Publications by authors named "Wei Cao"

1,203 Publications

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Fragment-interconnected nitrogen-doped porous carbon nanosheets loaded with platinum group metals for highly boosted hydrogen evolution reaction in alkaline solution.

J Colloid Interface Sci 2021 Jul 23;605:528-536. Epub 2021 Jul 23.

Institute of Materials, China Academy of Engineering Physics, Jiangyou 621908, China. Electronic address:

The rational design and preparation of advanced electrocatalysts for the hydrogen evolution reaction (HER) under alkaline conditions is the key to achieving sustainable hydrogen production. Herein, a new type of nitrogen-doped porous carbon nanosheets (NPCN) loaded with platinum group metals (Pd, Pt or Ru) were prepared. The introduction of melamine not only realized the doping of N-species, but also optimized the morphology and surface functional groups of the prepared catalysts. The prepared Pd-NPCN, Pt-NPCN and Ru-NPCN with a metal loading of about 10 wt% showed outstanding HER activity (21, 9 and 11 mv at 10 mA cm current density), small Tafel slopes (49, 30 and 30 mV dec) and good stability in 1.0 M KOH. In addition, the mechanism of the introduction of melamine to improve the catalytic performance of HER was also discussed. Therefore, this work provides promising alternatives to traditional Pt-based catalysts, and is instructive for the design of high-efficiency alkaline HER catalysts.
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http://dx.doi.org/10.1016/j.jcis.2021.07.096DOI Listing
July 2021

The Influence of Corticosteroids, Immunosuppressants and Biologics on Patients With Inflammatory Bowel Diseases, Psoriasis and Rheumatic Diseases in the Era of COVID-19: A Review of Current Evidence.

Front Immunol 2021 8;12:677957. Epub 2021 Jul 8.

Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.

Patients with inflammatory bowel disease, psoriasis or other rheumatic diseases treated with corticosteroids, immunomodulators and biologics might face additional risk during COVID-19 epidemic due to their immunocompromised status. However, there was still no unanimous opinion on the use of these therapy during COVID-19 epidemic. Current studies suggested that systemic corticosteroids might increase the risk of hospitalization, as well as risks of ventilation, ICU, and death among patients with immune-mediated inflammatory diseases. Anti-TNF agent was associated with lower rate of hospitalization, as well as lower risks of ventilation, ICU, and death. No significant changes in rates of hospitalization, ventilation, ICU and mortality were observed in patients treated with immunomodulators or biologics apart from anti-TNF agents. The underlying mechanism of these results might be related to pathway of antiviral immune response and cytokine storm induced by SARS-COV-2 infection. Decision on the use of corticosteroids, immunomodulators and biologics should be made after weighing the benefits and potential risks based on individual patients.
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http://dx.doi.org/10.3389/fimmu.2021.677957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317986PMC
July 2021

Characteristics of the bacterial microbiota in the upper respiratory tract of children.

Eur Arch Otorhinolaryngol 2021 Jul 24. Epub 2021 Jul 24.

Department of Laboratory Medicine, School of Medicine, RenJi Hospital, Shanghai Jiao Tong University, Shanghai, China.

Purpose: The respiratory tract microbiota are deemed as the gatekeeper to health. Consequently, microbiota dysbiosis can lead to the development of diseases. To identify the exact origins of the localized pathogenic bacteria, we investigated bacterial composition in the upper airway tract.

Methods: Separate mucosal swabs were collected from nostril or oropharynx of each participant. Meanwhile, the lymphoid tissues including adenoids and tonsils were collected during operation. DNAs were exacted from all the samples for the following 16S rRNA analysis.

Results: At the phylum level, the basic bacterial structures in the adenoids, tonsils, oropharynx, and nostrils were generally similar: five main phyla Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Fusobacteria form the majority of the microbiota. However, across these four sites, the microbiota composition differed. More specifically, the bacterial composition in the nostrils was unique. There, Firmicutes and Actinobacteria were the most abundant phyla, while Bacteroides and Fusobacteria were the least abundant. At the genus level, Staphylococcus, Dolosigranulum, Corynebacterium, and Moraxella were the most plentiful, while Fusobacteria was the least ample. Across all sites, Streptococcus displayed similar abundances. Fusobacteria exhibited higher abundances in the lymphoid tissues and oropharynx. Haemophilus and Neisseria were more plentiful in the tonsils and oropharynx. Notably, Klebsiella, which is normally localized to the gut, was abundant in the adenoids and tonsils.

Conclusion: Our data indicate that promising pathogenic bacteria originate from all sites in the upper airway. The upper tract lymphoid tissues, normally considered as immune organs, may also serve as reservoirs for pathogenic bacteria.
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http://dx.doi.org/10.1007/s00405-021-07013-yDOI Listing
July 2021

Dual-signal electrochemiluminescence immunosensor for Neuron-specific enolase detection based on "dual-potential" emitter Ru(bpy) functionalized zinc-based metal-organic frameworks.

Biosens Bioelectron 2021 Jul 16;192:113505. Epub 2021 Jul 16.

Collaborative Innovation Center for Green Chemical Manufacturing and Accurate Detection, University of Jinan, Jinan, 250022, Shandong, China; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China. Electronic address:

Neuron-specific enolase (NSE) is the preferred marker for monitoring small cell lung cancer and neuroblastoma. We devised a dual-signal ratiometric electrochemiluminescence (ECL) sensing strategy for sensitive detection of NSE. In this work, Ru (bpy) functionalized zinc-based metal-organic framework (Ru-MOF-5) nanoflowers (NFs) with plentiful carboxyl groups provide an excellent biocompatible sensing platform for the construction of immunosensor. Importantly, Ru-MOF-5 NFs possess stable and efficient "dual-potential" ECL emission of cathode (-1.5 V) and anode (1.5 V) in the existence of co-reactant KSO. Simultaneously, the cathode ECL emitter ZnO-AgNPs are employed as the secondary antibody marker, whose participation amplify the cathode ECL signal as well attenuate the anode ECL emission of Ru-MOF-5 NFs. By monitoring the ECL dual-signal of -1.5 V and 1.5 V and calculating their ratios, a ratiometric strategy of quantified readout proportional is implemented for the proposed immunosensor to precise analyze NSE. Based on optimization conditions, the ECL immunosensor displays the wide linear range of 0.0001 ng/mL to 200 ng/mL and the minimum detection limit is 0.041 pg/mL. The "dual-potential" ratiometric ECL immunosensor effectively reduces system error or background signal by self-calibration from both emissions and improves detection reliability. The dual-signal ratiometric strategy with satisfactory reproducibility and stability provides further development possibilities for other biomolecular detection and analysis.
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http://dx.doi.org/10.1016/j.bios.2021.113505DOI Listing
July 2021

Crohn's disease with pulmonary granuloma in a child: a case report and review of the literature.

