Publications by authors named "Yijun Zhang"

137 Publications

Neoadjuvant programmed death-1 blockade plus chemotherapy in locally advanced esophageal squamous cell carcinoma.

Ann Transl Med 2021 Aug;9(15):1254

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

Background: Immunotherapy is effective in treating unresectable esophageal squamous cell carcinoma (ESCC), but little is known about its role in the preoperative setting. The aim of this study was to evaluate the safety, feasibility and efficacy of neoadjuvant treatment with camrelizumab plus chemotherapy in locally advanced ESCC.

Methods: Patients diagnosed with locally advanced ESCC were retrospectively included if they had received neoadjuvant camrelizumab plus nab-paclitaxel and S1 capsule followed by radical esophagectomy between November, 2019 and June, 2020 at Sun Yat-sen University Cancer Center. Primary endpoints were safety and feasibility. In addition, pathological response and the relationship between tumor immune microenvironment (TIME)/tumor mutational burden (TMB) and treatment response were also investigated.

Results: Twelve patients were included and they all received three courses of preoperative treatment with camrelizumab plus nab-paclitaxel/S1. No grade 3 or higher toxicities occurred. No surgical delay or perioperative death was reported. Nine patients (75%) responded to the treatment, four with a complete pathological response (pCR) and five with a major pathological response (MPR). Neither programmed death-ligand 1 (PD-L1) expression nor TMB was correlated with treatment response. TIME analysis revealed that a higher abundance of CD56dim natural killer cells was associated with better pathological response in the primary tumor, while lower density of M2-tumor-associated macrophages was associated with better pathological response in the lymph nodes (LNs).

Conclusions: Neoadjuvant camrelizumab plus nab-paclitaxel and S1 is safe, feasible and effective in locally advanced ESCC and is worth further investigation.
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http://dx.doi.org/10.21037/atm-21-3352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421958PMC
August 2021

Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer.

Mol Med Rep 2021 11 10;24(5). Epub 2021 Sep 10.

Department of Pathology, The First Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110010, P.R. China.

Inhibin βA (INHBA) serves a prognostic and tumor‑promoting role in numerous types of cancer. The present study aimed to determine the clinical significance of INHBA in non‑small cell lung cancer (NSCLC) and the mechanisms underlying its potential tumor‑promoting effect. INHBA expression was detected in clinical NSCLC samples using immunohistochemistry. loss‑ and gain‑of‑function studies were performed to determine the effects of INHBA on NSCLC invasion. In addition, protein and mRNA expression levels of INHBA, yes‑associated protein (YAP), large tumor suppressor 1/2 kinase (LATS1/2), connective tissue growth factor, cysteine rich angiogenic inducer 61 and Merlin were assessed using western blotting and reverse transcription‑quantitative PCR, respectively, to investigate the mechanism by which INHBA may affect the invasion of NSCLC. The present study revealed that INHBA was significantly upregulated in 238 clinical NSCLC samples compared with its expression levels in paired adjacent non‑cancerous tissues, and in metastatic nodules compared with in primary tumors. Notably, high INHBA expression was statistically associated with clinicopathological features, including poor differentiation and advanced tumor stage. INHBA positivity was statistically related to decreased 5‑year overall survival, for which INHBA was an independent prognostic factor. Furthermore, INHBA promoted NSCLC invasion . In NSCLC, INHBA expression was associated with the nuclear levels of YAP and INHBA overexpression enhanced the invasive abilities of NSCLC cells via inhibiting the Hippo pathway. Mechanistically, INHBA inhibited l LATS1/2 phosphorylation and induced YAP nuclear translocation by downregulating the protein expression levels of Merlin. In conclusion, INHBA may negatively regulate the Hippo pathway to act as a tumor promotor, and could represent a marker of prognosis in NSCLC.
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http://dx.doi.org/10.3892/mmr.2021.12429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441965PMC
November 2021

Dynamic Event-Triggered Platooning Control of Automated Vehicles Under Random Communication Topologies and Various Spacing Policies.

IEEE Trans Cybern 2021 Aug 26;PP. Epub 2021 Aug 26.

This article addresses the problem of dynamic event-triggered platooning control of automated vehicles over a vehicular ad-hoc network (VANET) subject to random vehicle-to-vehicle communication topologies. First, a novel dynamic event-triggered mechanism is developed to determine whether or not the sampled data packets of each vehicle should be released into the VANET for intervehicle cooperation. More specifically, the threshold parameter in the triggering condition is dynamically adjusted over time according to the vehicular data variations, the dynamic threshold updating laws, and the bandwidth occupancy indication. Second, a unified platooning control framework is established to account for various spacing policies, randomly switching communication topologies, unknown leader control input, and external disturbances. Then, a new scheduling and platooning control co-design approach is presented such that the controlled vehicular platoon can successfully track the leader vehicle under random communication topologies and different spacing policies, including constant spacing, constant time headway spacing, and variable time headway spacing, meanwhile maintaining efficient bandwidth-aware resource management. Finally, comparative studies are provided to substantiate the effectiveness and merits of the proposed co-design approach.
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http://dx.doi.org/10.1109/TCYB.2021.3103328DOI Listing
August 2021

MicroRNA-137-mediated inhibition of lysine-specific demethylase-1 prevents against rheumatoid arthritis in an association with the REST/mTOR axis.

Mol Pain 2021 Jan-Dec;17:17448069211041847

Department of Orthopaedics Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Shandong, P.R. China.

Background: It has been increasingly reported that microRNAs (miRNAs) are related to rheumatoid arthritis (RA) pathogenesis. This present research was conducted to analyze the functions of miR-137 and the underlying molecular mechanism in RA progression.

Methods: Differentially expressed miRNAs in RA patients were analyzed using microarray-based analyses. Next, experiments involving miR-137 overexpression were performed to analyze the role of miR-137 in human fibroblast-like synoviocytes-RA (HFLS-RA) using cell counting kit-8 (CCK-8) assay, EdU staining, Transwell assay and flow cytometry, respectively. The function of miR-137 in inflammation was determined using ELISA. The binding relationship between miR-137 and LSD1 was confirmed by dual-luciferase reporter gene assay and ChIP test. Besides, a rat model with RA was established for experiments.

Results: miR-137 was downregulated in RA tissues and cells, which was negatively correlated with inflammatory factors. Upregulated miR-137 suppressed growth, migration and invasion of HFLS-RA, but promoted apoptosis. Lysine-specific demethylase-1 (LSD1) was a target of miR-137 and could be negatively regulated by miR-137. Moreover, LSD1 could activate REST through demethylation, while the REST/mTOR pathway induced levels of pro-inflammatory factors in RA. We observed the similar results in our study.

