Publications by authors named "Li Jia"

4,309 Publications

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A Novel Splicing Mutation c.335-1 G > A in the Cardiac Transcription Factor NKX2-5 Leads to Familial Atrial Septal Defect Through miR-19 and PYK2.

Stem Cell Rev Rep 2022 Jul 2. Epub 2022 Jul 2.

Department of Medical Genetics, College of Basic Medical Science, Army Medical University, 30#, Gaotanyan St., Shapingba District, Chongqing, People's Republic of China, 400038.

Mutations of NKX2-5 largely contribute to congenital heart diseases (CHDs), especially atrial septal defect (ASD). We identified a novel heterozygous splicing mutation c.335-1G > A in NKX2-5 gene in an ASD family via whole exome sequencing (WES) and linkage analysis. Utilizing the human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) as a disease model, we showed that haploinsufficiency of NKX2-5 contributed to aberrant orchestration of apoptosis and proliferation in ASD patient-derived hiPSC-CMs. RNA-seq profiling and dual-luciferase reporter assay revealed that NKX2-5 acts upstream of PYK2 via miR-19a and miR-19b (miR-19a/b) to regulate cardiomyocyte apoptosis. Meanwhile, miR-19a/b are also downstream mediators of NKX2-5 during cardiomyocyte proliferation. The novel splicing mutation c.335-1G > A in NKX2-5 and its potential pathogenic roles in ASD were demonstrated. Our work provides clues not only for deep understanding of NKX2-5 in cardia development, but also for better knowledge in the molecular mechanisms of CHDs.
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http://dx.doi.org/10.1007/s12015-022-10400-5DOI Listing
July 2022

Combining intramuscular and intranasal homologous prime-boost with a chimpanzee adenovirus-based COVID-19 vaccine elicits potent humoral and cellular immune responses in mice.

Emerg Microbes Infect 2022 Jul 1:1-27. Epub 2022 Jul 1.

Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing 102629, China.

The efficacy of many coronavirus disease 2019 (COVID-19) vaccines has been shown to decrease to varying extents against new severe acute respiratory syndrome coronavirus 2 variants, which are responsible for the continuing COVID-19 pandemic. Combining intramuscular and intranasal vaccination routes is a promising approach for achieving more potent immune responses. We evaluated the immunogenicity of prime-boost protocols with a chimpanzee adenovirus serotype 68 vector-based vaccine, ChAdTS-S, administered via both intranasal and intramuscular routes in BALB/c mice. Intramuscular priming followed by an intranasal booster elicited the highest levels of IgG, IgA, and pseudovirus neutralizing antibody titres among all the protocols tested at day 42 after prime immunization compared with the intranasal priming/intramuscular booster and prime-boost protocols using only one route. In addition, intramuscular priming followed by an intranasal booster induced high T-cell responses, measured using the IFN-γ ELISpot assay, that were similar to those observed upon intramuscular vaccination. All ChAdTS-S vaccination groups induced Th1-skewing of the T-cell response according to intracellular cytokine staining and Meso Scale Discovery cytokine profiling assays on day 56 after priming. This study provides reference data for assessing vaccination schemes of adenovirus-based COVID-19 vaccines with high immune efficacy.
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http://dx.doi.org/10.1080/22221751.2022.2097479DOI Listing
July 2022

A coupled framework for estimating pollutant emissions from open burning of specific crop residue: A case study for wheat.

Sci Total Environ 2022 Jun 27:156731. Epub 2022 Jun 27.

Key Laboratory of Beijing on Regional Air Pollution Control, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China.

Crop residue open burning is considered to be one of the main sources of pollutant emissions from rural areas. It is necessary to accurately establish an emissions inventory of specific crops which could reflect the specific spatiotemporal distribution characteristics of crop residue burning emissions. However, the information for emission estimation of specific crop in each province and year is seriously data-deficient, resulting in a large uncertainty in the emissions inventory. In this study, taking the open burning of wheat residue as an example, we propose a framework for estimating pollutant emissions for specific crop residue by combining phenological information, land use data, field investigation/statistical data, and fire detection information. The wheat residue open burning proportion (OBP) and the corresponding pollutant emissions were estimated for each province in mainland China from 2003 to 2019. The national average OBP and emissions of wheat crop residue open burning first increased and then decreased during this period, with the peak in 2012. The gridded spatial distribution showed that high-emission areas were mainly concentrated in central-eastern China, and the emission areas gradually shifted from south to north from April to September. The change of daily emissions from large-scale concentrated emissions to small-scale emissions demonstrated that straw open burning prohibition policies were effective in reducing the annual emissions and peak daily emissions. This study provides a promising method for the combination of data from multiple sources to estimate open burning of crop residues. The method can be used to obtain accurate and detailed emissions data to support research into biomass burning and the development of targeted mitigation strategies.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156731DOI Listing
June 2022

A Tandemly Activated Fluorescence Probe for Detecting Senescent Cells with Improved Selectivity by Targeting a Biomarker Combination.

ACS Sens 2022 Jun 30. Epub 2022 Jun 30.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

The heterogeneous and complex phenotypes of cellular senescence necessitate a biomarker combination for the accurate detection of senescent cells from others. However, this raises the challenge of detecting multiple senescent biomarkers in the same live cell simultaneously. Herein we reported the strategy of biomarker combination triggered tandem activation for designing senescence-specific fluorogenic probes, which resulted in the development of the probe . The fluorescence of can only be activated by the sequential stimulation by the senescent biomarker combination of β-galactosidase (βGal) and formaldehyde (FA), with βGal activating the sensing ability of the probe toward FA. Facilitated by probe , the simultaneous detection of a biomarker combination in the same live cell was realized. We have demonstrated the improved selectivity of probe toward senescent cells compared to the traditional single-biomarker-based probe. Probe was also successfully used to detect senescent cells in bleomycin-induced pulmonary fibrosis tissues. We expect probe to be a reliable tool for the study on cellular senescence and envision that this probe design strategy may be expanded to other biological events to improve accuracy.
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http://dx.doi.org/10.1021/acssensors.2c00719DOI Listing
June 2022

circFBXO7/miR-96-5p/MTSS1 axis is an important regulator in the Wnt signaling pathway in ovarian cancer.

Mol Cancer 2022 Jun 29;21(1):137. Epub 2022 Jun 29.

Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.

