Publications by authors named "Huan Chen"

1,084 Publications

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Exosomes in HIV infection.

Curr Opin HIV AIDS 2021 Jul 27. Epub 2021 Jul 27.

Beijing Institute of Hepatology Department of General Surgery, Beijing Youan Hospital, Capital Medical University, Beijing, China.

Purpose Of Review: The exosomes play a critical role in HIV infection, which constitute a pathway to release intracellular material and exchange material and information between cells. Exosomes have become a hotspot in the field of AIDS research. This review introduces the formation process of HIV particles and exosomes, and summarizes the role of exosomes in the progression of HIV disease from multiple aspects.

Recent Findings: Many components of the exosomes involved in HIV transfer and replication affect the occurrence, development, and outcome of AIDS, and are closely related to HIV infection. Exosomes can have a dual impact on HIV infection, and play an important role in activating the latent reservoir of HIV and affecting the chronic inflammation of HIV. The biological information carried by exosomes is also of great significance for the prediction of HIV disease.

Summary: The present review summarizes the role of exosomes in HIV disease progression in various aspects in order to further understand the underlying mechanism affecting the infection and providing a new idea for the clinical diagnosis and treatment of AIDS.
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http://dx.doi.org/10.1097/COH.0000000000000694DOI Listing
July 2021

Deep Penetration of Nanolevel Drugs and Micrometer-Level T Cells Promoted by Nanomotors for Cancer Immunochemotherapy.

J Am Chem Soc 2021 Jul 28. Epub 2021 Jul 28.

The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing University, Nanjing 210008, China.

The ability of nanomotors to promote the deep penetration of themselves and the loaded drugs in diseased tissues has been proposed and confirmed. However, whether such motion behavior of the nanomotors can also promote deep penetration of micrometer-sized immune cells in the diseased microenvironment, which is important for the immunotherapy of some diseases, has not been mentioned. Herein, we construct a nitric oxide (NO)-driven nanomotor that can move in the tumor microenvironment, focusing on its motion behavior and the role of NO, the beneficial product released during movement from this kind of nanomotor, in regulating the infiltration behavior and activity of immune cells. It can be found that the drug-loaded nanomotors with both NO-releasing ability and motility can promote the normalization of the tumor vasculature system and the degradation of the intrinsic extracellular matrix (ECM), which can significantly improve the tumor infiltration ability of T cells in vivo. The efficiency of T-cell infiltration in tumor tissue in vivo increased from 2.1 to 28.2%. Both subcutaneous and intraperitoneal implantation tumor models can validate the excellent antitumor effect of drug-loaded NO-driven nanomotors. This combination of motility of the power source from nanomotors and their physiological function offers a design idea for therapeutic agents for the future immunotherapy of many diseases.
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http://dx.doi.org/10.1021/jacs.1c03071DOI Listing
July 2021

A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5-Mediated GDF6 Expression.

Adv Sci (Weinh) 2021 Jul 28:e2004629. Epub 2021 Jul 28.

Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, P. R. China.

Angiogenesis is essential for vascular development. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating angiogenesis remain under-explored. Human embryonic stem cell-derived mesenchymal stem cells (hES-MSCs) are shown to exert more potent cardioprotective effects against cardiac ischemia than human bone marrow-derived MSCs (hBM-MSCs), associated with enhanced neovascularization. The purpose of this study is to search for angiogenic lncRNAs enriched in hES-MSCs, and investigate their roles and mechanisms. AC103746.1 is one of the most highly expressed intergenic lncRNAs detected in hES-MSCs versus hBM-MSCs, and named as SCDAL (stem cell-derived angiogenic lncRNA). SCDAL knockdown significantly reduce the angiogenic potential and reparative effects of hES-MSCs in the infarcted hearts, while overexpression of SCDAL in either hES-MSCs or hBM-MSCs exhibits augmented angiogenesis and cardiac function recovery. Mechanistically, SCDAL induces growth differentiation factor 6 (GDF6) expression via direct interaction with SNF5 at GDF6 promoter. Secreted GDF6 promotes endothelial angiogenesis via non-canonical vascular endothelial growth factor receptor 2 activation. Furthermore, SCDAL-GDF6 is expressed in human endothelial cells, and directly enhances endothelial angiogenesis in vitro and in vivo. Thus, these findings uncover a previously unknown lncRNA-dependent regulatory circuit for angiogenesis. Targeted intervention of the SCDAL-GDF6 pathway has potential as a therapy for ischemic heart diseases.
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http://dx.doi.org/10.1002/advs.202004629DOI Listing
July 2021

Efficient photochemical denitrification by UV/sulfite system: Mechanism and applications.

J Hazard Mater 2021 Jun 29:126448. Epub 2021 Jun 29.

Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Denitrification is an effective strategy to control eutrophication caused by excessive nitrate in water. However, the comparatively low efficiency of nitrate removal and N selectivity remains a challenge in the denitrification process. Herein, this study proposed a novel photochemical denitrification process by introducing hydrated electron (e) to reduce nitrate in UV/sulfite system. The results indicated that the optimized UV/sulfite system could effectively reduce nitrate to N with a nearly 100% denitrification efficiency in 90 min. e was identified as the mainly reactive species to achieve rapid removal of nitrate and nitrite, and the result was verified by quenching and laser flash photolysis tests. Benefiting from the high dispersion of e in water and the rapid reaction rate between e and the target, the generated NO is susceptible to be reduced, leading to a high selectivity of N that was confirmed by N-isotopic. Besides, thermodynamic results based on the density functional theory (DFT) calculations suggested that the photochemical denitrification process was exothermic process and tend to transform to N. Significantly, UV/sulfite system applied in the nickel-plating wastewater showed high denitrification efficiency, demonstrating that the novel photochemical denitrification process is promising for practical wastewater treatment.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126448DOI Listing
June 2021

ECCOR in 12 COVID-19 ARDS Patients With Extremely Low Compliance and Refractory Hypercapnia.

Front Med (Lausanne) 2021 8;8:654658. Epub 2021 Jul 8.

Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

A phenotype of COVID-19 ARDS patients with extremely low compliance and refractory hypercapnia was found in our ICU. In the context of limited number of ECMO machines, feasibility of a low-flow extracorporeal carbon dioxide removal (ECCOR) based on the renal replacement therapy (RRT) platform in these patients was assessed. Single-center, prospective study. Refractory hypercapnia patients with COVID-19-associated ARDS were included and divided into the adjusted group and unadjusted group according to the level of PaCO after the application of the ECCOR system. Ventilation parameters [tidal volume (VT), respiratory rate, and PEEP], platform pressure (Pplat) and driving pressure (DP), respiratory system compliance, arterial blood gases, and ECCOR system characteristics were collected. Twelve patients with refractory hypercapnia were enrolled, and the PaCO was 64.5 [56-88.75] mmHg. In the adjusted group, VT was significantly reduced from 5.90 ± 0.16 to 5.08 ± 0.43 ml/kg PBW; DP and Pplat were also significantly reduced from 23.5 ± 2.72 mmHg and 29.88 ± 3.04 mmHg to 18.5 ± 2.62 mmHg and 24.75 ± 3.41 mmHg, respectively. In the unadjusted group, PaCO decreased from 94 [86.25, 100.3] mmHg to 80 [67.50, 85.25] mmHg but with no significant difference, and the DP and Pplat were not decreased after weighing the pros and cons. A low-flow ECCOR system based on the RRT platform enabled CO removal and could also decrease the DP and Pplat significantly, which provided a new way to treat these COVID-19 ARDS patients with refractory hypercapnia and extremely low compliance. https://www.clinicaltrials.gov/, identifier NCT04340414.
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http://dx.doi.org/10.3389/fmed.2021.654658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295461PMC
July 2021

Early Prediction of Mortality, Severity, and Length of Stay in the Intensive Care Unit of Sepsis Patients Based on Sepsis 3.0 by Machine Learning Models.

Front Med (Lausanne) 2021 28;8:664966. Epub 2021 Jun 28.

Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Early prediction of the clinical outcome of patients with sepsis is of great significance and can guide treatment and reduce the mortality of patients. However, it is clinically difficult for clinicians. A total of 2,224 patients with sepsis were involved over a 3-year period (2016-2018) in the intensive care unit (ICU) of Peking Union Medical College Hospital. With all the key medical data from the first 6 h in the ICU, three machine learning models, logistic regression, random forest, and XGBoost, were used to predict mortality, severity (sepsis/septic shock), and length of ICU stay (LOS) (>6 days, ≤ 6 days). Missing data imputation and oversampling were completed on the dataset before introduction into the models. Compared to the mortality and LOS predictions, the severity prediction achieved the best classification results, based on the area under the operating receiver characteristics (AUC), with the random forest classifier (sensitivity = 0.65, specificity = 0.73, F1 score = 0.72, AUC = 0.79). The random forest model also showed the best overall performance (mortality prediction: sensitivity = 0.50, specificity = 0.84, F1 score = 0.66, AUC = 0.74; LOS prediction: sensitivity = 0.79, specificity = 0.66, F1 score = 0.69, AUC = 0.76) among the three models. The predictive ability of the SOFA score itself was inferior to that of the above three models. Using the random forest classifier in the first 6 h of ICU admission can provide a comprehensive early warning of sepsis, which will contribute to the formulation and management of clinical decisions and the allocation and management of resources.
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http://dx.doi.org/10.3389/fmed.2021.664966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288021PMC
June 2021

Comparative Whole Genome Sequence Analysis and Biological Features of Sequence Type 2.

Front Microbiol 2021 5;12:651520. Epub 2021 Jul 5.

School of Laboratory Medicine, Hangzhou Medical College, Hangzhou, China.

sequence type 2 (ST2) has been increasingly recognized as one of the major genotypes in China, while the genomic characteristics and biological phenotypes of Chinese ST2 strains remain to be determined. We used whole-genome sequencing and phylogenetic analysis to investigate the genomic features of 182 ST2 strains, isolated between 2011 and 2017. PCR ribotyping (RT) was performed, and antibiotic resistance, toxin concentration, and sporulation capacity were measured. The core genome Maximum-likelihood phylogenetic analysis showed that ST2 strains were distinctly segregated into two genetically diverse lineages [L1 (67.0% from Northern America) and L2], while L2 further divided into two sub-lineages, SL2a and SL2b (73.5% from China). The 36 virulence-related genes were widely distributed in ST2 genomes, but in which only 11 antibiotic resistance-associated genes were dispersedly found. Among the 25 SL2b sequenced isolates, RT014 (40.0%, = 10) and RT020 (28.0%, = 7) were two main genotypes with no significant difference on antibiotic resistance (χ = 0.024-2.667, > 0.05). A non-synonymous amino acid substitution was found in (Y1975D) which was specific to SL2b. Although there was no significant difference in sporulation capacity between the two lineages, the average toxin B concentration (5.11 ± 3.20 ng/μL) in SL2b was significantly lower in comparison to those in L1 (10.49 ± 15.82 ng/μL) and SL2a (13.92 ± 2.39 ng/μL) (χ = 12.30, < 0.05). This study described the genomic characteristics of ST2, with many virulence loci and few antibiotic resistance elements. The Chinese ST2 strains with the mutation in codon 1975 of the gene clustering in SL2b circulating in China express low toxin B, which may be associated with mild or moderate infection.
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http://dx.doi.org/10.3389/fmicb.2021.651520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287029PMC
July 2021

Preemptive donor-derived anti-CD19 CAR T-cell infusion showed a promising anti-leukemia effect against relapse in MRD-positive B-ALL after allogeneic hematopoietic stem cell transplantation.

Leukemia 2021 Jul 20. Epub 2021 Jul 20.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

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http://dx.doi.org/10.1038/s41375-021-01351-wDOI Listing
July 2021

TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway.

BMC Cancer 2021 Jul 20;21(1):841. Epub 2021 Jul 20.

Department of Urology, Changhai Hospital, Naval Medical University, Changhai Road No.168, Yangpu District, Shanghai, 200433, People's Republic of China.

