Publications by authors named "Jie Lu"

1,245 Publications

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Environmentally Persistent Free Radical Promotes Lung Cancer Progression by Regulating the Expression Profile of miRNAs.

Cancer Biother Radiopharm 2022 May 17. Epub 2022 May 17.

Shanghai Tobacco Group Corp, Shanghai, P.R. China.

Environmentally persistent free radicals (EPFRs) are generated in the combustion processes of solid waste and can cause adverse influences on human health, especially lung diseases. Lung cancer is one of the most serious malignancies in recent years, which the global deaths rate is about 1.6 million every year. In this study, we verified that ZnO/MCB EPFRs promote cell proliferation and migration, impedes cell apoptosis in lung cancer. Furthermore, we found that ZnO/MCB could influence the expression of miRNAs (miR-18a and miR-34a). , ZnO/MCB and ZnO EPFRs can reduce the weight and survival rate of BALB/c male mice more than that of BALB/c female mice. In the ZnO/MCB exposed group, male mice lung became even smaller, while the female mice the lung increased significantly. Taken together, our results provide evidence for assessing the potential health risks of persistent free radicals on fine particles. This study linked toxicity of EPFRs with miRNAs revealed the potential health hazard to human lung cancer.
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http://dx.doi.org/10.1089/cbr.2021.0378DOI Listing
May 2022

Extracts of Periplaneta americana alleviate hepatic fibrosis by affecting hepatic TGF-β and NF-κB expression in rats with pig serum-induced liver fibrosis.

Folia Histochem Cytobiol 2022 May 16. Epub 2022 May 16.

The First Affiliated Hospital, Kunming Medical University, Yunnan, Kunming 650000, China.

Introduction: Liver fibrosis is caused by continuous wound healing responses to various harmful stimuli, including viral infection, drugs, alcohol, and autoimmune liver disease. The purpose of this study was to examine the effects of extracts of Periplaneta americana (EPA) in rats with pig serum-induced liver fibrosis to preliminarily assess the antifibrotic effect of EPA.

Material And Methods: Seventy rats were randomly divided into 7 groups (10 rats in each group): HC, the healthy control group; FC, the fibrotic control group; TL, low-dose EPA treatment group group; TM, medium-dose EPA group; TH, high-dose EPA treatment group; TC1, Panax notoginseng/Salvia mitiorrhiza treatment control group 1; TC2, colchicine treatment control group 2. TC1 and TC2 were used as the positive control to demonstrate the difference between EPA and the effects of other compounds. The liver fibrosis model was induced by intraperitoneal injection of 0.5 mL pig serum twice a week for 13 weeks in all groups except for the HC group. The hepatic fibrosis model was established at the 7th week, and followingly, the corresponding compounds were administered once a day in all groups for 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was determined in rat blood serum. We also measured liver fibrosis-related serum markers, including hyaluronic acid (HA), mucin layer (LN), type III pre-collagen (PC-III) and type IV collagen (IV-C). Hematoxylin and eosin (H&E) and Masson stainings were used to assess liver morphology and determine the stage of fibrosis. Immunohistochemistry was used to detect the protein expression of NF-κB, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rat liver tissue.

Results: Compared with that of the HC group, the liver tissue of the FC group presented obvious liver damage and collagen deposition. The serum levels of ALT, AST, HA, LN, PC-Ⅲ and Ⅳ-C and the expression of NF-κB, α-SMA, TGF-β1 and TIMP-1 in the FC group were significantly higher than those in the HC group, the EPA treatment groups, the TC1 group and the TC2 group (P < 0.01). The levels of serum ALT, AST, HA, LN, PC-Ⅲ and Ⅳ-C and the expression of α-SMA, NF-κB, TGF-β1 and TIMP-1 in the TL, TC1 and TC2 groups were significantly higher than those TM and TH groups (P < 0.05). EPA treatment significantly improved liver function, decreased collagen deposition and reversed the pathological changes related to liver fibrosis.

Conclusions: We found that EPA could reduce liver inflammation, suppress liver cell degeneration and necrosis, and reduce the formation of liver fibrous tissue. Its mechanism might be associated with inhibiting the expression of TGF-β1, TIMP-1, NF-κB and α-SMA to block signal transduction pathways in the hepatic fibrosis process. Therefore, EPA, as a traditional Chinese medicine, might be potentially used to prevent and treat hepatic fibrosis in the future. However, further more experiments are necessary to verify its effectiveness and possible signaling pathways.
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http://dx.doi.org/10.5603/FHC.a2022.0011DOI Listing
May 2022

Gegen Qinlian Decoction Relieves Ulcerative Colitis via Adjusting Dysregulated Nrf2/ARE Signaling.

Evid Based Complement Alternat Med 2022 25;2022:2934552. Epub 2022 Apr 25.

Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Objective: Oxidative stress has been proven to be essential in the pathogenesis of ulcerative colitis (UC). Therefore, this study was designed to investigate the effect of Gegen Qinlian decoction (GQ) on the Nrf2 pathway in the treatment of UC and explore the potential mechanism.

Methods: The UC rat model was induced by 5% dextran sodium sulfate (DSS) aqueous solution, and UC rats were treated with GQ orally. The effect of GQ on UC rats was recorded. Human clonal colon adenocarcinoma cells (Caco-2) stimulated by tumor necrosis factor- (TNF-) were employed in this study. After being stimulated with TNF- for 2 hours, Caco-2 cells were cultured with GQ or its major components (puerarin, baicalin, berberine, and liquiritin) for 22 hours. In addition, the Nrf2 gene of Caco-2 cells was silenced and then cultured with GQ for 22 hours. The contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in colonic tissues and Caco-2 cells were detected by assay kits. Reactive oxygen species (ROS) in Caco-2 cells were analyzed by flow cytometry. Quantitative real-time PCR and western blot were employed to detect the mRNA and protein expression of Nrf2 and its related target genes in colon tissues and Caco-2 cells.

Results: GQ alleviated the injured colonic mucosa and activated the expression of Nrf2 in UC rats. In TNF- stimulated Caco-2 cells and Nrf2 silenced Caco-2 cells, GQ also reversed the inhibitory effect of Nrf2. Furthermore, the major components of GQ could activate Nrf2 signaling in TNF- stimulated cells as well. Moreover, the contents of SOD, GSH, MDA, and ROS were restored to normal after treatment with GQ or its major components. Among these components, puerarin, berberine, and liquiritin appear to have a better effect on activating Nrf2 in Overall, GQ can alleviate UC by increasing the activity of Nrf2/ARE signaling and enhancing the effect of antioxidant stress.
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http://dx.doi.org/10.1155/2022/2934552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060978PMC
April 2022

Mitigating the effects of choroidal hyper- and hypo-transmission defects on choroidal vascularity index assessments using optical coherence tomography.