Transl Pediatr 2021 Jun;10(6):1728-1736

Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

Crohn's disease (CD) is a chronic granulomatous disease that affects the gastrointestinal system. Additionally, CD has multiple extraintestinal manifestations, and bronchopulmonary manifestations are extremely rare. Pulmonary lesions can occur before the diagnosis of CD; thus, pulmonary manifestations are often overlooked, which leads to misdiagnoses. Herein, we present a case with pulmonary nodules being exhibited before the patient was diagnosed with CD. To the best of our knowledge, only a few cases concerning this phenomenon have been reported. We describe an 11-year-old boy with a two-year history of anemia and without any gastrointestinal symptoms. He did not receive any thorough inspection until arthralgia occurred. Multiple nodules were found in his bilateral lungs via computed tomography scan. Combined with the child's medical history, physical examinations, and all of the investigations, the final diagnosis was CD with pulmonary nodules and arthritis. After 2 months of treatment, the patient's symptoms had significantly improved. To summarize the clinical manifestations, auxiliary examination features, and treatments of CD in children with pulmonary involvement, we also review the relevant characteristics of pulmonary involvement in CD patients. This case indicates the importance of recognizing the pulmonary manifestations of CD. Clinicians should be aware of the possibility of CD when their patients have lung nodules, even in children with no typical manifestations of CD.
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http://dx.doi.org/10.21037/tp-21-41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261598PMC
June 2021

Thermoelectric Properties of Strained β-CuSe.

ACS Appl Mater Interfaces 2021 Jul 20;13(29):34367-34373. Epub 2021 Jul 20.

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, P. R. China.

In recent years, the high-temperature phase of CuSe, namely, β-CuSe, has attracted increasing attention due to its outstanding thermoelectric efficiency. The Cu ions in β-CuSe show a distinct ion-liquid behavior between the framework of a Se ion lattice. Many experimental operations may lead to a discrepancy in the lattice structure. Experimentally synthesized β-CuSe was p-type, and a thermoelectric device needs both p-type and n-type materials with a close figure of merit. Studying the effect of strain and the possibility of n-type β-CuSe is essential. Utilizing first-principles calculations and molecular dynamics simulations, we investigate the thermoelectric performance of strained β-CuSe. The results show that the n-type β-CuSe can exhibit superior values like the p-type one. Applying compressive strain is an effective way to promote the power factor. The tensile strain will lead to a low lattice thermal conductivity and thus boost the p-type values. The predicted maximum values for n-type and p-type β-CuSe can reach 1.65 and 1.71 at 800 K, respectively. Considering the fact that applying strain is challenging in experiments, we propose a feasible strategy to manipulate the lattice structure and carrier type: doping halogen elements. Our results provide a guide for CuSe-based thermoelectric devices.
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http://dx.doi.org/10.1021/acsami.1c08686DOI Listing
July 2021

Ultrafast imaging of spontaneous symmetry breaking in a photoionized molecular system.

Nat Commun 2021 Jul 9;12(1):4233. Epub 2021 Jul 9.

Wuhan National Laboratory for Optoelectronics and School of Physics, Huazhong University of Science and Technology, Wuhan, China.

The Jahn-Teller effect is an essential mechanism of spontaneous symmetry breaking in molecular and solid state systems, and has far-reaching consequences in many fields. Up to now, to directly image the onset of Jahn-Teller symmetry breaking remains unreached. Here we employ ultrafast ion-coincidence Coulomb explosion imaging with sub-10 fs resolution and unambiguously image the ultrafast dynamics of Jahn-Teller deformations of [Formula: see text] cation in symmetry space. It is unraveled that the Jahn-Teller deformation from C to C geometries takes a characteristic time of 20 ± 7 fs for this system. Classical and quantum molecular dynamics simulations agree well with the measurement, and reveal dynamics for the build-up of the C structure involving complex revival process of multiple vibrational pathways of the [Formula: see text] cation.
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http://dx.doi.org/10.1038/s41467-021-24309-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270947PMC
July 2021

Cadherin-11 Deficiency Attenuates Ang-II-Induced Atrial Fibrosis and Susceptibility to Atrial Fibrillation.

J Inflamm Res 2021 2;14:2897-2911. Epub 2021 Jul 2.

Department of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, People's Republic of China.

Background: Atrial fibrosis serves as a disease initiating mechanism in the development of atrial fibrillation. Angiotensin II (Ang-II), a key mediator for atrial fibrosis, aberrantly activates atrial fibroblasts (AFs) into myofibroblasts, resulting in subsequent excessive synthesis and deposition of extracellular matrix (ECM). Cadherin-11 (CDH11) is essential in the development of non-cardiac fibrotic diseases. In this study, we investigated its role in the pathogenesis and underlying mechanism of atrial fibrillation.

Methods: We obtained left atrial tissues from either patients with atrial fibrillation or Ang-II-induced atrial fibrosis mice. We utilized a global CDH11 knockout mouse (CDH11) model to determine the effect of CDH11 on AF cell proliferation, migration, ECM synthesis/deposition. RNA-Seq of isolated AFs from CDH11 or normal mice was performed and differential expressed genes were analyzed. The mouse susceptibility to atrial fibrillation was examined by cardiac electrophysiology.

