Publications by authors named "Yao He"

552 Publications

Ex vivo and in vivo fluorescence detection and imaging of adenosine triphosphate.

J Nanobiotechnology 2021 Jun 22;19(1):187. Epub 2021 Jun 22.

Laboratory of Nanoscale Biochemical Analysis, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, 215123, China.

Background: Ex vivo and in vivo detection and imaging of adenosine triphosphate (ATP) is critically important for the diagnosis and treatment of diseases, which still remains challenges up to present.

Results: We herein demonstrate that ATP could be fluorescently detected and imaged ex vivo and in vivo. In particular, we fabricate a kind of fluorescent ATP probes, which are made of titanium carbide (TC) nanosheets modified with the ROX-tagged ATP-aptamer (TC/Apt). In the constructed TC/Apt, TC shows superior quenching efficiency against ROX (e.g., ~ 97%). While in the presence of ATP, ROX-tagged aptamer is released from TC surface, leading to the recovery of fluorescence of ROX under the 545-nm excitation. Consequently, a wide dynamic range from 1 μM to 1.5 mM ATP and a high sensitivity with a limit of detection (LOD) down to 0.2 μM ATP can be readily achieved by the prepared TC/Apt. We further demonstrate that the as-prepared TC/Apt probe is feasible for accurate discrimination of ATP in different samples including living cells, body fluids (e.g., mouse serum, mouse urine and human serum) and mouse tumor models.

Conclusions: Fluorescence detection and imaging of ATP could be readily achieved in living cells, body fluids (e.g., urine and serum), as well as mouse tumor model through a new kind of fluorescent ATP nanoprobes, offering new powerful tools for the treatment of diseases related to abnormal fluctuation of ATP concentration.
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http://dx.doi.org/10.1186/s12951-021-00930-4DOI Listing
June 2021

The association between nutritional status and functional limitations among centenarians: a cross-sectional study.

BMC Geriatr 2021 Jun 21;21(1):376. Epub 2021 Jun 21.

Institute of geriatrics, the 2nd Medical Center, State Key Laboratory of Kidney Disease, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, Chinese PLA General Hospital, 28 Fuxing Road, 100853, Beijing, China.

Background: Although there have been studies on the association between nutritional status and functional limitations, there were few studies on Asian centenarians in community. Therefore, this study aims to identify associations between nutritional status and functional limitations among centenarians in China.

Methods: This cross-sectional study was conducted with the data from the China Hainan Centenarian Cohort Study. These data ultimately included basic characteristics, hematologic indicators, and chronic disease status for 1,002 centenarians. The nutritional status was evaluated using the Mini Nutritional Assessment Short-Form scale. The functional limitations were assessed using the activities of daily living (ADL) scale, namely Barthel Index and Lawton Scale. The association between nutritional status and ADL was assessed using multivariate logistic regression models.

Results: In this study, the prevalence of malnutrition was 20.8 % among centenarians, basic ADL (BADL) limitation was 28.6 %, and instrumental ADL (IADL) limitation was 64.7 %. As the nutritional status deteriorated, the risk of ADL limitations increased in total population (BADL limitation: OR = 17.060, 95 % CI: 8.093-35.964; IADL limitation: OR = 11.221, 95 % CI: 5.853-21.511; p for trend < 0.001). Similar results were found in both men and women after stratifying sex but were more prominent in women.

Conclusions: Malnutrition is associated with functional limitations among centenarians in China and more pronounced among women.
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http://dx.doi.org/10.1186/s12877-021-02312-9DOI Listing
June 2021

Correction to: Fluorescent Silicon Nanorods‑Based Nanotheranostic Agents for Multimodal Imaging‑Guided Photothermal Therapy.

Nanomicro Lett 2019 Oct 15;11(1):85. Epub 2019 Oct 15.

Laboratory of Nanoscale Biochemical Analysis Institute of Functional Nano & Soft Materials (FUNSOM), and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, People's Republic of China.

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http://dx.doi.org/10.1007/s40820-019-0318-5DOI Listing
October 2019

Fluorescent Silicon Nanorods-Based Nanotheranostic Agents for Multimodal Imaging-Guided Photothermal Therapy.

Nanomicro Lett 2019 Sep 9;11(1):73. Epub 2019 Sep 9.

Laboratory of Nanoscale Biochemical Analysis Institute of Functional Nano & Soft Materials (FUNSOM), and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, People's Republic of China.

The utilization of diagnosis to guide/aid therapy procedures has shown great prospects in the era of personalized medicine along with the recognition of tumor heterogeneity and complexity. Herein, a kind of multifunctional silicon-based nanostructure, i.e., gold nanoparticles-decorated fluorescent silicon nanorods ([email protected]), is fabricated and exploited for tumor-targeted multimodal imaging-guided photothermal therapy. In particular, the prepared [email protected] feature high photothermal conversion efficiency (~ 43.9%) and strong photothermal stability (photothermal performance stays constant after five-cycle NIR laser irradiation), making them high-performance agents for simultaneously photoacoustic and infrared thermal imaging. The [email protected] are readily modified with targeting peptide ligands, enabling an enhanced tumor accumulation with a high value of ~ 8.74% ID g. Taking advantages of these unique merits, the [email protected] are superbly suitable for specifically ablating tumors in vivo without appreciable toxicity under the guidance of multimodal imaging. Typically, all the mice treated with the [email protected] remain alive, and no distinct tumor recurrence is observed during 60-day investigation.
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http://dx.doi.org/10.1007/s40820-019-0306-9DOI Listing
September 2019

Photostable and Biocompatible Fluorescent Silicon Nanoparticles for Imaging-Guided Co-Delivery of siRNA and Doxorubicin to Drug-Resistant Cancer Cells.

Nanomicro Lett 2019 Mar 25;11(1):27. Epub 2019 Mar 25.

Laboratory of Nanoscale Biochemical Analysis, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.

