Publications by authors named "Yan Zhao"

3,684 Publications

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A comparative study of the efficiency and safety of chemotherapy as a therapeutic method for recurrent or resistant gestational trophoblastic neoplasia: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(24):e26263

Department of Obstetrics and Gynecology, the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.

Background: Gestational trophoblastic neoplasia (GTN) is an infrequent spectrum of placental malignant cases. Generally, single-agent or multiple-agent chemotherapy is used to treat the condition. The condition has a significant impact on women in the childbearing age, which makes post-chemo fertility and obstetrical results a significant contemplation. Nearly 25% of GTN tumors are recurrent, or have a likelihood of relapsing after, the first round of chemotherapy. Therefore, these resistive and recurring lesions require salvage chemotherapy with or without surgical treatment. Therefore, the current meta-analysis and systematic review will assess the effectiveness and level of safety when using chemotherapy to treat women with resistive or recurring GTN.

Methods: The current study will perform a comprehensive systematic search for randomized controlled trials (RCTs) that have assessed the efficacy and safeness of chemo as a line of treatment for women with resistive or recurring GTN. To this end, a search will be conducted on the following electronic databases: Web of Science, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), EMBASE, WanFang database, and the Cochrane Library. The search will cover the period from the inception of databases to May 2021. In order to identify additional related studies, we will manually search the reference lists of suitable research articles and related systematic reviews. A pair of independent authors will review the titles/abstracts of the studies to check if the studies are eligible, which is proceeded by screening the full texts. This study will employ a uniform data extraction table for data extraction. Moreover, based on the Cochrane Risk of Bias Tool, this protocol review also assesses the bias risk in the studies involved.

Results: A comprehensive synthesis of existing indication on chemo treatment for women with resistive or recurring GTN.

Conclusion: The results offer fresh references for evaluating the effectiveness and safeness of chemo-based treatment for women with resistive or recurring GTN.

Ethics And Dissemination: An ethical approval is not needed as all data are published.

Review Registration Number: May 17, 2021.osf.io/uwky7. (https://osf.io/uwky7/).
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http://dx.doi.org/10.1097/MD.0000000000026263DOI Listing
June 2021

ALA-PDT successfully treated multiple cSCC in situ and AK in a patient with Epidermodysplasia verruciformis.

Photodiagnosis Photodyn Ther 2021 Jun 11:102395. Epub 2021 Jun 11.

Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:

5-aminolaevulinic acid photodynamic therapy (ALA-PDT) has emerged as a non-invasive treatment modality for premalignant and malignant skin lesions. It has the advantage of better tolerance and providing better cosmetic outcomes than conventional treatment methods. Herein, we report a patient who suffered from multiple cutaneous squamous cell carcinoma (cSCC) in situ and actinic keratosis (AK) scattered in the body's sun-exposed areas, which had led him to undergo multiple surgical resections since the age of 16. Next-generation sequencing-based on a targeted gene capture panel revealed compound heterozygous mutations c.G559A and c.G1389A in the TMC8 gene. Combined with the typical clinical manifestations and mutation analysis, the patient was diagnosed with Epidermodysplasia verruciformis (EV). Due to the multiple AK and cSCC in situ lesions, ALA-PDT was applied. After 8 courses of ALA-PDT all lesions were successfully cleared without causing any scarring. Therefore, the use of ALA-PDT treatment may constitute a very promising and effective therapeutic modality for multiple cSCC in situ and AK secondary to EV.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102395DOI Listing
June 2021

Synthetic Glycosidase Distinguishing Glycan and Glycosidic Linkage in Its Catalytic Hydrolysis.

Authors:
Xiaowei Li Yan Zhao

ACS Catal 2020 Dec 12;10(23):13800-13808. Epub 2020 Nov 12.

Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111, USA.

Selective hydrolysis of carbohydrates is vital to the processing of these molecules in biology but has rarely been achieved with synthetic catalysts. The challenge is especially difficult because the catalyst needs to distinguish the inversion of a single hydroxyl and the α or β glycosidic bonds that join monosaccharide building blocks. Here we report synthetic glycosidase prepared through molecular imprinting within a cross-linked micelle. The nanoparticle catalyst resembles natural enzymes in dimension, water-solubility, and a hydrophilic/hydrophobic surface-core topology. Its boronic acid-functionalized active site binds its targeted glycoside substrate and an acid cofactor simultaneously, with the acidic group in close proximity to the exocyclic glycosidic oxygen. The hydrophobically anchored acid cofactor is tunable in acidity and causes selective cleavage of the targeted glycoside in mildly acidic water. Selectivity for both the glycan and the α/β glycosidic bond can be rationally designed through the molecular imprinting process.
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http://dx.doi.org/10.1021/acscatal.0c04038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189344PMC
December 2020

Decomposition of individual-specific and individual-shared components from resting-state functional connectivity using a multi-task machine learning method.

Neuroimage 2021 Jun 9;238:118252. Epub 2021 Jun 9.

School of Biological Science & Medical Engineering, Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, 100083, China.

Resting-state functional connectivity (RSFC) can be used for mapping large-scale human brain networks during rest. There is considerable interest in distinguishing the individual-shared and individual-specific components in RSFC for the better identification of individuals and prediction of behavior. Therefore, we propose a multi-task learning based sparse convex alternating structure optimization (MTL-sCASO) method to decompose RSFC into individual-specific connectivity and individual-shared connectivity. We used synthetic data to validate the efficacy of the MTL-sCASO method. In addition, we verified that individual-specific connectivity achieves higher identification rates than the Pearson correlation (PC) method, and the individual-specific components observed in 886 individuals from the Human Connectome Project (HCP) examined in two sessions over two consecutive days might serve as individual fingerprints. Individual-specific connectivity has low inter-subject similarity (-0.005±0.023), while individual-shared connectivity has high inter-subject similarity (0.822±0.061). We also determined the anatomical locations (region or subsystem) related to individual attributes and common features. We find that individual-specific connectivity exhibits low degree centrality in the sensorimotor processing system but high degree centrality in the control system. Importantly, the individual-specific connectivity estimated by the MTL-sCASO method accurately predicts behavioral scores (improved by 9.4% compared to the PC method) in the cognitive dimension. The decomposition of individual-specific and individual-shared components from RSFC provides a new approach for tracing individual traits and group analysis using functional brain networks.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118252DOI Listing
June 2021

Analysis of sagittal curvature and its influencing factors in adolescent idiopathic scoliosis.

