Publications by authors named "Tong Zhang"

1,844 Publications

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Phthalic acid esters in grains, vegetables, and fruits: concentration, distribution, composition, bio-accessibility, and dietary exposure.

Environ Sci Pollut Res Int 2022 Aug 8. Epub 2022 Aug 8.

Department of Environmental Science and Engineering, School of Geography and Tourism, Shaanxi Normal University, Xi'an, 710119, People's Republic of China.

Grain, vegetable, and fruit samples were collected from Xi'an City in Northwest China and analyzed for the characteristics, bio-accessibility, and dietary exposure of 22 phthalic acid esters (PAEs). All the studied PAEs were ubiquitously detected, except for diethyl phthalate in vegetables and fruits. In grains, the sum of detectable PAEs (∑22PAEs) varied between 0.0840 and 40.0 µg/g, with a mean of 4.19 µg/g, presenting rice >  > beans > flour, and the major PAEs were di-n-butyl phthalate (DnBP) and bis(2-ethylhexyl) phthalate (DEHP). In vegetables, the ∑21PAEs ranged from 0.190 to 56.8 µg/g, with a mean of 8.07 µg/g, exhibiting leafy vegetables > root vegetables > fruits-vegetables > fungus > cauliflower > beans, and the main PAEs were di-iso-butyl phthalate (DiBP), DnBP, DEHP, di-iso-nonyl phthalate (DiNP), and di-iso-decyl phthalate (DiDP). In fruits, the ∑21PAEs varied between 0.300 and 12.6 µg/g, with a mean of 3.97 µg/g, presenting spring-winter season fruits > summer-autumn season fruits and shell-less fruits > shelled fruits, and the predominant PAEs were DiBP, DnBP, DEHP, DiNP, and DiDP. The bio-accessibility of PAEs in the gastrointestinal fluid simulant was higher than that in the single gastric or intestinal fluid simulant. The bio-accessibility of PAEs was correlated with the physiochemical properties of PAEs. The estimated daily intakes (EDIs) of human dietary exposure to PAEs were lower than the reference doses of United States Environmental Protection Agency and the tolerable dairy intakes (TDIs) of European Food Safety Authority (EFSA), except for the EDI of DnBP in the grains and DiBP in the vegetables higher than or close to the TDI of the EFSA. The research suggested that special attention should be paid to human dietary exposure to DnBP and DiBP, especially for children and adolescents.
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http://dx.doi.org/10.1007/s11356-022-22415-zDOI Listing
August 2022

Harm of circadian misalignment to the hearts of the adolescent wistar rats.

J Transl Med 2022 08 6;20(1):352. Epub 2022 Aug 6.

School of Rehabilitation Medicine, Capital Medical University, Beijing, 100068, China.

Purpose: The purpose of this study was to observe the harm of circadian misalignment (CM), caused by an inverted photoperiod (IP), on the hearts of the adolescent Wistar rats, and to explore the mechanisms leading to harm.

Methods: An IP was used to create a CM model. A total of 174 Wistar rats were randomly divided into circadian alignment (CA) and CM groups (87 rats per group). The different activity rhythms of the two groups of rats were adjusted through different light/dark cycles for 90 days. We recorded the rhythmic activity trajectory and sleep time of the rats. After 90 days of modeling, we performed various analyses (i.e., blood pressure, weight, cardiac ultrasound tests, serological tests, cardiac tissue immunofluorescence, immunohistochemistry, transmission electron microscopy on myocardial mitochondria, western blotting, and quantitative polymerase chain reactions).

Results: (1) The IP protocol caused CM in rats. (2) CM rats showed significantly higher blood pressure during the day (resting phase). They also showed significantly higher serum levels of angiotensin II and epinephrine during the day compared to the CA rats. (3) CM caused up-regulation of gene expression of adrenergic receptors α1 (α1-AR) and β1 (β1-AR) and down-regulation of the glucocorticoid receptor (Gr) gene expression in rat hearts. It also caused downregulation of Bmal1 expression. In addition, the changes in Bmal1 and Per2 correlated with the changes in β1-AR and α1-AR. (4) CM had adverse effects on multiple molecular proteins of the heart. (5) CM increased the collagen fibers in the rat heart and increased the destruction of mitochondria. (6) Eventually, CM caused a decrease in the pumping function of the heart and decreased the coronary blood flow rate.

Conclusions: (1) CM significantly affected the cardiac structure and function in the adolescent rats through a variety of mechanisms. (2) CM can regulate the expression of myocardial clock genes, and it is likely to have an impact on the heart through this pathway.
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http://dx.doi.org/10.1186/s12967-022-03546-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356460PMC
August 2022

Sulfide modifies physicochemical properties and mercury adsorption of microplastics.

Sci Total Environ 2022 Aug 2:157802. Epub 2022 Aug 2.

Department of Civil and Environmental Engineering, Faculty of Science and Technology, University of Macau, Taipa, Macau. Electronic address:

Microplastics (MPs) tend to accumulate and undergo a sulfur weathering process that leads to significant surface changes in sulfur-rich anaerobic environments, such as sewage and wastewater treatment plants. Aged MPs can have a profound impact on environmental behaviors of various toxic pollutants, especially heavy metals. Although previous studies have investigated the adsorption characteristics of metal ions on MPs that are aged in aerobic environments, the sorptive interactions of sulfur-aged MPs in anaerobic environments with mercury, i.e., Hg(II), are largely unknown. In this study, laboratory investigations were conducted to study the sorptive behaviors of Hg(II) by six common MPs treated anaerobically in the presence of sulfide. Adsorption isotherms show that the sulfur aging process greatly enhances the MP sorption capacity of Hg(II). The mechanisms including changes in the specific surface area, electrostatic interactions, surface precipitation, and surface functional groups are responsible for the enhanced adsorption capacities of sulfur-aged MPs. The thiol group that forms on the MP surface plays a dominant role in enhancing the MP adsorption capacity of Hg(II), which is determined by the formation of unsaturated bonds in the molecular chains of MPs. Furthermore, the pathways of surface chemical transformation of MPs during sulfur aging have been proposed. This study promotes our understanding of the potential hazard of MPs as well as the fate and transport of heavy metals in the presence of aged MPs.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157802DOI Listing
August 2022

N-mytistoyltransferase 1 and 2 are potential tumor suppressors and novel targets of miR-182 in human non-small cell lung carcinomas.

Lung Cancer 2022 Jul 29;171:70-81. Epub 2022 Jul 29.

Department of Clinical Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China. Electronic address:

Background & Aims: Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancer diagnoses across the world. Despite recent appreciable improvements in treatment plans for patients with NSCLC, the prognosis for those with the cancer still remains poor. Recently, a growing number of studies have shown that N-myristoyltransferases (NMTs) may be critical in carcinogenesis, however, the functional and clinical significance of this pathway in NSCLC remains unclear and requires further research.

