Publications by authors named "Yu Chen"

6,210 Publications

  • Page 1 of 1

Effects of an individualized nutritional intervention on the prognosis of patients with liver failure.

Asia Pac J Clin Nutr 2022 ;31(2):215-221

Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing Youan Hospital, Capital Medical University, Beijing, China. Email:

Background And Objectives: Patients with liver failure often have energy metabolism disorders and malnutrition, which lead to poor prognosis, rendering nutritional interventions essential.

Methods And Study Design: Individualized nutritional interventions were offered according to the resting energy expenditure (REE) of patients with liver failure, and the patients were followed up for 180 days.

Results: Sixty patients with liver failure were enrolled and grouped by their prognosis and energy intake. Model for end-stage liver disease (MELD) score and body fat mass of the nonsurvival group were significantly higher than those of the survival group (p<0.05), whereas the mean energy intake/REE (MEI/REE) and mean respiratory quotient (RQ) of the nonsurvival group were significantly lower than those of the survival group (p<0.01). Prediction REE (PredREE) was calculated using the Harris-Benedict formula. Most patients in the nonsurvival and survival groups had hypometabolic (REE/PredREE <0.9) and normal metabolic status (0.9
Conclusions: Hypometabolism state and insufficient energy intake predict poor prognosis in patients with liver failure. Individualized nutritional interventions with energy intake ≥1.2 REE may improve the RQ and prognosis of such patients.
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http://dx.doi.org/10.6133/apjcn.202206_31(2).0007DOI Listing
January 2022

Exploring the potential of exosomes in diagnosis and drug delivery for PDAC.

Int J Cancer 2022 Jun 29. Epub 2022 Jun 29.

Department of Gastroduodenal and Pancreatic Surgery, Translational Medicine Joint Research Center of Liver Cancer of Hunan University, Laboratory of Digestive Oncology, Affiliated Cancer Hospital of Xiangya Medical School & Hunan Cancer Hospital, Central South University, Changsha, Hunan, China.

Pancreatic cancer (PC) is a cancer of the digestive system, and pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of all PC cases. Exosomes derived from PDAC (PDAC-exosomes) promote PDAC development and metastasis. Exosomes are nanoscale vesicles secreted by most cells, which can carry biologically active molecules and mediate communication and cargo transportation among cells. Recent studies have focused on transforming exosomes into good drug delivery systems (DDSs) to improve the clinical treatment of PDAC. This review considers PDAC as the main research object to introduce the role of PDAC-exosomes in PDAC development and metastasis. This review focuses on the following two themes: (1) the great potential of PDAC-exosomes as new diagnostic markers for PDAC, and (2) the transformation of exosomes into potential DDSs. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.34195DOI Listing
June 2022

The Role of OCT Criteria and Machine Learning in Multiple Sclerosis and Optic Neuritis Diagnosis.

Neurology 2022 Jun 28. Epub 2022 Jun 28.

- Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.

Background And Objectives: Recent studies have suggested that inter-eye differences (IEDs) in peripapillary retinal nerve fiber layer (pRNFL) or ganglion cell+inner plexiform (GCIPL) thickness by spectral-domain optical coherence tomography (SD-OCT) may identify people with a history of unilateral optic neuritis (ON). However, this requires further validation. Machine learning classification may be useful for validating thresholds for OCT IEDs and for examining added utility for visual function tests, such as low-contrast letter acuity (LCLA), in the diagnosis of people with multiple sclerosis (PwMS) and for unilateral ON history.

Methods: Participants were from 11 sites within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. pRNFL and GCIPL thicknesses were measured using SD-OCT. A composite score combining OCT and visual measures was compared individual measurements to determine the best model to distinguish PwMS from controls. These methods were also used to distinguish those with history of ON among PwMS. ROC curve analysis was performed on a training dataset (2/3 of cohort), then applied to a testing dataset (1/3 of cohort). Support vector machine (SVM) analysis was used to assess whether machine learning models improved diagnostic capability of OCT.

Results: Among 1,568 PwMS and 552 controls, variable selection models identified GCIPL IED, average GCIPL thickness (both eyes), and binocular 2.5% LCLA as most important for classifying PwMS vs. controls. This composite score performed best, with AUC=0.89 (95% CI 0.85, 0.93), sensitivity=81% and specificity=80%. The composite score ROC curve performed better than any of the individual measures from the model (p<0.0001). GCIPL IED remained the best single discriminator of unilateral ON history among PwMS (AUC=0.77, 95% CI 0.71,0.83, sensitivity=68%, specificity=77%). SVM analysis performed comparably to standard logistic regression models.

Conclusions: A composite score combining visual structure and function improved the capacity of SD-OCT to distinguish PwMS from controls. GCIPL IED best distinguished those with history of unilateral ON. SVM performed as well as standard statistical models for these classifications.

Classification Of Evidence: The study provides Class III evidence that SD-OCT accurately distinguishes multiple sclerosis from normal controls as compared to clinical criteria.
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http://dx.doi.org/10.1212/WNL.0000000000200883DOI Listing
June 2022

Identification of potential biomarkers and immune-related pathways related to immune infiltration in patients with acute myocardial infarction.

Transpl Immunol 2022 Jun 25:101652. Epub 2022 Jun 25.

Department of Cardiology, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian 223300, Jiangsu, China. Electronic address:

Background: Acute myocardial infarction (AMI), a medical condition caused by the ischemic necrosis of cardiac tissues, is due to sudden occlusion of the coronary arteries in patients including transplant recipients. It is the leading reason for death and disability worldwide. This study aimed to search potential biomarkers related to the progression of AMI and identify the related immune-related pathways, as also examine their association with the immune cell infiltration and diagnostic value for AMI.

Methods: Datasets of gene microarray were extracted from (www.ncbi.nlm.nih.gov/geo) the Gene Expression Omnibus (GEO) database and AMI-related biomarkers were obtained by differential expression analysis and weighted correlation network analysis (WGCNA). Subsequently, the support vector machine-recursive feature elimination (SVM-RFE) and the least absolute shrinkage and selection operator (LASSO) regression analyses were used to mine AIM-related hub markers. For the assessment of the diagnostic value of these markers for AMI, the receiver operator characteristic (ROC) curves were plotted. Additionally, the single-sample gene set enrichment analysis (ssGSEA) was performed to determine the immune cell infiltration.