Medicine (Baltimore) 2021 Jun;100(23):e26274

Department of Anatomy, Inner Mongolia Medical University.

Abstract: This study aimed to explore the characteristics of changes in the sagittal arrangement of the spine between adolescent patients with idiopathic scoliosis (AIS) and normal adolescents, the risk factors for AIS and the factors affecting the progress of AIS.X-ray images of the full length of the spine in standing position were taken in AIS patients and normal adolescents. Radiographic measurements made at intermediate follow-up included the following:C1 and C2 cervical lordosis and C2 - C7 curvature of cervical lordosis, C2-C7sagittal horizontal distance (C2-C7SagittalVerticalAxis, C2-C7SVA), TS-CL, after thoracic lobe (Thoracic Kyphosis, TK), thoracic lumbar segment Angle (thoracolumbar kyphosis, [TLK]), lumbar lordosis Angle (Lumbar Lordosis, LL), sacral slope Angle (Sacrum Slope, SS), pelvic tilt Angle (Pelvic Tilt, PT), pelvic incidence (PI), L5 Incidence (Lumbar5 Slope (L5S), L5 incidence (Lumbar5 Incidence (L5I), sagittal horizontal distance (CSVA), lower depression Angle of the 2nd cervical spine. The difference of sagittal plane parameters between AIS group and normal adolescent group was compared. To evaluate the progress of AIS, correlation analysis was conducted between diagonal 2 and other parameters. The main risk factors of AIS were determined by binary Logistic analysis.The CSVA of AIS patients was higher than that of healthy adolescents (AIS: 27.64 ± 19.56) mm. Healthy adolescents: (17.74 ± 12.8) mm), L5S (AIS: 19.93°= 7.07° and healthy adolescents: 15.38°= 7.78°, P = .024 < .05), C2 downward sag Angle (AIS: 15.12°= 2.7°;Healthy adolescents: 12.97°= 4.56°); AIS patients had lower TS-CL (AIS: 22.48 ± 6.09 and healthy adolescents: 28.26°= 10.32°), PT (AIS: 10.42°= 4.53° and healthy adolescents: 15.80°=7.68°), (AIS: 41.87°=9.72° and healthy adolescents: 48.75°= 8.22°). The main risk factor for idiopathic scoliosis in adolescents was L5 (OR = 1.239, 95%CI = 1.049-1.463, P = .012 < .05).L5S is a major risk factor for idiopathic scoliosis in adolescents. The larger PI is, the higher the risk of scoliosis progression is. In AIS patients, lumbar lordosis is increased, cervical lordosis is reduced, and even cervical kyphosis occurs.
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http://dx.doi.org/10.1097/MD.0000000000026274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202640PMC
June 2021

Tumor-Specific Multipath Nucleic Acid Damages Strategy by Symbiosed [email protected] with Synergistic Self-Cyclic Catalysis.

Small 2021 Jun 10:e2100766. Epub 2021 Jun 10.

State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan, 410082, China.

The high proliferation efficiency, redox imbalance, and elevated nucleic acid repair capabilities of tumor cells severely restrict the theranostic efficacy. Selectively interference chaotic tumors with devastating nucleic acid damages (NUDs) properties are expected to overcome theranostic barriers. Here, an exquisite catalytic-based strategy with comprehensive NUDs mechanisms is demonstrated. In this regard, enzyme (glucose oxidase, GOD) symbioses nanozyme Cu (PO ) through biomineralization (abbreviated as [email protected]), GOD can disorder the metabolism by consuming glucose, thereby inhibiting the nutrition supply for nucleic acid repair. GOD-catalyzed H O guarantees the self-cyclic glutathione depletion and reactive oxygen species generation caused by Cu (PO ) , resulted the reduced antioxidation defense and enhanced oxidation assault, ensures an indiscriminate NUDs ability. Moreover, the high photothermal effect of Cu (PO ) induces effective tumor inhibition. Consequently, this substantial multipath NUDs strategy, with potentials of suppressing the cytoprotective mechanisms, amplifying the cellular oxidative stress, and disrupting the redox balance to ensure substantial irreversible NUDs, completely breaks the obstacle of chaotic tumors, providing new conceptual thinking for tumor proliferation inhibition.
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http://dx.doi.org/10.1002/smll.202100766DOI Listing
June 2021

Emodin inhibits lipid accumulation and inflammation in adipose tissue of high-fat diet-fed mice by inducing M2 polarization of adipose tissue macrophages.

FASEB J 2021 Jul;35(7):e21730

Department of Nutrition and Food Hygiene & Department of Health Education and Health Management, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Air Force Medical University, Xi'an, China.

Adipose tissue macrophages (ATMs) represent the most abundant leukocytes in adipose tissue (AT). An increase in number and a phenotypical switch of ATMs during the development of obesity contribute to chronic inflammation and metabolic disorders, which have been regarded as potential therapeutic targets to restore AT homeostasis. Emodin has been shown to exert strong anti-inflammatory property via acting on macrophages in a range of disease models. However, whether emodin exerts a beneficial effect on obesity via modulating ATMs has not been reported. In high-fat diet (HFD)-induced obese mice, emodin significantly inhibited the increase of body weight and lipid accumulation in ATs. Emodin apparently reduced glucose and insulin levels and ameliorated serum lipid profiles in HFD-fed mice. Moreover, the local and systemic inflammation was dramatically alleviated by emodin. We next discovered that M2 macrophage percentage was greatly increased by emodin although total ATMs was not altered, which resulted in a net increase of M2 macrophages in AT. In vitro studies confirmed that emodin promoted the polarization of macrophages towards M2. Gene ontology (GO) analysis showed that myeloid leukocyte differentiation and activation were among the most significant biological processes in emodin-treated ATMs. We further identified that TREM2 was the most dramatically upregulated molecule by emodin and emodin-induced M2 macrophage polarization was dependent on TREM2. Furthermore, silencing TREM2 apparently abrogated the effect of emodin on AT inflammation and adipogenesis. We, for the first time, disclosed that emodin inhibited obesity by promoting M2 macrophage polarization via TREM2, suggesting that emodin may be explored as a clinical and translational candidate in preventing obesity and its related metabolic diseases.
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http://dx.doi.org/10.1096/fj.202100157RRDOI Listing
July 2021

Structure and mechanism of the human NHE1-CHP1 complex.