Methods: Initially, we evaluated the expression levels of NMT1 or NMT2 in a clinical cohort comprising of 303 paired primary NSCLC tissues and matched normal mucosae by using ELISA. We subsequently performed a tissue microarray analysis (TMA) to confirm its expression pattern in an independent validation cohort (n = 78). Then, we used a publicly available KM plotter database (n = 1921) to evaluate the prognostic impact of NMT1 and NMT2 in NSCLC. Lastly, a series of in-vitro molecular/cellular and animal experiments were performed for mechanistic understanding of the role of N-myristoyltransferases in NSCLC.

Results: Our ELISA data revealed that the expression level of NMT1 and NMT2 was down-regulated in tumor tissues (n = 303, P < 0.0001), which was confirmed in an independent validation cohort by TMA (n = 78, P = 0.014 for NMT1 and P < 0.0001 for NMT2). On the other hand, patients with low expression of NMT1 or NMT2 had shorter overall survival (P = 0.013, HR = 0.85 for NMT1; P = 0.00059, HR = 0.8, for NMT2). Mechanistically, we revealed that the interaction and co-localization of NMT1 and NMT2 in NSCLC, and N-terminus of NMT1 and NMT2 was observed to be crucial for their interaction as well as for their catalytic activity. Moreover, we found that NMT1 can significantly promote the expression of NMT2 by enhancing its stability. We corroborated these findings by performing functional assays in which the knockout of NMT1 and NMT2 resulted in enhanced cell proliferation, migration and invasion as well as increased tumorxenograftgrowth. In addition, we identified miR-182 as a novel regulator of both NMT1 and NMT2. More specifically, the overexpression or inhibition of miR-182 modulated globe N-myristoylation level, contributed to phenotypic alterations in NSCLS cells.

Conclusions: NMT1 and NMT2 can act as potential tumor suppressors in NSCLC, and the inhibition of miR-182 expression or therapeutic NMTs replenishment may be a promising treatment option for patients with NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2022.07.021DOI Listing
July 2022

Comparative Pharmacokinetics of Cinobufacini Capsule and Injection by UPLC-MS/MS.

Front Pharmacol 2022 18;13:944041. Epub 2022 Jul 18.

Experiment Center of Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Cinobufacini capsule and injection are two different formulations from the same source, obtained from the extraction of the skin of Cantor, which have been approved by the Chinese State Food and Drug Administration (CFDA) for the treatment of various cancers. Our previous study has found that the cinobufacini capsule and injection exhibited different anticancer effects, but their different pharmacokinetic behaviors, which could give a cause of that, have never been reported. So a sensitive and selective method for the simultaneous quantitation of 13 compounds in the rat plasma, including bufothionine, hellebrigenin, bufalin, gamabufotalin, telocinobufagin, cinobufagin, arenobufagin, cinobufotalin, desacetylcinobufotalin, bufotalin, pseudobufarenogin, resibufogenin, and desacetylcinobufagin, was established by using the Agilent 6460 mass spectrometer equipped with an ESI ion source in a multiple-reaction monitoring (MRM) mode. Chromatographic analysis was accomplished in 6 min by using an Agilent SB-C18 column and a mobile phase consisting of 0.1% formic acid in water and acetonitrile in an optimized gradient program at a flow rate of 0.3 ml/min. The correlation coefficients (r) of all analytes ranged from 0.9967 to 0.9996, while their lower limits of quantification ranged from 0.20 to 4.84 ng/ml. The method has been fully verified and applied for the pharmacokinetic difference study of the Cinobufacini capsule and injection in rats. The results showed that nine components could be quantitated in rat plasma samples after the administration of the cinobufacini capsule, while only bufothionine, bufalin, arenobufagin, and pseudobufarenogin could be detected in the cinobufacini injection group. Their pharmacokinetic studies indicated telocinobufagin, bufalin, desacetylcinobufagin, and arenobufagin were predicted as the potential active substances of the Cinobufacini capsule, while bufothionine was considered as a major ingredient in the cinobufacini injection due to its relatively high blood drug exposure. Also, the AUC of the nine components in cinobufacini capsule groups with three different doses showed a similar trend with significant differences, and the exposure increased with the increase of the dose. The pharmacokinetic characteristics of all major ingredients in cinobufacini capsules and injection were of wide variation, which could be used to explain differences in the efficacy of the cinobufacini capsule and injection and infer the pharmacodynamic ingredients of various cinobufacini preparations.
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http://dx.doi.org/10.3389/fphar.2022.944041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343874PMC
July 2022

PPARα: A potential therapeutic target of cholestasis.

Front Pharmacol 2022 18;13:916866. Epub 2022 Jul 18.

Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

The accumulation of bile acids in the liver leads to the development of cholestasis and hepatocyte injury. Nuclear receptors control the synthesis and transport of bile acids in the liver. Among them, the farnesoid X receptor (FXR) is the most common receptor studied in treating cholestasis. The activation of this receptor can reduce the amount of bile acid synthesis and decrease the bile acid content in the liver, alleviating cholestasis. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) have a FXR excitatory effect, but the unresponsiveness of some patients and the side effect of pruritus seriously affect the results of UDCA or OCA treatment. The activator of peroxisome proliferator-activated receptor alpha (PPARα) has emerged as a new target for controlling the synthesis and transport of bile acids during cholestasis. Moreover, the anti-inflammatory effect of PPARα can effectively reduce cholestatic liver injury, thereby improving patients' physiological status. Here, we will focus on the function of PPARα and its involvement in the regulation of bile acid transport and metabolism. In addition, the anti-inflammatory effects of PPARα will be discussed in some detail. Finally, we will discuss the application of PPARα agonists for cholestatic liver disorders.
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http://dx.doi.org/10.3389/fphar.2022.916866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342652PMC
July 2022

Adherence to Stroke Care Performance Measures in Different Regions in China, 2015-2019: Evidence From the Chinese Stroke Center Alliance.

Neurology 2022 Aug 2. Epub 2022 Aug 2.

China National Clinical Research Center for Neurological Diseases, Beijing, China.

Background And Objectives: To explore regional discrepancy of the adherence to guideline-recommended stroke interventions, with respect to the stroke belt division (north vs. south), the economic development division (east vs. middle vs. west), and potential interaction.

Methods: We conducted a retrospective observational study using data from the Chinese Stroke Center Alliance (CSCA) from August 2015 to August 2019. The primary outcome was hospital personnel adherence to eleven individual guideline-recommended treatments. The co-primary outcomes included two summary measures: a composite score (range, 0 [nonadherence] to 1[perfect adherence]), and an all-or-none binary outcome for adherence to evidence-based stroke. Regional disparities were assessed according to the stroke belt division and the economic development division respectively, as well as the interaction between these two divisions. Multivariate regression models with generalized estimating equations were used to analyze the outcomes.