The development of effective and safe vehicles to deliver small interfering RNA (siRNA) and chemotherapeutics remains a major challenge in RNA interference-based combination therapy with chemotherapeutics, which has emerged as a powerful platform to treat drug-resistant cancer cells. Herein, we describe the development of novel all-in-one fluorescent silicon nanoparticles (SiNPs)-based nanomedicine platform for imaging-guided co-delivery of siRNA and doxorubicin (DOX). This approach enhanced therapeutic efficacy in multidrug-resistant breast cancer cells (i.e., MCF-7/ADR cells). Typically, the SiNP-based nanocarriers enhanced the stability of siRNA in a biological environment (i.e., medium or RNase A) and imparted the responsive release behavior of siRNA, resulting in approximately 80% down-regulation of P-glycoprotein expression. Co-delivery of P-glycoprotein siRNA and DOX led to > 35-fold decrease in the half maximal inhibitory concentration of DOX in comparison with free DOX, indicating the pronounced therapeutic efficiency of the resultant nanocomposites for drug-resistant breast cancer cells. The intracellular time-dependent release behaviors of siRNA and DOX were revealed through tracking the strong and stable fluorescence of SiNPs. These data provide valuable information for designing effective RNA interference-based co-delivery carriers.
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http://dx.doi.org/10.1007/s40820-019-0257-1DOI Listing
March 2019

Nanoparticles as a Hedgehog signaling inhibitor for the suppression of cancer growth and metastasis.

Nanoscale 2021 Jun 17. Epub 2021 Jun 17.

Laboratory of Nanoscale Biochemical Analysis, Institute of Functional Nano and Soft Materials (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China.

Nanoparticles (NPs) have been intensively explored for the treatment of tumors during the past decade, yet little information has been provided on the NPs' inherent therapeutic activity against cancers. With this goal in mind, we reveal that biocompatible silicon (Si) NPs (SiNPs) feature excellent anti-growth and anti-metastasis activities against prostate cancer cells that show aberrant activation of the Hedgehog (HH) signaling pathway. Without activation by the Sonic hedgehog (Shh)-agonist, mouse embryonic fibroblast (NIH3T3) cells show no response to SiNP exposure. The distinct inhibitory effect of SiNPs on the HH signaling pathway leads to significant suppression of the proliferation, migration, and invasion of human prostate cancer cells. Crucially, in two mouse tumor models, the growth and metastasis of prostate cancer cells are also efficiently inhibited by SiNPs.
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http://dx.doi.org/10.1039/d1nr02157eDOI Listing
June 2021

Improved plant cytosine base editors with high editing activity, purity, and specificity.

Plant Biotechnol J 2021 May 27. Epub 2021 May 27.

Department of Biotechnology, School of Life Science and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, China.

Cytosine base editors (CBEs) are great additions to the expanding genome editing toolbox. To improve C-to-T base editing in plants, we first compared seven cytidine deaminases in the BE3-like configuration in rice. We found A3A/Y130F-CBE_V01 resulted in the highest C-to-T base editing efficiency in both rice and Arabidopsis. Furthermore, we demonstrated this A3A/Y130F cytidine deaminase could be used to improve iSpyMacCas9-mediated C-to-T base editing at A-rich PAMs. To showcase its applications, we first applied A3A/Y130F-CBE_V01 for multiplexed editing to generate microRNA-resistant mRNA transcripts as well as pre-mature stop codons in multiple seed trait genes. In addition, we harnessed A3A/Y130F-CBE_V01 for efficient artificial evolution of novel ALS and EPSPS alleles which conferred herbicide resistance in rice. To further improve C-to-T base editing, multiple CBE_V02, CBE_V03 and CBE_V04 systems were developed and tested in rice protoplasts. The CBE_V04 systems were found to have improved editing activity and purity with focal recruitment of more uracil DNA glycosylase inhibitors (UGIs) by the engineered single guide RNA 2.0 scaffold. Finally, we used whole-genome sequencing (WGS) to compare six CBE_V01 systems and four CBE_V04 systems for genome-wide off-target effects in rice. Different levels of cytidine deaminase-dependent and sgRNA-independent off-target effects were indeed revealed by WGS among edited lines by these CBE systems. We also investigated genome-wide sgRNA-dependent off-target effects by different CBEs in rice. This comprehensive study compared 21 different CBE systems, and benchmarked PmCDA1-CBE_V04 and A3A/Y130F-CBE_V04 as next-generation plant CBEs with high editing efficiency, purity, and specificity.
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http://dx.doi.org/10.1111/pbi.13635DOI Listing
May 2021

Targeted Noninvasive Treatment of Choroidal Neovascularization by Hybrid Cell-Membrane-Cloaked Biomimetic Nanoparticles.

ACS Nano 2021 Jun 26;15(6):9808-9819. Epub 2021 May 26.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong 510120, China.

Choroidal neovascularization (CNV) is the leading cause of vision loss in many blinding diseases, but current antiangiogenic therapies with invasively intravitreal injection suffer from poor patient compliance and a rate of devastating ocular complications. Here, we develop an alternative antiangiogenic agent based on hybrid cell-membrane-cloaked nanoparticles for noninvasively targeted treatment of CNV. The retinal endotheliocyte membrane coating provides as-fabricated nanoagents with homotypic targeting capability and binding ability to the vascular endothelial growth factor. The fusion of red blood cell membranes protects the hybrid membrane-coated nanoparticles from phagocytosis by macrophages. In a laser-induced wet age-related macular degeneration mouse model, a significantly enhanced accumulation is observed in CNV regions after intravenous delivery of the hybrid membrane-coated nanoparticles. Moreover, an excellent therapeutic efficacy is achieved in reducing the leakage and area of CNV. Overall, the biomimetic antiangiogenic nanoagents provide an effective approach for noninvasive treatment of CNV.
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http://dx.doi.org/10.1021/acsnano.1c00680DOI Listing
June 2021

Entrapment of Macrophage-Target Nanoparticles by Yeast Microparticles for Rhein Delivery in Ulcerative Colitis Treatment.

