Publications by authors named "Jun Xie"

841 Publications

One-step dynamic fabrication of asymmetric multi-layered porous films for sustained drug delivery.

Chem Commun (Camb) 2021 Jun 14. Epub 2021 Jun 14.

Department of Materials Science and Engineering, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, 315211, China. and State Key Laboratory Base of Novel Functional Materials and Preparation Science, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, China.

Asymmetric multi-layered porous films were prepared by casting inverse emulsion following the breath figure method. The porous morphologies both on the surface and in the bulk of the fabricated film could be dynamically manipulated by tuning the emulsion composition as well as the environmental conditions. The model drug was efficiently loaded into the porous film by direct encapsulation during film fabrication, and remarkable sustained drug release from the porous film for more than 28 days was achieved.
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http://dx.doi.org/10.1039/d1cc02450gDOI Listing
June 2021

Molecular simulation of nano polyhedral oligomeric silsesquioxane doping effect on the properties of two-component crosslinked epoxy resin.

J Mol Graph Model 2021 Jun 7;107:107961. Epub 2021 Jun 7.

State Key Laboratory of Power Transmission Equipment & System Security and New Technology, Chongqing University, Chongqing, China.

Epoxy resin (EP) has been extensively used in the field of insulation for its excellent electrical strength, mechanical property, chemical stability, and low cost. In this paper, computer molecular simulation is used to analyze the influence of nano-POSS (Nano-Polyhedral Oligomericsils Esquioxane) doping on the properties of epoxy composite from the micro point of view, which can provide a scientific basis for the optimization of the epoxy system. Two kinds of nano-POSS fillers with different mass fractions were doped into the base material of diglycidyl ether of bisphenol A (DGEBA) and 3,4-epoxycyclohexylmethyl 3,4-epoxycyclohexanecar (OSC). By molecular dynamics (MD) simulation the influence of nanofillers on the microstructure, thermal and mechanical properties of the composite were analyzed. Simulation results show that the doping of nano-POSS can improve the thermal and mechanical properties of the epoxy composite. Different nano-POSS has little effect on the glass transition temperature (T), coefficient of thermal expansion (CTE), and mechanical properties of the epoxy system, while the filling amount has an obvious improvement effect. Compared with EP/methyl-POSS system, the thermal and mechanical properties of the EP/phenyl-POSS system are better. At the same time, the doping of nano-POSS changed the microstructure parameters of epoxy composite. With the increase of nano-POSS filler content, fractional free volume (FFV) and mean square displacement (MSD) of both EP/POSS systems increased after the first drop. Besides, when the content of nano-POSS exceeded a certain range, the aggregation of filler itself hindered the accumulation of epoxy molecular chain segments.
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http://dx.doi.org/10.1016/j.jmgm.2021.107961DOI Listing
June 2021

Human endometrium-derived stem cell improves cardiac function after myocardial ischemic injury by enhancing angiogenesis and myocardial metabolism.

Stem Cell Res Ther 2021 Jun 10;12(1):344. Epub 2021 Jun 10.

The Laboratory of Stem Cell Regenerative Medicine Research, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Cell Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China.

Background: The human endometrium in premenopausal women is an active site of physiological angiogenesis, with regenerative cells present, suggesting that the endometrium contains adult angiogenic stem cells. In the context of cardiac repair after ischemic injury, angiogenesis is a crucial process to rescue cardiomyocytes. We therefore investigated whether human endometrium-derived stem cells (hEMSCs) can be used for cardiac repair after ischemic injury and their possible underlying mechanisms.

Methods: Comparisons were made between hEMSCs successfully isolated from 22 premenopausal women and human bone marrow mesenchymal stem cells (hBMSCs) derived from 25 age-matched patients. Cell proliferation, migration, differentiation, and angiogenesis were evaluated through in vitro experiments, while the ability of hEMSCs to restore cardiac function was examined by in vivo cell transplantation into the infarcted nude rat hearts.

Results: In vitro data showed that hEMSCs had greater proliferative and migratory capacities, whereas hBMSCs had better adipogenic differentiation ability. Human umbilical cord vein endothelial cells, treated with conditioned medium from hEMSCs, had significantly higher tube formation than that from hBMSCs or control medium, indicating greater angiogenic potentials for hEMSCs. In vivo, hEMSC transplantation preserved cardiac function, decreased infarct size, and improved tissue repair post-injury. Cardiac metabolism, assessed by F-FDG uptake, showed that F-FDG uptake at the infarction area was significantly higher in both hBMSC and hEMSC groups, compared to the PBS control group, with hEMSCs having the highest uptake, suggesting hEMSC treatment improves cardiomyocyte metabolism and survival after injury. Mechanistic assessment of the angiogenic potential for hEMSCS revealed that angiogenesis-related factors angiopoietin 2, Fms-like tyrosine kinase 1, and FGF9 were significantly upregulated in hEMSC-implanted infarcted hearts, compared to the PBS control group.

Conclusion: hEMSCs, compared to hBMSCs, have greater capacity to induce angiogenesis, and improved cardiac function after ischemic injury.
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http://dx.doi.org/10.1186/s13287-021-02423-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193887PMC
June 2021

Attention Enhancement for Exoskeleton-Assisted Hand Rehabilitation Using Fingertip Haptic Stimulation.

Front Robot AI 2021 21;8:602091. Epub 2021 May 21.

Department of Mechanical Engineering, University College London, London, United Kingdom.