Conclusion: This study suggested that miR-137 reduced LSD1 expression to inhibit the activation of REST/mTOR pathway, thus preventing against inflammation and ameliorating RA development. Our research may offer new insights into treatment of RA.
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http://dx.doi.org/10.1177/17448069211041847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404669PMC
August 2021

Improving spatial data in health geographics: a practical approach for testing data to measure children's physical activity and food environments using Google Street View.

Int J Health Geogr 2021 Aug 18;20(1):37. Epub 2021 Aug 18.

School of Nursing, University of Auckland, Private Bag 920019, Auckland, 1142, New Zealand.

Background: Geographic information systems (GIS) are often used to examine the association between both physical activity and nutrition environments, and children's health. It is often assumed that geospatial datasets are accurate and complete. Furthermore, GIS datasets regularly lack metadata on the temporal specificity. Data is usually provided 'as is', and therefore may be unsuitable for retrospective or longitudinal studies of health outcomes. In this paper we outline a practical approach to both fill gaps in geospatial datasets, and to test their temporal validity. This approach is applied to both district council and open-source datasets in the Taranaki region of Aotearoa New Zealand.

Methods: We used the 'streetview' python script to download historic Google Street View (GSV) images taken between 2012 and 2016 across specific locations in the Taranaki region. Images were reviewed and relevant features were incorporated into GIS datasets.

Results: A total of 5166 coordinates with environmental features missing from council datasets were identified. The temporal validity of 402 (49%) environmental features was able to be confirmed from council dataset considered to be 'complete'. A total of 664 (55%) food outlets were identified and temporally validated.

Conclusions: Our research indicates that geospatial datasets are not always complete or temporally valid. We have outlined an approach to test the sensitivity and specificity of GIS datasets using GSV images. A substantial number of features were identified, highlighting the limitations of many GIS datasets.
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http://dx.doi.org/10.1186/s12942-021-00288-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375212PMC
August 2021

Corticosteroid switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients with biochemical progression on abiraterone acetate plus prednisone.

BMC Cancer 2021 Aug 13;21(1):919. Epub 2021 Aug 13.

Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

Background: To assess the efficacies and potential predictors of a corticosteroid switch in metastatic castration-resistant prostate cancer (mCRPC) patients with biochemical progression on abiraterone acetate plus prednisone (A + P).

Methods: Patients with mCRPC treated between April 2016 and August 2020, who experienced biochemical progression on A + P and then switched to A plus dexamethasone (D), were retrospectively identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were PSA response, overall survival (OS), and safety.

Results: One hundred and thirty consecutive cases were enrolled. The median PFS and OS on A + D were 5.0 and 18.7 months, respectively. The best PSA decline of ≥50% (PSA50) and ≥ 30% (PSA30) were observed in 29.2 and 46.2% patients, respectively. Lower PSA at corticosteroid switch (≤ 20 ng/mL; median PFS, HR 0.63, p = 0.019; median OS, HR 0.38, p = 0.001) and longer mCRPC-free survival (≥ 18 months; median PFS, HR 0.61, p = 0.013; median OS, HR 0.51, p = 0.015) were identified as independent prognostic predictors associated with longer PFS and OS. A risk stratification tool was developed to select candidates for corticosteroid switch based on the independent prognostic predictors of PFS and OS.

Conclusions: A corticosteroid switch from prednisone to dexamethasone is effective for mCRPC which progressed on A + P treatment. Patients with lower PSA at corticosteroid switch and/or longer mCRPC-free survival may gain more benefits by the corticosteroid switch.
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http://dx.doi.org/10.1186/s12885-021-08670-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364094PMC
August 2021

Optimizing the Properties of LaSrCrO Thin Films through Post-Annealing for High-Temperature Sensing.

Nanomaterials (Basel) 2021 Jul 11;11(7). Epub 2021 Jul 11.

Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education & International Center for Dielectric Research, School of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

LaSrCrO (0.2LSCO) thin films were prepared via the RF sputtering method to fabricate thin-film thermocouples (TFTCs), and post-annealing processes were employed to optimize their properties to sense high temperatures. The XRD patterns of the 0.2LSCO thin films showed a pure phase, and their crystallinities increased with the post-annealing temperature from 800 °C to 1000 °C, while some impurity phases of CrO and SrCrO were observed above 1000 °C. The surface images indicated that the grain size increased first and then decreased, and the maximum size was 0.71 μm at 1100 °C. The cross-sectional images showed that the thickness of the 0.2LSCO thin films decreased significantly above 1000 °C, which was mainly due to the evaporation of Sr and Cr. At the same time, the maximum conductivity was achieved for the film annealed at 1000 °C, which was 6.25 × 10 S/cm. When the thin films post-annealed at different temperatures were coupled with Pt reference electrodes to form TFTCs, the trend of output voltage to first increase and then decrease was observed, and the maximum average Seebeck coefficient of 167.8 µV/°C was obtained for the 0.2LSCO thin film post-annealed at 1100 °C. Through post-annealing optimization, the best post-annealing temperature was 1000 °C, which made the 0.2LSCO thin film more stable to monitor the temperatures of turbine engines for a long period of time.
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http://dx.doi.org/10.3390/nano11071802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308239PMC
July 2021

ZNF326 promotes colorectal cancer epithelial-mesenchymal transition.

Pathol Res Pract 2021 Sep 22;225:153554. Epub 2021 Jul 22.

