Publications by authors named "Dan Zhang"

2,142 Publications

  • Page 1 of 1

A density-based matrix transformation clustering method for electrical load.

PLoS One 2022 11;17(8):e0272767. Epub 2022 Aug 11.

School of Business Administration, Liaoning Technical University, Huludao, Liaoning, China.

Feature extraction of electrical load plays a vital role in providing a reliable basis and guidance for power companies. In this paper, we propose a novel clustering algorithm named the Density-based Matrix Transformation (DBMT) Clustering method to extract features (peaks, valleys and trends) of electrical load curves. The main objective of the algorithm is to reorder the data items until the data items belonging to the same cluster are organized together; that is, the adjacent matrix is rearranged to the type of block diagonal. This method adaptively determines the number of clusters and filters out noise without input global parameters. Moreover, for the specific characteristics of raw electrical load data, we propose a variant of Dynamic Time Warp (DTW) distance, dsDTW, which aligns the peaks, valleys and trends of load curves meanwhile dealing with missing values in different situations. After feeding the dsDTW adjacent matrix to DBMT, the results indicate that our proposal can accurately extract the feature of the load curves compared to different clustering methods.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0272767PLOS
August 2022

J. Ellis extract GJ-4 attenuates hyperlipidemic vascular dementia in rats via regulating PPAR-γ-mediated microglial polarization.

Food Nutr Res 2022 19;66. Epub 2022 Jul 19.

State Key Laboratory of Bioactive Substrate and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: GJ-4 is extracted from J. Ellis (Fructus Gardenia) with crocin composition and has been demonstrated to improve memory deficits in several dementia models in our previous studies.

Objective: This study aimed to evaluate the effects of GJ-4 on hyperlipidemic vascular dementia (VD) and explore the underlying mechanisms.

Design: In the current study, we employed a chronic hyperlipidemic VD rat model by permanent bilateral common carotid arteries occlusion (2-VO) based on high-fat diet (HFD), which is an ideal model to mimic the clinical pathogenesis of human VD.

Results: Our results showed that GJ-4 could significantly reduce serum lipids level and improve cerebral blood flow in hyperlipidemic VD rats. Additionally, treatment with GJ-4 remarkedly ameliorated memory impairment and alleviated neuronal injury. Mechanistic investigation revealed that the neuroprotective effects of GJ-4 might be attributed to the inhibition of microglia-mediated neuro-inflammation via regulating the M1/M2 polarization. Our data further illustrated that GJ-4 could regulate the phenotype of microglia through activating the peroxisome proliferator-activated receptor-γ (PPAR-γ) and subsequently inhibited nuclear factor-κB (NF-κB) nuclear translocation and increased CCAAT/enhancer-binding protein β (C/EBPβ) expression.

Conclusion: Our results implied that GJ-4 might be a promising drug to improve VD through the regulation of microglial M1/M2 polarization and the subsequent inhibition of neuro-inflammation.
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http://dx.doi.org/10.29219/fnr.v66.8101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338452PMC
July 2022

Characterization of phenolics and discovery of α-glucosidase inhibitors in Artemisia argyi leaves based on ultra-performance liquid chromatography-tandem mass spectrometry and relevance analysis.

J Pharm Biomed Anal 2022 Aug 4;220:114982. Epub 2022 Aug 4.

Traditional Chinese Medicine Processing Technology Innovation Center of Hebei Province, School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, China; International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province, Hebei University of Chinese Medicine, Shijiazhuang 050200, China. Electronic address:

Artemisia argyi leaves (AAL) has been widely used as herbal medicine and food supplement and in China and other Asian countries. The aim of this work is to qualitative and quantitative characterization of phenolic compounds in AAL and screening of natural product inhibitors of α-glucosidase from AAL. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was employed to rapid and comprehensive identification of phenolic compounds in AAL, and a total of thirty-three phenolic compounds were identified. High performance liquid chromatography with diode array detection (HPLC-DAD) was established and validated to simultaneously determinate ten main bioactive phenolics compounds in different batches of AAL samples. Meanwhile, the inhibitory capacities of different batches of AAL samples on α-glucosidase were evaluated. Then, relevance analysis, including grey relational analysis and Pearson correlation analysis were employed to investigate the correlations between the contents of phenolic compounds and α-glucosidase inhibitory activities, and discover the α-glucosidase inhibitors in AAL. The relevance analysis results indicated that three phenolic compounds, 3-caffeoylquinic acid, 3,4-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid could be potential α-glucosidase inhibitors in AAL. Moreover, the α-glucosidase inhibitory activities of the three phenolic compounds were validated by in vitro and in vivo experiments. The possible inhibiting effect of the three phenolic compounds on α-glucosidase was also explored by molecular docking analysis, and the results indicated that the binding of the three α-glucosidase inhibitors to α-glucosidase mainly by hydrogen bonds, hydrophobic forces and ionic bonds. The present research provided a deep insight into phenolic compounds and α-glucosidase inhibitory activities of AAL, and discovered the α-glucosidase inhibitors in AAL.
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http://dx.doi.org/10.1016/j.jpba.2022.114982DOI Listing
August 2022

HJURP inhibits proliferation of ovarian cancer cells by regulating CENP-A/CENP-N.

Bull Cancer 2022 Aug 5. Epub 2022 Aug 5.

Department of Gnaecology, General Hospital, Fushun Mining Bureau, Liaoning Health Industry Group, 113008 Fushun, Liaoning Province, China. Electronic address:

Objective: High expression of Holliday Junction-Recognizing Protein (HJURP) has been shown to be a marker of poor prognosis in ovarian cancer. The objective of this study was to investigate the molecular mechanisms of HJURP in ovarian cancer (OC) progression.

Procedures: Gene Expression Profiling Interactive Analysis (GEPIA) was used to analyze the gene expression profile. Real-time quantitative PCR (qRT-PCR) was used to detect the expression level and correlation of HJURP and centromere protein-A (CENP-A) in OC tissues and cell lines. CCK-8 assay was used to detect cell proliferation. The expression level of apoptosis-related proteins and cell cycle-related proteins were detected by western blotting. Cell cycle and mitochondrial content were determined by flow cytometry.