Background: CircRNAs are a novel class of evolutionarily conserved noncoding RNA molecules that form covalently closed continuous loop structures without 5' caps and 3' poly(A) tails. Accumulating evidence suggests that circRNAs play important regulatory roles in cancer and are promising biomarkers for cancer diagnosis and prognosis, as well as targets for cancer therapy. In this study, we identify and explore the role of a novel circRNA, circFBXO7, in ovarian cancer.

Methods: rRNA-depleted RNA-sequencing was performed to identify differentially expressed circRNAs between ovarian cancerous and normal tissues. qRT-PCR and single-molecule RNA in-situ hybridization was used to quantify circFBXO7 expression in tumor tissues. The association of circFBXO7 expression with patient prognosis was evaluated by Kaplan-Meier survival analysis. The biological function of circFBXO7 was also investigated using loss-of-function and gain-of-function assays in vivo and in vitro. Luciferase reporter and TOP/FOP-Flash reporter assays were then conducted together with RNA immunoprecipitation and western blot to assess the circFBXO7/miR-96-5p/MTSS1/Wnt/β-catenin axis.

Results: circFBXO7 was downregulated in ovarian cancer which was associated with poor prognosis. Biologically, circFBXO7 overexpression significantly suppressed ovarian cancer cell proliferation, migration, and invasion in vitro, and inhibited tumor growth and metastasis in vivo, whereas its knockdown exerted an opposite role. Mechanistically, circFBXO7 functioned as a competing endogenous RNA for miR-96-5p to regulate the expression of MTSS1. Consequently, downregulation of MTSS1 led to excessive accumulation of β-catenin and increased phosphorylation of GSK3β, leading to the translocation of β-catenin to the nucleus, thereby activating the Wnt/β-catenin signaling pathway and ultimately promoting ovarian cancer progression.

Conclusions: Our findings indicate that circFBXO7 acts as a bone fide tumor suppressor in ovarian cancer and that the circFBXO7/miR-96-5p/MTSS1 axis is an important regulator in the Wnt/β-catenin signaling pathway which may provide a promising target for ovarian cancer therapy.
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http://dx.doi.org/10.1186/s12943-022-01611-yDOI Listing
June 2022

Effect of Orbital-Symmetry Matching in a Metal-Organic Framework for Highly Efficient CH/CH and CH/CO Separations.

Inorg Chem 2022 Jun 29. Epub 2022 Jun 29.

School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, China.

The detailed mechanism of metal-organic-framework (MOF)-based separation materials is still obscure, which obviously hinders their actual application. To address this problem, a trinuclear Cu-cluster-based MOF with a minimum metal-active plane was synthesized for the study of the very challenging CH/CH and CH/CO separations. Via dispersion-corrected density functional theory calculations, it is indicated that the difference of the adsorption energy accounts for the excellent separation properties toward CH/CH and CH/CO mixtures, while the frontier molecular orbitals demonstrate that the adsorption-energy difference originates from the orbital-symmetry difference of gas molecules. All of these results provide not only deep insight into the separation mechanism but also an alternative strategy to prepare efficient adsorbents.
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http://dx.doi.org/10.1021/acs.inorgchem.2c01218DOI Listing
June 2022

Aberrant DNA hydroxymethylation reshapes transcription factor binding in myeloid neoplasms.

Clin Epigenetics 2022 Jun 28;14(1):81. Epub 2022 Jun 28.

Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M University, Room 404, 2121. W. Holcombe Blvd, Houston, TX, 77030, USA.

Epigenetic abnormalities in DNA hydroxymethylation (5hmC) have been detected in patients with myeloid neoplasms, suggesting that 5hmC might act as a valuable epigenetic mark to reflect the disease status of myeloid neoplasms. Here, we report systematic genome-wide mapping of the DNA hydroxymethylomes in over 70 patients with myeloid neoplasms. Our integrative analysis leads to the identification of distinct 5hmC signatures that can sensitively discriminate patients from healthy individuals. At the molecular level, we unveiled dynamic 5hmC changes within key transcription factor (e.g., the CEBP family) binding motifs that are essential for hematopoiesis and myeloid lineage specification. 5hmC redistribution was found to alter the genome-wide binding of CEBP-α, thereby reprogramming transcriptional outputs to affect leukemia cell survival and stemness. Taken together, we provide a comprehensive 5hmC atlas representative of myeloid neoplasms, which sets the stage for future exploration on the epigenetic etiology of hematological malignancies. Mechanistically, our study further furnishes important insights into how abnormal 5hmC distribution in patients directly interrupts the binding of transcription factors to reshape transcriptional landscapes and aggravate leukemogenesis.
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http://dx.doi.org/10.1186/s13148-022-01297-5DOI Listing
June 2022

Lactobacillus plantarum 17-5 attenuates Escherichia coli-induced inflammatory responses via inhibiting the activation of the NF-κB and MAPK signalling pathways in bovine mammary epithelial cells.

BMC Vet Res 2022 Jun 28;18(1):250. Epub 2022 Jun 28.

College of Veterinary Medicine, Hebei Agricultural University, Baoding, 071001, Hebei, China.

Background: Mastitis is one of the most prevalent diseases and causes considerable economic losses in the dairy farming sector and dairy industry. Presently, antibiotic treatment is still the main method to control this disease, but it also brings bacterial resistance and drug residue problems. Lactobacillus plantarum (L. plantarum) is a multifunctional probiotic that exists widely in nature. Due to its anti-inflammatory potential, L. plantarum has recently been widely researched in complementary therapies for various inflammatory diseases. In this study, the apoptotic ratio, the expression levels of various inflammatory mediators and key signalling pathway proteins in Escherichia coli-induced bovine mammary epithelial cells (BMECs) under different doses of L. plantarum 17-5 intervention were evaluated.

Results: The data showed that L. plantarum 17-5 reduced the apoptotic ratio, downregulated the mRNA expression levels of TLR2, TLR4, MyD88, IL1β, IL6, IL8, TNFα, COX2, iNOS, CXCL2 and CXCL10, and inhibited the activation of the NF-κB and MAPK signalling pathways by suppressing the phosphorylation levels of p65, IκBα, p38, ERK and JNK.