Biomacromolecules 2021 Jun 21;22(6):2754-2767. Epub 2021 May 21.

State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China.

In this study, we developed an advanced colitis-targeted nanoparticles (NPs)-into-yeast cell wall microparticles (YPs) drug delivery system for ulcerative colitis (UC) therapy. In brief, YPs entrap hyaluronic acid (HA), and polyethylenimine (PEI) modified rhein (RH)-loaded ovalbumin NPs (HA/PEI-RH NPs) to form HA/PEI-RH NYPs. YPs can make HA/PEI-RH NPs pass through gastric environment stably and be degraded by β-glucanase to promote drug release from HA/PEI-RH NYPs in the colon. Cellular uptake evaluation confirmed that HA/PEI-RH NPs could specifically target and enhance the uptake rate via HA ligands. In biodistribution studies, HA/PEI-RH NYPs were able to efficiently accumulate in the inflammed colon in mice. In vivo experiments revealed that the HA/PEI-RH NYPs could significantly alleviate inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Therefore, HA/PEI-RH NYPs have advantages of good gastric stability, β-glucanase-sensitive release ability, macrophage-targeted ability, and anti-UC effects. These advantages indicate YPs-entrapped multifunctional NPs are a promising oral drug delivery system for UC therapy.
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http://dx.doi.org/10.1021/acs.biomac.1c00425DOI Listing
June 2021

Protection of surface layer protein from Enterococcus faecium WEFA23 against Listeria monocytogenes CMCC54007 infection by modulating intestinal permeability and immunity.

Appl Microbiol Biotechnol 2021 May 14;105(10):4269-4284. Epub 2021 May 14.

Jiangxi-OAI Joint Research Institute, Nanchang University, 235 Nanjing Donglu, Nanchang, Jiangxi, 330047, People's Republic of China.

Enterococcus faecium WEFA23 was previously found effectively against adherence and colonization of Listeria monocytogenes CMCC54007, which might be closely related to its surface layer protein (SLP). In this study, the protective of SLP of E. faecium WEFA23 against infection of L. monocytogenes CMCC54007 was systemically investigated. In vitro assay showed that SLP actively inhibited L. monocytogenes internalization into Caco-2 cell line, with decreasing mRNA level of pro-inflammation cytokines and virulence factors and restoring destroyed intestinal barrier. In vivo assay through excluding SLP of E. faecium WEFA23 by 5 M LiCl represented that SLP increased body weight, reduced mortality and cell counts of L. monocytogenes CMCC54007 in tissues of mice. Further researches showed that SLP protected against L. monocytogenes CMCC54007 infection by modulation of intestinal permeability and immunity, namely, it decreased fluorescein isothiocyanate (FITC)-Dextran in serum, ameliorated destroyed colon structure, and increased number of goblet cells and protein level of TJ protein (Claudin-1, Occludin, and ZO-1) in colon. For immunity, SLP decreased number of CD4 and CD8 T cells in liver, mRNA level, and content of pro-inflammatory factors IL-6, IL-1β, IFN-γ ,TNF-α, and NO, and restored the structure of liver and spleen. Key Points•SLP of E. faecium inhibited L. monocytogenes internalization and colonization•SLP of E. faecium ameliorated host intestinal barrier dysfunction•SLP of E. faecium decreased pro-inflammatory cytokines and cells.
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http://dx.doi.org/10.1007/s00253-021-11240-yDOI Listing
May 2021

Structures of telomerase at several steps of telomere repeat synthesis.

Nature 2021 May 12;593(7859):454-459. Epub 2021 May 12.

Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.

Telomerase is unique among the reverse transcriptases in containing a noncoding RNA (known as telomerase RNA (TER)) that includes a short template that is used for the processive synthesis of G-rich telomeric DNA repeats at the 3' ends of most eukaryotic chromosomes. Telomerase maintains genomic integrity, and its activity or dysregulation are critical determinants of human longevity, stem cell renewal and cancer progression. Previous cryo-electron microscopy structures have established the general architecture, protein components and stoichiometries of Tetrahymena and human telomerase, but our understandings of the details of DNA-protein and RNA-protein interactions and of the mechanisms and recruitment involved remain limited. Here we report cryo-electron microscopy structures of active Tetrahymena telomerase with telomeric DNA at different steps of nucleotide addition. Interactions between telomerase reverse transcriptase (TERT), TER and DNA reveal the structural basis of the determination of the 5' and 3' template boundaries, handling of the template-DNA duplex and separation of the product strand during nucleotide addition. The structure and binding interface between TERT and telomerase protein p50 (a homologue of human TPP1) define conserved interactions that are required for telomerase activation and recruitment to telomeres. Telomerase La-related protein p65 remodels several regions of TER, bridging the 5' and 3' ends and the conserved pseudoknot to facilitate assembly of the TERT-TER catalytic core.
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http://dx.doi.org/10.1038/s41586-021-03529-9DOI Listing
May 2021

A novel risk score predicts prognosis in melanoma: The combination of three tumor-infiltrating immune cells and four immune-related genes.

Clin Immunol 2021 Jul 8;228:108751. Epub 2021 May 8.

Department of Pharmacology and Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address:

Tumor-infiltrating immune cells (TIICs) and immune-related genes (IRGs) of melanoma are associated with prognosis. However, whether the combination of TIICs and IRGs can be used as prognostic clinical biomarkers are still unknown. Here, we downloaded transcription profile of melanoma from TCGA. Then, three TIICs and four IRGs that associated with the overall survival were used to constructed the Immune Cell Score (ICS) and Immune Gene Score (IGS) respectively. Next, to improve the accuracy of ICS and IGS for melanoma prognostic, we combined the ICS and IGS constructed the Immune Cell and Gene Score (ICGS) model. ICGS had higher accuracy and predictive ability than ICS or IGS. Meanwhile, ICGS model reliability was validated by two independent datasets of melanoma. Functional enrichment and protein-protein interaction network analysis based on ICGS were performed to identify T cell mediated immune and inflammatory response are highly associated with melanoma.
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http://dx.doi.org/10.1016/j.clim.2021.108751DOI Listing
July 2021

Overloading stress-induced progressive degeneration and self-repair in condylar cartilage.