Nat Commun 2021 06 9;12(1):3474. Epub 2021 Jun 9.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Sodium/proton exchanger 1 (NHE1) is an electroneutral secondary active transporter present on the plasma membrane of most mammalian cells and plays critical roles in regulating intracellular pH and volume homeostasis. Calcineurin B-homologous protein 1 (CHP1) is an obligate binding partner that promotes NHE1 biosynthetic maturation, cell surface expression and pH-sensitivity. Dysfunctions of either protein are associated with neurological disorders. Here, we elucidate structures of the human NHE1-CHP1 complex in both inward- and inhibitor (cariporide)-bound outward-facing conformations. We find that NHE1 assembles as a symmetrical homodimer, with each subunit undergoing an elevator-like conformational change during cation exchange. The cryo-EM map reveals the binding site for the NHE1 inhibitor cariporide, illustrating how inhibitors block transport activity. The CHP1 molecule differentially associates with these two conformational states of each NHE1 monomer, and this association difference probably underlies the regulation of NHE1 pH-sensitivity by CHP1.
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http://dx.doi.org/10.1038/s41467-021-23496-zDOI Listing
June 2021

Adenosine AR/AR Antagonists Enabling Additional HR Antagonism for the Treatment of Parkinson's Disease.

J Med Chem 2021 Jun 9. Epub 2021 Jun 9.

Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Duesseldorf, Universitaets street 1, 40225 Duesseldorf, Germany.

Adenosine A/A receptors (AR/AR) represent targets in nondopaminergic treatment of motor disorders such as Parkinson's disease (PD). As an innovative strategy, multitargeting ligands (MTLs) were developed to achieve comprehensive PD therapies simultaneously addressing comorbid symptoms such as sleep disruption. Recognizing the wake-promoting capacity of histamine H receptor (HR) antagonists in combination with the "caffeine-like effects" of AR/AR antagonists, we designed AR/AR/HR MTLs, where a piperidino-/pyrrolidino(propyloxy)phenyl HR pharmacophore was introduced with overlap into an adenosine antagonist arylindenopyrimidine core. These MTLs showed distinct receptor binding profiles with overall nanomolar HR affinities ( < 55 nM). Compound (, (AR) = 11.5 nM, (AR) = 7.25 nM) and (, (AR) = 11.2 nM, (AR) = 4.01 nM) were evaluated . l-DOPA-induced dyskinesia was improved after administration of compound (1 mg kg, i.p. rats). Compound (2 mg kg, p.o. mice) increased wakefulness representing novel pharmacological tools for PD therapy.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00914DOI Listing
June 2021

An optimized culture medium to isolate strains from the human intestinal tract.

Food Funct 2021 Jun 9. Epub 2021 Jun 9.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, P. R China. and School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China and (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China.

Research studies have shown that Lactobacillus fermentum generally exists in the human gut and has potential health benefits on host health due to its antimicrobial and antioxidant properties. However, the lack of an effective culture medium for the isolation of L. fermentum has presented a significant obstacle on the path to screen L. fermentum strains from the human intestinal tract with a large diversity of commensal microbes. In this study, a total of 51 Lactobacillus species are detected in 200 human fecal samples and we aim to distinguish L. fermentum from these common existing Lactobacillus species and design a more efficient culture medium for isolating L. fermentum strains from the human gut. Based on antibiotic susceptibility and sugar utilization tests, a new optimized medium called LFMATA containing arabinose as the carbon source and 20 mg L-1 vancomycin, 64 mg L-1 gentamicin and 256 mg L-1 streptomycin was developed. Genotype and phenotype analysis for antibiotic resistance and carbohydrate metabolism showed that though glycometabolism-related genes (araA, xylA, manX, bglX, treP and rbsK) correlated with the carbon utilization of Lactobacillus, the genes conferring resistance to streptomycin (gidB and rpsL) and gentamicin (tlyA) were not directly associated with the antibiotic resistance of Lactobacillus strains. This new selective medium greatly increased the efficiency of screening L. fermentum strains from human fecal samples, with the rate of L. fermentum isolation on LFMATA being 10-fold higher than that on LAMVAB.
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http://dx.doi.org/10.1039/d1fo00209kDOI Listing
June 2021

The BPAN and intellectual disability disease proteins WDR45 and WDR45B modulate autophagosome-lysosome fusion.

Autophagy 2021 Jun 9:1-2. Epub 2021 Jun 9.

Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, P.R. China.

WDR45 and WDR45B are β-propeller proteins belonging to the WIPI (WD repeat domain, phosphoinositide interacting) family. Mutations in and are genetically linked with beta-propeller protein-associated neurodegeneration (BPAN) and intellectual disability (ID), respectively. WDR45 and WDR45B are homologs of yeast Atg18. Atg18 forms a complex with Atg2 for autophagosome biogenesis, probably by transferring lipids from the ER to phagophores. We revealed that WDR45 and WDR45B are critical for autophagosome-lysosome fusion in neural cells. WDR45 and WDR45B, but not their disease-related mutants, bind to the tether protein EPG5 and facilitate its targeting to late endosomes/lysosomes. In -deficient cells, the formation of tether-SNARE fusion machinery is compromised. The macroautophagy/autophagy deficiency in DKO cells is ameliorated by suppression of -GlcNAcylation, which promotes autophagosome maturation. Thus, our results provide insights into the pathogenesis of and -related neurological diseases.
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http://dx.doi.org/10.1080/15548627.2021.1924039DOI Listing
June 2021

Single-Cell Transcriptome Analysis Uncovers Intratumoral Heterogeneity and Underlying Mechanisms for Drug Resistance in Hepatobiliary Tumor Organoids.

Adv Sci (Weinh) 2021 06 23;8(11):e2003897. Epub 2021 Mar 23.