Results: This study included 838,229 patients with acute ischemic stroke (AIS) from 1,473 hospitals. The overall quality of care in the non-belt regions (southern China) was higher than the stroke-belt regions (northern China), as reflected by a higher composite score (0.77vs 0.75; adjusted OR: 1.03 [95% CI, 1.02-1.04]; P < 0.001) and a higher all-or-none measure (25.5% vs 22.0%; 1.32 [1.17-1.49], P < 0.001). Patients in the East and the Central had higher odds of using intravenous tissue-type plasminogen activator (East: 1.81 [95% CI, 1.51-2.18], P < 0.001; Central: 1.57 [95% CI, 1.26-1.95], P < 0.001), early antithrombotics (East: 1.77 [1.49-2.11], P < 0.001; Central: 1.37 [1.12-1.66], P < 0.001), lipid-lowering medications (East: 1.29 [1.08-1.53], P < 0.001), and DVT prophylaxis (East: 1.28 [1.08-1.50], P = 0.003) compared to those in the West. Patients in the non-belt regions had higher odds of getting dysphagia screening (1.82 [1.55-2.13], P < 0.001) and rehabilitation assessment (which though varied among different economic development levels). Reflected by significant interaction effects, for patients in the East, those in the non-belt regions had greater odds of receiving anticoagulation (1.62 [1.34-1.96]; P < 0.001) but lower odds of receiving antihtrombotics (0.63 [0.52-0.77]; P < 0.001) and antidiabetic medication (0.87 [0.77-0.99]; P= 0.03); for patients in the West, those in the non-belt regions were less likely to receive antihypertensive (0.64 [0.46-0.88]; P = 0.004) and antidiabetic (0.66 [0.54-0.81]; P < 0.001) medications.

Discussion: Stroke care performance measures differed across regions, along the stroke-belt division, and the economic development division. The overall quality of care in the non-stroke-belt regions was higher than the stroke-belt regions. The two divisions had interaction effects on several individual measures.
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http://dx.doi.org/10.1212/WNL.0000000000201024DOI Listing
August 2022

Association between body composition and survival in head and neck cancer patients undergoing radiotherapy.

Head Neck 2022 Sep;44(9):2046-2054

Division of Medical and Surgical Nursing, School of Nursing, Peking University, Beijing, China.

Background: Body composition may influence the prognosis of head and neck cancer (HNC) patients. To find out the most crucial factors in this relationship, we explored the association between body composition and survival.

Methods: In this prospective longitudinal study, HNC patients who underwent radiotherapy (RT) from March 2017 to December 2018 were recruited. The association between body composition and survival was analyzed using Cox proportional hazard regression.

Results: Final analysis included 316 patients, with a median follow-up of 34.4 months. Multivariable analysis revealed that weight loss 6 months before RT and body composition changes during RT did not affect the survival outcome. However, patients with low appendicular skeletal muscle mass index (ASMI) before RT exhibited poor overall survival (OS). ASMI before RT was an independent prognostic factor for OS.

Conclusions: Body composition loss was common during RT, and ASMI before RT independently influenced the survival outcomes of HNC patients.
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http://dx.doi.org/10.1002/hed.27065DOI Listing
September 2022

Nanoscale Bimetallic AuPt-Functionalized Metal Oxide Chemiresistors: Ppb-Level and Selective Detection for Ozone and Acetone.

ACS Sens 2022 Jul 28. Epub 2022 Jul 28.

State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012, P. R. China.

As the most widely used gas sensors, metal oxide semiconductor (MOS)-based chemiresistors have been facing great challenges in achieving ppb-level and selective detection of the target gas. The rational design and employment of bimetallic nanocatalysts (NCs) are expected to address this issue. In this work, the well-shaped and monodispersed AuPt NCs (diameter ≈ 9 nm) were functionalized on one-dimensional (1D) InO nanofibers (NFs) to construct efficient gas sensors. The sensor demonstrated dual-selective and ppb-level detection for ozone (O) and acetone (CHO) at different optimal working temperatures. For the possible application exploitation, a circuit was designed to monitor O concentration and provide warnings when the concentration safety limit (50 ppb) was exceeded. Moreover, simulated exhaled breath measurements were also carried out to diagnose diabetes through CHO concentration. The selective detection for O and CHO was further analyzed by principal component analysis (PCA). The drastically enhanced sensing performances were attributed to the synergistic catalytic effect of AuPt NCs. Both the "spillover effect" and the Schottky barrier at the interfaces of AuPt NCs and InO NFs promoted the sensing processes of O and CHO.
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http://dx.doi.org/10.1021/acssensors.2c00214DOI Listing
July 2022

Study on the mechanism of thrombus ablation in vitro by burst-mode femtosecond laser.

J Biophotonics 2022 Jul 27:e202200197. Epub 2022 Jul 27.

Department of Vascular Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.

The burst-mode femtosecond laser has the potential to be a novel thrombus removal technique. This paper proposed to investigate the mechanism of thrombus ablation in vitro by burst-mode femtosecond laser. A simulation model of the interaction between femtosecond laser and thrombus was established. An in vitro thrombus model was prepared. Combined the high-speed galvanometer and femtosecond laser, the ablation experiments in vitro were performed. The experimental results showed that the ablative threshold was 0.27 times and the efficiency was about 1.4 times of burst-mode femtosecond laser as those of traditional mode femtosecond laser. These phenomena were related to the residual temperature and free electrons on the thrombus surface, which confirmed to the simulating results and had relationship with incubation effects. The high ablative efficiency and safety of burst-mode femtosecond laser for thrombus ablation was verified, which may help to achieve the femtosecond pulse output through flexible fiber easily and stably. The burst-mode femtosecond laser represents an important technological advancement of the method in terms of endovascular treatment with femtosecond laser. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jbio.202200197DOI Listing
July 2022

Twin-Screw Extrusion of Oat: Evolutions of Rheological Behavior, Thermal Properties and Structures of Extruded Oat in Different Extrusion Zones.

Foods 2022 Jul 25;11(15). Epub 2022 Jul 25.

College of Engineering, China Agricultural University, No. 17 QinghuaEast Road, Haidian District, P.O. Box 50, Beijing 100083, China.

Further investigation of material properties during the extrusion process is essential to achieve precise control of the quality of the extrudate. Whole oat flour was used to produce low moisture puffed samples by a twin-screw extruder. X-ray diffraction (XRD), Scanning electron microscopy (SEM), infrared spectroscopy (FTIR), thermal analysis, and rheological experiments were used to deeply characterize changes in the structure and cross-linking of oats in different extrusion zones. Results indicated that the melting region was the main region that changed oat starch, including the major transformation of oat starch crystal morphology and the significant decrease of enthalpy representing the starch pasting peak in the differential scanning calorimeter (DSC) pattern ( < 0.05). Moreover, the unstable structure of the protein increased in the barrel and then decreased significantly ( < 0.05) after being extruded through the die head. The viscosity of oats increased in the cooking zone but decreased after the melting zone. A transformation occurred from elastic-dominant behavior to viscoelastic-dominant behavior for oats in the melting zone and after being extruded. This study provides further theoretical support for the research of the change of materials during extrusion and the development of oat-based food.
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http://dx.doi.org/10.3390/foods11152206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329829PMC
July 2022

Metal-Organic Frameworks for Electrocatalytic Sensing of Hydrogen Peroxide.