Results: A total of 1273 differentially expressed genes (DEGs) were obtained. Nine co-expression modules were obtained after WGCNA. Among them, the brown-colored module was identified as the hub for AMI (correlation [cor] = 0.73, P = 1.1e-87), and intersected with the DEGs yielded a total of 88 shared genes. Subsequently, five hub genes were obtained from the analysis of the LASSO regression and SVM-RFE algorithm. Ultimately, using the ROC curves, the diagnostic values of these genes for AMI were confirmed. The five hub genes were also found to be significantly associated with the infiltration levels of multiple immune cells. Moreover, the DEGs were mainly enriched in the inflammatory and immune-related gene sets evidenced by the functional enrichment analysis.

Conclusion: The five hub genes may serve as potential markers for AMI diagnosis and the findings have implications for further investigations on the molecular mechanisms underlying AMI.
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http://dx.doi.org/10.1016/j.trim.2022.101652DOI Listing
June 2022

self-assembly of polydopamine inside injectable hydrogels: antibacterial activity and photothermal therapy for superbug-infected wound healing.

Biomater Sci 2022 Jun 28. Epub 2022 Jun 28.

Key Laboratory of Photochemical conversion and Optoelectronic Material, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

Inspired by the mussel foot proteins, polydopamine nanoparticles (PDA NPs) are often used to design hydrogel wound dressings due to their strong wet adhesion. However, additional antibiotics or nanometal bactericides are always required to enhance their poor antibacterial activity, which will cause drug resistance and toxic side effects. Herein, self-assembly confined PDA NPs (SC-PDA NPs, <50 nm) are employed as a freestanding antibacterial ingredient for constructing an ideal hydrogel wound dressing, which maintains relatively strong reducibility and size effect. Through a rapid gelation (within 10 s) strategy triggered by electrostatic complexation, an antibacterial hydrogel system is obtained, in which the self-assembly of the SC-PDA NPs continues, endowing the gel with outstanding antibacterial activity, especially against methicillin-resistant (MRSA, >99.9%). With the continuous self-assembly, the size of the PDA NPs increases (>200 nm), eventually giving the gel an efficient photothermal therapy effect. Moreover, the gel presents a relatively strong wet adhesion (63 kPa), superior biocompatibility and non-immunogenicity. This work offers innovative insights into the antibacterial mechanism of SC-PDA NPs and provides a novel design for constructing safe antibacterial hydrogel wound dressings, demonstrating great potential applications in superbug-infected wound healing.
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http://dx.doi.org/10.1039/d2bm00310dDOI Listing
June 2022

Pueraria lobata starch regulates gut microbiota and alleviates high-fat high-cholesterol diet induced non-alcoholic fatty liver disease in mice.

Food Res Int 2022 Jul 26;157:111401. Epub 2022 May 26.

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China. Electronic address:

The dried roots of Pueraria lobata (Willd.) Ohwi as an edible medicinal herb are enriched with starch. However, the structure, physiology, and biological bioactivity of P. lobata starch (PLS) has not yet been fully investigated. This study showed that PLS consisted of mixed population of granules with polyhedral or spherical surface. The apparent content of resistant starch was 23.14%, and the molecular weight was 1.93 × 10 Da. PLS showed a branching degree and an average polymerization rate of 2.06% and 20.74%, respectively, with fairly high proportion of B1 short chains. The solubility and swelling power of PLS were 38.51% and 28.10 g/g, respectively, showing high hot stability of the viscosity. In vitro fermentation of PLS resulted in specifically altered composition of gut microbiota and increased production of SCFAs, showing a potential prebiotic effect. Moreover, PLS remarkably alleviated inflammation, hepatic steatosis and dyslipidemia in mice with high-fat high-cholesterol diet induced non-alcoholic fatty liver disease (NAFLD). The protective effect of PLS was associated with amelioration of NAFLD-associated gut dysbiosis through specifically increasing the abundance of Lactobacillus, Bifidobacterium and Turicibacter, and decreasing Desulfovibrio. The results would support the use of PLS as a functional prebiotic for protecting against NAFLD.
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http://dx.doi.org/10.1016/j.foodres.2022.111401DOI Listing
July 2022

Delta-like ligand 3-targeted radioimmunotherapy for neuroendocrine prostate cancer.

Proc Natl Acad Sci U S A 2022 Jul 27;119(27):e2203820119. Epub 2022 Jun 27.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065.

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer with limited meaningful treatment options. NEPC lesions uniquely express delta-like ligand 3 (DLL3) on their cell surface. Taking advantage of DLL3 overexpression, we developed and evaluated lutetium-177 (Lu)-labeled DLL3-targeting antibody SC16 (Lu-DTPA-SC16) as a treatment for NEPC. SC16 was functionalized with DTPA-CHX-A" chelator and radiolabeled with Lu to produce Lu-DTPA-SC16. Specificity and selectivity of Lu-DTPA-SC16 were evaluated in vitro and in vivo using NCI-H660 (NEPC, DLL3-positive) and DU145 (adenocarcinoma, DLL3-negative) cells and xenografts. Dose-dependent treatment efficacy and specificity of Lu-DTPA-SC16 radionuclide therapy were evaluated in H660 and DU145 xenograft-bearing mice. Safety of the agent was assessed by monitoring hematologic parameters. Lu-DTPA-SC16 showed high tumor uptake and specificity in H660 xenografts, with minimal uptake in DU145 xenografts. At all three tested doses of Lu-DTPA-SC16 (4.63, 9.25, and 27.75 MBq/mouse), complete responses were observed in H660-bearing mice; 9.25 and 27.75 MBq/mouse doses were curative. Even the lowest tested dose proved curative in five (63%) of eight mice, and recurring tumors could be successfully re-treated at the same dose to achieve complete responses. In DU145 xenografts, Lu-DTPA-SC16 therapy did not inhibit tumor growth. Platelets and hematocrit transiently dropped, reaching nadir at 2 to 3 wk. This was out of range only in the highest-dose cohort and quickly recovered to normal range by week 4. Weight loss was observed only in the highest-dose cohort. Therefore, our data demonstrate that Lu-DTPA-SC16 is a potent and safe radioimmunotherapeutic agent for testing in humans with NEPC.
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http://dx.doi.org/10.1073/pnas.2203820119DOI Listing
July 2022

Inducible nitric oxide synthase regulates macrophage polarization via the MAPK signals in concanavalin A-induced hepatitis.