Background: The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC.

Methods: The mRNA levels of TRIM27 and Kaplan-Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression.

Results: We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation.

Conclusions: Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.
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http://dx.doi.org/10.1186/s12885-021-08562-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293539PMC
July 2021

NMDAR in bladder smooth muscle is not a pharmacotherapy target for overactive bladder in mice.

PeerJ 2021 7;9:e11684. Epub 2021 Jul 7.

Public Center of Experimental Technology and The School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China.

Overactive bladder (OAB) is a common condition that affects a significant patient population. The N-methyl-D-aspartate receptor (NMDAR) has a role in developing bladder overactivity, pharmacological inhibition of which inhibits bladder overactivity. The common pathogenesis of OAB involves bladder smooth muscle (BSM) overactivity. In this study, a smooth muscle-specific NMDAR knockout () mouse model was generated. The bladders from mice displayed normal size and weight with an intact bladder wall and well-arranged BSM bundles. Besides, mice had normal voiding patterns and urodynamics and BSM contractility, indicating that NMDAR in BSM was not essential for normal physiological bladder morphology and function. Unexpectedly, cyclophosphamide (CYP)-treated and wild-type (WT) mice had similar pathological changes in the bladder. Furthermore, mice displayed similar altered voiding patterns and urodynamic abnormalities and impaired BSM contractility compared with WT mice after CYP treatment. MK801 partially reversed the pathological bladder morphology and improved bladder dysfunction induced by CYP, but did not cause apparent differences between WT mice and mice, suggesting that NMDAR in BSM was not involved in pathological bladder morphology and function. Moreover, the direct instillation of NMDAR agonists or antagonists into the CYP-induced OAB did not affect bladder urodynamic function, indicating that NMDAR in BSM was not the pharmacotherapy target of MK801 for CYP-induced cystitis. The findings indicated that NMDAR in BSM was not essential for normal physiological or pathological bladder morphology and function, and MK801 improving pathological bladder function was not mediated by an action on NMDAR in BSM.
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http://dx.doi.org/10.7717/peerj.11684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272467PMC
July 2021

Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells.

BMC Pharmacol Toxicol 2021 Jul 15;22(1):44. Epub 2021 Jul 15.

The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.

Background: Helicobacter pylori (H. pylori) is a common pathogen in development of peptic ulcers with pyroptosis. Rabeprazole, a critical component of standard triple therapy, has been widely used as the first-line regimen for H. pylori infectious treatment. The aim of this study to explore the function of Rabeprazole on cell pyroptosis in vitro.

Methods: The clinical sample from patients diagnosed with or without H. pylori-infection were collected to analyze by Immunohistochemistry (IHC). Real-time quantitative PCR (qPCR), western blot (WB) and enzyme linked immunosorbent assay (Elisa) were performed to analyze the effect of Rabeprazole on cell pyroptosis, including LDH, IL-1β and IL-18.

Results: In this study, we showed that Rabeprazole regulated a phenomenon of cell pyroptosis as confirmed by lactate dehydrogenase (LDH) assay. Further results showed that Rabeprazole inhibited cell pyroptosis in gastric epithelial cells by alleviating GSDMD-executed pyroptosis, leading to decrease IL-1β and IL-18 mature and secretion, which is attributed to NLRP3 inflammasome activation inhibition. Further analysis showed that ASC, NLRP3 and Caspase-1, was significantly repressed in response to Rabeprazole stimulation, resulting in decreasing cleaved-caspase-1 expression. Most important, NLRP3 and GSDMD is significantly increased in gastric tissue of patients with H. pylori infection.

Conclusion: These findings revealed a critical role of Rabeprazole in cell pyroptosis in patients with H. pylori infection, suggesting that targeting cell pyroptosis is an alternative strategy in improving H. pylori treatment.
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http://dx.doi.org/10.1186/s40360-021-00509-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283986PMC
July 2021

Response of Growth Performance, Blood Biochemistry Indices, and Rumen Bacterial Diversity in Lambs to Diets Containing Supplemental Probiotics and Chinese Medicine Polysaccharides.

Front Vet Sci 2021 24;8:681389. Epub 2021 Jun 24.

Jiangxi Province Key Laboratory of Animal Nutrition/Engineering Research Center of Feed Development, Jiangxi Agricultural University, Nanchang, China.

This study aims to investigate the effects of probiotics and Chinese medicine polysaccharides (CMPs) on growth performance, blood indices, rumen fermentation, and bacteria composition in lambs. Forty female lambs were randomly divided into four groups as follows: control, probiotics, CMP, and compound (probiotics + CMP) groups. The results showed that probiotics treatment increased the concentrations of blood glucose (GLU) and immunoglobulin G (IgG) and enhanced rumen microbial protein contents but declined the value of pH in rumen fluid compared with the control ( < 0.05). Furthermore, supplementation with CMP enhanced the average daily gain (ADG) and the contents of IgA, IgG, and IgM in the serum but decreased the F:G ratio compared with the control ( < 0.05). Besides, both CMP and compound (probiotics + CMP) treatments decreased the ratio of acetic acid and propionic acid compared with the control ( < 0.05). High-throughput sequencing data showed that at the genus level, the relative abundance of in the probiotics group was increased, the relative abundance of and in the CMP group were enhanced, and the relative abundance of in the compound group was raised compared with the control ( < 0.05). In summary, supplementation with probiotics can promote rumen protein fermentation but decrease the diversity of bacteria in rumen fluid; however, CMP treatment increased the relative abundance of , changed rumen microbial fermentation mode, increased the immune function, and ultimately improved the growth performance.
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http://dx.doi.org/10.3389/fvets.2021.681389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264418PMC
June 2021

Identification of pathogen(s) in infectious diseases using shotgun metagenomic sequencing and conventional culture: a comparative study.

PeerJ 2021 29;9:e11699. Epub 2021 Jun 29.

Sepsis Translational Medicine Key Lab of Hunan Province, Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, China.