Department of Pathology, College of Basic Medical Science, and the First Affiliated Hospital of China Medical University, Shenyang, China. Electronic address:

Zinc-finger protein 326 (ZNF326) activity has been reported in different tumors, but its expression and possible mechanism of action in colorectal cancer are not known. In this study, we applied immunohistochemistry to detect the expression of ZNF326 in colorectal tissues. Next, we used a ZNF326 expression plasmid and small interfering (si) RNA-ZNF326 (siZNF326) to transfect colorectal cancer cell lines in order to determine the effect of ZNF326 on cell migration and as well as its potential role in promoting epithelial-mesenchymal transition (EMT). A higher ZNF326 expression in the nuclei of colorectal tumor cells compared to normal mucosa was observed (70.3%, 109/155 specimens vs. 23.2%, 36/155 specimens). A high ZNF326 expression level was positively correlated with tumor differentiation, tumor-node-metastasis (TNM) staging, and lymph node metastasis. Transfection of cancer cell lines (SW480 and SW620) with a ZNF326-overexpression vector promoted colorectal cancer cell invasion and altered the expression of EMT-related proteins. Vimentin, N-cadherin, Snail, and Slug were upregulated, whereas E-cadherin and zonula occludens-1 (ZO-1) were downregulated. In contrast, downregulation of ZNF326 expression using siRNA-ZNF326 in cancer cell lines (CL187 and RKO) resulted in the opposite findings. ZNF326 overexpression also upregulated the expression of latent transforming growth factor beta binding protein 4 (LTBP4) and p-Smad2/3. In conclusion, ZNF326 promoted the EMT and invasiveness of colorectal cancer cells. These findings are likely due to LTBP4 and p-Smad2/3 upregulation and, in turn, transforming growth factor beta (TGF-β) signaling activation.
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http://dx.doi.org/10.1016/j.prp.2021.153554DOI Listing
September 2021

Lung segmentation and automatic detection of COVID-19 using radiomic features from chest CT images.

Pattern Recognit 2021 Nov 2;119:108071. Epub 2021 Jun 2.

Department of Applied Computing, Michigan Technological University, Houghton, MI 49931, USA.

This paper aims to develop an automatic method to segment pulmonary parenchyma in chest CT images and analyze texture features from the segmented pulmonary parenchyma regions to assist radiologists in COVID-19 diagnosis. A new segmentation method, which integrates a three-dimensional (3D) V-Net with a shape deformation module implemented using a spatial transform network (STN), was proposed to segment pulmonary parenchyma in chest CT images. The 3D V-Net was adopted to perform an end-to-end lung extraction while the deformation module was utilized to refine the V-Net output according to the prior shape knowledge. The proposed segmentation method was validated against the manual annotation generated by experienced operators. The radiomic features measured from our segmentation results were further analyzed by sophisticated statistical models with high interpretability to discover significant independent features and detect COVID-19 infection. Experimental results demonstrated that compared with the manual annotation, the proposed segmentation method achieved a Dice similarity coefficient of 0.9796, a sensitivity of 0.9840, a specificity of 0.9954, and a mean surface distance error of 0.0318 mm. Furthermore, our COVID-19 classification model achieved an area under curve (AUC) of 0.9470, a sensitivity of 0.9670, and a specificity of 0.9270 when discriminating lung infection with COVID-19 from community-acquired pneumonia and healthy controls using statistically significant radiomic features. The significant features measured from our segmentation results agreed well with those from the manual annotation. Our approach has great promise for clinical use in facilitating automatic diagnosis of COVID-19 infection on chest CT images.
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http://dx.doi.org/10.1016/j.patcog.2021.108071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169223PMC
November 2021

Secure Distributed Adaptive Platooning Control of Automated Vehicles Over Vehicular Ad-Hoc Networks Under Denial-of-Service Attacks.

IEEE Trans Cybern 2021 May 25;PP. Epub 2021 May 25.

This article deals with the problem of secure distributed adaptive platooning control of automated vehicles over vehicular ad-hoc networks (VANETs) in the presence of intermittent denial-of-service (DoS) attacks. The platoon, which is wirelessly connected via directed vehicle-to-vehicle (V2V) communication, is composed of a group of following vehicles subject to unknown heterogeneous nonlinearities and external disturbance inputs, and a leading vehicle subject to unknown nonlinearity and external disturbance as well as an unknown control input. Under such a platoon setting, this article aims to accomplish secure distributed platoon formation tracking with the desired longitudinal spacing and the same velocities and accelerations guided by the leader regardless of the simultaneous presence of nonlinearities, uncertainties, and DoS attacks. First, a new logical data packet processor is developed on each vehicle to identify the intermittent DoS attacks via verifying the time-stamps of the received data packets. Then, a scalable distributed neural-network-based adaptive control design approach is proposed to achieve secure platooning control. It is proved that under the established design procedure, the vehicle state estimation errors and platoon tracking errors can be regulated to reside in small neighborhoods around zero. Finally, comparative simulation studies are provided to substantiate the effectiveness and merits of the proposed control design approach on maintaining the desired platooning performance and attack tolerance.
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http://dx.doi.org/10.1109/TCYB.2021.3074318DOI Listing
May 2021

Vascular Risk Factors, Imaging, and Outcomes in Transient Ischemic Attack/Ischemic Stroke Patients with Neuroimaging Evidence of Probable/Possible Cerebral Amyloid Angiopathy.

Oxid Med Cell Longev 2021 26;2021:9958851. Epub 2021 Apr 26.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: In TIA/ischemic stroke patients, the clinical significance of lobar microbleeds potentially indicating cerebral amyloid angiopathy (CAA) is unknown. We assessed vascular risk factors and outcomes, including cognition, in TIA/ischemic stroke patients with neuroimaging evidence of probable/possible CAA.

Methods: This prospective cohort was conducted from August 2015 and January 2018 at 40 centers. 2625 participants were collected. Eligible participants were aged at least 55 years. Montreal Cognitive Assessment (MoCA) score is less than or equal to 26. A total of 1620 patients were included. 1604 (99.0%) and 1582 (97.7%) participants are followed up at 3 and 12 months. The primary outcomes were death or disability (mRS score, 3-6) and Montreal Cognitive Assessment (MoCA) at 3 months and 12 months. Demographic and vascular risk factors were measured at baseline (smoking, alcohol, diabetes, atrial fibrillation, hypertension, hypercholesterolemia, coronary artery disease, ischemic stroke, and transient ischemic attack). Blood samples were collected within 24 hours of admission. MRI was recommended for all patients. MoCA score was evaluated at baseline and follow-up.

Results: In total, 291/1620 patients with ischemic stroke/TIA (32.7% female and mean age, 67.8 years) had neuroimaging evidence of probable/possible CAA. Higher age, history of hypertension, atrial fibrillation, ischemic stroke, alcohol, and high glucose at the admission were more common in the patients. Mean MoCA changed from 21.4 at 3 months (SD 5.2) to 22.3 at 12 months (SD 4.7), difference 0.3 (SD 3.8). At the 3-month and 12-month follow-up, there were significant differences in age, education level, and sex among different cognitive groups. Higher age, lower education (less than high school), and female sex were the predictors of changing in MoCA score from 3 months to 12 months. Moreover, age (more than 66 years) and education (less than high school) are strongly associated with MoCA at 3- and 12-month follow-up. 30 of 286 (10.5%) and 37 of 281 (13.2%) patients had poor outcome of death or disability (modified Rankin Scale score, 3-6) at follow-up 3 and 12 months. Cortical superficial siderosis (cSS) was associated with higher mRS at follow-up. cSS status, cSS count 1-2, cSS strictly lobar, and strictly deep might be the risks of outcomes in adjusted analyses.