Immun Inflamm Dis 2022 Jul;10(7):e643

Institute of Immune Precision Diagnosis and Therapy & Translational Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.

Introduction: Acute liver inflammatory reactions contribute to many health problems; thus, it is critical to understand the underlying pathogenic mechanisms of acute hepatitis. In this study, an experimental in vivo model of concanavalin A (ConA)-induced hepatitis was used.

Materials And Methods: C57BL/6 (wild-type, WT) or inducible nitric oxide synthase-deficient (iNOS ) mice were injected with PBS or 15 mg/kg ConA via tail vein. Detection of liver injury by histological examination and apoptosis, and flow cytometry to detect the effect of immune cells on liver injury.

Results: iNOS  mice had lower levels of the liver enzymes aspartate aminotransferase and alanine aminotransferase, suggesting that they were protected against ConA-induced pathological liver injury and that iNOS participated in the regulation of hepatitis. Furthermore, iNOS deficiency was found to lower CD86 expression and suppressed the messenger RNA levels of inflammatory factors in the liver. In vitro experiments also demonstrated that iNOS deficiency suppressed the sequential phosphorylation of the mitogen-activated protein kinase pathway cascade, thereby inhibiting the M1 polarization of macrophages and consequently suppressing the transcription of inflammation factors.

Conclusion: iNOS may contribute to ConA-induced inflammation by promoting the activation of proinflammatory macrophages.
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http://dx.doi.org/10.1002/iid3.643DOI Listing
July 2022

Tumor-targeted/reduction-triggered composite multifunctional nanoparticles for breast cancer chemo-photothermal combinational therapy.

Acta Pharm Sin B 2022 Jun 10;12(6):2710-2730. Epub 2021 Sep 10.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.

Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reduction-responsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targeting peptide cyclo(Asp-d-Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy.
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http://dx.doi.org/10.1016/j.apsb.2021.08.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214336PMC
June 2022

Early Serum Metabolism Profile of Post-operative Delirium in Elderly Patients Following Cardiac Surgery With Cardiopulmonary Bypass.

Front Aging Neurosci 2022 10;14:857902. Epub 2022 Jun 10.

Department of Anesthesiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Cardiac surgery with cardiopulmonary bypass (CPB) is considered to be one of the surgical types with the highest incidence of post-operative delirium (POD). POD has been associated with a prolonged intensive care and hospital stay, long-term neurocognitive deterioration, and increased mortality. However, the specific pathogenesis of POD is still unclear. Untargeted metabolomics techniques can be used to understand the changes of serum metabolites in early POD to discover the relationship between serum metabolites and disease.

Materials And Methods: The present study recruited 58 elderly patients undergoing cardiac surgery with CPB. Serum was collected within the first 24 h after surgery. The Confusion Assessment Method (CAM) and ICU-CAM assessments were used to identify patients who experienced POD. All patients with normal post-operative cognitive assessment were included in the non-POD groups. Moreover, we collected serum from 20 healthy adult volunteers. We performed untargeted analyses of post-operative serum metabolites in all surgical groups, as well as serum metabolites in healthy non-surgical adults by using liquid chromatography mass spectrometry (LC/MS) and analyzed metabolic profiles and related metabolites.

Results: The probability of POD after cardiac surgery were 31%. There were statistically significant differences in post-operative mechanical ventilation time, ICU stay time and post-operative hospital stay between POD and non-POD group ( < 0.05). And ICU stay time was an independent risk factor for POD. The analysis revealed that a total of 51 differentially expressed metabolites (DEMs) were identified by comparing the POD and non-POD group, mostly lipids and lipid-like molecules. Three phosphatidylinositol (PI) were down-regulated in POD group, i.e., PI [18:0/18:2 (9Z, 12Z)], PI [20:4 (8Z, 11Z, 14Z, 17Z)/18:0], and PI [18:1 (9Z)/20:3 (8Z, 11Z, 14Z)]. The receiver operating characteristic (ROC) curve analysis showed that three kinds of PI metabolites had the highest area under the curve (AUC), which were 0.789, 0.781, and 0.715, respectively. Correlation analysis showed that the expression of three PIs was negatively correlated with the incidence of POD.

Conclusion: Our findings suggest that lipid metabolism plays an important role in the serum metabolic profile of elderly patients with POD in the early post-operative period. Low serum lipid metabolic PI was associated with incidence of POD in elderly following cardiac bypass surgery, which may provide new insights into the pathogenesis of POD.
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http://dx.doi.org/10.3389/fnagi.2022.857902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226449PMC
June 2022

Cuscuta chinensis Lam. Protects Against Light-Induced Retinal Degeneration: Therapeutic Implications for Photoreceptor Degenerative Disorders.

Front Pharmacol 2022 8;13:904849. Epub 2022 Jun 8.

Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Lam. (CCL) is a medicinal herb widely used in traditional Chinese medicine for the treatment of ophthalmic diseases, including age-dependent vision-threatening retinal degenerative disorders that involve irreversible loss of the first-order retinal neurons, photoreceptors. However, evidence is lacking if CCL is pharmacologically active at protecting against loss of photoreceptors and photoreceptor degeneration-associated retinal structural and functional impairment. The current study thus evaluates the potential photoreceptor protective effects of CCL to better support its clinical applications in the prevention and treatment of photoreceptor degenerative diseases. Non-invasive full-retinal optical coherence tomography, electroretinography, histological examination, immunohistochemistry and real-time qPCR analysis were performed to assess the retinal protective effects of CCL in light-exposed BALB/c mice characterized by photooxidative stress-mediated photoreceptor loss and associated retinal morphological and functional impairment. The results showed that CCL treatment protected against light-induced degeneration of the photoreceptor structure and deterioration of the retinal function. Furthermore, CCL treatment increased the retinal expression of rhodopsin, S-opsin and M-opsin, supporting the protective effects of CCL in both rod and cone photoreceptors. CCL treatment suppressed photoreceptor cell death in the light-exposed retinas. The morphological integrity of the second-order retinal neurons was also preserved as a result of CCL treatment. In addition, CCL treatment attenuated light-induced reactive müller gliosis, microglial activation and inflammation in the retina. In conclusion, the current work demonstrates for the first time that CCL protects against photooxidative stress-mediated degeneration of photoreceptors and associated disturbance of structural, functional and immune homeostasis of the retina. The findings here thus provide novel experimental evidence supporting the clinical application of CCL in the prevention and treatment photoreceptor degenerative diseases.
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http://dx.doi.org/10.3389/fphar.2022.904849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214205PMC
June 2022

Modeling the effect of gut microbiome on therapeutic efficacy of immune checkpoint inhibitors against cancer.

