Publications by authors named "Chen Hu"

732 Publications

Non-invasive transcutaneous vagal nerve stimulation improves myocardial performance in doxorubicin-induced cardiotoxicity.

Cardiovasc Res 2021 Jun 18. Epub 2021 Jun 18.

Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, Hubei, PR China.

Aims: The clinical use of antitumor agent doxorubicin (DOX) is hampered by its dose-dependent cardiotoxicity. Development of highly efficient and safe adjuvant intervention for preventing DOX-induced adverse cardiac events is urgently needed. We aimed to investigate whether transcutaneous vagal nerve stimulation (tVNS) plays a cardio-protective role in DOX-induced cardiotoxicity.

Methods And Results: Healthy male adult Sprague Dawley rats were used in the experiment and were randomly divided into four groups including control, DOX, tVNS and DOX+tVNS groups. A cumulative dose of 15 mg/kg DOX was intraperitoneally injected into rats to generate cardiotoxicity. Non-invasive tVNS was conducted for 6 weeks (30 min/day). After six-week intervention, the indices from the echocardiography revealed that tVNS significantly improved left ventricular function compared to the DOX group. The increased malondialdehyde (MDA) and Interleukin-1β (IL-1β), and decreased superoxide dismutase (SOD) were observed in the DOX group, while tVNS significantly prevented these changes. From cardiac histopathological analysis, the DOX+tVNS group showed a mild myocardial damage, and decreases in cardiac fibrosis and myocardial apoptosis compared to the DOX group. Heart rate variability (HRV) analysis showed that tVNS significantly inhibited DOX-induced sympathetic hyperactivity compared to the DOX group. Additionally, the results of RNA-sequencing analysis showed that there were 245 differentially expressed genes in the DOX group compared to the control group, among which 39 genes were downregulated by tVNS and most of these genes were involved in immune system. Moreover, tVNS significantly downregulated the relative mRNA expressions of chemokine-related genes and macrophages recruitment compared to the DOX group.

Conclusion: These results suggest that tVNS prevented DOX-induced cardiotoxicity by rebalancing autonomic tone, ameliorating cardiac dysfunction and remodeling. Notably, crosstalk between autonomic neuromodulation and innate immune cells macrophages mediated by chemokines might be involved in the underlying mechanisms.

A Translational Perspective: Non-invasive tVNS has been identified an effective neuromodulation strategy exerting beneficial effects on rebalancing autonomic tone and cardiac pathological conditions. The present study provided direct evidence for a beneficial role of tVNS in preventing DOX-induced autonomic dysfunction and cardiotoxicity in vivo. Additionally, recent studies revealed the importance of sympathetic nerve fibers involving in tumorigenesis and the benefits of higher vagal tone for tumor prognosis either in animal or human trials. Together, tVNS may not only become a novel, nonpharmacological adjuvant therapy for preventing doxorubicin-induced cardiotoxicity, but also may be beneficial for prognosis of cancer patients during chemotherapy. In our future study, we would investigate the effect of tVNS on both combined chemotherapy-induced cardiotoxicity and the antitumor efficacy of DOX in tumor models.
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http://dx.doi.org/10.1093/cvr/cvab209DOI Listing
June 2021

Ultrafast in-situ forming halloysite nanotube-doped chitosan/oxidized dextran hydrogels for hemostasis and wound repair.

Carbohydr Polym 2021 Sep 11;267:118155. Epub 2021 May 11.

Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, China; Guangdong Key Lab of Orthopedic Technology and Implant Materials, General Hospital of Southern Theater Command of PLA, The First School of Clinical Medicine of Southern Medical University, Guangzhou 510010, China. Electronic address:

A series of halloysite nanotube (HNT)-doped chitosan (CS)/oxidized dextran (ODEX) adhesive hydrogels were developed through a Schiff base reaction. The resultant CS/ODEX/HNT hydrogels could not only form in situ on wounds within only 1 s when injected, but could also adapt to wounds of different shapes and depths after injection. We established four rat and rabbit hemorrhage models and demonstrated that the hydrogels are better than the clinically used gelatin sponge for reducing hemostatic time and blood loss, particularly in arterial and deep noncompressible bleeding wounds. Moreover, the natural antibacterial features of CS and ODEX provided the hydrogels with strong bacteria-killing effects. Consequently, they significantly promoted methicillin-resistant Staphylococcus aureus -infected-wound repair compared to commercial gelatin sponge and silver-alginate antibacterial wound dressing. Hence, our multifunctional hydrogels with facile preparation process and utilization procedure could potentially be used as first-aid biomaterials for rapid hemostasis and infected-wound repair in emergency injury events.
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http://dx.doi.org/10.1016/j.carbpol.2021.118155DOI Listing
September 2021

MAGIC: Manifold and Graph Integrative Convolutional Network for Low-Dose CT Reconstruction.

IEEE Trans Med Imaging 2021 Jun 10;PP. Epub 2021 Jun 10.

Low-dose computed tomography (LDCT) scans, which can effectively alleviate the radiation problem, will degrade the imaging quality. In this paper, we propose a novel LDCT reconstruction network that unrolls the iterative scheme and performs in both image and manifold spaces. Because patch manifolds of medical images have low-dimensional structures, we can build graphs from the manifolds. Then, we simultaneously leverage the spatial convolution to extract the local pixel-level features from the images and incorporate the graph convolution to analyze the nonlocal topological features in manifold space. The experiments show that our proposed method outperforms both the quantitative and qualitative aspects of state-of-the-art methods. In addition, aided by a projection loss component, our proposed method also demonstrates superior performance for semi-supervised learning. The network can remove most noise while maintaining the details of only 10% (40 slices) of the training data labeled.
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http://dx.doi.org/10.1109/TMI.2021.3088344DOI Listing
June 2021

Delayed Rise of Oral Fluid Antibodies, Elevated BMI, and Absence of Early Fever Correlate With Longer Time to SARS-CoV-2 RNA Clearance in a Longitudinally Sampled Cohort of COVID-19 Outpatients.

Open Forum Infect Dis 2021 Jun 16;8(6):ofab195. Epub 2021 Apr 16.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Sustained molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the upper respiratory tract (URT) in mild to moderate coronavirus disease 2019 (COVID-19) is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection.