Results: The results showed that HJURP was up-regulated in OC tissues and cell lines, while the cell proliferation was inhibited after transfecting by si-HJURP. Knockdown of HJURP promoted cell apoptosis. Meanwhile, low-expression of HJURP could down-regulate cell replication cycle-related proteins (Cyclin-dependent kinase 2, cyclinD1 and Cyclin-dependent kinase 4) and make cell replication stay in the S phase. Moreover, further studies showed that HJURP was positively correlated with CENP-A in OC tissues. Finally, the rescue experiment further verified that HJURP targeted regulation of CENP-A in OC.

Conclusions: The study indicated that HJURP plays a significant role in OC and could target CENP-A to regulate OC cell growth. These findings provide a clue to the diagnosis and treatment of OC.
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http://dx.doi.org/10.1016/j.bulcan.2021.12.011DOI Listing
August 2022

Effect of ABCB1 gene variants on rivaroxaban pharmacokinetic and hemorrhage event occurred in patients with non-valvular atrial fibrillation.

Biopharm Drug Dispos 2022 Aug 8. Epub 2022 Aug 8.

Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, China.

Hemorrhage events occurred most frequently in non-valvular atrial fibrillation (NVAF) anticoagulant therapy. Rivaroxaban was widely used for routine anticoagulation care. Genetic polymorphisms are thought to contribute to the wide intraindividual variability seen in rivaroxaban metabolism and anticoagulant response. The aim of this study was to evaluate the effect of drug transport related single-nucleotide polymorphisms (SNPs) on rivaroxaban metabolism and risk of hemorrhage event. A total of 216 Chinese patients with NVAF were enrolled in the study. Rivaroxaban was treated for anticoagulation therapy. Rivaroxaban plasma concentrations were detected using a validated UPLC-MS/MS method. Seven single-nucleotide polymorphisms (SNPs) in four genes were genotyped using the Sanger dideoxy DNA sequencing method. Associations between genotype variants, the incidence of hemorrhage events and time of bleeding were analyzed. ABCB1 2677G (rs2032582) variation was highly associated with dose-adjusted rivaroxaban peak concentration in plasma (C /D) (P = 0.025, FDR = 0.042). The ABCB1 G allele carriers had higher rivaroxaban C /D than non-carriers. Logistic regression showed rivaroxaban C /D and ABCB1 genotype variants were associated with higher incidence of hemorrhage events. No statistically significant difference was found between ABCB1 genotypes and the time of bleeding after anticoagulant therapy in 30 days. These results indicated that ABCB1 2677G (rs2032582) genetic variant affects rivaroxaban C /Dose and the incidence of hemorrhage events significantly. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/bdd.2327DOI Listing
August 2022

Intra and inter: Alterations in functional brain resting-state networks in patients with functional constipation.

Front Neurosci 2022 22;16:957620. Epub 2022 Jul 22.

Department of Anorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Background: Functional constipation (FCon), is a symptom-based functional gastrointestinal disorder without an organic etiology and altering brain structure and function. However, previous studies mainly focused on isolated brain regions involved in brain plasticity. Therefore, little is known about the altered large-scale interaction of brain networks in FCon.

Methods: For this study, we recruited 20 patients with FCon and 20 healthy controls. We used group independent component analysis to identify resting-state networks (RSNs) and documented intra- and inter-network alterations in the RSNs of the patients with FCon.

Results: We found 14 independent RSNs. Differences in the intra-networks included decreased activities in the bilateral caudate of RSN 3 (strongly related to emotional and autonomic processes) and decreased activities in the left precuneus of RSN 10 (default mode network). Notably, the patients with FCon exhibited significantly decreased interactive connectivity between RSNs, mostly involving the connections to the visual perception network (RSN 7-9).

Conclusion: Compared with healthy controls, patients with FCon had extensive brain plastic changes within and across related RSNs. Furthermore, the macroscopic brain alterations in FCon were associated with interoceptive abilities, emotion processing, and sensorimotor control. These insights could therefore lead to the development of new treatment strategies for FCon.
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http://dx.doi.org/10.3389/fnins.2022.957620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354924PMC
July 2022

The association between embryo storage time and treatment success in women undergoing freeze-all embryo transfer.

Fertil Steril 2022 Aug 4. Epub 2022 Aug 4.

Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.

Objective: To investigate the relationship between the embryo frozen time and live birth rate (LBR) in women having a freeze-all cycle.

Design: Retrospective cohort study.

Setting: Academic hospital.

Patient(s): Women who underwent their first vitrified-warmed cycles from January 2013 to December 2019.

Intervention(s): Embryo storage time.

Main Outcome Measure(s): The primary outcome was the LBR.

Result(s): A total of 14,928 women were eligible for the analysis. Women with the frozen time of transferred embryos for 2-5 months were associated with a higher LBR compared with other groups. The results were confirmed by an inverted U curve in the restricted cubic splines before as well as after adjustment for covariables, which suggested that an embryo storage time of 3-4 months was associated with the highest LBR. Subgroup analyses demonstrated that the inverted U curve relationship between embryo storage time and LBR was only observed in women with the high response. Sensitivity analyses in women with at least one good-quality embryo for transfer, in women aged <36 years at embryo transfer, or in women with double cleavage embryo transfer showed that the association remained valid. The association was weakened in women with single blastocyst transfer probably because of the small sample size in these women.

Conclusion(s): An inverted U-shaped relationship was found between embryo storage time and treatment success in women with high ovarian response in freeze-all embryo transfer cycles. Prolonged storage time of >6 months was associated with reduced pregnancy rates.
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http://dx.doi.org/10.1016/j.fertnstert.2022.06.003DOI Listing
August 2022

Dual-mode colorimetric determination of As(III) based on negatively-charged aptamer-mediated aggregation of positively-charged AuNPs.

Anal Chim Acta 2022 Aug 23;1221:340111. Epub 2022 Jun 23.