National Center for Liver Cancer, Shanghai, 200441, China.

Molecular heterogeneity of hepatobiliary tumor including intertumoral and intratumoral disparity always leads to drug resistance. Here, seven hepatobiliary tumor organoids are generated to explore heterogeneity and evolution via single-cell RNA sequencing. HCC272 with high status of epithelia-mesenchymal transition proves broad-spectrum drug resistance. By examining the expression pattern of cancer stem cells markers (e.g., PROM1, CD44, and EPCAM), it is found that CD44 positive population may render drug resistance in HCC272. UMAP and pseudo-time analysis identify the intratumoral heterogeneity and distinct evolutionary trajectories, of which catenin beta-1 (CTNNB1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and nuclear paraspeckle assembly transcript 1 (NEAT1) advantage expression clusters are commonly shared across hepatobiliary organoids. CellphoneDB analysis further implies that metabolism advantage organoids with enrichment of hypoxia signal upregulate NEAT1 expression in CD44 subgroup and mediate drug resistance that relies on Jak-STAT pathway. Moreover, metabolism advantage clusters shared in several organoids have similar characteristic genes (GAPDH, NDRG1 (N-Myc downstream regulated 1), ALDOA, and CA9). The combination of GAPDH and NDRG1 is an independent risk factor and predictor for patient survival. This study delineates heterogeneity of hepatobiliary tumor organoids and proposes that the collaboration of intratumoral heterogenic subpopulations renders malignant phenotypes and drug resistance.
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http://dx.doi.org/10.1002/advs.202003897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188185PMC
June 2021

Predicting Risk of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: CSTAR Cohort Study.

Arthritis Rheumatol 2021 Jun 9. Epub 2021 Jun 9.

Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Objectives: Pulmonary arterial hypertension is a life-threatening complication of systemic lupus erythematosus. However, there is no algorithm to identify those at high risk. We aimed to develop a prediction model for pulmonary arterial hypertension in lupus patients that provides individualized risk estimates.

Methods: A multicenter, longitudinal cohort study was undertaken from January 2003 to January 2020. The study collected data on 3,624 consecutively evaluated patients diagnosed with lupus. The diagnosis of pulmonary arterial hypertension was confirmed by right heart catheterization. Cox proportional hazards regression and least absolute shrinkage and selection operator were used to fit the model. Model discrimination, calibration, and decision curve analysis were assessed for validation.

Results: Ninety-two lupus patients developed pulmonary arterial hypertension (2.54%) at a median follow-up of 4.84 years (interquartile range, 2.42-8.84). The final prediction model included five clinical variables (acute/subacute cutaneous lupus, arthritis, renal disorder, thrombocytopenia, and interstitial lung disease) and three autoantibodies (anti-RNP, anti-Ro/SSA and anti-La/SSB). A 10-year pulmonary arterial hypertension probability-predictive nomogram was established. The model was internally validated by C statistic (0.78), the Brier score (0.03), and a satisfactory calibration curve. According to the net benefit and predicted probability thresholds, we recommend annual screening in high-risk (> 4.62 %) lupus patients.

Conclusion: We developed a risk stratification model using routine clinical assessments. This new tool may effectively predict the future risk of pulmonary arterial hypertension in patients with systemic lupus erythematosus.
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http://dx.doi.org/10.1002/art.41740DOI Listing
June 2021

Fabrics with Novel Air-Oil Amphibious, Spontaneous One-Way Water-Transport Capability for Oil/Water Separation.

ACS Appl Mater Interfaces 2021 Jun 8. Epub 2021 Jun 8.

College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China.

Porous media with directional water-transport capability have great applications in oil-water separation, moisture-harvesting, microfluidics, and moisture-management textiles. However, the previous directional water-transport materials chiefly work in the air. The materials with directional water-transport capability in the oil phase have been less reported. Here, we fabricated a novel Janus fabric with amphibious directional water-transport capability that can work both in the air and oil phases. It was prepared using dip coating and spraying to develop an oleophobic-hydrophobic to oleophobic-hydrophilic gradient across the thickness of the fabric substrate. The fabric allowed water droplets to rapidly transport from the hydrophobic to the hydrophilic side when the fabric was either in the air environment or fully immersed in oil. However, it hindered water transport in the opposite direction. More importantly, the fabric can overcome gravity to capture water from oil. Such an air-oil amphibious water-transport fabric showed excellent water collecting capability. In oil, it does not require any prewetting or extra pressure to perform directional water transport, which is vital for water-oil separation and microfluidics. Such amphibious directional water-transport function may be useful for the development of smart membranes and directional liquid delivery.
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http://dx.doi.org/10.1021/acsami.1c06489DOI Listing
June 2021

Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu).

Stem Cell Res Ther 2021 Jun 7;12(1):331. Epub 2021 Jun 7.

Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.

Background: Local ischemia and defective osteogenesis are implicated in the progression of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies have revealed that exosomes released from adipose-derived stem cells (ASCs) play important roles in ONFH therapy. The present study aimed to investigate whether exosomes derived from miR-378-overexpressing ASCs (miR-378-ASCs-Exos) could promote angiogenesis and osteogenesis in GC-induced ONFH.

Methods: In vitro, we investigated the osteogenic potential of miR-378-ASCs-Exos on bone marrow stromal cells (BMSCs) by alkaline phosphatase staining and western blotting. The angiogenic effects of miR-378-ASCs-Exos on human umbilical vein endothelial cells (HUVECs) were examined by evaluating their proliferation, migration, and tube-forming analyses. We identified the underlying mechanisms of miR-378 in osteogenic and angiogenic regulation. In addition, an ONFH rat model was established to explore the effects of miR-378-ASCs-Exos through histological and immunohistochemical staining and micro-CT in vivo.

Results: Administration of miR-378-ASCs-Exos improved the osteogenic and angiogenic potentials of BMSCs and HUVECs. miR-378 negatively regulated the suppressor of fused (Sufu) and activated Sonic Hedgehog (Shh) signaling pathway, and recombinant Sufu protein reduced the effects triggered by miR-378-ASCs-Exos. In vivo experiments indicated that miR-378-ASCs-Exos markedly accelerated bone regeneration and angiogenesis, which inhibited the progression of ONFH.