Methods: Ninety-five symptomatic outpatients self-collected midturbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models.

Results: Viral RNA clearance, as measured by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR), in 507 URT samples occurred a median (interquartile range) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR-positive samples tested. All participants but 1 with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.92-0.99; = .020) and body mass index (BMI) ≥25 kg/m (aHR, 0.37; 95% CI, 0.18-0.78; = .009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as 1 of first 3 COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR, 2.06; 95% CI, 1.02-4.18; = .044).

Conclusions: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.
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http://dx.doi.org/10.1093/ofid/ofab195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083254PMC
June 2021

CT Reconstruction with PDF: Parameter-Dependent Framework for Data from Multiple Geometries and Dose Levels.

IEEE Trans Med Imaging 2021 Jun 4;PP. Epub 2021 Jun 4.

The current mainstream computed tomography (CT) reconstruction methods based on deep learning usually need to fix the scanning geometry and dose level, which significantly aggravates the training costs and requires more training data for real clinical applications. In this paper, we propose a parameter-dependent framework (PDF) that trains a reconstruction network with data originating from multiple alternative geometries and dose levels simultaneously. In the proposed PDF, the geometry and dose level are parameterized and fed into two multilayer perceptrons (MLPs). The outputs of the MLPs are used to modulate the feature maps of the CT reconstruction network, which condition the network outputs on different geometries and dose levels. The experiments show that our proposed method can obtain competitive performance compared to the original network trained with either specific or mixed geometry and dose level, which can efficiently save extra training costs for multiple geometries and dose levels.
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http://dx.doi.org/10.1109/TMI.2021.3085839DOI Listing
June 2021

Topological structure of electrospun membrane regulates immune response, angiogenesis and bone regeneration.

Acta Biomater 2021 May 31. Epub 2021 May 31.

The Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu, Sichuan 610065, China. Electronic address:

The fate of biomaterials is orchestrated by biocompatibility and bioregulation characteristics, reported to be closely related to topographical structures. For the purpose to investigate the topography of fibrous membranes on the guided bone regeneration performance, we successfully fabricated poly (lactate-co-glycolate)/fish collagen/nano-hydroxyapatite (PFCH) fibrous membranes with random, aligned and latticed topography by electrospinning. The physical, chemical and biological properties of the three topographical PFCH membranes were systematically investigated by in vitro and in vivo experiments. The subcutaneous implantation of C57BL6 mice showed an acceptable mild foreign body reaction of all three topological membranes. Interestingly, the latticed PFCH membrane exhibited superior abilities to recruit macrophage/monocyte and induce angiogenesis. We further investigated the osteogenesis of the three topographical PFCH membranes via the critical-size calvarial bone defect model of rats and mice and the results suggested that latticed PFCH membrane manifested promising performance to promote angiogenesis through upregulation of the HIF-1α signaling pathway; thereby enhancing bone regeneration. Our research illustrated that the topological structure of fibrous membranes, as one of the characteristics of biomaterials, could regulate its biological functions, and the fibrous structure of latticed topography could serve as a favorable surface design of biomaterials for bone regeneration. STATEMENT OF SIGNIFICANCE: In material-mediated regeneration medicine, the interaction between the biomaterial and the host is key to successful tissue regeneration. The micro-and nano-structure becomes one of the most critical physical clues for designing biomaterials. In this study, we fabricated three topological electrospun membranes (Random, Aligned and Latticed) to understand how topological structural clues mediate bone tissue regeneration. Interestingly, we found that the Latticed topographical PFCH membrane promotes macrophage recruitment, angiogenesis, and osteogenesis in vivo, indicating the fibrous structure of latticed topography could serve as a favorable surface design of biomaterials for bone regeneration.
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http://dx.doi.org/10.1016/j.actbio.2021.05.042DOI Listing
May 2021

Carrier Blocking Layer Materials and Application in Organic Photodetectors.

Nanomaterials (Basel) 2021 May 26;11(6). Epub 2021 May 26.

Key Laboratory of Advanced Display and System Applications of Ministry of Education, Shanghai University, 149 Yanchang Road, Shanghai 200072, China.

As a promising candidate for next-generation photodetectors, organic photodetectors (OPDs) have gained increasing interest as they offer cost-effective fabrication methods using solution processes and a tunable spectral response range, making them particularly attractive for large area image sensors on lightweight flexible substrates. Carrier blocking layers engineering is very important to the high performance of OPDs that can select a certain charge carriers (holes or electrons) to be collected and suppress another carrier. Carrier blocking layers of OPDs play a critical role in reducing dark current, boosting their efficiency and long-time stability. This Review summarizes various materials for carrier blocking layers and some of the latest progress in OPDs. This provides the reader with guidelines to improve the OPD performance via carrier blocking layers engineering.
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http://dx.doi.org/10.3390/nano11061404DOI Listing
May 2021

Comparison of Duration of Response vs Conventional Response Rates and Progression-Free Survival as Efficacy End Points in Simulated Immuno-oncology Clinical Trials.

JAMA Netw Open 2021 May 3;4(5):e218175. Epub 2021 May 3.

Merck & Co Inc, Kenilworth, New Jersey.

Importance: Phase 2 trials and early efficacy end points play a crucial role in informing decisions about whether to continue to phase 3 trials. Conventional end points, such as objective response rate (ORR) and progression-free survival (PFS), have demonstrated inconsistent associations with overall survival (OS) benefits in immune checkpoint inhibitor (ICI) trials. Restricted mean duration of response (DOR) is a rigorous metric that combines both response status and duration information. However, its utility in clinical development has not been comprehensively explored.

Objective: To determine whether using restricted mean DOR in phase 2 trials can advance promising regimens to phase 3 trials sooner and eliminate unfavorable regimens earlier and with a higher degree of confidence compared with PFS and ORR.

Design, Setting, And Participants: This simulated modeling study randomized phase 2 screening trials by resampling 1376 patients from 2 completed randomized phase 3 trials of ICIs. Data were analyzed from August 2019 to July 2020.

Exposures: Use of ICIs.