School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai, 200240, China; Key Laboratory of Urban Agriculture, Ministry of Agriculture and Rural Affairs, 800 Dongchuan Rd., Shanghai, 200240, China; Bor S. Luh Food Safety Research Center, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai, 200240, China; Shanghai Urban Forest Ecosystem Research Station, National Forestry and Grassland Administration, 800 Dongchuan Rd., Shanghai, 200240, China; Shanghai Yangtze River Delta Eco-environmental Change and Management Observation and Research Station, Ministry of Science and Technology, China. Electronic address:

The aggregation and redispersion of positively-charged AuNPs ((+)AuNPs) modified with cysteamine (CS) could be regulated by the negatively charged As(III)-specific aptamer (As(III)-apt). In general, (+)AuNPs aggregated with increasing inducer concentration. However, in the present study, it was found that (+)AuNPs re-dispersed after a certain high concentration of As(III)-apt was reached. By optimizing the concentration of As(III)-apt that resulted in the aggregation and redispersion behavior of (+)AuNPs, a dual-mode colorimetric aptasensor for As(III) determination was established. It was not only able to quantify As(III) sensitively over a ranges of As(III) concentrations, but also to selectively differentiate As(III) and eliminate false results from other control ions by dual-mode.
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http://dx.doi.org/10.1016/j.aca.2022.340111DOI Listing
August 2022

Construction of a cross-species cell landscape at single-cell level.

Nucleic Acids Res 2022 Aug 5. Epub 2022 Aug 5.

Women's Hospital, and Institute of Genetics, Zhejiang University School of Medicine, Hangzhou 310058, China.

Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging.
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http://dx.doi.org/10.1093/nar/gkac633DOI Listing
August 2022

Clinical observations on infliximab treatment of infantile onset Takayasu arteritis.

Pediatr Rheumatol Online J 2022 Aug 4;20(1):61. Epub 2022 Aug 4.

Department of Rheumatology, Capital Institute of Pediatrics, 2 Yabao Road, Chaoyang District, 100020, Beijing, China.

Background: There is insufficient evidence on the clinical effectiveness and safety of infliximab (IFX) treatment of Takayasu arteritis (TA) in infants.

Methods: We evaluated the therapeutic effectiveness and safety of IFX in a retrospective case series of 10 infantile TA patients. Observations included assessment of clinical symptoms, laboratory testing, and vascular imaging.

Results: Fever was the presenting symptom for 8 of 10 infants with TA. During acute episodes, leucocyte and inflammatory indices were significantly increased. Vascular imaging showed the most commonly involved arteries to be carotid arteries, abdominal aortas, and coronary arteries (9 cases, 90%). Two weeks after initiating IFX treatment, leukocyte and platelet counts decreased and hemoglobin levels increased. There were statistically significant clinical improvements 6 weeks after starting treatment compared with before treatment (p < 0.05). Inflammatory indices decreased 2 weeks after starting IFX treatment compared with before treatment (p < 0.05). Vascular lesions began to recover within 1.5-3 months of initiating IFX therapy, and involved vessels significantly recovered within 13 months. Some arteries remained stenotic, with intimal thickening and uneven lumen wall thicknesses. The only adverse event was a treatment-responsive allergic reaction during IFX infusion in one infant.

Conclusions: Fever was the main manifestation of illness and was often accompanied by significantly increased inflammatory indices. IFX treatment was apparently effective and reduced or eliminated need for glucocorticoids. IFX had a reasonably good safety profile.
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http://dx.doi.org/10.1186/s12969-022-00708-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351063PMC
August 2022

GNAS mutation is an unusual cause of primary adrenal insufficiency: a case report.

BMC Pediatr 2022 08 4;22(1):472. Epub 2022 Aug 4.

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, P. R. China.

Background: Primary adrenal insufficiency in children has non-specific and extensive clinical features, so the diagnosis of its etiology is complex and challenging. Although congenital adrenal hyperplasia is the most common cause, more and more other genetic causes have been identified. GNAS mutation is easily overlooked as a rare cause of primary adrenal insufficiency. Here we firstly report a neonatal case of primary adrenal insufficiency caused by GNAS mutation.

Case Presentation: A boy was diagnosed with congenital hypothyroidism 10 days post-partum and treated immediately. He also had persistent hyperkalaemia and hyponatraemia with elevated adrenocorticotropic hormone. At 70 days after birth, he was transferred to our hospital on suspicion of congenital adrenal hyperplasia. Physical examination found no other abnormalities except for growth retardation. Laboratory examination revealed increased aldosterone and normal cortisol, 17-hydroxyprogesterone, and androstenedione levels. Abnormally elevated parathyroid hormone was accompanied by normal blood calcium. Genetic assessment found a de novo, heterozygous c.432 + 1G > A variant in GNAS.

Conclusions: We report this case to highlight that GNAS mutation is an unusual cause of primary adrenal insufficiency. The combination of primary hypothyroidism and /or pseudohypoparathyroidism will provide diagnostic clues to this condition.
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http://dx.doi.org/10.1186/s12887-022-03517-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351131PMC
August 2022

Histologic Screening of Malignant Melanoma, Spitz, Dermal and Junctional Melanocytic Nevi Using a Deep Learning Model.

Am J Dermatopathol 2022 Jul 19. Epub 2022 Jul 19.

Department of Pathology and Laboratory Medicine, Medical University of South Carolina.

Objective: The integration of an artificial intelligence tool into pathologists' workflow may lead to a more accurate and timely diagnosis of melanocytic lesions, directly patient care. The objective of this study was to create and evaluate the performance of such a model in achieving clinical-grade diagnoses of Spitz nevi, dermal and junctional melanocytic nevi, and melanomas.

Methods: We created a beginner-level training environment by teaching our algorithm to perform cytologic inferences on 136,216 manually annotated tiles of hematoxylin and eosin-stained slides consisting of unequivocal melanocytic nevi, Spitz nevi, and invasive melanoma cases. We sequentially trained and tested our network to provide a final diagnosis-classification on 39 cases in total. Positive predictive value (precision) and sensitivity (recall) were used to measure our performance.

Results: The tile-classification algorithm predicted the 136,216 irrelevant, melanoma, melanocytic nevi, and Spitz nevi tiles at sensitivities of 96%, 93%, 94% and 73%, respectively. The final trained model was able to correctly classify and predict the correct diagnosis in 85.7% of unseen cases (n = 28), reporting at or near screening-level performances for precision and recall of melanoma (76.2%, 100.0%), melanocytic nevi (100.0%, 75.0%), and Spitz nevi (100.0%, 75.0%).