Authors:
Yu Chen Xiulan Lai

Math Biosci 2022 Jun 23:108868. Epub 2022 Jun 23.

Institute for Mathematical Sciences, Renmin University of China, Beijing, 100872, China. Electronic address:

Immune checkpoint inhibitors have been shown to be highly successful against some solid metastatic malignancies, but only for a subset of patients who show durable clinical responses. The overall patient response rate is limited due to the interpatient heterogeneity. Preclinical and clinical studies have recently shown that the therapeutic responses can be improved through the modulation of gut microbiome. However, the underlying mechanisms are not fully understood. In this paper, we explored the effect of favorable and unfavorable gut bacteria on the therapeutic efficacy of anti-PD-1 against cancer by modeling the tumor-immune-gut microbiome interactions, and further examined the predictive markers of responders and non-responders to anti-PD-1. The dynamics of the gut bacteria was fitted to the clinical data of melanoma patients, and virtual patients data were generated based on the clinical patient survival data. Our simulation results show that low initial growth rate and low level of favorable bacteria at the initiation of anti-PD-1 therapy are predictive of non-responders, while high level of favorable bacteria at the initiation of anti-PD-1 therapy is predictive of responders. Simulation results also confirmed that it is possible to promote patients' response rate to anti-PD-1 by manipulating the gut bacteria composition of non-responders, whereby achieving long-term progression-free survival.
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http://dx.doi.org/10.1016/j.mbs.2022.108868DOI Listing
June 2022

Inhibition of S-adenosylhomocysteine hydrolase induces endothelial senescence via hTERT downregulation.

Atherosclerosis 2022 Jun 6;353:1-10. Epub 2022 Jun 6.

Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China; Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, People's Republic of China. Electronic address:

Background And Aims: It has been established that endothelial senescence plays a critical role in the development of atherosclerosis. Elevated S-adenosylhomocysteine (SAH) level induced by inhibition of S-adenosylhomocysteine hydrolase (SAHH) is one of the risk factors of atherosclerosis; however, the interplay between endothelial senescence and inhibition of SAHH is largely unknown.

Methods: Human umbilical vein endothelial cells (HUVECs) after serial passage were used. SAHH-specific inhibitor adenosine dialdehyde (ADA) and SAHH siRNA treated HUVECs and SAHHmice were used to investigate the effect of SAHH inhibition on endothelial senescence.

Results: HUVECs exhibited distinct senescence morphology as HUVECs were passaged, together with a decrease in intracellular SAHH expression and an increase in intracellular SAH levels. SAHH inhibition by ADA or SAHH siRNA elevated SA β-gal activity, arrested proliferation, and increased the expression of p16, p21 and p53 in HUVECs and the aortas of mice. In addition, decreased expression of hTERT and reduced occupancy of H3K4me3 over the hTERT promoter region were observed following SAHH inhibition treatment. To further verify the role of hTERT in the endothelial senescence induced by SAHH inhibition, hTERT was overexpressed with a plasmid vector under CMV promoter. hTERT overexpression rescued the senescence phenotypes in endothelial cells induced by SAHH inhibition.

Conclusions: SAHH inhibition induces endothelial senescence via downregulation of hTERT expression, which is associated with attenuated histone methylation over the hTERT promoter region.
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http://dx.doi.org/10.1016/j.atherosclerosis.2022.06.002DOI Listing
June 2022

Foreign gene expression attenuates a virulent Newcastle disease virus in chickens.

Virus Genes 2022 Jun 25. Epub 2022 Jun 25.

Key Laboratory of Animal Infectious Diseases, School of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Newcastle disease virus (NDV) is an important pathogen for poultry and is used as a vector for developing novel poultry vaccines. Previous studies showed that foreign gene insertion in NDV vector decreases virulence determined by in vitro assays; however, the impact of foreign gene expression on the pathogenicity of NDV in susceptible chickens is not fully investigated. In this study, a recombinant NDV based on a velogenic strain carrying the orange fluorescent protein (OFP) gene between the phosphoprotein (P) and matrix (M) genes was generated using reverse genetics. Biological characteristics, including virus replication, virulence, and OFP expression, and the pathogenicity in chickens were evaluated. The recombinant NDV showed comparable replication capacity in eggs and cells as the parental virus, whereas OFP insertion resulted in a mild impairment of virulence, evidenced by longer mean death time in embryos. High OFP expression was detected in the cells inoculated with the recombinant NDV. In addition, the recombinant NDV induced delayed onset of disease, lower severity of clinical signs, and lower mortality in chickens compared to the parental virus. Moreover, high titers of the parental virus were detected in the spleen, lung, and intestinal tract, while no recombinant NDV was recovered from these tissues. Our findings suggest that in vitro characteristics related to the insertion of the OFP gene in a virulent NDV do not correlate to alteration of the pathogenicity in chickens. Our results provided new information regarding assessment of the impact of foreign gene expression on the pathogenicity of NDV.
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http://dx.doi.org/10.1007/s11262-022-01922-8DOI Listing
June 2022

Progressive dysbiosis of human orodigestive microbiota along the sequence of gastroesophageal reflux, Barrett's esophagus, and esophageal adenocarcinoma.

Int J Cancer 2022 Jun 24. Epub 2022 Jun 24.

Department of Pathology, NYU School of Medicine, New York, New York, USA.