Main Outcomes And Measures: Restricted mean DOR, PFS, ORR, and OS were estimated and compared between groups. Three scenarios were considered: (1) significant differences in OS, PFS, and ORR; (2) significant differences in OS and noticeable differences in ORR but not PFS; and (3) no differences in OS, PFS, or ORR. For each setting, 5000 randomized phase 2 trials with different sample sizes were simulated, with additional censoring applied to mimic staggered accruals and ensure fair comparisons between different analysis methods. Probabilities of concluding positive phase 2 trials using PFS, ORR, and DOR were summarized and compared.

Results: The restricted mean DOR difference correctly estimated a positive OS benefit more frequently than did the ORR or PFS tests, across different sample sizes, significance levels, and censoring levels evaluated. When both OS and PFS differed, the ranges of true-positive or power rates were 79.2% to 98.7% for DOR, 56.3% to 93.2% for PFS, and 67.0% to 96.0% for ORR. When OS differed but PFS did not, the ranges of power rates were 24.0% to 76.0% for DOR, 3.0% to 19.0% for PFS, and 10.5% to 38.0% for ORR. When OS was similar, the false-positive rate of restricted mean DOR test was close to the chosen significance level.

Conclusions And Relevance: These findings suggest that restricted mean DOR in randomized phase 2 trials is potentially more sensitive and useful than PFS and ORR in estimating the subsequent phase 3 conclusions and, thus, may be considered to complementarily facilitate decision-making in future clinical development.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.8175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164100PMC
May 2021

Electron-Catalyzed Dehydrogenation in a Single-Molecule Junction.

J Am Chem Soc 2021 Jun 27;143(22):8476-8487. Epub 2021 May 27.

Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.

Investigating how electrons propagate through a single molecule is one of the missions of molecular electronics. Electrons, however, are also efficient catalysts for conducting radical reactions, a property that is often overlooked by chemists. Special attention should be paid to electron catalysis when interpreting single-molecule conductance results for the simple reason that an unexpected reaction mediated or triggered by electrons might take place in the single-molecule junction. Here, we describe a counterintuitive structure-property relationship that molecules, both linear and cyclic, employing a saturated bipyridinium-ethane backbone, display a similar conductance signature when compared to junctions formed with molecules containing conjugated bipyridinium-ethene backbones. We describe an ethane-to-ethene transformation, which proceeds in the single-molecule junction by an electron-catalyzed dehydrogenation. Electrochemically based ensemble experiments and theoretical calculations have revealed that the electrons trigger the redox process, and the electric field promotes the dehydrogenation. This finding not only demonstrates the importance of electron catalysis when interpreting experimental results, but also charts a pathway to gaining more insight into the mechanism of electrocatalytic hydrogen production at the single-molecule level.
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http://dx.doi.org/10.1021/jacs.1c03141DOI Listing
June 2021

Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing.

Sci Adv 2021 May 26;7(22). Epub 2021 May 26.

Department of Oral Implantology and State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.

The structural properties of biomaterials play crucial roles in guiding cell behavior and influencing immune responses against the material. We fabricated electrospun membranes with three types of surface topography (random, aligned, and latticed), introduced them to dorsal skin excisional wounds in mice and rats, and evaluated their effects on wound healing and immunomodulatory properties. An overview of different immune cells in the microenvironment with the help of single-cell RNA sequencing revealed diverse cellular heterogeneity in vivo. The time course of immune response was advanced toward an adaptive immunity-dominant stage by the aligned scaffold. In mice without mature T lymphocytes, lack of wound-induced hair neogenesis indicated a regulatory role of T cells on hair follicle regeneration. The microenvironment around scaffolds involved an intricate interplay of immune and cutaneous cells.
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http://dx.doi.org/10.1126/sciadv.abf0787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153724PMC
May 2021

Development of a 3D printable and highly stretchable ternary organic-inorganic nanocomposite hydrogel.

J Mater Chem B 2021 Jun;9(22):4535-4545

Functional Polymer Materials, Chair for Advanced Materials Synthesis, Institute for Functional Materials and Biofabrication, Department of Chemistry and Pharmacy, Julius-Maximilians-University Würzburg, Röntgenring 11, 97070 Würzburg, Germany. and Soft Matter Chemistry, Department of Chemistry, and Helsinki Institute of Sustainability Science, Faculty of Science, University of Helsinki, 00014 Helsinki, Finland.

Hydrogels that can be processed with additive manufacturing techniques and concomitantly possess favorable mechanical properties are interesting for many advanced applications. However, the development of novel ink materials with high intrinsic 3D printing performance has been proven to be a major challenge. Herein, a novel 3D printable organic-inorganic hybrid hydrogel is developed from three components, and characterized in detail in terms of rheological property, swelling behavior and composition. The nanocomposite hydrogel combines a thermoresponsive hydrogel with clay LAPONITE® XLG and in situ polymerized poly(N,N-dimethylacrylamide). Before in situ polymerization, the thermogelling and shear thinning properties of the thermoresponsive hydrogel provides a system well-suited for extrusion-based 3D printing. After chemical curing of the 3D-printed constructs by free radical polymerization, the resulting interpenetrating polymer network hydrogel shows excellent mechanical strength with a high stretchability to a tensile strain at break exceeding 550%. Integrating with the advanced 3D-printing technique, the introduced material could be interesting for a wide range of applications including tissue engineering, drug delivery, soft robotics and additive manufacturing in general.
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http://dx.doi.org/10.1039/d1tb00484kDOI Listing
June 2021

Transcriptomics identifies STAT3 as a key regulator of hippocampal gene expression and anhedonia during withdrawal from chronic alcohol exposure.

Transl Psychiatry 2021 May 20;11(1):298. Epub 2021 May 20.

Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA.