Quant Imaging Med Surg 2022 May;12(5):2932-2946

Department of Bioengineering, University of Washington, Seattle, WA, USA.

Background: Changes in choroidal vascularity index (CVI) are associated with multiple choroid-related ocular diseases. CVI is calculated as the area/volume ratio of vessels in the choroid, which could be affected by alterations in regional signal intensities due to hypo-transmission defects (hypoTDs) caused by drusen and retinal pigment epithelium (RPE) detachments, and hyper-transmission defects (hyperTDs) caused by the absence of RPE. To develop a simulation model to verify the CVI assessments in eyes with hyper/hypoTDs and demonstrate that accurate CVIs can be achieved after attenuation correction on swept-source optical coherence tomography (SS-OCT).

Methods: A simulation model was developed on 6×6 mm macular scans from normal subjects. Signal intensity in a cylindrical region below RPE was altered to mimic hyper/hypoTDs. CVIs were compared inside and outside the simulated regions before and after attenuation correction. CVI assessments of OCT scans from patients with hyperTDs due to geographic atrophy (GA) and from patients with hypoTDs due to drusen that subsequently resolved with the disappearance of the hypoTDs were compared with and without attenuation correction.

Results: Ten normal eyes were recruited to generate the hyper/hypoTD simulation model. In eyes with hypoTDs, CVIs were overestimated, and in eyes with hyperTDs, the CVIs were underestimated (P<0.001). After attenuation correction, the uneven distribution of signal intensity was eliminated and the resulting CVI showed no significant difference compared with the 'ground truth', which is measured from the original scans. Attenuation correction successfully eliminated the influence of hyperTDs caused by GA on CVI measurements (n=38). Quantitatively, no significant difference was found in the CVIs of eyes before and after drusen collapse with attenuation correction (n=8).

Conclusions: The simulation model could reveal the impact of hypo/hyperTDs on CVI quantification in eyes with choroid-involved ocular diseases. The importance of attenuation correction to ensure accuracy in choroidal vessel segmentation was demonstrated by analyzing eyes with GA or drusen.
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http://dx.doi.org/10.21037/qims-21-1093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014140PMC
May 2022

Hypocholesterolemia and Inflammatory Biomarkers Act as Predictors of Severe Vitamin D Deficiency in Patients With Crohn's Disease: A Clinical Analysis of 862 Patients in China.

Front Nutr 2022 13;9:806887. Epub 2022 Apr 13.

Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: In this study, we enrolled 862 patients with Crohn's disease (CD) in China to investigate the correlation between serum vitamin D (SVD) and serum lipids, inflammatory biomarkers, and important clinical parameters.

Materials And Methods: 25(OH)D was measured by LS/MS/MS. Correlation analysis, chi-square tests, and logistic regression analysis were performed to determine the correlations between vitamin D and potential risk factors when vitamin D levels were lower than 10 ng/mL or 20 ng/mL.

Results: The incidence of severe vitamin D deficiency (SVD < 10 ng/mL) in patients with CD was significantly higher than that in healthy controls (28.9 vs. 9.5%). Multinomial logistic regression analysis showed that penetrating disease [odds ratio (OR) = 2.18], low levels of high-density lipoprotein cholesterol (HDL) ( = 1.91), high erythrocyte sedimentation rate ( = 1.73), and platelet count (PLT) ( = 2.71) were regarded as predictors of severe vitamin D deficiency, while only PLT ( = 1.90) and HDL ( = 1.76) were considered as predictors of mild vitamin D deficiency (SVD 10-20 ng/mL).

Conclusion: Our results confirm a higher incidence of severe vitamin D deficiency in patients with CD in China and show that vitamin D deficiency could result from the combined effects of penetrating disease, inflammation, and low levels of HDL.
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http://dx.doi.org/10.3389/fnut.2022.806887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043686PMC
April 2022

Time Interval From Early-Term Antenatal Corticosteroids Administration to Delivery and the Impact on Neonatal Outcomes.

Front Pediatr 2022 11;10:836220. Epub 2022 Apr 11.

Department of Neonatology, The First Affiliated Hospital of Zheng Zhou University, Zhengzhou, China.

Objectives: To determine the association between the time interval from antenatal corticosteroids administration to delivery and neonatal complications in diabetic mothers undergoing early term (37+0 to 38+6 weeks) scheduled cesarean section (ETSCS).

Study Design: A retrospective cohort study of women with any form of diabetes in pregnancy undergoing ETSCS was included. Cases were stratified into the following groups based on the time interval from the first dose of corticosteroids administration to delivery: <2, 2-7, and >7 days. Women undergoing ETSCS, who did not receive corticosteroids were included as controls. We assessed the association between the time interval and neonatal outcomes in a multivariate regression model that controlled for potential confounders. Primary outcomes were the incidence of respiratory distress syndrome (RDS)/transient tachypnea of the newborn (TTN) and neonatal hypoglycemia.

Results: The study cohort comprised 1,165 neonates. Of those, 159 (13.6%) were delivered within 2 days of maternal corticosteroids administration, 131 (11.2%) were delivered within 2-7 days after maternal corticosteroids administration, and 137 (11.8%) delivered more than 7 days after maternal corticosteroids administration. The remaining 738 (63.3%) were not exposed to corticosteroids. Multivariate analysis demonstrated that delivery within any time of antenatal corticosteroids administration was not associated with decreased risks of RDS/TTN. The risk of neonatal hypoglycemia was highest in the delivery of <2 days group (adjusted odds ratio [aOR]: 2.684, 95% confidence interval [CI]: 1.647-4.374 for control group; aOR: 2.827, 95% CI: 1.250-6.392 for delivery 2-7 days group; aOR:2.975, 95% CI: 1.265-6.996 for delivery >7 days group).

Conclusions: Corticosteroids treatment for diabetic mothers undergoing ETSCS was not associated with beneficial neonatal respiratory outcomes. In addition, delivery, <2 days after antenatal corticosteroids administration was associated with an increased risk of neonatal hypoglycemia.
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http://dx.doi.org/10.3389/fped.2022.836220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035847PMC
April 2022

Modulation effect of substantia nigra iron deposition and functional connectivity on putamen glucose metabolism in Parkinson's disease.

