Publications by authors named "Xin Meng"

362 Publications

Effects of a 4-year intervention on hand hygiene compliance and incidence of healthcare associated infections: a longitudinal study.

Infection 2021 May 14. Epub 2021 May 14.

School of Public Health, Zhengzhou University, 100 Kexue Avenue, Gaoxin District, Zhengzhou, 450001, China.

Purpose: Studies have demonstrated improvements in hand hygiene (HH) compliance through interventions, noting the negative association of HH and healthcare associated infections (HAIs), but how to sustain long-term improvement is still unknown in the Chinese population. This study sought to determine the extent of change in HH compliance after multimodal HH interventions, and to evaluate the relationship between that change and HAI incidence.

Methods: We conducted a longitudinal study in a general teaching hospital in China from 2017 to 2020. Trained investigators observed HH practices based on the World Health Organization's 5 moments for HH. We identified the incidence of HAIs using semi-automated constant surveillance software. We used the Cochran-Mantel-Haenszel test to assess the secular trend of HH compliance and HAIs. The Spearman correlation coefficient (r) was used to evaluate the relationship between the incidence of HAIs and compliance with HH.

Results: The study made 480,943 observations, where HH was occurring between 2017 and 2020. HH compliance increased from 68.90 to 91.76% during that period (P < 0.01), while the incidence of HAIs decreased from 1.10 to 0.91%. Compliance also increased for each moment type and for each healthcare worker (P < 0.01). Lower HH compliance was observed in before-patient contact and after contact with patient surroundings, and among interns and cleaners. We also observed a weak but statistically significant negative correlation between the monthly HH compliance and incidence of HAIs (r =  - 0.27; P = 0.037).

Conclusions: The multimodal HH implementation delivered sustained improvement in HH compliance, and this change was associated with a decline in the incidence of HAIs.
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http://dx.doi.org/10.1007/s15010-021-01626-5DOI Listing
May 2021

Nursing-sensitive quality indicators for pernicious placenta previa in obstetrics: A Delphi study based across Chinese institutions.

Nurs Open 2021 May 7. Epub 2021 May 7.

Department of Obstetrics, Affiliated Hospital of Qingdao University, Qingdao, China.

Aim: To identify a set of scientific, systematic and clinically applicable nursing-sensitive quality indicators for pernicious placenta previa (PPP).

Design: A modified Delphi-Consensus Technique.

Methods: According to literature retrieval published between 2009-2019, 38 nursing-sensitive quality indicators were chosen and a questionnaire was designed. An online survey was conducted in 20 hospitals in China, and data of experts' opinions were collected and analysed by improved Delphi method.

Results: 38 nursing-sensitive quality indicators were identified. The response rates in the two rounds of expert consultation were 97.4% and 100%, and the authoritative coefficients were 0.89 and 0.92. The coefficients of variation ranged from 0.04-0.28. The nursing-sensitive quality indicators were successfully constructed based on the modified Delphi technique.
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http://dx.doi.org/10.1002/nop2.895DOI Listing
May 2021

Automated delineation of orbital abscess depicted on CT scan using deep learning.

Med Phys 2021 Apr 27. Epub 2021 Apr 27.

Departments of Radiology and Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Objectives: To develop and validate a deep learning algorithm to automatically detect and segment an orbital abscess depicted on computed tomography (CT).

Methods: We retrospectively collected orbital CT scans acquired on 67 pediatric subjects with a confirmed orbital abscess in the setting of infectious orbital cellulitis. A context-aware convolutional neural network (CA-CNN) was developed and trained to automatically segment orbital abscess. To reduce the requirement for a large dataset, transfer learning was used by leveraging a pre-trained model for CT-based lung segmentation. An ophthalmologist manually delineated orbital abscesses depicted on the CT images. The classical U-Net and the CA-CNN models with and without transfer learning were trained and tested on the collected dataset using the 10-fold cross-validation method. Dice coefficient, Jaccard index, and Hausdorff distance were used as performance metrics to assess the agreement between the computerized and manual segmentations.

Results: The context-aware U-Net with transfer learning achieved an average Dice coefficient and Jaccard index of 0.78±0.12 and 0.65±0.13, which were consistently higher than the classical U-Net or the context-aware U-Net without transfer learning (p < 0.01). The average differences of the abscess between the computerized results and the experts in terms of volume and Hausdorff distance were 0.10±0.11 mL and 1.94±1.21 mm, respectively. The context-aware U-Net detected all orbital abscess without false positives.

Conclusions: The deep learning solution demonstrated promising performance in detecting and segmenting orbital abscesses on CT images in strong agreement with a human observer.
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http://dx.doi.org/10.1002/mp.14907DOI Listing
April 2021

Chitosan/alginate/hyaluronic acid polyelectrolyte composite sponges crosslinked with genipin for wound dressing application.

Int J Biol Macromol 2021 Apr 10;182:512-523. Epub 2021 Apr 10.

Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin 300457, PR China; Institute of Medical Support Technology, Academy of Military Sciences, Tianjin 300161, PR China. Electronic address:

Wound dressing composed of polyelectrolyte complexes (PECs), based on chitosan/alginate/hyaluronic acid (CS/ALG/HYA) crosslinked by genipin, was prepared by freeze-dried molding. Genipin as excellent natural biological crosslinker was chose for high biocompatibility and improving mechanical properties of materials. The CS/ALG/HYA sponges (CAHSs) were characterized by FTIR, XRD, DSC and SEM. Porosity, swelling behavior and mechanical properties and in vitro degradation of CAHSs were investigated. The cytotoxicity assay was carried out on HUVEC cells in vitro and the result proves the good biocompatibility of CAHSs. Hemolysis tests indicated that the prepared CAHSs were non-hemolytic material (hemolysis ratio < 5%, no cytotoxicity). PT and aPPT coagulation tests demonstrated that CAHS2 and CAHS3 could both activate the extrinsic and intrinsic coagulation pathway and thus accelerated blood coagulation. Further, in a rat full-thickness wounds model, the CAHS2 sponge significantly facilitates wound closure compared to other groups. CAHSs exhibited adjustable physical, mechanical and biological properties. Thus, the chitosan-based polyelectrolyte composite sponges exhibit great potential as promising wound dressings.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.044DOI Listing
April 2021

Correction: Wu, H.; et al. A Purified Aspartic Protease from Plays an Important Role in Degrading Muc2. 2020, , 72.