Ann N Y Acad Sci 2021 May 7. Epub 2021 May 7.

Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, China.

Overloading stress-induced condylar cartilage degeneration acts as the main pathologic change in temporomandibular joint osteoarthritis (TMJ-OA). However, the progression of degeneration and the ability for self-repair remain poorly understood. Here, we explored the progression of cartilage degeneration by dividing pathological stages using a steady mouth-opening mouse model. Then, we observed changes of cartilage by removing the loading at different stages to test the potential self-repair after degeneration induced. Three-dimensional confocal microscopy combined with histology and micro-CT scanning was applied to examine TMJ at different stages of degeneration before and after self-repair. We found the cartilage underwent progressive and thorough degeneration as the overloading stress developed. During the initial adaptation stage, robust proliferation of posteromedial cartilage began at the area of direct loading. Subsequently, widespread chondrocyte apoptosis was found, followed by new chondrocyte proliferation in aggregates with matrix degradation and subchondral bone catabolism. Finally, with cartilage surface damage, the degeneration reached a point where the lesion could not be reversed by self-repair. While the cartilage nearly returned to normal when the interference was removed within 5 days. These results suggested overloading force induces a pathological process of successive degeneration in TMJ cartilage, which can be reversed by self-repair at early stages.
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http://dx.doi.org/10.1111/nyas.14606DOI Listing
May 2021

Association of intracranial vessel wall enhancement and cerebral hemorrhage in moyamoya disease: a high-resolution magnetic resonance imaging study.

J Neurol 2021 May 6. Epub 2021 May 6.

Department of Radiology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.

Background And Purpose: This study aimed to investigate the enhancement characteristics of vessel wall in patients with moyamoya disease (MMD) using 3D high-resolution magnetic resonance (MR) imaging and their relationship with initial and recurrent intracranial hemorrhage.

Methods: Consecutive patients with MMD were retrospectively analyzed and classified as intracranial hemorrhagic and non-hemorrhagic groups according to the CT or MR images. The clinical features and vessel wall characteristics were compared between the two groups. Logistic regression was performed to relate the vessel wall characteristics to the initial hemorrhage in MMD patients. Patients in hemorrhagic group were followed up after surgery to evaluate the relationship between vessel wall characteristics and recurrent hemorrhage.

Results: A total of 507 MMD patients including 79 hemorrhagic and 428 non-hemorrhagic MMD patients were recruited in the study. We found that hemorrhagic group had more patients with vessel wall enhancements (40.5% vs. 25.7%, p = 0.009) and more eccentric enhanced lesions (17.7% vs. 6.5%, p = 0.001) compared to those in non-hemorrhage group and vessel wall enhancements were independently associated with ipsilateral initial hemorrhage after adjusted for clinical factors (OR = 1.99, CI 1.20-3.28, p = 0.007). Furthermore, three recurrent intracranial hemorrhagic episodes in the present study were all observed in MMD patients with vessel wall enhancement during the long-term follow-up after surgery.

Conclusions: Wall enhancement of intracranial vessels was significantly associated with intracranial hemorrhage in MMD patients. Our findings suggest that vessel wall enhancement may serve as a marker of intracranial hemorrhage.
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http://dx.doi.org/10.1007/s00415-021-10587-6DOI Listing
May 2021

Hydrothermal Synthesis of Zinc-Doped Silica Nanospheres Simultaneously Featuring Stable Fluorescence and Long-Lived Room-Temperature Phosphorescence.

Angew Chem Int Ed Engl 2021 Apr 26. Epub 2021 Apr 26.

Laboratory of Nanoscale Biochemical Analysis, Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Jiangsu, Suzhou, 215123, China.

Fluorescence and phosphorescence are known as two kinds of fundamental optical signals, which have been used for myriad applications. To date, simultaneous activation of stable fluorescence and long-lived room-temperature phosphorescence (RTP) emission in the aqueous phase remains a big challenge. We prepare zinc-doped silica nanospheres ([email protected]) with fluorescence and RTP properties using a facile hydrothermal synthetic strategy. For the as-prepared [email protected], the recombination of electrons and holes in defects and defect-stabilized excitons derived from oxygen vacancy/C=N bonds lead to the production of stable fluorescence and long-lived RTP (emission lasting for ≈9 s, quantum yield (QY): ≈33.6 %, RTP lifetime: ≈236 ms). The internal Si-O bonded networks and hydrophilic surface in [email protected] can reduce nonradiative decay to form self-protective RTP, and also provide high water solubility, excellent pH- and photostability.
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http://dx.doi.org/10.1002/anie.202103200DOI Listing
April 2021

Anthropogenic-Driven Alterations in Black Carbon Sequestration and the Structure in a Deep Plateau Lake.

Environ Sci Technol 2021 05 22;55(9):6467-6475. Epub 2021 Apr 22.

Yunnan Research Academy of Eco-environmental Science, Kunming 650034, China.