Conclusion: Our study indicated that miR-378-ASCs-Exos enhances osteogenesis and angiogenesis by targeting Sufu to upregulate the Shh signaling pathway, thereby attenuating GC-induced ONFH development.
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http://dx.doi.org/10.1186/s13287-021-02390-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186190PMC
June 2021

The ester derivatives obtained by C-ring modification of podophyllotoxin induce apoptosis and inhibited proliferation in PC-3M cells via down-regulation of PI3K/Akt signaling pathway.

Bioorg Med Chem Lett 2021 Jun 11;46:128174. Epub 2021 Jun 11.

The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address:

Podophyllotoxin (PPT) has been reported to have many pharmacological activities, especially its anti-tumor effects. To improve the cytotoxicity and selective effect of PPT, in this study, we have designed and synthesized 20 ester derivatives by introducing Boc-amino acids or organic acids at the C-4 position of PPT. The cytotoxicity of these compounds was evaluated with PC-3M, HemECs, A549, MCF-7 and HepG2 cells. We observed that the proliferation of PC-3M cells was inhibited by all 20 ester derivatives in the largest degree, comparing to the other cell lines. Comparing to PPT (IC = 234.90 ± 20.7 nM), eight derivatives had better performance in inhabiting proliferation of PC-3M cells, six of them belong to Boc-amino acid ester derivatives, and the derivative named V-05 (IC = 1.28 ± 0.1 nM) had the strongest inhibitation effect. Changes in cell proliferation and apoptotic signaling pathways were studied by DAPI staining, colony formation assay, migration assay, flow cytometry and western blot analysis. We found that V-05 were able to inhibit PC-3M cells proliferation and migration, and induced apoptosis by downregualting p-PI3K, p-Akt and Bcl-2, and upregulating Cleaved caspase-3 and Bax. Our research provides the first insight for the application of PPT derivatives in PC-3M cells, which may offer information to the effective medicine development for human prostate cancer treatment.
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http://dx.doi.org/10.1016/j.bmcl.2021.128174DOI Listing
June 2021

pH-Controlled Nanoparticle Catalysts for Highly Selective Tandem Henry Reaction from Mixtures.

ACS Catal 2020 Dec 17;10(23):13973-13977. Epub 2020 Nov 17.

Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111, United States.

Nature has a remarkable ability to perform selective transformation of complex biological mixtures into desired products using enzymatic catalysts. We report the preparation of nanoparticle catalysts through molecular imprinting within cross-linked micelles. These catalysts were highly selective for their targeted substrates and could selectively hydrolyze less reactive acetals over more reactive ones even under basic conditions. Their catalytic activity and selectivity were tunable through rational postmodification of the active site. These properties enabled the nanoparticle catalysts to produce the desired β-nitro alcohol from a four-component acetal mixture in a tandem deprotection/Henry reaction that required incompatible acidic and basic catalysts in the two steps.
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http://dx.doi.org/10.1021/acscatal.0c03468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171280PMC
December 2020

Cyclooctatetraene-conjugated cyanine mitochondrial probes minimize phototoxicity in fluorescence and nanoscopic imaging.

Chem Sci 2020 Jul 27;11(32):8506-8516. Epub 2020 Jul 27.

Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University Beijing China

Modern fluorescence-imaging methods promise to unveil organelle dynamics in live cells. Phototoxicity, however, has become a prevailing issue when boosted illumination applies. Mitochondria are representative organelles whose research heavily relies on optical imaging, yet these membranous hubs of bioenergy are exceptionally vulnerable to photodamage. We report that cyclooctatetraene-conjugated cyanine dyes (PK Mito dyes), are ideal mitochondrial probes with remarkably low photodynamic damage for general use in fluorescence cytometry. In contrast, the nitrobenzene conjugate of Cy3 exhibits enhanced photostability but unaffected phototoxicity compared to parental Cy3. PK Mito Red, in conjunction with Hessian-structural illumination microscopy, enables 2000-frame time-lapse imaging with clearly resolvable crista structures, revealing rich mitochondrial dynamics. In a rigorous stem cell sorting and transplantation assay, PK Mito Red maximally retains the stemness of planarian neoblasts, exhibiting excellent multifaceted biocompatibility. Resonating with the ongoing theme of reducing photodamage using optical approaches, this work advocates the evaluation and minimization of phototoxicity when developing imaging probes.
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http://dx.doi.org/10.1039/d0sc02837aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161535PMC
July 2020

Changes in lipid properties of duck egg yolks under extreme processing conditions.

Poult Sci 2021 Mar 22;100(7):101140. Epub 2021 Mar 22.

Engineering Research Center of Biomass Conversion, Ministry of Education, Nanchang University, Nanchang 330047, China; State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China. Electronic address:

The changes in lipid properties of duck egg yolks during processing may affect the quality of egg yolks. In this paper, various physicochemical and instrumental methods were used to study the changes of lipid characteristics of duck egg yolks under extreme processing conditions such as high salt, high salt-heat synergy and strong alkali. The results showed that both the high salt and high salt-heat treatments resulted in the decrease of the moisture content and the increase of the oil exudation of egg yolks. The iodine value of the lipid extracted from salted egg yolks with or without heat treatment decreased. However, strong alkali treatment increased the moisture content of egg yolks, and the oil exudation increased at first and then decreased. The iodine value of the lipid obtained from preserved egg yolks showed an overall trend with first increase and then decrease, and the saponification value of the lipid got from preserved egg yolks was lower than the lipid got from the raw salted egg yolks. According to the conjugated diene acid value and thiobarbituric acid value, the lipid of egg yolks was oxidized to different degrees under the three processing conditions. At the end of pickling, the fatty acid content of the lipid acquired from egg yolks all increased. Therefore, all three extreme treatments significantly changed the lipid properties of duck egg yolks.
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http://dx.doi.org/10.1016/j.psj.2021.101140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182270PMC
March 2021

Assessment of Streptococcus mutans biofilms on orthodontic adhesives over 7 days.

Am J Orthod Dentofacial Orthop 2021 Jun 2. Epub 2021 Jun 2.