Conclusion: This study suggested that an increasing number of vascular risk factors and imaging markers were significantly associated with outcomes of TIA/ischemic stroke patients with CAA pattern. Male, young patients with high education should get better cognitive recovery.
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http://dx.doi.org/10.1155/2021/9958851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096555PMC
April 2021

Association of Polyvascular Disease and Elevated Interleukin-6 With Outcomes in Acute Ischemic Stroke or Transient Ischemic Attack.

Front Neurol 2021 13;12:661779. Epub 2021 Apr 13.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Polyvascular disease (PolyVD) and interleukin (IL)-6 are associated with poor outcomes in patients with stroke respectively. However, whether combined PolyVD and elevated IL-6 levels would increase the risk of poor outcomes of stroke patients is yet unclear. Data were obtained from the Third China National Stroke Registry (CNSR-III). PolyVD was defined as acute ischemic stroke (AIS) or transient ischemic attack (TIA) with coronary artery disease (CAD) and/or peripheral artery disease (PAD). Patients were divided into four groups according to the combination of vascular beds number (non-PolyVD or PolyVD) and IL-6 levels (IL-6 < 2.64 pg/mL or IL-6 ≥ 2.64 pg/mL). The primary outcome was a recurrent stroke at 1-year follow-up. Cox proportional hazard models were employed to identify the association of the combined effect of PolyVD and IL-6 with the prognosis of patients. A total of 10,773 patients with IL-6 levels and 1-year follow-up were included. The cumulative incidence of recurrent stroke was 9.87% during the 1-year follow-up. Compared to non-PolyVD and IL-6<2.64 pg/mL patients, patients had non-PolyVD with IL-6 ≥ 2.64 pg/mL (HR 1.245 95%CI 1.072-1.446; < 0.001) and PolyVD with IL-6 <2.64 pg/mL (HR 1.251 95%CI 1.002-1.563; = 0.04) were associated with an increased risk of recurrent stroke during 1-year follow-up. Likewise, patients with PolyVD and IL-6 ≥ 2.64 pg/mL (HR 1.290; 95% CI 1.058-1.572; = 0.01) had the highest risk of recurrent stroke at 1-year follow-up among groups. PolyVD and elevated IL-6 levels are both associated with poor outcomes in patients with AIS or TIA. Moreover, the combination of them increases the efficiency of stroke risk stratification compared with when used alone. More attention and intensive treatment should be given to those patients with both PolyVD and elevated IL-6 levels.
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http://dx.doi.org/10.3389/fneur.2021.661779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076541PMC
April 2021

Cumulative burden of lipid profiles predict future incidence of ischaemic stroke and residual risk.

Stroke Vasc Neurol 2021 Apr 7. Epub 2021 Apr 7.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Objectives: Incident ischaemic stroke (IS) risk may increase not only with lipids concentration but also with longer duration of exposure. This study aimed to investigate the impact of cumulative burden of lipid profiles on risk of incident IS.

Methods: A total of 43 836 participants were enrolled who participated in four surveys during 2006-2013. Individual cumulative lipid burden was calculated as number of years (2006-2013) multiplied by the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and triglyceride (TG), respectively. The primary outcome was defined as the incident IS during 2012-2017.

Results: During 4.67 years (±0.70 years) follow-up on average, we identified 1023 (2.33%) incident IS. Compared with respective reference groups, the HRs (95% CIs) of the upper tertile in cumulative TG burden, cumulative LDL-C burden, cumulative TC burden and cumulative non-HDL-C burden were 1.26 mmol/L (1.02-1.55 mmol/L), 1.47 mmol/L (1.25-1.73 mmol/L), 1.33 mmol/L (1.12-1.57 mmol/L) and 1.51 mmol/L (1.28-1.80 mmol/L) for incidence of IS, respectively. However, this association was not significant in cumulative HDL-C burden and IS (HR: 1.09; 95% CI: 0.79 to 1.52), after adjustment for confounding variables. Among 16 600 participants with low cumulative LDL-C burden, HRs (95% CI) for TC, TG, non-HDL-C and HDL-C with IS were 1.63 mmol/L (1.03-2.57 mmol/L), 1.65 mmol/L (1.19-2.31 mmol/L), 1.57 mmol/L (1.06-2.32 mmol/L) and 0.98 mmol/L (0.56-1.72 mmol/L), respectively.

Conclusions: We observed the correlation between cumulative burden of lipid profiles, except for cumulative burden of HDL-C, with the risk of incident IS. Cumulative burden of TC, TG and non-HDL-C may still predict IS in patients with low cumulative LDL-C burden.

Trial Registration Number: ChiCTR-TNRC-11001489.
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http://dx.doi.org/10.1136/svn-2020-000726DOI Listing
April 2021

QT Interval Dispersion as a Predictor of Clinical Outcome in Acute Ischemic Stroke.

Front Neurol 2020 22;11:974. Epub 2021 Jan 22.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

QT dispersion (QTd) abnormalities are widely documented in stroke patients. This study aims to investigate the association between QTd and clinical outcomes in IS patients. IS patients registered in the Blood Pressure and Clinical Outcome in transient ischemic attack (TIA) or IS (BOSS) registry between 2012 and 2014 within 24 h of onset were analyzed. In this prospective observational study, we identified 1,522 IS cases with adequate electrocardiographic evaluations to assess QTd after the index stroke. Patients were classified into four groups based on the quartile of QTd, with the lowest group as the reference. The primary stroke outcome was defined as a modified Rankin Scale score ≥3 at 1-year. Multiple logistic regressions were utilized to investigate the association between QTd and outcome events. The mean QTd across all cases was 57 ms (40-83). Functional dependency or death was documented in 214 (14.98%) cases at 1 year. After adjusting for confounders, the prevalence of death and major disability (mRS ≥ 3) showed significant differences according to the quartile of QTd, with the risk of death and major disability (mRS ≥ 3) at 1 year being significantly higher for patients in Q4 than for those in Q1 (adjusted OR = 1.626, 95% CI:1.033-2.560). However, there were no significant correlation between QTd and the event outcomes at 1 year. QTd was associated with poor functional outcomes at 1 year. QTd is a useful surrogate marker for adverse functional prognosis, which might help to stratify risk in patients with acute IS.
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http://dx.doi.org/10.3389/fneur.2020.00974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863974PMC
January 2021

The Beneficial Effects of Saffron Extract on Potential Oxidative Stress in Cardiovascular Diseases.