Conclusions: The results proved that L. plantarum 17-5 exerted alleviative effects in Escherichia coli-induced inflammatory responses of BMECs.
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http://dx.doi.org/10.1186/s12917-022-03355-9DOI Listing
June 2022

[Mechanisms of electroacupuncture in improving obesity-induced insulin resistance via TLR4/NF-κB inflammatory pathway in liver].

Zhen Ci Yan Jiu 2022 Jun;47(6):504-9

College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan 430061; Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Wuhan 430061.

Objective: To investigate the effect of electroacupuncture (EA) on the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) inflammatory pathway in the liver of obese rats with insulin resistance, and explore its mechanism.

Methods: Male Wistar rats were randomly divided into a normal group (=15) and an experimental group (=30). The obesity-induced insulin resistance model was induced by the high-fat diet (HFD) in rats of the experimental group for 8 weeks. Subsequently, the model rats were further divided into a model group (=15) and an EA group (=15). EA was applied at "Zhongwan "(CV12), "Guanyuan" (CV4), "Zusanli "(ST36) and "Fenglong "(ST40) in the EA group for 10 min, three times a week for 8 weeks. The body weight of rats in each group was measured before intervention and at the 2nd, 4th, 6th, and 8th weeks during the intervention. Glucose infusion rate (GIR) was measured by glucose clamp test before and after treatment. After treatment, fast blood glucose (FBG) was detected by the glucometer, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The contents of fasting insulin (FINS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were determined by ELISA. The protein expressions of TLR4, IκB kinase β (IKKβ), phosphorylated IKKβ (p-IKKβ), NF-κB p65, and TNF-α related to the TLR4/NF-κB signaling pathway in the liver of rats were detected by Western blot.

Results: Compared with the normal group, the body weight, HOMA-IR levels, serum levels of FINS, TNF-α, and IL-6 were up-regulated (<0.01), and the GIR level was down-regulated (<0.01), the protein expressions of TLR4, IKKβ, p-IKKβ, NF-κB p65 and TNF-α in liver tissues were increased(<0.05) in the model group. Compared with the model group, the EA group showed weight loss from the 6th week, and the HOMA-IR levels,serum levels of FINS, TNF-α, and IL-6 were decreased(<0.01, <0.05), the GIR level was up-regulated (<0.01), the protein expressions of TLR4, IKKβ, p-IKKβ, NF-κB p65 and TNF-α in liver tissues were down-regulated (<0.05).

Conclusion: EA can reduce the inflammatory response and improve peripheral insulin sensitivity by inhibiting the TLR4/NF-κB pathway in liver tissues of obese rats with insulin resistance, showing a good regulatory effect on insulin resistance induced by obesity.
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http://dx.doi.org/10.13702/j.1000-0607.20210362DOI Listing
June 2022

Effects of Microplastics on Higher Plants: A Review.

Bull Environ Contam Toxicol 2022 Jun 26. Epub 2022 Jun 26.

College of Environmental Science and Engineering, Yangzhou University, Yangzhou, 225127, China.

Microplastics pose great risks to terrestrial systems owing to their large quantity and strong persistence. Higher plants, an irreplaceable part of the terrestrial ecosystem, are inevitably exposed to microplastics. This review highlights the effects of microplastics on higher plant growth and performance. The tested microplastics, plant species, and cultural methods used in existing studies were summarized. We discussed the reasons why these microplastics, plants, and methods were selected. The various responses of higher plants to microplastics in both soils and waters were critically reviewed. We also highlighted the influencing mechanisms of microplastics on higher plants. Conclusively, more than 13 types of common microplastics and more than 30 species of higher plants have been selected and studied by the published literatures. Soil culture tests and hydroponic experiments are almost equally divided. The effects of microplastics on higher plants varied among microplastic properties, plant species, and environmental factors. Microplastics had no or positive effects on higher plants under certain experimental conditions. However, more studies showed that microplastics can inhibit higher plant growth and performance. We reduced the inhibitory mechanisms into direct and indirect mechanisms. The direct mechanisms include blocking pores or light, causing mechanical damage to roots, hindering genes expression, and releasing additives. The indirect mechanisms contain changing soil properties, affecting soil microbes or soil animals, and affecting bioavailability of other pollutants. This review improves the understanding of effects and influencing mechanisms of microplastics on higher plants.
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http://dx.doi.org/10.1007/s00128-022-03566-8DOI Listing
June 2022

Synovitis mediates the association between bone marrow lesions and knee pain in osteoarthritis: data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium.

Osteoarthritis Cartilage 2022 Jun 21. Epub 2022 Jun 21.

Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. Electronic address:

Objectives: Although subchondral bone marrow lesions (BMLs) and synovitis have been well acknowledged as important sources of pain in knee osteoarthritis (KOA), it is unclear if synovitis plays the mediating role in the relationship between BMLs and knee pain.

Methods: We analyzed 600 subjects with magnetic resonance imaging (MRI) in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort at baseline and 24-month. BMLs and synovitis were measured according to the MRI Osteoarthritis Knee Score (MOAKS) scoring system. BMLs were scored in five subregions. A summary synovitis score of effusion and Hoffa-synovitis was calculated. Knee pain was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Linear regression models were applied to analyze the natural direct effect (NDE) of BMLs and synovitis with knee pain, respectively, and natural indirect effect (NIE) mediated by synovitis.

Results: 590 participants (58.8% females, with a mean age of 61.5) were included in the present analyses. For NDE, knee pain was cross-sectionally associated with medial femorotibial BMLs (β= 0.23, 95% CI: 0.09, 0.38) and synovitis (β= 0.40, 95% CI: 0.20, 0.60). Longitudinal associations retained significant [medial femorotibial BMLs (β=0.37, 95% CI: 0.21, 0.53); synovitis (0.72, 95% CI: 0.45, 0.99)]. In the NIE analyses, synovitis mediated the association between medial femorotibial BML and knee pain at baseline (β=0.051, 95% CI: 0.01, 0.09) and over 24 months (β= 0.079, 95% CI: 0.023, 0.15), with the mediating proportion of 17.8% and 22.4%, respectively.

Conclusion: Synovitis partially mediates the association between medial femorotibial BMLs and knee pain.
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http://dx.doi.org/10.1016/j.joca.2022.06.004DOI Listing
June 2022

Adoptive Cellular Therapy with Autologous Tumor-Infiltrating Lymphocytes and T-cell Receptor-Engineered T Cells Targeting Common p53 Neoantigens in Human Solid Tumors.