Results: We found that cadherin-11 was significantly up-regulated in fibrotic atrial tissue from patients with atrial fibrillation and Ang-II-induced mice. Both normal and CDH11 mice did not develop atrial fibrosis at resting state. However, after Ang-II infusion, unlike severe atrial fibrosis occurred in normal mice, CDH11 mice displayed a reduced atrial fibrosis. Atrial fibroblasts with CDH11 deletion from CDH11 mice showed reduction in Ang-II-induced cell proliferation, migration and ECM synthesis/deposition, indicating the involvement of CDH11 in atrial fibrosis. Consistently, RNA-Seq of CDH11-null AFs uncovered significant decrease in pro-fibrotic gene expression. In addition, we identified reduction of transcripts associated with Smad2/3, ERK1/2 and JNK pathways. Further, CDH11 mice showed a significantly attenuated Ang-II-induced susceptibility to atrial fibrillation.

Conclusion: Our results indicate that CDH11 potentiates Ang-II-induced activation of AFs. The pathogenesis of atrial fibrosis is through CDH11 mediated stimulation of Smad2/3, ERK1/2 and JNK pathways. Thus, CDH11 might serve as a novel therapeutic target for ameliorating the development of atrial fibrillation.
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http://dx.doi.org/10.2147/JIR.S306073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259948PMC
July 2021

Divergence between serum creatine and cystatin C in estimating glomerular filtration rate of critically ill COVID-19 patients.

Ren Fail 2021 Dec;43(1):1104-1114

Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Background: The clinical use of serum creatine (sCr) and cystatin C (CysC) in kidney function evaluation of critically ill patients has been in continuous discussion. The difference between estimated glomerular filtration rate calculated by sCr (eGFRcr) and CysC (eGFRcysc) of critically ill COVID-19 patients were investigated in this study.

Methods: This is a retrospective, single-center study of critically ill patients with COVID-19 admitted in intensive care unit (ICU) at Wuhan, China. Control cases were moderate COVID-19 patients matched in age and sex at a ratio of 1:1. The eGFRcr and eGFRcysc were compared. The association between eGFR and death were analyzed in critically ill cases. The potential factors influencing the divergence between eGFRcr and eGFRcysc were explored.

Results: A total of 76 critically ill COVID-19 patients were concluded. The mean age was 64.5 ± 9.3 years. The eGFRcr (85.45 (IQR 60.58-99.23) ml/min/1.73m) were much higher than eGFRcysc (60.6 (IQR 34.75-79.06) ml/min/1.73m) at ICU admission. About 50 % of them showed eGFRcysc < 60 ml/min/1.73 m while 25% showed eGFRcr < 60 ml/min/1.73 m (χ = 10.133,  = 0.001). This divergence was not observed in moderate group. The potential factors influencing the divergence included serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α) level as well as APACHEII, SOFA scores. Reduced eGFRcr (<60 mL/min/1.73 m) was associated with death (HR = 1.939, 95%CI 1.078-3.489,  = 0.027).

Conclusions: The eGFRcr was generally higher than eGFRcysc in critically ill COVID-19 cases with severe inflammatory state. The divergence might be affected by inflammatory condition and illness severity. Reduced eGFRcr predicted in-hospital death. In these patients, we advocate for caution when using eGFRcysc.
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http://dx.doi.org/10.1080/0886022X.2021.1948428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274508PMC
December 2021

Bifunctional squaramide catalyzed asymmetric synthesis of chiral α-mercaptosilanes.

Org Biomol Chem 2021 Jul;19(29):6412-6416

Key Laboratory of Flexible Electronics & Institute of Advanced Materials, Nanjing Tech University, 30 South Puzhu Road, Nanjing 211816, China.

Bifunctional squaramide-catalyzed nucleophilic addition of thiophenols to easily available β-silyl α,β-unsaturated carbonyl compounds has been successfully developed. A structurally diverse set of chiral α-mercaptosilanes was efficiently prepared in good to excellent yields with acceptable enantioselectivities. The reaction features mild reaction conditions, a broad substrate scope, and easy scale-up.
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http://dx.doi.org/10.1039/d1ob00981hDOI Listing
July 2021

Analysis of Risk Factors of Bleeding Complications in Percutaneous Needle Biopsy of Liver Occupying Lesions.

Int J Gen Med 2021 28;14:2893-2899. Epub 2021 Jun 28.

School of Medical Imaging of Guizhou Medical University, Guiyang, 550002, People's Republic of China.

Purpose: To search for risk factors for bleeding complications after percutaneous biopsy of primary or secondary space-occupying lesions of liver guided by imaging.

Methods: Consecutive 555 patients with liver space-occupying lesions who underwent ultrasound or CT-guided percutaneous biopsy in our hospital from January 2015 to January 2021 were retrospectively analyzed. Those who cannot cooperate with breath-holding and cannot successfully complete the operation, cytology, and incomplete clinical data. After screening, a total of 502 patients were enrolled, including 313 males and 189 females. Abdominal cavity or liver subcapsular hemorrhage after procedure was used as the dependent variable, and patient's gender, age, pathological results, tumor size, preoperative platelets and international normalized ratio (INR) and hemoglobin as independent variables. All independent variables were analyzed by a single factor logistic regression analysis. The independent variables with P<0.05 were included in the regression model and analyzed by multivariate logistic regression analysis to search for the risk factors for bleeding complications of liver space-occupying lesions.

Results: A total of 502 patients with liver space-occupying lesions undergoing percutaneous liver biopsy guided by imaging equipment were included. Twenty-six of 502 (5.2%) patients occurred abdominal cavity or liver sub-capsule bleeding after procedure. Univariate logistic regression analysis observed that liver cirrhosis, the number of punctured tissues and the depth of puncture were related to bleeding complications after puncturing. Multivariate logistic regression analysis showed that liver cirrhosis and puncture depth were risk factors for bleeding complications (P<0.05). The ROC curve for predicting bleeding complications after needle biopsy in patients with liver cirrhosis has a sensitivity of 94.3% and a specificity of 46.2%.