Hum Brain Mapp 2022 Apr 26. Epub 2022 Apr 26.

Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.

Neurodegeneration of the substantia nigra affects putamen activity in Parkinson's disease (PD), yet in vivo evidence of how the substantia nigra modulates putamen glucose metabolism in humans is missing. We aimed to investigate how substantia nigra modulates the putamen glucose metabolism using a cross-sectional design. Resting-state fMRI, susceptibility-weighted imaging, and [ F]-fluorodeoxyglucose-PET (FDG-PET) data were acquired. Forty-two PD patients and 25 healthy controls (HCs) were recruited for simultaneous PET/MRI scanning. The main measurements of the current study were images representing iron deposition (28 PD and 25 HCs), standardized uptake value ratio (SUVr) images representing FDG-uptake (33 PD and 25 HCs), and resting state functional connectivity maps from resting state fMRI (34 PD and 25 HCs). An interaction term based on the general linear model was used to investigate the joint modulation effect of nigral iron deposition and nigral-putamen functional connectivity on putamen FDG-uptake. Compared with HCs, we found increased iron deposition in the substantia nigra (p = .007), increased FDG-uptake in the putamen (left: P  < 0.001; right: P  < 0.001), and decreased functional connectivity between the substantia nigra and the anterior putamen (left P  < 0.001, right: P  = 0.007). We then identified significant interaction effect of nigral iron deposition and nigral-putamen connectivity on FDG-uptake in the putamen (p = .004). The current study demonstrated joint modulation effect of the substantia nigra iron deposition and nigral-putamen functional connectivity on putamen glucose metabolic distribution, thereby revealing in vivo pathological mechanism of nigrostriatal neurodegeneration of PD.
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http://dx.doi.org/10.1002/hbm.25880DOI Listing
April 2022

High-performance cellulose acetate-based gas barrier films via tailoring reduced graphene oxide nanosheets.

Int J Biol Macromol 2022 Jun 22;209(Pt A):1450-1456. Epub 2022 Apr 22.

Liaoning Key Lab of Lignocellulose Chemistry and BioMaterials, Liaoning Collaborative Innovation Center for Lignocellulosic Biorefinery, College of Light Industry and Chemical Engineering, Dalian Polytechnic University, Dalian 116034, China. Electronic address:

Improving the gas molecule barrier performance and structural stability of bio-plastic films dramatically contribute to packaging and protective fields. Herein, we proposed a novel nanocomposite film consisting of cellulose acetate (CA)/polyethyleneimine (PEI)/reduced graphene oxide (rGO)-NiCoFeO) with high gas barrier property by applying "molecular glue" and "nano-patching" strategies. Systematical investigations demonstrated that the CA/rGO interfacial interaction was effectively enhanced due to the "molecular glue" role of PEI chains via physical/chemical bonds and the defective regions in rGO plane were nano-patched through hydrophilic interactions between edged oxygen-containing functional groups and ultrafine NiCoFeO nanoparticles (~3 nm). As a result, the oxygen and moisture transmission rates of the prepared CA/PEI/rGO-NPs hybrid film were significantly reduced to 0.31 cm ∗ μm/(m ∗ d ∗ kPa) and 314.23 g/m ∗ 24 h, respectively, which were 99.60% and 54.69% lower than pristine CA films. Meanwhile, the tensile strength of hybrid film was increased from 25.90 MPa to 40.67 MPa. More importantly, the designed nanocomposite film possesses excellent structural stability without obvious GO layer shedding and hydrophobicity attenuation after persistent bending at least 100 times. The exceptional robust and high gas barrier film displays great promising application in food, agriculture, pharmaceuticals and electronic instruments packaging industry.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.04.115DOI Listing
June 2022

Identification of the Wheat (&nbsp;) Gene Family and an Expression Analysis of Candidate Genes Associated with Seed Dormancy and Germination.

Int J Mol Sci 2022 Apr 7;23(8). Epub 2022 Apr 7.

State Key Laboratory of Wheat Biology and Genetic Improvement on Southern Yellow & Huai River Valley, Ministry of Agriculture and Rural Affairs, School of Agronomy, Anhui Agricultural University, Hefei 230036, China.

The IQ67 Domain () gene family plays important roles in plant developmental processes and stress responses. Although IQDs have been characterized in model plants, little is known about their functions in wheat (), especially their roles in the regulation of seed dormancy and germination. Here, we identified 73 members of the gene family from the wheat genome and phylogenetically separated them into six major groups. Gene structure and conserved domain analyses suggested that most members of each group had similar structures. A chromosome positional analysis showed that were unevenly located on 18 wheat chromosomes. A synteny analysis indicated that segmental duplications played significant roles in expansion, and that the gene family underwent strong purifying selection during evolution. Furthermore, a large number of hormone, light, and abiotic stress response elements were discovered in the promoters of , implying their functional diversity. Microarray data for 50 showed different expression levels in 13 wheat tissues. Transcriptome data and a quantitative real-time PCR analysis of wheat varieties with contrasting seed dormancy and germination phenotypes further revealed that seven genes (//////) likely participated in seed dormancy and germination through the abscisic acid-signaling pathway. The study results provide valuable information for cloning and a functional investigation of candidate genes controlling wheat seed dormancy and germination; consequently, they increase our understanding of the complex regulatory networks affecting these two traits.
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http://dx.doi.org/10.3390/ijms23084093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025732PMC
April 2022

Effects of acute ammonia nitrogen exposure on metabolic and immunological responses in the Hong Kong oyster Crassostrea hongkongensis.

Ecotoxicol Environ Saf 2022 Jun 18;237:113518. Epub 2022 Apr 18.

Key Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China. Electronic address:

Ammonia nitrogen, a major oxygen-consuming pollutant in the environment, can adversely affect aquatic organisms such as fish, bivalves, and crustaceans. We investigated the toxic effects of ammonia nitrogen on the Hong Kong oyster, Crassostrea hongkongensis, using flow cytometry and H nuclear magnetic resonance metabolomics. Exposure to ammonia nitrogen caused time- and concentration-dependent alterations in various immune parameters in hemocytes and impaired the metabolic profiles of the gills. We observed changes in the rate of apoptosis, esterase activity, lysosomal mass, hemocyte counts, phagocytic activity, and mitochondrial mass. Exposure affected metabolic pathways involved in energy metabolism, osmotic balance, and oxidative stress. We concluded that ammonia nitrogen induces metabolic and hematological dysfunction in C. hongkongensis, and our findings provide insights into the biochemical defense strategies of bivalves exposed to acute high-concentration ammonia nitrogen.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113518DOI Listing
June 2022

Glucose-sensitive delivery of tannic acid by a photo-crosslinked chitosan hydrogel film for antibacterial and anti-inflammatory therapy.