Oxid Med Cell Longev 2021 19;2021:6699821. Epub 2021 Jan 19.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.

Saffron is commonly used in traditional medicines and precious perfumes. It contains pharmacologically active compounds with notably potent antioxidant activity. Saffron has a variety of active components, including crocin, crocetin, and safranal. Oxidative stress plays an important role in many cardiovascular diseases, and its uncontrolled chain reaction is related to myocardial injury. Numerous studies have confirmed that saffron exact exhibits protective effects on the myocardium and might be beneficial in the treatment of cardiovascular disease. In view of the role of oxidative stress in cardiovascular disease, people have shown considerable interest in the potential role of saffron extract as a treatment for a range of cardiovascular diseases. This review analyzed the use of saffron in the treatment of cardiovascular diseases through antioxidant stress from four aspects: antiatherosclerosis, antimyocardial ischemia, anti-ischemia reperfusion injury, and improvement in drug-induced cardiotoxicity, particularly anthracycline-induced. Although data is limited in humans with only two clinically relevant studies, the results of preclinical studies regarding the antioxidant stress effects of saffron are promising and warrant further research in clinical trials. This review summarized the protective effect of saffron in cardiovascular diseases and drug-induced cardiotoxicity. It will facilitate pharmacological research and development and promote utilization of saffron.
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http://dx.doi.org/10.1155/2021/6699821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840270PMC
September 2021

Preparation, characterization and in vitro stability of iron-chelating peptides from mung beans.

Food Chem 2021 Jul 19;349:129101. Epub 2021 Jan 19.

Anhui Engineering Laboratory for Agro-products Processing, Anhui Agricultural University, Hefei 230036, China; Anhui Engineering Research Center of Functional Food for Plant Active Peptides, Hefei 230036, Anhui, China; College of Tea and Food Science & Technology, Anhui Agricultural University, Hefei 230036, Anhui, China. Electronic address:

Mung bean protein was enzymatically hydrolyzed with either alcalase, neutral protease, or papain. The mung bean protein hydrolysates (MPH) showed good ability to chelate ferrous ions, and the chelates had high stability in vitro. The hydrolysates prepared by alcalase showed the highest degree of hydrolysis and the highest ferrous chelating rate. Single factor tests showed that the pH and the material ratio had significant effects on ferrous chelating rates. The optimal MPH to FeCl·4HO material ratio was 8:1 (w/w) and the optimal pH of the reaction was 7.0, which yielded a chelating rate of 96.19 ± 0.94%. The fraction 3 with the highest ferrous chelating activity up to 61.25 ± 1.02 μg/mg was obtained from MPH by affinity chromatography. Meanwhile, the MPH-Fe complex had higher digestive stability than just MPH in both in vitro and acid-alkali tolerance assays. The characterization results showed that ferrous ions mainly combined with the amino, carboxyl, imidazole and other chelating active groups in mung bean peptides to form peptide-iron chelates. Scanning electron microscopy (SEM) analysis showed that mung bean peptide chelated ferrous ions to form polymer particles. These results provided insight into ways to develop functional foods such as iron-fortified cereals.
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http://dx.doi.org/10.1016/j.foodchem.2021.129101DOI Listing
July 2021

Importin α phosphorylation promotes TPX2 activation by GM130 to control astral microtubules and spindle orientation.

J Cell Sci 2021 02 19;134(4). Epub 2021 Feb 19.

Department of Cell Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA

Spindle orientation is important in multiple developmental processes as it determines cell fate and function. The orientation of the spindle depends on the assembly of a proper astral microtubule network. Here, we report that the spindle assembly factor TPX2 regulates astral microtubules. TPX2 in the spindle pole area is activated by GM130 (GOLGA2) on Golgi membranes to promote astral microtubule growth. GM130 relieves TPX2 inhibition by competing for importin α1 (KPNA2) binding. Mitotic phosphorylation of importin α at serine 62 (S62) by CDK1 switches its substrate preference from TPX2 to GM130, thereby enabling competition-based activation. Importin α S62A mutation impedes local TPX2 activation and compromises astral microtubule formation, ultimately resulting in misoriented spindles. Blocking the GM130-importin α-TPX2 pathway impairs astral microtubule growth. Our results reveal a novel role for TPX2 in the organization of astral microtubules. Furthermore, we show that the substrate preference of the important mitotic modulator importin α is regulated by CDK1-mediated phosphorylation.
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http://dx.doi.org/10.1242/jcs.258356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904092PMC
February 2021

Radical photoinitiation with LEDs and applications in the 3D printing of composites.

Chem Soc Rev 2021 Mar 1;50(6):3824-3841. Epub 2021 Feb 1.

Université de Haute-Alsace, CNRS, IS2M UMR 7361, F-68100 Mulhouse, France.

Radical initiation upon LED light irradiation is discussed herein as well as its application in additive manufacturing. The ability of manufacturing complex structures, freedom of design, low energy consumption, fast prototyping, and excellent spatial resolution are the main benefits of the 3D printing technology by photopolymerization. Therefore, the 3D printing of composites through photopolymerization processes is developing rapidly in the academia and industry, and has been a turning point of additive manufacturing (AM). In the present review, an overview of radical initiation with LEDs (i.e., the photopolymerization LED technology, the photoinitiating systems, and the polymerizable media) and of the main 3D printing methods by photopolymerization, materials, and their applications in different fields has been carried out. As a challenging topic, the issue of light penetration in a filled matrix for the access to composites is discussed, including the light transmittance of the composite, the mismatch of the refractive index between the filler and the monomer, the factors of the filler, and the adverse influence of low light penetration on the 3D printing process. In particular, the popular applications of 3D printing by photopolymerization in biomedical science, electronic industry, materials for adsorption, and 4D printing are discussed. Overall, this review gives an overview of the 3D printing of polymer matrix composites through photopolymerization processes as a benchmark for future research and development.
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http://dx.doi.org/10.1039/d0cs01411gDOI Listing
March 2021

Convex-Meniscus-Assisted Self-Assembly at the Air/Water Interface to Prepare a Wafer-Scale Colloidal Monolayer Without Overlap.