Active enrollment in rehabilitation training yields better treatment outcomes. This paper introduces an exoskeleton-assisted hand rehabilitation system. It is the first attempt to combine fingertip cutaneous haptic stimulation with exoskeleton-assisted hand rehabilitation for training participation enhancement. For the first time, soft material 3D printing techniques are adopted to make soft pneumatic fingertip haptic feedback actuators to achieve cheaper and faster iterations of prototype designs with consistent quality. The fingertip haptic stimulation is synchronized with the motion of our hand exoskeleton. The contact force of the fingertips resulted from a virtual interaction with a glass of water was based on data collected from normal hand motions to grasp a glass of water. System characterization experiments were conducted and exoskeleton-assisted hand motion with and without the fingertip cutaneous haptic stimulation were compared in an experiment involving healthy human subjects. Users' attention levels were monitored in the motion control process using a Brainlink EEG-recording device and software. The results of characterization experiments show that our created haptic actuators are lightweight (6.8 ± 0.23 g each with a PLA fixture and Velcro) and their performance is consistent and stable with small hysteresis. The user study experimental results show that participants had significantly higher attention levels with additional haptic stimulations compared to when only the exoskeleton was deployed; heavier stimulated grasping weight (a 300 g glass) was associated with significantly higher attention levels of the participants compared to when lighter stimulated grasping weight (a 150 g glass) was applied. We conclude that haptic stimulations increase the involvement level of human subjects during exoskeleton-assisted hand exercises. Potentially, the proposed exoskeleton-assisted hand rehabilitation with fingertip stimulation may better attract user's attention during treatment.
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http://dx.doi.org/10.3389/frobt.2021.602091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176106PMC
May 2021

Water-soluble alkaloids isolated from Portulaca oleracea L.

Bioorg Chem 2021 Aug 26;113:105023. Epub 2021 May 26.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, China. Electronic address:

Fifteen new water-soluble alkaloids were obtained from the fresh herbs of Portulaca oleracea L. The structures of 15 alkaloids 1-15 were established according to spectroscopic data, and the stereoconfigurations were determined based on experimental and calculated electronic circular dichroism (ECD) data and single crystal X-ray diffraction. Alkaloids 1-15 were found to display good anti-inflammatory activity at 10 μM and could significantly reduce the interleukin-6 (IL-6) and nitric oxide (NO) levels induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages.
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http://dx.doi.org/10.1016/j.bioorg.2021.105023DOI Listing
August 2021

Molecular Dynamics Simulation for the Effect of Fluorinated Graphene Oxide Layer Spacing on the Thermal and Mechanical Properties of Fluorinated Epoxy Resin.

Nanomaterials (Basel) 2021 May 20;11(5). Epub 2021 May 20.

State Key Laboratory of Power Transmission Equipment & System Security and New Technology, Chongqing University, Chongqing 400044, China.

Traditional epoxy resin (EP) materials have difficulty to meet the performance requirements in the increasingly complex operating environment of the electrical and electronic industry. Therefore, it is necessary to study the design and development of new epoxy composites. At present, fluorinated epoxy resin (F-EP) is widely used, but its thermal and mechanical properties cannot meet the demand. In this paper, fluorinated epoxy resin was modified by ordered filling of fluorinated graphene oxide (FGO). The effect of FGO interlayer spacing on the thermal and mechanical properties of the composite was studied by molecular dynamics (MD) simulation. It is found that FGO with ordered filling can significantly improve the thermal and mechanical properties of F-EP, and the modification effect is better than that of FGO with disordered filling. When the interlayer spacing of FGO is about 9 Å, the elastic modulus, glass transition temperature, thermal expansion coefficient, and thermal conductivity of FGO are improved with best effect. Furthermore, we calculated the micro parameters of different systems, and analyzed the influencing mechanism of ordered filling and FGO layer spacing on the properties of F-EP. It is considered that FGO can bind the F-EP molecules on both sides of the nanosheets, reducing the movement ability of the molecular segments of the materials, so as to achieve the enhancement effect. The results can provide new ideas for the development of high-performance epoxy nanocomposites.
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http://dx.doi.org/10.3390/nano11051344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160737PMC
May 2021

Construction of Smart Nanotheranostic Platform [email protected]: Multimodal CT/PA Imaging-Guided PDT/PTT for Cancer Therapy.

ACS Omega 2021 Apr 14;6(16):10723-10734. Epub 2021 Apr 14.

School of Medicine, Xiamen University, Xiamen 361005, China.

High-efficiency nanotheranostic agents with multimodal imaging guidance have attracted considerable interest in the field of cancer therapy. Herein, novel silver-decorated bismuth-based heterostructured polyvinyl pyrrolidone nanoparticles (NPs) with good biocompatibility ([email protected] NPs) were synthesized for accurate theranostic treatment, which can integrate computed tomography (CT)/photoacoustic (PA) imaging and photodynamic therapy/photothermal therapy (PDT/PTT) into one platform. The [email protected] NPs can enhance light absorption and achieve a better photothermal effect than bismuth NPs. Moreover, after irradiation under an 808 nm laser, the [email protected] NPs can efficiently induce the generation of reactive oxygen species (ROS), thereby synergizing PDT/PTT to exert an efficient tumor ablation effect both in vitro and in vivo. Furthermore, [email protected] NPs can also be employed to perform enhanced CT/PA imaging because of their high X-ray absorption attenuation and enhanced photothermal conversion. Thus, they can be utilized as a highly effective CT/PA imaging-guided nanotheranostic agent. In addition, an excellent antibacterial effect was achieved. After irradiation under an 808 nm laser, the [email protected] NPs can destroy the integrity of , thereby inhibiting growth, which can minimize the risk of infection during cancer therapy. In conclusion, our study provides a novel nanotheranostic platform that can achieve CT/PA-guided PDT/PTT synergistic therapy and have potential antibacterial properties. Thus, this work provides an effective strategy for further broad clinical application prospects.
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http://dx.doi.org/10.1021/acsomega.1c00225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153791PMC
April 2021

The complete chloroplast genome of Maxim.

