GSIS) and autophagic flux inhibited by treatment with CQ. TXNIP overexpression induced upregulation of LC3B-I, LC3B-II and P62, accentuating the increase in autophagy and organelle destruction induced by FFA, and exacerbated the effect of BAF on the accumulation of autophagy proteins. Increasing TXNIP levels reduced GSIS, which was reversed by treatment with RAP. In summary, our study suggested that TXNIP is a critical link between autophagy disorders and pancreatic β-cell dysfunction.
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http://dx.doi.org/10.1007/s12020-020-02471-6DOI Listing
December 2020

[Clinical-radiological-pathological Characteristics of 297 Cases of Surgical Pathology Confirmed Benign Pulmonary Lesions in Which Malignancy Could Not Be Excluded in Preoperative Assessment: A Retrospective Cohort Analysis in a Single Chinese Hospital].

Zhongguo Fei Ai Za Zhi 2020 Sep 10;23(9):792-799. Epub 2020 Aug 10.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Background: Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease.

Methods: From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted.

Results: 297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%).

Conclusions: Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.104.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519955PMC
September 2020

Kupffer Cells in Non-alcoholic Fatty Liver Disease: Friend or Foe?

Int J Biol Sci 2020 23;16(13):2367-2378. Epub 2020 Jun 23.

Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing all around the world and it may become the primary cause of terminal liver disease in adults and children in the next few decades. However, the pathogenesis of NAFLD is complex, and the Food and Drug Administration (FDA) has not approved any drugs for its treatment. Kupffer cells are the key cells regulating immunity in the liver, and the effect of their unique polarization on NAFLD has received increasing attention. Kupffer cells mainly reside in the lumen of hepatic sinusoids and account for 80% to 90% of colonized macrophages in the human body. They are phagocytic cells with the capacity for self-renewal that rarely migrate from their niche in the liver, and play a crucial role in regulating and maintaining homeostasis. Upon liver damage, Kupffer cells will be activated, releasing a good deal of inflammatory cytokines and chemokines. This review summarizes the multiple roles of Kupffer cells in the pathogenesis of NAFLD, the role of infiltrating macrophages in the pathogenesis of NAFLD is also briefly discussed, and aims to provide a theoretical basis for designing an NAFLD treatment strategy with Kupffer cells as the therapeutic target.
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http://dx.doi.org/10.7150/ijbs.47143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378652PMC
June 2020

Supplementation in a Low Fish-Meal Diet Improved Immune Response and Intestinal Health of Juvenile .

Front Physiol 2020 30;11:613. Epub 2020 Jun 30.

Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals, Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

The aim of the present experiment was to evaluate the effects of supplementation on the immune response, gut microbiota, and health of fed a low fish-meal (FM) diet. A diet containing 25% FM was used as a control (Diet A), and three other diets were formulated to contain 15% FM and supplemented with 0, 0.75, and 1.5% (Diet B, C, and D, respectively). The experiment was carried out in quadruplicates (30 shrimp per replicate, average weight 1.01 ± 0.01 g), and the shrimps were fed the test diets to apparent satiation three times daily for 8 weeks. Shrimp fed diet B and D showed lower weight gain than those fed diet A. Supplementation of 0.75% enhanced expression of antioxidative genes (superoxide dismutase and catalase) and immune-response-related genes in hepatopancreas but could not affect the gene expression of immune deficiency in hepatopancreas and Tube in the intestine. A low FM diet induced endoplasmic reticulum swelling of the intestinal epithelial cells, which was alleviated by supplementation. Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry was employed to analyze the changes of hemolymph metabolomics, 49 significantly different metabolites were identified, and lysoPCs, deoxyinosine, inosine, and highly unsaturated fatty acids were lower in fish fed with low FM diets. Intestinal microbial diversity was lower in shrimp fed Diet B than those fed the control diet. Dietary supplementation of 0.75% increased intestinal microbial diversity of shrimp and decreased the ratio of pathogenic bacterium ( and ). These results indicated that supplementing into a low FM diet improves the growth performance, immune response, and intestinal health of . The optimum inclusion level of seems to be 0.75% of diet.
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http://dx.doi.org/10.3389/fphys.2020.00613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344155PMC
June 2020

Research on the enhanced biological nitrogen removal of wastewater by the ultrasound-hydrolysis acidification of excess sludge.

Water Environ Res 2020 Jul 26. Epub 2020 Jul 26.

