Publications by authors named "Xiaoqin Wang"

419 Publications

Sustainable Antibacterial Surgical Suture Using a Facile Scalable Silk-Fibroin-Based Berberine Loading System.

ACS Biomater Sci Eng 2021 Jun 27;7(6):2845-2857. Epub 2021 May 27.

National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China.

Medical sutures with sustainable antibacterial properties can effectively inhibit pathogens, thus avoiding the occurrence of surgical site infection and reducing the recurrence of patients resulting in postoperative death. This paper describes a facile scalable antibacterial surgical suture with sustainable antibacterial function and fair mechanical and biocompatible properties using a simple, efficient, and eco-friendly method. Silk filaments were braided into a core-shell structure using a braiding machine, and then silk fibroin (SF) films loaded with different percentages of berberine (BB) were coated onto the surface of the suture. The drug-loaded sutures performed a slow drug-release profile of more than 7 days. Retention of the knot-pull tensile strength of all groups was above 87% during degradation within 42 days. The sutures had no toxicity to the cells' cytotoxicity. The results of the biocompatibility test showed mild inflammation and clear signs of supporting angiogenesis in the implantation site of the rats. This work provides a new route for achieving a BB-loaded and high-performance antibacterial suture, which is of great potential in applications for surgical operations.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00481DOI Listing
June 2021

Modulating the activity of right temporo-parietal junction increases bidding behavior in lottery contests.

Neurosci Lett 2021 May 24;757:135875. Epub 2021 May 24.

School of Economics and Management, Southwest Petroleum University, Chengdu, 610500, China; Experimental research Center for Behavioral science and Decision-neuroscience of School of Economics and Management, Southwest Petroleum University, Chengdu, 610500, China.

Contest often involves bids that are higher than the Nash equilibrium, and overbidding behaviour closely relates to personal reasoning and judgement. The right temporo-parietal junction (rTPJ) plays an important role in social, cognitive and inference decision-making. In the present study, we investigated the effect of transcranial direct current stimulation (tDCS) of the rTPJ on overbidding behaviour by using a modified model-lottery contests task. Our results showed that participants that received cathodal-stimulation had significantly higher expenditure compared to participants that received anodal and sham stimulation. Cathodal-stimulation may reduce the participants' ability to infer other contestants' intention or may modulate the non-monetary utility of winning. Our data indicate that excitability of the rTPJ may contribute to overbidding behaviour.
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http://dx.doi.org/10.1016/j.neulet.2021.135875DOI Listing
May 2021

Biosensing of β-Amyloid Peptide Aggregation Dynamics using a Biological Nanopore.

Sens Actuators B Chem 2021 Jul 29;338. Epub 2021 Mar 29.

Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA.

Alzheimer's disease and other neurodegenerative disorders are becoming more prevalent as advances in technology and medicine increase living standards and life expectancy. Alzheimer's disease is thought to initiate development early in the patient's life and progresses continuously into old age. This process is characterized molecularly by the amyloid hypothesis, which asserts that self-aggregating amyloid peptides are core to the pathophysiology in Alzheimer's progression. Precise quantification of amyloid peptides in human bodily fluid samples ( cerebrospinal fluid, blood) may inform diagnosis and prognosis, and has been studied using established biosensing technologies like liquid chromatography, mass spectrometry, and immunoassays. However, existing methods are challenged to provide single molecule, quantitative analysis of the disease-causing aggregation process. Ultra-sensitive nanopore biosensors can step in to fill this role as a dynamic mapping tool. The work in this paper establishes characteristic signals of β-amyloid 40 monomers, oligomers, and soluble aggregates, as well as a proof-of-concept foundation where a biological nanopore biosensor is used to monitor the extent of β-amyloid 40 peptide aggregation at the single molecule level. This foundation allows for future work to expand in drug screening, diagnostics, and aggregation dynamic experiments.
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http://dx.doi.org/10.1016/j.snb.2021.129863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078859PMC
July 2021

Functional Connectome Prediction of Anxiety Related to the COVID-19 Pandemic.

Am J Psychiatry 2021 Apr 26:appiajp202020070979. Epub 2021 Apr 26.

Key Laboratory of Cognition and Personality of Ministry of Education, Faculty of Psychology, Southwest University, Chongqing, China (He, Wei, W. Yang, Zhuang, Q. Chen, Ren, Y. Li, Wang, Mao, Z. Chen, Q. He, Lei, T. Feng, H. Chen, Qiu); Guangdong Mental Health Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China (F. Yang); Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China (Zhang, Cheng, J. Feng); Department of Psychiatry, the Second Xiangya Hospital of Central South University, Changsha, China (Liao, Su, L. Li); Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Cui, C. Li); Department of Neurology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Xie); Oxford Center for Computational Neuroscience, Oxford, U.K. (Rolls); Department of Computer Science, University of Warwick, Coventry, U.K. (Rolls); and Southwest University Branch, Collaborative Innovation Center of Assessment Toward Basic Education Quality, Beijing Normal University, Beijing, China (Qiu).

Objective: Increased anxiety in response to the COVID-19 pandemic has been widely noted. The purpose of this study was to test whether the prepandemic functional connectome predicted individual anxiety induced by the pandemic.