Alcohol use disorder (AUD) is highly comorbid with depression. Withdrawal from chronic alcohol drinking results in depression and understanding brain molecular mechanisms that drive withdrawal-related depression is important for finding new drug targets to treat these comorbid conditions. Here, we performed RNA sequencing of the rat hippocampus during withdrawal from chronic alcohol drinking to discover key signaling pathways involved in alcohol withdrawal-related depressive-like behavior. Data were analyzed by weighted gene co-expression network analysis to identify several modules of co-expressed genes that could have a common underlying regulatory mechanism. One of the hub, or highly interconnected, genes in module 1 that increased during alcohol withdrawal was the transcription factor, signal transducer and activator of transcription 3 (Stat3), a known regulator of immune gene expression. Total and phosphorylated (p)STAT3 protein levels were also increased in the hippocampus during withdrawal after chronic alcohol exposure. Further, pSTAT3 binding was enriched at the module 1 genes Gfap, Tnfrsf1a, and Socs3 during alcohol withdrawal. Notably, pSTAT3 and its target genes were elevated in the postmortem hippocampus of human subjects with AUD when compared with control subjects. To determine the behavioral relevance of STAT3 activation during alcohol withdrawal, we treated rats with the STAT3 inhibitor stattic and tested for sucrose preference as a measure of anhedonia. STAT3 inhibition alleviated alcohol withdrawal-induced anhedonia. These results demonstrate activation of STAT3 signaling in the hippocampus during alcohol withdrawal in rats and in human AUD subjects, and suggest that STAT3 could be a therapeutic target for reducing comorbid AUD and depression.
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http://dx.doi.org/10.1038/s41398-021-01421-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170676PMC
May 2021

Trends in cause-related comorbidities in hospitalized patients with secondary hypertension in China from 2013 to 2016: a retrospective analysis of hospital quality monitoring system data.

J Hypertens 2021 May 10. Epub 2021 May 10.

Department of Cardiology, Peking University First Hospital, Beijing People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Peking University People's Hospital, Beijing The First Affiliated Hospital of Fujian Medical University, Fujian First Hospital of Shanxi Medical University, Shanxi Huashan Hospital, Fudan University, Shanghai The First Affiliated Hospital with Nanjing Medical University, Jiangsu Scientific Project department, China Standard Medical Information Research Center, Shenzhen Clinical Trial Unit, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou Bureau of Medical Administration National Health Commission of the People's Republic of China, Beijing Tibet Autonomous Region People's Hospital, Tibet, China.

Background: Secondary hypertension has emerged as a major public health problem in China. Early diagnosis and treatment can significantly improve the clinical outcomes. However, data on the current cause composition in China are seldom reported.

Objective: To describe the trends in cause-related comorbidities in hospitalized patients with secondary hypertension in China from 2013 to 2016.

Methods: This was a retrospective analysis based on the national Hospital Quality Monitoring System (HQMS) database, which collects information from the front pages of in-hospital medical records. Hospitalized patients with secondary hypertension from 746 tertiary hospitals that consistently uploaded data to the HQMS from 2013 to 2016 were enrolled. All diagnoses were identified using International Classification of Diseases version 10 (ICD-10) diagnostic codes. Descriptive analyses were used to determine the proportions of secondary hypertension causes and changing trends over 4 years.

Result: The study collected data on 402 371 hospitalized patients with secondary hypertension from the HQMS during 2013-2016. Secondary hypertension caused by renal parenchymal disease ranked first and accounted for more than 50%. Obstructive sleep apnea syndrome (OSAS) followed closely with a rate of approximately 25%. Primary aldosteronism presented the highest proportion among all causes of endocrine hypertension. Regarding longitudinal changes over time, the rates of renal hypertension showed a significant downward trend from 2013 to 2016 (P < 0.001). In contrast, OSAS, endocrine hypertension, renal vascular disease, and aorta diseases maintained a significant upward trend from 2013 to 2016 (P < 0.001). The rates of these diseases in women with common secondary hypertension was higher than that of men, except in patients with OSAS (P < 0.001). In addition, renal parenchymal diseases and renal vascular diseases gradually decreased with age, whereas OSAS and aortic diseases gradually increased with age. The proportion of endocrine hypertension in the middle-aged group was higher than the other two age groups.

Conclusion: The study provides important information on the changing trends of cause rate of secondary hypertension modified by age and sex in China during 2013-2016. Renal parenchymal disease is still the most common cause of secondary hypertension with a decreasing trend, followed by OSAS with an increasing trend.
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http://dx.doi.org/10.1097/HJH.0000000000002891DOI Listing
May 2021

Stage-dependent conditional survival and failure hazard of non-metastatic nasopharyngeal carcinoma after intensity-modulated radiation therapy: Clinical implications for treatment strategies and surveillance.

Cancer Med 2021 Jun 6;10(11):3613-3621. Epub 2021 May 6.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Purpose: Conditional survival (CS) and failure hazard estimations can provide important dynamic prognostic information for clinical decision-making and surveillance counseling. The current study aimed to investigate the CS and dynamic failure hazard in non-metastatic nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).

Methods: Conditional overall survival (COS) and progression-free survival (CPFS) estimates adjusted for age and gender against each AJCC 8th stage were calculated. Multivariable Cox regression (MCR) models were fitted in the entire population at baseline and subsequently separate MCR models were fitted in patients who have maintained event-free time of 1 to 10 years to generate respective hazard ratio (HR). Annual hazard rates of death and progression over 10 years for each stage were also estimated.

Results: A total of 1993 patients were eligible for analysis. The estimated 5-year OS and PFS for entire cohort were 79.0% and 70.7% at initial diagnosis. After 5 years of event-free follow-up, additional 5-year COS and CPFS increased to 85.9% and 85.5%, respectively. Stage I/II maintained dramatically favorable CS and low hazard (< 5%) of death and progression over time. Relative to stage I/II, stage III manifested non-significantly higher failure hazard for the first 3 years of survivorship and approached to similar level of stage I/II afterwards. Stage IVA presented most impressive improvement in terms of both COS (∆=9.8%) and CPFS (∆ = 16.8%) whereas still drastically inferior to that of stage I-III across all conditional time points. After 4 years of follow-up, progression hazard of stage IVA became relatively steady of approximate 6%.

Conclusions: Survival prospect of non-metastatic NPC improves over years with distinct dynamic patterns across stages, providing important implications for personalized decision-making in terms of both clinical management and surveillance counseling. Stage-dependent and hazard-adapted clinical management and surveillance are warranted.
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http://dx.doi.org/10.1002/cam4.3917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178506PMC
June 2021

Construction of dual-functional nitrogen-enriched fluorescent porous organic polymers for detecting m-dinitrobenzene, picric acid and capturing iodine.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Sep 17;258:119852. Epub 2021 Apr 17.