School of Municipal & Environmental Engineering, Shandong Jianzhu University, Jinan, China.

To simultaneously improve the removal of nitrogen and phosphorus from wastewater with a low C/N ratio and reduce excess sludge production, in this paper, excess sludge ultrasound-hydrolysis acidification (UHA) pretreatment was coupled with the anaerobic-anoxic-oxic (AAO) process to provide carbon source and enhance biological nitrogen removal performance, and the experimental results can be summarized as follows. First, the total nitrogen (TN) concentrations in the effluent of the system decreased from 16.94 mg/L to 5.74 mg/L, and the removal rate of TN increased by 25.5%. In addition, the concentrations for ammonia nitrogen (NH -N) in the system decreased 12.59 mg/L, and the removal rate of this index increased by 29.0%. Furthermore, the specific oxygen uptake rate (SOUR) in the anoxic zone increased significantly because the application of UHA products enhanced the microbial activity, and the addition of UHA products had an effect on the microbial community structure in the system. The amounts of denitrifying bacteria such as Betaproteobacteria and Alphaproteobacteria also increased, which enhanced the nitrogen removal efficiency of wastewater biological treatment. PRACTITIONER POINTS: Treatment of excess sludge in UHA device as an additional carbon source. Nitrogen removal efficiency was greatly improved after adding UHA products. Input of UHA products enhanced microbial activity in AAO system. Denitrifying bacteria increased with the addition of UHA products.
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http://dx.doi.org/10.1002/wer.1414DOI Listing
July 2020

Chemokine Receptor 2-targeted Molecular Imaging in Pulmonary Fibrosis. A Clinical Trial.

Am J Respir Crit Care Med 2021 01;203(1):78-89

Department of Radiology.

Idiopathic pulmonary fibrosis (IPF) is a progressive inflammatory lung disease without effective molecular markers of disease activity or treatment responses. Monocyte and interstitial macrophages that express the C-C motif CCR2 (chemokine receptor 2) are active in IPF and central to fibrosis. To phenotype patients with IPF for potential targeted therapy, we developed Cu-DOTA-ECL1i, a radiotracer to noninvasively track CCR2 monocytes and macrophages using positron emission tomography (PET). CCR2 cells were investigated in mice with bleomycin- or radiation-induced fibrosis and in human subjects with IPF. The CCR2 cell populations were localized relative to fibrotic regions in lung tissue and characterized using immunolocalization, single-cell mass cytometry, and RNA hybridization and then correlated with parallel quantitation of lung uptake by Cu-DOTA-ECL1i PET. Mouse models established that increased Cu-DOTA-ECL1i PET uptake in the lung correlates with CCR2 cell infiltration associated with fibrosis ( = 72). As therapeutic models, the inhibition of fibrosis by IL-1β blockade ( = 19) or antifibrotic pirfenidone ( = 18) reduced CCR2 macrophage accumulation and uptake of the radiotracer in mouse lungs. In lung tissues from patients with IPF, CCR2 cells concentrated in perifibrotic regions and correlated with radiotracer localization ( = 21). Human imaging revealed little lung uptake in healthy volunteers ( = 7), whereas subjects with IPF ( = 4) exhibited intensive signals in fibrotic zones. These findings support a role for imaging CCR2 cells within the fibrogenic niche in IPF to provide a molecular target for personalized therapy and monitoring.Clinical trial registered with www.clinicaltrials.gov (NCT03492762).
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http://dx.doi.org/10.1164/rccm.202004-1132OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781144PMC
January 2021

Optimization of isolation and transfection conditions of maize endosperm protoplasts.

Plant Methods 2020 9;16:96. Epub 2020 Jul 9.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Chengdu, China.

Background: Endosperm-trait related genes are associated with grain yield or quality in maize. There are vast numbers of these genes whose functions and regulations are still unknown. The biolistic system, which is often used for transient gene expression, is expensive and involves complex protocol. Besides, it cannot be used for simultaneous analysis of multiple genes. Moreover, the biolistic system has little physiological relevance when compared to cell-specific based system. Plant protoplasts are efficient cell-based systems which allow quick and simultaneous transient analysis of multiple genes. Typically, PEG-calcium mediated transfection of protoplast is simple and cost-effective. Notably, starch granules in cereal endosperm may diminish protoplast yield and integrity, if the isolation and transfection conditions are not accurately measured. Prior to this study, no PEG-calcium mediated endosperm protoplast system has been reported for cereal crop, perhaps, because endosperm cells accumulate starch grains.