Molecules 2022 Jul 18;27(14). Epub 2022 Jul 18.

Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, Jiangsu Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, Institute of Energy Supply Technology for High-End Equipment, School of Environmental Science and Engineering, Nanjing University of Information Science & Technology, Nanjing 210044, China.

The electrochemical detection of hydrogen peroxide (HO) has become more and more important in industrial production, daily life, biological process, green energy chemistry, and other fields (especially for the detection of low concentration of HO Metal organic frameworks (MOFs) are promising candidates to replace the established HO sensors based on precious metals or enzymes. This review summarizes recent advances in MOF-based HO electrochemical sensors, including conductive MOFs, MOFs with chemical modifications, MOFs-composites, and MOF derivatives. Finally, the challenges and prospects for the optimization and design of HO electrochemical sensors with ultra-low detection limit and long-life are presented.
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http://dx.doi.org/10.3390/molecules27144571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316108PMC
July 2022

Comprehensive Analysis of circRNA-miRNA-mRNA Regulatory Network and Novel Potential Biomarkers in Acute Myocardial Infarction.

Front Cardiovasc Med 2022 7;9:850991. Epub 2022 Jul 7.

Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Background: Circular RNA (circRNA) plays an important role in the regulation of gene expression and the occurrence of human diseases. However, studies on the role of circRNA in acute myocardial infarction (AMI) are limited. This study was performed to explore novel circRNA-related regulatory networks in AMI, aiming to better understand the molecular mechanism of circRNAs involvement in AMI and provide basis for further scientific research and clinical decision-making.

Methods: The AMI-related microarray datasets GSE160717 (circRNA), GSE31568 (miRNA), GSE61741 (miRNA), and GSE24519 (mRNA) were obtained from the Gene Expression Omnibus (GEO) database. After differential expression analysis, the regulatory relationships between these DERNAs were identified by online databases circBank, circInteractome, miRDB, miRWalk, Targetscan, and then two circRNA-miRNA-mRNA regulatory networks were constructed. Differentially expressed genes (DEGs) in this network were selected followed by enrichment analysis and protein-protein interaction (PPI) analysis. Hub genes were identified using Cytohubba plug-in of Cytoscape software. Hub genes and hub gene-related miRNAs were used for receiver operating characteristic curve (ROC) analysis to identify potential biomarkers. The relative expression levels of these biomarkers were further assessed by GSE31568 (miRNA) and GSE66360 (mRNA). Finally, on the basis of the above analysis, myocardial hypoxia model was constructed to verify the expression of Hub genes and related circRNAs.

Results: A total of 83 DEcircRNAs, 109 CoDEmiRNAs and 1204 DEGs were significantly differentially expressed in these datasets. The up-regulated circRNAs and down-regulated circRNAs were used to construct a circRNA-miRNA-mRNA regulatory network respectively. These circRNA-related DEGs were mainly enriched in the terms of "FOXO signaling pathway," "T cell receptor signaling pathway," "MAPK signaling pathway," "Insulin resistance," "cAMP signaling pathway," and "mTOR signaling pathway." The top 10 hub genes ATP2B2, KCNA1, GRIN2A, SCN2B, GPM6A, CACNA1E, HDAC2, SRSF1, ANK2, and HNRNPA2B1 were identified from the PPI network. Hub genes GPM6A, SRSF1, ANK2 and hub gene-related circRNAs hsa_circ_0023461, hsa_circ_0004561, hsa_circ_0001147, hsa_circ_0004771, hsa_circ_0061276, and hsa_circ_0045519 were identified as potential biomarkers in AMI.

Conclusion: In this study, the potential circRNAs associated with AMI were identified and two circRNA-miRNA-mRNA regulatory networks were constructed. This study explored the mechanism of circRNA involvement in AMI and provided new clues for the selection of new diagnostic markers and therapeutic targets for AMI.
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http://dx.doi.org/10.3389/fcvm.2022.850991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300925PMC
July 2022

Regulation of hyperoxia-induced neonatal lung injury via post-translational cysteine redox modifications.

Redox Biol 2022 Jul 19;55:102405. Epub 2022 Jul 19.

Pulmonary Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. Electronic address:

Preterm infants and patients with lung disease often have excess fluid in the lungs and are frequently treated with oxygen, however long-term exposure to hyperoxia results in irreversible lung injury. Although the adverse effects of hyperoxia are mediated by reactive oxygen species, the full extent of the impact of hyperoxia on redox-dependent regulation in the lung is unclear. In this study, neonatal mice overexpressing the beta-subunit of the epithelial sodium channel (β-ENaC) encoded by Scnn1b and their wild type (WT; C57Bl6) littermates were utilized to study the pathogenesis of high fraction inspired oxygen (FiO)-induced lung injury. Results showed that O-induced lung injury in transgenic Scnn1b mice is attenuated following chronic O exposure. To test the hypothesis that reversible cysteine-redox-modifications of proteins play an important role in O-induced lung injury, we performed proteome-wide profiling of protein S-glutathionylation (SSG) in both WT and Scnn1b overexpressing mice maintained at 21% O (normoxia) or FiO 85% (hyperoxia) from birth to 11-15 days postnatal. Over 7700 unique Cys sites with SSG modifications were identified and quantified, covering more than 3000 proteins in the lung. In both mouse models, hyperoxia resulted in a significant alteration of the SSG levels of Cys sites belonging to a diverse range of proteins. In addition, substantial SSG changes were observed in the Scnn1b overexpressing mice exposed to hyperoxia, suggesting that ENaC plays a critically important role in cellular regulation. Hyperoxia-induced SSG changes were further supported by the results observed for thiol total oxidation, the overall level of reversible oxidation on protein cysteine residues. Differential analyses reveal that Scnn1b overexpression may protect against hyperoxia-induced lung injury via modulation of specific processes such as cell adhesion, blood coagulation, and proteolysis. This study provides a landscape view of protein oxidation in the lung and highlights the importance of redox regulation in O-induced lung injury.
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http://dx.doi.org/10.1016/j.redox.2022.102405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307955PMC
July 2022

Efficient management of the nitritation-anammox microbiome through intermittent aeration: absence of the NOB guild and expansion and diversity of the NOx reducing guild suggests a highly reticulated nitrogen cycle.

Environ Microbiome 2022 Jul 22;17(1):39. Epub 2022 Jul 22.

Microbial Ecology and Technology Lab, Department of Environmental Engineering, Technical University of Denmark, Kgs Lyngby, Denmark.