Conclusion: Liver cirrhosis and puncture depth are risk factors for bleeding complications during percutaneous biopsy of liver occupying lesions.
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http://dx.doi.org/10.2147/IJGM.S313407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254094PMC
June 2021

Epidemiologic Features, Radiological Findings andClinical Outcomes of 19 Patients with COVID-19in a Single Center in Beijing, China.

Chin Med Sci J 2021 Jun;36(2):85-96

Department of Radiology,Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

ObjectiveTo describe the epidemiologic, clinical, laboratory, and radiological characteristics and prognoses of COVID-19 confirmed patients in a single center in Beijing, China. Methods The study retrospectively included 19 patients with nucleic acid-confirmed SARS-CoV-2 infection at our hospital from January 20 to March 5, 2020. The final follow-up date was March 14, 2020. The epidemiologic and clinical information was obtained through direct communication with the patients or their family members. Laboratory results retrieved from medical records and radiological images were analyzed both qualitatively by two senior chest radiologists as well as quantitatively via an artificial intelligence software. Results We identified 5 family clusters (13/19, 68.4%) from the study cohort. All cases had good clinical prognoses and were either mild (3/19) or moderate (16/19) clinical types. Fever (15/19, 78.9%) and dry cough (11/19, 57.9%) were common symptoms. Two patients received negative results for more than three consecutive viral nucleic acid tests. The longest interval between an initial CT abnormal finding and a confirmed diagnosis was 30 days. One patient's nucleic acid test turned positive on the follow-up examination after discharge. The presence of radiological abnormalities was non-specific for the diagnosis of COVID-19. Conclusions COVID-19 patients with mild or no clinical symptoms are common in Beijing, China. Radiological abnormalities are mostly non-specific and massive CT examinations for COVID-19 screening should be avoided. Analyses of the contact histories of diagnosed cases in combination with clinical, radiological and laboratory findings are crucial for the early detection of COVID-19. Close monitoring after discharge is also recommended.
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http://dx.doi.org/10.24920/003821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265916PMC
June 2021

Synthesis of NaSO mediated cleavable affinity tag for labeling of O-GlcNAc modified proteins via azide-alkyne cycloaddition.

Bioorg Med Chem Lett 2021 Jul 3;48:128244. Epub 2021 Jul 3.

Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, School of Basic Medicine Science, Henan University, 475004 Kaifeng, China. Electronic address:

A facile and convergent procedure for the synthesis of azobenzene-based probe was reported, which could selectively release interested proteins conducted with sodium dithionite. Besides, the cleavage efficiency is closely associated with the structural features, in which an ortho-hydroxyl substituent is necessary for reactivity. In addition, the azobenzene tag applied in the AcGlcNAz-labled proteins demonstrated high efficiency and selectivity in comparison with Biotin-PEG-Alkyne, which provides a useful platform for enrichment of any desired bioorthogonal proteomics.
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http://dx.doi.org/10.1016/j.bmcl.2021.128244DOI Listing
July 2021

Decoration of amine functionalized zirconium metal organic framework/silver iodide heterojunction on carbon fiber cloth as a filter- membrane-shaped photocatalyst for degrading antibiotics.

J Colloid Interface Sci 2021 Jun 23;603:582-593. Epub 2021 Jun 23.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, State Environmental Protection Engineering Center for Pollution Treatment and Control in Textile Industry, College of Environmental Science and Engineering, Donghua University, Shanghai, 201620, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai, 200092, China. Electronic address:

The development of recyclable photocatalyst with high adsorption and excellent photocatalytic performance has attracted considerable attention. Herein, we report a three-component photocatalyst by constructing porous amine functionalized zirconium metal organic framework (UiO-66-NH) and broad photo-responsive AgI on flexible carbon fiber cloth (CFC). UiO-66-NH nanoparticles (200-400 nm) were in-situ grown on the surface of CFC (16.5 ± 0.5 μm, 4 × 4 cm) by a solvothermal route, then AgI particles (50-100 nm) were synthesized on CFC/UiO-66-NH via a modified chemical bath deposition method. The obtained CFC/UiO-66-NH/AgI can effectively adsorb 19.0% levofloxacin (LVFX) or 18.4% ciprofloxacin (CIP) in 60 min in the dark and degrade 84.5% LVFX or 79.6% CIP in 120 min under visible light irradiation. Furthermore, the filter-membrane-shaped CFC/UiO-66-NH/AgI can be utilized to treat the flowing sewage (CIP, 10 mg/L, ~1 L/h), and the removing efficiency of CIP reached 71.0% after 10 grades. Therefore, this work demonstrates the huge application prospect of recyclable CFC/UiO-66-NH/AgI with high adsorption and photocatalytic capacity in flowing sewage treatment under visible light illumination.
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http://dx.doi.org/10.1016/j.jcis.2021.06.112DOI Listing
June 2021

Sugar-Sweetened Beverage Consumption Status and Its Association with Childhood Obesity among Chinese Children Aged 6-17 Years.

Nutrients 2021 Jun 27;13(7). Epub 2021 Jun 27.

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: There is a remarkable growth in sugar-sweetened (SSB) production and obesity prevalence among school-aged children in China. This paper describes SSB consumption and its association with obesity among Chinese children aged 6-17 years in 2012.

Methods: in total, 25,553 children aged 6~17 years enrolled in the China Nutrition and Health Surveillance 2010-2013 were included in this study. Data of SSB consumption frequency and quantity were obtained from a food frequency questionnaire, and the children's nutritional status was assessed. Multivariate logistic regression was used to evaluate the association between SSB consumption and obesity status.

Results: SSB intake was estimated as 181.0 g/day, occurring 2.2 times/week. Older children, males, children from urban areas, and children with higher socioeconomic status were more likely to consume SSBs. Children who consumed SSBs 1~<5 times/week (11.7%) and >5 times/week (12.9%) were more likely to be overweight/obesity than those who consumed SSBs less than once/week.