Langmuir 2021 Jan 23;37(1):249-256. Epub 2020 Dec 23.

R&D Center of Healthcare Electronics, Institute of Microelectronics, Chinese Academy of Sciences, Beijing 100029, China.

Self-assembly at the air/water interface (AWI) has proven to be an efficient strategy for fabricating two-dimensional (2D) colloidal monolayers, which was widely used as the template for nanosphere lithography in nanophononics, optofluidics, and solar cell studies. However, the monolayers fabricated at the AWI usually suffer from a small domain area and quasi-double layer structure caused by submerged particles. To overcome this, we proposed an improved protocol to prepare 2D colloidal monolayers free of overlapping nanospheres at the AWI. Utilizing the stable suspension infusion to the water surface, a convex meniscus, whose height is related to viscous force, was formed adjoining the three-phase boundary. As a result of the resistance of the convex meniscus, the polystyrene nanospheres in the initial suspension directly self-assembled into a preliminary monolayer, which proved effective in preventing nanospheres' sinking and increasing the colloidal crystal domain size. An optimal parameter for transferring the monolayer was also developed based on the numerical simulation results. Finally, a wafer-scale monolayer, covered with less than one nanosphere per 100 μm × 100 μm area, was achieved on the desired substrate with an average domain size attaining centimeter scale. The high-quality 2D colloidal crystal may further promote the application of nanosphere lithography, especially in the fields that require a defect-free template.
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http://dx.doi.org/10.1021/acs.langmuir.0c02851DOI Listing
January 2021

Impact of immunohistochemistry-based molecular subtype on predicting chemotherapy response and survival in patients with T1 stage bladder cancer after bladder-preserving treatment.

Jpn J Clin Oncol 2021 Mar;51(3):424-433

Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.

Objective: To explore the immunohistochemistry-based molecular subtypes of bladder cancer, and their impact on the prognosis and the chemotherapy response between gemcitabine plus cisplatin intra-arterial chemotherapy and epirubicin-inducted intravesical chemotherapy, in patients with T1 stage bladder cancer after bladder-preserving treatment.

Methods: One hundred and seventy-six patients with T1 stage bladder cancer were selected for this study. Thirty-three patients underwent radical cystectomy, 43 received gemcitabine plus cisplatin intra-arterial chemotherapy and 100 received intravesical chemotherapy. The markers labeled with luminal (GATA3, Uroplakin II, CK20) and basal (CK5/6, CK14, CD44) phenotypes were chosen as candidate markers.

Results: One hundred and seventy-six patients were divided into 76 patients as basal/squamous (BASQ), 45 as the luminal A and 55 as the luminal B. Compared with the luminal B and BASQ tumors, the luminal A tumors showed a trend for better recurrence-free survival (P = 0.105) and progression-free survival (P = 0.093). The combination of CK20 and GATA3 was practical to identify the molecular phenotypes with total 84.9% accuracy and significantly associated with recurrence-free survival (P = 0.025) and progression-free survival (P = 0.004). The patient with BASQ tumors who received intravesical chemotherapy showed a trend for worse progression-free survival than the patient who received gemcitabine plus cisplatin intra-arterial chemotherapy or radical cystectomy. Furthermore, the patients with BASQ tumors experienced a significant improvement in progression-free survival after gemcitabine plus cisplatin intra-arterial chemotherapy compared with the patients who received intravesical chemotherapy (P = 0.011).

Conclusions: The immunohistochemistry-based molecular subtypes could predict the patient's prognosis and clinically different chemotherapeutic survival outcomes in patients with T1 stage bladder cancer after bladder-preserving treatment.
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http://dx.doi.org/10.1093/jjco/hyaa219DOI Listing
March 2021

Rapid degradation of GRASP55 and GRASP65 reveals their immediate impact on the Golgi structure.

J Cell Biol 2021 01;220(1)

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX.

GRASP55 and GRASP65 have been implicated in stacking of Golgi cisternae and lateral linking of stacks within the Golgi ribbon. However, RNAi or gene knockout approaches to dissect their respective roles have often resulted in conflicting conclusions. Here, we gene-edited GRASP55 and/or GRASP65 with a degron tag in human fibroblasts, allowing for induced rapid degradation by the proteasome. We show that acute depletion of either GRASP55 or GRASP65 does not affect the Golgi ribbon, while chronic degradation of GRASP55 disrupts lateral connectivity of the ribbon. Acute double depletion of both GRASPs coincides with the loss of the vesicle tethering proteins GM130, p115, and Golgin-45 from the Golgi and compromises ribbon linking. Furthermore, GRASP55 and/or GRASP65 is not required for maintaining stacks or de novo assembly of stacked cisternae at the end of mitosis. These results demonstrate that both GRASPs are dispensable for Golgi stacking but are involved in maintaining the integrity of the Golgi ribbon together with GM130 and Golgin-45.
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http://dx.doi.org/10.1083/jcb.202007052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735681PMC
January 2021

Severity of Nonalcoholic Fatty Liver Disease and Risk of Future Ischemic Stroke Events.

Stroke 2021 01 4;52(1):103-110. Epub 2020 Dec 4.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (J.X., L.D., Y.Z., A.W., H.L., Yilong Wang, X.M., Yongjun Wang).

Background And Purpose: We assessed prospectively whether nonalcoholic fatty liver disease (NAFLD) and its severity predict future ischemic stroke (IS) events in a community-based cohort.

Methods: From the Kailuan study, participants free of history of stroke, cancer, or myocardial infarction were enrolled after excluding alcohol abuse and other liver diseases. NAFLD was evaluated through ultrasonography. Participants with NAFLD were further stratified into mild, moderate, and severe groups. The outcome was the first occurrence of IS. The secondary outcomes included myocardial infarction and combined vascular events. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of incident IS according to presence and severity of NAFLD, adjusting for age, sex, physical activity, body mass index, smoker, history of hypertension, diabetes, hypercholesterolemia, lipid-lowering medication, HDL (high-density lipoprotein), triglyceride, hsCRP (high-sensitivity C-reactive protein), and fasting blood glucose.

Results: During a median of 10.34 years of follow-up, we documented 3490 incident stroke cases among 79 905 participants. NAFLD was found in 24 874 (31.18%) participants. Relative to participants without NAFLD at the baseline, those with NAFLD had a 16% higher risk (95% CI, 1.07-1.26) of developing ischemic stroke, after adjusted for confounding variables. The hazard ratios for patients with mild, moderate, and severe NAFLD were 1.15 (95% CI, 1.05-1.25), 1.19 (95% CI, 1.06-1.34), and 1.21 (95% CI, 1.08-1.50), respectively.