Division of Dental Biomaterials, Department of Restorative Sciences, College of Dentistry, University of Oklahoma Health Sciences Center, Oklahoma City, Okla. Electronic address:

Introduction: The purpose of this study was to compare the metabolism of Streptococcus mutans biofilms after 1-7 days of growth on different orthodontic adhesives.

Methods: Specimens of 6 commercial orthodontic adhesives were fabricated in custom-made molds and polymerized using a light-emitting diode light-curing unit. Bioluminescent S mutans (UA159:JM10) biofilms were grown on ultraviolet-sterilized specimens for 1, 3, 5, and 7 days (n = 18 biofilms/d/product) in anaerobic conditions at 37°C. The metabolism of biofilms (relative luminescence unit [RLU]) was measured 0, 2, 4, and 6 minutes after exposure to D-luciferin solution using a microplate reader. A linear mixed-effects model was used to analyze the logarithm of RLU (log RLU). The model included fixed effects of products, days, and minutes. Tukey-Kramer post-hoc tests were then performed on the significant predictors of log RLU (α = 0.05).

Results: Days (P <0.0001) and minutes (P <0.0001) were independent predictors of log RLU, but the products were not (P = 0.5869). After adjusting for minutes, the log RLU was analyzed with a post-hoc test, and all differences between days were significant with the exceptions of day 3 from day 5 (P = 0.0731) and day 5 from day 7 (P = 0.8802). After adjusting for day, log RLU was analyzed with a post-hoc test and all differences in minutes were significant.

Conclusions: No significant differences in the metabolism of S mutans biofilms were observed among the 6 orthodontic adhesives. Biofilms that were grown for 3 days demonstrated the highest levels of biofilm metabolism as evidenced by higher mean log RLU values relative to 1, 5, and 7-day growth durations.
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http://dx.doi.org/10.1016/j.ajodo.2020.03.026DOI Listing
June 2021

Chlorine-assisted synthesis of [email protected](Cu,Co)Cl(OH) heterostructures with an efficient nanointerface for electrocatalytic oxygen evolution.

J Colloid Interface Sci 2021 May 25;601:437-445. Epub 2021 May 25.

College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China. Electronic address:

The demand for sustainable energy sources urges the development of efficient and earth-abundant electrocatalysts. Herein, chlorine assisted ion-exchange and in-situ sulfurization processes were combined to construct [email protected](Cu,Co)Cl(OH) heterostructures from Cu(OH) nanoarrays. Chlorine element in the cobalt source stimulated the formation of (Cu,Co)Cl(OH) precursor, and further facilitated partial transformation of the precursor to CuCoS on the surface to achieve composite structure. The mixed valences of Co element (Co in CuCoS and Co in (Cu,Co)Cl(OH)) and OS interpenetrated nanointerface in the composite catalysts provided low electron transfer resistance for good alkaline oxygen evolution reaction (OER) activities. In 1 mol L KOH electrolyte, the overpotentials of the optimal composite catalyst reached 253 and 290 mV respectively at the current density of 20 and 50 mA cm, which is comparable to the activity of commercial Ir/C (281 [email protected] mA cm). These findings could provide opportunities for designing effective and inexpensive composite electrocatalysts through nanointerface engineering strategy.
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http://dx.doi.org/10.1016/j.jcis.2021.05.129DOI Listing
May 2021

Seasonal variation and positive matrix factorization result reveal the sources of giant pandas' exposure to POPs.

Ecotoxicol Environ Saf 2021 Aug 1;219:112363. Epub 2021 Jun 1.

Shaanxi Wild Animal Research Center, Zhouzhi, Xi'an 710402, China.

Persistent organic pollutant (POPs) contamination was analyzed in samples collected from wild and captive giant pandas to characterize seasonal variation in concentrations of POPs and possible sources. POP concentrations in bamboo and fecal samples collected from captive pandas showed significant fluctuations compared with those collected from wild pandas in each season. The highest polychlorinated biphenyl (PCB) and organochlorine pesticide (OCP) concentrations were 1380 pg g dw and 3140 pg g dw, respectively, which were observed in captive bamboo samples in the summer. PCBs varied seasonally, whereas OCPs did not show apparent seasonal variation. Based on the seasonal variability, component analysis, and the positive matrix factorization results, we determined that the secondary volatilization of POPs during periods of high temperatures was the leading cause of the exposure of pandas to pollutants (45%), and atmospheric transport played a crucial role in the secondary distribution of pollutants in panda food. The other two sources of pollution were historical residues transmitted over long distances to protected areas (28%), as well as UP-POPs and new inputs from agricultural activities (27%). The concentrations of pollutants in bamboo shoots were significantly lower than those in bamboo. Therefore, bamboo shoots should be incorporated into the diet of captive pandas in the spring to reduce their exposure to pollutants. The absorption capacity of pollutants associated with the consumption of bamboo shoots was significantly lower than that associated with the consumption of bamboo. The diet of young captive pandas in the summer should also be managed with caution given their slightly stronger ability to absorb pollutants.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112363DOI Listing
August 2021

Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis.

Am J Emerg Med 2021 May 18;49:62-70. Epub 2021 May 18.

Department of Pediatrics, People's Hospital of Chongqing Banan District, Chongqing 401320, China. Electronic address:

Objective: A meta-analysis of laboratory cardiac markers for multisystem inflammatory syndrome in children (MIS-C) was performed in patients with coronavirus disease 2019 (COVID-19).

Methods: Eight databases were searched until April 10, 2021, for studies on cardiac markers, including B-type natriuretic peptide (BNP)/N-terminal pro-BNP (NT-proBNP), troponin, aspartate aminotransferase (AST), in MIS-C patients.