Int J Mol Sci 2021 Mar 18;22(6). Epub 2021 Mar 18.

Vascular Biology Program, Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.

The authors wish to make the following corrections to this paper [...].
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http://dx.doi.org/10.3390/ijms22063122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048705PMC
March 2021

Transcatheter Closure of Mitral Paravalvular Leak via Multiple Approaches.

J Interv Cardiol 2021 2;2021:6630774. Epub 2021 Mar 2.

Department of Cardiovascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.

Objectives: The purpose of this study was to review the experiences with transcatheter closure of mitral PVL after surgical valve replacement.

Background: Transcatheter closure of paravalvular leak (PVL) is an intricate alternative to surgical closure. But it represents one of the most intricate procedures in the field of structural heart interventions, especially for patients with mitral PVL.

Methods: From January 2015 through January 2019, 35 patients with mitral PVL after valve replacement underwent transcatheter closure. We reviewed the catheter techniques, perioperative characteristics, and prognosis. The median follow-up was 26 (3-48) months.

Results: Acute procedural success was achieved in 33/35 (94.3%) patients. Twenty-five patients had single mitral prosthetic valve replacements; 10 had combined aortic and mitral prosthetic valve replacements previously; 28 had mechanical valves; and 7 had bioprosthetic valves. All percutaneous procedures were performed with local anesthesia except for seven transapical cases with general anesthesia. Multiple approaches were used: transfemoral, transapical, and transseptal via an arteriovenous loop. Multiple devices were deployed. There were no hospital deaths. The procedural time was 67-300 (124 ± 62) minutes. Fluoroscopic time was 17-50 (23.6 ± 12.1) minutes. The hospital stay was 5-17 (8.3 ± 3.2) days. Complications included recurrent hemolysis, residual regurgitation, acute renal insufficiency, and anemia. Twenty-seven (77.1%) patients improved by ≥1 New York Heart Association functional class at the 1-year follow-up.

Conclusions: Transcatheter mitral PVL closure requires complex catheter techniques. However, this minimally invasive treatment could provide reliable outcomes and shorter hospital stays in selected patients. This trial is registered with NCT02917980.
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http://dx.doi.org/10.1155/2021/6630774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943287PMC
March 2021

miR-101-3p sensitizes lung adenocarcinoma cells to irradiation via targeting BIRC5.

Oncol Lett 2021 Apr 10;21(4):282. Epub 2021 Feb 10.

Department of Laboratory Medicine, Anyang Maternity and Child Healthcare Hospital, Anyang, Henan 455000, P.R. China.

Lung adenocarcinoma (LUAD) has been considered as the most common cause of cancer-associated mortality. Radiotherapy resistance is one of the main reasons for LUAD treatment failure. The microRNA (miR)-101-3p has been previously reported to function as a tumor suppressor in several types of cancer, including LUAD. The present study aimed to explore the role and mechanism of miR-101-3p on radioresistance of lung adenocarcinoma cells through bioinformatics analysis and biological experiments. Based on the analysis of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data, it was demonstrated that the expression of miR-101-3p was low in LUAD tissues compared with normal lung tissues and was associated with poor prognosis of patients with LUAD. The results of the CCK-8 assay, colony formation assay, immunofluorescence staining, caspase-3 activity assay and western blotting demonstrated that miR-101-3p overexpression sensitized LUAD cells to ionizing radiation by decreasing the abilities of LUAD cell proliferation, colony formation, DNA damage repair and increasing caspase-3 activity and apoptosis of LUAD cells following ionizing radiation. Furthermore, according to bioinformatics analysis and luciferase assay, baculoviral IAP repeat containing 5 (BIRC5) was identified as a direct target of miR-101-3p. Increased BIRC5 expression reversed the miR-101-3p-mediated increase in LUAD cell radiotherapy sensitivity. Taken together, the results of the present study demonstrated that miR-101-3p may be considered as a potential target that can enhance LUAD cell sensitivity to radiotherapy, which may provide a new strategy to improve therapy in patients with LUAD.
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http://dx.doi.org/10.3892/ol.2021.12543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905603PMC
April 2021

Study on Particulate Structure Characteristics of Diesel Engines Fueled with a Methanol/Biodiesel Blend.

ACS Omega 2021 Mar 23;6(9):6081-6087. Epub 2021 Feb 23.

School of Mechanical and Electrical Engineering, Xuzhou University of Technology, Xuzhou 221008, China.

Methanol and biodiesel are both alternative fuels of diesel engines. In order to study the effects of methanol on the microstructure of particulates produced from the diesel engine fueled with a methanol/biodiesel blend, the methanol/biodiesel blend fuels with 0, 10, and 20% methanol were prepared (named B100, BM10, and BM20, respectively). SEM and TG experiments have been carried out, and the structural and oxidative characteristics of particulates for the methanol/biodiesel blend were investigated. The results showed that the average diameters of B100, BM10, and BM20 particulates were 35, 32.6, and 31.2 nm, respectively. With the increase of methanol blending ratio, the HO and SOF (soluble organic fraction) contents were increased and the soot content in particulates was reduced slightly. In addition, the activation energy of the particulate pyrolysis reaction was reduced with the increase of methanol mixing ratio, and the oxidative reaction of particulates was easier to carry out.
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http://dx.doi.org/10.1021/acsomega.0c04371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948238PMC
March 2021

Underlying metastasis mechanism and clinical application of exosomal circular RNA in tumors (Review).

Int J Oncol 2021 Mar 28;58(3):289-297. Epub 2021 Jan 28.

Department of Urology, Sheng Jing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.