Mitochondrial DNA B Resour 2021 May 12;6(5):1614-1616. Epub 2021 May 12.

College of Forestry, Gansu Agricultural University, Lanzhou, P. R. China.

The complete chloroplast genome of Maxim. was sequenced and assembled. It is a circular form of 155949 bp in length, which was separated into four distinct regions, a large single copy (LSC) of 84375 bp, a small single copy region (SSC) of 18894 bp, two inverted repeats (IR) of 26340 bp. After annotation, a total of 115 genes were predicted, of which, 70 encode proteins, 8 rRNA, 37 tRNA. The evolutionary history, inferred using Neighbour-Joining method, indicates that was grouped within Rosaceae, and comprised a clade with G.Don, another species in Spirea, with 100% BS value.
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http://dx.doi.org/10.1080/23802359.2021.1926351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118401PMC
May 2021

sRAGE Inhibits the Mucus Hypersecretion in a Mouse Model with Neutrophilic Asthma.

Immunol Invest 2021 May 21:1-14. Epub 2021 May 21.

Pediatric Department, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P.R. China.

: Neutrophilic asthma (NA) may result in irreversible airflow limitations. Soluble advanced glycosylation receptor (sRAGE) has been shown to be associated with neutrophilic airway inflammation. However, the association between sRAGE and mucus hypersecretion in NA remains unknown. This study aims to assess the function of sRAGE on mucus hypersecretion.: A NA mouse model was established and treated with adeno-associated virus 9 (AAV9)-sRAGE and inhibitors. Collagen deposition and goblet cell hyperplasia in the lungs were evaluated by periodic acid-Schiff (PAS) and Masson staining. sRAGE and mucin levels in bronchoalveolar lavage fluid were measured by ELISA. Pathway molecule expression levels were determined by RT-qPCR and western blotting.: The results showed that the NA mouse model exhibited airway mucus hypersecretion. Mice can be effectively transfected by AAV9-sRAGE via tail-vein injection and intranasal drip. AAV9-sRAGE increased the sRAGE levels but it inhibited the collagen deposition, the PAS score, as well as the expression of MUC5AC and MUC5B. Inhibitors of high-mobility group protein 1 (HMGB1), receptor for advanced glycation end product (RAGE) and phosphatidylinositol 3-kinase (PI3K) suppressed the MUC5AC levels in NA mice as well as in cultured HMGB1-induced human bronchial epithelial cells. Furthermore, the phospho- extracellular signal-regulated kinase (ERK) protein in NA was increased while the sRAGE intervention inhibited this elevation.: These results suggest that sRAGE may be a potential target for the treatment of mucus hypersecretion in NA.
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http://dx.doi.org/10.1080/08820139.2021.1928183DOI Listing
May 2021

Nalmefene non-enantioselectively targets myeloid differentiation protein 2 and inhibits toll-like receptor 4 signaling: wet-lab techniques and simulations.

Phys Chem Chem Phys 2021 Jun;23(21):12260-12269

Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China. and Department of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China.

Nalmefene is an opiate derivative having a similar structure to naltrexone. Recent evidence suggests that nalmefene, acting as the innate immune protein toll-like receptor 4 (TLR4) antagonist, effectively reduces the injury of lung ischemia-reperfusion and prevents neuroinflammation. However, the molecular recognition mechanism, especially the enantioselectivity, of nalmefene by the innate immune receptor is not well understood. Herein in vitro assays and in silico simulations were performed to dissect the innate immune recognition of nalmefene at the atomic, molecular, and cellular levels. Biophysical binding experiments and molecular dynamic simulations provide direct evidence that (-)-nalmefene and (+)-nalmefene bind to the hydrophobic cavity of myeloid differentiation protein 2 (MD-2) and behave similarly, which is primarily driven by hydrophobic interactions. The inhibition activity and the calculated binding free energies show that no enantioselectivity was observed during the interaction of nalmefene with MD-2 as well as the inhibition of TLR4 signaling. Interestingly, nalmefene showed ∼6 times better TLR4 antagonisic activity than naltrexone, indicating that the bioisosteric replacement with the methylene group is critical for the molecular recognition of nalmefene by MD-2. In all, this study provides molecular insight into the innate immune recognition of nalmefene, which demonstrates that nalmefene is non-enantioselectively sensed by MD-2.
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http://dx.doi.org/10.1039/d1cp00237fDOI Listing
June 2021

Psychological Health Issues of Medical Staff During the COVID-19 Outbreak.

Front Psychiatry 2021 30;12:611223. Epub 2021 Apr 30.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The outbreak of novel coronavirus disease 2019 (COVID-19) has caused public panic and psychological health problems, especially in medical staff. We aimed to investigate the psychological effect of the COVID-19 outbreak on medical staff. A cross-sectional study was conducted to examine the psychological impact of medical staff working in COVID-19 designated hospitals from February to March 2020 in China. We assessed psychological health problems using the Symptom Check List 90 (SCL-90). Among 656 medical staff, 244 were frontline medical staff and 412 general medical staff. The prevalence of psychological health problems was 19.7%. The SCL-90 scores in frontline medical staff were significantly higher than that in general medical staff (mean: 141.22 vs. 129.54, < 0.05). Furthermore, gender [odds ratio (OR) = 1.53, 95% CI = (1.02, 2.30), = 0.042 for female vs. male] and the burden of current work [OR = 7.55, 95% CI = (3.75, 15.21), < 0.001 for high burden; OR = 2.76, 95% CI = (1.80, 4.24), < 0.001 for moderate burden vs. low burden] were associated with increased risk of poor psychological status. Medical staff experienced a high risk of psychological health problems during the outbreak of COVID-19, especially for frontline medical staff. Psychological health services are expected to arrange for medical staff in future unexpected infectious disease outbreaks.
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http://dx.doi.org/10.3389/fpsyt.2021.611223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119643PMC
April 2021

Phantom and clinical assessment of small pulmonary nodules using Q.Clear reconstruction on a silicon-photomultiplier-based time-of-flight PET/CT system.