Methods: Anxiety scores from healthy undergraduate students were collected during the severe and remission periods of the pandemic (first survey, February 22-28, 2020, N=589; second survey, April 24 to May 1, 2020, N=486). Brain imaging data and baseline (daily) anxiety ratings were acquired before the pandemic. The predictive performance of the functional connectome on individual anxiety was examined using machine learning and was validated in two external undergraduate student samples (N=149 and N=474). The clinical relevance of the findings was further explored by applying the connectome-based neuromarkers of pandemic-related anxiety to distinguish between individuals with specific mental disorders and matched healthy control subjects (generalized anxiety disorder, N=43; major depression, N=536; schizophrenia, N=72).

Results: Anxiety scores increased from the prepandemic baseline to the severe stage of the pandemic and remained high in the remission stage. The prepandemic functional connectome predicted pandemic-related anxiety and generalized to the external sample but showed poor performance for predicting daily anxiety. The connectome-based neuromarkers of pandemic-related anxiety further distinguished between participants with generalized anxiety and healthy control subjects but were not useful for diagnostic classification in major depression and schizophrenia.

Conclusions: These findings demonstrate the feasibility of using the functional connectome to predict individual anxiety induced by major stressful events (e.g., the current global health crisis), which advances our understanding of the neurobiological basis of anxiety susceptibility and may have implications for developing targeted psychological and clinical interventions that promote the reduction of stress and anxiety.
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http://dx.doi.org/10.1176/appi.ajp.2020.20070979DOI Listing
April 2021

Effectiveness of Chinese herbal medicine combined with Western medicine on deferring dialysis initiation for nondialysis chronic kidney disease stage 5 patients: a multicenter prospective nonrandomized controlled study.

Ann Transl Med 2021 Mar;9(6):490

Department of Nephrology, First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang, China.

Background: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD.

Methods: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors' advice and the patients' wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up.

Results: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching.

Conclusions: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD patients.
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http://dx.doi.org/10.21037/atm-21-871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039672PMC
March 2021

Sustained Photosynthesis and Oxygen Generation of Microalgae-Embedded Silk Fibroin Hydrogels.

ACS Biomater Sci Eng 2021 Jun 9;7(6):2734-2744. Epub 2021 Apr 9.

National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China.

Microalgae immobilized in hydrogels offer advantages over those cultured in suspension culture in terms of carbon fixation and oxygen emission. However, alginate as a commonly used hydrogel for microalgal immobilization encounters problems with mechanical strength and stability. To address this limitation, silk fibroin (silk) hydrogels prepared by ultrasonication were utilized to host microalgae when mixed with the presonicated protein solution prior to its gelation. The gelation time, stability, and light transmission of these silk gels were evaluated, and a silk concentration of 4% w/v and a gel thickness of 1 mm provided mechanical strength and stability during algal culture in comparison to alginate hydrogels. Furthermore, silk hydrogels with algal cell densities of 7.6 × 10 and 7.8 × 10 cells/mL had better stability than those with a lower cell density (3.2 × 10 cells/mL), likely due to cell confinement and impact on proliferation. The silk hydrogels with microalgae at a high density generated 6.13 mg/L of oxygen continuously for 7 days. An oxygen-generating device was fabricated by coating the surface of a dialysis tube with a thin layer of the microalgae-embedded silk hydrogel, where the microalgal cells were nourished with culture medium prefilled in the dialysis tube. When suspended in a sealed flask filled with CO gas, the system continuously produced oxygen (151 mL) for at least 60 days, with an oxygen production efficiency 6 times that of microalgal suspension culture controls. This microalgae embedding and cultivation technique could have potential utility in air purification, tissue repair, and other applications due to the efficient and sustained generation of oxygen.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00168DOI Listing
June 2021

Insight into the effects of electrochemical factors on host-guest interaction induced signature events in a biological nanopore.

Nanotechnol Precis Eng 2020 Mar 23;3(1):2-8. Epub 2020 Dec 23.

Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208, USA.

The signature events caused by host-guest interactions in the nanopore system can be used as a novel and characteristic signal in quantitative detection and analysis of various molecules. However, the effect of several electrochemical factors on the host-guest interactions in nanopore still remains unknown. Here, we systematically studied host-guest interactions, especially oscillation of DNA-azide [email protected][6] in α-Hemolysin nanopore under varying pH, concentration of electrolytes and counterions (Li, Na, K). Our results indicate correlations between the change of pH and the duration of the oscillation signal. In addition, the asymmetric electrolyte concentration and the charge of the counterions affects the frequency of signature events in oscillation signals, and even the integrity of the protein nanopore. This study provides insight into the design of a future biosensing platform based on signature oscillation signals of the host-guest interaction within a nanopore.
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http://dx.doi.org/10.1016/j.npe.2019.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006565PMC
March 2020

Effects of vitamin K combined with methotrexate against mitogen-activated peripheral blood mononuclear cells of healthy subjects and rheumatoid arthritis patients.

Fundam Clin Pharmacol 2021 Mar 29. Epub 2021 Mar 29.

Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan.

Background: Methotrexate (MTX) is used as anchor drug for patients with early and established rheumatoid arthritis (RA). Vitamin K administration was also reported to be associated with decreased disease activity in RA.

Objectives: Immunosuppressive pharmacodynamics of vitamin K combined with MTX was investigated.

Methods: Mitogen-activated peripheral blood mononuclear cells (PBMCs) were used to evaluate immunosuppressive pharmacodynamics of drugs in vitro.