AnHui Province Key Laboratory of Optoelectronic and Magnetism Functional Materials, School of Chemistry and Chemical Engineering, Anqing Normal University, Anqing 246011, China.

Two novel nitrogen-enriched porous organic polymers (POPs), HBP and TBP, were constructed via nucleophilic substitution reactions with high nitrogen contents up to 24.91% and 32.92% for sensing to nitroaromatic compounds (NACs) and adsorbing iodine. They were all systematically characterized by solid-state C NMR, FT-IR, elemental analysis, solid-state UV-Vis, and other material analysis methods. The experimental data proved that both POPs possess high chemical and thermal stability, excellent fluorescence performance, and porous properties with Brunauer-Emmett-Teller (BET) specific surface areas of 32.88 and 68.00 m g. The two POPs have dual functions of fluorescence sensing and adsorption. On the one hand, due to their excellent conjugated properties and nitrogen-enriched structures, HBP and TBP exhibited incredibly high sensitivity to m-dinitrobenzene (m-DNB) and picric acid (PA) with K values of 2.57 × 10 and 4.93 × 10 L mol and limits of detection of 1.17 × 10 and 6.08 × 10 mol L, respectively. On the other hand, owing to the plenty of nitrogen affinity sites, they exhibited excellent volatile iodine adsorption with 2.23 and 2.66 g g, respectively.
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http://dx.doi.org/10.1016/j.saa.2021.119852DOI Listing
September 2021

Charge transport physics of a unique class of rigid-rod conjugated polymers with fused-ring conjugated units linked by double carbon-carbon bonds.

Sci Adv 2021 Apr 28;7(18). Epub 2021 Apr 28.

Optoelectronics Group, Cavendish Laboratory, JJ Thomson Avenue, Cambridge CB3 0HE, UK.

We investigate the charge transport physics of a previously unidentified class of electron-deficient conjugated polymers that do not contain any single bonds linking monomer units along the backbone but only double-bond linkages. Such polymers would be expected to behave as rigid rods, but little is known about their actual chain conformations and electronic structure. Here, we present a detailed study of the structural and charge transport properties of a family of four such polymers. By adopting a copolymer design, we achieve high electron mobilities up to 0.5 cm V s Field-induced electron spin resonance measurements of charge dynamics provide evidence for relatively slow hopping over, however, long distances. Our work provides important insights into the factors that limit charge transport in this unique class of polymers and allows us to identify molecular design strategies for achieving even higher levels of performance.
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http://dx.doi.org/10.1126/sciadv.abe5280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081371PMC
April 2021

Molecular mechanism of lateral bud differentiation of Pinus massoniana based on high-throughput sequencing.

Sci Rep 2021 Apr 27;11(1):9033. Epub 2021 Apr 27.

Guangxi Forestry Research Institute of Science, Nanning, 530002, People's Republic of China.

Knot-free timber cultivation is an important goal of forest breeding, and lateral shoots affect yield and stem shape of tree. The purpose of this study was to analyze the molecular mechanism of lateral bud development by removing the apical dominance of Pinus massoniana young seedlings through transcriptome sequencing and identify key genes involved in lateral bud development. We analyzed hormone contents and transcriptome data for removal of apical dominant of lateral buds as well as apical and lateral buds of normal development ones. Data were analyzed using an comprehensive approach of pathway- and gene-set enrichment analysis, Mapman visualization tool, and gene expression analysis. Our results showed that the contents of auxin (IAA), Zea and strigolactone (SL) in lateral buds significantly increased after removal of apical dominance, while abscisic acid (ABA) decreased. Gibberellin (GA) metabolism, cytokinin (CK), jasmonic acid, zeatin pathway-related genes positively regulated lateral bud development, ABA metabolism-related genes basically negatively regulated lateral bud differentiation, auxin, ethylene, SLs were positive and negative regulation, while only A small number of genes of SA and BRASSINOSTEROID, such as TGA and TCH4, were involved in lateral bud development. In addition, it was speculated that transcription factors such as WRKY, TCP, MYB, HSP, AuxIAA, and AP2 played important roles in the development of lateral buds. In summary, our results provided a better understanding of lateral bud differentiation and lateral shoot formation of P. massoniana from transcriptome level. It provided a basis for molecular characteristics of side branch formation of other timber forests, and contributed to knot-free breeding of forest trees.
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http://dx.doi.org/10.1038/s41598-021-87787-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079368PMC
April 2021

Bone density and fracture risk following SBRT for non-spine bone metastases.

J Radiosurg SBRT 2021 ;7(3):199-206

Johns Hopkins University School of Medicine, Department of Radiation Oncology and Molecular Radiation Sciences, Baltimore, MD, USA.

Purpose/methods: This retrospective study evaluated local recurrence (LR) and fracture risk in non-spine bone metastases treated with SBRT.

Results: 181 lesions in 116 patients are reported. The median dose was 27 Gy (range 15-40) in 3 fractions (range 1-6). The cumulative incidence of LR was 2.8%, 7.2% and 12.5% at 6 mo, 1 yr and 2 yrs. Fractures occurred in 11 lesions (6%). Radioresistant histology and increasing PTV predicted for LR on univariate analysis, while rib location was associated with control. Increasing PTV remained a significant predictor for LR on multivariate analysis. Univariate predictors of fracture risk included female gender, lytic lesions and poorer KPS. Average CT-approximated L1 trabecular attenuation in patients with fracture was significantly lower than in patients without fracture (112.2 vs. 142.6 Hounsfield units).

Conclusion: In the largest series to date, we report excellent local control for SBRT to non-spine bone metastases and a novel relationship between CT-based bone quality assessment and fracture risk.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055232PMC
January 2021

Preconceptional and the first trimester exposure to PM and offspring neurodevelopment at 24 months of age: Examining mediation by maternal thyroid hormones in a birth cohort study.

Environ Pollut 2021 Apr 11;284:117133. Epub 2021 Apr 11.

Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, And State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. Electronic address:

Prenatal fine particulate matter (PM) exposure has been associated with impaired offspring neurodevelopment; however, the association of PM exposure during preconception with offspring's neurodevelopment and factors responsible for this association are still unclear. This study estimated the associations of PM exposure during preconception and the first trimester with offspring neurodevelopment and evaluated whether maternal thyroid hormones mediate these associations. We recruited 1329 mother-child pairs between 2013 and 2015 in Wuhan, China. PM exposure levels of each woman during the 3 months preconception and the first trimester were estimated using land-use regression models. Offspring neurodevelopment characterized by mental developmental index (MDI) and psychomotor developmental index (PDI) were measured at 24 months of age. Maternal serum levels of free thyroxine (FT3), free triiodothyronine (FT4), and thyroid-stimulating hormone (TSH) during early pregnancy were measured of a subset of the 1329 women (551 women). Generalized estimation equation and general linear regression models were used to estimate the associations between maternal PM exposure, thyroid hormones, and offspring neurodevelopment. After adjusting for potential confounders, we found that either among all participants or the subset, PM exposure during preconception and the first trimester was negatively associated with offspring PDI. Double increment in the first trimester PM exposure was significantly associated with 3.43 and 6.48 points decrease in offspring MDI. In the subset, each doubling of PM exposure during preconception and the first trimester was significantly associated with 7.93 and 8.02 points decrease in maternal FT4 level, respectively. Increased maternal FT4, in turn, was associated with increased PDI (β = 16.69, 95% CI: 5.39, 27.99). About 7.7% (95% CI: 2.0%-19.4%) and 8.6% (95% CI: 3.0%, 22.1%) of the effect of PM exposure during preconception on offspring PDI was mediated through maternal FT4 and the FT4/FT3 ratio, respectively.
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http://dx.doi.org/10.1016/j.envpol.2021.117133DOI Listing
April 2021

Suppressing bias stress degradation in high performance solution processed organic transistors operating in air.

Nat Commun 2021 04 21;12(1):2352. Epub 2021 Apr 21.

Department of Physics and Center for Functional Materials, Wake Forest University, Winston Salem, NC, USA.

Solution processed organic field effect transistors can become ubiquitous in flexible optoelectronics. While progress in material and device design has been astonishing, low environmental and operational stabilities remain longstanding problems obstructing their immediate deployment in real world applications. Here, we introduce a strategy to identify the most probable and severe degradation pathways in organic transistors and then implement a method to eliminate the main sources of instabilities. Real time monitoring of the energetic distribution and transformation of electronic trap states during device operation, in conjunction with simulations, revealed the nature of traps responsible for performance degradation. With this information, we designed the most efficient encapsulation strategy for each device type, which resulted in fabrication of high performance, environmentally and operationally stable small molecule and polymeric transistors with consistent mobility and unparalleled threshold voltage shifts as low as 0.1 V under the application of high bias stress in air.
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http://dx.doi.org/10.1038/s41467-021-22683-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060299PMC
April 2021

A population-based study on associations of stool microbiota with atopic diseases in school-age children.

J Allergy Clin Immunol 2021 Apr 15. Epub 2021 Apr 15.

Division of Respiratory Medicine and Allergolog, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Division of Neonatology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address:

Background: Infants with less diverse gut microbiota seem to have higher risks of atopic diseases in early life, but any associations at school age are unclear.

Objectives: This study sought to examine the associations of diversity, relative abundance, and functional pathways of stool microbiota with atopic diseases in school-age children.

Methods: We performed a cross-sectional study within an existing population-based prospective cohort among 1440 children 10 years of age. On stool samples, 16S ribosomal RNA gene sequencing was performed, and taxonomic and functional tables were produced. Physician-diagnosed eczema, allergy, and asthma were measured by questionnaires, allergic sensitization by skin prick tests, and lung function by spirometry.

Results: The α-diversity of stool microbiota was associated with a decreased risk of eczema (odds ratio [OR], 0.98; 95% CI, 0.97, 1.00), and β-diversity was associated with physician-diagnosed inhalant allergy (R = 0.001; P = .047). Lachnospiraceae, Ruminococcaceae_UCG-005, and Christensenellaceae_R-7_group species were associated with decreased risks of eczema, inhalant allergic sensitization, and physician-diagnosed inhalant allergy (OR range, 0.88-0.94; 95% CI range, 0.79-0.96 to 0.88-0.98), while Agathobacter species were associated with an increased risk of physician-diagnosed inhalant allergy (OR, 1.23; 95% CI, 1.08-1.42). Functional pathways related to heme and terpenoid biosynthesis were associated with decreased risks of physician-diagnosed inhalant allergy and asthma (OR range, 0.89-0.86; 95% CI range, 0.80-0.99 to 0.73-1.02). No associations of stool microbiota with lung function were observed.

Conclusions: The diversity, relative abundance and functional pathways of stool microbiota were most consistently associated with physician-diagnosed inhalant allergy in school-age children and less consistently with other atopic diseases.
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http://dx.doi.org/10.1016/j.jaci.2021.04.001DOI Listing
April 2021

VPS34 suppression reverses osimertinib resistance via simultaneously inhibiting glycolysis and autophagy.

Carcinogenesis 2021 Jun;42(6):880-890

Department of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China.

Autophagy and glycolysis are associated with osimertinib resistance. The energy complement and dynamic balance between these two processes make it difficult to block the process of drug resistance; breaking the complementary relationship between them may effectively overcome drug resistance. However, the exact mechanisms and the key players for regulating autophagy and glycolysis remain unclear. In this study, we demonstrate that autophagy and glycolysis levels in osimertinib-resistant cells were markedly higher than parental cells, and a dynamic balance existed between them. Inhibition of the class III phosphoinositide 3-kinase vacuolar protein sorting 34 (VPS34) with 3-methyladenine or small interfering RNA can not only inhibit abnormally enhanced autophagy but also inhibit glycolysis by inhibiting the location of epidermal growth factor receptor (EGFR) and the expression of hexokinase II. By demonstrating that VPS34 is the key player controlling autophagy and glycolysis simultaneously, our study may provide a new strategy for overcoming osimertinib resistance for treatment of EGFR-mutant non-small cell lung cancer patients.
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http://dx.doi.org/10.1093/carcin/bgab030DOI Listing
June 2021

Sympathetic Nervous System Mediates Cardiac Remodeling After Myocardial Infarction in a Circadian Disruption Model.