Results: Here, we showed the uniqueness of maize endosperm-protoplast system (EPS) in conducting endosperm cell-based experiments. By using response surface designs, we established optimized conditions for the isolation and PEG-calcium mediated transfection of maize endosperm protoplasts. The optimized conditions of 1% cellulase, 0.75% macerozyme and 0.4 M mannitol enzymolysis solution for 6 h showed that more than 80% protoplasts remained viable after re-suspension in 1 ml MMG. The EPS was used to express GFP protein, analyze the subcellular location of ZmBT1, characterize the interaction of O2 and PBF1 by bimolecular fluorescent complementation (BiFC), and simultaneously analyze the regulation of expression by ZmMYB14.

Conclusions: The described optimized conditions proved efficient for reasonable yield of viable protoplasts from maize endosperm, and utility of the protoplast in rapid analysis of endosperm-trait related genes. The development of the optimized protoplast isolation and transfection conditions, allow the exploitation of the functional advantages of protoplast system over biolistic system in conducting endosperm-based studies (particularly, in transient analysis of genes and gene regulation networks, associated with the accumulation of endosperm storage products). Such analyses will be invaluable in characterizing endosperm-trait related genes whose functions have not been identified. Thus, the EPS will benefit the research of cereal grain yield and quality improvement.
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http://dx.doi.org/10.1186/s13007-020-00636-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346502PMC
July 2020

Autophagy: a promising process for the treatment of acetaminophen-induced liver injury.

Arch Toxicol 2020 09 11;94(9):2925-2938. Epub 2020 Jun 11.

Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, China.

Toxicity from drugs has become an important cause of acute liver failure. Acetaminophen, a commonly used analgesic, can cause severe acute liver injury that can worsen into acute liver failure. Autophagy, a protective cell programme, has been reported to have protective effects in a variety of diseases such as cancer, immune diseases, neurodegenerative diseases, and inflammatory diseases. In this review, we describe how an excess of acetaminophen causes liver injury step by step, from the formation of the initial protein adduct to the final hepatocyte necrosis, as well as the induction of autophagy and its beneficial effects on diseases. Emphasis is placed on the potential effect of autophagy on improving the damage of acetaminophen to hepatocytes. Finally, we are committed to providing insights into the treatment of acute liver failure through the mechanism of acetaminophen induced liver injury, the mechanism of autophagy, and the link between autophagy and liver injury.
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http://dx.doi.org/10.1007/s00204-020-02780-9DOI Listing
September 2020

Protein Expression Profile in IVF Follicular Fluid and Pregnancy Outcome Analysis in Euthyroid Women with Thyroid Autoimmunity.

ACS Omega 2020 May 14;5(20):11439-11447. Epub 2020 May 14.

Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

The objective of this study is to investigate the influence of the thyroid autoantibodies on the protein expression in follicular fluid and the clinical outcome of assisted reproductive technology. A total of 602 patients treated for infertility were screened; 49 euthyroid women who were positive for thyroid autoantibodies and 63 negative controls were recruited. Follicular fluid samples were analyzed using proteomics. Validation of target proteins in follicular fluid was performed by using parallel reaction monitoring. Differentially expressed proteins in follicular fluid, clinical pregnancy rate, abortion rate, and live-birth rate were analyzed. Clinical pregnancy rates and take-home baby rates in the thyroid autoimmunity (TAI) group were less than in the control group, but abortion rates in the TAI group were higher than in the control group (all < 0.005). A total of 49 proteins were differentially expressed in the TAI-positive group. In Gene Ontology secondary annotations of all the proteins identified, five types of proteins were associated with the reproductive process. Among 11 proteins quantitatively identified by parallel reaction monitoring, angiotensinogen and fetuin-B were associated with reproduction. These differentially expressed proteins identified in this study involved multiple pathways according to the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Our study provides evidence that some differentially expressed proteins between TAI-positive women and controls were associated with the reproductive process and closely related to important physiologic effects, which could partially explain the underlying mechanism link between TAI and the adverse outcomes of assisted reproductive technology.
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http://dx.doi.org/10.1021/acsomega.0c00463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254522PMC
May 2020

Identification of heme oxygenase-1 from golden pompano (Trachinotus ovatus) and response of Nrf2/HO-1 signaling pathway to copper-induced oxidative stress.