J Biomater Sci Polym Ed 2022 May 4:1-20. Epub 2022 May 4.

School and Hospital of Stomatology, Shanxi Medical University, Taiyuan, China.

A glucose-sensitive antibacterial and anti-inflammatory hydrogel film with controlled release of tannic acid (TA) was synthesized using chitosan (CS). Specifically, the photo-crosslinked CS hydrogel was first obtained and then immersed in TA solution to generate composite hydrogel film with enhanced mechanical properties. Subsequently, N-hydroxysuccinimide/1-ethyl-3-(3-dimethylaminopropyl) carbodiimide based coupling chemistry was used to covalently crosslink glucose oxidase (GOx) to CS to obtain glucose sensitivity. The physicochemical properties, including chemical composition, enzyme-related characteristics, glucose responsiveness, and mechanical strength, were thoroughly investigated, followed by the cytotoxicity, antibacterial and anti-inflammatory tests. The results showed that the GOx immobilized on the film surface by covalent bonding gave better stability than those that were physically adsorbed. In addition, it could quickly and correspondingly modify its inner pore structure in response to the glucose stimulus and then control the loaded TA release. Meanwhile, the TA addition could enhance the film's mechanical properties. The composite hydrogel film demonstrated adequate biocompatibility and can inhibit NO, IL-6, and TNF-α production in stimulated macrophages, as well as growth, demonstrating effective antibacterial and anti-inflammatory activity.
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http://dx.doi.org/10.1080/09205063.2022.2068948DOI Listing
May 2022

Flame retardancy effects between expandable graphite and halloysite nanotubes in silicone rubber foam.

RSC Adv 2021 Apr 13;11(23):13821-13831. Epub 2021 Apr 13.

College of Materials Science and Engineering, Xi'an University of Science and Technology Xi'an 710054 P. R. China.

The effect of expandable graphite (EG) and modified halloysite nanotubes (HNTs) on the flame retardant properties of silicone rubber foam (SiF) was studied in this paper. Modified HNTs were obtained by surface modification of the silane-coupling agent A-171. The flame retardancy of SiF was studied by limiting oxygen index (LOI), vertical combustion and cone calorimeter tests. The mechanical properties of SiF were analyzed by a universal mechanical testing machine. The LOI results showed that EG/[email protected] could enhance the LOI of SiF. The cone calorimeter test results showed that EG/[email protected] effectively reduced the peak heat release rate, the total heat release rate, the smoke production rate, the total smoke production rate, the CO production rate and the CO production rate and increased the carbon residue rate. TGA shows that main chain pyrolysis temperature of the SiF is delayed by 123 °C. The mechanical properties test results showed that EG/[email protected] improved the tensile strength of SiF. These results indicated that EG/[email protected] can significantly improve the flame retardant performance of SiF.
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http://dx.doi.org/10.1039/d1ra01409aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8697518PMC
April 2021

Simple and sensitive colorimetric sensors for the selective detection of Cu(ii).

RSC Adv 2021 Mar 23;11(19):11732-11738. Epub 2021 Mar 23.

Harway Pharma Tech Co., Ltd. China.

A simple, sensitive colorimetric probe for detecting Cu(ii) ions with fast response has been established with a detection limit of 2.82 μM. UV-Vis spectroscopy along with metal ion response, selectivity, stoichiometry, competition was investigated. In the presence of copper(ii), the UV-Vis spectrum data showed significant changes and the colorimetric detection showed a color change from colorless to yellow. After the selective binding of receptor L with Cu(ii), the UV-visible absorption at 355 nm decreased dramatically, a new absorbance band appeared at 398 nm and its intensity enhanced with the increase in the amount of Cu(ii). Moreover, it exhibited highly selective and sensitive recognition towards Cu(ii) ions in the presence of other cations over the pH range of 7-11. The complex structure was verified by FT-IR spectroscopy, elemental analysis and quantum mechanical calculations using B3LYP/6-31G(d) to illustrate the complex formation between L and Cu(ii). According to the Job plot and the quantum mechanical calculations, the stoichiometric ratio for the complex formation was proposed to be 1 : 1.
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http://dx.doi.org/10.1039/d0ra09910dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695964PMC
March 2021

Triglyceride-Glucose Index Is Related to Carotid Plaque and Its Stability in Nondiabetic Adults: A Cross-Sectional Study.

Front Neurol 2022 24;13:823611. Epub 2022 Mar 24.

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Carotid plaque plays an important role in the development of stroke. The triglyceride-glucose (TyG) index is a reliable alternative marker of insulin resistance. However, there are limited data regarding the relationship between TyG index and carotid plaque and its stability in nondiabetic adults.

Methods: This study was carried out on 24,895 urban workers (10,978 men and 13,917 women) aged 20 years or older who participated in a comprehensive health screening between January 2016 and December 2017 at the First Affiliated Hospital of Zhengzhou University, China. Carotid plaque was assessed using ultrasonography. TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL) /2]. Logistic regression models and restricted cubic spline (RCS) models were used to estimate the association of the TyG index with carotid plaque and its stability by odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Carotid plaque was detected in 5,668 (22.8%) respondents, with stable and unstable plaque accounting for 2,511 (10.1%) and 3,158 (12.7%), respectively. There was a significant positive association between the prevalence of carotid plaque and TyG index quartile levels, and the same associations were observed for the prevalence of stable and unstable carotid plaque ( for trend <0.0001). The multivariable-adjusted ORs (95% CIs) for the highest vs. lowest quartile of TyG index were 1.30 (1.15-1.47) for carotid plaque, 1.38 (1.17-1.63) for stable carotid plaque, and 1.24 (1.07-1.43) for unstable carotid plaque. The RCS analysis showed a linear association between TyG index and carotid plaque, and linear associations were also observed between TyG index and both stable carotid plaque and unstable carotid plaque ( for linearity<0.05).

Conclusion: Our findings suggested that the TyG index was significantly associated with carotid plaque and might be a useful indicator for the early identification of carotid plaque in nondiabetic subjects.
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http://dx.doi.org/10.3389/fneur.2022.823611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987979PMC
March 2022

Novel Polymer/Barium Intercalated Vanadium Pentoxide with Expanded Interlayer Spacing as High-Rate and Durable Cathode for Aqueous Zinc-Ion Batteries.