The incidence of esophageal adenocarcinoma (EA) has drastically increased in the United States since 1970s for unclear reasons. We hypothesized that the widespread usage of antibiotics has increased the procarcinogenic potential of the orodigestive microbiota along the sequence of gastroesophageal reflux (GR), Barrett's esophagus (BE), and EA phenotypes. This case control study included normal controls (NC) and three disease phenotypes GR, BE, and EA. Microbiota in the mouth, esophagus, and stomach, and rectum were analyzed using 16S rRNA gene sequencing. Overall, we discovered 44 significant pairwise differences in abundance of microbial taxa between the four phenotypes, with 12 differences in the mouth, 21 in the esophagus, two in the stomach, and nine in the rectum. Along the GR→BE→EA sequence, oral and esophageal microbiota were more diversified, the dominant genus Streptococcus was progressively depleted while six other genera Atopobium, Actinomyces, Veillonella, Ralstonia, Burkholderia, and Lautropia progressively enriched. In NC, Streptococcus appeared to control populations of other genera in the foregut via numerous negative and positive connections, while in disease states, the rich network was markedly simplified. Inferred gene functional content showed a progressive enrichment through the stages of EA development in genes encoding antibiotic resistance, ligands of Toll-like and NOD-like receptors, nitrate-nitrite-nitric oxide pathway, and acetaldehyde metabolism. The orodigestive microbiota is in a progressive dysbiotic state along the GR-BE-EA sequence. The increasing dysbiosis and antibiotic and procarcinogenic genes in the disease states warrants further study to define their roles in EA pathogenesis. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.34191DOI Listing
June 2022

Engineering 2D Silicene-Based Mesoporous Nanomedicine for In Vivo Near-Infrared-Triggered Analgesia.

Adv Sci (Weinh) 2022 Jun 24:e2202735. Epub 2022 Jun 24.

Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, P. R. China.

The utilization of local anesthetics for postoperative analgesia represents an effective approach, but generally suffers from short half-lives and brachychronic local neurotoxicity. A desirable anesthetic with controllable and sustainable drug-releasing performance for adequate analgesia effect is highly required. In this work, the core/shell-structured two-dimenional (2D) silicene nanosheets coated with mesoporous silica layer (abbreviated as [email protected]) have been rationally constructed as localized drug-delivery system in sciatic nerve block to achieve on-demand release of loaded ropivacaine (RP) in mesoporous silica layer for local analgesia. Based on the specific photothermal performance of 2D silicene core, this local anesthesia system can be triggered by near-infrared laser to release the loaded RP, resulting in on-demand and long-lasting regional anesthesia. The analgesia effect is assessed by pain behavior tests, which demonstrates that the RP-loaded [email protected] core/shell nanosystem behaves almost five times longer analgesia effect than free RP. Furthermore, the activation of pain-related neurons in nerve conduction pathways is tested to explore the underlying analgesia mechanism, revealing that the designed nanosystem can improve the pain threshold, reduce the activation of neurons in dorsal root ganglion and excitability in spinal substantia gelatinosa neurons. This designed anesthetic nanomedicine provides a facile but effective methodology for long-lasting regional anesthesia.
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http://dx.doi.org/10.1002/advs.202202735DOI Listing
June 2022

Study on Spraying Construction Method of a Non-Water Reacting Polymer Layer in the Tunnel.

Materials (Basel) 2022 Jun 10;15(12). Epub 2022 Jun 10.

School of Civil Engineering, Southwest Jiaotong University, Chengdu 610031, China.

Non-water reacting double-component foamed polyurethane has been increasingly used in the field of transportation. Particularly, it is recognized that a polymer damping layer between tunnel linings and surrounding rocks can improve the seismic performance of tunnels. To facilitate the application of this polymer in tunnels, a spraying construction method of polymer damping layers was proposed. The polymer damping layer was prepared with hydraulic spraying equipment, and the construction process included the pre-treatment of the tunnel base surface, the pressure control of the spraying equipment, the adjustment of the spray gun working parameters and spraying quality control. In this paper, the effects of material ratio, material temperature, environmental factors (i.e., temperature, humidity and wind speed), spraying pressure and spray gun parameters (i.e., speed, distance from the sprayed surface and spray angle) on the layer formation were investigated. Thus, spraying parameters for better spraying performance were recommended. This study will provide technical support for polymer damping layer construction in the seismic design of tunnels.
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http://dx.doi.org/10.3390/ma15124138DOI Listing
June 2022

Risks and Protective Factors of Hispanic Families and Their Young Children during the COVID-19 Pandemic.

Children (Basel) 2022 May 27;9(6). Epub 2022 May 27.

School of Education, University of California, Irvine, CA 92697, USA.

This study examines the risk-related factors during the pandemic and protective factors that might reduce its effects on family functioning in a sample of 161 low-income Hispanic parents in the United States, recruited from an ongoing longitudinal intervention study. They were surveyed about family functioning six months into the pandemic. We focused on the associations between social (e.g., exposure to the virus) and economic (e.g., job loss) pandemic-related risks on parental stress, parenting, and children's socioemotional problems and skills, as well as the degree to which coparenting support, parents' positivity, economic support, and access to services and information mitigated (protected) the negative effects of these stressors on family functioning. We found that increases in economic risk were associated with more child competence skills, whereas increases in social risk were associated with less parental engagement. Positivity and economic support moderated the effects of economic risk on parental stress and engagement. These findings show that to intervene effectively with low-income Hispanic families, we need to strengthen and support the resources for coping with adversity.
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http://dx.doi.org/10.3390/children9060792DOI Listing
May 2022

Visualization of Electrochemically Accessible Sites in Flow-through Mode for Maximizing Available Active Area toward Superior Electrocatalytic Ammonia Oxidation.

Environ Sci Technol 2022 Jun 23. Epub 2022 Jun 23.

Center for Water and Ecology, State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China.

Active chlorine species-mediated electrocatalytic oxidation is a promising strategy for ammonia removal in decentralized wastewater treatment. Flow-through electrodes (FTEs) provide an ideal platform for this strategy because of enhanced mass transport and sufficient electrochemically accessible sites. However, limited insight into spatial distribution of electrochemically accessible sites within FTEs inhibits the improvement of reactor efficiency and the reduction of FTE costs. Herein, a microfluidic-based electrochemical system is developed for the observation of microspatial reactions within pore channels, which reveals that reactions occur only in the surface layer of the electrode thickness. To further quantify the spatial distribution, finite element simulations demonstrate that over 75.0% of the current is accumulated in the 20.0% thickness of the electrode surface. Based on these findings, a gradient-coated method for the active layer was proposed and applied to a Ti/RuO porous electrode with an optimized pore diameter of ∼25 μm, whose electrochemically accessible surface area was 381.7 times that of the planar electrode while alleviating bubble entrapment. The optimized reactor enables complete ammonia removal with an energy consumption of 60.4 kWh kg N, which was 24.2% and 39.9% less than those with pore diameters of ∼3 μm and ∼90 μm, respectively.
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http://dx.doi.org/10.1021/acs.est.2c01707DOI Listing
June 2022

Chiral RuII-PtII Complexes Inducing Telomere Dysfunction against Cisplatin-Resistant Cancer Cells.