Results: Vitamin K alone dose-dependently suppressed T cell mitogen-activated proliferation of PBMCs of both healthy subjects and RA patients. 446.5 and 2232.5 ng/mL vitamin K significantly decreased the IC values of MTX on the proliferation of PBMCs of RA patients, with little influences on the pharmacodynamics of MTX in the healthy PBMCs. 4465 ng/mL vitamin K potentiated the pharmacodynamics of MTX in both RA patients and healthy PBMCs. The additional effects of vitamin K to potentiate the suppressive effects of MTX seemed not to be related to the regulation of CD4 CD25 T cells or CD4 CD25 Foxp3 Treg cells. MTX alone at 100 ng/mL significantly decreased the percentage of CD4 T cells in PBMCs of healthy subjects (p < 0.001) with a slight influence in that of RA patients (not significant) and the combination did not show synergistic inhibitory effect. Vitamin K alone tended to suppress the secretion of IL-17, IFN-γ, and TNF-α from the activated PBMCs of RA patients with smaller influences on the cytokine productions from healthy PBMCs. These additional effects of vitamin K were also observed in combination with MTX.

Conclusion: The above information may partially elucidate the potentiation effects of vitamin K on the immunosuppressive efficacy of MTX.
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http://dx.doi.org/10.1111/fcp.12676DOI Listing
March 2021

Multiplex quantitative detection of SARS-CoV-2 specific IgG and IgM antibodies based on DNA-assisted nanopore sensing.

Biosens Bioelectron 2021 Jun 3;181:113134. Epub 2021 Mar 3.

Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA; Department of Chemical Engineering, College of Engineering and Computing, University of South Carolina, Columbia, SC 29208, USA. Electronic address:

The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread into a global pandemic. Early and accurate diagnosis and quarantine remain the most effective mitigation strategy. Although reverse transcriptase polymerase chain reaction (RT-qPCR) is the gold standard for COVID-19 diagnosis, recent studies suggest that nucleic acids were undetectable in a significant number of cases with clinical features of COVID-19. Serologic assays that detect human antibodies to SARS-CoV-2 serve as a complementary method to diagnose these cases, as well as to identify asymptomatic cases and qualified convalescent serum donors. However, commercially available enzyme-linked immunosorbent assays (ELISA) are laborious and non-quantitative, while point-of-care assays suffer from low detection accuracy. To provide a serologic assay with high performance and portability for potential point-of-care applications, we developed DNA-assisted nanopore sensing for quantification of SARS-CoV-2 related antibodies in human serum. Different DNA structures were used as detection reporters for multiplex quantification of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the nucleocapsid protein of SARS-CoV-2 in serum specimens from patients with conformed or suspected infection. Comparing to a clinically used point-of-care assay and an ELISA assay, our technology can reliably quantify SARS-CoV-2 antibodies with higher accuracy, large dynamic range, and potential for assay automation.
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http://dx.doi.org/10.1016/j.bios.2021.113134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927651PMC
June 2021

Role of Active Components of Medicinal Food in the Regulation of Angiogenesis.

Front Pharmacol 2020 22;11:594050. Epub 2021 Jan 22.

Department of Pharmacy, Inner Mongolia Medical University, Hohhot, China.

Angiogenesis refers to the formation of new blood vessels from the endothelial cells of existing arteries, veins, and capillaries. Angiogenesis is involved in a variety of physiological and pathological processes, such as the formation of malignant and development of atherosclerosis and other diseases. In recent years, many studies have shown that the active components of food have a certain regulatory effect on angiogenesis and negligible clinical limitations. With the increasing attention being paid to medicine and food homology, exploring the effect of active food components on angiogenesis is of great significance. In this review, we discuss the source, composition, pharmacological activity, and mechanism of action of certain active components of medicinal foods in detail. These could help prevent angiogenesis-related complications or provide a basis for healthier dietary habits. This review can provide a theoretical basis for the research and development of highly efficient anti-angiogenic drugs with low toxicity.
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http://dx.doi.org/10.3389/fphar.2020.594050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944143PMC
January 2021

Comparison of Azacitidine and Decitabine in Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Network Meta-analysis.

Clin Lymphoma Myeloma Leuk 2021 Jun 24;21(6):e530-e544. Epub 2021 Feb 24.

Department of Hematology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

Background: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies that mostly affect the elderly and have a poor prognosis. Azacitidine (AZA) and decitabine (DAC) are the most widely used hypomethylating agents. However, few randomized controlled trials (RCTs) have compared AZA and DAC head to head in MDS or AML. This study intended to conduct a network meta-analysis to compare the 2 drugs to provide more guidance using evidence-based medicine.

Patients And Methods: A comprehensive search for RCTs was performed till July 31, 2020. The network meta-analysis was conducted using the Markov chain Monte Carlo method. The primary endpoints were overall survival (OS) and the incidence of adverse events, and the secondary endpoints were complete remission (CR) rate, overall remission rate (ORR), and AML-free survival. There were 6 RCTs with 1072 MDS patients, and 3 RCTs with 1256 AML patients.

Results: In MDS, AZA showed better AML-free survival (hazard ratio = 0.62; 95% CI, 0.43-0.9), whereas DAC had the possibility of achieving better CR and ORR, and AZA had the possibility of obtaining better OS with lower toxicity. As for elderly AML patients, DAC had the possibility of achieving superior CR, ORR, and OS, while the toxicity was relatively higher. Furthermore, subgroup analysis for patients ≥ 75 years old or of high risk in MDS suggested that AZA achieved better OS.