Obtaining efficient autotrophic ammonia removal (aka partial nitritation-anammox, or PNA) requires a balanced microbiome with abundant aerobic and anaerobic ammonia oxidizing bacteria and scarce nitrite oxidizing bacteria. Here, we analyzed the microbiome of an efficient PNA process that was obtained by sequential feeding and periodic aeration. The genomes of the dominant community members were inferred from metagenomes obtained over a 6 month period. Three Brocadia spp. genomes and three Nitrosomonas spp. genomes dominated the autotrophic community; no NOB genomes were retrieved. Two of the Brocadia spp. genomes lacked the genomic potential for nitrite reduction. A diverse set of heterotrophic genomes was retrieved, each with genomic potential for only a fraction of the denitrification pathway. A mutual dependency in amino acid and vitamin synthesis was noted between autotrophic and heterotrophic community members. Our analysis suggests a highly-reticulated nitrogen cycle in the examined PNA microbiome with nitric oxide exchange between the heterotrophs and the anammox guild.
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http://dx.doi.org/10.1186/s40793-022-00432-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306079PMC
July 2022

Effects of the m6Am methyltransferase PCIF1 on cell proliferation and survival in gliomas.

Biochim Biophys Acta Mol Basis Dis 2022 Jul 19;1868(11):166498. Epub 2022 Jul 19.

Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China; Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou 221002, China. Electronic address:

Background: Previous studies have suggested an important role for N6-methyladenosine (m6A) modification in the proliferation of glioma cells. N6, 2'-O-dimethyladenosine (m6Am) is another methylated form affecting the fate and function of most RNA. PCIF1 has recently been identified as the sole m6Am methyltransferase in mammalian mRNA. However, it remains unknown about the role of PCIF1 in the growth and survival of glioma cells.

Methods: We constructed glioma cell lines that stably downregulated/upregulated PCIF1, established intracranial xenograft models using these cell lines, and employed the following methods for investigations: CCK-8, EdU, colony formation, flow cytometry, qRT-PCR, Western blot, and immunohistochemistry.

Findings: Downregulating PCIF1 promoted glioma cell proliferation, while overexpressing PCIF1 showed the opposite effects. Overexpression of PCIF1 blocked cell cycle progression and induced apoptosis in glioma cells, which was further confirmed by alterations in the expression of cell checkpoint proteins and apoptotic markers. Interestingly, disruption of PCIF1 methyltransferase activity slightly reversed the effect of PCIF1 overexpression on cell proliferation, but had no significant reversal effects on cell cycle progression or apoptosis. Knockdown of PCIF1 promoted the growth of gliomas, while overexpressing PCIF1 inhibited tumor growth and prolonged the survival time of tumor-bearing mice. In addition, the mRNA and protein levels of PCIF1 were gradually decreased with the increase of WHO grade in glioma tissues, but there was no significant correlation with patient survival.

Interpretation: These results indicated that PCIF1 played a suppressing role in glioma growth and survival, which may not entirely depend on its methyltransferase activity.
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http://dx.doi.org/10.1016/j.bbadis.2022.166498DOI Listing
July 2022

Yolk-shell-structured [email protected] nanoparticles for high-performance lithium-ion batteries.

RSC Adv 2022 Jun 6;12(30):19678-19685. Epub 2022 Jul 6.

Sunwoda Electronic Co., Ltd Shenzhen 518000 P. R. China.

The huge volume expansion of over 300%, dreadful electrical conductivity and labile solid electrolyte interphase (SEI) are the principal reasons of the sluggish development of Si anodes for lithium-ion batteries (LIBs). Therefore, we propose, for the first time, that titanium nitride (TiN) be utilized as a coating layer to fabricate yolk-shell-structured [email protected] nanoparticles. The design of the yolk-shell structure can reserve excrescent space for the volume expansion of Si electrodes, which helps to mitigate volumetric changes. Moreover, the TiN protecting layer is beneficial to the formation of a stable and flimsy SEI film, avoiding the excessive consumption of electrolytes. Finally, the ultrahigh conductivity (4 × 10 S cm) as well as the high mechanical modulus of TiN can significantly promote charge transfer and avoid the crushing of the SEI film caused by excessive local stress during reduplicative Li deposition/stripping. Accordingly, the [email protected] composites show excellent electrochemical properties and suppressed volume expansion compared with pure silicon nanoparticles (Si NPs). Here, these yolk-shell-structured [email protected] nanoparticles exhibit improved rate performance and excellent long cycling stability with 2047 mA h g at 1000 mA g after 180 cycles. This paradigm may provide a feasible engineering protocol to push the properties of Si anodes for next-generation LIBs.
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http://dx.doi.org/10.1039/d2ra02042dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258785PMC
June 2022

Family support and transport cost: understanding health service among older people from the perspective of social-ecological model.

Arch Public Health 2022 Jul 19;80(1):173. Epub 2022 Jul 19.

Institute of Advanced Studies in Humanities and Social Sciences, Beijing Normal University, Jinfeng Rd. 18, Zhuhai, 519087, China.

Background: This study is to investigate the interaction of family support, transport cost (ex-post), and disabilities on health service seeking behavior among older people from the perspective of social ecological model.

Method: We conduct a series of regressions including the Poisson model and Multiple logit model. The Heckman two-stage procedure is also conducted to check the robustness.

Results: Given that health care resources are generally concentrated in densely populated urban areas, access to services of higher-class health care facilities is found associated with higher transport cost (ex-post). Family support could also promote the access to higher-class health care facilities. Although disability may impede such access, this effect may be mitigated by paying higher transport cost (ex-post).

Conclusions: Alleviating transport deprivation and promoting family support are critical for access to better healthcare services among older people with disabilities.
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http://dx.doi.org/10.1186/s13690-022-00923-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295433PMC
July 2022

Self-Activated Cascade Biocatalysis of Glucose Oxidase-Polycation-Iron Nanoconjugates Augments Cancer Immunotherapy.

ACS Appl Mater Interfaces 2022 Jul 18. Epub 2022 Jul 18.

Department of Geriatric Dentistry, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing 100081, China.

Biocatalytic therapy by reactive-oxygen-species-generating enzymes not only kills cancer cells directly but also stimulates an anticancer immune response and inverses the immunosuppressive microenvironment of a variety of solid tumors, which is potentially beneficial to overcoming the limitations of cancer immunotherapy. Herein, we report the in situ growth of polycation chains from glucose oxidase to generate glucose oxidase-polycation conjugates, which can be used as a template for the in situ reduction of ferrous ions into iron nanoparticles to yield glucose oxidase-polycation-iron nanoconjugates. The nanoconjugates exhibit enhanced cellular uptake and cancer retention as well as self-activated cascade biocatalysis that consumes glucose and generates highly toxic hydroxyl radicals, leading to enhanced starvation-like and chemodynamic cancer therapy. The cancer treatment with the nanoconjugates efficiently triggers the program of immunogenic cell death for enhanced immune checkpoint blockade therapy. The synergy of self-activated cascade biocatalysis and immune checkpoint blockade not only eradicates primary cancers but also inhibits the progression of distant cancers, which leads to the abscopal effect on cancers. Our findings provide a method for the in situ synthesis of self-activated cascade nano-biocatalysts for cascade biocatalysis-enhanced immunotherapy of cancer.
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http://dx.doi.org/10.1021/acsami.2c04894DOI Listing
July 2022

Diagnostic study on clinical feasibility of an AI-based diagnostic system as a second reader on mobile CT images: a preliminary result.