Circular RNA (circRNA) is a long non‑coding RNA molecule with a closed loop structure lacking a 5'cap and 3'tail. circRNA is stable, difficult to cleave and resistant to RNA exonuclease or RNase R degradation. circRNA molecules have several clinical applications, especially in tumors. For instance, circRNA may be used for non‑invasive diagnosis, therapy and prognosis. Exosomes play a crucial role in the development of tumors. Exosomal circRNA in particular has led to increased research interest into tumorigenesis and tumor progression. Additionally, exosomal circRNA plays a role in cell‑cell communication. Exosomal circRNA facilitates tumor metastasis by altering the tumor microenvironment and the pre‑metastatic niche. Additionally, studies have revealed the mechanism by which exosomal circRNA affects malignant progression through signal transduction. Moreover, exosomal circRNA promotes tumor metastasis by regulating gene expression, RNA transcription and protein translation. In this review, the biological features and clinical application of exosomal circRNA are described, highlighting the underlying mechanisms through which they regulate tumor metastasis. The application of circRNA as clinical diagnostic biomarkers and in the development of novel therapeutic strategies is also discussed.
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http://dx.doi.org/10.3892/ijo.2021.5179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864150PMC
March 2021

Evaluating the biotoxicity of surface water in a grassy lake in North China.

J Environ Sci (China) 2021 Apr 20;102:316-325. Epub 2020 Oct 20.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of the Chinese Academy of Science, Beijing 100049, China. Electronic address:

The biological toxicity of aquatic ecosystems should be considered when assessing the effects of toxicity on the water environment. The aim of this study was to identify the main pollutants in the Baiyangdian (BYD) and the factors that contribute to biological toxicity. We determined various physical and chemical indicators in the surface water of the BYD, including nutrients and heavy metals, and the biological toxicity. We also explored the sources of the main pollutants and how the pollutants contributed to toxicity in the lake, using correlation analysis and an index of the biological toxicity. The results showed that total nitrogen (TN), ammoniacal nitrogen (NH-N), chromium (Cr), and zinc (Zn) were the main pollutants in the BYD surface water. The average concentration of Cr was 2.3 times greater than the Class V threshold, and the concentrations at about 65% of the sampling points, mainly those in the southern part of the BYD, exceeded the threshold standard. The average concentration of Zn was 1.25 times higher than the Class V threshold, with the concentrations of about 35% of the samples greater than the threshold concentration. The integrated toxicity of the surface water to luminescent bacteria ranged from 0.51% to 58%, and averaged 24.07%, which was within the range of moderate toxicity. The inhibition rates were high near Diantou (59%) and Duan (51.6%). The pollutant levels in the BYD tend to be related to the population density, with pollution mainly caused by sewage and domestic garbage, with little influence from local industries. Cr and TN were strongly correlated, but the biological toxicity was not correlated with any of the individual environmental indicators, which suggests that the toxicity in the surface water of the BYD reflected the combined effects of the environmental factors, rather than a single factor. The information from this study, about the main pollutants and the relationships between the physical and chemical properties of the surface water in the BYD, can be used to support plans for restoring the BYD.
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http://dx.doi.org/10.1016/j.jes.2020.09.028DOI Listing
April 2021

Inhibiting microRNA-155 attenuates atrial fibrillation by targeting CACNA1C.

J Mol Cell Cardiol 2021 Feb 24;155:58-65. Epub 2021 Feb 24.

Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; Medical School of University of Chinese Academy of Sciences, Beijing, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China. Electronic address:

Background: Reduction in L-type Ca current (I) density is a hallmark of the electrical remodeling in atrial fibrillation (AF). The expression of miR-155, whose predicted target gene is the α1c subunit of the calcium channel (CACNA1C), was upregulated in atrial cardiomyocytes (aCMs) from patients with paroxysmal AF.The study is to determine miR-155 could target the gene expression of I and contribute to electrical remodeling in AF.

Methods: The expression of miR-155 and CACNA1C was assessed in aCMs from patients with paroxysmal AF and healthy control. I properties were observed after miR-155 transfection in human induced pluripotent stem cell derived atrial cardiomyocytes (hiPSC-aCMs). Furthermore, an miR-155 transgene (Tg) and knock-out (KO) mouse model was generated to determine whether miR-155 was involved in I-related electrical remodeling in AF by targeting CACNA1C.

Results: The expression level of miR-155 was increased, while the expression level of CACNA1C reduced in the aCMs of patients with AF. miR-155 transfection in hiPSC-aCMs produced changes in I properties qualitatively similar to those produced by AF. miR-155/Tg mice developed a shortened action potential duration and increased vulnerability to AF, which was associated with decreased I and attenuated by an miR-155 inhibitor. Finally, the genetic inhibition of miR-155 prevented AF induction in miR-155/KO mice with no changes in I properties.

Conclusions: The increased miR-155 expression in aCMs was sufficient for the reduction in the density of I and the underlying electronic remodeling. The inhibition of miR-155 prevented I-related electric remodeling in AF and might constitute a novel anti-AF approach targeting electrical remodeling.
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http://dx.doi.org/10.1016/j.yjmcc.2021.02.008DOI Listing
February 2021

Identification of glycolysis related pathways in pancreatic adenocarcinoma and liver hepatocellular carcinoma based on TCGA and GEO datasets.

Cancer Cell Int 2021 Feb 19;21(1):128. Epub 2021 Feb 19.

Department of gynaecology, Shengjing Hospital of China Medical University, NO.36 Sanhao street, Heping district, 110000, Shenyang, Liaoning, China.

Background: Abnormal energy metabolism is one of the characteristics of tumor cells, and it is also a research hotspot in recent years. Due to the complexity of digestive system structure, the frequency of tumor is relatively high. We aim to clarify the prognostic significance of energy metabolism in digestive system tumors and the underlying mechanisms.

Methods: Gene set variance analysis (GSVA) R package was used to establish the metabolic score, and the score was used to represent the metabolic level. The relationship between the metabolism and prognosis of digestive system tumors was explored using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Volcano plots and gene ontology (GO) analyze were used to show different genes and different functions enriched between different glycolysis levels, and GSEA was used to analyze the pathway enrichment. Nomogram was constructed by R package based on gene characteristics and clinical parameters. qPCR and Western Blot were applied to analyze gene expression. All statistical analyses were conducted using SPSS, GraphPad Prism 7, and R software. All validated experiments were performed three times independently.