Conclusion: For MDS, especially patients with intermediate or high risk disease with advanced age and poor general condition, AZA may be a better choice, while DAC may be of more benefit in elderly AML patients.
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http://dx.doi.org/10.1016/j.clml.2021.01.024DOI Listing
June 2021

The mTORC1/eIF4E/HIF-1α Pathway Mediates Glycolysis to Support Brain Hypoxia Resistance in the Gansu Zokor, .

Front Physiol 2021 23;12:626240. Epub 2021 Feb 23.

National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Science, Shaanxi Normal University, Xi'an, China.

The Gansu zokor () is a subterranean rodent species that is unique to China. These creatures inhabit underground burrows with a hypoxia environment. Metabolic energy patterns in subterranean rodents have become a recent focus of research; however, little is known about brain energy metabolism under conditions of hypoxia in this species. The mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) coordinates eukaryotic cell growth and metabolism, and its downstream targets regulate hypoxia inducible factor-1α (HIF-1α) under conditions of hypoxia to induce glycolysis. In this study, we compared the metabolic characteristics of hypoxia-tolerant subterranean Gansu zokors under hypoxic conditions with those of hypoxia-intolerant Sprague-Dawley rats with a similar-sized surface area. We exposed Gansu zokors and rats to hypoxia I (44 h at 10.5% O) or hypoxia II (6 h at 6.5% O) and then measured the transcriptional levels of mTORC1 downstream targets, the transcriptional and translational levels of glycolysis-related genes, glucose and fructose levels in plasma and brain, and the activity of key glycolysis-associated enzymes. Under hypoxia, we found that α transcription was upregulated the mTORC1/eIF4E pathway to drive glycolysis. Furthermore, Gansu zokor brain exhibited enhanced fructose-driven glycolysis under hypoxia through increased expression of the GLUT5 fructose transporter and ketohexokinase (KHK), in addition to increased KHK enzymatic activity, and utilization of fructose; these changes did not occur in rat. However, glucose-driven glycolysis was enhanced in both Gansu zokor and rat under hypoxia II of 6.5% O for 6 h. Overall, our results indicate that on the basis of glucose as the main metabolic substrate, fructose is used to accelerate the supply of energy in Gansu zokor, which mirrors the metabolic responses to hypoxia in this species.
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http://dx.doi.org/10.3389/fphys.2021.626240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940537PMC
February 2021

Bupi Yishen Formula Versus Losartan for Non-Diabetic Stage 4 Chronic Kidney Disease: A Randomized Controlled Trial.

Front Pharmacol 2020 29;11:627185. Epub 2021 Jan 29.

Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou, China.

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF ( = 283) or losartan ( = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: -2.25 ml/min/1.73 m/year, 95% confidence interval [CI]: -4.03,-0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects. http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.
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http://dx.doi.org/10.3389/fphar.2020.627185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941267PMC
January 2021

Role of H2B mono-ubiquitination in the initiation and progression of cancer.

Bull Cancer 2021 Apr 6;108(4):385-398. Epub 2021 Mar 6.

Tianjin University of Science and Technology, College of Biotechnology, Tianjin 300457, PR China; Wuhan University of Science and Technology, Institute of Biology and Medicine, Wuhan 430081, PR China. Electronic address:

Numerous epigenetic alterations are observed in cancer cells, and dysregulation of mono-ubiquitination of histone H2B (H2Bub1) has often been linked to tumorigenesis. H2Bub1 is a dynamic post-translational histone modification associated with transcriptional elongation and DNA damage response. Histone H2B monoubiquitination occurs in the site of lysine 120, written predominantly by E3 ubiquitin ligases RNF20/RNF40 and deubiquitinated by ubiquitin specific peptidase 22 (USP22). RNF20/40 is often altered in the primary tumors including colorectal cancer, breast cancer, ovarian cancer, prostate cancer, and lung cancer, and the loss of H2Bub1 is usually associated with poor prognosis in tumor patients. The purpose of this review is to summarize the current knowledge of H2Bub1 in transcription, DNA damage response and primary tumors. This review also provides novel options for exploiting the potential therapeutic target H2Bub1 in personalized cancer therapy.
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http://dx.doi.org/10.1016/j.bulcan.2020.12.007DOI Listing
April 2021

Increased interleukin-11 associated with disease activity and development of interstitial lung disease in patients with rheumatoid arthritis.

Clin Exp Rheumatol 2021 Mar 2. Epub 2021 Mar 2.

Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, Jiangsu Province, China.

Objectives: To investigate the association of serum interleukin-11 (IL-11) with disease activity and occurrence of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA).

Methods: One hundred and six RA patients were included, including 31 with ILD. All patients were divided into two groups according to the 28-joint Disease Activity Score (DAS28), active-disease group (DAS28>3.2) and target-achieved group (DAS28≤3.2). Serum IL-11 was detected by ELISA. Serum autoantibodies [anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF)], inflammatory markers [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)], and complete blood count were measured with routine methods.

Results: Serum IL-11 was upregulated in RA patients compared with healthy controls (HC), and increased more significantly in patients with ILD (RA-ILD) than patients without ILD (RA-nonILD). In both RA-ILD and RA-nonILD patients, serum level of IL-11 was higher in the active-disease group than that in the target-achieved group. Pearson correlation analysis confirmed that IL-11 was positively correlated with DAS28. No significant correlation was found between serum level of IL-11 and ACPA or RF. IL-11 was positively correlated with ESR and CRP levels and PLT count in RA patients.

Conclusions: IL-11 was found to be involved in the development of arthritis and ILD in RA patients, and might constitute a potential target for the treatment of RA-ILD.
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March 2021

Dynamics of a stochastic HBV infection model with cell-to-cell transmission and immune response.