The continuous flux of organic carbon (OC) from terrestrial ecosystems into inland water is an important component of the global carbon cycle. The buried OC pool in inland water sediments is considerable, and black carbon (BC) is a significant contributor to this OC pool because of the continuous growth in BC emissions. Therefore, determining the effect of BC on total OC burial and variations in the structure of BC during the burial process will contribute significantly to our understanding of lacustrine carbon cycling. This study investigated BC burial and its structural variations in response to anthropogenic drivers using four dated sedimentary cores from a deep plateau lake in China. The BC burial rate rose from 0.96 ± 0.64 g·m·y (mean of sedimentary cores pre-1960s) to 4.83 ± 1.25 g·m·y (after 2000), which is a 5.48 ± 2.12-fold rise. The increase of char was similar to those of BC. The growth rate of soot was 7.20 ± 4.30 times, which is higher than that of BC and char, increasing from 0.12 ± 0.08 to 0.64 ± 0.23 g·m·y. There was a decreasing trend in the ratio of char and soot at a mean rate of 62.8 ± 6.46% (excluding core 3) in relation to increased fossil fuel consumption. The contribution of BC to OC burial showed a significant increasing trend from the past to the present, particularly in cores 3 and 4, and the mean contribution of the four cores was 11.78 ± 2.84%. Source tracer results from positive matrix factorization confirmed that the substantial use of fossil fuels has promoted BC burial and altered the BC structure. This has resulted in BC with a higher aromatic content in the lake sediment, which exhibits reduced reactivity and increased stability. The strong correlation between BC and allochthonous total OC indicates that the input pathways of the buried BC in this plateau lake sediment were terrestrial surface processes and not atmospheric deposition.
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http://dx.doi.org/10.1021/acs.est.1c00106DOI Listing
May 2021

Real-time characterization of aerosol particle composition, sources and influences of increased ventilation and humidity in an office.

Indoor Air 2021 Apr 20. Epub 2021 Apr 20.

State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing, China.

Most of human exposure to atmospheric pollutants occurs indoors, and the components of outdoor aerosols may have been changed in the way before reaching indoor spaces. Here we conducted real-time online measurements of mass concentrations and chemical composition of black carbon and the non-refractory species in PM in an occupied office for approximately one month. The open-close windows and controlled dampness experiments were also performed. Our results show that indoor aerosol species primarily originate from outdoors with indoor/outdoor ratio of these species typically less than unity except for certain organic aerosol (OA) factors. All aerosol species went through filtration upon transport indoors. Ammonium nitrate and fossil fuel OA underwent evaporation or particle-to-gas partitioning, while less oxidized secondary OA (SOA) underwent secondary formation and cooking OA might have indoor sources. With higher particulate matter (PM) mass concentration outdoors than in the office, elevated natural ventilation increased PM exposure indoors and this increased exposure was prolonged when outdoor PM was scavenged. We found that increasing humidity in the office led to higher indoor PM mass concentration particularly more oxidized SOA. Overall, our results highlight that indoor exposure of occupants is substantially different from outdoor in terms of mass concentrations and chemical species.
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http://dx.doi.org/10.1111/ina.12838DOI Listing
April 2021

Bone marrow mesenchymal stem cells-derived exosomal microRNA-19b-3p targets SOCS1 to facilitate progression of esophageal cancer.

Life Sci 2021 Aug 13;278:119491. Epub 2021 Apr 13.

The First Clinical Medicine College of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China.

Objective: Exosomes can convey particular microRNAs (miRNAs) to affect biological functions of cancer cells. Nevertheless, the impact of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-exos) transmitting miR-19b-3p on esophageal cancer (EC) progression remains scarcely studied. We aimed to explore the role of BMSC-exos mediating miR-19b-3p in EC cell growth.

Methods: Eighty-three cases of EC patients were included in this study and the expression of miR-19b-3p and suppressor of cytokine signaling 1 (SOCS1) in cancer and adjacent normal tissues from the patients were assessed. BMSCs were cultured and BMSC-exos were extracted, which were then transfected with altered miR-19b-3p and SOCS1 to assess their roles in proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and apoptosis of EC cells. Targeting relationship between miR-19b-3p and SOCS1 was verified by Targetscan and dual luciferase reporter gene assay. MiR-19b-3p and SOCS1 expression was assessed in TE-2 cells.

Results: MiR-19b-3p was upregulated and SOCS1 was downregulated in EC tissues. BMSC-exos or exosomal miR-19b-3p promoted malignant behaviors of EC cells. MiR-19b-3p was upregulated and targeted SOCS1 in EC cells. MiR-19b-3p inhibition or SOCS1 overexpression suppressed proliferation, migration, invasion and EMT, and induced apoptosis of EC cells. SOCS1 silencing abrogated these effect of miR-19b-3p inhibition on EC cells.

Conclusion: BMSC-derived exosomal miR-19b-3p promotes progression of EC through targeting SOCS1. This study provides a novel understanding on molecular mechanisms of EC.
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http://dx.doi.org/10.1016/j.lfs.2021.119491DOI Listing
August 2021

Dietary behaviors and patterns of centenarians in Hainan: A cross-sectional study.

Nutrition 2021 Mar 4;89:111228. Epub 2021 Mar 4.

Institute of Geriatrics, State Key Laboratory of Kidney Disease, Beijing Key Laboratory of Aging and Geriatrics, the 2nd Clinical Center, Chinese PLA General Hospital, Beijing, China. Electronic address:

Objectives: The aim of this study was to understand the diet-related behaviors of Hainan centenarians and to analyze dietary factors that affect their nutritional status.

Methods: Data were collected from the China Hainan Centenarian Cohort Study, a full sample survey including questionnaires, physical examinations, and physiologic indices of the centenarian population. The study included 1002 centenarians. The diet-related behaviors were assessed using the food frequency questionnaire; nutritional status was determined according to the Mini Nutritional Assessment - short form scale scores. We used logistic regression models to analyze the main dietary risk factors of malnutrition.

Results: Of all the centenarians, 94.6% maintained regular meals, 80.4% had three meals a day, 53.4% ate each meal until 80% full, 88.7% ate vegetables daily, and 70% drank one to two cups of water daily. Centenarians ate rice-based staple foods; eggs, dairy, legumes, nuts, and poultry were not popular. The main sources of meat were red meat and seafood. None liked fried food, and 19.3% preferred sweet flavors. People with normal nutritional status accounted for 12.3% of the population, whereas those with malnutrition comprised 20.8%. Dietary factors that affected nutritional status included three meals a day (odds ratio [OR], 0.366; 95% confidence interval [CI], 0.173-0.778), tea drinking (OR, 0.236; 95% CI, 0.087-0.641), and the frequency of poultry (OR, 0.261; 95% CI, 0.088-0.771), seafood (OR, 0.247; 95% CI, 0.110-0.554), nuts (OR, 0.381; 95% CI, 0.150-0.965), and pastry (OR, 0.219; 95% CI, 0.080-0.600) consumption.