Chemosphere 2020 Aug 8;253:126654. Epub 2020 Apr 8.

State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animal and Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Science, Sun Yat-sen University, Guangzhou, 510275, PR China. Electronic address:

Heme oxygenase-1(HO-1) is a stress-inducible enzyme that mediates antioxidative and cytoprotective effects to maintain cellular redox homeostasis. In the present study, the full sequence of HO-1 was cloned from golden pompano(Trachinotus ovatus) by RT-PCR and RACE-PCR. The full cDNA sequence of HO-1 was 1349 bp in length which comprised of a 726 bp open reading frame (ORF) preceded by 262 bp 5'-untranslated region (UTR), and followed by a 360 bp 3'UTR, encoding 241 amino acid residues. Phylogenetic analysis revealed that HO-1 showed highest similarity to that of Takifugu rubripes. Tissue distribution analysis showed that the expression level of HO-1 was relatively high in heart, liver and spleen. A trial was conducted to investigate the response of Nrf2/HO-1 signaling pathway to oxidative stress induced by copper. The results showed that mRNA expression of NF-E2-related nuclear factor2 (Nrf2), Kelch-like-ECH-associated protein1 (keap1), superoxide dismutase (SOD), catalase (CAT), HO-1, NAD(P)H quinone oxidoreductase 1 (NQO1) and Glutathione peroxidase (GSH-PX) all significantly increased in copper treated group than that in the control group. This work provides new insight into the molecular mechanism underlying the Nrf2/HO-1 pathway in oxidative response in T. ovatus.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126654DOI Listing
August 2020

Targeted PET Imaging of Chemokine Receptor 2-Positive Monocytes and Macrophages in the Injured Heart.

J Nucl Med 2021 Jan 22;62(1):111-114. Epub 2020 May 22.

Department of Radiology, Washington University School of Medicine, St. Louis, Missouri

Proinflammatory macrophages are important mediators of inflammation after myocardial infarction and of allograft injury after heart transplantation. The aim of this study was to image the recruitment of proinflammatory chemokine receptor 2-positive (CCR2+) cells in multiple heart injury models. Cu-DOTA-extracellular loop 1 inverso (ECL1i) PET was used to image CCR2+ monocytes and macrophages in a heart transplantation mouse model. Flow cytometry was performed to characterize CCR2+ cells. Autoradiography on a human heart specimen was conducted to confirm binding specificity. Cu- and Ga-DOTA-ECL1i were compared in an ischemia-reperfusion injury mouse model. Cu-DOTA-ECL1i showed sensitive and specific detection of CCR2+ cells in all tested mouse models, with efficacy comparable to that of Ga-DOTA-ECL1i. Flow cytometry demonstrated specific expression of CCR2 on monocytes and macrophages. The tracer binds to human CCR2. This work establishes the utility of Cu-DOTA-ECL1i to image CCR2+ monocytes and macrophages in mouse models and provides the requisite preclinical information to translate the targeted clinical-grade CCR2 imaging probe for clinical investigation of heart diseases.
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http://dx.doi.org/10.2967/jnumed.120.244673DOI Listing
January 2021

Deciphering ion transporters, kinases and PDZ-adaptor molecules that mediate guanylate cyclase C agonist-dependent intestinal fluid loss in vivo.

Biochem Pharmacol 2020 08 16;178:114040. Epub 2020 May 16.

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address:

Background: The molecular basis for heat-stable Escherichia coli enterotoxin (STa) action and its synthetic analogue linaclotide is well understood at the enterocyte level. Pharmacologic strategies to prevent STa-induced intestinal fluid loss by inhibiting its effector molecules, however, have achieved insufficient inhibition in vivo.

Aims And Experimental Approach: To investigate whether the currently discussed effector molecules and signaling mechanisms of STa/linaclotide-induced diarrhea have similar relevance in vivo than at the enterocyte level, we studied the effect of 10M of the STa analogue linaclotide on short circuit current (Isc) of chambered isolated jejunal mucosa, and on the in vivo action on fluid transport in a perfused segment of proximal jejunum of anesthetized mice. The selected mice were deficient of transport (NHE3, CFTR, Slc26a3/a6), adaptor (NHERF1-3), or signal transduction molecules [cGMP-dependent kinase II (GKII)] considered to be downstream effectors after STa/linaclotide binding to guanylate cyclase C (GCC). Selective NHE3 inhibition by tenapanor was also employed.