Ann Transl Med 2022 Jun;10(12):668

Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.

Background: Artificial intelligence (AI) has breathed new life into the lung nodules detection and diagnosis. However, whether the output information from AI will translate into benefits for clinical workflow or patient outcomes in a real-world setting remains unknown. This study was to demonstrate the feasibility of an AI-based diagnostic system deployed as a second reader in imaging interpretation for patients screened for pulmonary abnormalities in a clinical setting.

Methods: The study included patients from a lung cancer screening program conducted in Sichuan Province, China using a mobile computed tomography (CT) scanner which traveled to medium-size cities between July 10, 2020 and September 10, 2020. Cases that were suspected to have malignant nodules by junior radiologists, senior radiologists or AI were labeled a high risk (HR) tag as HR-junior, HR-senior and HR-AI, respectively, and included into final analysis. The diagnosis efficacy of the AI was evaluated by calculating negative predictive value and positive predictive value when referring to the senior readers' final results as the gold standard. Besides, characteristics of the lesions were compared among cases with different HR labels.

Results: In total, 251/3,872 patients (6.48%, male/female: 91/160, median age, 66 years) with HR lung nodules were included. The AI algorithm achieved a negative predictive value of 88.2% [95% confidence interval (CI): 62.2-98.0%] and a positive predictive value of 55.6% (95% CI: 49.0-62.0%). The diagnostic duration was significantly reduced when AI was used as a second reader (223±145.6 . 270±143.17 s, P<0.001). The information yielded by AI affected the radiologist's decision-making in 35/145 cases. Lesions of HR cases had a higher volume [309.9 (214.9-732.5) . 141.3 (79.3-380.8) mm, P<0.001], lower average CT number [-511.0 (-576.5 to -100.5) . -191.5 (-487.3 to 22.5), P=0.010], and pure ground glass opacity rather than solid.

Conclusions: The AI algorithm had high negative predictive value but low positive predictive value in diagnosing HR lung lesions in a clinical setting. Deploying AI as a second reader could help avoid missed diagnoses, reduce diagnostic duration, and strengthen diagnostic confidence for radiologists.
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http://dx.doi.org/10.21037/atm-22-2157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279799PMC
June 2022

Association of NFKB1 gene rs28362491 mutation with the occurrence of major adverse cardiovascular events.

BMC Cardiovasc Disord 2022 07 13;22(1):313. Epub 2022 Jul 13.

People's Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Urumqi, 830054, Xinjiang, China.

Background: Several studies have reported that NFKB1 gene rs28362491 polymorphism was associated with susceptibility to coronary heart disease in populations of different genetic backgrounds. To date, there have been no studies on the association between NFKB1 gene rs28362491 polymorphism and the occurrence of major adverse cardiac and cerebrovascular event (MACCE). The present study was to explore the relationship between NFKB1 gene rs28362491 polymorphism and MACCEs to investigate whether identifying NFKB1 gene polymorphism is beneficial to evaluating MACCE risks and patients' prognoses.

Methods: We recruited 257 high-risk of cardiovascular disease patients with chest pain or precordial discomfort. The SNPscan™ were used to analyze the NFKB1 gene rs28362491 polymorphism. All patients were followed up in the clinic or by telephone interview for MACCEs.

Results: During the followed-up time (mean: 30.1 months) 49 patients had MACCEs (19.1%). Patients with the different genotypes of NFKB1 rs28362491 had different incidence rate of MACCE. The incidence of MACCE in patients carried II, ID and DD genotype was 16.5%, 15.9%, 32.6%, respectively. Log-rank analysis showed that the survival rate in patients with NFKB1 rs28362491 DD genotype was much lower than that in II or ID genotype carriers (P = 0.034). After excluding the influence of traditional risk factors of MACCEs, Cox regression showed that the DD genotype carriers had 2.294-fold relative risk of MACCEs comparing with patients carried II or ID genotype.

Conclusion: The NFKB1 gene rs28362491 mutant was an independent predictor of worse long-term prognosis for MACCEs. Therefore, identifying NFKB1 gene rs28362491 mutant may be used as a good way for guiding the standardized management of patients with high-risk of cardiovascular diseases.
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http://dx.doi.org/10.1186/s12872-022-02755-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281072PMC
July 2022

First Report of Leaf Spot of Caused by in Zhejiang province, China.

Plant Dis 2022 Jul 11. Epub 2022 Jul 11.

Laboratory of Medicinal Plant Biotechnology, School of pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, Hangzhou, Zhejiang, China.

Koidz is a very common herbs in China, also famous for its high medicinal value (Lee et al., 2007). In summer of 2019, in Fuyang county of Zhejiang province, the main production area of China, 74 plants of from a total of about 300 plants, showed black leaf spots . The incidence of the disease was 25% and increased under high temperature and humidity conditions. Initial leaf symptoms appeared as black or tan spots surrounded by brown margins and expanded irregularly. Finally, large blackish brown spots appeared on the leaves, elliptical or irregular, 1.0 to 1.5 cm in diameter, and then lesions turned necrotic. To isolate the pathogen, small pieces (5×5 mm) from the margin of symptomatic leaves were surface-sterilized with 75% ethanol for 30 s and 2% sodium hypochlorite for 2 min, rinsed five times with sterile water, and incubated on potato dextrose agar (PDA) at 28°C in darkness. Purified colonies were white to pink with densely floccose to fluffy aerial mycelium and peach-orange pigmentation. Macroconidia, usually three-septate, were 26.7 to 43.3×3.1 to 5.3μm (n=50), thin-walled, slightly curved, with apical and basal cells curved when cultured in continuous darkness. Microconidia were mostly aseptate, ovate-oblong, straight to slightly curved, and measuring 5.9 to 14.3×2.3 to 3.9μm in size (n=50). Spherical chlamydospores were produced singly or in pairs from mycelium and spores. These characteristics were consistent with the description of spp. (Leslie and Summerell, 2006). To identify the species, the translation elongation factor-1 alpha regions (TEF-1α) and the mitochondrial small subunit (mtSSU) were amplified using primers EF-3/ EF-22 (Palmore et al.,2010 and O'Donnell et al., 1998) and MS3F/ MS3R (Stenglein et al., 2010), respectively. Sequences were deposited in GenBank (MT263720, OM203177, OM203178, OM203179, OM203180, OM203181 and MN853662, MZ028170.1, MZ028171.1, MZ028172.1, MZ028173.1, MZ028174.1). These six isolates clustered in the clade with 100% and 98% similarity, respectively. To test pathogenicity of every isolate, five 8-week-old potted plants were wound-inoculated and mycelial discs of 5-mm diameter were used to inoculate. As a control, five plants were inoculated with 5-mm PDA plugs. All plants were individually covered with a plastic bag and kept in a greenhouse at 25 ± 2°C with a 12-h photoperiod at 70 to 80% relative humidity. Typical symptoms similar to those of the field appeared only in inoculated plants after five days. In addition, a conidial suspension (1×10 spores/ml) was sprayed onto young leaves of three potted healthy plants. Three plants sprayed with sterile distilled water served as controls. After 7 days, typical symptoms were observed on all inoculated leaves. Experiments were replicated three times. was successfully re-isolated from diseased plants. Based on morphological and molecular identification, the pathogen was identified as In China, (Zhuang, 2005), (Tan et al., 2012), (Sang et al., 2006) and (Zhang et al., 2018) were reported as causal agents of the leaf spot disease of . To our knowledge, this is the first report of leaf spot disease on caused by in China. Effective control strategies need to be established to reduce the losses.
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http://dx.doi.org/10.1094/PDIS-11-20-2501-PDNDOI Listing
July 2022