Conclusion: SSB consumption was common among Chinese school-aged children, especially among males, older children, and children from urban areas. High consumption of SSBs was associated with a higher prevalence of overweight/obesity. Actions and plans are required to reduce SSB consumption and control childhood obesity in China.
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http://dx.doi.org/10.3390/nu13072211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308281PMC
June 2021

Steroids Enable Mesenchymal Stromal Cells to Promote CD8 T Cell Proliferation Via VEGF-C.

Adv Sci (Weinh) 2021 06 2;8(12):2003712. Epub 2021 May 2.

CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 China.

Mesenchymal stromal cells (MSCs) function as a formidable regulator of inflammation and tissue homeostasis and expanded MSCs are shown to be effective in treating various inflammatory diseases. Their therapeutic effects require the existence of certain inflammatory cytokines. However, in the absence of sufficient proinflammatory stimuli or in the presence of anti-inflammatory medications, MSCs are animated to promote immune responses and unable to alleviate inflammatory disorders. In this study, it is demonstrated that steroid co-administration interferes the efficacy of MSCs in treating acute graft-versus-host disease (aGvHD). Molecular analysis reveals that vascular endothelial growth factor C (VEGF-C) is highly induced in MSCs by steroids and TNF and VEGF-C in turn promotes CD8 T cell response. This immune promoting effect is abolished by blockade or specific genetic ablation of VEGFR3 in CD8 T cells. Additionally, administration of VEGF-C alone exacerbates aGvHD progression through eliciting more vigorous CD8 T cell activation and proliferation. Further studies demonstrate that VEGF-C augments the PI3K/AKT signaling process and the expression of downstream genes, such as Cyclin D1. Thus, the data demonstrate that steroids can reverse the immunosuppressive effect of MSCs via promoting VEGF-C-augmented CD8 T cell response and provide novel information for designing efficacious MSC-based therapies.
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http://dx.doi.org/10.1002/advs.202003712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224440PMC
June 2021

Efficient Synthesis of Icetexane Diterpenes and Apoptosis Inducing Effect by Upregulating BiP-ATF4-CHOP Axis in Colorectal Cells.

J Nat Prod 2021 Jul 25;84(7):2012-2019. Epub 2021 Jun 25.

Xiangya School of Pharmaceutical Science, Central South University, Changsha, 410013 Hunan, China.

We herein present an efficient and robust synthetic strategy toward 12 icetexane diterpenes and their derivatives, which features a PPh/DIAD-mediated rearrangement of the reduced carnosic acid derivative () to give (-)-barbatusol () in a regioselective and scalable way. MTT assay led to the identification of (+)-grandione () and (-)-demethylsalvicanol -quinone derivative () as highly cytotoxic agents against HCT-116, COLO-205, and Caco-2 cells. Interestingly, (+)-grandione () induced the HCT-116 cell apoptosis in a dose-dependent manner, which might be attributed to the upregulation of the BiP-ATF4-CHOP axis and promotion of the BiP-ATF4 interactions, thereby leading to endoplasmic reticulum (ER) stress. This work not only paves an efficient and scalable pathway to access icetexane diterpenes but also provides new leads for the development of anticolorectal agents with a unique mode of action.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00310DOI Listing
July 2021

Therapeutic prediction of HIV-1 DNA decay: a multicenter longitudinal cohort study.

BMC Infect Dis 2021 Jun 22;21(1):592. Epub 2021 Jun 22.

Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China.

Background: Factors predicting peripheral blood total HIV-1 DNA size in chronically infected patients with successfully suppressed viremia remain unclear. Prognostic power of such factors are of clinical significance for making clinical decisions.

Methods: Two sets of study populations were included: 490 China AIDS Clinical Trial (CACT) participants (Training cohort, followed up for 144 to 288 weeks) and 117 outpatients from Peking Union Medical College Hospital (PUMCH) (Validation cohort, followed up for more than 96 weeks). All patients were chronically HIV-1-infected and achieved successful HIV-1 plasma RNA suppression within week 48. Total HIV-1 DNA in blood at baseline, 12, 24, 48, 96, 144 and 288 weeks after combined antiretroviral therapy (cART) initiation were quantified. Generalized estimating equations and logistic regression methods were used to derive and validate a predictive model of total HIV-1 DNA after 96 weeks of cART.

Results: The total HIV-1 DNA rapidly decreased from baseline [median = 3.00 log copies/10 peripheral blood mononuclear cells (PBMCs)] to week 24 (median = 2.55 log copies/10 PBMCs), and leveled off afterwards. Of the 490 patients who had successful HIV-1 plasma RNA suppression by 96 w post-cART, 92 (18.8%) had a low total HIV-1 DNA count (< 100 copies/10 PBMCs) at week 96. In the predictive model, lower baseline total HIV-1 DNA [risk ratio (RR) = 0.08, per 1 log copies/10 PBMCs, P < 0.001] and higher baseline CD4+ T cell count (RR = 1.72, per 100 cells/μL, P < 0.001) were significantly associated with a low total HIV-1 DNA count at week 96. In an independent cohort of 117 patients, this model achieved a sensitivity of 75.00% and specificity of 69.52%.

Conclusions: Baseline total HIV-1 DNA and CD4+ T cell count are two independent predictors of total HIV-1 DNA after treatment. The derived model based on these two baseline factors provides a useful prognostic tool in predicting HIV-1 DNA reservoir control during cART.
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http://dx.doi.org/10.1186/s12879-021-06267-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218450PMC
June 2021

Validation of the promotion mechanism between bromide and UDMH to form NDMA during ozonation.

Sci Total Environ 2021 Jun 7;792:148316. Epub 2021 Jun 7.

Institute of Municipal and Environmental Engineering, College of Civil Engineering, Huaqiao University, Fujian 361021, China.