Conclusions: Our pilot study proves that convolutional networks trained on cellular morphology to classify melanocytic proliferations can be used as a powerful tool to assist pathologists in screening for melanoma versus other benign lesions.
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http://dx.doi.org/10.1097/DAD.0000000000002232DOI Listing
July 2022

A rare case of arrhythmogenic right ventricular cardiomyopathy associated with mutation: A case report and literature review.

Front Med (Lausanne) 2022 18;9:922347. Epub 2022 Jul 18.

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disorder that predominantly affects the right ventricle. Mutations in genes that encode components of desmosomes, the adhesive junctions that connect cardiomyocytes, are the predominant cause of ARVC. A case with novel heterozygous mutation in the gene is reported here. The protein encoded by gene is the α2 chain of laminin-211 protein, which establishes a stable relationship between the muscle fiber membrane and the extracellular matrix. We explored the potential mechanism and the relationship between the mutation and ARVC.

Case Presentation: At the age of 8, the patient developed syncope and palpitation after exercise. Dynamic electrocardiogram recorded continuous premature ventricular beats, and MRI showed the right ventricle was significantly enlarged and there were many localized distensions at the edge of the right ventricular wall. The patient was diagnosed with ARVC and received heart transplantation at the age of 14 due to severe heart dysfunction. The myocardial histological pathological staining revealed a large amount of fibrosis and adipose migration. Whole exome sequencing (WES) identified the heterozygous mutation in the gene [NM_000426.3: c.8842G > A (p.G2948S)]. This is the first report of these variants. Analysis was performed on genetic disorders to reveal splice site changes and damage to protein structure. predicted unstable protein structure and impaired function. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were established. RNA-seq and the western blot were performed on IPSC-CMs to explore the ARVC-related signaling pathway.

Conclusion: This is the first case report to describe an ARVC phenotype in patients possessing a novel > () mutation. Our results aid in understanding of the pathogenesis of ARVC. The molecular mechanism of leading to ARVC disease still needs further study.
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http://dx.doi.org/10.3389/fmed.2022.922347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339636PMC
July 2022

Facile preparation of antibacterial hydrogel with multi-functions based on carboxymethyl chitosan and oligomeric procyanidin.

RSC Adv 2022 Jul 21;12(32):20897-20905. Epub 2022 Jul 21.

School of Life Science, Zhengzhou University 100 Science Road Zhengzhou 450001 P. R. China

Hydrogel-based antibacterial materials with multi-functions are of great significance for healthcare. Herein, a facile and one-step method was developed to fabricate an injectable hydrogel (named CMCS/OPC hydrogel) based on carboxymethyl chitosan (CMCS) and oligomeric procyanidin (OPC). In this hydrogel system, OPC serves as the dynamic crosslinker to bridge CMCS macromolecules mainly through dynamical hydrogen bonds, which endows this hydrogel with excellent injectable, self-healing, and adhesive abilities. In addition, due to the inherent antibacterial properties of CMCS and OPC, this hydrogel shows excellent antibacterial activity. Therefore, the well-designed CMCS/OPC hydrogel has great prospects as an antibacterial material in the biomedical field.
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http://dx.doi.org/10.1039/d2ra04049bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301940PMC
July 2022

Inhibition of Dyrk1A Attenuates LPS-Induced Neuroinflammation via the TLR4/NF-κB P65 Signaling Pathway.

Inflammation 2022 Aug 2. Epub 2022 Aug 2.

State Key Laboratory of Bioactive Substrate and Function of Natural Medicine, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xian Nong Tan Street, Beijing, 100050, China.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) is a highly conserved protein kinase, playing a key role in the regulation of physiological brain functions and pathological processes. In Alzheimer's disease (AD), Dyrk1A promotes hyperphosphorylation of tau protein and abnormal aggregation of amyloid-β protein (Aβ). This study investigated the role of Dyrk1A in regulating neuroinflammation, another critical factor that contributes to AD. In the present study, we used an immortalized murine BV2 microglia cell line induced by lipopolysaccharide (LPS) to study neuroinflammation. The expression and activity of Dyrk1A kinase were both increased by inflammation. Dyrk1A inhibition using harmine or siRNA silencing significantly reduced the production of proinflammatory factors in LPS-stimulated BV2 cells. Reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), as well as the expression of the inflammatory proteins, cyclooxygenase 2 (COX2), and inducible nitric synthase (iNOS), were attenuated. In vivo, in ICR mice injected with LPS into the left lateral cerebral ventricle, harmine (20 mg/kg) administration decreased the expression of inflammatory proteins in the cortex and hippocampus of mice brain. In addition, immunohistochemical detection of ionized calcium-binding adapter molecule 1 (Iba1) and Nissl staining showed that harmine significantly attenuated microglia activation and neuronal damage in the CA1 region of hippocampus. Further mechanistic studies indicated that Dyrk1A suppression may be related to inhibition of the TLR4/NF-κB signaling pathway in LPS-induced neuroinflammation. Taken together, our studies suggest that Dyrk1A may be a novel target for the treatment of neurodegenerative diseases with an inflammatory component.
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http://dx.doi.org/10.1007/s10753-022-01699-wDOI Listing
August 2022

Vernodalin suppresses tumor proliferation and increases apoptosis of gastric cancer cells through attenuation of FAK/PI3K/AKT/mTOR and MAPKs signaling pathways.

Curr Pharm Biotechnol 2022 Jul 28. Epub 2022 Jul 28.

Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People\'s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.

Background: Gastric cancer (GC) is the most aggressive malignant tumor with limited treatment alternatives post metastasis. Vernodalin (VN) induced apoptosis has been reported in various types of human cancer cells. However, the precise molecular mechanisms underlying the anti-metastasis action of VN on GC cells are yet to be elucidated.

Objective: In this study, we investigated the anti-metastatic and apoptotic effects of VN on SGC-7901 and AGS cells, with a purpose of gaining a deeper understanding of the anti-metastatic mechanisms of VN on gastric carcinoma. To attenuate the activation of PI3K/AKT/mTOR and mitogen-activated protein kinase (MAPK) signaling pathways by VN in GC cells.