Background: Early and accurate diagnosis of microorganism(s) is important to optimize antimicrobial therapy. Shotgun metagenomic sequencing technology, an unbiased and comprehensive method for pathogen identification, seems to potentially assist or even replace conventional microbiological methodology in the diagnosis of infectious diseases. However, evidence in clinical application of this platform is relatively limited.

Methods: To evaluate the capability of shotgun metagenomic sequencing technology in clinical practice, both shotgun metagenomic sequencing and conventional culture were performed in the PCR-positive body fluid specimens of 20 patients with suspected infection. The sequenced data were then analyzed for taxonomic identification of microbes and antibiotic resistance gene prediction using bioinformatics pipeline.

Results: Shotgun metagenomic sequencing results showed a concordance of 17/20 compared with culture results in bacterial detection, and a concordance of 20/20 compared with culture results in fungal detection. Besides, drug-resistant types annotated from antibiotic resistance genes showed much similarity with antibiotic classes identified by susceptibility tests, and more than half of the specimens had consistent drug types between shotgun metagenomic sequencing and culture results.

Conclusions: Pathogen identification and antibiotic resistance gene prediction by shotgun metagenomic sequencing identification had the potential to diagnose microorganisms in infectious diseases, and it was especially helpful for multiple microbial co-infections and for the cases where standard culture approached failed to identify microorganisms.
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http://dx.doi.org/10.7717/peerj.11699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253115PMC
June 2021

Identification and Characterization of Robust Hepatocellular Carcinoma Prognostic Subtypes Based on an Integrative Metabolite-Protein Interaction Network.

Adv Sci (Weinh) 2021 Jul 11:e2100311. Epub 2021 Jul 11.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.

Metabolite-protein interactions (MPIs) play key roles in cancer metabolism. However, our current knowledge about MPIs in cancers remains limited due to the complexity of cancer cells. Herein, the authors construct an integrative MPI network and propose a MPI network based hepatocellular carcinoma (HCC) subtyping and mechanism exploration workflow. Based on the expressions of hub proteins on the MPI network, two prognosis-distinctive HCC subtypes are identified. Meanwhile, multiple interdependent features of the poor prognostic subtype are observed, including hypoxia, DNA hypermethylation of metabolic pathways, fatty acid accumulation, immune pathway up-regulation, and exhausted T-cell infiltration. Notably, the immune pathway up-regulation is probably induced by accumulated unsaturated fatty acids which are predicted to interact with multiple immune regulators like SRC and TGFB1. Moreover, based on tumor microenvironment compositions, the poor prognostic subtype is further divided into two sub-populations showing remarkable differences in metabolism. The subtyping shows a strong consistency across multiple HCC cohorts including early-stage HCC. Overall, the authors redefine robust HCC prognosis subtypes and identify potential MPIs linking metabolism to immune regulations, thus promoting understanding and clinical applications about HCC metabolism heterogeneity.
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http://dx.doi.org/10.1002/advs.202100311DOI Listing
July 2021

Microplastics interaction with terrestrial plants and its impacts on agriculture.

J Environ Qual 2021 Jul 10. Epub 2021 Jul 10.

Laboratory of Plant Molecular Biology and Biotechnology, Department of Biology, University of North Carolina Greensboro, Greensboro, North Carolina, 27402, United States.

Microplastics (MPs) are widespread in natural ecosystems and have attracted considerable attention from scientists all over the world because they are believed to threaten every life form. In addition to their potential physical and chemical effects on organisms, MPs may act as a carrier for transferring many micropollutants including antibiotics, heavy metals and others. Over the last 10-15 years, extensive research has been carried out on MPs in marine environment, its sources, fate and toxicity. However, studies concerning their accumulation in soil ecosystem, uptake, internalization and impacts on photosynthetic components of the terrestrial ecosystem, and risk assessment have been scanty. Thus, there is a large knowledge gap on the extent to which terrestrial environments, especially agroecosystems are affected by MPs, and their subsequent risks to human health. This review summarizes up-to-date findings about MPs on terrestrial environments and would provide some guidelines for future studies regarding the phytotoxic effects of MPs on plants, mechanism of uptake and translocation in plant tissues, detection tools for MPs in plants, impacts on plant growth, development and agricultural productivity, and most importantly the future prospects of MPs interaction and accumulation in plants. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jeq2.20264DOI Listing
July 2021

Lasso estimation of hierarchical interactions for analyzing heterogeneity of treatment effect.

Stat Med 2021 Jul 8. Epub 2021 Jul 8.

Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Individuals differ in how they respond to a given treatment. In an effort to predict the treatment response and analyze the heterogeneity of treatment effect, we propose a general modeling framework by identifying treatment-covariate interactions honoring a hierarchical condition. We construct a single-step norm penalty procedure that maintains the hierarchical structure of interactions in the sense that a treatment-covariate interaction term is included in the model only when either the covariate or both the covariate and treatment have nonzero main effects. We developed a constrained Lasso approach with two parameterization schemes that enforce the hierarchical interaction restriction differently. We solved the resulting constrained optimization problem using a spectral projected gradient method. We compared our methods to the unstructured Lasso using simulation studies including a scenario that violates the hierarchical condition (misspecified model). The simulations showed that our methods yielded more parsimonious models and outperformed the unstructured Lasso for correctly identifying nonzero treatment-covariate interactions. The superior performance of our methods are also corroborated by an application to a large randomized clinical trial data investigating a drug for treating congestive heart failure (N = 2569). Our methods provide a well-suited approach for doing secondary analysis in clinical trials to analyze heterogeneous treatment effects and to identify predictive biomarkers.
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http://dx.doi.org/10.1002/sim.9132DOI Listing
July 2021

Application of 5G Technology to Conduct Real-Time Teleretinal Laser Photocoagulation for the Treatment of Diabetic Retinopathy.

JAMA Ophthalmol 2021 Jul 8. Epub 2021 Jul 8.

Department of Ophthalmology, Peking Union Medical College Hospital, Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Importance: Interest in teleophthalmology has been growing, especially during the COVID-19 pandemic. The advent of fifth-generation (5G) wireless systems has the potential to revolutionize teleophthalmology, but these systems have not previously been leveraged to conduct therapeutic telemedicine in the ophthalmology field.