Angew Chem Int Ed Engl 2022 Jun 23. Epub 2022 Jun 23.

Sun Yat-Sen University, Chemistry, Xingang Xilu 135#, 510275, Guangzhou, CHINA.

The application of G-quadruplex stabilizers presents a promising anticancer strategy. However, the molecular crowding conditions within cells diminish the potency of current G-quadruplex stabilizers. Herein, chiral Ru(II)-Pt(II) dinuclear complexes were developed as highly potent G-quadruplex stabilizers even under challenging molecular crowding conditions. The compounds were encapsulated with biotin-functionalized DNA cages to enhance sub-cellular localization and provide cancer selectivity. The nanoparticles were able to efficiently inhibit the endogenous activities of telomerase in cisplatin-resistant cancer cells and cause cell death by apoptosis. The nanomaterials demonstrated high antitumor activity towards cisplatin-resistant tumor cells as well as tumor-bearing mice. To the best of our knowledge, this study presents the first example of a Ru(II)-Pt(II) dinuclear complex as a G-quadruplex stabilizer with an anti-cancer effect towards drug-resistant tumors inside an animal model.
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http://dx.doi.org/10.1002/anie.202204866DOI Listing
June 2022

Negatively Charged MOF-Based Composite Anion Exchange Membrane with High Cation Selectivity and Permeability.

Membranes (Basel) 2022 Jun 10;12(6). Epub 2022 Jun 10.

Key Laboratory of Environment-Friendly Polymeric Materials of Anhui Province, School of Chemistry & Chemical Engineering, Anhui University, Hefei 230601, China.

Every metal and metallurgical industry is associated with the generation of wastewater, influencing the living and non-living environment, which is alarming to environmentalists. The strict regulations about the dismissal of acid and metal into the environment and the increasing emphasis on the recycling/reuse of these effluents after proper remedy have focused the research community's curiosity in developing distinctive approaches for the recovery of acid and metals from industrial wastewaters. This study reports the synthesis of UiO-66-(COOH) using dual ligand in water as a green solvent. Then, the prepared MOF nanoparticles were introduced into the DMAM quaternized QPPO matrix through a straightforward blending approach. Four defect-free UiO-66-(COOH)/QPPO MMMs were prepared with four different MOF structures. The BET characterization of UiO-66-(COOH) nanoparticles with a highly crystalline structure and sub-nanometer pore size (~7 Å) was confirmed by XRD. Because of the introduction of MOF nanoparticles with an electrostatic interaction and pore size screening effect, a separation coefficient (S) of 565 and U of 0.0089 m·h for U-C(60)/QPPO were perceived when the loading dosage of the MOF content was 10 wt%. The obtained results showed that the prepared defect-free MOF membrane has broad prospects in acid recovery applications.
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http://dx.doi.org/10.3390/membranes12060601DOI Listing
June 2022

Antifibrotic effect of AD-1 on lipopolysaccharide-mediated fibroblast injury in L929 cells and bleomycin-induced pulmonary fibrosis in mice.

Food Funct 2022 Jun 23. Epub 2022 Jun 23.

Shenyang Pharmaceutical University, Shenyang 110016, China.

20()-25-methoxyl-dammarane-3β,12β,20-triol (25-OCH-PPD, AD-1) is a dammarane ginsenoside that is isolated from . The present study aimed to explore its anti-pulmonary fibrosis (PF) effect and . L929 cells were treated with 10 μg mL lipopolysaccharide (LPS) to establish a PF model and mice were administered with 3.5 mg kg bleomycin (BLM) by endotracheal intubation to establish a PF model for investigating the anti-PF effect and its potential mechanism. The results demonstrated that AD-1 reduced the injury, extracellular matrix (ECM) buildup and α-smooth muscle actin (α-SMA) protein expression levels of L929 induced by LPS. Oral administration of AD-1 downregulated the expression of interleukins (such as IL-1β, IL-6 and IL-18), increased the expression of superoxide dismutase (SOD) and glutathione (GSH), reduced the lung coefficient and the content of hydroxyproline (HYP), and mediated the Bax/Bcl-2 protein ratio and P-p53, β-catenin and SIRT3 expression in the lung tissue of mice. Furthermore, AD-1 inhibited the expression levels of TGF-β1, TIMP-1 and α-SMA and reduced inflammatory cell infiltration and collagen deposition in the lung tissue of PF mice. These results indicated that AD-1 could alleviate PF both and , and the underlying mechanism may be related to the decrease in ECM deposition and inflammation, the enhancement of antioxidant capacity, and the mediation of lung cell apoptosis and the TGF-β1/TIMP-1/α-SMA signaling pathway, which provide a theoretical basis for the rehabilitation treatment of PF.
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http://dx.doi.org/10.1039/d1fo04212bDOI Listing
June 2022

FGFR1 SUMOylation coordinates endothelial angiogenic signaling in angiogenesis.

Proc Natl Acad Sci U S A 2022 Jun 21;119(26):e2202631119. Epub 2022 Jun 21.

MOE Laboratory of Biosystems Homeostasis & Protection of College of Life Sciences, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province of Sir Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310058, China.

Angiogenesis contributes fundamentally to embryonic development, tissue homeostasis, and wound healing. Basic fibroblast growth factor (FGF2) is recognized as the first proangiogenic molecule discovered, and it facilitates angiogenesis by activating FGF receptor 1 (FGFR1) signaling in endothelial cells. However, the precise roles of FGFR and the FGF/FGFR signaling axis in angiogenesis remain unclear, especially because of the contradictory phenotypes of in vivo FGF and FGFR gene deficiency models. Our previous study results suggested a potential role of posttranslational small ubiquitin-like modifier modification (SUMOylation), with highly dynamic regulatory features, in vascular development and disorder. Here, we identified SENP1-regulated endothelial FGFR1 SUMOylation at conserved lysines responding to proangiogenic stimuli, while SENP1 functioned as the deSUMOylase. Hypoxia-enhanced FGFR1 SUMOylation restricted the tyrosine kinase activation of FGFR1 by modulating the dimerization of FGFR1 and FGFR1 binding with its phosphatase PTPRG. Consequently, it facilitated the recruitment of FRS2α to VEGFR2 but limited additional recruitment of FRS2α to FGFR1, supporting the activation of VEGFA/VEGFR2 signaling in endothelial cells. Furthermore, SUMOylation-defective mutation of FGFR1 resulted in exaggerated FGF2/FGFR1 signaling but suppressed VEGFA/VEGFR2 signaling and the angiogenic capabilities of endothelial cells, which were rescued by FRS2α overexpression. Reduced angiogenesis and endothelial sprouting in mice bearing an endothelial-specific, FGFR1 SUMOylation-defective mutant confirmed the functional significance of endothelial FGFR1 SUMOylation in vivo. Our findings identify the reversible SUMOylation of FGFR1 as an intrinsic fine-tuned mechanism in coordinating endothelial angiogenic signaling during neovascularization; SENP1-regulated FGFR1 SUMOylation and deSUMOylation controls the competitive recruitment of FRS2α by FGFR1 and VEGFR2 to switch receptor-complex formation responding to hypoxia and normoxia angiogenic environments.
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http://dx.doi.org/10.1073/pnas.2202631119DOI Listing
June 2022