Results: Of the 2583 participants enrolled in 24 studies, 1613 patients were diagnosed with MIS-C. MIS-C patients exhibited higher BNP levels than patients with non-severe COVID-19 [SMD (95% CI): 1.13 (0.48, 1.77), p < 0.05]. No significant differences in BNP levels were observed between patients with MIS-C and severe COVID-19 [SMD (95% CI): 0.29 (-0.07, 0.65), p = 0.117]. Comparisons of MIS-C patients to all COVID-19 patients revealed no significant differences in levels of troponin [SMD (95% CI): 0.13 (-0.07, 0.32), p = 0.212] or AST [SMD (95% CI): 0.10 (-0.11, 0.31), p = 0.336]. Compared to patients with non-severe MIS-C, those with severe MIS-C exhibited higher levels of BNP [SMD (95% CI): 0.26 (0.04, 0.48), p < 0.05], but no differences in troponin [SMD (95% CI): 0.05 (-0.06, 0.16) p = 0.387] or AST [SMD (95% CI): 0.19 (-0.34, 0.71), p = 0.483] were observed. Moreover, there was no significant difference in BNP [SMD (95% CI): -0.21 (-1.07, 0.64), p = 0.624] or troponin [SMD (95% CI): -0.07 (-0.45, 0.31), p = 0.710] between MIS-C with and without coronary artery abnormality. Sensitivity analyses were performed to assess stability. No publication bias was detected based on Begg's test.

Conclusions: The key cardiac marker that showed differences between patients with MIS-C/non-severe COVID-19 and between patients with severe/non-severe MIS-C was BNP. Other markers, such as troponin and AST, did not exhibit notable differences in indicating cardiac injury between patients with MIS-C and COVID-19.
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http://dx.doi.org/10.1016/j.ajem.2021.05.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129790PMC
May 2021

Chemical Analysis Combined with Multivariate Statistical Methods to Determine the Geographical Origin of Milk from Four Regions in China.

Foods 2021 May 18;10(5). Epub 2021 May 18.

Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Traceability of milk origin in China is conducive to the implementation of the protection of regional products. In order to distinguish milk from different geographical distances in China, we traced the milk of eight farms in four neighboring provinces of China (Inner Mongolia autonomous region, Hebei, Ningxia Hui autonomous and Shaanxi), and multivariate data analysis was applied to the data including elemental analysis, stable isotope analysis and fatty acid analysis. In addition, orthogonal partial least squares discriminant analysis (OPLS-DA) is used to determine the optimal classification model, and it is explored whether the combination of different technologies is better than a single technical analysis. It was confirmed that in the inter-provincial samples, the combination of the two techniques was better than the analysis using a single technique (fatty acids: R = 0.716, Q = 0.614; fatty acid-binding isotopes: R = 0.760, Q = 0.635). At the same time, milk produced by farms with different distances of less than 11 km in each province was discriminated, and the discriminant distance was successfully reduced to 0.7 km (Ningxia Hui Autonomous Region: the distance between the two farms was 0.7 km, R = 0.771, Q = 0.631). For short-distance samples, the combination multiple technologies are not completely superior to a single technique, and sometimes, it is easy to cause model over-fitting.
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http://dx.doi.org/10.3390/foods10051119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158098PMC
May 2021

Synthesizing Photoluminescent Au28(SCH2Ph-tBu)22 Nanoclusters with Feature Structures by Using A Joint Method.

Angew Chem Int Ed Engl 2021 Jun 1. Epub 2021 Jun 1.

Institute of Solid State Physics Chinese Academy of Sciences, Nanomaterials and nanotechnologies, CHINA.

Metal nanoclusters are currently widely researched; however, some fundamental studies, such as studies to improve the understanding of the kernel evolution pattern and structural photoluminescence, are far from complete due to the limitations of the synthesis method. Herein, we introduced a novel strategy-the joint of the current synthesis methods for atomically precise nanocluster synthesis. As an illustration, we introduced the reducing-ligand induction joint method and synthesized a novel nanocluster, which was determined to be Au 28 (SCH 2 Ph- t Bu) 22 with the same number of gold atoms as existing Au 28 (SR) 20 nanoclusters but different ligands (hetero-staple-homo-size). Compared with the latter, the former has distinct properties and structures. In particular, a novel kernel evolution pattern was first reported, i.e., the quasi-linear growth of Au 4 -tetrahedron by sharing one vertex and feature structures, including a tritetrahedron kernel with two bridging thiolates and two Au 6 (SCH 2 Ph- t Bu) 6 hexamer chair-like rings on the kernel surface were also first reported, which endow Au 28 (SCH 2 Ph- t Bu) 22 with the best photoluminescence quantum yield among hydrophobic thiolated gold nanoclusters so far, probably due to the enhanced charge transfer from the bi-ring to the kernel via Au-Au bonds.
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http://dx.doi.org/10.1002/anie.202105530DOI Listing
June 2021

Substrate Protection in Controlled Enzymatic Transformation of Peptides and Proteins.

Authors:
Yan Zhao

Chembiochem 2021 May 31. Epub 2021 May 31.

Department of Chemistry, Iowa State University, Ames, IA 50011-3111, USA.

Proteins are involved in practically every single biological process. The many enzymes involved in their synthesis, cleavage, and posttranslational modification (PTM) carry out highly specific tasks with no usage of protecting groups. Yet, the chemists' strategy of protection/deprotection potentially can be highly useful, for example, when a specific biochemical reaction catalyzed by a broad-specificity enzyme needs to be inhibited, during infection of cells by enveloped viruses, in the invasion and spread of cancer cells, and upon mechanistic investigation of signal-transduction pathways. Doing so requires highly specific binding of peptide substrates in aqueous solution with biologically competitive affinities. Recent development of peptide-imprinted cross-linked micelles allows such protection and affords previously impossible ways of manipulating peptides and proteins in enzymatic transformations.
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http://dx.doi.org/10.1002/cbic.202100217DOI Listing
May 2021

Application of single-sperm sequencing in a male with Marfan syndrome: a case report and a literature review.

J Genet 2021 ;100

Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, People's Republic of China.