Results: High glycolysis metabolism score was significantly associated with poor prognosis in pancreatic adenocarcinoma (PAAD) and liver hepatocellular carcinoma (LIHC). The STAT3 (signal transducer and activator of transcription 3) and YAP1 (Yes1-associated transcriptional regulator) pathways were the most critical signaling pathways in glycolysis modulation in PAAD and LIHC, respectively. Interestingly, elevated glycolysis levels could also enhance STAT3 and YAP1 activity in PAAD and LIHC cells, respectively, forming a positive feedback loop.

Conclusions: Our results may provide new insights into the indispensable role of glycolysis metabolism in digestive system tumors and guide the direction of future metabolism-signaling target combined therapy.
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http://dx.doi.org/10.1186/s12935-021-01809-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893943PMC
February 2021

Effects of phosphorus deficiency on the absorption of mineral nutrients, photosynthetic system performance and antioxidant metabolism in Citrus grandis.

PLoS One 2021 17;16(2):e0246944. Epub 2021 Feb 17.

College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, China.

Phosphorus (P) is an essential macronutrient for plant growth, development and production. However, little is known about the effects of P deficiency on nutrient absorption, photosynthetic apparatus performance and antioxidant metabolism in citrus. Seedlings of 'sour pummelo' (Citrus grandis) were irrigated with a nutrient solution containing 0.2 mM (Control) or 0 mM (P deficiency) KH2PO4 until saturated every other day for 16 weeks. P deficiency significantly decreased the dry weight (DW) of leaves and stems, and increased the root/shoot ratio in C. grandis but did not affect the DW of roots. The decreased DW of leaves and stems might be induced by the decreased chlorophyll (Chl) contents and CO2 assimilation in P deficient seedlings. P deficiency heterogeneously affected the nutrient contents of leaves, stems and roots. The analysis of Chl a fluorescence transients showed that P deficiency impaired electron transport from the donor side of photosystem II (PSII) to the end acceptor side of PSI, which showed a greater impact on the performance of the donor side of PSII than that of the acceptor side of PSII and photosystem I (PSI). P deficiency increased the contents of ascorbate (ASC), H2O2 and malondialdehyde (MDA) as well as the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) in leaves. In contrast, P deficiency increased the ASC content, reduced the glutathione (GSH) content and the activities of SOD, CAT, APX and monodehydroascorbate reductase (MDHAR), but did not increase H2O2 production, anthocyanins and MDA content in roots. Taking these results together, we conclude that P deficiency affects nutrient absorption and lowers photosynthetic performance, leading to ROS production, which might be a crucial cause of the inhibited growth of C. grandis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246944PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888624PMC
February 2021

Cryo-EM structural analysis of FADD:Caspase-8 complexes defines the catalytic dimer architecture for co-ordinated control of cell fate.

Nat Commun 2021 02 5;12(1):819. Epub 2021 Feb 5.

MRC Toxicology Unit, University of Cambridge, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, UK.

Regulated cell death is essential in development and cellular homeostasis. Multi-protein platforms, including the Death-Inducing Signaling Complex (DISC), co-ordinate cell fate via a core FADD:Caspase-8 complex and its regulatory partners, such as the cell death inhibitor c-FLIP. Here, using electron microscopy, we visualize full-length procaspase-8 in complex with FADD. Our structural analysis now reveals how the FADD-nucleated tandem death effector domain (tDED) helical filament is required to orientate the procaspase-8 catalytic domains, enabling their activation via anti-parallel dimerization. Strikingly, recruitment of c-FLIP into this complex inhibits Caspase-8 activity by altering tDED triple helix architecture, resulting in steric hindrance of the canonical tDED Type I binding site. This prevents both Caspase-8 catalytic domain assembly and tDED helical filament elongation. Our findings reveal how the plasticity, composition and architecture of the core FADD:Caspase-8 complex critically defines life/death decisions not only via the DISC, but across multiple key signaling platforms including TNF complex II, the ripoptosome, and RIPK1/RIPK3 necrosome.
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http://dx.doi.org/10.1038/s41467-020-20806-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864959PMC
February 2021

Glycyrrhizin micelle as a genistein nanocarrier: Synergistically promoting corneal epithelial wound healing through blockage of the HMGB1 signaling pathway in diabetic mice.

Exp Eye Res 2021 Mar 23;204:108454. Epub 2021 Jan 23.

Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China; Key Laboratory of Pharmaceutical Research for Metabolic Diseases, Qingdao University of Science and Technology, Qingdao, China. Electronic address:

The purpose of this study was to explore the feasibility of targeting the HMGB1 signaling pathway to treat diabetic keratopathy with a dipotassium glycyrrhizinate-based micelle ophthalmic solution encapsulating genistein (DG-Gen), and to evaluate whether these dipotassium glycyrrhizinate (DG) micelles could synergistically enhance the therapeutic effect of encapsulated genistein (Gen). An optimized DG-Gen ophthalmic solution was fabricated with a Gen/DG weight of ratio 1:15, and this formulation featured an encapsulation efficiency of 98.96 ± 0.82%, and an average particle size of 29.50 ± 2.05 nm. The DG-Gen ophthalmic solution was observed to have good in vivo ocular tolerance and excellent in vivo corneal permeation, and to remarkably improve in vitro antioxidant activity. Ocular topical application of the DG-Gen ophthalmic solution significantly prompted corneal re-epithelialization and nerve regeneration in diabetic mice, and this efficacy might be due to the inhibition of HMGB1 signaling through down-regulation of HMGB1 and its receptors RAGE and TLR4, as well as inflammatory factor interleukin (IL)-6 and IL-1β. In conclusion, these data showed that HMGB1 signaling is a potential regulation target for the treatment of diabetic keratopathy, and novel DG-micelle formulation encapsulating active agents such as Gen could synergistically cause blockage of HMGB1 signaling to prompt diabetic corneal and nerve wound healing.
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http://dx.doi.org/10.1016/j.exer.2021.108454DOI Listing
March 2021

Structural characterization and effect on leukopenia of fucoidan from Durvillaea antarctica.