Sci Rep 2021 May 14;11(1):10328. Epub 2021 May 14.

Department of Nuclear Medicine, First Hospital of Shanxi Medical University, No. 85 South Jiefang Road, Taiyuan, 030001, Shanxi, People's Republic of China.

To evaluate the quantification accuracy of different positron emission tomography-computed tomography (PET/CT) reconstruction algorithms, we measured the recovery coefficient (RC) and contrast recovery (CR) in phantom studies. The results played a guiding role in the partial-volume-effect correction (PVC) for following clinical evaluations. The PET images were reconstructed with four different methods: ordered subsets expectation maximization (OSEM), OSEM with time-of-flight (TOF), OSEM with TOF and point spread function (PSF), and Bayesian penalized likelihood (BPL, known as Q.Clear in the PET/CT of GE Healthcare). In clinical studies, SUVmax and SUVmean (the maximum and mean of the standardized uptake values, SUVs) of 75 small pulmonary nodules (sub-centimeter group: < 10 mm and medium-size group: 10-25 mm) were measured from 26 patients. Results show that Q.Clear produced higher RC and CR values, which can improve quantification accuracy compared with other methods (P < 0.05), except for the RC of 37 mm sphere (P > 0.05). The SUVs of sub-centimeter fludeoxyglucose (FDG)-avid pulmonary nodules with Q.Clear illustrated highly significant differences from those reconstructed with other algorithms (P < 0.001). After performing the PVC, highly significant differences (P < 0.001) still existed in the SUVmean measured by Q.Clear comparing with those measured by the other algorithms. Our results suggest that the Q.Clear reconstruction algorithm improved the quantification accuracy towards the true uptake, which potentially promotes the diagnostic confidence and treatment response evaluations with PET/CT imaging, especially for the sub-centimeter pulmonary nodules. For small lesions, PVC is essential.
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http://dx.doi.org/10.1038/s41598-021-89725-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121798PMC
May 2021

RACK1 modulates polyglutamine-induced neurodegeneration by promoting ERK degradation in Drosophila.

PLoS Genet 2021 May 13;17(5):e1009558. Epub 2021 May 13.

National Institute of Biological Sciences, Beijing, China.

Polyglutamine diseases are neurodegenerative diseases caused by the expansion of polyglutamine (polyQ) tracts within different proteins. Although multiple pathways have been found to modulate aggregation of the expanded polyQ proteins, the mechanisms by which polyQ tracts induced neuronal cell death remain unknown. We conducted a genome-wide genetic screen to identify genes that suppress polyQ-induced neurodegeneration when mutated. Loss of the scaffold protein RACK1 alleviated cell death associated with the expression of polyQ tracts alone, as well as in models of Machado-Joseph disease (MJD) and Huntington's disease (HD), without affecting proteostasis of polyQ proteins. A genome-wide RNAi screen for modifiers of this rack1 suppression phenotype revealed that knockdown of the E3 ubiquitin ligase, POE (Purity of essence), further suppressed polyQ-induced cell death, resulting in nearly wild-type looking eyes. Biochemical analyses demonstrated that RACK1 interacts with POE and ERK to promote ERK degradation. These results suggest that RACK1 plays a key role in polyQ pathogenesis by promoting POE-dependent degradation of ERK, and implicate RACK1/POE/ERK as potent drug targets for treatment of polyQ diseases.
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http://dx.doi.org/10.1371/journal.pgen.1009558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118270PMC
May 2021

Maternal Glycemia during pregnancy and Early Offspring Development: A Prospective Birth Cohort Study.

J Clin Endocrinol Metab 2021 May 13. Epub 2021 May 13.

Department of Maternal, Child & Adolescent Health, School of Public Health, Anhui Medical University, Hefei, China.

Context: The association of maternal gestational diabetes mellitus (GDM) with neurodevelopmental outcomes remains controversial and evidence that maternal increasing levels of glucose during pregnancy associated with the risk for impaired neurodevelopment were limited.

Objective: To identify the continuous association of increasing maternal glucose levels with neurodevelopmental disorders in offspring and explore the potential contribution of cord metabolites to this association.

Methods: The prospective birth cohort study included 1036 mother-child pairs. Primary predictors were maternal exposure GDM and maternal glucose values at a 75-g oral-glucose-tolerance test (OGTT) at 24-28 weeks during pregnancy. Primary neurodevelopmental outcomes at 12 mo in offspring were assessed by the ASQ-3.

Results: Maternal GDM was associated with failing the communication domain in offspring in the adjusted models [RR with 95% CI: 1.97(1.11, 3.52)]. Increasing levels of fasting plasma glucose (FPG), 1 h plasma glucose (1-h PG) and 2 h plasma glucose (2-h PG) with one SD change were at higher risks in failing the personal social domain of ASQ [RRs with 95% CI for FPG: 1.49(1.09, 2.04); for 1-h PG: 1.70(1.27, 2.29); for 2-h PG: 1.36(1.01, 1.84)]. The linear association was also demonstrated. Compared with girls, boys exposed to higher maternal glucose levels were inclined to the failure of the personal social domain. Mediation analysis showed the contribution of maternal GDM to failure of communication domain mediated by C-peptide.