Methods: We employed VN and gastric cancer cells in experiments such as, MTT assay, apoptosis, MMP, DAPI, Rh-123, cell adhesion assay, and western blot analysis on GC SGC-7901 and AGS cells.

Result: Our results revealed that VN inhibits the cell proliferation, adhesion, and metastasis and induces apoptosis of both GC cells. VN potentially reduced the protein expressions of MMP-2, MMP-9, and uPA, whereas intensified expressions of TIMP-1 and TIMP-2. Also, VN attenuates the expression of FAK, p-PI3K, p-AKT, p-mTOR, p-JNK, p-p38MAPK, and p-ERK. Thus, it is inferred that VN treatment reduced the activities of MMP-2 and MMP-9 via the FAK/PI3K/AKT/mTOR, and MAPKs signaling pathways. Our results confirm that VN prevented GC growth, invasion and metastasis and induce apoptosis in GC cells.

Conclusion: Our findings suggest that VN is a potential natural therapeutic compound as a new remedy for GC chemotherapy treatment.
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http://dx.doi.org/10.2174/1389201023666220728150544DOI Listing
July 2022

Circular RNA circPBX3 promotes cisplatin resistance of ovarian cancer cells via interacting with IGF2BP2 to stabilize ATP7A mRNA expression.

Hum Cell 2022 Jul 30. Epub 2022 Jul 30.

Department of Obstetrics and Gynecology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Street, Chaoyang, Beijing, 100015, China.

Circular RNAs (circRNAs) are a class of non-coding RNAs with a unique covalently closed loop structure. Recent studies indicate that dysregulation of circRNAs acts a role in cancer progression and chemotherapy resistance via interacting with RNA-binding proteins (RBPs). Herein, we identified circPBX3 to be involved in cisplatin resistance of ovarian cancer. In our study, two cisplatin-resistant ovarian cancer cell lines were established, and transcriptome RNA-sequencing was performed and circPBX3 was identified as significantly upregulated circRNA in these cells. The characteristics of circPBX3 and potential function of circPBX3 were evaluated. We found that circPBX3 was upregulated in ovarian tumor tissues and cisplatin-resistant ovarian cancer cells. CircPBX3 overexpression increased the half maximal inhibitory rate (IC) of cisplatin, promoted colony formation and tumor xenografts growth, and reduced cell apoptosis of ovarian cancer cells under cisplatin treatment, while silencing circPBX3 showed opposite effects. Furthermore, circPBX3 could interact with the RNA-binding protein IGF2BP2, thus increased the stability of ATP7A mRNA and elevated ATP7A protein level. In addition, silencing ATP7A in ovarian cancer cells abrogated the effect of circPBX3 overexpression on cisplatin tolerance. Our findings provided a novel role of circPBX3 in cisplatin resistance of ovarian cancer.
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http://dx.doi.org/10.1007/s13577-022-00748-8DOI Listing
July 2022

In vivo Realization of Combined Photodynamic and Photothermal Therapy for Melanoma by Mitochondria Targeting Dinuclear Ruthenium Complexes under Civil Infrared Low-power Laser.

Angew Chem Int Ed Engl 2022 Jul 30. Epub 2022 Jul 30.

Yunnan University, Chemistry, No.2 Cuihu Road North, 650091, Kunming, CHINA.

A series of dinuclear Ru(II) complexes with extremely high TPA cross sections in the range of 800-900 nm have been designed. The amphiphilic complex Ru3 containing tert-butyl groups has balanced performance in singlet oxygen generation and photothermal conversion and becomes the ideal drug candidate of the series. Ru3 targets mitochondria without penetrating the nucleus, which substantially increases its photodynamic therapy activity and reduces its dark cytotoxicity. Ru3 successfully suppresses melanoma tumor growth in vitro and in vivo with combined photodynamic and photothermal therapy under low light dose irradiation of an 808 nm low-power laser, avoiding the known PDT resistance in melanoma. The excellent therapeutic effect of Ru3 facilitates its applications in further human trials for larger or deeper buried tumors, thereby becoming a prospective candidate for a new generation of low-power IR-driven dual PDT/PTT drugs.
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http://dx.doi.org/10.1002/anie.202208721DOI Listing
July 2022

Antitumor Potential and Structure Characterization of Polysaccharides From Maxim in the Tibetan Plateau.

Front Nutr 2022 12;9:921892. Epub 2022 Jul 12.

College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China.

This study purified two polysaccharides (LBMPs) from Maxim in several steps. The chemical structure of LBMP-2 was determined by HPGPC, FT-IR, IC, H and C NMR, AFM, SEM, and TEM. The results show that LBMP-2 was mainly composed of GalA, and the Mw of LBMP-2 is 23.799 kDa. In addition, the antioxidant activity, and the antitumor activity and were studied. LBMP-2 has excellent antioxidant and antitumor capacity. The inhibition of tumor cell proliferation may result in the inhibition of aerobic respiration and glycolysis. Tumor growth inhibition may inhibit the expression of AMPK in tumors and enhance spleen function. Compared with conventional chemotherapy drug cyclophosphamide, LBMP-2 is less harmful to the body and safer. Therefore, LBMP-2 provides a potential source of antitumor drugs.
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http://dx.doi.org/10.3389/fnut.2022.921892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320327PMC
July 2022

Characteristics of Laryngopharyngeal Reflux in the Chinese Nurse Population.

J Voice 2022 Jul 24. Epub 2022 Jul 24.

Department of Otolaryngology, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing, China.

Objectives: To investigate the prevalence of laryngopharyngeal reflux (LPR) and knowledge of LPR in the Chinese nurse population.

Method: From October 2021 through December 2021, participants were recruited from the PLA General Hospital's Sixth Medical Center. All included participants completed the Reflux Symptom Index (RSI), and LPR was defined as RSI > 13. In addition, each participant was asked to record whether they had any habits such as preferring to consume high-fat food and carbonated beverages, over-eating at dinner, sedentary after meals and lying down within 2 hour after meals, as well as whether they were aware of LPR. For the participants with RSI >13 points, they were treated using diet and lifestyle behavioral recommendations and were prescribed a twice daily pantoprazole (20 mg, 3 months).