Effectiveness and safety of ultrasound-guided high-intensity focused ultrasound ablation for the treatment of colorectal cancer liver metastases.

Int J Hyperthermia 2022 ;39(1):829-834

Department of Imaging and Interventional Radiology, Zhongshan-Xuhui Hospital of Fudan University/Shanghai Xuhui Central Hospital, Shanghai, China.

Objective: To investigate the effectiveness and safety of high-intensity focused ultrasound (HIFU) ablation for patients with colorectal liver metastases (CRLMs) who were unsuitable for hepatectomy.

Methods: This is a multicenter retrospective study. 238 CRLM patients underwent ultrasound-guided HIFU (USgHIFU) ablation in three medical centers from October 2014 to December 2020. Patients who had complete colorectal cancer resection, but exhibited extra-hepatic metastasis were excluded from this study. HIFU ablation procedure was performed, and contrast-enhanced MR imaging and/or contrast-enhanced CT examinations were conducted and mRECIST was used for the assessment of tumor ablation effectiveness before and after treatment, and every 3 months thereafter. Adverse events and complications were recorded.

Results: 43 CRML patients (27 male, 16 female, aged 29-82 years) were enrolled and underwent a USgHIFU ablation procedure. CR (complete response) was achieved in 21 patients, while PR (partial response) was observed in 21 patients and SD (stable disease) was achieved in one patient, respectively. The objective response rate was 97.7%. Median OS (overall survival) was estimated to be 31 months, and1-year and 18-month overall survival was 90.7% (39/43) and 72.1% (31/43), respectively. For CR and PR patients, the median OS was 35 months and 23 months, respectively ( = 0.00). The majority of adverse events were pain in 22 cases (51.2%) and local skin edema in 33 cases (76.7%). No severe adverse events or complications were reported and recorded.

Conclusions: USgHIFU ablation is a safe and effective treatment option for CRLM patients, especially for patients who are unsuitable for hepatectomy.
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http://dx.doi.org/10.1080/02656736.2022.2086712DOI Listing
June 2022

Protective effect of hydroxysafflor yellow A on cyclosporin A-induced renal oxidative stress in vitro and in vivo.

Authors:
Jiyuan Wang Yu Chen

Acta Cir Bras 2022 15;37(3):e370305. Epub 2022 Jun 15.

MSc. Second Military Medical University - Shanghai ChangZheng Hospital - Department of Organ Transplantation - Shanghai, China.

Purpose: To explore the mechanism and investigate the protective effect of hydroxysafflor yellow A (HSYA) on renal oxidative stress, which cyclosporine A (CsA) induces.

Methods: HK-2 cells were treated with CsA to get CsA-induced oxidative stress. The effects on oxidative stress and apoptosis of HK-2 cells were detected. The contents of SOD, MDA, GSH-Px, ROS, and CAT in serum were measured, and the expression of apoptosis-related proteins was detected by western blot. Then, established the renal oxidative stress injury rats to verify the efficacy of HSYA.

Results: HSYA could reduce the ROS and MDA contents induced by CsA. Compared with the CsA group, the activities of SOD, CAT, and GSH-Px increased significantly when treated with HSYA. HSYA could inhibit CsA-induced apoptosis in HK-2 cells, and promote the protein of Bcl-2 and inhibit the expression of Bax. Animal experiments showed that HSYA could reduce CsA-induced renal cell injury by reducing glomerular cell vacuoles and inflammatory factors in tissues. It also decreased serum creatinine (Crea) and blood urea nitrogen, increased Crea clearance significantly.

Conclusions: HSYA could significantly improve the antioxidant capacity of the kidney cells and inhibit cell apoptosis, thereby effectively ameliorating CsA-induced oxidative stress in vitro and in vivo.
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http://dx.doi.org/10.1590/acb370305DOI Listing
June 2022

Facile fabrication of hierarchical textures for substrate-independent and durable superhydrophobic surfaces.

Nanoscale 2022 Jun 22. Epub 2022 Jun 22.

Hunan Key Laboratory of Nanophotonics and Devices, School of Physics and Electronics, Central South University, Changsha 410083, China.

On account of their wide range of applications in self-cleaning, anti-icing, frost suppression, ., superhydrophobic surfaces have attracted considerate attention. However, most of the superhydrophobic surfaces can only be prepared on the surfaces of specific materials and are easily damaged in the case of friction. In this work, we propose a facile method to achieve superhydrophobicity on various substrate surfaces. By femtosecond laser direct processing, micron-level grooves and protrusions are constructed on substrates to form a protective layer. Then, the substrates covered by polytetrafluoroethylene (PTFE) were scanned to make the surfaces of the substrates superhydrophobic. Since the PTFE micro-nano-particles are evenly distributed on the grooves and protrusions, the surfaces exhibit robust superhydrophobicity with excellent anti-friction performance that is independent of the substrate properties. This work provides an efficient and environmentally friendly path for achieving robust superhydrophobic surfaces on various substrates.
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http://dx.doi.org/10.1039/d2nr02157aDOI Listing
June 2022

IQGAP1 is positively correlated with PD-L1 and regulates its expression via mediating STAT proteins phosphorylation.

Int Immunopharmacol 2022 Jul 31;108:108897. Epub 2022 May 31.