Conclusions: Maternal glucose levels below those diagnostic of diabetes are continuously associated with impaired neurodevelopment in offspring at 12 mo.
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http://dx.doi.org/10.1210/clinem/dgab331DOI Listing
May 2021

Targeted Sequencing Analysis of Predominant Histological Subtypes in Resected Stage I Invasive Lung Adenocarcinoma.

J Cancer 2021 2;12(11):3222-3229. Epub 2021 Apr 2.

Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, China.

Lung adenocarcinoma (LADC) is classified into five main histological subtypes with distinct clinicopathologic characteristics: lepidic-predominant adenocarcinoma (LPA), acinar-predominant adenocarcinoma (APA), papillary-predominant adenocarcinoma (PPA), micropapillary-predominant adenocarcinoma (MPA) and solid-predominant adenocarcinoma (SPA). However, the mutational profiles of predominant histological subtypes have not been well defined. In this study, we aimed to reveal the genomic landscape of 5 main histological subtypes. We performed next-generation sequencing (NGS) in a cohort of 86 stage I invasive adenocarcinoma (IAC) patients, using a customized panel including 168 cancer-associated genes. Our analysis identified a total of 302 genomic alterations. Five subtypes showed different mutation profiles with LPA, APA, PPA, MPA and SPA had an average mutation rate of 1.95 (range: 0-5), 2.56 (range: 1-6), 3.5 (range: 1-7), 3.75 (range: 1-8) and 6.05 (range: 2-12), respectively (p=4.17e-06). Driver mutations occurred in 96.55% (83/86) of all patients. EGFR (73.3%), KRAS (9.3%), ALK (4.7%) and MET (4.7%) are the most commonly mutated lung cancer driver genes, TP53 is the top mutated tumor suppressor gene. SPA patients harbored more driver mutations and higher frequency of TP53 than LPA patients. Interestingly, mutations, which has been reported to be associated with high tumor mutation burden and better response to immunotherapy, were only detected from 5 SPA patients (p=0.001). No patients from other four cohorts harbored mutations. We revealed distinctive mutation landscape of the 5 major histological subtypes of LADC, evident by distinctive average mutation rate with SPA and LPA having the highest and lowest average mutation rate, respectively. SPA patients showed higher mutation rate of LRP1B and higher rates for PD-L1 positivity, indicating that SPA patients may have better response to immunotherapy.
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http://dx.doi.org/10.7150/jca.51405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100815PMC
April 2021

Soil type shapes the antibiotic resistome profiles of long-term manured soil.

Sci Total Environ 2021 Sep 27;786:147361. Epub 2021 Apr 27.

College of Resources and Environment, Southwest University, Chongqing 400716, China. Electronic address:

Animal manure fertilization facilitates the proliferation and dissemination of antibiotic resistance genes (ARGs) in soil, posing high risks to humans and ecosystem health. Although studies suggest that soil types could shape the ARG profiles in greenhouse soil, there is still a lack of comparative studies on the fate of ARGs in different types of manured soils under field trials. Thus, a metagenomic approach was used to decipher the fate of ARGs in 12-year long-term fertilized (inorganic fertilizer, compost manure and a mix of them) acidic, near-neutral and alkaline soils. A total of 408 unique ARG subtypes with multidrug, glycopeptide, beta-lactam and aminoglycoside resistance genes were identified as the most universal ARG types in all soil samples. Genes conferred to beta-lactam was the predominant ARG type in all the manure-amended soils. Genomic and statistical analyses showed that manure application caused the enrichment of 98 and 91 ARG subtypes in acidic and near-neutral soils, respectively, and 8 ARG subtypes in alkaline soil. The abundances of Proteobacteria (acidic and near-neutral soils) and Actinobacteria (alkaline soil), which are the potential hosts of ARGs, were clearly increased in manured soils. Random forest modelling and Pearson correlation analysis revealed that the soil properties (pH and bio-available Zn) and mobile genetic elements had considerable impacts on the transmission of ARGs. A structural equation model further indicated that soil types shaped the ARG profiles by significantly (P < 0.01) influencing the soil properties, bacterial abundance and bacterial diversity, where bacterial abundance was the major factor influencing the ARG profiles. This study systematically explored the mechanisms shaping the ARG profiles of long-term manured soils, and this information could support strategies to manage the dissemination of ARGs in different soil types.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147361DOI Listing
September 2021

Automatic magnetic projection for one-step separation of mixed plastics using ring magnets.

Sci Total Environ 2021 Sep 21;786:147217. Epub 2021 Apr 21.

State Key Lab of Fluid Power Transmission and Control, School of Mechanical Engineering, Zhejiang University, Hangzhou, China; Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, China; Jiangsu Jianghuai Magnetic Industry Co., Ltd., Xuyi 211700, China. Electronic address:

Magnetic projection, a novel separation method proposed recently, can separate multiple mixed materials in an efficient and low-cost way. Although promising, existing magnetic projection method cannot achieve the automatic feeding of mixed materials, which limits its applications. To address this challenge, ring magnets were used to replace conventional square magnets in this research. Specifically, a mixture of particles with different densities were fed through the hole of ring magnets and then projected to the corresponding area. Moreover, to increase the magnetic field strength, magnets were superimposed. To predict the projection process, magnetic field analysis was conducted. And from the results, an interesting trap area was found, where the separated materials may be constrained, leading to the failure of projection. The simulation of the projection process revealed that with the increase of the number of magnets (1-3 magnets), the magnetic field strength increased. However, the projection distance will not keep increasing with the increase of the magnetic field strength, which also was verified by experiments (Err within 10%). Based on this principle, an automatic feeding device with ring track and pendulum was designed and manufactured. In the separation experiment, six different plastics, that were PP, ABS, PC, PLA, PET and PVC, were used to verify the separation effect. The experimental results showed that the proposed method can automatically separate a plastic mixture with a recovery rate of over 95%. This study presents a break-through in magnetic projection, laying the foundation for the practical application of magnetic projection.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147217DOI Listing
September 2021

Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study.