Objective: To assess the feasibility of 5G real-time laser photocoagulation as a telemedicine-based treatment for diabetic retinopathy (DR).

Design, Setting, And Participants: This was a prospective study involving a retinal specialist from the Peking Union Medical College Hospital in Beijing, China, who performed online 5G real-time navigated retinal laser photocoagulation to treat participants with proliferative or severe nonproliferative DR who had been recruited in the Huzhou First People's Hospital in Zhejiang Province, China, located 1200 km from Beijing from October 2019 to July 2020.

Interventions: These teleretinal DR and laser management procedures were conducted using a teleophthalmology platform that used the videoconference platform for teleconsultation, after which telelaser planning and intervention were conducted with a laser system and a platform for remote computer control, which were connected via 5G networks.

Main Outcomes And Measures: Diabetic eye prognosis and the real-time laser therapy transmission speed were evaluated.

Results: A total of 6 participants (9 eyes) were included. Six eyes were treated via panretinal photocoagulation alone, while 1 eye underwent focal/grid photocoagulation and 2 eyes underwent both panretinal photocoagulation and focal/grid photocoagulation. The mean (SD) age was 53.7 (13.6) years (range, 32-67 years). The mean (SD) duration of diabetes was 14.3 (6.4) years (range, 3-20 years). The mean (SD) logMAR at baseline was 0.32 (0.20) (20/30 Snellen equivalent). Retinal telephotocoagulation operations were performed on all eyes without any noticeable delay during treatment. The mean (SD) number of panretinal photocoagulation laser spots per eye in 1 session was 913 (243).

Conclusions And Relevance: This study introduces a novel teleophthalmology paradigm to treat DR at a distance. Applying novel technologies may continue to ensure that remote patients with DR and other conditions have access to essential health care. Further studies will be needed to compare this approach with the current standard of care to determine whether visual acuity or safety outcomes differ.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.2312DOI Listing
July 2021

Ticagrelor and Dapagliflozin Have Additive Effects in Ameliorating Diabetic Nephropathy in Mice with Type-2 Diabetes Mellitus.

Cardiovasc Drugs Ther 2021 Jul 7. Epub 2021 Jul 7.

The Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Blvd, BSB 648, Galveston, TX, 77555, USA.

Purpose: Ticagrelor and dapagliflozin can suppress the activation of the NOD-like receptor 3 (NLRP3)-inflammasome and activate AMP-activated protein kinase (AMPK). The anti-inflammatory effects of dapagliflozin has been shown to depend on AMPK activation. Dapagliflozin and ticagrelor have been shown to have additive effects on the progression of diabetic cardiomyopathy in BTBR ob/ob mice with type-2 diabetes. We assessed whether dapagliflozin and ticagrelor have additive effects on the activation of the NLRP3-inflammasome and the progression of diabetic nephropathy in mice with type-2 diabetes.

Methods: Eight-week-old BTBR received either no-drug, dapagliflozin (1.5 mg/kg/d), ticagrelor (100 mg/kg/d), or their combination for 12 weeks. Blood was assessed weekly for glucose and urine for glucose and albumin. After 12 weeks, blood creatinine, cystatin C, inflammasome activation, and insulin were assessed by ELISA. Renal cortex samples were assessed by hematoxylin and eosin and periodic acid-Schiff staining. RT-PCR and immunoblotting were used to evaluate fibrosis and the activation of Akt, AMPK and the inflammasome.

Results: Both ticagrelor and dapagliflozin reduced serum creatinine and cystatin C levels and urinary albumin. Both drugs attenuated the increase in glomerular area and mesangial matrix index. Both drugs decreased collagen-1 and collagen-3 expression and the activation of the NLRP3-inflammasome. Both drugs increased P-AMPK levels, but only dapagliflozin increased P-Akt levels. Overall, the protective effects of dapagliflozin and ticagrelor were additive.

Conclusions: Dapagliflozin and ticagrelor attenuated the progression of diabetic nephropathy in BTBR ob/ob mice with additive effects of the combination. This was associated with AMPK activation and reduced activation of the NLRP3 inflammasome, whereas only dapagliflozin increased Akt activation.
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http://dx.doi.org/10.1007/s10557-021-07222-xDOI Listing
July 2021

A scoring system for predicting the prognosis of late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation.

Transplant Cell Ther 2021 Jul 3. Epub 2021 Jul 3.

Peking University People's Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. Electronic address:

Background: Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developed during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with LOSP have high mortality, so it is important to identify prognostic factors.

Objectives: In this study, we aimed to develop a risk score system with broad applicability that could help predict the risk of LOSP-associated mortality.

Study Design: We retrospectively analyzed 100 patients with LOSP after allo-HSCT from June 2009 to July 2017. The assessment variables included immune, nutritional and metabolic parameters at the onset of LOSP.

Results: Of all 100 patients who suffered LOSP after allo-HSCT, 45 (45%) patients eventually died, and 55 (55%) patients were positive for organisms, with the most common being viruses. In the multivariate analysis, higher monocyte (≥0.20 vs. <0.20 × 10/L, P=0.001), higher albumin (≥30.5 vs. <30.5 g/L, P=0.044), lower lactic dehydrogenase (<250 vs. ≥250 U/L, P=0.008) and lower blood urea nitrogen (<7.2 vs. ≥7.2 mmol/L, P=0.026) levels at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the above results showed that the probability of 60-day survival decreased with increasing risk factors and were 96.3% (low-risk group), 49.1% (intermediate-risk group) and 12.5% (high-risk group).

Conclusions: The results indicated that the scoring system used 4 variables could stratify patients with different probabilities of survival after LOSP, which suggested patients' immune, nutritional and metabolic status were crucial for outcome.
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http://dx.doi.org/10.1016/j.jtct.2021.06.031DOI Listing
July 2021

Forkhead box family transcription factors as versatile regulators for cellular reprogramming to pluripotency.