Results: A total of 828 participants were included. The positivity and awareness rates of LPR were 3.38% and 55.96%, respectively. RSI scores were significantly higher in LPR-positive subjects than in LPR-negative (16.79 ± 4.43 vs. 1.33 ± 2.33). Among the participants with LPR, there were significant positive association between RSI scores and preferring to consume high-fat food and carbonated beverages, over-eating at dinner, lying down within 2 hour after a meal, and sedentary after meals. RSI scores in 63% of participants with LPR significantly decreased from baseline to 1 month posttreatment. From 1 to 3 months posttreatment, 90% of participants had significantly lower RSI scores than pretreatment.

Conclusions: There are a certain number of LPR patients in the Chinese nurse population, however, knowledge of LPR among nurses is unsatisfactory. Over-eating at dinner, lying down within 2 hour after a meal and sedentary after meals are risk factors for LPR. With combined regular dietary and lifestyle behavioral change and acid-suppressing treatment, most patients with LPR achieve effective remission.
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http://dx.doi.org/10.1016/j.jvoice.2022.06.031DOI Listing
July 2022

Sparse-based Domain Adaptation Network for OCTA Image Super-Resolution Reconstruction.

IEEE J Biomed Health Inform 2022 Jul 27;PP. Epub 2022 Jul 27.

Retinal Optical Coherence Tomography Angiography (OCTA) with high-resolution is important for the quantification and analysis of retinal vasculature. However, the resolution of OCTA images is inversely proportional to the field of view at the same sampling frequency, which is not conducive to clinicians for analyzing larger vascular areas. In this paper, we propose a novel Sparse-based domain Adaptation Super-Resolution network (SASR) for the reconstruction of realistic [Formula: see text]/low-resolution (LR) OCTA images to high-resolution (HR) representations. To be more specific, we first perform a simple degradation of the [Formula: see text]/high-resolution (HR) image to obtain the synthetic LR image. An efficient registration method is then employed to register the synthetic LR with its corresponding [Formula: see text] image region within the [Formula: see text] image to obtain the cropped realistic LR image. We then propose a multi-level super-resolution model for the fully-supervised reconstruction of the synthetic data, guiding the reconstruction of the realistic LR images through a generative-adversarial strategy that allows the synthetic and realistic LR images to be unified in the feature domain. Finally, a novel sparse edge-aware loss is designed to dynamically optimize the vessel edge structure. Extensive experiments on two OCTA sets have shown that our method performs better than state-of-the-art super-resolution reconstruction methods. In addition, we have investigated the performance of the reconstruction results on retina structure segmentations, which further validate the effectiveness of our approach.
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http://dx.doi.org/10.1109/JBHI.2022.3194025DOI Listing
July 2022

A Study on Nurse Manager Competency Model of Tertiary General Hospitals in China.

Int J Environ Res Public Health 2022 Jul 12;19(14). Epub 2022 Jul 12.

Institute for Hospital Management, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.

(1) Background: The nurse manager competency model is widely used in hospitals in the management of nursing human resources. This study aimed to construct a scientific and practical model of nurse manager competency, which can be used as a tool by hospitals to select nurse managers. (2) Methods: The nurses' competency indicators were first collected through a literature review and behavioral event interview, and the preliminary screening of competency elements was based on the Delphi method. Then, questionnaires and statistical analyses were used to determine the elements of the model. The reliability was determined using Cronbach's alpha. Factor analysis was used to delineate the dimensions of the model. (3) Results: The results of the factor analysis show that the 22 competency elements were grouped into the four dimensions of leadership and management ability, personal traits, professional quality, and professional ability. The Cronbach's alpha coefficients of the four dimensions ranged from 0.745 to 0.885, which indicated a high level of reliability. The result of the factor analysis indicated a high structural validity and fitting effect. (4) Conclusions: Our study indicates that the nurse manager competency model of tertiary general hospitals is an instrument with fair reliability and validity that fully reflects the characteristics of nurses in Chinese public hospitals.
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http://dx.doi.org/10.3390/ijerph19148513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322922PMC
July 2022

Insights into growth-promoting effect of nanomaterials: Using transcriptomics and metabolomics to reveal the molecular mechanisms of MWCNTs in enhancing hyperaccumulator under heavy metal(loid)s stress.

J Hazard Mater 2022 Jul 20;439:129640. Epub 2022 Jul 20.

School of Agriculture and Biology, Shanghai Jiao Tong University, 200240, China; Key Laboratory of Urban Agriculture, Ministry of Agriculture and Rural Areas, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai Yangtze River Delta Eco-Environmental Change and Management Observation and Research Station, Ministry of Science and Technology, Ministry of Education, 800 Dongchuan Rd, Shanghai 200240, China; Yunnan Dali Research Institute, Shanghai Jiao Tong University, Dali, Yunnan 671000, China. Electronic address:

Carbon nanotubes present potential applications in soil remediation, particularly in phytoremediation. Yet, how multi-walled carbon nanotubes (MWCNTs) induced hyperaccumulator growth at molecular level remains unclear. Here, physio-biochemical, transcriptomic, and metabolomic analyses were performed to determine the effect of MWCNTs on Solanum nigrum L. (S. nigrum) growth under cadmium and arsenic stresses. 500 mg/kg MWCNTs application significantly promoted S. nigrum growth, especially for root tissues. Specially, MWCNTs application yields 1.38-fold, 1.56-fold, and 1.37-fold enhancement in the shoot length, root length, and fresh biomass, respectively. Furthermore, MWCNTs significantly strengthened P and Fe absorption in roots, as well as the activities of antioxidative enzymes. Importantly, the transcriptomic analysis indicated that S. nigrum gene expression was sensitive to MWCNTs, and MWCNTs upregulated advantageous biological processes under heavy metal(loid)s stress. Besides, MWCNTs reprogramed metabolism that related to defense system, leading to accumulation of 4-hydroxyphenylpyruvic acid (amino acid), 4-hydroxycinnamic acid (xenobiotic), and (S)-abscisic acid (lipid). In addition, key common pathways of differentially expressed metabolites and genes, including "tyrosine metabolism" and "isoquinoline alkaloid biosynthesis" were selected via integrating transcriptome and metabolome analyses. Combined omics technologies, our findings provide molecular mechanisms of MWCNTs in promoting S. nigrum growth, and highlight potential application of MWCNTs in soil remediation.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129640DOI Listing
July 2022

Genome Size Variation and Evolution Driven by Transposable Elements in the Genus .