BMC Musculoskelet Disord 2021 May 7;22(1):425. Epub 2021 May 7.

Shanghai University of Traditional Chinese Medicine, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, 200052, CN, China.

Background: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA).

Methods: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay.

Results: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05).

Conclusion: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA.

Trial Registration: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).
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http://dx.doi.org/10.1186/s12891-021-04307-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105956PMC
May 2021

Effect of the TEACCH program on the rehabilitation of preschool children with autistic spectrum disorder: A randomized controlled trial.

J Psychiatr Res 2021 Jun 30;138:420-427. Epub 2021 Apr 30.

School of Health Sciences, Wuhan University, Wuhan, China; Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China; Population and Health Research Center, Wuhan University, Wuhan, China. Electronic address:

Objectives: This study aimed to explore the effect of Treatment and Education of Autistic and Communication Handicapped Children (TEACCH) intervention on the rehabilitation of preschool children having autism spectrum disorder (ASD) in China.

Methods: Sixty children with ASD were randomly assigned to the intervention group (n = 30) or the control group (n = 30). The intervention group received TEACCH training plus Discrete Trial Teaching (DTT) for six months, while the control group received only DTT. The Chinese version of the Psycho-educational Profile (3rd ed.) (CPEP-3) was used to assess participants at baseline, posttest and at six-month follow-up. The results were analyzed using descriptive statistics, t test, χ or Fisher's exact test, and repeated-measures analysis of variance (ANOVA).

Results: No significant difference was found between the two groups at baseline (p > 0.05). Repeated-measures ANOVA showed that the CPEP-3 subscales had a significant time effect (p < 0.001). The two groups significantly differed in expressive language, affective expression, social reciprocity, problem behavior, and personal self-care at posttest and six-month follow-up (p < 0.05). They also significantly differed in receptive language, fine motor at posttest (p < 0.05), but not at follow-up.

Conclusions: This study demonstrated that TEACCH-based group rehabilitation training effectively improved the development of children having ASD. It provided enhanced rehabilitation strategies that assisted children with ASD to learn, function, and reach their goals.
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http://dx.doi.org/10.1016/j.jpsychires.2021.04.025DOI Listing
June 2021

Diverse immunoglobulin gene usage and convergent epitope targeting in neutralizing antibody responses to SARS-CoV-2.

Cell Rep 2021 05 24;35(6):109109. Epub 2021 Apr 24.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address:

It is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD. Neutralization by 47D1 is achieved independent of interfering RBD-ACE2 binding. A crystal structure of the mAb-RBD complex shows that the IF motif at the tip of 47D1 CDR H2 interacts with a hydrophobic pocket in the RBD. Diverse immunoglobulin gene usage and convergent epitope targeting characterize neutralizing antibody responses to SARS-CoV-2, suggesting that vaccines that effectively present the receptor binding site on the RBD will likely elicit neutralizing antibody responses in a large fraction of the population.
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http://dx.doi.org/10.1016/j.celrep.2021.109109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064889PMC
May 2021

The atypical binding mechanism of second calcium on phospholipase A2 group IIE.

Biochem Biophys Res Commun 2021 Jun 21;557:267-272. Epub 2021 Apr 21.

Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. Electronic address:

Secreted phospholipase A2s (sPLA2s) are calcium dependent enzymes involved in various biological events such as lipid metabolism and inflammation. We previously identified the second calcium (Ca2) binding site of human sPLA2 Group IIE (hGIIE) by structural study and suggested that Asn21 act as the switch of Ca2 binding to modulate the enzymatic activity, but the detailed Ca2 binding mechanism is still unclear. Combined with enzymatic assay, model analysis and calcium binding affinity data for mutated hGIIE proteins, we herein further demonstrate that the flexibly bound Ca2 is essential for the catalysis of hGIIE, unlike the stable binding of Ca2 in hGIIA that replenishes the calcium in the typical loop during the reaction. The atypical Ca2 binding feature of hGIIE will provide a better understanding on the catalytic mechanism of hGIIE.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.030DOI Listing
June 2021

Mixotrophic Chlorella pyrenoidosa as cell factory for ultrahigh-efficient removal of ammonium from catalyzer wastewater with valuable algal biomass coproduction through short-time acclimation.

Bioresour Technol 2021 Aug 20;333:125151. Epub 2021 Apr 20.

Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Chinese Academy of Fishery Sciences Pearl River Fisheries Research Institute, Guangzhou, China.