Conclusion: This was the first study on the dietary behaviors and nutritional status of centenarians using survey data. We highlighted the factors affecting nutritional status and provided scientific support for dietary strategies that may improve the nutritional status of the elderly population.
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http://dx.doi.org/10.1016/j.nut.2021.111228DOI Listing
March 2021

Association between serum uric acid and major chronic diseases among centenarians in China: based on the CHCCS study.

BMC Geriatr 2021 04 7;21(1):231. Epub 2021 Apr 7.

Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, State Key Laboratory of Kidney Diseases, Institute of Geriatrics, Second Medical Center of Chinese PLA General Hospital, Beijing, China.

Background: This study aims to analyze the distribution of serum uric acid (SUA) level based on more than 1000 centenarians and to explore the association with three common diseases including hypertension, diabetes and dyslipidemia.

Methods: All the 1002 centenarians from the CHCCS were included. Household survey was conducted.

Results: The mean SUA level of centenarians was 329.04 ± 97.75 μmol/L and the prevalence of hyperuricemia in centenarians was 26.5%. There was no statistical difference in the distribution of SUA levels among centenarians with or without hypertension/diabetes. For dyslipidemia, there was an independent positive association. The risk of dyslipidemia among those with hyperuricemia was 1.646 (95%CI: 1.078-2.298) compared with those who didn't have hyperuricemia. By comparing different subtypes of dyslipidemia, hyperuricemia was positively associated with hypertriglyceridemia and low-density lipoprotein cholesterolemia, with the corresponding ORs of 2.553 (95%CI: 1.282-5.083) and 1.927 (95%CI: 1.273-2.917) respectively, while there was no statistically significant association with hypercholesterolemia 0.998 (95%CI: 0.574-1.732).

Conclusions: There was no relation between SUA with hypertension or diabetes, while there was independently and positively association with hypertriglyceridemia and low-density lipoprotein cholesterolemia. The health benefits of controlling SUA in centenarians still require evidence based on prospective studies.
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http://dx.doi.org/10.1186/s12877-021-02185-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028058PMC
April 2021

Central and Peripheral Adiposity Had Different Effect on Disability in Centenarians.

Front Endocrinol (Lausanne) 2021 16;12:635205. Epub 2021 Mar 16.

State Key Laboratory of Kidney Disease, Beijing Key Laboratory of Aging and Geriatrics, The 2nd Medical Center, Institute of Geriatrics, Chinese PLA General Hospital, Beijing, China.

Purpose: To explore the correlations between waist circumference, body mass index, calf circumference (CC), and waist-calf circumference ratio (WCR) and activities of daily living (ADLs) and instrumental activities of daily living (IADLs) in Hainan centenarians.

Patients And Methods: A total of 1,002 Hainan centenarians were selected by full sample household survey. ADLs and IADLs were used to investigate the ability of activity and instrumental activity in daily living. The possible non-linear associations were further analyzed using restricted cubic spline.

Results: After adjusting for demographic characteristics (gender, age, ethnicity, marital status, educational level, and type of residence) and lifestyle (smoking, drinking, and exercise), the odds ratio (OR) of CC (continuous variable) on ADL disability in centenarians was 0.90 (95% CI: 0.85-0.96), while high WCR (continuous variable) was related with high risk of ADL disability (OR=1.73; 95% confidence interval[CI], 1.07-2.80). The ORs of CC and WCR for IADL severe disability were 0.86 (95% CI, 0.82-0.91) and 2.23 (95% CI, 1.52-3.28), respectively.

Conclusion: Central (WCR) and peripheral (CC) adiposity had different effects on disability (ADL and IADL) in centenarians. Even in centenarians, maintaining muscle mass (with higher calf circumference) and avoiding central obesity are of positive significance for the prevention of ADL/IADL disability.
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http://dx.doi.org/10.3389/fendo.2021.635205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008817PMC
March 2021

Vertical Distributions of Primary and Secondary Aerosols in Urban Boundary Layer: Insights into Sources, Chemistry, and Interaction with Meteorology.

Environ Sci Technol 2021 04 26;55(8):4542-4552. Epub 2021 Mar 26.

State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing 100029, China.

Vertical measurements are essential for the characterization of aerosol and boundary layer interactions; yet, our knowledge of vertical profiles of primary and secondary aerosol species in megacities is limited. Here, we conducted comprehensive vertical measurements of aerosol particle composition on a 325 m meteorological tower with two aerosol chemical speciation monitors in winter in urban Beijing. The simultaneous measurements at ground level, 140, and 240 m illustrated similar aerosol bulk composition at these three heights. However, the vertical ratios varied significantly among different aerosol species. Particularly, the vertical ratios of the aqueous phase and photochemical-related secondary organic aerosol (SOA) (aqOOA/OOA) decreased significantly, accompanied by the increases in ratios of secondary to primary OA, highlighting different chemical properties of OA between ground level and aloft, and the large impacts of vertical changes in meteorology and gaseous precursors on SOA formation. The vertical changes in NO/SO ratios, however, were mostly insignificant, likely due to the low relative humidity and aerosol water content that inhibited nocturnal heterogeneous reactions in the residual layer. Considerable increases in the ratios of 240 m to ground level in the early morning were also observed for most aerosol species, demonstrating impact of residual layer on the air pollution of 2nd day.
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http://dx.doi.org/10.1021/acs.est.1c00479DOI Listing
April 2021

High throughput microRNAs sequencing profile of serum exosomes in women with and without polycystic ovarian syndrome.