Fear Stress During Pregnancy Affects Placental m6A-Modifying Enzyme Expression and Epigenetic Modification Levels.

Front Genet 2022 22;13:927615. Epub 2022 Jun 22.

Medicine College, Henan University of Chinese Medicine, Zhengzhou, China.

As the hub connecting mother and offspring, the placenta's normal development is vital for fetal growth. Fear stress can cause some structural alterations in the placenta and affect placental development and function. N6-methyladenosine (m6A) is the most common mRNA modification and is involved in regulating the development of the placenta and embryo. There are no reports on the potential role of m6A modification in placental damage caused by fear stress during pregnancy. In this study, we demonstrated that fear stress during pregnancy increases the levels of methylated enzymes (METTL3, METTL14, and WTAP), decreases the levels of demethylase FTO, and increases the overall methylation levels in the placenta of pregnant rats. MeRIP-seq data analysis revealed 22,010 m6A peaks associated with 12,219 genes in the placenta of the model and 21,060 m6A peaks associated with 11,730 genes in the placenta of the control. The peaks were mainly concentrated in the coding region and the 3' untranslated region. In addition, 50 genes with abnormal modification and expression (double aberrant genes) were screened out by combining MeRIP-seq and RNA-seq data. , , and were selected from 50 double aberrant genes, and MeRIP-qPCR and real-time quantitative polymerase chain reaction were used to verify their modification and expression levels. Our findings suggest that m6A modifications play an important role in placental dysfunction induced by fear stress during pregnancy.
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http://dx.doi.org/10.3389/fgene.2022.927615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257140PMC
June 2022

Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy.

Front Immunol 2022 24;13:791158. Epub 2022 Jun 24.

State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and it is the major cause of kidney cancer death. Understanding tumor immune microenvironments (TMEs) is critical in cancer immunotherapies. Here, we studied the immune characterization at single-cell resolution by integrating public data of ccRCC across different tissue types, and comparing the transcriptome features and tumor TME differences in tumors, normal adjacent tissue, and peripheral blood. A total of 16 different types of cell components of ccRCC were identified. We revealed that there is an overall increase in T-cell and myeloid populations in tumor-infiltrated immune cells compared to normal renal tissue, and the B-cell population in the tumor showed a sharp decrease, which indicates that the cells in tumor tissue undergo strong immune stress. In addition, the cell-cell communication analysis revealed specific or conserved signals in different tissue types, which may aid to uncover the distinct immune response. By combining and analyzing publicly available ccRCC bulk RNA-seq datasets, 10 genes were identified as marker genes in specific cell types, which were significantly associated with poor prognosis. Of note, UBE2C, which may be a good indicator of tumor proliferation, is positively associated with reductions in overall survival and highly associated with tumor grade. Our integrated analysis provides single-cell transcriptomic profiling of ccRCC and their TME, and it unmasked new correlations between gene expression, survival outcomes, and immune cell-type components, enabling us to dissect the dynamic variables in the tumor development process. This resource provides deeper insight into the transcriptome features and immune response of ccRCC and will be helpful in kidney cancer immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2022.791158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263726PMC
June 2022

A green 3-step combined modification for the preparation of biomass sorbent from waste chestnut thorns shell to efficient removal of methylene blue.

Bioresour Technol 2022 Jul 6;360:127593. Epub 2022 Jul 6.

College of Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing 100083, China. Electronic address:

Although several green methods for the preparation of biomass adsorbents have been proposed, the low adsorption performance of the biomass adsorbents prepared by these methods has limited the development of this technological route. This is the first work that uses an ultrasound-assisted binary solvent system and low temperature ice crystal fixation to achieve high adsorption performance of a biomass sorbent. Chestnut thorns shell (CTS) sorbent with high adsorption performance on MB was successfully prepared with an adsorption performance of 305.81 mg/g, which is on par with most high temperature carbonized adsorbents. Further reaction kinetics, TEM, XPS and FTIR studies showed that the MB adsorption of CTS was through electrostatic attraction, hydrogen bonding, ion-dipole interaction and π-π interaction. After five cycles, the adsorption capacity of the adsorbent remained at a high level. This work provided an effective strategy for safer and greener preparation of high adsorption performance adsorbents from agroforestry waste.
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http://dx.doi.org/10.1016/j.biortech.2022.127593DOI Listing
July 2022

Comparision of the phenol red, gravimetric, and synthesized mPEG-PR methods for correcting water flux using the single-pass intestinal perfusion method.

Eur J Pharm Sci 2022 Sep 5;176:106255. Epub 2022 Jul 5.

College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address:

Phenol red and PEG-4000, the usual non-absorbable indicators, have non-negligible absorption problems in measuring water flux. mPEG-PR, combined phenol red with mPEG-4000, was first synthesized and could decrease absorption. However, its application has not been confirmed. The purpose of this study was to explore the applicability of mPEG-PR as a novel non-absorption indicator in the in situ single-pass intestinal perfusion (SPIP) experiment. Six model drugs (atenolol ranitidine, ibuprofen, ketoprofen, antipyrine, hydrochlorothiazide) were used to compare the accuracy of four measuring methods including phenol red, mPEG-PR, gravimetric, and non-corrected methods of correcting intestinal fluid transport. Moreover, we evaluated the correlations between the effective permeability coefficients (P) in rat and fraction dose absorbed (F) in human, P in human, and apparent permeability coefficients (P) by the Ussing Chamber system using human tissue. Among these methods, mPEG-PR was the most reliable approach, which avoided the absorption of phenol red method and mucous shedding or water evaporation of gravimetric method. An excellent correlation was obtained between the P of rat and F of human. Our results of this study indicated that mPEG-PR was a stable and accurate non-absorbable indicator to correct water flux in the in situ SPIP model, which could be developed to predict the human F.
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http://dx.doi.org/10.1016/j.ejps.2022.106255DOI Listing
September 2022

Travel experience and health service amongst older people from the perspective of social exclusion: Policy implications of alleviating transport deprivation.

Health Soc Care Community 2022 Jul 5. Epub 2022 Jul 5.