Math Biosci Eng 2020 12;18(1):616-642

School of Mathematics and Statistics, Huaiyin Normal University, Huaian 223300, China.

In this paper, considering the proven role of exosomes and the inevitable randomization within-host, we establish a hepatitis B virus (HBV) model with cell-to-cell transmission and CTL immune response from a deterministic framework to a stochastic differential equation (SDE). By introducing the reproduction number $ R_0 $, we prove that $ R_0 $ can be used to govern the stochastic dynamics of the SDE HBV model. Under certain assumptions, if $ R_{0}\leq1 $, the solution of the SDE model always fluctuates around the infection-free equilibrium of the deterministic model, which indicates that the HBV will eventually disappear almost surely; if $ R_{0} > 1 $, under extra conditions, the solution of the SDE model fluctuates around endemic equilibrium of the corresponding deterministic model, which leads to the stochastic persistence of the HBV with probability one. One of the most interesting findings is that the fluctuation amplitude is positively related to the intensity of the white noise, which can provide us some useful control strategies to regulate HBV infection dynamics.
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http://dx.doi.org/10.3934/mbe.2021034DOI Listing
December 2020

Ductility and Porosity of Silk Fibroin Films by Blending with Glycerol/Polyethylene Glycol and Adjusting the Drying Temperature.

ACS Biomater Sci Eng 2020 02 23;6(2):1176-1185. Epub 2020 Jan 23.

National Engineering Laboratory for Modern Silk, Soochow University, Suzhou 215123, P.R. China.

Ductility and porosity of biofunctional films (BFFs) are critical properties for mechanical compliance and intercellular communication in tissue engineering. However, it remains a significant challenge to integrate these two key properties into BFFs. Herein, silk fibroin (SF) films with tunable ductility and porosity were prepared by adjusting the protein self-assembly process through combinations with glycerol (Gly) and polyethylene glycol 400 (PEG400) and regulating the film-casting temperature. Typically, among various conditions screened, the BFFs with a mass ratio of SF/PEG400/Gly of 10:5:3 (SPG1053) prepared at 4 °C exhibited remarkable ductility with a tensile strength of 2.7 ± 0.2 MPa and an elongation at break of 164.24 ± 24.20%, superior to films prepared from SF alone, SF/Gly, or SF/PEG400, demonstrating a synergistic plasticizing effect. Furthermore, the SPG1053 films prepared at 4 °C had a permeation efficiency of 56.32 ± 0.85% for fluorescently labeled dextran (dextran-TMR, MW: 10 kDa) after 204 h, significantly higher than films prepared at 20 °C (34.67 ± 3.63%) and 60 °C (15.4 ± 1.16%). Finally, the ductile and porous SPG1053 had excellent cell compatibility with human fibroblasts (Hs 865.SK). Given the demonstrated ductility, molecule-sieving property, and cytocompatibility, these new SPG films should offer new options for cell culture and tissue engineering.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01567DOI Listing
February 2020

Flexible Water-Absorbing Silk-Fibroin Biomaterial Sponges with Unique Pore Structure for Tissue Engineering.

ACS Biomater Sci Eng 2020 03 13;6(3):1641-1649. Epub 2020 Feb 13.

National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China.

Silk fibroin (SF) scaffolds are widely used in tissue engineering due to their biocompatibility and slow biodegradability. However, the relatively stiff mechanical properties and low permeability of these systems can limit some applications. In this study, a new type of water-stable silk sponge (ASF-PEG-S) was obtained by inducing nanoparticle (50-300 nm in diameter) formation in SF solution by autoclaving followed by freeze-drying and rinsing the dry sponges with low-molecular weight (400 Da) polyethylene glycol (PEG400) to induce SF β-sheet structure formation and thus stability in water. With further extraction, the SF nanoparticles embedded in the sponges were removed, leaving nanopores in the walls of round-shaped micro-size pores. The unique pore structure resulted in enhanced permeability and flexibility of ASF-PEG-S when compared to other types of SF sponges, especially with respect to commonly used methanol-annealed SF sponges. In addition, ASF-PEG-S absorbed water nearly 40 times more than its dry weight, while the methanol-annealed sponges absorbed half this amount. When human fibroblasts were seeded and cultured on ASF-PEG-S versus traditional SF methanol-processed sponges, improved cell encapsulation, distribution, and consistency in growth were observed, suggesting utility in tissue engineering and tissue repair applications in the future.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01721DOI Listing
March 2020

Tuning Microcapsule Shell Thickness and Structure with Silk Fibroin and Nanoparticles for Sustained Release.

ACS Biomater Sci Eng 2020 08 22;6(8):4583-4594. Epub 2020 Jul 22.

National Engineering Laboratory for Modern Silk, Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu 215123, P. R. China.