Cell Regen 2021 Jul 2;10(1):17. Epub 2021 Jul 2.

Joint School of Life Science, Guangzhou Institutes of Biomedicine and Health, Chinese Academic and Sciences, Guangzhou Medical School, Guangzhou, 511436, China.

Forkhead box (Fox) transcription factors play important roles in mammalian development and disease. However, their function in mouse somatic cell reprogramming remains unclear. Here, we report that FoxD subfamily and FoxG1 accelerate induced pluripotent stem cells (iPSCs) generation from mouse fibroblasts as early as day4 while FoxA and FoxO subfamily impede this process obviously. More importantly, FoxD3, FoxD4 and FoxG1 can replace Oct4 respectively and generate iPSCs with germline transmission together with Sox2 and Klf4. On the contrary, FoxO6 almost totally blocks reprogramming through inhibiting cell proliferation, suppressing the expression of pluripotent genes and hindering the process of mesenchymal to epithelial transition (MET). Thus, our study uncovers unexpected roles of Fox transcription factors in reprogramming and offers new insights into cell fate transition.
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http://dx.doi.org/10.1186/s13619-021-00078-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249537PMC
July 2021

Predictive Value of Dynamic Peri-Transplantation MRD Assessed By MFC Either Alone or in Combination with Other Variables for Outcomes of Patients with T-Cell Acute Lymphoblastic Leukemia.

Curr Med Sci 2021 Jun 28;41(3):443-453. Epub 2021 Jun 28.

Peking University People's Hospital and Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.

We performed a retrospective analysis to investigate dynamic peri-hematopoietic stem cell transplantation (HSCT) minimal/measurable residual disease (MRD) on outcomes in patients with T-cell acute lymphoblastic leukemia (T-ALL). A total of 271 patients were enrolled and classified into three groups: unchanged negative MRD pre- and post-HSCT group (group A), post-MRD non-increase group (group B), and post-MRD increase group (group C). The patients in group B and group C experienced a higher cumulative incidence of relapse (CIR) (42% vs. 71% vs. 16%, P<0.001) and lower leukemia-free survival (LFS) (46% vs. 21% vs. 70%, P<0.001) and overall survival (OS) (50% vs. 28% vs. 72%, P<0.001) than in group A, but there was no significant difference in non-relapse mortality (NRM) among three groups (14% vs. 12% vs. 8%, P=0.752). Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR (HR=2.392, 95% CI, 1.816-3.151, P<0.001), LFS (HR=1.964, 95% CI, 1.546-2.496, P<0.001) and OS (HR=1.731, 95% CI, 1.348-2.222, P<0.001). We also established a risk scoring system based on dynamic peri-HSCT MRD combined with remission status pre-HSCT and onset of chronic graft-versus-host disease (GVHD). This risk scoring system could better distinguish CIR (c=0.730) than that for pre-HSCT MRD (c=0.562), post-HSCT MRD (c=0.616) and pre- and post-MRD dynamics (c=0.648). Our results confirm the outcome predictive value of dynamic peri-HSCT MRD either alone or in combination with other variables for patients with T-ALL.
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http://dx.doi.org/10.1007/s11596-021-2390-6DOI Listing
June 2021

Association between STAT4 gene polymorphism and type 2 diabetes risk in Chinese Han population.

BMC Med Genomics 2021 Jun 27;14(1):169. Epub 2021 Jun 27.

Department of Endocrinology and Second Department of Geriatrics, The First Affiliated Hospital of Xi'an Jiaotong University, #277 West Yanta Road, Xi'an, 710061, Shaanxi, China.

Background: Evidence from genetic epidemiology indicates that type 2 diabetes (T2D) has a strong genetic basis. Activated STAT4 has an inflammatory effect, and STAT4 is an important mediator of inflammation in diabetes. Our study aimed to study the association between STAT4 single nucleotide polymorphisms (SNPs) and T2D susceptibility in Chinese Han population.

Methods: We conducted a 'case-control' study among 500 T2D patients and 501 healthy individuals. 5 candidate STAT4 SNPs were successfully genotyped. The association between SNPs and T2D susceptibility under different genetic models was evaluated by logistic regression analysis. 'SNP-SNP' interaction was analyzed and completed by multi-factor dimensionality reduction (MDR). Finally, we evaluated the differences of clinical characteristics under different genotypes by one-factor analysis of variance.

Results: The overall results showed that STAT4 rs3821236 was associated with increasing T2D risk under allele (OR 1.23, p = 0.020), homozygous (OR 1.51, p = 0.025), dominant (OR 1.36, p = 0.029), and additive models (OR 1.23, p = 0.020). The results of stratified analysis showed that rs3821236, rs11893432, and rs11889341 were risk factors for T2D among participants ≤ 60 years old. Only rs11893432 was associated with increased T2D risk among female participants. There was also a potential association between rs3821236 and T2D with nephropathy risk. STAT4 rs11893432, rs7574865 and rs897200 were significantly associated with lysophosphatidic acid, cystatin C and thyroxine t4, respectively.

Conclusion: The genetic polymorphisms of STAT4 is potentially associated with T2D susceptibility of Chinese population. In particular, rs3821236 is significantly associated with T2D risk both in the overall and several subgroup analyses. Our study may provide new ideas for T2D individualized diagnosis/protection.
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http://dx.doi.org/10.1186/s12920-021-01000-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237503PMC
June 2021

Chinese women's attitudes towards postpartum interventions to prevent type 2 diabetes after gestational diabetes: a semi-structured qualitative study.

Reprod Health 2021 Jun 26;18(1):133. Epub 2021 Jun 26.

Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK.

Background: Gestational diabetes (GDM) is a global problem affecting millions of pregnant women, including in mainland China. These women are at high risk of Type II diabetes (T2DM). Cost-effective and clinically effective interventions are needed. We aimed to explore Chinese women's perspectives, concerns and motivations towards participation in early postpartum interventions and/or research to prevent the development of T2DM after a GDM-affected pregnancy.