Cancer Immunol Res 2022 Jun 24:OF1-OF15. Epub 2022 Jun 24.

Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Adoptive cellular therapy (ACT) targeting neoantigens can achieve durable clinical responses in patients with cancer. Most neoantigens arise from patient-specific mutations, requiring highly individualized treatments. To broaden the applicability of ACT targeting neoantigens, we focused on TP53 mutations commonly shared across different cancer types. We performed whole-exome sequencing on 163 patients with metastatic solid cancers, identified 78 who had TP53 missense mutations, and through immunologic screening, identified 21 unique T-cell reactivities. Here, we report a library of 39 T-cell receptors (TCR) targeting TP53 mutations shared among 7.3% of patients with solid tumors. These TCRs recognized tumor cells in a TP53 mutation- and human leucocyte antigen (HLA)-specific manner in vitro and in vivo. Twelve patients with chemorefractory epithelial cancers were treated with ex vivo-expanded autologous tumor-infiltrating lymphocytes (TIL) that were naturally reactive against TP53 mutations. However, limited clinical responses (2 partial responses among 12 patients) were seen. These infusions contained low frequencies of mutant p53-reactive TILs that had exhausted phenotypes and showed poor persistence. We also treated one patient who had chemorefractory breast cancer with ACT comprising autologous peripheral blood lymphocytes transduced with an allogeneic HLA-A*02-restricted TCR specific for p53R175H. The infused cells exhibited an improved immunophenotype and prolonged persistence compared with TIL ACT and the patient experienced an objective tumor regression (-55%) that lasted 6 months. Collectively, these proof-of-concept data suggest that the library of TCRs targeting shared p53 neoantigens should be further evaluated for the treatment of patients with advanced human cancers. See related Spotlight by Klebanoff .
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http://dx.doi.org/10.1158/2326-6066.CIR-22-0040DOI Listing
June 2022

Genome-Wide Analysis and Expression Profiling of Gene Family in Revealed Higher Expression of in Roots under Cd Stress.

Front Biosci (Landmark Ed) 2022 Jun;27(6):186

School of Agriculture, Forestry and Food Engineering, Yibin University, 644000 Yibin, Sichuan, China.

Background: Tomato is an important part of daily food, rich source of multitude nutrients, suitable candidate for bio-pharmaceutical production due to berry size and has numerous health benefits. Transcriptional regulation of metalloregulatory heat shock protein-70 family plays pivotal role in plants tolerance against abiotic stress factors including salinity, heat, cold, drought and trace metal elements such as cadmium (Cd2+).

Methods: Here, we provide comprehensive report on identification of family genes in tomato () and their expression in tomato qPCR analysis under broad range of trace metal elements.

Results: analysis revealed 23 family genes in tomato, phylogenetically divided into four groups I-IV and displayed expression in all tissues. Gene Ontology (GO) analysis revealed that SlHSP70 proteins were membrane localized which were involved in metal ions translocation and oxidoreductase activity to counter hyper-accumlation of reactive oxygen species (ROS).

Conclusions: Cd2+ is a widespread heavy metal soil contaminent which is continously polluting fertile soils, a knotty issue which has serious implications over photosynthesis, nitrogen assimilation, minerals and water absorption by plants. Plants exposure to Cd2+ and subsequent qRT-PCR analysis revealed increased expression of in tomato roots, which can be employed in breeding low Cd2+ enriched tomato varieties.
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http://dx.doi.org/10.31083/j.fbl2706186DOI Listing
June 2022

Chidamide Maintenance Therapy Following Induction Therapy in Patients With Peripheral T-Cell Lymphoma Who Are Ineligible for Autologous Stem Cell Transplantation: Case Series From China.

Front Oncol 2022 7;12:875469. Epub 2022 Jun 7.

Department of Hematology, The First Hospital of Jilin University, Changchun, China.

Objective: To assess the potential benefit of chidamide maintenance therapy after induction treatment in peripheral T-cell lymphoma (PTCL).

Materials And Methods: The clinical data of 48 transplantation-ineligible patients with different PTCL subtypes who received continuous chidamide treatment after first-line therapy were collected. Progression-free survival (PFS), overall survival (OS), and safety were analyzed.

Results: In total, 68.8% of patients were male (33/48), the median age was 59.5 years (22~80). The pathological subtypes were angioimmunoblastic T-cell lymphoma (AITL, 43.8%), anaplastic large cell lymphoma (ALCL, 16.6%), PTCL-not otherwise specified (NOS, 25%), NK/T-cell lymphoma (NKT, 14.6%). 35.4% (7/48) patients had intermediate or high risk (IPI=3~5). 20 patients (41.7%) received chidamide as a maintenance treatment after achieving a complete response (CR). 57.1% (16/28) exhibited a better response after chidamide (9 cases partial response [PR] to CR, 7 from stable disease [SD] to PR). The CR and overall response rate (ORR) were 60.4% and 93.8%, respectively. In addition, 21/21 AITL, 10/12 PTCL-NOS, and 8/8 ALCL, 6/7 NK/T exhibited CR/PR as the best response during the follow-up period. Meanwhile, the CR and ORR did not differ by age (<60 ≥60: 50.0% 70.8%, P = 0.091; and 91.7% 95.8%, P = 0.551). The median follow-up period was 12.8 months (3.0-66.6), 14 patients developed PD (29.2%), 10 of them died of lymphoma (20.8%). Totally, the 40 cases achieved CR/PR from 1st line regimen got better PFS as well as OS than the rest 8 cases (the 1-year PFS was 80.8% 46.9% and the 2-year PFS was 71.9% 46.9%, P=0.012. the 1-year OS was 89.9% 72.6% and the 2-year OS was 85.9% 48.6%, P=0.032). No patients discontinued treatment because of adverse events. The most common toxicities were neutropenia (75.0%), anemia (79.2%), thrombocytopenia (58.3%), and anorexia (45.8%), and fatigue (43.8%).

Conclusion: Chidamide maintenance therapy led to improvements of PFS and OS with a manageable safety profile in patients with PTCL. Further randomized studies are required to examine the role of chidamide maintenance therapy in PTCL.
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http://dx.doi.org/10.3389/fonc.2022.875469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209709PMC
June 2022

Effect of Lindau Addition on Black Tea Flavor Quality and Volatile Metabolite Content.