Front Plant Sci 2022 7;13:921937. Epub 2022 Jul 7.

Institution of Genomics and Bioinformatics, South China Agricultural University, Guangzhou, China.

Genome size variation and evolutionary forces behind have been long pursued in flowering plants. The genus , consisting of approximately 25 wild species and two cultivated rice, harbors eleven extant genome types, six of which are diploid (AA, BB, CC, EE, FF, and GG) and five of which are tetraploid (BBCC, CCDD, HHJJ, HHKK, and KKLL). To obtain the most comprehensive knowledge of genome size variation in the genus , we performed flow cytometry experiments and estimated genome sizes of 166 accessions belonging to 16 non-AA genome species. -mer analyses were followed to verify the experimental results of the two accessions for each species. Our results showed that genome sizes largely varied fourfold in the genus , ranging from 279 Mb in (FF) to 1,203 Mb in (HHJJ). There was a 2-fold variation (ranging from 570 to 1,203 Mb) in genome size among the tetraploid species, while the diploid species had 3-fold variation, ranging from 279 Mb in (FF) to 905 Mb in (EE). The genome sizes of the tetraploid species were not always two times larger than those of the diploid species, and some diploid species even had larger genome sizes than those of tetraploids. Nevertheless, we found that genome sizes of newly formed allotetraploids (BBCC-) were almost equal to totaling genome sizes of their parental progenitors. Our results showed that the species belonging to the same genome types had similar genome sizes, while genome sizes exhibited a gradually decreased trend during the evolutionary process in the clade with AA, BB, CC, and EE genome types. Comparative genomic analyses further showed that the species with different rice genome types may had experienced dissimilar amplification histories of retrotransposons, resulting in remarkably different genome sizes. On the other hand, the closely related rice species may have experienced similar amplification history. We observed that the contents of transposable elements, long terminal repeats (LTR) retrotransposons, and particularly LTR/ retrotransposons varied largely but were significantly correlated with genome sizes. Therefore, this study demonstrated that LTR retrotransposons act as an active driver of genome size variation in the genus .
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http://dx.doi.org/10.3389/fpls.2022.921937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301470PMC
July 2022

The effects of inorganic anions on degradation kinetics and isotope fractionation during the transformation of tris(2-chloroethyl) phosphate (TCEP) by UV/persulfate.

Sci Total Environ 2022 Jul 19:157462. Epub 2022 Jul 19.

Key Laboratory of Pollution Control Chemistry and Environmental Functional Materials for Qinghai-Tibet Plateau of the National Ethnic Affairs Commission, School of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, China; Key Laboratory of General Chemistry of the National Ethnic Affairs Commission, School of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, China.

Tris(2-chloroethyl) phosphate (TCEP), as a typical chlorinated flame retardant, is attracting more attention as a carcinogen. Although persulfate-based oxidation exhibits good performance in removing refractory organic pollutants, the kinetics of persulfate-based remediation are affected by inorganic anions, which causes inaccurate remediation efficiency. This study combines steady-state radical concentration modelling with isotope fractionation to investigate the effects of inorganic anions on TCEP degradation by UV/persulfate (UV/PS). In the absence of anions during UV/PS system, the observed degradation rate was (9.7 ± 0.1) × 10 s, which was approximately 93 % attributed to sulfate radical (SO•) oxidation based on radical modelling. Carbon isotope fractionation, coupled with the identification of transformation products by mass spectrometry, suggests a carbon bond split during TCEP degradation with a carbon isotopic fractionation value (ε) of -1.6 ± 0.2 ‰ (± 95 % confidence intervals). With respect to co-existing anions in UV/PS system, the addition of chloride (Cl) had a negligible effect on degradation rates, while the addition of hydrogencarbonate (HCO) caused them to decrease, and the addition of hydrogenphosphate (HPO) caused them to increase. Radical modelling suggested that SO• was transformed to chlorine radicals (Cl•/Cl•), phosphate radicals (HPO•), and carbonate radicals (CO•). Furthermore, the overlapping 95 % confidence intervals (C.I.) and the statistical tests (p > 0.05) both agree that Cl and HPO gain identical ε values. Nevertheless, when HCO coexisted in the UV/PS system, the ε values were distinct. The addition of HCO would result in ε variation of TCEP in the UV activated PS process, which should receive more attention when applying remediation.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157462DOI Listing
July 2022

Injectable Self-Healing Adhesive Chitosan Hydrogel with Antioxidative, Antibacterial, and Hemostatic Activities for Rapid Hemostasis and Skin Wound Healing.

ACS Appl Mater Interfaces 2022 Aug 20;14(30):34455-34469. Epub 2022 Jul 20.

School of Life Science, Zhengzhou University, 100 Science Road, Zhengzhou 450001, P. R. China.

Engineered wound dressing materials with excellent injectability, self-healing ability, tissue-adhesiveness, especially the ones possessing potential therapeutic effects have great practical significance in healthcare. Herein, an injectable quaternary ammonium chitosan (QCS)/tannic acid (TA) hydrogel based on QCS and TA was designed and fabricated by facile mixing of the two ingredients under physiological conditions. In this system, hydrogels were mainly cross-linked by dynamic ionic bonds and hydrogen bonds between QCS and TA, which endows the hydrogel with excellent injectable, self-healing, and adhesive properties. Benefitting from the inherent antioxidative, antibacterial, and hemostatic abilities of TA and QCS, this hydrogel showed superior reactive oxygen species scavenging activity, broad-spectrum antibacterial ability, as well as rapid hemostatic capability. Moreover, the QCS/TA hydrogel (containing 2.5% TA) exhibited excellent biocompatibility. The in vivo experiments also showed that QCS/TA hydrogel dressing not only rapidly stopped the bleeding of arterial and deep incompressible wounds in mouse tail amputation, femoral artery hemorrhage, and liver incision models but also significantly accelerated wound healing in a full-thickness skin wound model. For the great potentials listed above, this multifunctional QCS/TA hydrogel offers a promising network as a dressing material for both rapid hemostasis and skin wound repair.
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http://dx.doi.org/10.1021/acsami.2c08870DOI Listing
August 2022

Progerin modulates the IGF-1R/Akt signaling involved in aging.