ACS Appl Mater Interfaces 2022 Apr 7;14(15):17415-17425. Epub 2022 Apr 7.

School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.

Rechargeable aqueous zinc-ion batteries (AZIBs) exhibit great potential in large-scale energy storage systems. However, limited reaction kinetics and poor long-cycle stability restrict the application of vanadium oxide cathode materials. Herein, we designed and successfully synthesized a novel composite material with polyethylene glycol (PEG) and barium cation (Ba) preintercalated between the layers of vanadium pentoxide, denoted as PEG-BaVO·HO (PEG-BVO), as a cathode material of AZIBs. The optimized PEG-BVO material shows a uniform nanobelt-like structure with the expanded interlayer spacing of 1.07 nm, significantly promoting the transport kinetics of zinc ions. The theoretical calculation results unravel that an interlayer spacing of 1.07 nm may be at the most stable state for this layered composite structure, ensuring a robust architecture for rapid reversible (de)intercalation of zinc ions. As a result, the PEG-BVO electrode (with a large mass loading of 4 mg cm) exhibits an outstanding electrochemical performance including a high specific capacity (345 mAh g at 0.1 A g), decent rate capability (up to 175 mAh g at 10 A g), and long-term cycling stability (98.8% capacity retention upon 4000 cycles at 6 A g). Our discovery provides a new guest preinsertion strategy to construct a robust layered vanadium-based electrode with the expanded interlayer spacing, and the as-prepared PEG-BaVO·HO shows great potential as a high-rate positive electrode for AZIBs.
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http://dx.doi.org/10.1021/acsami.2c01698DOI Listing
April 2022

Mesoporous [email protected] nanofiber membranes single-nozzle electrospinning for urine metabolism analysis of smokers.

Analyst 2022 Apr 11;147(8):1688-1694. Epub 2022 Apr 11.

Department of Chemistry, Fudan University, Shanghai, 200433, PR China.

An effective matrix is very important for impact laser desorption/ionization mass spectrometry (LDI-MS), and the physicochemical properties of the matrix nanostructures can impact the LDI-MS performance. In this study, a simple and efficient single-nozzle electrospinning strategy using polystyrene (PS) spheres and polyvinyl pyrrolidone (PVP) to construct a mesoporous [email protected] nanofiber membrane was developed. Compared with the NiO and ZnO nanomaterials alone, the obtained [email protected] nanofiber membrane was proven to be an efficient material as the matrix to increase the intensity of the mass spectrum speaks of small molecules. The [email protected] nanofiber membrane was used as the matrix for the LDI-MS method for the urine metabolism analysis of smokers, which revealed differences in the metabolic and the possible metabolic markers of smokers through the statistical analysis of the urine samples of 27 smokers and 11 nonsmoker controls.
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http://dx.doi.org/10.1039/d2an00033dDOI Listing
April 2022

Correction to: [18F]FDG PET/MRI and magnetoencephalography may improve presurgical localization of temporal lobe epilepsy.

Eur Radiol 2022 May;32(5):3611

Department of Radiology and Nuclear Medicine, Xuanwu Hospital Capital Medical University, Beijing, 100053, China.

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http://dx.doi.org/10.1007/s00330-022-08546-4DOI Listing
May 2022

Integrated Positron Emission Tomography/Magnetic Resonance Imaging for Resting-State Functional and Metabolic Imaging in Human Brain: What Is Correlated and What Is Impacted.

Front Neurosci 2022 2;16:824152. Epub 2022 Mar 2.

Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.

Integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) could simultaneously obtain both functional MRI (fMRI) and F-fluorodeoxyglucose (FDG) PET and thus provide multiparametric information for the analysis of brain metabolism. In this study, we aimed to, for the first time, investigate the interplay of simultaneous fMRI and FDG PET scan using a randomized self-control protocol. In total, 24 healthy volunteers underwent PET/MRI scan for 30-40 min after the injection of FDG. A 22-min brain scan was separated into MRI-off mode (without fMRI pulsing) and MRI-on mode (with fMRI pulsing), with each one lasting for 11 min. We calculated the voxel-wise fMRI metrics (regional homogeneity, amplitude of low-frequency fluctuations, fractional amplitude of low-frequency fluctuations, and degree centrality), resting networks, relative standardized uptake value ratios (SUVr), SUVr slope, and regional cerebral metabolic rate of glucose (rCMRGlu) maps. Paired two-sample -tests were applied to assess the statistical differences between SUVr, SUVr slope, correlation coefficients of fMRI metrics, and rCMRGlu between MRI-off and MRI-on modes, respectively. The voxel-wise whole-brain SUVr revealed no statistical difference ( > 0.05), while the SUVr slope was significantly elevated in sensorimotor, dorsal attention, ventral attention, control, default, and auditory networks ( < 0.05) during fMRI scan. The task-based group independent-component analysis revealed that the most active network components derived from the combined MRI-off and MRI-on static PET images were frontal pole, superior frontal gyrus, middle temporal gyrus, and occipital pole. High correlation coefficients were found among fMRI metrics with rCMRGlu in both MRI-off and MRI-on mode ( < 0.05). Our results systematically evaluated the impact of simultaneous fMRI scan on the quantification of human brain metabolism from an integrated PET/MRI system.
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http://dx.doi.org/10.3389/fnins.2022.824152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926297PMC
March 2022

Association between cardiorespiratory fitness and risk of all-cause and cause-specific mortality.

Eur J Clin Invest 2022 Mar 16:e13770. Epub 2022 Mar 16.

Department of Social Medicine and Health Service Management, College of Public Health, Zhengzhou University, Zhengzhou, China.

Objective: The association of cardiorespiratory fitness (CRF) with all-cause and cause-specific mortality remains unclear in Chinese population. This study aimed to evaluate the risk of all-cause, cardiovascular disease (CVD), cancer and other-cause mortality in Chinese adults using estimated CRF (eCRF).

Patients And Methods: We analysed data for 15,566 participants aged ≥20 years recruited in The Rural Chinese Cohort Study during 2007 to 2008 and followed for mortality during 2013 to 2014. eCRF was calculated with sex-specific longitudinal non-exercise algorithms. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality risk according to baseline eCRF.