Foods 2022 Jun 7;11(12). Epub 2022 Jun 7.

Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China.

The characteristic aroma of Chinese black tea (BT) produced in summer usually lacks intensity and persistence, reducing consumer acceptance and market demand. Lindau (STL) possesses excellent biological characteristics, making it a promising novel tea ingredient. We investigated the effects of different addition methods and concentrations for the novel additive STL on the sensory quality of BT. A 20:1500 g/g addition to rolled tea leaves was identified as the best BT with STL (BoS) treatment. We identified 141 volatile metabolites (VMs) for the first time in STL, with high alcohol, ester, ketone, enyne, alkyne, and alkane contents. Partial least-squares discriminant analysis distinguished the samples and revealed 28, 26, and 14 differential VMs in STL vs. BoS, BT vs. STL, and BT vs. BoS comparisons, respectively. Using a combination of Venn, multiple experiment viewer, and odor activity value analysis, 16 key differential VMs were identified. Compared to BT, the 1-octen-3-ol, 1-hexanol, 1-dodecanol, (E)-3-hexen-1-ol, phenylethyl alcohol, and 2-methoxy-3-(2-methylpropyl)-pyrazine contents in BoS were 394.7%, 53.6%, 34.1%, 24.4%, 9.9%, and 5.7% higher, respectively. BoS combined the aromatic properties of BT and STL into a sweet and glutinous rice flavor. The results provide theoretical support for future research and development of novel BT-based products.
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http://dx.doi.org/10.3390/foods11121678DOI Listing
June 2022

Synthesis of Group VIII Magnetic Transition-Metal-Doped Monolayer MoSe.

ACS Nano 2022 Jun 23. Epub 2022 Jun 23.

Hunan Key Laboratory of Two-Dimensional Materials, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University Changsha 410082, China.

The limitation on the spintronic applications of van der Waals layered transition-metal dichalcogenide semiconductors is ascribed to the intrinsic nonmagnetic feature. Recent studies have proved that substitutional doping is an effective route to alter the magnetic properties of two-dimensional transition-metal dichalcogenides (TMDs). However, highly valid and repeatable substitutional doping of TMDs remains to be developed. Herein, we report group VIII magnetic transition metal-doped molybdenum diselenide (MoSe) single crystals a one-pot mixed-salt-intermediated chemical vapor deposition method with high controllability and reproducibility. The high-angle annular dark-field scanning transmission electron microscopy studies further confirm that the sites of Fe are indeed substitutionally incorporated into the MoSe monolayer. The Fe-doped MoSe monolayer with a concentration from 0.93% to 6.10% could be obtained by controlling the ratios of FeCl/NaMoO. Moreover, this strategy can be extended to create Co(Ni)-doped MoSe monolayers. The magnetic hysteresis () measurements demonstrate that group VIII magnetic transition-metal-doped MoSe samples exhibit room-temperature ferromagnetism. Additionally, the Fe-doped MoSe field effect transistor shows n-type semiconductor characteristics, indicating the obtainment of a room-temperature dilute magnetic semiconductor. Our approach is universal in magnetic transition-metal substitutional doping of TMDs, and it inspires further research interest in the study of related spintronic and magnetoelectric applications.
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http://dx.doi.org/10.1021/acsnano.2c02214DOI Listing
June 2022

Quality Management of Pulmonary Nodule Radiology Reports Based on Natural Language Processing.

Bioengineering (Basel) 2022 Jun 1;9(6). Epub 2022 Jun 1.

Information Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

To investigate the feasibility of automated follow-up recommendations based on findings in radiology reports, this paper proposed a Natural Language Processing model specific for Pulmonary Nodule Radiology Reports. Unstructured findings used to describe pulmonary nodules in 48,091 radiology reports were processed in this study. We established an NLP model to extract information entities from findings of radiology reports, using deep learning and conditional random-field algorithms. Subsequently, we constructed a knowledge graph comprising 168 entities and four relationships, based on the export recommendations of the internationally renowned Fleischner Society for pulmonary nodules. These were employed in combination with rule templates to automatically generate follow-up recommendations. The automatically generated recommendations were then compared to the impression part of the reports to evaluate the matching rate of proper follow ups in the current situation. The NLP model identified eight types of entities with a recognition accuracy of up to 94.22%. A total of 43,898 out of 48,091 clinical reports were judged to contain appropriate follow-up recommendations, corresponding to the matching rate of 91.28%. The results show that NLP can be used on Chinese radiology reports to extract structured information at the content level, thereby realizing the prompt and intelligent follow-up suggestion generation or post-quality management of follow-up recommendations.
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http://dx.doi.org/10.3390/bioengineering9060244DOI Listing
June 2022

and inhibited oral squamous cell carcinomas by regulating genome stability.

Bioengineered 2022 Jun;13(6):14094-14106

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

Periodontitis is a risk factor for the development of oral squamous cell carcinomas (OSCC). Both DNA damage response (DDR) and activation of inflammasomes induced by the microbiome might play important roles in the development of tumors, in relation to genome stability of tumor cells. Herein, we explored whether periodontitis negative-associated bacteria ( and , namely called 'PNB'), which were highly abundant in healthy populations, could inhibit OSCC by promoting genome stability. Firstly, a murine SCC-7 tumor-bearing model that colonized with PNB was designed and used in this study. Then, cyclin D1 was detected by immunohistochemistry. Levels of DDR, NLRP3 inflammasomes and pro-inflammatory cytokines in tumors were detected by RT-qPCR or Western blot. Immune cells in spleens were detected by immunohistochemistry or immunofluorescence. Finally, the anti-cancer activity of PNB was assessed using CCK-8 assays and flow cystometry. Compared with the control, PNB decreased tumor weights from 0.77 ± 0.26 g to 0.42 ± 0.15 g and downregulated the expression of Cyclin D1. PNB activated the DDR by up-regulating γ-H2AX, p-ATR, and p-CHK1. PNB activated NLRP3 inflammasome-mediated pyroptosis via increases of NLRP3, gasdermin D, and mRNA levels of apoptosis-associated speck-like protein, Caspase-1. PNB suppressed the inflammatory response by down-regulating mRNA levels of NF-κΒ and IL-6 in tumors as well as the populations of CD4+ T cells and CD206+ immune cells in spleens. PNB inhibited proliferation and promoted cell death of HSC-3 cells. In conclusion, and showed a 'probiotic bacterial' potential to inhibit OSCC by regulating genome stability.
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http://dx.doi.org/10.1080/21655979.2022.2078556DOI Listing
June 2022

Modified and alternative Baveno VI criteria based on age for ruling out high-risk varices in patients with compensated cirrhosis.