Microcapsules have attracted widespread interest for their unique properties in encapsulation, protection, and separation of active ingredients from the surrounding environment. However, microcapsule carriers with controllable shell thickness, permeability, good mechanical properties, and thermostability are challenging to obtain. Herein, robust and versatile composite microcapsules were fabricated using SiO nanoparticle-stabilized (Pickering) oil emulsions as core templates, while silk fibroin (SF) was assembled at the oil/water interface. This process resulted in the formation of physically and chemically stable microcapsules with a thick (∼800 nm) shell that protected the encapsulated ingredient from high shear forces and high temperatures during spray-drying. SiO nanoparticles were randomly distributed in the shell matrix after preparation, making the microcapsules mechanically robust (4.48 times higher than control samples prepared using surfactant Tween 80 instead of the SiO nanoparticles), as well as thermostable (retained shape to 900 °C). The microcapsules displayed tunable drug release by adjusting the SF content in the shell. Under optimal conditions (weight ratio of SiO/SF = 7:10, corn oil content about 55 wt %), a model drug (curcumin) was encapsulated in the SF microcapsules with an encapsulation efficiency up to 95%. The in vitro drug release from these SF microcapsules lasted longer than control microcapsules, demonstrating the capability of these novel microcapsules in sustaining drug release.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00835DOI Listing
August 2020

Generation of Nano-pores in Silk Fibroin Films Using Silk Nanoparticles for Full-Thickness Wound Healing.

Biomacromolecules 2021 02 15;22(2):546-556. Epub 2021 Jan 15.

National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China.

Silk fibroin films are used in tissue engineering due to their biocompatibility, optical clarity, and slow biodegradability. However, the relatively smooth surface and low permeability of these systems may limit some applications; thus, here, a method was developed to generate nano-pores in methanol or ethanol-treated silk fibroin films. The first step was to induce the formation of nanoparticles (50-300 nm diam.) in silk fibroin solutions by autoclaving. After drying in air, the films formed were treated to induce silk β-sheet structures, which condense the bulk silk phase and nanoparticles and phase separation and enlarge the space of bulk silk phase and nanoparticles. These films were then extracted with water to allow the condensed nanoparticles to escape, leaving homogeneous nano-pores (50-300 nm) in the silk fibroin matrix. The introduction of nano-pores resulted in enhanced permeability and minimized loss of the mechanical properties of the nano-porous silk fibroin films (NSFs) when compared to the un-autoclaving-treated silk fibroin films. NSFs promoted cell (human fibroblasts) proliferation and oxygen/nutrition perfusion and significantly enhanced the complete skin-thickness wound healing in a rat model, suggesting the potential use in tissue regeneration or as wound dressing biomaterials for clinical applications.
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http://dx.doi.org/10.1021/acs.biomac.0c01411DOI Listing
February 2021

Low-Density Silk Nanofibrous Aerogels: Fabrication and Applications in Air Filtration and Oil/Water Purification.

ACS Nano 2021 01 13;15(1):1048-1058. Epub 2021 Jan 13.

Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, United States.

A method was developed to fabricate light, water-insoluble silk fibroin nanofibrous aerogels (SNFAs) through solvent welding of lyophilized silk nanofibrous 3D networks at the junction points while converting silk structures from random-coils to β-sheets (water insoluble). Aromatic alcohols, especially phenethyl alcohol (PEA), supported robust solvent welding and the structural conversion of silk. PEA vapor treatment was a better approach than solvent infusion to retain volume, density, and mechanical strength of the SNFAs. The mechanical properties of highly orientated SNFAs were superior to randomly distributed fibers. The SNFAs had a low density (3.5 mg/cm), high hydrophobicity (140.9°), and a porous surface morphology on the individual nanofibers, resulting in high efficiency and selectivity for absorbing particulate matter and oils. Compared with commonly used inorganic aerogels, the SNFAs developed in this study are biocompatible, easily functionalized, environmentally friendly, and low-cost and therefore have potential for air and water purification, biosensors, drug delivery, and tissue engineering.
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http://dx.doi.org/10.1021/acsnano.0c07896DOI Listing
January 2021

The reporting checklist for public versions of guidelines: RIGHT-PVG.

Implement Sci 2021 Jan 11;16(1):10. Epub 2021 Jan 11.

Oregon Health & Science University, Portland, OR, USA.

Background: Public or patient versions of guidelines (PVGs) are derivative documents that "translate" recommendations and their rationale from clinical guidelines for health professionals into a more easily understandable and usable format for patients and the public. PVGs from different groups and organizations vary considerably in terms of quality of their reporting. In order to address this issue, we aimed to develop a reporting checklist for developers of PVGs and other potential users.

Methods: First, we collected a list of potential items through reviewing a sample of PVGs, existing guidance for developing and reporting PVGs or other similar evidence-based patient tools, as well as qualitative studies on original studies of patients' needs about the content and/or reporting of information in PVGs or similar evidence-based patient tools. Second, we conducted a two-round Delphi consultation to determine the level of consensus on the items to be included in the final reporting checklist. Third, we invited two external reviewers to provide comments on the checklist.

Results: We generated the initial list of 45 reporting items based on a review of a sample of 30 PVGs, four PVG guidance documents, and 46 relevant studies. After the two-round Delphi consultation, we formed a checklist of 17 items grouped under 12 topics for reporting PVGs.

Conclusion: The RIGHT-PVG reporting checklist provides an international consensus on the important criteria for reporting PVGs.
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http://dx.doi.org/10.1186/s13012-020-01066-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798200PMC
January 2021

Modulating the activity of right temporo-parietal junction by anodal tDCS enhances the agent's repayment in hold-up game.

Brain Res Bull 2021 Mar 25;168:17-24. Epub 2020 Dec 25.

School of Economics and Management, Southwest Petroleum University, Chengdu, China; Experimental Research Center for Behavioral Science and Decision-Neuroscience of School of Economics and Management, Southwest Petroleum University, Chengdu, China.