PeerJ 2021 12;9:e10998. Epub 2021 Mar 12.

Shaoxing Maternity and Child Health Care Hospital, Shaoxing, China.

Background: Polycystic ovary syndrome (PCOS) is the most common type of endocrine disorder, affecting 5-11% of women of reproductive age worldwide. microRNAs (miRNAs) stably exist in circulating blood encapsulated in extracellular vesicles such as exosomes; therefore, serum miRNAs have the potential to serve as novel PCOS biomarkers.

Methods: To identify miRNA biomarkers that are associated with PCOS, we performed a comprehensive sequence-based characterization of the PCOS serum miRNA landscape. The serum exosomes were successfully isolated and characterized in a variety of ways. Next, sequence-based analysis was performed on serum exosomes to screen the differentially expressed miRNAs in women with and without PCOS.

Results: The sequence data revealed that the levels of 54 miRNAs significantly differed between PCOS patients and normal controls. The levels of these miRNAs were detected by RT-qPCR. The results show that hsa-miR-1299, hsa-miR-6818-5p hsa-miR-192-5p, and hsa-miR-145-5p are significantly differentially expressed in PCOS patients serum exosomes and identify these microRNAs as potential biomarkers for PCOS. Furthermore, Gene Ontology (GO) analyses and KEGG pathway analyses of the miRNA targets further allowed to explore the potential implication of the miRNAs in PCOS.

Conclusion: Our findings suggest that serum exosomal miRNAs serve important roles in PCOS and may be used as novel molecular biomarkers for clinical diagnosis.
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http://dx.doi.org/10.7717/peerj.10998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958896PMC
March 2021

Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8 T cell immunity.

Cell Metab 2021 May 23;33(5):988-1000.e7. Epub 2021 Mar 23.

Institute for Immunology, School of Medicine, Tsinghua University, Beijing 100084, China; Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing 100084, China. Electronic address:

Recent studies in both mice and humans have suggested that gut microbiota could modulate tumor responsiveness to chemo- or immunotherapies. However, the underlying mechanism is not clear yet. Here, we found that gut microbial metabolites, especially butyrate, could promote the efficacy of oxaliplatin by modulating CD8 T cell function in the tumor microenvironment. Butyrate treatment directly boosted the antitumor cytotoxic CD8 T cell responses both in vitro and in vivo in an ID2-dependent manner by promoting the IL-12 signaling pathway. In humans, the oxaliplatin responder cancer patients exhibited a higher amount of serum butyrate than did non-responders, which could also increase ID2 expression and function of human CD8 T cells. Together, our findings suggest that the gut microbial metabolite butyrate could promote antitumor therapeutic efficacy through the ID2-dependent regulation of CD8 T cell immunity, indicating that gut microbial metabolites could be effective as a part of cancer therapy.
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http://dx.doi.org/10.1016/j.cmet.2021.03.002DOI Listing
May 2021

Light absorption of black carbon and brown carbon in winter in North China Plain: comparisons between urban and rural sites.

Sci Total Environ 2021 May 27;770:144821. Epub 2021 Jan 27.

State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing 100029, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China. Electronic address:

The light absorption black carbon (BC) and brown carbon (BrC) are two important sources of uncertainties in radiative forcing estimate. Here we investigated the light absorption enhancement (E) of BC due to coated materials at an urban (Beijing) and a rural site (Gucheng) in North China Plain (NCP) in winter 2019 by using a photoacoustic extinctiometer coupled with a thermodenuder. Our results showed that the average (±1σ) E was 1.32 (±0.15) at the rural site, which was slightly higher than that at the urban site (1.24 ± 0.15). The dependence of E on coating materials was found to be relatively limited at both sites. However, E presented considerable increases as a function of relative humidity below 70%. Further analysis showed that E during non-heating period in Beijing was mainly caused by secondary components, while it was dominantly contributed by enhanced primary emissions in heating season at both sites. In particular, aerosol particles mixed with coal combustion emissions had a large impact on E (>1.40), while the fresh traffic emissions and freshly oxidized secondary OA (SOA) had limited E (1.00-1.23). Although highly aged or aqueous-phase processed SOA coated on BC showed the largest E, their contributions to the bulk absorption enhancement were generally small. We also quantified the absorption of BrC and source contributions. The results showed the BrC absorption at the rural site was nearly twice that of urban site, yet absorption Ångström exponents were similar. Multiple linear regression analysis highlighted the major sources of BrC being coal combustion emissions and photochemical SOA at both sites with additional biomass burning at the rural site. Overall, our results demonstrated the relatively limited winter light absorption enhancement of BC in different chemical environments in NCP, which needs be considered in regional climate models to improve BC radiative forcing estimates.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144821DOI Listing
May 2021

The emerging role of ferroptosis in intestinal disease.

Cell Death Dis 2021 03 17;12(4):289. Epub 2021 Mar 17.

Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.

Ferroptosis is a newly recognised type of regulated cell death (RCD) characterised by iron-dependent accumulation of lipid peroxidation. It is significantly distinct from other RCDs at the morphological, biochemical, and genetic levels. Recent reports have implicated ferroptosis in multiple diseases, including neurological disorders, kidney injury, liver diseases, and cancer. Ferroptotic cell death has also been associated with dysfunction of the intestinal epithelium, which contributes to several intestinal diseases. Research on ferroptosis may provide a new understanding of intestinal disease pathogenesis that benefits clinical treatment. In this review, we provide an overview of ferroptosis and its underlying mechanisms, then describe its emerging role in intestinal diseases, including intestinal ischaemia/reperfusion (I/R) injury, inflammatory bowel disease (IBD), and colorectal cancer (CRC).
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http://dx.doi.org/10.1038/s41419-021-03559-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969743PMC
March 2021

The path linking disease severity and cognitive function with quality of life in Parkinson's disease: the mediating effect of activities of daily living and depression.