Results: During a median of 6.01 years of follow-up, 859 deaths occurred, including 359 from CVD, 221 from cancer, and 279 from other causes. Each 1 metabolic equivalent increment in eCRF was associated with decreased risk of all-cause mortality (men: HR 0.70, 95% CI [0.66-0.74]; women: 0.59, [0.54-0.64]); CVD mortality (men: 0.70 [0.64-0.77]; women: 0.55, [0.48-0.62]); and other-cause mortality (men: 0.68 [0.62-0.75]; women: 0.57, [0.49-0.66]). The area under receiver operating characteristic curve was significantly higher for eCRF than its modifiable components (waist circumference, body mass index and resting heart rate) in predicting all-cause and cause-specific mortality incidence (all p < .001).

Conclusion: eCRF was inversely associated with all-cause, CVD and other-cause mortality.
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http://dx.doi.org/10.1111/eci.13770DOI Listing
March 2022

Characterization of the wheat VQ protein family and expression of candidate genes associated with seed dormancy and germination.

BMC Plant Biol 2022 Mar 15;22(1):119. Epub 2022 Mar 15.

College of Agronomy, Key Laboratory of Wheat Biology and Genetic Improvement On Southern Yellow & Huai River Valley, Ministry of Agriculture and Rural Affairs, Anhui Agricultural University, Hefei, 230036, Anhui, China.

Background: Seed dormancy and germination determine wheat resistance to pre-harvest sprouting and thereby affect grain yield and quality. Arabidopsis VQ genes have been shown to influence seed germination; however, the functions of wheat VQ genes have not been characterized.

Results: We identified 65 TaVQ genes in common wheat and named them TaVQ1-65. We identified 48 paralogous pairs, 37 of which had Ka/Ks values greater than 1, suggesting that most TaVQ genes have experienced positive selection. Chromosome locations, gene structures, promoter element analysis, and gene ontology annotations of the TaVQs showed that their structures determined their functions and that structural changes reflected functional diversity. Transcriptome-based expression analysis of 62 TaVQ genes and microarray analysis of 11 TaVQ genes indicated that they played important roles in diverse biological processes. We compared TaVQ gene expression and seed germination index values among wheat varieties with contrasting seed dormancy and germination phenotypes and identified 21 TaVQ genes that may be involved in seed dormancy and germination.

Conclusions: Sixty-five TaVQ proteins were identified for the first time in common wheat, and bioinformatics analyses were used to investigate their phylogenetic relationships and evolutionary divergence. qRT-PCR data showed that 21 TaVQ candidate genes were potentially involved in seed dormancy and germination. These findings provide useful information for further cloning and functional analysis of TaVQ genes and introduce useful candidate genes for the improvement of PHS resistance in wheat.
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http://dx.doi.org/10.1186/s12870-022-03430-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8925178PMC
March 2022

Epidemiology of extrapulmonary tuberculosis among pediatric inpatients in mainland China: a descriptive, multicenter study.

Emerg Microbes Infect 2022 Dec;11(1):1090-1102

Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China.

Pediatric tuberculosis (TB) is a serious infectious disease that affects many children worldwide and is more likely to be extrapulmonary than adult TB. However, the clinical and epidemiological profile, and cost burden of pediatric extrapulmonary TB (EPTB) in China remain unknown. Here, we conducted a descriptive, multicenter study of pediatric TB patients from 22 hospitals across all six regions in China from October 2015 to December 2018. Of 4,654 patients, 54.23% (2,524) had pulmonary TB (PTB), 17.76% (827) had EPTB, and 28.00% (1,303) had concurrent extrapulmonary and pulmonary TB (combined TB). Compared with PTB, EPTB and combined TB were associated with lower hospitalization frequency (2.43 and 2.21 vs. 3.16 times), longer length of stay (10.61 and 11.27 vs. 8.56 days), and higher rate of discharge against medical advice (8.46% and 9.44% vs. 5.67%). EPTB was associated with higher mortality (0.97% vs. 0.24% and 0.31%), higher rate of low birth weight (17.69% vs. 6.79% and 6.22%), worse diagnosis at the first visit (21.16% vs. 34.67% and 44.47%), and worse hospitalization plan situation (4.35% vs. 7.81% and 7.44%), compared with PTB and combined TB. EPTB and combined TB had higher financial burdens (17.67% and 16.94% vs. 13.30%) and higher rates of catastrophic expenditure (8.22% and 9.59% vs. 5.03%), compared with PTB. Meningitis TB (34.18%) was the most frequent form of total extrapulmonary infection and had the highest cost burden and rate of catastrophic expenditure. In conclusion, improved screening approaches for pediatric EPTB are needed to reduce diagnostic challenges and financial burden.
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http://dx.doi.org/10.1080/22221751.2022.2054367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009909PMC
December 2022

Beyond the Motor Cortex: Thalamic Iron Deposition Accounts for Disease Severity in Amyotrophic Lateral Sclerosis.

Front Neurol 2022 24;13:791300. Epub 2022 Feb 24.

Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objective: Previous studies have reliably identified iron deposition in the motor cortex as potential pathogenesis of amyotrophic lateral sclerosis (ALS). Here, we intended to investigate iron deposition, gray matter (GM) atrophy, and their associations with disease severity in the motor cortex and the thalamus in patients with ALS.

Methods: A total of 34 patients with ALS (age 51.31 ± 8.24 years, 23 males) and 34 nonneurological controls (age 50.96 ± 9.35 years, 19 males) were enrolled between 2018 and 2020. The Revised ALS Functional Rating Scale (ALSFRS-R) and the Penn upper motor neuron (UMN) score were measured. MRI data included quantitative susceptibility mapping (QSM) for iron deposition and three-dimensional (3D) T1 for gray matter volume. After a between-group comparison, Pearson's correlation coefficient was used for identifying correlations of iron deposition, GM volume, and clinical measurements.

Results: The two-sample -tests revealed increased iron deposition in the left precentral gyrus (peak voxel = 4.78, = 0.03) and the thalamus (peak voxel: right: = 6.38, < 0.001; left: = 4.64, = 0.02) in patients with ALS. GM volume of the precentral gyrus ( = -2.42, = 0.02) and the bilateral thalamus ( = -4.10, < 0.001) were reduced. Negative correlations were found between the increased QSM values and the decreased GM volume ( < 0.04, one-tailed) in patients with ALS. Iron deposition in the left precentral gyrus was positively correlated with the UMN score ( = 0.40, = 0.02) and the GM volume was negatively correlated with the UMN score ( = -0.48, = 0.004). Negative correlation between thalamic iron deposition and the ALSFRS-R ( = -0.36, = 0.04) score was observed.