Hepatol Int 2022 Jun 21. Epub 2022 Jun 21.

Department of Gastroenterology and Hepatology, Tianjin Second People's Hospital, Tianjin, China.

Background: The Baveno VI criteria (B6C) have been recommended to screen high-risk varices (HRV) in patients with liver cirrhosis to avoid the use of esophagogastroduodenoscopy (EGD). Due to conservative nature of B6C and the general unavailability of transient elastography in the medical institutions, clinical application of B6C is restricted. We aimed to optimize B6C and attempted to replace the liver stiffness (LS) score with other parameters that could help patients avoid EGD.

Methods: A total of 1,188 patients with compensated cirrhosis were analyzed and divided into the training cohort (TC) and validating cohort (VC) by the split-sample method. Variables were selected to develop new criteria in the TC before verification in the VC.

Results: The parameters of age ≥ 50 years, LS, platelet count (PLT), and spleen area (SA) were independently associated with HRV. The risk of HRV was 2.39 times greater in patients over 50 years, hence alternative B6C (AB6C) and modified B6C (MB6C) criteria were built based on age. MB6C was built by adjusting the cut-off value of LS and PLT (patients aged < 50 years with PLT > 100 × 10/L and LS < 30 kPa; patients aged ≥ 50 years with a combined PLT > 125 × 10/L and LS < 20 kPa). MB6C helped avoid EGD in 310 (51.2%) patients, whereas 7 (2.3%) cases of HRV were missed. The predicting performance HRV showed no statistical difference between PLT, SA, or LS. SA was selected to replace LS and in the built AB6C (patients aged < 50 years with PLT > 100 × 10/L and SA < 55 cm; patients aged ≥ 50 years with a combined PLT > 125 × 10/L and SA < 44 cm). Using AB6C avoided 297 (49.1%) EGDs with a total of 8 (2.7%) cases of HRV that were missed.

Conclusions: Our novel MB6C and AB6C were stratified by age and provided excellent performance for ruling out HRV, which performed better than B6C and EB6C (expanded B6C) in helping to avoid EGD screening.

Clinical Trial Registration Number: ChiCTR-DDD-17013845.
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http://dx.doi.org/10.1007/s12072-022-10359-yDOI Listing
June 2022

Particle-in-Molybdenum Disulfide-Coated Cavity Structure with a Raman Internal Standard for Sensitive Raman Detection of Water Contaminants from Ions to <300 nm Nanoplastics.

J Phys Chem Lett 2022 Jun 21;13(25):5815-5823. Epub 2022 Jun 21.

Shandong Provincial Engineering and Technical Center of Light Manipulation, School of Physics and Electronics, Shandong Normal University, Jinan 250014, P. R. China.

To develop a universal and precise detection strategy that can be applied to water contaminants of various sizes, we designed a particle-in-MoS coated cavity structure of AAO/MoS/Ag with a Raman internal standard. This modified particle-in-cavity structure not only successfully integrates both "surface hot spots" and "volume hot spots" via dressing and manipulating the cascaded optical-field mode inside the cavity but also introduces the chemical enhancement and internal standard attribute of MoS. Because of its unique three-dimensional structure, AAO/MoS/Ag accurately detects water contaminants of various sizes from ions to nanoplastics (<300 nm) for the first time. This work proposes a novel and universal surface-enhanced Raman scattering strategy for detecting multiple-size water contaminants and demonstrates the potential to build a security line in early warning systems for the prevention of water pollution.
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http://dx.doi.org/10.1021/acs.jpclett.2c01534DOI Listing
June 2022

Contribution of brain network connectivity in predicting effects of polygenic risk and childhood trauma on state-trait anxiety.

J Psychiatr Res 2022 Jun 14;152:119-127. Epub 2022 Jun 14.

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address:

Background: Anxiety is usually attributed to adverse environmental factors, but it is known as a polygenic inheritance disease. Gene-environment interactions on the occurrence and severity of anxiety are still unclear. The role of brain network connectivity in the gene-environment effects on anxiety has not been explored and may be key to understanding neuropathogenesis and guiding treatment.

Methods: This study recruited 177 young adults from the community that completed functional magnetic resonance imaging, Childhood Trauma Questionnaire (CTQ), state-trait anxiety scores, and whole exome sequencing. We calculated polygenic risk score (PRS) for anxiety and the sum score of CTQ, which are genetic and environmental factors that may affect anxiety, respectively. Abnormal brain network connectivity determined by the gene-environment effects and its associations with anxiety scores were then explored.

Results: Except for the main effect of PRS or CTQ on intra-network connectivity, significant interactions were found in intra-network connectivity of visual network, default mode network, self-reference network, and sensorimotor network. Moreover, altered network connectivity was related to anxious tendency. In particular, the effect of CTQ on trait anxiety was mediated by the disrupted sensorimotor network, accompanied by a significant direct effect. However, the PRS influence on anxiety was mainly mediated through sensorimotor network paths, which exceeded the direct influence and was moderated by childhood trauma levels.

Conclusions: These network-specific functional changes related to individual gene-environment risks advance our understanding of psychiatric pathogenesis of anxiety and provide new insights for clinical intervention.
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http://dx.doi.org/10.1016/j.jpsychires.2022.06.027DOI Listing
June 2022

Tuberculous Thoracic Aortic Pseudoaneurysm Associated With Spinal Tuberculosis: A Case Report and Literature Review.

Front Med (Lausanne) 2022 26;9:882697. Epub 2022 May 26.

Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Thoracic aortic pseudoaneurysm associated with spinal tuberculosis is a rare but fatal condition. The risk of pseudoaneurysm rupture is extremely high and this disease needs greater awareness. The present study reported a case of thoracic aortic pseudoaneurysm caused by paravertebral cold abscess with spinal tuberculosis.

Case Presentation: A 35-year-old woman with back pain was diagnosed with thoracic aortic pseudoaneurysm with spinal tuberculosis, and endovascular aneurysm repair (EVAR) was performed. The patient's symptoms disappeared after EVAR, following which she was discharged.