Key Results, Conclusions And Implications: The comparison allowed the separation of effectors for stimulation of electrogenic anion secretion and for inhibition of electrolyte/fluid absorption in response to STa/linaclotide. The cGKII-NHERF1-CFTR and cGKII-NHERF2-NHE3 interactions are indeed major effectors of small intestinal fluid loss downstream of GCC activation in vitro and in vivo, but 50% of the linaclotide-induced fluid loss in vivo, while dependent on CFTR activation and NHE3 inhibition, does not involve cGKII, and 30% does not depend on NHERF1 or NHERF2. A combined NHERF1 and NHERF2 inhibition appears nevertheless a good pharmacological strategy against STa-mediated fluid loss.
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http://dx.doi.org/10.1016/j.bcp.2020.114040DOI Listing
August 2020

Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains.

BMC Infect Dis 2020 Apr 28;20(1):313. Epub 2020 Apr 28.

Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.

Background: There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance.

Methods: We used the BLAST search program followed by phylogenetic analysis to identify additional CRF65_cpx pol sequences from the Los Alamos HIV Sequence Database. Maximum likelihood phylogeny was estimated to clarify the epidemiological relationship of CRF65_cpx strains. Genotypic resistance was determined by submitting sequences to the Stanford HIV Drug Resistance Database.

Results: A total of 32 CRF65_cpx pol sequences were obtained. The CRF65_cpx strains were detected in seven provinces with large geographic distance. Yunnan CRF65_cpx sequences were mainly derived from a heterosexual risk group, whereas the CRF65_cpx sequences in other provinces were almost exclusively derived from an MSM population. With one exception of V179E, the other 31 strains harbored V179D mutation. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients.

Conclusions: This study confirmed the expansion CRF65_cpx in China. Furthermore, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. Our findings highlight the contribution of polymorphic mutations to drug resistance and underscore the challenges in treating patients harboring CRF65_cpx strains.
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http://dx.doi.org/10.1186/s12879-020-05007-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189696PMC
April 2020

Astaxanthin Attenuates Fish Oil-Related Hepatotoxicity and Oxidative Insult in Juvenile Pacific White Shrimp ().

Mar Drugs 2020 Apr 17;18(4). Epub 2020 Apr 17.

State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Provincial Key Laboratory for Aquatic Economic Animals, School of Life Science, Sun Yat-sen University, Guangzhou 510275, China.

The present study investigated the effect of dietary astaxanthin (AX) on the growth performance, antioxidant parameters, and repair of hepatopancreas damage in Pacific white shrimp (). To evaluate the hepatopancreas protective function of AX in shrimps, we compared the effect of five isonitrogenous and isoenergetic diets under oxidized fish oil conditions with varying AX levels during the 50-day experimental period. The formulated diets were as follows: (i) OFO (oxidized fish oil); (ii) OFO/AX150 (oxidized fish oil + AX150 mg/kg); (iii) OFO/AX250 (oxidized fish oil + AX250 mg/kg); (iv) OFO/AX450 (oxidized fish oil + AX450 mg/kg); and, (v) control group (fresh fish oil). Results showed that the oxidized fish oil with 275.2 meq/kg peroxide value (POV) resulted in a substantial decrease in the final body weight of ( > 0.05) and induced some visible histopathological alterations in the hepatopancreas. Growth performance was significantly higher in shrimps fed with the OFO/AX450 diet than those fed with the OFO diet ( < 0.05). However, no significant difference was observed when the OFO/AX450 diet was compared to the control diet containing fresh fish oil ( > 0.05). Moreover, shrimps under the OFO/AX450 diet displayed a significant improvement in hepatopancreatic health and showed a reduction of malondialdehyde (MDA) compared to those under the OFO diet ( < 0.05). Dietary AX improved the antioxidant capacity of by increasing the catalase (CAT) activity in the hemolymph. Acute salinity change test showed a higher shrimp survival rate under OFO/AX450 diet than the OFO diet ( < 0.05), suggesting that AX can contribute to enhanced stress tolerance. In conclusion, our data suggest that AX confers dose-dependent protection against OFO-induced oxidative insults and hepatopancreatic damage in shrimp.
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http://dx.doi.org/10.3390/md18040218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230248PMC
April 2020