Institute of Advanced Studies in Humanities and Social Sciences, Beijing Normal University, Zhuhai, China.

The vulnerable population are often faced with the transport deprivation resulting in social exclusion (e.g. lack of access to healthcare service or suffering from lower health service quality). The disparity in travel experience can lead to different results of healthcare service seeking amongst the vulnerable population such as older adults with and without disabilities. This study applies Heckman's two-stage procedure and the data from China Health and Retirement Longitudinal Study. Based on having controlled the influence of individual financial situation and self-rated health, results show that longer travel time is observed in older adults who have paid the visit to the higher class healthcare facilities (HHCF). Besides, the visit to HHCF is negatively associated with disability and positively with travel mode with less discomfort. Further, the relationship between disability and the class of visited healthcare facilities is found to be conditioned on the travel time and travel mode, wherein such relationship could be intensified by longer travel time and be alleviated by travel mode with less discomfort. Therefore, social policies to alleviate transport deprivation are critical for accessing better healthcare services amongst older people with disabilities.
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http://dx.doi.org/10.1111/hsc.13902DOI Listing
July 2022

A rapid and non-invasive proteomic analysis using DBS and buccal swab for multiplexed second-tier screening of Pompe disease and Mucopolysaccharidosis type I.

Mol Genet Metab 2022 08 28;136(4):296-305. Epub 2022 Jun 28.

Seattle Children's Research Institute, Seattle, WA, United States of America; Biochemical Genetics Clinic, Seattle Children's Hospital, Seattle, WA, United States of America; Department of Pediatrics, Division of Genetic Medicine, University of Washington School of Medicine, Seattle, WA, United States of America. Electronic address:

Purpose: Current newborn screening programs for Pompe disease (PD) and mucopolysaccharidosis type I (MPS I) suffer from a high false positive rate and long turnaround time for clinical follow up. This study aimed to develop a novel proteomics-based assay for rapid and accurate second-tier screening of PD and MPS I. A fast turnaround assay would enable the identification of severe cases who need immediate clinical follow up and treatment.

Methods: We developed an immunocapture coupled with mass spectrometry-based proteomics (Immuno-SRM) assay to quantify GAA and IDUA proteins in dried blood spots (DBS) and buccal swabs. Sensitivity, linearity, reproducibility, and protein concentration range in healthy control samples were determined. Clinical performance was evaluated in known PD and MPS I patients as well as pseudodeficiency and carrier cases.

Results: Using three 3.2 mm punches (~13.1 μL of blood) of DBS, the assay showed reproducible and sensitive quantification of GAA and IDUA. Both proteins can also be quantified in buccal swabs with high reproducibility and sensitivity. Infantile onset Pompe disease (IOPD) and severe MPS I cases are readily identifiable due to the absence of GAA and IDUA, respectively. In addition, late onset Pompe disease (LOPD) and attenuated MPS I patients showed much reduced levels of the target protein. By contrast, pseudodeficiency and carrier cases exhibited significant higher target protein levels compared to true patients.

Conclusion: Direct quantification of endogenous GAA and IDUA peptides in DBS by Immuno-SRM can be used for second-tier screening to rapidly identify severe PD and MPS I patients with a turnaround time of <1 week. Such patients could benefit from immediate clinical follow up and possibly earlier treatment.
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http://dx.doi.org/10.1016/j.ymgme.2022.06.006DOI Listing
August 2022

Quantification of SARS-CoV-2 RNA in wastewater treatment plants mirrors the pandemic trend in Hong Kong.

Sci Total Environ 2022 Jul 1:157121. Epub 2022 Jul 1.

Environmental Microbiome Engineering and Biotechnology Lab, Center for Environmental Engineering Research, Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China. Electronic address:

Wastewater-based epidemiology (WBE) for the SARS-CoV-2 virus in wastewater treatment plants (WWTPs) has emerged as a cost-effective and unbiased tool for population-level testing in the community. In the present study, we conducted a 6-month wastewater monitoring campaign from three WWTPs of different flow rates and catchment area characteristics, which serve 28 % (2.1 million people) of Hong Kong residents in total. Wastewater samples collected daily or every other day were concentrated using ultracentrifugation and the SARS-CoV-2 virus RNA in the supernatant was detected using the N1 and E primer sets. The results showed significant correlations between the virus concentration and the number of daily new cases in corresponding catchment areas of the three WWTPs when using 7-day moving average values (Kendall's tau-b value: 0.227-0.608, p < 0.001). SARS-CoV-2 virus concentration was normalized to a fecal indicator using PMMoV concentration and daily flow rates, but the normalization did not enhance the correlation. The key factors contributing to the correlation were also evaluated, including the sampling frequency, testing methods, and smoothing days. This study demonstrated the applicability of wastewater surveillance to monitor overall SARS-CoV-2 pandemic dynamics in a densely populated city like Hong Kong, and provides a large-scale longitudinal reference for the establishment of the long-term sentinel surveillance in WWTPs for WBE of pathogens which could be combined into a city-wide public health observatory.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249664PMC
July 2022

Antidepressant effect of Jujuboside A on corticosterone-induced depression in mice.

Biochem Biophys Res Commun 2022 09 25;620:56-62. Epub 2022 Jun 25.

School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China. Electronic address:

Objective: The aim of this study was to investigate the antidepressant effect of Jujuboside A (JuA) on corticosterone (CORT)-induced depression in mice and explore the underlying mechanisms.

Methods: The mice models were submitted to CORT and treated with JuA (10 and 30 mg/kg) for three weeks. Experiments were also performed on mice with brain-derived neurotrophic factor knockdown (BDNF (±)) as control subjects. Behavioral tests, including the open field test (OFT), tail suspension test (TST), forced swimming test (FST) and Morris water maze (MWM), were then performed to evaluate the antidepressant effect of JuA. The expression levels of BDNF, tyrosine kinase receptor B (TrkB), and cyclic AMP response element binding protein (CREB) in the hippocampi of mice were examined by immunohistochemistry (IHC) and Western blot. The effect of JuA on the viability of mouse hippocampal cells (HT22) was also assessed by CCK-8 assay.

Results: JuA significantly decreased the OFT and TST immobility time of the mice, the total distance travelled and the time spent in the central area also effectively increased in the OFT. In the MWM, the escape latencies of the mice decreased remarkably, while the number of times the mice crossed the platform and the target quadrant increased significantly after treatment with JuA. In addition, the BDNF, TrkB, and CREB expression levels were significantly increased in the hippocampi of the mice treated with JuA. Furthermore, JuA clearly attenuated CORT-induced cell injury, as evidenced by the increased viability of the HT22 cells.

Conclusion: These findings demonstrated that JuA may exhibit potential antidepressant effect in mice by increasing protein expression levels of BDNF, TrkB, CREB, and improving the viability of the hippocampal cells.
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http://dx.doi.org/10.1016/j.bbrc.2022.06.076DOI Listing
September 2022
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