Health Qual Life Outcomes 2021 Mar 17;19(1):92. Epub 2021 Mar 17.

Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Department of Health Statistics, School of Public Health, Shanxi Medical University, 56 South XinJian Road, Taiyuan, 030001, People's Republic of China.

Background: Research on quality of life (QOL) with Parkinson's disease (PD) has examined direct influencing factors, not mediators. The study aim was to explore whether PD severity and poor cognitive function may decrease physical and mental QOL by reducing activities of daily living (ADL) and increasing depression in sequence.

Methods: We conducted a cross-sectional questionnaire study of 150 PD hospital patients in China. PD severity, cognitive function, ADL, depression, and QOL were evaluated. We used structural equation modeling to analyze the mediating effects of ADL and depression on the association between PD severity/cognition and the physical health and mental health component summary scores measured by the SF36 quality of life instrument.

Results: There was a significant mediating effect of PD severity on physical health via ADL and depression (95% CI: - 0.669, - 0.026), and a significant direct effect (p < 0.001). The mediating effect of PD severity on mental health via ADL and depression was significant (95% CI: - 2.135, - 0.726), but there was no direct effect (p = 0.548). There was a significant mediating effect of cognitive function on physical health via ADL and depression (95% CI: 0.025, 0.219) and a significant direct effect (p < 0.001). The mediating effect of cognitive function on mental health via ADL and depression was significant (95% CI: 0.256, 0.645), but there was no direct effect (p = 0.313). The physical health models showed a partial mediation, and the mental health models showed a complete mediation, of ADL and depression.

Conclusions: PD severity and cognitive function increase depression by reducing ADL, leading to lower QOL, and directly or indirectly affect physical health and mental health through different pathways.
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http://dx.doi.org/10.1186/s12955-021-01740-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972188PMC
March 2021

MALAT1 maintains the intestinal mucosal homeostasis in Crohn's disease via the miR-146b-5p-CLDN11/NUMB pathway.

J Crohns Colitis 2021 Mar 2. Epub 2021 Mar 2.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China.

Background & Aims: Intestinal homeostasis disorder is critical for developing Crohn's disease (CD). Maintaining mucosal barrier integrity is essential for intestinal homeostasis, preventing intestinal injury and complications. Among the remarkably altered long non-coding RNAs (lncRNAs) in CD, we aimed to investigate whether metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) modulated CD and consequent disruption of intestinal homeostasis.

Methods: Microarray analyses on intestinal mucosa of CD patients and controls were performed to identify dysregulated lncRNAs. MALAT1 expression was investigated via qRT-PCR and its distribution in intestinal tissues was detected using BaseScope. Intestines from MALAT1 knockout mice with colitis were investigated using histological, molecular and biochemical approaches. Effects of intestinal epithelial cells transfected with MALAT1 lentiviruses and Smart Silencer, on monolayer permeability and apical junction complex (AJC) proteins were analysed. MiR-146b-5p were confirmed as a critical MALAT1 mediator in cells transfected with miR-146b-5p mimic/inhibitor and in colitis mice administered with agomir-146b-5p/antagomir-146b-5p. Interaction between MALAT1 and miR-146b-5p was predicted via bioinformatics and validated using Dual-luciferase reporter assay and Ago2-RIP.

Results: MALAT1 was aberrantly downregulated in the intestine mucosa of CD patients and mice with experimental colitis. MALAT1 knockout mice were hypersensitive to DSS-induced experimental colitis. MALAT1 regulated intestinal mucosal barrier and regained intestinal homeostasis by sequestering miR-146b-5p and maintaining the expression of the AJC proteins NUMB and CLDN11.

Conclusions: Downregulation of MALAT1 contributed to the pathogenesis of CD by disrupting AJC. Thus, a specific MALAT1-miR-146b-5p-NUMB/CLDN11 pathway that plays a vital role in maintaining intestinal mucosal homeostasis may serve as a novel target for CD treatment.
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http://dx.doi.org/10.1093/ecco-jcc/jjab040DOI Listing
March 2021

The Role of BMI and Blood Pressure in the Relationship Between Total Cholesterol and Disability in Chinese Centenarians: A Cross-Sectional Study.

Front Med (Lausanne) 2021 16;8:608941. Epub 2021 Feb 16.

Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatrics Diseases, Second Medical Center of Chinese PLA General Hospital, Beijing, China.

Lower serum lipid metabolism might be associated with the decline of activity of daily living in the extreme longevity group. However, studies on models and possible paths of this correlation between total cholesterol (TC) and disability in centenarians are scarce. The aim of this study was to verify this correlation and explore the mediating effect of BMI and blood pressure on this relationship in Hainan centenarians. We conducted a cross-sectional analysis of 1002 centenarians from the China Hainan Centenarians Cohort Study (CHCCS). Data on demographics, anthropometry data, lifestyle, and TC levels were collected through interviews, physical examinations, and laboratory tests. The Barthel index and Lawton index, measuring the disability status, were used to estimate the activity of daily living (ADL) and instrumental activity of daily living (IADL). A multivariable logistic regression model was used to explore the correlation between disability and TC levels. Mediation analyses were used to explore the both direct and indirect effects of TC level on disability. After adjusting for covariates, with 1 mmol/L increment in TC, the adjusted odds ratios (ORs) of ADL severe disability and ADL moderate & severe disability were 0.789(95%CI: 0.650-0.959) and 0.822(95%CI: 0. 0.699-0.966), respectively. There was a significant declining trend in the prevalence of different types of disability with increment in TC. The correlation was more pronounced among Hainan female centenarians. In the analysis of mediating effect among the female population, BMI significantly mediated the effect of TC levels on different types of disability. BMI and SBP, as chain mediators, multiply and chain mediated the effect of TC levels on IADL. Low TC levels might be correlated with a higher frequency of disability in female centenarians, and this correlation might be mediated by BMI and blood pressure.
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http://dx.doi.org/10.3389/fmed.2021.608941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921456PMC
February 2021