Front Cardiovasc Med 2021 26;8:668387. Epub 2021 Mar 26.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Circadian rhythms have a considerable impact on the daily physiology of the heart, and their disruption causes pathology. Several studies have revealed that circadian disruption impaired cardiac remodeling after myocardial infarction (MI); however, the underlying brain-heart mechanisms remain unknown. We aim to discuss whether circadian disruption facilitates cardiac remodeling after MI by activating sympathetic nervous system. Rats were randomly divided into three groups: Sham group (Sham), MI group (MI), and MI+ circadian disruption group (MI+Dis); rats were treated with pseudorabies virus (PRV) injections for trans-synaptic retrograde tracing; rats were randomly divided into two groups: MI+ circadian disruption + Empty Vector+ clozapine N-oxide (CNO) (Empty Vector), and MI+ circadian disruption + hM4D(Gi)+ CNO [hM4D(Gi)]. Circadian disruption significantly facilitated cardiac remodeling after MI with lower systolic function, larger left ventricular volume, and aggravated cardiac fibrosis. Cardiac sympathetic remodeling makers and serum norepinephrine levels were also significantly increased by circadian disruption. PRV virus-labeled neurons were identified in the superior cervical ganglion (SCG), paraventricular nucleus (PVN), and suprachiasmatic nucleus (SCN) regions. Ganglionic blockade via designer receptors exclusively activated by designer drugs (DREADD) technique suppressed the activity of sympathetic nervous system and significantly alleviated the disruption-related cardiac dysfunction. Circadian disruption adversely affected cardiac remodeling after MI possibly by activating sympathetic nervous system, and suppressing sympathetic activity can attenuate this disruption-related cardiac dysfunction.
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http://dx.doi.org/10.3389/fcvm.2021.668387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032890PMC
March 2021

Effects of partial substitution of NaCl on myofibrillar protein properties from pearl mussel Hyriopsis cumingii muscle: Structural characteristics and aggregation behaviors.

Food Chem 2021 Sep 31;356:129734. Epub 2021 Mar 31.

College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 30045, China. Electronic address:

The effects of NaCl and its partial substitutes (KCl, MgCl and CaCl) on solubility, structural characteristics and aggregation behaviors of myofibrillar protein (MP) from pearl mussel muscle were investigated and compared. MP at 0.6 M NaCl was beneficial to protein unfolding and showed excellent potential functional properties. When NaCl was substituted in low level, MPs also showed good solubility and ordered microstructure as well as NaCl, especially MgCl and CaCl, due to the unfolding of α-helical structures and subsequently exposed tyrosine residues and hydrophobic groups. However, the obviously increased disulfide bonds and hydrophobic interactions in high substitution level indicated the excessive non-sodium salts had negative effects on molecular rearrangement, leading to irregular and overly tight of microstructure. Thus, NaCl partially substituted by KCl, MgCl and CaCl in low substitution level is promising to improve functional properties of MP in low-sodium meat products.
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http://dx.doi.org/10.1016/j.foodchem.2021.129734DOI Listing
September 2021

E47 upregulates ΔNp63α to promote growth of squamous cell carcinoma.

Cell Death Dis 2021 04 8;12(4):381. Epub 2021 Apr 8.

Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.

Targeted therapy has greatly improved both survival and prognosis of cancer patients. However, while therapeutic treatment of adenocarcinoma has been advanced greatly, progress in treatment of squamous cell carcinoma (SCC) has been slow and ineffective. Therefore, it is of great importance to decipher mechanisms and identify new drug targets involved in squamous cell carcinoma development. In this study, we demonstrate that E47 plays the distinctive and opposite roles on cell proliferation in adenocarcinoma and squamous cell carcinoma. While E47 suppresses cell proliferation in adenocarcinoma cells, it functions as a oncoprotein to promote cell proliferation and tumor growth of squamous cell carcinoma. Mechanistically, we show that E47 can directly bind to the promoter and transactivate ΔNp63 gene expression in squamous cell carcinoma cells, resulting in upregulation of cyclins D1/E1 and downregulation of p21, and thereby promoting cell proliferation and tumor growth. We further show that expression of E2A (E12/E47) is positively correlated with p63 and that high expression of E2A is associated with poor outcomes in clinical samples of squamous cell carcinoma. These results highlight that the E47-ΔNp63α axis may be potential therapeutic targets for treatment of squamous cell carcinoma.
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http://dx.doi.org/10.1038/s41419-021-03662-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032790PMC
April 2021

External Validation of the Bone Metastases Ensemble Trees for Survival (BMETS) Machine Learning Model to Predict Survival in Patients With Symptomatic Bone Metastases.

JCO Clin Cancer Inform 2021 03;5:304-314

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.

Purpose: The Bone Metastases Ensemble Trees for Survival (BMETS) model uses a machine learning algorithm to estimate survival time following consultation for palliative radiation therapy for symptomatic bone metastases (SBM). BMETS was developed at a tertiary-care, academic medical center, but its validity and stability when applied to external data sets are unknown.

Patients And Methods: Patients treated with palliative radiation therapy for SBM from May 2013 to May 2016 at two hospital-based community radiation oncology clinics were included, and medical records were retrospectively reviewed to collect model covariates and survival time. The Kaplan-Meier method was used to estimate overall survival from consultation to death or last follow-up. Model discrimination was estimated using time-dependent area under the curve (tAUC), which was calculated using survival predictions from BMETS based on the initial training data set.

Results: A total of 216 sites of SBM were treated in 182 patients. Most common histologies were breast (27%), lung (23%), and prostate (23%). Compared with the BMETS training set, the external validation population was older (mean age, 67 62 years; < .001), had more primary breast (27% 19%; = .03) and prostate cancer (20% 12%; = .01), and survived longer (median, 10.7 6.4 months). When the BMETS model was applied to the external data set, tAUC values at 3, 6, and 12 months were 0.82, 0.77, and 0.77, respectively. When refit with data from the combined training and external validation sets, tAUC remained 0.79.

Conclusion: BMETS maintained high discriminative ability when applied to an external validation set and when refit with new data, supporting its generalizability, stability, and the feasibility of dynamic modeling.
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http://dx.doi.org/10.1200/CCI.20.00128DOI Listing
March 2021

Neural basis of corruption in power-holders.

Elife 2021 03 24;10. Epub 2021 Mar 24.