Methods: We conducted a qualitative study in two hospitals in Chengdu, Southwest China. Face-to-face semi-structured interviews were conducted with 20 women with recent experience of GDM: 16 postpartum women and 4 pregnant women. Women were asked about their attitudes towards postpartum screening for type 2 diabetes, lifestyle interventions, mHealth delivered interventions and pharmacologic interventions (specifically metformin). An inductive approach to analysis was used. Interviews were recorded, transcribed, and coded using NVivo 12 Pro.

Results: Most women held positive attitudes towards participating in T2DM screening, and were willing to participate in postpartum interventions to prevent T2DM through lifestyle change or mHealth interventions. Women were less likely to agree to pharmacological intervention, unless they had family members with diabetes or needed medication themselves during pregnancy. We identified seven domains influencing women's attitudes towards future interventions: (1) experiences with the health system during pregnancy; (2) living in an enabling environment; (3) the experience of T2DM in family members; (4) knowledge of diabetes and perception of risk; (5) concerns about personal and baby health; (6) feelings and emotions, and (7) lifestyle constraints. Those with more severe GDM, an enabling environment and health knowledge, and with experience of T2DM in family members expressed more favourable views of postpartum interventions and research participation to prevent T2DM after GDM. Those who perceived themselves as having mild GDM and those with time/lifestyle constraints were less likely to participate.

Conclusions: Women with experiences of GDM in Chengdu are generally willing to participate in early postpartum interventions and/or research to reduce their risk of T2DM, with a preference for non-drug, mHealth based interventions, integrating lifestyle change strategies, blood glucose monitoring, postpartum recovery and mental health.
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http://dx.doi.org/10.1186/s12978-021-01180-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236134PMC
June 2021

Aging and Mesenchymal Stem Cells: Therapeutic Opportunities and Challenges in the Older Group.

Gerontology 2021 Jun 23:1-14. Epub 2021 Jun 23.

Hunan Key Laboratory of Oral Health Research, Hunan 3D Printing Engineering Research Center of Oral Care, Hunan Clinical Research Center of Oral Major Diseases and Oral Health, Xiangya Stomatological Hospital, and Xiangya School of Stomatology, Central South University, Changsha, China.

With aging, a portion of cells, including mesenchymal stem cells (MSCs), become senescent, and these senescent cells accumulate and promote various age-related diseases. Therefore, the older age group has become a major population for MSC therapy, which is aimed at improving tissue regeneration and function of the aged body. However, the application of MSC therapy is often unsatisfying in the aged group. One reasonable conjecture for this correlation is that aging microenvironment reduces the number and function of MSCs. Cellular senescence also plays an important role in MSC function impairment. Thus, it is necessary to explore the relationship between senescence and MSCs for improving the application of MSCs in the elderly. Here, we present the influence of aging on MSCs and the characteristics and functional changes of senescent MSCs. Furthermore, current therapeutic strategies for improving MSC therapy in the elderly group are also discussed.
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http://dx.doi.org/10.1159/000516668DOI Listing
June 2021

Near-Infrared Light-Driven Multifunctional Tubular Micromotors for Treatment of Atherosclerosis.

ACS Appl Mater Interfaces 2021 Jul 22;13(26):30930-30940. Epub 2021 Jun 22.

Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.

One of the difficulties in atherosclerosis treatment is that the ablation of inflammatory macrophages, repair of vascular endothelial injury, and anti-tissue proliferation should be considered. However, there are few studies that can solve the abovementioned problems simultaneously. Herein, we present a kind of near-infrared (NIR) light-driven multifunctional mesoporous/macroporous tubular micromotor which can rapidly target the damaged blood vessels and release different drugs. Their motion effect can promote themselves to penetrate into the plaque site, and the generated heat effect caused by NIR irradiation can realize the photothermal ablation of inflammatory macrophages. Furthermore, these micromotors can rapidly release the vascular endothelial growth factor for endothelialization and slowly release paclitaxel for antiproliferation to achieve synergistic treatment of atherosclerosis. results demonstrated that the micromotors can achieve a good therapeutic effect for atherosclerosis. This kind of micro/nanomotor technology with a complex porous structure for drug loading will bring a more potential treatment platform for the disease.
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http://dx.doi.org/10.1021/acsami.1c03600DOI Listing
July 2021

Study on correlation between coagulation indexes and disease progression in patients with cirrhosis.

Am J Transl Res 2021 15;13(5):4614-4623. Epub 2021 May 15.

Digestive Internal Medicine, Xiangnan University Affiliated Hospital Chenzhou, Hunan Province, China.

Objective: To inquire into the significance of coagulation indexes in the progression of cirrhosis.

Methods: A total of 108 patients with cirrhosis treated in our hospital were collected as the research group (RG), and 105 healthy people who underwent concurrent physical examination were selected as the control group (CG). The coagulation indexes of all the participants were tested to determine their significance in cirrhosis progression.

Results: Compared with the CG, prothrombin time (PT), activated partial thrombin time (APTT) and thrombin time (TT) in the RG were statistically prolonged, while fibrinogen (FIB) was notably decreased (P<0.05). With the increase of Child-Pugh score, PT, APTT and TT prolonged and FIB reduced gradually (P<0.05). The coagulation indexes of patients were correlated with Child-Pugh score (P<0.05). Patients in the RG showed markedly higher alanine aminotransferase (ALT), total bilirubin (TBil), total bile acid (TBA), mean platelet volume (MPV), platelet distribution width (PDW) and platelet-large cell ratio (P-LCR), with notably lower albumin (ALB), prealbumin (PA), platelet count (PLT) and coagulation factors compared with the CG. As the Child-Pugh score increased, the ALT, TBil, TBA, MPV, PDW and P-LCR gradually elevated in the RG (P<0.05), whilst coagulation factors, ALB, PLT and PA all gradually decreased (P<0.05). The value of area under the curve (AUC) of each coagulation index for early diagnosis of cirrhosis was >0.80, and the sensitivity was >80% (P<0.05).