Unsymmetrical dimethylhydrazine (UDMH) is found to generate substantial carcinogenic nitroso-dimethylamine (NDMA) during ozonation, moreover, its formation is promoted by ubiquitous bromide ions (Br) in water matrixes, but the mechanism is still unclear. In this study, effects of Br on NDMA formation during ozonation of UDMH were studied, meanwhile, its promotion pathways were also determined. The results demonstrated that Br promoted NDMA formation from UDMH during ozonation, the formation rate constant with Br is over 7 times of that without Br. NDMA amount raised from 142.5 to 327.5 μg/L when Br dosages increased from 0 to 100 μM. No matter with or without Br, the augment of O dosages facilitated NDMA formation; the maximum value was achieved at pH 8. NDMA decreased dramatically from 173.8 to 123.5 μg/L with HCO raising from 0 to 160 μM, while increasing remarkably to 222.5 μg/L with SO dosing. In addition, NOM inhibited NDMA formation from UDMH during ozonation. The mass spectrum of LC-MS/MS verified that the generation of Br-UDMH was main cause for promoting NDMA formation. Moreover, hypobromous acid (HBrO) was confirmed to be responsible for Br-UDMH formation. In addition, the position that oxidants and Br attacked was demonstrated based on Gaussian calculation. The results of this study could provide theoretical basis for the application of ozonation in bromine-containing water matrixes.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148316DOI Listing
June 2021

Role of IL-6-IL-27 Complex in Host Antiviral Immune Response.

J Immunol 2021 Jun 18. Epub 2021 Jun 18.

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China; and

The IL family of cytokines participates in immune response and regulation. We previously found that soluble IL-6 receptor plays an important role in the host antiviral response. In this study, we detected the IL-6-IL-27 complex in serum and throat swab samples from patients infected with influenza A virus. A plasmid expressing the IL-6-IL-27 complex was constructed to explore its biological function. The results indicated that the IL-6-IL-27 complex has a stronger antiviral effect than the individual subunits of IL-6, IL-27A, and EBV-induced gene 3. Furthermore, the activity of the IL-6-IL-27 complex is mainly mediated by the IL-27A subunit and the IL-27 receptor α. The IL-6-IL-27 complex can positively regulate virus-triggered expression of IFN and IFN-stimulated genes by interacting with adaptor protein mitochondrial antiviral signaling protein, potentiating the ubiquitination of TNF receptor-associated factors 3 and 6 and NF-κB nuclear translocation. The secreted IL-6-IL-27 complex can induce the phosphorylation of STAT1 and STAT3 and shows antiviral activity. Our results demonstrate a previously unrecognized mechanism by which IL-6, IL-27A, and EBV-induced gene 3 form a large complex both intracellularly and extracellularly, and this complex acts in the host antiviral response.
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http://dx.doi.org/10.4049/jimmunol.2100179DOI Listing
June 2021

Structural characteristics of a hypoglycemic polysaccharide from Fructus Corni.

Carbohydr Res 2021 Aug 3;506:108358. Epub 2021 Jun 3.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, School of Chemistry & Pharmacy, Northwest A&F University, Yangling, 712100, China; Department of Pharmacology and Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, China. Electronic address:

PFC-3 is a homogeneous polysaccharide extracted from the dried pulps of Fructus Corni with a molecular weight of 40.3 kDa. The crude polysaccharide was obtained and further purified by DEAE-Sephadex A-25 and Sephadex G-100 columns to investigate its structure and glycemic effect. The monosaccharides in the PFC-3, determined by high-performance liquid chromatography, consisted of glucose (Glc), xylose (Xyl), and galactose (Gal) with a mass molar ratio of 2.35:12.49:1.00. The methylation analysis combined with 1D (H and C), and 2D NMR (H-H COSY, HSQC, and HMBC) further demonstrated that PFC-3 was mainly composed of 1,3-α-D-Xylp, 1,6-α-D-Galp, 1,2-α-D-Glcp, and T-α-D-Galp, and contained a backbone fragment of →6)-α-D-Galp-(1 → 2)-α-D-Glcp-(1 → 3)-α-D-Xylp-(1 → . The hypoglycemic effect of PFC-3 in vitro was evaluated by glucose uptake and consumption assays, and the results showed that PFC-3 concentration-dependently enhanced glucose uptake and significantly improved glucose consumption in insulin-resistant HepG2 cells. Furthermore, PFC-3 significantly reduced fasting blood glucose level, glycosylated hemoglobin level, amylase activity, ameliorate lipid metabolism, and hepatic lesions in streptozotocin-induced diabetic rats. Our research provided insights into the hypoglycemic activities of PFC-3.
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http://dx.doi.org/10.1016/j.carres.2021.108358DOI Listing
August 2021

Changes in trabecular bone score and bone mineral density in Chinese HIV-Infected individuals after one year of antiretroviral therapy.

J Orthop Translat 2021 Jul 20;29:72-77. Epub 2021 May 20.

Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences and Peking Union Medical College, Beijing, 100730, China.

Objective: Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with reduced bone mineral density (BMD) in persons with HIV (PWH). BMD provides information only about bone mineral quantity. Trabecular bone score (TBS) is a noninvasive tool that estimates bone microarchitecture. The aim of this study is to measure BMD and TBS of Chinese PWH after one-year ART.

Methods: We designed a retrospective study of adult Chinese PWH. Patients with a dual-energy X-ray absorptiometry (DXA) scan prior to ART initiation, and again 48 weeks later were included. Information regarding demographic and clinical history, HIV treatment history, BMD and TBS were collected. We analyzed differences in BMD and TBS over 48 weeks and associations between key risk factors and changes in BMD and TBS.

Results: Our study included 233 ​PWH (mean age ​= ​36.6 ​± ​11.1 years). Before ART initiation, 19.3% of PWH had normal BMD but abnormal TBS. Both BMD and TBS decreased after one-year ART. TDF and LPV/r-containing regimens were associated with greater declines in BMD at different site. Traditional risk factors such as old age, low BMI and female sex were associated with lower baseline TBS. Greater change in TBS over one year was associated with lower BMI and lower baseline CD4+ cell count, but unlike BMD measures, it was not correlated with treatment with TDF and LPV/r in our study population.