Conclusions: The severity of NAFLD is associated with a higher risk of future ischemic stroke events.
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http://dx.doi.org/10.1161/STROKEAHA.120.030433DOI Listing
January 2021

Theoretical modeling and simulation-based assessment of graded-bandgap AlGaAs/GaAs electron-injection cathode.

Ultramicroscopy 2020 Dec 14;219:113121. Epub 2020 Sep 14.

School of Electronic and Optical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.

The electron emission model of a negative electron affinity graded-bandgap AlGaAs/GaAs electron-injection cathode was developed from two-dimensional continuity equations. The emission current was obtained from a simulation of the model, and the emission current efficiency and emission current per unit length were calculated. Based on the simulation results and preparation conditions, the range of optimum parameters for the cathode structure were determined. The ranges of optimum thickness for the p-AlGaAs and the graded-bandgap p-AlGaAs layers were 0.05-0.15 μm and 0.1-0.3 μm, respectively. The optimum width of the base electrode ranged from 1 to 4 μm, and the optimum molar ratios of Al in the p-AlGaAs and the n-AlGaAs layers were 0.2-0.3 and 0.4-0.5, respectively. This abrupt PN heterojunction inhibited the hole current and increased the emission current efficiency, with a maximum value of 25.3%. According to the emission current per unit length, the optimum range of width of emission unit surface was 6 to 10 μm, and the peak emission current per unit length reached 43.2 μA/μm.
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http://dx.doi.org/10.1016/j.ultramic.2020.113121DOI Listing
December 2020

Novel Photoinitiators Based on Benzophenone-Triphenylamine Hybrid Structure for LED Photopolymerization.

Macromol Rapid Commun 2020 Dec 21;41(23):e2000460. Epub 2020 Sep 21.

Institut de Science des Matériaux de Mulhouse, IS2M-UMR CNRS 7361, UHA, 15, rue Jean Starcky, Mulhouse Cedex, 68057, France.

In this study, a new generation of photoinitiator (PI) based on hybrid structures combining benzophenone and triphenylamine is proposed. Remarkably, these photoinitiators (noted monofunctional benzophenone-triphenylamine (MBP-TPA) and trifunctional benzophenone-triphenylamine (TBP-TPA)) are designed and developed for the photopolymerization under light-emitting diodes (LEDs). Benzoyl substituents connected with triphenylamine moiety contribute to the excellent absorption properties which results in both high final conversions and polymerization rates in free radical photopolymerization (FRP). Remarkably, TBP-TPA owning trifunctional benzophenone group exhibits a better Type II PI behavior than well-known 2-isopropylthioxanthone for photopolymerization under [email protected] and 405 nm irradiation. FRP and cationic photopolymerization of TBP-TPA-based systems are applied on 3D printing experiments, and good profiles of the 3D patterns are observed. The high molecular weight of TBP-TPA associated with it trifunctional character can also be very interesting for a better migration stability of PIs that is a huge challenge. The development of this new generation of photoinitiators based on benzophenone hybrid structures is a real breakthrough. It reveals that the novel versatile photoinitiators based on benzophenone-triphenylamine hybrid structures have great potentials for future industrial applications (e.g., 3D printing, composites, etc.).
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http://dx.doi.org/10.1002/marc.202000460DOI Listing
December 2020

The Association between Green Space and Adolescents' Mental Well-Being: A Systematic Review.

Int J Environ Res Public Health 2020 09 11;17(18). Epub 2020 Sep 11.

School of Nursing, The University of Auckland, Auckland 1142, New Zealand.

This systematic review summarised and evaluated the evidence for associations between green space and adolescents' mental well-being. The PRISMA statement guidelines were followed for reporting systematic reviews. Fourteen articles met the inclusion criteria for this review. Synthesis suggests beneficial associations between green space exposure and reduced stress, positive mood, less depressive symptoms, better emotional well-being, improved mental health and behaviour, and decreased psychological distress in adolescents. Several studies found the relationship varied by demographic and socio-economic factors. The limited number of studies and the risk of bias were the main limitations, together with heterogeneity regarding green space and mental well-being assessments. Overall, this review highlights the potential contribution of green space in schoolyards. Improving the availability, accessibility and quality of green space is likely to generate positive impacts on adolescents' mental well-being. More consistent evidence on the use of different types of green space and perceptions of features are needed in the future.
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http://dx.doi.org/10.3390/ijerph17186640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557737PMC
September 2020

Transformation of pollution control and green development: Evidence from China's chemical industry.

J Environ Manage 2020 Dec 25;275:111246. Epub 2020 Aug 25.

School of Business, Central South University, Changsha, Hunan, 410083, China; Institute of Metal Resources Strategy, Central South University, Changsha, Hunan, 410083, China. Electronic address:

The Air Pollution Prevention and Control Action Plan (APCP) is an important pollution control policy formulated by the Chinese government to promote green development. However, there are few studies of its impact. Based on a province-level panel dataset from 2007 to 2017, we use a three-hierarchy meta-frontier slack-based data envelopment analysis (SBM-DEA) model and the global Malmquist (GM) index to estimate the green total factor productivity (GTFP) of China's chemical sub-industries. Next, we use the difference-in-differences (DID) method to explore the effect of the implementation of the APCP in 2013 on the GTFP of China's chemical industry. We find an increasing trend in the GTFP of China's chemical industry between 2007 and 2017. A decomposition of the change in GTFP shows that technical progress was the main driving factor and management inefficiency was the main inhibitory factor. The APCP had a significant positive effect on GTFP. Overall, in the post-implementation period, the increase in the GTFP of the treatment group was approximately 7.9% greater than in the control group. The APCP also significantly improved the technical efficiency change index. A dynamic effect analysis shows that the positive effect of the APCP on GTFP had an inverted U-shaped trend. A series of robustness tests, including counterfactual, re-grouping, and quasi-DID tests, suggest that our findings are reliable. In addition, changes in exports, capital deepening, and energy prices all significantly improved the GTFP of China's chemical industry.
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http://dx.doi.org/10.1016/j.jenvman.2020.111246DOI Listing
December 2020

Highly Elastic Block Copolymer Binders for Silicon Anodes in Lithium-Ion Batteries.