Discussion: Iron deposition in the thalamus, in addition to the motor cortex, is accompanied by GM atrophy and is associated with disease severity in patients with ALS, indicating that the thalamus is also a pathological region in patients with ALS.
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http://dx.doi.org/10.3389/fneur.2022.791300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8907117PMC
February 2022

Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination.

Ann Rheum Dis 2022 Mar 11. Epub 2022 Mar 11.

Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, China

Objectives: COVID-19 vaccination often triggers a constellation of transitory inflammatory symptoms. Gout is associated with several comorbidities linked to poor outcomes in COVID-19, and gout flares can be triggered by some vaccinations. We analysed the risk of gout flares in the first 3 months after COVID-19 vaccination with inactivated virus, and whether colchicine can prevent gout flares following post-COVID-19 vaccination.

Methods: A clinical delivery population-based cross-sectional study was conducted in the Gout Clinic at the Affiliated Hospital of Qingdao University between February and October 2021. Study participants were selected using a systematic random sampling technique among follow-up patients with gout. We collected data, including vaccinations and potential risk factors, using a combination of interviews, health QR codes and medical records. Logistic regression was used to adjust for covariates.

Results: We enrolled 549 gout participants (median age 39 years, 84.2% vaccinated). For the 462 patients who received COVID-19 vaccine, 203 (43.9%) developed at least one gout flare in the 3 months after vaccination. Most of these flares were experienced within 1 month after the first (99/119 (83.2%)) or second (70/115 (60.9%)) dose of vaccine. Compared with unvaccinated participants, COVID-19 vaccination was associated with higher odds of gout flare within 3 months (adjusted OR 6.02; 95% CI 3.00 to 12.08). Colchicine use was associated with 47% less likelihood of postvaccine gout flare.

Conclusion: COVID-19 vaccination was associated with increased odds of gout flare, which developed mainly in month 1 after each vaccine dose, and was negatively associated with colchicine prophylaxis.
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http://dx.doi.org/10.1136/annrheumdis-2022-222199DOI Listing
March 2022

Free-Breathing, Non-Gated Heart-To-Brain CTA in Acute Ischemic Stroke: A Feasibility Study on Dual-Source CT.

Front Neurol 2022 22;13:616964. Epub 2022 Feb 22.

Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Purpose: To validate the feasibility of free-breathing, non-gated, high-pitch heart-to-brain computed tomography arteriography (CTA) in acute ischemic stroke and the capability of non-gated heart-to-brain CTA in showing cardiac anatomy.

Materials And Methods: The study protocol was approved by the institutional medical ethics review board. Free-breathing, non-gated, high-pitch heart-to-brain CTA was performed on patients with acute ischemic stroke referred for multimodal CT using a third-generation dual-source CT. Patients scheduled for ECG-triggered heart-to-brain CTA served as controls. Quantitative and/or qualitative image quality of the four cardiac chambers, left atrial appendage, interventricular and interatrial septa, carotid arteries, and coronary arteries were evaluated and compared between the two groups.

Results: Free-breathing, non-gated, high-pitch heart-to-brain CTA was performed on 30 patients with acute ischemic stroke, whereas the control group included 31 cases. There is no significant difference in the image quality of CTAs between the two groups at cardiac chambers and carotid arteries. The image quality of coronary arteries also showed no significant difference between the two groups. The mean dose length products of CTA in the two groups were 129.1 ± 30.5 mGy cm and 121.6 ± 30.3 mGy cm, respectively. Cardiac abnormality can be shown in patients with acute ischemic stroke.

Conclusion: It is feasible to use free-breathing, non-gated, high-pitch heart-to-brain CTA with dual-source CT in acute ischemic stroke for cardiac etiology screening.
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http://dx.doi.org/10.3389/fneur.2022.616964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8902348PMC
February 2022

Heterogeneous Multidomain Recommender System Through Adversarial Learning.

IEEE Trans Neural Netw Learn Syst 2022 Mar 10;PP. Epub 2022 Mar 10.

To solve the user data sparsity problem, which is the main issue in generating user preference prediction, cross-domain recommender systems transfer knowledge from one source domain with dense data to assist recommendation tasks in the target domain with sparse data. However, data are usually sparsely scattered in multiple possible source domains, and in each domain (source/target) the data may be heterogeneous, thus it is difficult for existing cross-domain recommender systems to find one source domain with dense data from multiple domains. In this way, they fail to deal with data sparsity problems in the target domain and cannot provide an accurate recommendation. In this article, we propose a novel multidomain recommender system (called HMRec) to deal with two challenging issues: 1) how to exploit valuable information from multiple source domains when no single source domain is sufficient and 2) how to ensure positive transfer from heterogeneous data in source domains with different feature spaces. In HMRec, domain-shared and domain-specific features are extracted to enable the knowledge transfer between multiple heterogeneous source and target domains. To ensure positive transfer, the domain-shared subspaces from multiple domains are maximally matched by a multiclass domain discriminator in an adversarial learning process. The recommendation in the target domain is completed by a matrix factorization module with aligned latent features from both the user and the item side. Extensive experiments on four cross-domain recommendation tasks with real-world datasets demonstrate that HMRec can effectively transfer knowledge from multiple heterogeneous domains collaboratively to increase the rating prediction accuracy in the target domain and significantly outperforms six state-of-the-art non-transfer or cross-domain baselines.
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http://dx.doi.org/10.1109/TNNLS.2022.3154345DOI Listing
March 2022

Distinct Functional Alterations and Therapeutic Options of Two Pathological De Novo Variants of the T292 Residue of GABRA1 Identified in Children with Epileptic Encephalopathy and Neurodevelopmental Disorders.

Int J Mol Sci 2022 Mar 1;23(5). Epub 2022 Mar 1.

Djavad Mowafaghian Centre for Brain Health and Department of Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.