Department of Oncology, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital to Nanjing Medical University, Wuxi 214023, China. Electronic address:

IQ motif containing GTPase activating protein 1 (IQGAP1) is a scaffold protein to transduce multiple signals from the extracellular microenvironment. However, whether IQGAP1 mediates EGF-induced cancer progression has been not observed. In this research, we explored the immunological correlations of IQGAP1. IQGAP1 was up-regulated in most cancer and related to poor prognosis in ovarian cancer. In addition, IQGAP1 was correlated with immune-related genes and tumor-infiltrating lymphocytes. IQGAP1 was a novel EGF-response gene, which was up-regulated by EGF. As the downstream of EGFR, IQGAP1 mediated EGF-induced proliferation, migration and invasion of tumor cells and was essential for EGF-induced PD-L1 expression as well. Mechanically, IQGAP1 interacted with STATs and mediated their phosphorylation. Furthermore, Curcumin inhibited EGFR/IQGAP1 axis to down-regulate PD-L1 and suppress cancer progression. To sum up, IQGAP1 responds to EGF stimulation and mediates EGF-induced phosphorylation of STATs, which is a novel promising target for blocking the EGF-induced cancer progression.
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http://dx.doi.org/10.1016/j.intimp.2022.108897DOI Listing
July 2022

miR-146a/KLF4 axis in epileptic mice: a novel regulator of synaptic plasticity involving STAT3 signaling.

Brain Res 2022 Jun 18:147988. Epub 2022 Jun 18.

Department of Neurology, the First Hospital of Changsha, Changsha, Hunan 410005, PR China.

Objective: This study is aimed to investigate the mechanism of miR-146a/KLF4 axis regarding epilepsy seizure and synaptic plasticity.

Methods: Pentylenetetrazol (PTZ)-kindling mouse model of epilepsy was established and evaluated by Racine's scale. PTZ-treated mice were subjected to stereotactic injection of miR-146a antagomir and pre-KLF4 to verify the role of miR-146a and KLF4 in mice. Primary hippocampal neurons from fetal mouse were isolated and identified through immunofluorescence for microtubule-associated protein (MAP)-2. Cellular models of epilepsy were prepared using magnesium-free extracellular fluid and then the neurons were transfected with miR-146a antagomir, miR-146a agomir, miR-146a agomir + pre-KLF4, AG490 (an inhibitor of STAT3 signal pathway) or miR-146a agomir + AG490. The binding site between miR-146a and KLF4 was predicted and identified. The expression levels of miR-146a, KLF4, CREB, Synaptotagmin-11 (SYT11), and STAT3-related proteins were measured in addition to the morphology of neurons and length of neurite. The severity of synaptic plasticity was assessed according to the levels of CREB and SYT11.

Results: The expression of miR-146a was elevated and KLF4 expression was decreased in epileptic mice. Stereotactic injection of miR-146a antagomir and pre-KLF4 reduced the seizure scores of epileptic mice. Transfection of miR-146a antagomir or pre-KLF4 could attenuate synaptic plasticity in epileptic mice and epileptic cellular models. miR-146a can negatively regulate KLF4 in epileptic cellular models to mediate synaptic plasticity. Epilepsy was attenuated in AG490 and miR-146a agomir + AG490 groups compared with that in Model group.

Conclusion: miR-146a inhibits KLF4 to activate STAT3, thus promoting synaptic plasticity in epileptic mice.
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http://dx.doi.org/10.1016/j.brainres.2022.147988DOI Listing
June 2022

In Operando Visualization and Dynamic Manipulation of Electrochemical Processes at the Electrode-Solution Interface.

Angew Chem Int Ed Engl 2022 Jun 21. Epub 2022 Jun 21.

Tsinghua University, Center for Water and Ecology, CHINA.

Revealing the dynamic processes at the electrode-solution interface is imperative for understanding electrochemical phenomena. Most techniques have been developed to sense the electrode surface changes at the nanoscale, but provide limited information on potential-induced interfacial ion redistribution at the mesoscale. Herein, we present an in operando visualization method utilizing a microfabricated electrochemical cell combined with a laser scanning confocal microscope to observe high-resolution and fast-response interfacial processes. We report potential-induced formation and transformation of the Nernst diffusion layer, demonstrating that pulsed voltage dynamically perturbs the interface and promotes ion diffusion. This provides an additional insight into developing a dynamic manipulation method to control the electrochemical process. Our novel visualization method can easily be applied to monitor different ionic behaviors in electrochemical reactions at the mesoscale.
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http://dx.doi.org/10.1002/anie.202206236DOI Listing
June 2022

Obstructive sleep apnea and the risk of Alzheimer's disease and Parkinson disease: A Mendelian randomization study OSA, Alzheimer's disease and Parkinson disease.

Sleep Med 2022 Jun 9;97:55-63. Epub 2022 Jun 9.

Department of Otorhinolaryngology Head and Neck Surgery, the Shengjing Hospital of China Medical University, No 39 Haxiang Road, Tiexi District, Shenyang, Liaoning Province, China. Electronic address:

Background: Previous studies reported that obstructive sleep apnea (OSA) was associated with neurodegenerative diseases. However, whether these associations are causal are still unsettled. In our study, we investigated the causal effects of genetically-predicted OSA on Alzheimer's disease (AD) and Parkinson disease (PD).

Methods: We implemented two-sample Mendelian randomization to judge causation using summary statistics from three independent and large genome-wide association studies on OSA (cases n = 16,761, controls n = 201,194), AD (cases n = 71,880, controls n = 383,378) and PD (cases n = 33,774, controls n = 449,056). Four single nucleotide polymorphisms (SNPs) with genome-wide significance associated with OSA served as instrumental variables. We prioritized the inverse variance weighted method when generating unconfounded estimates. Besides, MR-Egger regression, weighted mode, and weighted median methods were adopted as a supplement to the inverse variance weighted method.

Results: We found no evidence supporting significant causal relationships between OSA and AD or PD among European population. The risk ratio of AD was 0.99 (95% confidence interval (CI) [0.92,1.08]) and that of PD was 0.82 (95%CI [0.47, 1.40]). Results from alternative approaches were generally consistent with that of the inverse variance weighted method.

Conclusion: The present study found no evidence for causal associations between OSA and the risk of AD or PD in individuals of European ancestry.
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http://dx.doi.org/10.1016/j.sleep.2022.06.004DOI Listing
June 2022
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