Conclusions: We present the first longitudinal analysis of change in TBS over 48 weeks compared with BMD among Asian PWH receiving ART. Before ART initiation, approximately 20% of PWH with impaired bone microarchitecture would not have been identified if DXA were used alone to assess for bone damage. Both BMD and TBS decreased after one-year ART. Change in TBS was not associated with different antiretroviral agents.

The Translational Potential Of This Article: The trabecular microarchitecture measured indirectly by TBS may provide clinicians additional information about bone damage in PWH.
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http://dx.doi.org/10.1016/j.jot.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164002PMC
July 2021

Identification of the hub genes and prognostic indicators of gastric cancer and correlation of indicators with tumor-infiltrating immune cell levels.

J Cancer 2021 13;12(13):4025-4038. Epub 2021 May 13.

Henan Institute of Medical and Pharmaceutical Science, Zhengzhou University, No. 40 Daxue Road, Zhengzhou 450052, China.

To identify the hub genes and prognostic indicators of gastric cancer (GC) and determine the correlation between prognostic indicators and the tumor-infiltrating immune cell levels so as to provide useful information for future GC diagnosis and treatment. The Cancer Genome Atlas (TCGA) stomach adenocarcinoma dataset and two microarray datasets were used to screen the overlapping differentially expressed genes (DEGs) between normal gastric and GC tissue samples. Hub genes were screened via protein-protein interaction networks and module analysis of the overlapping DEGs. Their expression was validated at the cell level and tissue level using the ONCOMINE database. The prognostic indicators of overall survival (OS) and disease-free survival was identified by Cox proportional hazards regression analysis based on tumor grade and cancer stage. The expression of hub genes was validated at the cell level. The correlation of prognostic indicators with the tumor-infiltrating immune cell levels was analyzed using Tumor IMmune Estimation Resource. Ten hub genes, namely , , , , , , , , , and , were screened and their upregulation in the GC tissue was verified. Three prognostic factors, namely , , and , were identified; their expression was higher in GC cells than in normal cells. , , and were correlated with tumor-infiltrating immune cell levels in GC. The identified hub genes and prognostic indicators of GC could be useful indicators for future GC diagnosis and treatment.
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http://dx.doi.org/10.7150/jca.52105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176244PMC
May 2021

Naïve CD4 cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study.

BMC Immunol 2021 Jun 3;22(1):36. Epub 2021 Jun 3.

Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Background: Some long-term non-progressors (LTNPs) have decreasing CD4 T cell counts and progress to AIDS. Exploring which subsets of CD4 T cell decreasing and the determinants associated with the decay in these patients will improve disease progression surveillance and provide further understanding of HIV pathogenesis.

Methods: Twenty-five LTNPs infected with HIV by blood products were classified as decreased (DG) if their CD4 cell count dropped to < 400 cells/μL during follow-up or as non-decreased (non-DG) if their CD4 cell count was ≥400 cells/μL. Laboratory and clinical assessments were conducted at 6 consecutive visits to identify DG characteristics.

Results: The LTNPs were infected with HIV for 12 (IQR: 11.5-14) years, and 23 were classified as the B' subtype. Six individuals lost LTNP status 14.5 (IQR: 12.5-17.5) years after infection (DG), and the CD4 T cell count decreased to 237 (IQR: 213-320) cells/μL at the latest visit. The naïve CD4 T cell count decrease was greater than that of memory CD4 T cells [- 128 (IQR: - 196, - 107) vs - 64 (IQR: - 182, - 25) cells/μL)]. Nineteen individuals retained LTNP status (non-DG). At enrolment, the viral load (VL) level (p = 0.03) and CD8CD38 percentage (p = 0.03) were higher in DG than non-DG individuals. During follow-up, viral load and CD8CD38 percentage were significantly increased and negatively associated with CD4 cell count [(r = - 0.529, p = 0.008), (r = - 0.476, p = 0.019), respectively]. However, the CD8CD28 percentage and B cell count dropped in DG and were positively correlated with CD4 T cell count [(r = 0.448, p = 0.028), (r = 0.785, p < 0.001)].

Conclusion: Immunological progression was mainly characterized by the decrease of naïve CD4 T cell in LTNPs infected with HIV by blood products and it may be associated with high HIV RNA levels.
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http://dx.doi.org/10.1186/s12865-021-00426-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173962PMC
June 2021

Bee Pollen: Current Status and Therapeutic Potential.

Nutrients 2021 May 31;13(6). Epub 2021 May 31.

Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom 32512, Egypt.

Bee pollen is a combination of plant pollen and honeybee secretions and nectar. The Bible and ancient Egyptian texts are documented proof of its use in public health. It is considered a gold mine of nutrition due to its active components that have significant health and medicinal properties. Bee pollen contains bioactive compounds including proteins, amino acids, lipids, carbohydrates, minerals, vitamins, and polyphenols. The vital components of bee pollen enhance different bodily functions and offer protection against many diseases. It is generally marketed as a functional food with affordable and inexpensive prices with promising future industrial potentials. This review highlights the dietary properties of bee pollen and its influence on human health, and its applications in the food industry.
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http://dx.doi.org/10.3390/nu13061876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230257PMC
May 2021

Effect of the regulator of G-protein signaling 2 on the proliferation and invasion of oral squamous cell carcinoma cells and its molecular mechanism.

Hua Xi Kou Qiang Yi Xue Za Zhi 2021 Jun;39(3):320-327

Dept. of Oral and Maxillofacial-Head and Neck Oncology, Ninth People,s Hospital, Shanghai Jiao Tong University, School of Medicine; National Clinical Research Center for Oral Disease; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China.

Objectives: This study aims to investigate the effect of the regulator of G-protein signaling 2 (RGS2) on the proliferation and invasion of oral squamous cell carcinoma (OSCC) cells and its potential molecular mechanism. Metho⁃ds The expression status and clinical significance of RGS2 in head and neck squamous cell carcinomas and matched adjacent normal tissues were evaluated using TCGA database. Three OSCC cell lines (i.e., SCC-9, Cal27, and Fadu) were overexpressed with RGS2, and the effect of RGS2 on cell proliferation and invasion was determined using the Transwell, clone formation, and cell counting kit (CCK)-8 assays. Moreover, the yeast two-hybrid scree-ning and co-immunoprecipitation (Co-IP) assays were conducted to detect the correlation of RGS2, four and a half LIM domains protein 1 (FHL1), and damage DNA-binding protein 1 (DDB1).