ACS Appl Mater Interfaces 2020 Aug 17;12(34):38132-38139. Epub 2020 Aug 17.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, China.

Silicon (Si) is a promising anode material to replace the broadly adopted graphite due to its high capacity and abundant source. However, Si anodes suffer from severe problems of huge volume change (∼300%), and the commonly used binders like poly(vinylidene fluoride) (PVDF) cannot accommodate such changes. Here, we report a tough block copolymer PVDF--Teflon (PTFE) binder that can coalesce pulverized Si and thus enhance the stability of Si anodes. The suspension copolymerization of vinylidene fluoride and tetrafluoroethylene produces elastic PVDF--PTFE with large breaking elongations of >250% and high viscosity as well as high ionic conductivity and thermal stability. We show that 5 wt % of the binder forms elastic cobweb structures in the electrode matrix that can effectively coalesce Si particles and conductive agents together, enabling long cycling stability (>250 cycles) and high rate performance (1 C) for electrodes at a commercial-level Si loading of 1 mg·cm. The findings point out to a promising strategy for developing highly elastic and tenacious binders for electrodes with large volume changes during the electrochemical reactions.
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http://dx.doi.org/10.1021/acsami.0c10005DOI Listing
August 2020

Immunophenotypes Based on the Tumor Immune Microenvironment Allow for Unsupervised Penile Cancer Patient Stratification.

Cancers (Basel) 2020 Jul 4;12(7). Epub 2020 Jul 4.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

The tumor immune microenvironment (TIME) plays an important role in penile squamous cell carcinoma (peSCC) pathogenesis. Here, the immunophenotype of the TIME in peSCC was determined by integrating the expression patterns of immune checkpoints (programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4), and Siglec-15) and the components of tumor-infiltrating lymphocytes, including CD8 or Granzyme B T cells, FOXP3 regulatory T cells, and CD68 or CD206 macrophages, in 178 patients. A high density of Granzyme B, FOXP3, CD68, CD206, PD-1, and CTLA-4 was associated with better disease-specific survival (DSS). The patients with diffuse PD-L1 tumor cell expression had worse prognoses than those with marginal or negative PD-L1 expression. Four immunophenotypes were identified by unsupervised clustering analysis, based on certain immune markers, which were associated with DSS and lymph node metastasis (LNM) in peSCC. There was no significant relationship between the immunophenotypes and high-risk human papillomavirus (hrHPV) infection. However, the hrHPV-positive peSCC exhibited a higher density of stromal Granzyme B and intratumoral PD-1 than the hrHPV-negative tumors ( = 0.049 and 0.002, respectively). In conclusion, the immunophenotypes of peSCC were of great value in predicting LNM and prognosis, and may provide support for clinical stratification management and immunotherapy intervention.
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http://dx.doi.org/10.3390/cancers12071796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407624PMC
July 2020

Monocomponent Photoinitiators based on Benzophenone-Carbazole Structure for LED Photoinitiating Systems and Application on 3D Printing.

Polymers (Basel) 2020 Jun 22;12(6). Epub 2020 Jun 22.

Université de Haute-Alsace, CNRS, IS2M UMR 7361, F-68100 Mulhouse, France.

In this article, different substituents (benzoyl, acetyl, styryl) are introduced onto the carbazole scaffold to obtain 8 novel carbazole derivatives. Interestingly, a benzoyl substituent, connected to a carbazole group, could form a benzophenone moiety, which composes a monocomponent Type II benzophenone-carbazole photoinitiator (PI). The synergetic effect of the benzophenone moiety and the amine in the carbazole moiety is expected to produce high performance photoinitiating systems (PISs) for the free radical photopolymerization (FRP). For different substituents, clear effects on the light absorption properties are demonstrated using UV-Visible absorption spectroscopy. Benzophenone-carbazole PIs can initiate the FRP of acrylates alone (monocomponent Type II photoinitiator behavior). In addition, fast polymerization rates and high function conversions of acrylate are observed when an amine and/or an iodonium salt are added in systems. Benzophenone-carbazole PIs have good efficiencies in cationic photopolymerization (CP) upon LED @ 365 nm irradiation in the presence of iodonium salt. In contrast, other PIs without synergetic effect demonstrate unsatisfied photopolymerization profiles in the same conditions. The best PIS identified for the free radical photopolymerization were used in three-dimensional (3D) printing. Steady state photolysis and fluorescence quenching experiments were carried out to investigate the reactivity and the photochemistry and photophysical properties of PIs. The free radicals, generated from the studied PISs, are detected by the electron spin resonance - spin trapping technique. The proposed chemical mechanisms are provided and the structure/reactivity/efficiency relationships are also discussed. All the results showed that the benzophenone-carbazole PIs have a good application potential, and this work provides a rational design route for PI molecules. Remarkably, BPC2-BPC4, C6, C8 were never synthetized before; therefore, 5 of the 8 compounds are completely new.
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http://dx.doi.org/10.3390/polym12061394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362224PMC
June 2020

YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis.

Mol Ther Nucleic Acids 2020 Sep 21;21:86-97. Epub 2020 May 21.

Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China. Electronic address:

Hepatocellular carcinoma is one of the most common gastrointestinal malignancies. Anti-angiogenesis therapies have recently demonstrated promise in the treatment of malignancies, although early treatment benefits may be accompanied by metastasis over time. Additional and more effective anti-angiogenic treatment modalities are therefore needed. We previously found that Yes-associated protein 1 (YAP1) expression is increased in hepatocellular carcinoma (HCC), particularly around tumor-associated blood vessels, suggesting a role in angiogenesis. The YAP1 inhibitor verteporfin is presently in anti-angiogenic clinical trials for the treatment of various cancers. Depleted YAP1 from vascular endothelial cells effectively reduced proliferation and tube formation, validating its utility as an anti-angiogenesis target. We also showed that YAP1 depletion or inhibition in vascular endothelial cells leads to increased release of exosomes containing the long non-coding RNA (lncRNA) MALAT1 into the tumor microenvironment. Direct exosomal transfer of MALAT1 to hepatic cells leads to increased hepatic cell invasion and migration via activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. These observations may explain the occurrence of distant tumor metastasis with YAP1-associated anti-angiogenic therapy over time. It provides insight into new pathways and treatment paradigms that may be targeted to increase the long-term success of anti-angiogenic therapies.
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http://dx.doi.org/10.1016/j.omtn.2020.05.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281784PMC
September 2020
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