Hold-up problem is very common in non-contractible relation-specific investment transactions. And this problem can affect by trust, cooperation and altruism behavior of human beings. Recent neuroscience researches had explored a network of right temporo-parietal junction (rTPJ) involved in human cooperation and altruism behavior. The purpose of this study is to modulate the activation of rTPJ through transcranial direct current stimulation (tDCS), and to study the influence of rTPJ on investment and offer behavior in hold-up game. The results of our study showed that the anodal stimulation significantly increased participants' offer compared with the cathodal and sham stimulation. A possible explanation is that changes in rTPJ activity induced by anodal stimulation improve the accuracy of agents' mental reasoning and promote cooperation by influencing agents' offer behavior.
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http://dx.doi.org/10.1016/j.brainresbull.2020.12.013DOI Listing
March 2021

Underwater, Multifunctional Superhydrophobic Sensor for Human Motion Detection.

ACS Appl Mater Interfaces 2021 Jan 28;13(3):4740-4749. Epub 2020 Dec 28.

College of Chemical Engineering, Fuzhou University, Fuzhou 350116, P. R. China.

Superhydrophobic conductive materials have received a great amount of interest due to their wide applications in oil-water separation, electrically driven smart surface, electromagnetic shielding, and body motion detection. Herein, a highly conductive superhydrophobic cotton cloth is prepared by a facile method. A layer of polydopamine/reduced graphene oxide (PDA/rGO) was first coated on the cotton fabric, and then copper nanoparticles were in situ grown on the prepared surface. After further modification with stearic acid (STA), the wettability of the cotton surface changed from superhydrophilic to superhydrophobic (water contact angle (WCA) = 153°). The electrical conductivity of the PDA/rGO/Cu/STA cotton is as high as 6769 S·m, while the stearic acid effectively protects Cu NPs from oxidation. As a result, the superhydrophobic PDA/rGO/Cu/STA cotton has shown excellent electrical stability and can be used in detecting human motions in both ambient and underwater conditions. The sensor can recognize human motion from air into water and other underwater activities (e.g., underwater bending, stretching, and ultrasound). This multifunctional cotton device can be used as an ideal sensor for underwater intelligent devices and provides a basis for further research.
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http://dx.doi.org/10.1021/acsami.0c19704DOI Listing
January 2021

Connectome-based evidence for creative thinking as an emergent property of ordinary cognitive operations.

Neuroimage 2021 02 11;227:117632. Epub 2020 Dec 11.

Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing 400715, China; School of Psychology, Southwest University (SWU), Chongqing 400715, China; Southwest University Branch, Collaborative Innovation Center of Assessment Toward Basic Education Quality at Beijing Normal University, Chongqing 400715, China. Electronic address:

Creative thinking is a hallmark of human cognition, which enables us to generate novel and useful ideas. Nevertheless, its emergence within the macro-scale neurocognitive circuitry remains largely unknown. Using resting-state fMRI data from two large population samples (SWU: n = 931; HCP: n = 1001) and a novel "travelling pattern prediction analysis", here we identified the modularized functional connectivity patterns linked to creative thinking ability, which concurrently explained individual variability across ordinary cognitive abilities such as episodic memory, working memory and relational processing. Further interrogation of this neural pattern with graph theoretical tools revealed both hub-like brain structures and globally-efficient information transfer paths that together may facilitate higher creative thinking ability through the convergence of distinct cognitive operations. Collectively, our results provide reliable evidence for the hypothesized emergence of creative thinking from core cognitive components through neural integration, and thus allude to a significant theoretical advancement in the study of creativity.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117632DOI Listing
February 2021

Bone in the breast: A case report of a metaplastic breast cancer with osseous differentiation.

Radiol Case Rep 2021 Jan 12;16(1):136-139. Epub 2020 Nov 12.

Department of Radiology and Markey Cancer Center, University of Kentucky, 800 Rose Street, HX-302, Lexington, KY 40536, USA.

Metaplastic breast carcinoma is an uncommon malignant tumor with various pathologic subtypes. Diagnosis is often challenging due to the wide spectrum of clinical and imaging presentations. Here, we present the case of a very rare subtype of metaplastic breast carcinoma-a mixed-type metaplastic breast cancer with osseous differentiation in a 55-year-old female patient. The clinical presentation, imaging-pathology diagnosis, and treatment options are reviewed. Knowing this rarely reported but aggressive breast cancer is very important for clinicians to establish a timely diagnosis for effective management.
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http://dx.doi.org/10.1016/j.radcr.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666369PMC
January 2021

Choroidal vascular changes in age-related macular degeneration: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2020 Nov;99(46):e23200

Department of Ophthalmology, West China Hospital, Sichuan University.

Background: As an increasing age-related eye disease, age-related macular degeneration (AMD) is becoming a common cause of irreversible visual loss in elder population. The mechanism of AMD remains uncertain and covers a complex risk factors. Choroidal vascularity index (CVI) is a sensitive parameter obtained by enhanced depth imaging of optical coherence tomography which allows the choroid in more detail and accurate assessment in the pathogenesis of AMD. The objective of this current study is to evaluate choroidal structural alternations measured by CVI in AMD.

Methods: We will review 4 English databases (PubMed, Embase, Cochrane Library, and Web of Science) from their inception until present to select eligible articles. English-language and case-control studies will be accepted. The data extraction content and quantitative analysis will be performed systematically by 2 independent authors. The primary outcome is the alternation of CVI in AMD. The secondary outcomes consist of choroidal thickness (CT), luminal area (LA), stromal area (SA), and total choroidal area (TCA). Subgroup analysis, sensitivity analysis, and publication bias will be performed to check the robustness of the pooled outcome data.