Carbohydr Polym 2021 Mar 17;256:117529. Epub 2020 Dec 17.

Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China; Marine Biomedical Research Institute of Qingdao, Qingdao, 266071, China. Electronic address:

Fucoidans from brown seaweed shows various bioactive properties and promising prospects in biomedical field. Here, a novel fucoidan (F-4) was extracted and purified from Durvillaea antarctica. The structure of F-4 was characterized by HPLC, HPGPC, GC-MS, together with IR and NMR spectral analysis. F-4 is a sulfated polysaccharide mainly composed of fucose (Fuc), galactose (Gal), and glucose (Glc) in a molar ratio of 26.4: 7.1: 1.0. The backbone of F-4 is composed of (1→3) and (1→4)-linked-α-L-Fucp residues, which sulfated at C-4 or C-2 positions and branched with α-L-Fuc, β-D-Gal, and β-D-Glc residues. Furthermore, F-4 can effectively promote the growth of leukocyte in a mouse model induced by cyclophosphamide, possibly by activating hematopoietic progenitor cells and regulating the hematopoietic microenvironment of bone marrow. Our data provide useful information for further investigation of fucoidan in the treatment of chemotherapy-induced leukopenia.
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http://dx.doi.org/10.1016/j.carbpol.2020.117529DOI Listing
March 2021

Follow-up of a Rickettsia felis encephalitis: Some new insights into clinical and imaging features.

Int J Infect Dis 2021 Mar 11;104:300-302. Epub 2021 Jan 11.

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, China. Electronic address:

Rickettsia felis (R. felis) infection is a cause of unspecified encephalitis. However, the incidence has been underestimated due to the intracellular features of the pathogen and insufficient understanding of its clinical picture. This study reported a case of R. felis infection in a 26-year-old female who only manifested with certain neurological symptoms. With a lack of specific systemic inflammatory symptoms, the diagnosis was initially misdiagnosed as a brain glioma. However, a brain tissue biopsy showed prominent perivascular inflammatory infiltrations, which indicated inflammatory disease. Spinal fluid metagenomic next-generation sequencing (mNGS) was taken after ruling out other common infectious and autoimmune diseases. The results suggested R. felis infection, which was also supported by Weil-Felix reaction in the serum. After the diagnosis was corrected as R. felis encephalitis, the patient was successfully treated with doxycycline and had a good prognosis at the 1-year follow-up.
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http://dx.doi.org/10.1016/j.ijid.2020.12.090DOI Listing
March 2021

Design, synthesis and biological evaluation of novel thiohydantoin derivatives as potent androgen receptor antagonists for the treatment of prostate cancer.

Bioorg Med Chem 2021 Feb 16;31:115953. Epub 2020 Dec 16.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China; School of Pharmacy, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, PR China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, PR China. Electronic address:

Prostate cancer (PC) is the most common malignancy in men worldwide. Here, two series of novel thiohydantoin derivatives of enzalutamide as potent androgen receptor (AR) antagonists were designed and synthesized. Among them, compound 31c was identified as an AR antagonist which is 2.3-fold more potent than enzalutamide. Molecular docking studies were performed to explain the improved potency of 31c at AR. In cell proliferation assays, 31c exhibited similar anti-proliferative activities with enzalutamide against hormone sensitive LNCaP cells and AR-overexpressing LNCaP/AR cells. These data indicate that 31c can be a good lead compound for further structure optimization for the treatment of prostate cancer.
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http://dx.doi.org/10.1016/j.bmc.2020.115953DOI Listing
February 2021

Synthesis and immunogenicity of Brucella monovalent neoglycoconjugate.

Carbohydr Res 2021 Jan 20;499:108196. Epub 2020 Nov 20.

Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin, 300457, PR China. Electronic address:

Brucellosis is a highly infectious zoonotic disease caused by Brucella. It is necessary to control and eliminate brucellosis. The cell wall O-polysaccharides of pathogenic Brucella species are homopolymers of the rare sugar 4,6-dideoxy-4-formamido-α-d-mannopyranose. Herein, one neoglycoconjugate was successfully synthesized based on disaccharide [Rha4NFo(1 → 2)Rha4NFo] as epitope. Disaccharide specific antibodies were detected by ELISA and the immune protective effect was further evaluated with PBS as control. The result showed that the synthetic neoglycoconjugate can produce moderate immune responses in mice and significantly decreased splenic Brucella M5 burden comparing with control group. The chemically defined antigen identified the A antigenic determinant and provided a structural basis for understanding the fine specificity of polyclonal antibodies that bind the A antigen. The neoglycoconjugate shows the potential in detection reagent or vaccine development for brucellosis.
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http://dx.doi.org/10.1016/j.carres.2020.108196DOI Listing
January 2021

Long-term exposure to PM2.5 and Children's lung function: a dose-based association analysis.

J Thorac Dis 2020 Oct;12(10):6379-6395

Beijing Innovation Center for Engineering Science and Advanced Technology, State Key Joint Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, And Center for Environment and Health, Peking University, Beijing, China.

Background: The current literature is still not consist regarding the effect of long-term exposure to PM2.5 and children's lung function, partly due to inadequate or inaccurate exposure assessment. In this study, we aim to investigate the associations between long-term exposure to PM2.5, estimated as average daily dose (ADD), and lung function in school-age children.

Methods: We recruited 684 participants of 7-12 years old from the city of Lanzhou located in northwestern China. Participants underwent spirometric tests for lung function and responded to a questionnaire survey. Detailed information about individual air exposure and personal information were collected, including length of school hours, home address, age, gender, etc. Combining the spatial distribution of PM2.5 concentrations in the past 5 years and individual time-activity data, we estimated annual ADD for 5 years preceding the lung function tests and 5-year average ADD, respectively. We used multiple linear regression models to examine the associations between ADD values and lung function, controlling for a range of individual-level covariates.