Results: The expression level of RGS2 in OSCC was significantly lower than that in matched adjacent normal tissues (=0.023). The high RGS2 expression level was negatively correlated with lymphovascular invasion (<0.001). After transfection with lentiv-RGS2, the expression of RGS2 was increased, and the invasion and proliferation abilities of OSCC cell lines were evidently inhibited. FHL1 could competitively bind with RGS2, which decreased the integration of DDB1 and RGS2, inhibited the ubiquitination process of RGS2, and maintained the stability of the RGS2 protein.

Conclusions: RGS2 plays an important role in the inhibition of OSCC proliferation and invasion. The structure stability of RGS2 is competitively regulated by FHL1 and DDB1.
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http://dx.doi.org/10.7518/hxkq.2021.03.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218255PMC
June 2021

Identification of prognostic genes and construction of a novel gene signature in the skin melanoma based on the tumor microenvironment.

Medicine (Baltimore) 2021 May;100(21):e26017

Dermatological Department, Baoji Central Hospital, Shanxi, China.

Abstract: Skin melanoma remains a highly prevalent and yet deadly form of cancer, with the exact degree of melanoma-associated mortality being strongly dependent upon the local tumor microenvironment. The exact composition of stromal and immune cells within this microenvironmental region has the potential to profoundly impact melanoma progression and prognosis. As such, the present study was designed with the goal of clarifying the predictive relevance of stromal and immune cell-related genes in melanoma patients through comprehensive bioinformatics analyses. We therefore analyzed melanoma sample gene expression within The Cancer Genome Atlas database and employed the ESTIMATE algorithm as a means of calculating both stromal and immune scores that were in turn used for identifying differentially expressed genes (DEGs). Subsequently, univariate analyses were used to detect DEGs associated with melanoma patient survival, and through additional functional enrichment analyses, we determined that these survival-related DEGs are largely related to inflammatory and immune responses. A prognostic signature comprised of 10 genes (IL15, CCL8, CLIC2, SAMD9L, TLR2, HLA.DQB1, IGHV1-18, RARRES3, GBP4, APOBEC3G) was generated. This 10-gene signature effectively separated melanoma patients into low- and high-risk groups based upon their survival. These low- and high-risk groups also exhibited distinct immune statuses and differing degrees of immune cell infiltration. In conclusion, our results offer novel insights into a number of microenvironment-associated genes that impact survival outcomes in melanoma patients, potentially highlighting these genes as viable therapeutic targets.
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http://dx.doi.org/10.1097/MD.0000000000026017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154473PMC
May 2021

Dynamic Core Polarization in High Harmonic Generation from Solids: The Example of MgO Crystals.

Phys Rev Lett 2021 May;126(18):187401

Wuhan National Laboratory for Optoelectronics and School of Physics, Huazhong University of Science and Technology, Wuhan 430074, China.

Previously, the strong field processes in solids have always been explained by the single-active-electron (SAE) model with a frozen core excluding the fluctuation of background electrons. In this work, we demonstrate the strong field induced dynamic core polarization effect and propose a model for revealing its role in high harmonic generation (HHG) from solids. We show that the polarized core induces an additional polarization current beyond the SAE model based on the frozen cores. It gives a new mechanism for HHG and leads to new anisotropic structures, which are experimentally observed with MgO. Our experiments indicate that the influences of dynamic core polarization on HHG are obvious for both linearly and elliptically polarized laser fields. Our work establishes the bridge between the HHG and the dynamic changes of the effective many-electron interaction in solids, which paves the way to probe the ultrafast electron dynamics.
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http://dx.doi.org/10.1103/PhysRevLett.126.187401DOI Listing
May 2021

N-Heterocyclic carbene-catalyzed [3 + 3] annulation of bromoenals with 2-aminochromones to access chromeno[2,3-]pyridinones.

Org Biomol Chem 2021 Jun;19(22):4882-4886

Key Laboratory of Flexible Electronics & Institute of Advanced Materials, Nanjing Tech University, 30 South Puzhu Road, Nanjing 211816, China.

N-Heterocyclic carbene-catalyzed [3 + 3] annulation of bromoenals with 2-aminochromones has been successfully developed. A structurally diverse set of chromeno[2,3-b]pyridinones was efficiently constructed in acceptable to excellent yields. The reaction features mild reaction conditions, a broad substrate scope, and easy scale-up.
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http://dx.doi.org/10.1039/d1ob00720cDOI Listing
June 2021

Inducible ATP1B1 Upregulates Antiviral Innate Immune Responses by the Ubiquitination of TRAF3 and TRAF6.

J Immunol 2021 Jun 19;206(11):2668-2681. Epub 2021 May 19.

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China

The antiviral innate immune responses are crucial steps during host defense and must be strictly regulated, but the molecular mechanisms of control remain unclear. In this study, we report increased expression of human ATPase Na/K transporting subunit β 1(ATP1B1) after DNA and RNA virus infections. We found that the expression of ATP1B1 can inhibit viral replication and increase the levels of IFNs, IFN-stimulated genes, and inflammatory cytokines. Knockdown of ATP1B1 by specific short hairpin RNA had the opposite effects. Upon viral infection, ATP1B1 was induced, interacted with TRAF3 and TRAF6, and potentiated the ubiquitination of these proteins, leading to increased phosphorylation of downstream molecules, including TGF-β-activated kinase 1 (TAK1) and TANK-binding kinase 1 (TBK1). These results reveal a previously unrecognized role of ATP1B1 in antiviral innate immunity and suggest a novel mechanism for the induction of IFNs and proinflammatory cytokines during viral infection.
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http://dx.doi.org/10.4049/jimmunol.2001262DOI Listing
June 2021
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