Laboratory of Neuroeconomics, Institut des Sciences Cognitives Marc Jeannerod, CNRS, Lyon, France.

Corruption often involves bribery, when a briber suborns a power-holder to gain advantages usually at a cost of moral transgression. Despite its wide presence in human societies, the neurocomputational basis of bribery remains elusive. Here, using model-based fMRI, we investigated the neural substrates of how a power-holder decides to accept or reject a bribe. Power-holders considered two types of moral cost brought by taking bribes: the cost of conniving with a fraudulent briber, encoded in the anterior insula, and the harm brought to a third party, represented in the right temporoparietal junction. These moral costs were integrated into a value signal in the ventromedial prefrontal cortex. The dorsolateral prefrontal cortex was selectively engaged to guide anti-corrupt behaviors when a third party would be harmed. Multivariate and connectivity analyses further explored how these neural processes depend on individual differences. These findings advance our understanding of the neurocomputational mechanisms underlying corrupt behaviors.
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http://dx.doi.org/10.7554/eLife.63922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990503PMC
March 2021

Association between nasal and nasopharyngeal bacterial colonization in early life and eczema phenotypes.

Clin Exp Allergy 2021 May 6;51(5):716-725. Epub 2021 Apr 6.

Department of Dermatology, University Medical Center Rotterdam, Erasmus MC, Rotterdam, The Netherlands.

Background: An association has been reported between early life Staphylococcus aureus nasal carriage and higher risk of childhood eczema, but it is unclear whether this relationship is causal and associations with other bacterial species are unclear.

Objective: To examine the associations of early life nasal and nasopharyngeal bacterial carriage with eczema phenotypes, and the direction of any associations identified.

Methods: Among 996 subjects of a population-based prospective cohort study, nasal swabs for Staphylococcus  aureus, and nasopharyngeal swabs for Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae were collected and cultured from age 6 weeks to 6 years. Never, early, mid-, late transient and persistent eczema phenotypes were identified from parental-reported physician-diagnosed eczema from age 6 months until 10 years. Multinomial regression models and cross-lagged models were applied.

Results: Staphylococcus aureus nasal carriage at 6 months was associated with an increased risk of early transient and persistent eczema (OR (95% CI): 2.69 (1.34, 5.39) and 4.17 (1.12, 15.51)). The associations between Staphylococcus aureus nasal carriage and eczema were mostly cross-sectional, and not longitudinal. No associations of Staphylococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza nasopharyngeal bacterial carriage with eczema and eczema phenotypes were observed (OR range (95% CI): 0.71 (0.35, 1.44) to 1.77 (0.84, 3.73)).

Conclusions: Early life Staphylococcus aureus nasal carriage, but not Staphylococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenza nasopharyngeal carriage, was associated with early transient and persistent eczema. Staphylococcus aureus nasal carriage and eczema were mostly cross-sectionally associated, and not longitudinally, making a causal relationship in either direction unlikely.
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http://dx.doi.org/10.1111/cea.13869DOI Listing
May 2021

Japanese encephalitis virus manipulates lysosomes membrane for RNA replication and utilizes autophagy components for intracellular growth.

Vet Microbiol 2021 Apr 8;255:109025. Epub 2021 Mar 8.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China; Key Laboratory of Zoonosis, Ministry of Agriculture and Rural Affairs, Guangzhou, 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, Guangzhou, 510642, China; Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou, 510642, China. Electronic address:

Japanese encephalitis virus is absolutely dependent on their host cells and has evolved various strategies to manipulate the cellular secretory pathways for viral replication. However, how cellular secretory pathways are hijacked, and the origin of the viral vesicles remains elusive during JEV replication. Here we show how JEV manipulates multiple components of the cellular secretory pathway, including autophagic machinery, to generate a superior environment for genome replication. We utilized double-strand RNA antibodies to label JEV RNA complex seeking the viral replication compartments and found that JEV genome replication takes place in lysosomes (LAMP1), not in autophagosomes (LC3). Subsequently, in situ hybridization results showed that viral RNAs (vRNAs) of JEV strongly colocalized with LAMP1. What surprised us was that JEV vRNAs markedly colocalized with LC3, indicating that autophagy plays an active role in JEV replication. Interestingly, we found that JEV utilized autophagic components for intracellular growth in an autophagy-dependent manner and the fusion of autophagosome-lysosome plays a positive role in JEV post-RNA replication processes. Collectively, our findings demonstrate that JEV can manipulate cellular secretory pathway to form genome replication organelles and exploit autophagy components for intracellular growth, providing new insights into the life cycle of JEV and uncovering an attractive target for antiviral drugs.
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http://dx.doi.org/10.1016/j.vetmic.2021.109025DOI Listing
April 2021

Purification and Structural Characterization of Dendrobium officinale Polysaccharides and Its Activities.

Chem Biodivers 2021 May 21;18(5):e2001023. Epub 2021 Apr 21.

Shijiazhuang Yiling Pharmaceutical Co., Ltd., No. 238 Tianshan Road, Hi Tech Industrial Development Zone, Shijiazhuang, 050035, P. R. China.

In this study, Dendrobium officinale polysaccharide (named DOPS-1) was isolated from the stems of Dendrobium officinale by hot-water extraction and purified by using Sephadex G-150 column chromatography. The structural characterization, antioxidant and cytotoxic activity were carried out. Based on the results of HPLC, GC, Congo red experiment, together with periodate oxidation, Smith degradation, SEM, FT-IR, and NMR spectral analysis, it expressed that DOPS-1 was largely composed of mannose, glucose and galacturonic acid in a molar ratio of 3.2 : 1.3 : 1. The molecular weight of DOPS-1 was 1530 kDa and the main chain was composed of (1→4)-β-D-Glcp, (1→4)-β-D-Manp and 2-O-acetyl-(1→4)-β-D-Manp. The measurement results of antioxidant activity showed that DOPS-1 had the strong scavenging activities on hydroxyl radicals, DPPH radicals and superoxide radicals and the high reducing ability in vitro. Moreover, DOPS-1 was cytotoxic to all three human cancer cells of MDA-MB-231, A549 and HepG2.
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http://dx.doi.org/10.1002/cbdv.202001023DOI Listing
May 2021