Results: The 5-year average ADD among all the participants was 50.5 µg/kg-d, with higher values estimated for children living in the urban area than the suburban area, for boys than girls, and for children whose parents received a lower education attainment. We found that a 1 μg/kg-d increment in ADD of PM2.5 was associated with a 10.49 mL (95% CI: -20.47, -0.50) decrease in forced vital capacity (FVC) and a 7.68 mL (95% CI: -15.80, -0.44) decrease in forced exploratory volume in 1 second (FEV). Among the annual ADDs estimated for the preceding 5 years, the immediate past year prior to lung function measurement had the greatest effect on lung function. The effect was greater in girls than in boys. We found no associations between annual exposure of PM2.5 (instead of ADD) and lung function when defined concentration was used as an exposure variable.

Conclusions: Long-term PM2.5 exposure, when estimated as exposure dose averaged over a year or longer, was associated with statistically significant reductions in FVC and FEV1 in children of elementary-school age. Future studies may consider the use of individual-level dose estimates (as opposed to exposure concentrations) to improve the dose-response assessment.
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http://dx.doi.org/10.21037/jtd-19-crh-aq-007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656332PMC
October 2020

Changes in children's asthma prevalence over two decades in Lanzhou: effects of socioeconomic, parental and household factors.

J Thorac Dis 2020 Oct;12(10):6365-6378

Beijing Innovation Center for Engineering Science and Advanced Technology, State Key Joint Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, And Center for Environment and Health, Peking University, Beijing, China.

Background: The prevalence of childhood asthma may have changed with rapid economic development. This study aims to ascertain potential changes in asthma prevalence in relation to changes in socioeconomic, parental and household factors, based on a comparison between two periods spanning over 20 years in Lanzhou, a large northwestern city of China.

Methods: Cross-sectional studies using the same protocols were performed in Lanzhou, China in 1994-1995 (Period I) and in 2017 (Period II). Children of 6-12 years old from elementary schools were selected by a multistage sampling method. Information on the presence of asthma and asthma-related symptoms of children, socioeconomic status, feeding methods, parental illness and behavior patterns, as well as household characteristics, were collected through a questionnaire survey. Logistic regression models were used to estimate odds ratios of asthma prevalence with regard to socioeconomic, parental and household factors, respectively.

Results: Significant prevalence reductions were observed for paternal smoking, household coal use, and parental asthma, while the prevalence increased significantly for children sleeping in their own rooms or own beds, ventilation use during cooking, and parental occupation and education level after 22 years. In children, the prevalence of ever-diagnosed asthma decreased from 3.2% in period I to 1.5% in Period II (P<0.001); the prevalence of wheeze also decreased from 15.4% to 9.3% (P<0.001). Passive smoking (OR =1.531, 95% CI: 1.032-2.270) and poor household ventilation (OR =1.709, 95% CI: 1.208-2.416) were significantly associated with an increased prevalence of wheeze in Period I, whereas household mold (OR =2.112, 95% CI: 1.203-3.811) was significantly associated with prevalence of wheeze. Parental asthma history was associated with increased prevalence of asthma and asthma-related symptoms. Breastfeeding was significantly associated with reduced risk of asthma in period II children.

Conclusions: The prevalence of asthma and that of asthma-related symptoms were lower in 2017 than in 1994-1995 in school children living in Lanzhou. In 2017 with increased urbanization and industrialization, breastfeeding became a significant protective factor and household mold was a significant risk factor for asthma diagnosis and asthma-related symptoms. Promoting breastfeeding and household mold control is recommended to reduce the risk of childhood asthma in contemporary Lanzhou.
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http://dx.doi.org/10.21037/jtd-19-crh-aq-008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656413PMC
October 2020

miR319c acts as a positive regulator of tomato against Botrytis cinerea infection by targeting TCP29.

Plant Sci 2020 Nov 4;300:110610. Epub 2020 Aug 4.

Key Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang Province, College of Life Sciences and medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China. Electronic address:

miR319 family is one of the oldest and most conservative miRNA families in plant and plays an important role in plant development and abiotic stress response. In our previous study, the abundance of sly-miR319c was increased in tomatoes infected by B. cinerea, but the roles and regulatory mechanisms of sly-miR319c in B. cinerea-infected tomato remain unclear. In this study, we confirmed that miR319c was increased in tomato with B. cinerea infection. In contrast, A TCP transcript factor, TCP29, targeted by sly-miR319c was decreased in B. cinerea-infected tomato. Therefore, transgenic Arabidopsis overexpressing sly-miR319c or its target were generated for understanding the biological roles and molecular mechanism of miR319c in B.cinerea-infected plants. Results showed that miR319c overexpression improved the resistance of transgenic plants to B. cinerea, whereas TCP29 overexpression increased the susceptibility of transgenic plant to B. cinerea. So far, TCP transcription factors have been reported mainly in developmental processes. Our data indicate that TCP29 act as a negative regulator to B.cinerea infection. In conclusion, our results indicate that sly-miR319c is a positive regulator of tomato resistance to B. cinerea infection by targeting TCP29.
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http://dx.doi.org/10.1016/j.plantsci.2020.110610DOI Listing
November 2020

The lncRNA MEG3/miR-16-5p/VGLL4 regulatory axis is involved in etoposide-induced senescence of tumor cells.

J Gene Med 2021 Feb 22;23(2):e3291. Epub 2020 Dec 22.

Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.

Background: The senescence of tumor cells is an important tumor suppressor mechanism. The present study aimed to investigate the role of long non-coding RNA (lncRNA) MEG3 (maternally expressed gene 3) in the senescence process of tumor cells and its potential molecular mechanism by competitively binding with microRNA miR-16-5p to regulate the expression of VGLL4 (encoding vestigial like family member 4).