Conclusions: The case highlighted that in cases where non-enhanced computed tomography (CT) revealed that the aortic vessel was surrounded by a paravertebral abscess, magnetic resonance imaging (MRI) should be performed to confirm whether the presence of a pseudoaneurysm. Upon diagnosis of pseudoaneurysm, surgery should be performed immediately. In recent times, EVAR has emerged as a promising alternative to open surgery.
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http://dx.doi.org/10.3389/fmed.2022.882697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198831PMC
May 2022

[Determination of organophosphorus pesticide residues in milk of cows and sheep by ultra-high-performance liquid chromatography- tandem mass spectrometry combined with passing type purification method].

Wei Sheng Yan Jiu 2022 May;51(3):483-489

Beijing Center for Disease Control and Prevention, Beijing Key Laboratory for Tracing Technology of Food Poisoning Diagnosis, Beijing 100013, China.

Objective: A method for the rapid determination of dichlorvos, trichlorfon, fenthion, fenthion-sulfone, fenthion-sulfoxide, fenthion-oxon, fenthion-oxon-sulfone, fenthion-oxon-sulfoxide, phoxim, propetamphos, malathion, diazinon and coumaphos 13 common organophosphorus pesticides and their metabolites poison residues in milk of cows and sheep by ultra-high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) with passing type solid phase extraction(SPE) purification was developed.

Methods: After centrifugation at 4 ℃, the milk was purified by passing type SPE with acetonitrile precipitating protein and determined by UPLC-MS/MS in electrospray positive ion mode(ESI+) and multi-reaction monitoring scanning(MRM), external standard method for quantitative analysis with matrix matching standard curve.

Results: The recoveries of 13 target compounds were between 81.5% and 107.5% and relative standard deviation was between 1.24% and 6.23% at three spiked levels of 5, 10, 20 μg/L. The detection limits of 13 target compounds were between 0.015 and 0.15 μg/L, and the quantitative limits were between 0.05 and 0.50 μg/L. No organophosphorus pesticide residues were detected in 20 samples of cows and sheep milk.

Conclusion: The method has the advantages of good linear independence, low detection limit, high precision and accuracy, and can be used for daily monitoring of milk and related products.
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http://dx.doi.org/10.19813/j.cnki.weishengyanjiu.2022.03.023DOI Listing
May 2022

Biomechanical comparison of different interspinous process devices in the treatment of lumbar spinal stenosis: a finite element analysis.

BMC Musculoskelet Disord 2022 Jun 17;23(1):585. Epub 2022 Jun 17.

Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, 101100, China.

Background: Lumbar spinal stenosis (LSS) is a common disease among elderly individuals, and surgery is an effective treatment. The development of minimally invasive surgical techniques, such as the lumbar interspinous process device (IPD), has provided patients with more surgical options.

Objective: To investigate the biomechanical properties of different IPDs, including BacFuse, X-Stop and Coflex, in the treatment of LSS.

Methods: Based on the computed tomography images of a patient with LSS, four finite element (FE) models of L3-S5 were created in this study. The FE models included a surgical model of the intact lumbar spine and surgical models of the lumbar IPDs BacFuse, X-Stop, and Coflex. After validating the models, they were simulated for four physiological motions: flexion, extension, lateral bending and axial rotation, and range of motion (ROM). Stress distribution of discs and facet joints in each segment, stress distribution of the spinous process in the operated section, and stress distribution of the internal fixation were compared and analysed.

Results: Compared to the model of the intact lumbar spine, the other three models showed a decrease in ROM and disc and facet joint stresses in the surgical segment during movement and an increase in ROM and disc and facet joint stresses in the adjacent segments. These effects were greater for the proximal adjacent segment with BacFuse and more pronounced for the distal adjacent segment with Coflex, while X-Stop had the greatest stress effect on the spinous process in the surgical segment.

Conclusion: BacFuse, Coflex and X-Stop could all be implemented to effectively reduce extension and disc and facet joint stresses, but they also increase the ROM and disc and facet joint stresses in adjacent segments, which may cause degeneration.
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http://dx.doi.org/10.1186/s12891-022-05543-yDOI Listing
June 2022

D--Inositol facilitates adiponectin biosynthesis and activates the AMPKα/PPARs pathway to inhibit high-fat diet-induced obesity and liver lipid deposition.

Food Funct 2022 Jun 16. Epub 2022 Jun 16.

College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, People's Republic of China.

D--Inositol (DCI) is a natural cyclohexanol isomer that widely exists in all living beings, which can effectively prevent glucose and lipid metabolism disorders in mammals. This study revealed the DCI elevated adiponectin levels to reduce obesity and hepatic lipid deposition in high-fat diet (HFD) fed mice. Twelve weeks of DCI supplementation (50 and 100 mg per kg body weight per day) lowered body weight and serum triglyceride, total cholesterol, insulin, and fasting glucose levels. Histopathology analysis revealed that DCI inhibited hepatic steatosis and adipocyte expansion. Remarkably, DCI significantly increased serum adiponectin levels and upgraded the expressions of adiponectin receptors (AdipoR1 and AdipoR2) in the liver. The results of western blot and qRT-PCR showed that DCI impeded the inhibitory effect of HFD on liver AMPKα and PPARs activities through activating AdipoRs and regulated downstream fatty acid metabolism. In addition, we analyzed the concentration difference of DCI in mouse liver and adipose tissue by the HRLC-MS/MS technology, indicating the preference of DCI in different tissues. Therefore, DCI relieved liver lipid deposition and hyperlipidemia potentially by promoting adiponectin synthesis in white adipose tissue and activating the AdipoR-AMPKα/PPARs pathway in the liver.
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http://dx.doi.org/10.1039/d2fo00869fDOI Listing
June 2022

Metal-Free Aminohalogenation of Quinones With Alkylamines and NXS at Room Temperature.

Front Chem 2022 20;10:917371. Epub 2022 May 20.

Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

A simple and practical strategy for intermolecular aminohalogenation of quinone with alkyl amines and NXS was developed, in which haloamines generated were employed as bifunctional reagents. The reaction system is reliable, efficient and wide in substrate range, which is suitable for the two-fold aminochlorination of 1, 4-benzoquinones, large-scale reaction and late-stage modification of pharmaceuticals.
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http://dx.doi.org/10.3389/fchem.2022.917371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189915PMC
May 2022

Vps33B controls Treg cell suppressive function through inhibiting lysosomal nutrient sensing complex-mediated mTORC1 activation.