Sci Adv 2022 Jul 8;8(27):eabo0322. Epub 2022 Jul 8.

College of Basic Medical Sciences, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.

Progerin, a product of mutation, leads to multiple nuclear abnormalities in patients with Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disorder. Progerin also accumulates during physiological aging. Here, we demonstrate that impaired insulin-like growth factor 1 receptor (IGF-1R)/Akt signaling pathway results in severe growth retardation and premature aging in mice, a mouse model of progeria. Mechanistically, progerin mislocalizes outside of the nucleus, interacts with the IGF-1R, and down-regulates its expression, leading to inhibited mitochondrial respiration, retarded cell growth, and accelerated cellular senescence. Pharmacological treatment with the PTEN (phosphatase and tensin homolog deleted on chromosome 10) inhibitor bpV (HOpic) increases Akt activity and improves multiple abnormalities in Zmpste24-deficient mice. These findings provide previously unidentified insights into the role of progerin in regulating the IGF-1R/Akt signaling in HGPS and might be useful for treating -associated progeroid disorders.
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http://dx.doi.org/10.1126/sciadv.abo0322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269893PMC
July 2022

Eye movement indices as predictors of conversion to psychosis in individuals at clinical high risk.

Eur Arch Psychiatry Clin Neurosci 2022 Jul 20. Epub 2022 Jul 20.

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China.

Eye movement abnormalities have been established as an "endophenotype" of schizophrenia. However, less is known about the possibility of these abnormalities as biomarkers for psychosis conversion among clinical high risk (CHR) populations. In the present study, 108 CHR individuals and 70 healthy controls (HC) underwent clinical assessments and eye-tracking tests, comprising fixation stability and free-viewing tasks. According to three-year follow-up outcomes, CHR participants were further stratified into CHR-converter (CHR-C; n = 21) and CHR-nonconverter (CHR-NC; n = 87) subgroups. Prediction models were constructed using Cox regression and logistic regression. The CHR-C group showed more saccades of the fixation stability test (no distractor) and a reduced saccade amplitude of the free-viewing test than HC. Moreover, the CHR-NC group exhibited excessive saccades and an increased saccade amplitude of the fixation stability test (no distractor; with distractor) compared with HC. Furthermore, two indices could effectively discriminate CHR-C from CHR-NC with an area under the receiver-operating characteristic (ROC) curve of 0.80, including the saccade number of the fixation stability test (no distractor) and the saccade amplitude of the free-viewing test. Combined with negative symptom scores of the Scale of Prodromal Symptoms, the area was 0.81. These findings support that eye movement alterations might emerge before the onset of clinically overt psychosis and could assist in predicting psychosis transition among CHR populations.
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http://dx.doi.org/10.1007/s00406-022-01463-zDOI Listing
July 2022

Malignant perivascular epithelioid cell tumor (PEComa) of uterus: A case report.

Asian J Surg 2022 Jul 15. Epub 2022 Jul 15.

Department of Pathology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.07.016DOI Listing
July 2022

[Tianma Gouteng Decoction regulates MFN2 expression to delay vascular aging in spontaneously hypertensive rats].

Zhongguo Zhong Yao Za Zhi 2022 Jul;47(14):3844-3852

International Medical Department, Xiangya Hospital, Central South University Changsha 410008, China Department of Geriatrics, Xiangya Hospital, Central South University Changsha 410008, China National Center for Clinical Medicine of Geriatric Diseases, Xiangya Hospital, Central South University Changsha 410008, China.

We studied the effect of Tianma Gouteng Decoction on vascular aging in spontaneously hypertensive rats(SHRs) to explore the molecular mechanism of the decoction in improving arterial vascular aging by regulating the expression of mitofusin 2(MFN2).Twenty 64-weeks-old SHRs were randomly assigned into the aging group and the treatment group(Tianma Gouteng Decoction 5.48 mg·kg~(-1)).Wistar-Kyoto(WKY) rats of 64 weeks old were taken as the normal group and SHR rats of 14 weeks old as the young group.The intervention with Tianma Gouteng Decoction lasted for 12 weeks.We then employed HE staining and Masson staining to observe the morphology of thoracic aorta under an electron microscope and measured the malondialdehyde(MDA) content, superoxide dismutase(SOD) activity, respiratory chain complex Ⅲ level, and thioredoxin peroxidase(TPX) activity.The vascular aging was detected via the biomarker senescence-associated beta-galactosidase(SA-β-Gal).The expression levels of MFN2 and aging marker proteins silent information regulator 1(SIRT1), Klotho, p21, and p53 in thoracic aorta were detected by immunohistochemistry/fluorescence, qRT-PCR, and Western blot.Compared with the young group and the normal group, the aging group had risen blood pressure, lumen stenosis caused by thickened intima of blood vessels, decreased SOD and TPX activities, increased MDA and mitochondrial respiratory chain complex Ⅲ levels, down-regulated expression of MFN2, SIRT1, and Klotho, and up-regulated expression of p21 and p53(P<0.01 or P<0.05).The treatment with Tianma Gouteng Decoction significantly lowered blood pressure, mitigated vascular intimal thickening, increased SOD and TPX activities, and decreased MDA and mitochondrial respiratory chain complex Ⅲ levels, thus alleviating vascular aging.At the same time, the decoction up-regulated the expression of MFN2, SIRT1, and Klotho, while down-regulated that of p21 and p53(P<0.01 or P<0.05).In summary, Tianma Gouteng Decoction can significantly delay the vascular aging in hypertension.Specifically, it may up-regulate the expression of MFN2 and regulate the expression of aging-related proteins to alleviate oxidative stress.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20220207.703DOI Listing
July 2022
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