Results: Changes of quantitative parameters such as CVI will be obtained in patients with AMD.

Conclusion: This study will elucidate alternations of choroidal vascular and stromal component in AMD and provide robust evidence on the pathophysiology of AMD.

Registration Number: INPLASY.
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http://dx.doi.org/10.1097/MD.0000000000023200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668498PMC
November 2020

Adsorption of proteins on oral Zn doped iron oxide nanoparticles in mouse stomach and : triggering nanoparticle aggregation.

Nanoscale 2020 Nov;12(44):22754-22767

Department of Chemistry, University of Science and Technology of China, Hefei, 230026, P. R. China.

Oral route is one of the most important portals of nanoparticle entry to the body. However, in vivo protein corona formed in the gastrointestinal tract has not been studied owing to the difficulty for the recovery of nanoparticles from the in vivo environment. In this study, by using the magnetic property of iron oxide nanoparticles (Fe3O4 NPs) and Zn2+ doped iron oxide nanoparticles (Zn0.4Fe2.6O4 NPs), the nanoparticles were separated from the gastric fluid after oral administration in mice. The effects of Zn2+ doping and static magnetic field (SMF) treatment on the protein adsorption on the nanoparticles were investigated in vitro and in vivo. Zn2+ doping decreases the adsorption of pepsin on the nanoparticles in vitro and affects the composition of the protein corona in vivo and enhances protein adsorption-induced aggregation of the nanoparticles in vitro and in vivo. SMF treatment affects the composition of the protein corona of Fe3O4 NPs and Zn0.4Fe2.6O4 NPs, and enhances the aggregation of Fe3O4 NPs and Zn0.4Fe2.6O4 NPs in vivo. Furthermore, the results demonstrate that electrostatic attraction is the crucial force to drive adsorption of proteins on Fe3O4 NPs and Zn0.4Fe2.6O4 NPs and protein adsorption-induced change in the surface charge of nanoparticles plays an important role in the pH-dependent aggregation of the nanoparticles. In addition, the work provides the evidence that the protein adsorption-induced aggregation of Fe3O4 NPs and Zn0.4Fe2.6O4 NPs has no effect on their magnetic susceptibility. The results highlight that Zn0.4Fe2.6O4 NPs may be used as a potential oral magnetic resonance imaging contrast agent in diagnosis of gastrointestinal disease.
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http://dx.doi.org/10.1039/d0nr06315kDOI Listing
November 2020

Variability in emotion regulation strategy use is negatively associated with depressive symptoms.

Cogn Emot 2021 Mar 5;35(2):324-340. Epub 2020 Nov 5.

Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing, People's Republic of China.

Variability in the emotion regulation (ER) strategies one uses throughout daily life has been suggested to reflect adaptive ER ability and to act as a protective factor in mental health. Moreover, psychological inflexibility and persistent negative affect (or ) are key features of depression and other forms of mental illness and are often further exacerbated by rigid or overly passive regulatory behaviours. The current study investigated the hypothesis that ER variability might serve as a protective factor against depressive symptoms and affective inertia. Using experience-sampling ( = 213), we tested whether two indictors of ER variability (between- and within-strategy SDs) were related to depressive symptoms and affective inertia. We found that people with higher between-strategy variability and within-strategy variability (specifically for reappraisal and distraction) reported fewer depressive symptoms. Both within- and between-strategy variability were negatively related to negative affective inertia. Between-strategy variability and negative affective inertia had unique effects on depression, when used as simultaneous predictors. Altogether, this study provides further evidence for the utility of ER as a factor buffering against depressive symptoms and particularly for the use of variable ER strategies.
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http://dx.doi.org/10.1080/02699931.2020.1840337DOI Listing
March 2021

Ghrelin promotes angiogenesis by activating the Jagged1/Notch2/VEGF pathway in preeclampsia.

J Obstet Gynaecol Res 2021 Feb 3;47(2):486-494. Epub 2020 Nov 3.

Department of Gynecology and Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.

Aim: Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has been found to be involved in the regulation of blood pressure; however, its effects in preeclampsia (PE) and the potential underlying mechanism remain poorly understood. In this study, we aimed to investigate the correlation between ghrelin and PE and reveal the possible mechanism underlying any relationship.

Methods: The levels of ghrelin and VEGF in the plasma of 6 early-onset PE (EOPE), 6 late-onset PE (LOPE) and 12 healthy pregnant (HP) women were detected using enzyme-linked immunosorbent assay (ELISA). The recombinant plasmid, pCDH-ghrelin, was designed to overexpress ghrelin in human umbilical vein endothelial cells (HUVECs). We analyzed angiogenesis in vitro and investigated the mechanism using MTT assay, colony formation assay, transwell migration assay, Matrigel-induced tube formation assay and western blotting.

Results: Ghrelin was significantly decreased in EOPE patients (P < 0.05) but elevated in LOPE patients compared to HP groups (P > 0.05). There was a significant decrease in plasma level of VEGF in EOPE and LOPE patients compared to the controls (P < 0.05). The proliferation, migration and tube formation ability of HUVECs were enhanced after transfection with pCDH-ghrelin. Ghrelin increased VEGF by activating the Jagged1/Notch2 pathway.

Conclusion: Our study uncovered that ghrelin has the potential to improve endothelial function by promoting angiogenesis through Jagged1/Notch2/VEGF pathway.
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http://dx.doi.org/10.1111/jog.14555DOI Listing
February 2021