To achieve ultrahigh-efficient ammonium removal and valuable biomass coproduction, Chlorella-mediated short-time acclimation was implemented in photo-fermentation. The results demonstrated short-time acclimation of mixotrophic Chlorella pyrenoidosa could significantly improve NH removal and biomass production in shake flasks. After acclimation through two batch cultures in 5-L photo-fermenter, the maximum NH removal rate (1,400 mg L d) were achieved under high NH level (4,750 mg L) in batch 3. In 50-L photo-fermenter, through one batch acclimated culture, the maximum NH removal rate (2,212 mg L d) and biomass concentration (58.4 g L) were achieved in batch 2, with the highest productivities of protein (5.56 g L d) and total lipids (5.66 g L d). The hypothetical pathway of nutrients assimilation in mixotrophic cells as cell factory was proposed with detailed discussion. This study provided a novel strategy for high-ammonium wastewater treatment without dilution, facilitating the algae-based "waste-to-treasure" bioconversion process for green manufacturing.
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http://dx.doi.org/10.1016/j.biortech.2021.125151DOI Listing
August 2021

Visible-light-mediated cascade cyanoalkylsulfonylation/cyclization of alkynoates leading to coumarins via SO insertion.

Org Biomol Chem 2021 Apr 23;19(14):3181-3190. Epub 2021 Mar 23.

Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang 414006, China.

A visible-light-mediated tandem cyanoalkylsulfonylation/cyclization of alkynoates with cycloketone oxime compounds for the preparation of 3-cyanoalkylsulfonylcoumarins via SO insertion is reported. The difunctionalization of carbon-carbon triple bonds includes a radical mechanism and involves the formation of an iminyl radical, ring-opening of the cycloketone, insertion of SO, addition of the sulfonyl radical to carbon-carbon triple bonds, ipso-cyclization and ester migration.
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http://dx.doi.org/10.1039/d1ob00142fDOI Listing
April 2021

Long non‑coding RNA SChLAP1 regulates the proliferation of triple negative breast cancer cells via the miR‑524‑5p/HMGA2 axis.

Mol Med Rep 2021 Jun 13;23(6). Epub 2021 Apr 13.

Department of Biochemistry and Molecular Biology, Shanxi Provincial Cancer Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

Long non‑coding RNA (lncRNA) second chromosome locus associated with prostate‑1 (SChLAP1), also named LINC00913, has been reported to accelerate the carcinogenesis of prostate cancer. The aim of this study was to explore the role and mechanism of SChLAP1 in triple negative breast cancer (TNBC). The expression of SChLAP1 in TNBC tissues and cells was determined by reverse transcription quantitative PCR. The effects of SChLAP1 on the growth of TNBC cells was evaluated by detecting cell viability, colony formation and apoptosis. The present study determined that SChLAP1 was upregulated in TNBC tissues and was associated with the long‑distant lymph node metastasis of patients with TNBC. Knockdown of SChLAP1 significantly inhibited cell viability and colony formation, and triggered apoptosis of TNBC cells. Bioinformatics analysis suggested that SChLAP1 acted as a sponge of microRNA (miR)‑524‑5p and negatively modulated the expression of miR‑524‑5p. An inverse correlation was also identified between the expression levels of SChLAP1 and miR‑524‑5p in TNBC tissues. Furthermore, the results demonstrated that SChLAP1 interacted with miR‑524‑5p, and subsequently regulated the expression level of High Mobility Group AT‑Hook 2 (HMGA2) in TNBC cells. It was also found that the overexpression of HMGA2 rescued the suppressed viability of TNBC cells induced by SChLAP1 knockdown. In conclusion, the present findings demonstrated that SChLAP1 modulated the malignant tumor behaviors of TNBC cells by regulating HMGA2 and subsequently restraining miR‑524‑5p.
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http://dx.doi.org/10.3892/mmr.2021.12085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060801PMC
June 2021

PTIP Inhibits Cell Invasion in Esophageal Squamous Cell Carcinoma Modulation of EphA2 Expression.

Front Oncol 2021 23;11:629916. Epub 2021 Mar 23.

Department of Neurosurgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy and treatment failure is largely due to metastasis and invasion. Aberrant tumor cell adhesion is often associated with tumor progression and metastasis. However, the exact details of cell adhesion in ESCC progression have yet to be determined. In our study, the clinical relevance of Pax2 transactivation domain-interacting protein (PTIP/PAXIP1) was analyzed by immunohistochemistry of ESCC tissues. We found that low expression of PTIP was associated with lymph node metastasis in ESCC, and loss-of-function approaches showed that depletion of PTIP promoted ESCC cell migration and invasion both and . Analysis integrating RNA-seq and ChIP-seq data revealed that PTIP directly regulated ephrin type-A receptor 2 (EphA2) expression in ESCC cells. Moreover, PTIP inhibited EphA2 expression by competing with Fosl2, which attenuated the invasion ability of ESCC cells. These results collectively suggest that PTIP regulates ESCC invasion through modulation of EphA2 expression and hence presents a potential therapeutic target for its treatment.
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http://dx.doi.org/10.3389/fonc.2021.629916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021923PMC
March 2021

Both TGF-β1 and Smad4 regulate type I collagen expression in the muscle of grass carp, Ctenopharyngodon idella.

Fish Physiol Biochem 2021 Apr 4. Epub 2021 Apr 4.

Key Laboratory of Tropical & Subtropical Fishery Resource Application & Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China.