Conclusion: Coagulation indexes, coagulation factors, platelet parameters and liver function all effectively reflect the level of liver injury; especially which, coagulation indexes are related to the severity of liver injury, and can provide evidence for the early diagnosis of cirrhosis patients, with clinical significance.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205686PMC
May 2021

Electrocatalytic and Photocatalytic Reduction of Carbon Dioxide by Earth-abundant Bimetallic Molecular Catalysts.

Chemphyschem 2021 Jun 18. Epub 2021 Jun 18.

Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Hong Kong, China.

Converting CO into useful resources by electrocatalysis and photocatalysis is a promising strategy for recycling of the gas and electrification of industries. Numerous studies have shown that multinuclear metal catalysts have higher selectivity and catalytic activity than monometallic catalysts due to the synergistic effects between the metal sites. In this review, we summarize some of the recent progress on the electrocatalytic and photocatalytic reduction of CO by earth-abundant bimetallic molecular catalysts.
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http://dx.doi.org/10.1002/cphc.202100330DOI Listing
June 2021

Structural Engineering of Hierarchical Aerogels Comprised of Multi-dimensional Gradient Carbon Nanoarchitectures for Highly Efficient Microwave Absorption.

Nanomicro Lett 2021 Jun 15;13(1):144. Epub 2021 Jun 15.

School of Physics, Dalian University of Technology, Dalian, 116024, Liaoning, People's Republic of China.

Recently, multilevel structural carbon aerogels are deemed as attractive candidates for microwave absorbing materials. Nevertheless, excessive stack and agglomeration for low-dimension carbon nanomaterials inducing impedance mismatch are significant challenges. Herein, the delicate "3D helix-2D sheet-1D fiber-0D dot" hierarchical aerogels have been successfully synthesized, for the first time, by sequential processes of hydrothermal self-assembly and in-situ chemical vapor deposition method. Particularly, the graphene sheets are uniformly intercalated by 3D helical carbon nanocoils, which give a feasible solution to the mentioned problem and endows the as-obtained aerogel with abundant porous structures and better dielectric properties. Moreover, by adjusting the content of 0D core-shell structured particles and the parameters for growth of the 1D carbon nanofibers, tunable electromagnetic properties and excellent impedance matching are achieved, which plays a vital role in the microwave absorption performance. As expected, the optimized aerogels harvest excellent performance, including broad effective bandwidth and strong reflection loss at low filling ratio and thin thickness. This work gives valuable guidance and inspiration for the design of hierarchical materials comprised of dimensional gradient structures, which holds great application potential for electromagnetic wave attenuation.
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http://dx.doi.org/10.1007/s40820-021-00667-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206232PMC
June 2021

Fatty Acid Synthase Is Involved in Classical Swine Fever Virus Replication by Interaction with NS4B.

J Virol 2021 Jun 16:JVI0078121. Epub 2021 Jun 16.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

Classical swine fever virus (CSFV), a member of the genus Pestivirus of the family , relies on host machinery to complete its life cycle. Previous studies have shown a close connection between virus infection and fatty acid biosynthesis, mainly regulated by fatty acid synthase (FASN). However, the molecular action of how FASN participates in CSFV replication remains to be elucidated. In this study, two chemical inhibitors of the fatty acid synthesis pathway (TOFA and C75) significantly impaired the late stage of viral propagation, suggesting CSFV replication required fatty acid synthesis. We next found that CSFV infection stimulated the expression of FASN, whereas knockdown of FASN inhibited CSFV replication. Furthermore, confocal microscopy showed that FASN participated in the formation of replication complex (RC), which was associated with the endoplasmic reticulum (ER). Interestingly, CSFV NS4B interacted with FASN and promoted overexpression of FASN, which is regulated by functional Rab18. Moreover, we found that FASN regulated the formation of lipid droplets (LDs) upon CSFV infection, promoting the virus proliferation. Taken together, our work provides mechanistic insight into the role of FASN in the viral life of CSFV, and it highlights the potential antiviral target for the development of therapeutics against pestiviruses. Classical swine fever, caused by CSFV, is one of the notifiable diseases by the World Organization for Animal Health (OIE) and causes significant financial losses to the pig industry globally. CSFV, like other (+) strand RNA viruses, requires lipid and sterol biosynthesis for efficient replication. However, the role of lipid metabolism in CSFV replication remains unknown. Here, we found that fatty acid synthase (FASN) was involved in viral propagation. Moreover, FASN is recruited to CSFV replication sites in the ER and interacts with NS4B to regulate CSFV replication that requires Rab18. Furthermore, we speculated lipid droplets (LDs) biosynthesis, indirectly regulated by FASN, ultimately promotes CSFV replication. Our results highlight a critical role for fatty acid synthesis in CSFV infection, which might help control this devastating virus.
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http://dx.doi.org/10.1128/JVI.00781-21DOI Listing
June 2021

Nutritional targeting modification of silkworm pupae oil catalyzed by a smart hydrogel immobilized lipase.

Food Funct 2021 Jul 15;12(14):6240-6253. Epub 2021 Jun 15.

Jiangsu Key Laboratory Sericutural Biology and Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212100, China.

To prepare a nutritional supplement using silkworm pupae oil (SPO) as a feedstock, a microfluidic reactor with a smart hydrogel immobilized lipase was first constructed to reduce the relative content of palmitic acid at sn-1,3 and improve the nutritional function. The effects of flow rate, reaction temperature, and substrate molar ratio were investigated. In vitro digestion and pH-stat models were employed to analyze the digestion feature after the modification of SPO, while HPLC-ELSD, zeta potential, DSC, and TGA were used to evaluate the nutritional function. The relative content of "OOO" and "OPO" type triglycerides was increased by 49.48% and 107.67%, and that of palmitic acid at sn-1,3 was decreased by 49.61% in 10 s. After the verification of the in vitro digestion model, the fatty acid release rate of the modified SPO was significantly improved by 22.07%, indicating the nutritional function improvement of SPO. Therefore, the nutritional function of SPO has been improved successfully by the application of a microchannel reactor with photo-immobilized lipase, which could set a reference for the utilization of insect oil resources.
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http://dx.doi.org/10.1039/d1fo00913cDOI Listing
July 2021
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