Cell Rep 2022 Jun;39(11):110943

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

The suppressive function of regulatory T (Treg) cells is tightly controlled by nutrient-fueled mechanistic target of rapamycin complex 1 (mTORC1) activation, yet its dynamics and negative regulation remain unclear. Here we show that Treg-specific depletion of vacuolar protein sorting 33B (Vps33B) in mice results in defective Treg cell suppressive function and acquisition of effector phenotype, which in turn leads to disturbed T cell homeostasis and boosted antitumor immunity. Mechanistically, Vps33B binds with lysosomal nutrient-sensing complex (LYNUS) and promotes late endosome and lysosome fusion and clearance of the LYNUS-containing late endosome/lysosome, and therefore suppresses mTORC1 activation. Vps33B deficiency in Treg cells results in disordered endosome lysosome fusion, which leads to accumulation of LYNUS that causes elevated mTORC1 activation and hyper-glycolytic metabolism. Taken together, our study reveals that Vps33B maintains Treg cell suppressive function through sustaining endolysosomal homeostasis and therefore restricting amino acid-licensed mTORC1 activation and metabolism.
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http://dx.doi.org/10.1016/j.celrep.2022.110943DOI Listing
June 2022

A qualitative analysis method for multi-component gas mixtures terahertz rotational spectroscopy.

Anal Methods 2022 Jun 30;14(25):2479-2484. Epub 2022 Jun 30.

Department of Automation, Beijing National Research Center for Information Science and Technology, Tsinghua University, Beijing 100084, China.

Terahertz rotational spectroscopy is one of the most effective methods of gas sensing. However, the rich and dense spectral peaks of multi-component gas mixtures in the terahertz band increase the difficulty of gas identification. A novel qualitative analysis method is proposed based on the collision broadening mechanism coupled with terahertz spectroscopy technology. First of all, a broadening coefficients database of acetonitrile, formic acid, and formaldehyde colliding with nitrogen was established by experimental measurements and a spectral peak fitting technique. Then the broadening coefficients of the isolated peaks in binary and ternary mixtures perturbed by nitrogen were derived. Finally, the components were identified by matching the broadening coefficients of these isolated peaks with the established database. The proposed qualitative analysis method based on the collision broadening mechanism would be a new approach for identifying multi-component gas mixtures in analytical chemistry.
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http://dx.doi.org/10.1039/d2ay00596dDOI Listing
June 2022

Ginsenoside Rb1 inhibits astrocyte activation and promotes transfer of astrocytic mitochondria to neurons against ischemic stroke.

Redox Biol 2022 Jun 8;54:102363. Epub 2022 Jun 8.

State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China; Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China. Electronic address:

Astrocytes activation in response to stroke results in altered mitochondrial exchange with neurons. Ginsenoside Rb1is a major ginsenoside of Panax ginseng particularly known for its neuroprotective potential. This work aimed to investigate if Rb1 could rescue neurons from ischemic insult via astrocyte inactivation and mitochondrial transfer. We prepared conditioned astrocytes-derived medium for co-culture with neurons and examined the role of Rb1 in mitochondrial transfer from astrocytes to neurons. The neuroprotective potential of Rb1 was further confirmed in vivo using a mouse model of brain ischemia. In response to oxygen-glucose deprivation and reperfusion (OGD/R), astrocytes were reactivated and produced reactive oxygen species (ROS), an action that was blocked by Rb1. Mechanistically, Rb1 inhibited NADH dehydrogenase in mitochondrial complex I to block reverse electron transport-derived ROS production from complex I, and thus inactivated astrocytes to protect the mitochondria. Mitochondrial signal, mitochondrial membrane potential and ATP production detected in conditioned astrocyte-derived medium indicated that Rb1 protected functional mitochondria and facilitated their transfer. When neurons were injured by OGD/R insult, co-culturing with conditioned medium increased mitochondrial membrane potential and oxygen consumption rate within the neurons, indicating the protection conferred on them by Rb1 via mitochondrial transfer from astrocytes. Using the ischemic mouse brain model, CD38 knockdown in the cerebral ventricles diminished the neuroprotective effects of Rb1, providing evidence in support of the role of astrocyte mitochondrial transfer. Transient inhibition of mitochondrial complex I by Rb1 reduced mitochondrial ROS production and consequently avoided astrocyte activation. Astrocyte mitochondrial transfer therefore seemed a means by which Rb1 could promote neuronal survival and function. Different from the neurocentric view, these findings suggest the astrocytes may be a promising target for pharmacological interventions in ischemic brain injury.
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http://dx.doi.org/10.1016/j.redox.2022.102363DOI Listing
June 2022

Heterogeneous lattice strain strengthening in severely distorted crystalline solids.

Proc Natl Acad Sci U S A 2022 Jun 13;119(25):e2200607119. Epub 2022 Jun 13.

Department of Materials Science and Engineering; Mechanical Behavior Division of Shenyang National Laboratory for Materials Science, College of Engineering, City University of Hong Kong, Kowloon Tong, Kowloon, Hong Kong SAR 999077, China.

Multi-principal element alloys (MPEAs) exhibit outstanding mechanical properties because the core effect of severe atomic lattice distortion is distinctly different from that of traditional alloys. However, at the mesoscopic scale the underlying physics for the abundant dislocation activities responsible for strength-ductility synergy has not been uncovered. While the Eshelby mean-field approaches become insufficient to tackle yielding and plasticity in severely distorted crystalline solids, here we develop a three-dimensional discrete dislocation dynamics simulation approach by taking into account the experimentally measured lattice strain field from a model FeCoCrNiMn MPEA to explore the heterogeneous strain-induced strengthening mechanisms. Our results reveal that the heterogeneous lattice strain causes unusual dislocation behaviors (i.e., multiple kinks/jogs and bidirectional cross slips), resulting in the strengthening mechanisms that underpin the strength-ductility synergy. The outcome of our research sheds important insights into the design of strong yet ductile distorted crystalline solids, such as high-entropy alloys and high-entropy ceramics.
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http://dx.doi.org/10.1073/pnas.2200607119DOI Listing
June 2022
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