Type I collagen is proven to make an important contribution to fish muscle quality. Our previous study has shown the Smad4-dependent regulation of type I collagen expression in the muscle of crisp grass carp fed with faba bean. However, the regulatory roles of TGF-β1 or TGF-β1/Smad4 on type I collagen remain unclear in ordinary grass carp fed with normal diets or in other fish species. To clarify this point, the effect of TGF-β1 and Smad4 over-expression and RNAi knockdown on type I collagen (COL1-α1 and COL1-α2) expression were tested in vitro (zebrafish ZF4 cells) and in vivo (grass carp) along with the TGF-β1/Smad4 co-expression and co-knockdown. The mRNA levels of TGF-β1, Smad4, and type I collagen were upregulated in the groups with over-expressed TGF-β1 and Smad4 and downregulated in the groups of TGF-β1 and Smad4 RNAi in comparison to controls in vitro (P < 0.05). Similarly, in the in vivo experiment, the mRNA abundance of TGF-β1, Smad4, and type I collagen of over-expression group was higher than the controls at 36 h (P < 0.05). Co-injection of TGF-β1/Smad4 over-expression and RNAi vectors generally showed the higher efficacy. This study revealed that TGF-β1 and Smad4 genes regulated type I collagen expression in grass carp muscle and zebrafish. These findings will provide references for the collagen regulation of other freshwater fishes.
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http://dx.doi.org/10.1007/s10695-021-00941-wDOI Listing
April 2021

Energy Consumption and Environment Performance Analysis of Induction-Healed Asphalt Pavement by Life Cycle Assessment (LCA).

Materials (Basel) 2021 Mar 5;14(5). Epub 2021 Mar 5.

State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan 430070, China.

In this paper, the sustainability of induced healing asphalt pavement is demonstrated by comparing the impact of asphalt pavement maintained by induced healing asphalt pavement technology and traditional maintenance methods (such as milling and overlaying). The functional unit selected is a 1-km lane with an analysis period of 20 years. The stages to be considered are material manufacturing, paving, maintenance, milling and demolition. Two case studies were analyzed to assess the impact of different technologies on the energy consumption and environmental performance of each maintenance alternative. By comparing the energy consumption and environmental emissions of the whole life cycle of pavement under the two technical conditions, the results show that the total energy consumption of traditional asphalt pavement is about 2.5 times that of induction-healed asphalt pavement, and the total greenhouse gas (GHG) emissions of the former are twice as much as that of the latter.
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http://dx.doi.org/10.3390/ma14051244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961576PMC
March 2021

Towards Improving the Quality of Electrophysiological Signal Recordings by Using Microneedle Electrode Arrays.

IEEE Trans Biomed Eng 2021 Apr 2;PP. Epub 2021 Apr 2.

Electrophysiological signals are recorded generally by metal electrodes placed on body surface. For long term use, the signal quality may decay with the change of interface impedance between electrodes and skin due to the conductive hydrogel dehydration. Besides, electrodes may shift during body movements, which causes unstable signal recordings. To improve the quality of electrophysiological signal recordings on human body surface, in this work, a type of microneedle electrode array (MEA) with microneedles around 550 m in length was fabricated with a magnetization-induce self-assembly method. The experiments showed that compared with the commonly used dry electrode array, the MEA has lower and more stable interface impedance, especially when the electrode-skin interface is under unstable pressures. For electrophysiological signal recording, the MEA can acquire electromyography (EMG) with significantly lower noise energy, higher signal-to-noise ratio, and higher motion-classification accuracy based on the EMG pattern-recognition method. Additionally, high quality electrocardiography (ECG) can be recorded by using the MEA, where more accurate R-peaks are extracted in different scenarios. Besides, there was no report about any discomfort like bleeding or inflammation by all the subjects. These findings suggest that the microneedles on the MEA can penetrate through the corneum and reach the epidermis of the subjects, which could avoid the influence of corneum and fix the electrode on the body surface for high-quality signal recording especially during body movements. Furthermore, the microneedles would not touch the dermis, enabling a painless signal acquisition, which is beneficial to the applications of wearable human-machine interface technology.
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http://dx.doi.org/10.1109/TBME.2021.3070541DOI Listing
April 2021

Weighted correlation network analysis identifies FN1, COL1A1 and SERPINE1 associated with the progression and prognosis of gastric cancer.

Cancer Biomark 2021 ;31(1):59-75

Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China.

Background: Gastric cancer (GC) is one of the most deadliest tumours worldwide, and its prognosis remains poor.

Objective: This study aims to identify and validate hub genes associated with the progression and prognosis of GC by constructing a weighted correlation network.

Methods: The gene co-expression network was constructed by the WGCNA package based on GC samples and clinical data from the TCGA database. The module of interest that was highly related to clinical traits, including stage, grade and overall survival (OS), was identified. GO and KEGG pathway enrichment analyses were performed using the clusterprofiler package in R. Cytoscape software was used to identify the 10 hub genes. Differential expression and survival analyses were performed on GEPIA web resources and verified by four GEO datasets and our clinical gastric specimens. The receiver operating characteristic (ROC) curves of hub genes were plotted using the pROC package in R. The potential pathogenic mechanisms of hub genes were analysed using gene set enrichment analysis (GSEA) software.

Results: A total of ten modules were detected, and the magenta module was identified as highly related to OS, stage and grade. Enrichment analysis of magenta module indicated that ECM-receptor interaction, focal adhesion, PI3K-Akt pathway, proteoglycans in cancer were significantly enriched. The PPI network identified ten hub genes, namely COL1A1, COL1A2, FN1, POSTN, THBS2, COL11A1, SPP1, MMP13, COMP, and SERPINE1. Three hub genes (FN1, COL1A1 and SERPINE1) were finally identified to be associated with carcinogenicity and poor prognosis of GC, and all were independent risk factors for GC. The area under the curve (AUC) values of FN1, COL1A1 and SERPINE1 for the prediction of GC were 0.702, 0.917 and 0.812, respectively. GSEA showed that three hub genes share 15 common upregulated biological pathways, including hypoxia, epithelial mesenchymal transition, angiogenesis, and apoptosis.

Conclusion: We identified FN1, COL1A1 and SERPINE1 as being associated with the progression and poor prognosis of GC.
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http://dx.doi.org/10.3233/CBM-200594DOI Listing
January 2021