Marfan syndrome (MFS) is caused by a mutation. Many organ systems are affected in patients with MFS, including the skeletal, ocular, cardiovascular and pulmonary systems. Cardiovascular manifestations are the main cause of mortality in patients with MFS. The mode of inheritance of MFS is autosomal dominant inheritance and the offspring are at great risk for the disease. Thus, the genetic testing for monogenic disease during preimplantation (PGT-M) is routinely advised for patients with MFS. PGT-M is a clinical genetic method to obtain normal embryos which are not affected by the monogenetic disorder. However, allele drop out (ADO) typically results in misdiagnosis during the PGT-M in the autosomal dominant disorder. Thus, a linkage analysis of polymorphic sites is used to identify ADO and improve the accuracy of PGT-M. However, when there are no family members affected, or the patients carry a mutation, a linkage analysis cannot be performed to position the abnormal chromatid. Here, we performed single-sperm sequencing of preimplantation genetic testing in a male patient with MFS with a mutation in . We constructed the chromosomal haplotype of the male patient by analysing information at the mutation site and at polymorphic sites. Next, the normal embryos were selected based on the results of high-throughput sequencing and haplotyping, and the one frozen embryo was transferred to the uterus. Finally, the preimplantation genetic testing results were confirmed by the prenatal genetic diagnosis during pregnancy, which showed that the foetus did not carry the pathogenic mutation. In conclusion, our research showed that single-sperm sequencing and haplotype analysis can be used in male patients with monogenetic disorders caused by mutations to improve the accuracy of the preimplantation genetic diagnosis.
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January 2021

Crystallization, Mechanical, and Antimicrobial Properties of Diallyl Cyanuric Derivative-Grafted Polypropylene.

ACS Omega 2021 May 3;6(19):12794-12800. Epub 2021 May 3.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University, Shanghai 200438, China.

A functional -halamine precursor with double bonds, 1-3-diallyl--triazine-2,4,6-trione (DTT), was synthesized and grafted onto polypropylene using dicumyl peroxide (DCP) as an initiator via melt blending at 200 °C. The DTT content grafted onto the polypropylene (PP) backbone was depended on both DTT and DCP concentrations in feed. The crystallization temperature of PP increased from 116 °C (neat PP) to 123 °C (10% DTT) with the increasing DTT content. Meanwhile, the crystallization rate and relative crystallinity of PP were significantly increased after introduction of the -halamine precursor. Moreover, the incorporation of DTT had partial compensation for the decreasing mechanical properties of polypropylene, which resulted from degradation. When the amount of added DTT reached up to 5%, the chlorinated DTT-modified PP sheets were able to kill 10 cfu/mL (CMCC 44103) and (ATCC 6538) within 10 min. The DTT-modified PP with the regenerating antibacterial property may have great potential for application in packaging, filters, and hygienic products.
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http://dx.doi.org/10.1021/acsomega.1c01100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154233PMC
May 2021

Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS.

Front Immunol 2021 13;12:652782. Epub 2021 May 13.

Department of Pharmacology, Dalian Medical University, Dalian, China.

Pyroptosis is a newly discovered form of cell death. Peroxiredoxin 3 (PRX3) plays a crucial role in scavenging reactive oxygen species (ROS), but its hepatoprotective capacity in acetaminophen (APAP)-induced liver disease remains unclear. The aim of this study was to assess the role of PRX3 in the regulation of pyroptosis during APAP-mediated hepatotoxicity. We demonstrated that pyroptosis occurs in APAP-induced liver injury accompanied by intense oxidative stress and inflammation, and liver specific PRX3 silencing aggravated the initiation of pyroptosis and liver injury after APAP intervention. Notably, excessive mitochondrial ROS (mtROS) was observed to trigger pyroptosis by activating the NLRP3 inflammasome, which was ameliorated by Mito-TEMPO treatment, indicating that the anti-pyroptotic role of PRX3 relies on its powerful ability to regulate mtROS. Overall, PRX3 regulates NLRP3-dependent pyroptosis in APAP-induced liver injury by targeting mitochondrial oxidative stress.
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http://dx.doi.org/10.3389/fimmu.2021.652782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155593PMC
May 2021

Ameliorative Effects of Osthole on Experimental Renal Fibrosis and by Inhibiting IL-11/ERK1/2 Signaling.

Front Pharmacol 2021 13;12:646331. Epub 2021 May 13.

Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Natural product, osthole, has been proven to have a protective effect on organ fibrosis, including renal fibrosis. All of these studies are mainly focused on the regulation of TGF-β/Smad signaling pathway. However, due to the pleiotropic roles of TGF-β/Smad signaling, direct TGF-β-targeted treatments are unlikely to be therapeutically feasible in clinic. Recently, the downstream IL-11/ERK1/2 signaling of TGF-β has become an attractive therapeutic target without upstream disadvantages. Based on that, this study was designed to identify the potential effects of osthole on IL-11/ERK1/2 signaling pathway in renal fibrosis. The renal fibrosis model was established and , we investigated the effects of osthole on unilateral ureteral obstruction (UUO)-induced renal fibrosis and TGF-β-induced HK-2 cells. After preliminarily confirming the antifibrogenic effects of osthole and the link between its antifibrogenic effects and the inhibition of IL-11/ERK1/2 signaling, we applied a direct IL-11-induced HK-2 cells fibrosis model to further explore the inhibitory effects of osthole on IL-11/ERK1/2 signaling pathway. Our results confirmed that osthole can decrease the secretion of fibrosis proteins, such as α-smooth muscle actin (α-SMA), collagen I, and fibronectin, ameliorate experimental renal fibrosis and , and the effect was associated with suppressing TGF-β1/Smad signaling. More importantly, we found that IL-11/ERK1/2 signaling in UUO-induced renal fibrosis and TGF-β-induced HK-2 cell model was obviously upregulated, and osthole treatment also significantly inhibited the abnormal IL-11/ERK1/2 signaling activation. Given the direct link between TGF-β/Smad signaling and IL-11/ERK1/2 signaling pathway, we have verified that osthole has a direct inhibitory effect on IL-11/ERK1/2 signaling independent of TGF-β signaling by using an IL-11-induced HK-2 cells fibrosis model. Osthole treatment decreased the protein expression of α-SMA, collagen I and fibronectin without changing their mRNA levels in IL-11-induced HK-2 cells. Moreover, it was observed that the IL-11/ERK1/2 inhibitor, U0126, partly blocked the antifibrogenic effects of osthole. In this study, we found that osthole has a previously unrecognized role in inhibiting IL-11/ERK1/2 signaling pathway. Our work demonstrated that the antifibrogenic effect of osthole is not only mediated by TGF-β/Smad2/3 signaling, but also directly mediated by IL-11/ERK1/2 signaling pathway independent of TGF-β1 signaling.
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http://dx.doi.org/10.3389/fphar.2021.646331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155534PMC
May 2021