Methods: We used etoposide to construct senescence models of tumor cells. The degree of cellular senescence was detected by senescence-associated β-galactosidase, cell cycle and senescence-associated secretory phenotype. The expression of lncRNA MEG3, miR-16-5p and VGLL4 in senescent or non-senescent cells was evaluated using a quantitative real-time reverse transcriptase-PCR (qRT-PCR) or western blotting. Dual luciferase reporter assays were used to detect the binding of miR-16-5p to lncRNA MEG3 and VGLL4. The mRNA and protein expression levels of senescence-related markers (p53, p21 and p16) were detected using qRT-PCR or western blotting.

Results: Compared to the control group, the expression of lncRNA MEG3 and VGLL4 was significantly up-regulated in senescent cells. Knockdown of lncRNA MEG3 and VGLL4 reduced the degree of senescence and the expression of p21 and p16. lncRNA MEG3 interfered with the expression of miR-16-5p in senescent A549 and MCF-7 cells. The expression of VGLL4 was regulated by miR-16-5p in senescent A549 and MCF-7 cells. lncRNA MEG3 participated in the senescent progress of tumor cells induced by etoposide via the miR-16-5p/VGLL4 axis.

Conclusions: The present study has confirmed the regulatory role of the lncRNA MEG3/miR-16-5p/VGLL4 axis in the low-dose etoposide-induced tumor cell senescence model, which has potential clinical application with respect to treating malignant tumors.
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http://dx.doi.org/10.1002/jgm.3291DOI Listing
February 2021

MLAA-34 knockdown shows enhanced antitumor activity via JAK2/STAT3 signaling pathway in acute monocytic leukemia.

J Cancer 2020 30;11(23):6768-6781. Epub 2020 Sep 30.

Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Department of Hematology, 157 Xiwu Road, Xi'an, Shaanxi, China.

MLAA-34 is a novel leukemia-associated gene closely related to the carcinogenesis of acute monocytic leukemia (AML). MLAA-34 over expression has been observed to inhibit apoptosis . JAK2/STAT3 pathway plays an important role in cell proliferation, differentiation and inhibition of apoptosis in number of cancers. However, the relationship and interaction between MLAA-34 and JAK2/STAT3 has never been investigated in AML. This study investigates and reports a novel relationship between MLAA-34 and JAK2/STAT3 pathway in AML both and . We constructed MLAA-34 knockdown vector and transfected U937 cells to observe its apoptotic activities in relation to JAK2/STAT3 signaling pathway and then in mouse model. Levels of expression of MLAA-34 and JAK2/STAT3 and its downstream targets were also measured in AML patients and a few volunteers. We found that MLAA-34 knockdown increased U937 apoptosis and inhibited tumor growth . Components of the canonical JAK2/STAT3 pathway or its downstream targets, including c-myc, bcl-2, Bax, and caspase-3, were shown to be involved in the carcinogenesis of AML. We also found that the JAK2/STAT3 pathway positively regulated MLAA-34 expression. We additionally identified a STAT3 binding site in the MLAA-34 promoter where STAT3 binds directly and activates MLAA-34 expression. In addition, MLAA-34 was found to form a complex with JAK2 and was enhanced by JAK2 activation. Correlation of MLAA-34 and JAK2/STAT3 was further confirmed in AML patients. In conclusion, MLAA-34 is a novel regulator for JAK2/STAT3 signaling, and in turn, is regulated by this interaction in a positive feedback loop. Thus we report a novel model of interaction mechanism between MLAA-34 and JAK2/STAT3 which can be utilized as a potential target for a novel therapeutic approach in AML.
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http://dx.doi.org/10.7150/jca.46670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592008PMC
September 2020

A bibliometric analysis of publication of funded studies in nursing research from Web of Science, 2008-2018.

J Adv Nurs 2021 Jan 29;77(1):176-188. Epub 2020 Oct 29.

School of Nursing, Shanxi Medical University, Taiyuan, Shanxi Province, China.

Aim: To analyse the current status and publication trends of funded studies in nursing-related research from 2008 to 2018, available in the Web of Science.

Design: A longitudinal bibliometric analysis of publications of funded studies in nursing-related research, obtained from the Web of Science, was conducted.

Methods: On 10 May 2019, we accessed 77,772 funded studies (2008-2018) from the Web of Science. Bibliometric methods and indicators were used to classify the publications and summarize the overall number, countries/regions, institutions, journals, and other parameters of the publications.

Results: The global output of nursing-related funded research publications increased significantly over time. The three leading countries with the highest number of funded publications were the United States, Australia, and the United Kingdom, with the United States accounting for 15 of the top 20 institutions associated with funded publications, which mostly included institutions of higher education. The most common disciplines of these publications were oncology, psychiatry, and paediatrics. The top three journals that published the largest number of nursing-related funded publications were the Journal of Clinical Nursing, the Journal of Advanced Nursing, and the International Journal of Nursing Studies. Keywords with the highest frequency of occurrence included "nurses," "qualitative research," "older people," "quality of life," "depression," "cancer," and "children."

Conclusions: Nursing-related research has been drawing increasing attention over the years. Analysing the output of funded publications and monitoring the new dynamics of the international development of academic research in the field of nursing are crucial for determining future directions of nursing-related research development.

Impact: The results of this study will provide a reference for scholars to evaluate the current utilization efficiency of global nursing-related research funding and demonstrate the development and trends in nursing-related research.
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http://dx.doi.org/10.1111/jan.14578DOI Listing
January 2021

Inactivation of Pancreatic Stellate Cells by Exendin-4 Inhibits the Migration and Invasion of Pancreatic Cancer Cells.

Onco Targets Ther 2020 24;13:9455-9463. Epub 2020 Sep 24.

Department of Hospital Infection Management, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, People's Republic of China.

Background: Pancreatic stellate cells (PSCs) are precursor cells of cancer-associated fibroblasts that promote tumor proliferation, invasion, and metastasis. The glucagon-like peptide-1 receptor agonist exendin-4 has been reported to exhibit anticancer effects against several tumor cells; however, the function and mechanism underlying the effects of exendin-4 on pancreatic cancer cells remain unclear.