Mutations of GABAR have reportedly led to epileptic encephalopathy and neurodevelopmental disorders. We have identified a novel de novo T292S missense variant of GABRA1 from a pediatric patient with grievous global developmental delay but without obvious epileptic activity. This mutation coincidentally occurs at the same residue as that of a previously reported GABRA1 variant T292I identified from a pediatric patient with severe epilepsy. The distinct phenotypes of these two patients prompted us to compare the impacts of the two mutants on the receptor function and to search for suitable therapeutics. In this study, we used biochemical techniques and patch-clamp recordings in HEK293 cells overexpressing either wild-type or mutated rat recombinant GABARs. We found that the α1T292S variant significantly increased GABA-evoked whole-cell currents, shifting the dose-response curve to the left without altering the maximal response. In contrast, the α1T292I variant significantly reduced GABA-evoked currents, shifting the dose-response curve to the right with a severely diminished maximum response. Single-channel recordings further revealed that the α1T292S variant increased, while the α1T292I variant decreased the GABAR single-channel open time and open probability. Importantly, we found that the T292S mutation-induced increase in GABAR function could be fully normalized by the negative GABAR modulator thiocolchicoside, whereas the T292I mutation-induced impairment of GABAR function was largely rescued with a combination of the GABAR positive modulators diazepam and verapamil. Our study demonstrated that α1T292 is a critical residue for controlling GABAR channel gating, and mutations at this residue may produce opposite impacts on the function of the receptors. Thus, the present work highlights the importance of functionally characterizing each individual GABAR mutation for ensuring precision medicine.
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http://dx.doi.org/10.3390/ijms23052723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911174PMC
March 2022

Isolation, Structural Characterization and Macrophage Activation Activity of an Acidic Polysaccharide from Raspberry Pulp.

Molecules 2022 Mar 3;27(5). Epub 2022 Mar 3.

College of Ecological and Environmental Engineering, Qinghai University, Xining 810016, China.

The discovery of safe and effective plant polysaccharides with immunomodulatory effects has become a research hotspot. Raspberry is an essential commercial fruit and is widely distributed, cultivated, and consumed worldwide. In the present study, a homogeneous acidic polysaccharide (RPP-2a), with a weight-average molecular weight (Mw) of 55582 Da, was isolated from the pulp of raspberries through DEAE-Sepharose Fast Flow and Sephadex G-200 chromatography. RPP-2a consisted of rhamnose, arabinose, galactose, glucose, xylose, galacturonic acid and glucuronic acid, with a molar ratio of 15.4:9.6:7.6:3.2:9.1:54.3:0.8. The results of Fourier transform infrared spectroscopy (FT-IR), gas chromatography-mass spectrometer (GC-MS), 1D-, and 2D-nuclear magnetic resonance (NMR) analyses suggested that the backbone of RPP-2a was primarily composed of →2)--L-Rha-(1→, →2,4)--L-Rha-(1→, →4)--D-GalA-(1→, and →3,4)--D-Glc-(1→ sugar moieties, with side chains of -L-Ara-(1→, -L-Ara-(1→, and -D-Gal-(1→3)--D-Gal-(1→ residues linked to the O-4 band of rhamnose and O-3 band of glucose residues. Furthermore, RPP-2a exhibited significant macrophage activation activity by increasing the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and the expression of inducible nitric oxide synthase (iNOS) and cytokines at the transcriptional level in RAW264.7 cells. Overall, the results indicate that RPP-2a can be utilized as a potential natural immune-enhancing agent.
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http://dx.doi.org/10.3390/molecules27051674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911918PMC
March 2022

Coordinated Cross-Talk Between the Myc and Mlx Networks in Liver Regeneration and Neoplasia.

Cell Mol Gastroenterol Hepatol 2022 5;13(6):1785-1804. Epub 2022 Mar 5.

Division of Hematology/Oncology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania; Hillman Comprehensive Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Department of Microbiology and Molecular Genetics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address:

Background & Aims: The c-Myc (Myc) Basic helix-loop-helix leucine zipper (bHLH-ZIP) transcription factor is deregulated in most cancers. In association with Max, Myc controls target genes that supervise metabolism, ribosome biogenesis, translation, and proliferation. This Myc network crosstalks with the Mlx network, which consists of the Myc-like proteins MondoA and ChREBP, and Max-like Mlx. Together, this extended Myc network regulates both common and distinct gene targets. Here, we studied the consequence of Myc and/or Mlx ablation in the liver, particularly those pertaining to hepatocyte proliferation, metabolism, and spontaneous tumorigenesis.

Methods: We examined the ability of hepatocytes lacking Mlx (MlxKO) or Myc+Mlx (double KO [DKO]) to repopulate the liver over an extended period of time in a murine model of type I tyrosinemia. We also compared this and other relevant behaviors, phenotypes, and transcriptomes of the livers with those from previously characterized MycKO, ChrebpKO, and MycKO × ChrebpKO mice.

Results: Hepatocyte regenerative potential deteriorated as the Extended Myc Network was progressively dismantled. Genes and pathways dysregulated in MlxKO and DKO hepatocytes included those pertaining to translation, mitochondrial function, and hepatic steatosis resembling nonalcoholic fatty liver disease. The Myc and Mlx Networks were shown to crosstalk, with the latter playing a disproportionate role in target gene regulation. All cohorts also developed steatosis and molecular evidence of early steatohepatitis. Finally, MlxKO and DKO mice showed extensive hepatic adenomatosis.

Conclusions: In addition to showing cooperation between the Myc and Mlx Networks, this study showed the latter to be more important in maintaining proliferative, metabolic, and translational homeostasis, while concurrently serving as a suppressor of benign tumorigenesis. GEO accession numbers: GSE181371, GSE130178, and GSE114634.
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http://dx.doi.org/10.1016/j.jcmgh.2022.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046243PMC
May 2022

A protein vaccine with Alum/c-GAMP/poly(I:C) rapidly boosts robust immunity against SARS-CoV-2 and variants of concern.

Chem Commun (Camb) 2022 Mar 22;58(24):3925-3928. Epub 2022 Mar 22.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, College of Chemistry, Central China Normal University, Wuhan 430079, China.

Adjuvants are important components in vaccines to increase the immunogenicity of proteins and induce optimal immunity. In this study, we designed a novel ternary adjuvant system Alum + c-GAMP + poly(I:C) with STING agonist 3,3'-c-GAMP (c-GAMP) and TLR3 agonist poly(I:C) co-adsorbed on the conventional adjuvant aluminum gel (Alum), and further constructed an S1 protein vaccine. Two doses of vaccination with the ternary adjuvant vaccine were sufficient to induce a balanced Th1/Th2 immune response and robust humoral and cellular immunity. Additionally, the ternary adjuvant group had effective neutralizing activity against live virus SARS-CoV-2 and pseudovirus of all variants of concern (alpha, beta, gamma, delta and omicron). These results indicate that the ternary adjuvants have a significant synergistic effect and can rapidly trigger potent immune responses; the combination of the ternary adjuvant system with S1 protein is a promising COVID-19 vaccine candidate.
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http://dx.doi.org/10.1039/d2cc00271jDOI Listing
March 2022
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