Methods: Gene expression levels were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assay. Cell viability, migration and invasion were assessed using the cell counting kit-8 (CCK-8), wound healing, and transwell assays, respectively. A xenografted tumor model was established in mouse to evaluate the effects of exendin-4 in vivo.

Results: Exendin-4 treatment led to the inactivation of PSCs and suppressed their proliferation and migration. Moreover, we also found that exendin-4 attenuated NF-κB-dependent SDF-1 secretion. Furthermore, pancreatic cancer cells incubated with conditioned medium obtained from exendin-4-treated PSCs showed a decreased ability to proliferate, migrate, and invade as compared to the control cells, which is similar to the effects induced by the CXCR4 inhibitor, AMD3100. Consistent with in vitro results, we also confirmed that exendin-4 indirectly targeted pancreatic cancer cells in vivo by attenuating the function of PSCs and suppressing the deposition of extracellular matrix.

Conclusion: These results revealed that exendin-4-treated PSCs could suppress pancreatic cancer cell proliferation and invasion, offering a potential strategy for the treatment of pancreatic cancer.
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http://dx.doi.org/10.2147/OTT.S259853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522302PMC
September 2020

Probing the Potential Energy Surfaces of BrCN by Dissociative Electron Attachment.

J Phys Chem Lett 2020 Nov 13;11(21):9110-9116. Epub 2020 Oct 13.

Hefei National Laboratory for Physical Sciences at the Microscale, Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, China.

State coupling certainly determines the topologic features of the molecular potential energy surface (PES) and potentially diversifies chemical reaction pathways. Here we report the new PESs of BrCN in the low-lying electronic states that are distinctly different from the previous predictions in the short Br-CN bond region but validated by the high-resolution ion velocity imaging measurements of low-energy dissociative electron attachment (DEA) to BrCN. Besides the vibrating CN ions produced in the fast Br-CN bond stretching motions, we confirm that the ro-vibrating CN ions with a nearly isotropic angular distribution are produced by receiving a torque in the combinational motion of Br-CN bond bending and stretching. The latter process is closely related to the potential well of BrCN at the first excited state Π that arises from the Π-Σ state couplings. Our findings not only suggest that the PESs of other anionic cyanogen halides are in dire need of reexamination but also show that ion velocity imaging of the DEA process is a powerful experimental method for evaluating the theoretical PESs of molecular anions.
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http://dx.doi.org/10.1021/acs.jpclett.0c02991DOI Listing
November 2020

Organocatalytic Enantioselective Conjugate Alkynylation of β-Aminoenones: Access to Chiral β-Alkynyl-β-Amino Carbonyl Derivatives.

Org Lett 2020 10 23;22(19):7427-7432. Epub 2020 Sep 23.

Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P.R. China.

Readily available potassium alkynyltrifluoroborates were used for organocatalytic asymmetric conjugate alkynylation of β-enaminones. The interception of a modified binaphthol catalyst and in situ generated organodifluoroboranes proved important to access functionalized β-alkynyl-β-amino carbonyls and derivatives with improved chemo-reactivity and enantio-induction. Mechanistic studies revealed the impact of molecular sieves on efficiency and stereocontrol. The products undergo additional functionalization to yield a diverse set of valuable β-alkynyl-β-amino carbonyl scaffolds.
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http://dx.doi.org/10.1021/acs.orglett.0c02394DOI Listing
October 2020

Lack of FGF21 promotes NASH-HCC transition hepatocyte-TLR4-IL-17A signaling.

Theranostics 2020 7;10(22):9923-9936. Epub 2020 Aug 7.

Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USA.

Hepatocellular carcinoma (HCC) has been increasingly recognized in nonalcoholic steatohepatitis (NASH) patients. Fibroblast growth factor 21 (FGF21) is reported to prevent NASH and delay HCC development. In this study, the effects of FGF21 on NASH progression and NASH-HCC transition and the potential mechanism(s) were investigated. NASH models and NASH-HCC models were established in FGF21Knockout (KO) mice to evaluate NASH-HCC transition. IL-17A signaling was investigated in the isolated hepatic parenchymal cells, splenocytes, and hepatocyte and HCC cell lines. Lack of FGF21 caused significant up-regulation of the hepatocyte-derived IL-17A via Toll-like receptor 4 (TLR4) and NF-κB signaling. Restoration of FGF21 alleviated the high NAFLD activity score (NAS) and attenuated the TLR4-triggered hepatocyte-IL-17A expression. The HCC nodule number and tumor size were significantly alleviated by treatments of anti-IL-17A antibody. This study revealed a novel anti-inflammatory mechanism of FGF21 via inhibiting the hepatocyte-TLR4-IL-17A signaling in NASH-HCC models. The negative feedback loop on the hepatocyte-TLR4-IL-17A axis could be a potential anti-carcinogenetic mechanism for FGF21 to prevent NASH-HCC transition.
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http://dx.doi.org/10.7150/thno.45988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481424PMC
August 2020

Efficient chemoenzymatic synthesis of fluorinated sialyl Thomsen-Friedenreich antigens and investigation of their characteristics.

Eur J Med Chem 2020 Dec 29;208:112776. Epub 2020 Aug 29.

China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, China. Electronic address:

A set of fluorinated sialyl-T derivatives were efficiently synthesized using one-pot multi-enzyme (OPME) chemoenzymatic approach. The P. multocida α2-3-sialyltransferase (PmST1) involved in the synthesis showed extremely flexible donor and acceptor substrate specificities. These sialosides have been successfully investigated with stability towards Clostridium perfringens sialidase substrate specificity assay using H NMR spectroscopy. Hydrolysis studies monitored by H NMR clearly demonstrated that the fluorine substitution obviously reduced hydrolysis rate of Clostridium perfringens sialidase. To further investigate the fluorine influence, structure-dependent variation of sialoside-lectin binding was observed for MAL and different sialoside-immobilized surfaces. Subtle changes on the ligand of carbohydrate-binding protein were distinguished by SPR. These fluorinated sialyl-T derivatives obtained are valuable probes for further biological studies or antitumor drug design.
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http://dx.doi.org/10.1016/j.ejmech.2020.112776DOI Listing
December 2020