Publications by authors named "Na Tian"

137 Publications

hnRNPA1 enhances FOXP3 stability to promote the differentiation and functions of regulatory T cells.

FEBS Lett 2021 Jun 3. Epub 2021 Jun 3.

Shanghai Institute of Immunology & Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Regulatory T cells (Tregs) are indispensable for the maintenance of immunological self-tolerance and homeostasis. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is required for optimal Treg induction. Here, we reveal that human induced Tregs (iTregs) lacking hnRNPA1 show reduced expression of the transcription factor FOXP3, increased ubiquitination level of FOXP3, and impaired suppressive abilities. Human naïve CD4 T cells with hnRNPA1 knockdown show a decreased Treg differentiation ratio. hnRNPA1 could interact with FOXP3 as well as with the E3 ligase Stub1. The phosphorylation at hnRNPA1-S199 could increase both interactions. The overexpression of FOXP3 in Tregs containing shhnRNPA1 could not recover the phenotype caused by hnRNPA1 knockdown. Therefore, there might be multiple essential pathways regulated by hnRNPA1 in Tregs. In conclusion, we present a new role of hnRNPA1 in promoting Treg function, indicating it as a promising target for tumor therapies.
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http://dx.doi.org/10.1002/1873-3468.14142DOI Listing
June 2021

Selective and Efficient Photoinactivation of Intracellular and MRSA with Little Accumulation of Drug Resistance: Application of a Ru(II) Complex with Photolabile Ligands.

J Med Chem 2021 06 25;64(11):7359-7370. Epub 2021 May 25.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

Novel antibacterial agents capable of efficiently sterilizing intracellular and methicillin-resistant (MRSA) but with low cytotoxicity and low resistance development are quite appealing. In this work, three Ru(II) complexes with photolabile ligands were explored to realize such a goal. Complex (5 μM) can inhibit more than 90% growth of /MRSA that has invaded in J774A.1 cells upon visible light irradiation, being much more efficient than vancomycin. In similar conditions, negligible dark- and phototoxicity were found toward the host cells. The bactericidal activity is highly correlated with DNA covalent binding by the Ru(II) fractions generated after ligand photodissociation. Moreover, quickly developed resistance toward vancomycin, while negligible resistance toward complex even after 700 generations was obtained. These appealing results may pave a new way for fighting against intracellular antibiotic-resistant pathogens.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02257DOI Listing
June 2021

MicroRNA-370 carried by M2 macrophage-derived exosomes alleviates asthma progression through inhibiting the FGF1/MAPK/STAT1 axis.

Int J Biol Sci 2021 23;17(7):1795-1807. Epub 2021 Apr 23.

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Emerging evidence has suggested the functions of exosomes in allergic diseases including asthma. By using a mouse model with asthma induced by ovalbumin (OVA), we explored the roles of M2 macrophage-derived exosomes (M2Φ-Exos) in asthma progression. M2Φ-Exos significantly alleviated OVA-induced fibrosis and inflammatory responses in mouse lung tissues, as well as inhibited abnormal proliferation, invasion, and fibrosis-related protein production in platelet derived growth factor (PDGF-BB) treated primary mouse airway smooth muscle cells (ASMCs). The OVA administration in mice or the PDGF-BB treatment in ASMCs reduced the expression of miR-370, which was detected in M2Φ-Exos by miRNA sequencing. However, treating the mice or ASMCs with M2Φ-Exos reversed the inhibitory effect of OVA or PDGF-BB on miR-370 expression. We identified that the target of miR-370 was fibroblast growth factor 1 (). Downregulation of miR-370 by Lv-miR-370 inhibitor or overexpression of FGF1 by Lv-FGF1 blocked the protective roles of M2Φ-Exos in asthma-like mouse and cell models. M2Φ-Exos were found to inactivate the MAPK signaling pathway, which was recovered by miR-370 inhibition or FGF1 overexpression. Collectively, we conclude that M2Φ-Exos carry miR-370 to alleviate asthma progression through downregulating FGF1 expression and the MAPK/STAT1 signaling pathway. Our study may offer a novel insight into asthma treatment.
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http://dx.doi.org/10.7150/ijbs.59715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120458PMC
April 2021

Genome-wide identification and expression pattern analysis of lipoxygenase gene family in banana.

Sci Rep 2021 May 11;11(1):9948. Epub 2021 May 11.

College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

The LOX genes have been identified and characterized in many plant species, but studies on the banana LOX genes are very limited. In this study, we respectively identified 18 MaLOX, 11 MbLOX, and 12 MiLOX genes from the Musa acuminata, M. balbisiana and M. itinerans genome data, investigated their gene structures and characterized the physicochemical properties of their encoded proteins. Banana LOXs showed a preference for using and ending with G/C and their encoded proteins can be classified into 9-LOX, Type I 13-LOX and Type II 13-LOX subfamilies. The expansion of the MaLOXs might result from the combined actions of genome-wide, tandem, and segmental duplications. However, tandem and segmental duplications contribute to the expansion of MbLOXs. Transcriptome data based gene expression analysis showed that MaLOX1, 4, and 7 were highly expressed in fruit and their expression levels were significantly regulated by ethylene. And 11, 12 and 7 MaLOXs were found to be low temperature-, high temperature-, and Fusarium oxysporum f. sp. Cubense tropical race 4 (FocTR4)-responsive, respectively. MaLOX8, 9 and 13 are responsive to all the three stresses, MaLOX4 and MaLOX12 are high temperature- and FocTR4-responsive; MaLOX6 and MaLOX17 are significantly induced by low temperature and FocTR4; and the expression of MaLOX7 and MaLOX16 are only affected by high temperature. Quantitative real-time PCR (qRT-PCR) analysis revealed that the expression levels of several MaLOXs are regulated by MeJA and FocTR4, indicating that they can increase the resistance of banana by regulating the JA pathway. Additionally, the weighted gene co-expression network analysis (WGCNA) of MaLOXs revealed 3 models respectively for 5 (MaLOX7-11), 3 (MaLOX6, 13, and 17), and 1 (MaLOX12) MaLOX genes. Our findings can provide valuable information for the characterization, evolution, diversity and functionality of MaLOX, MbLOX and MiLOX genes and are helpful for understanding the roles of LOXs in banana growth and development and adaptations to different stresses.
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http://dx.doi.org/10.1038/s41598-021-89211-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113564PMC
May 2021

Exceptional Cocatalyst-Free Photo-Enhanced Piezocatalytic Hydrogen Evolution of Carbon Nitride Nanosheets from Strong In-Plane Polarization.

Adv Mater 2021 May 8:e2101751. Epub 2021 May 8.

Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing, 100083, China.

Utilizing mechanical energy to produce hydrogen is emerging as a promising way to generate renewable energy, but is challenged by low efficiency and scanty cognition. In this work, graphitic carbon nitride (g-C N ) with an atomically thin sheet-like structure is applied for prominent piezocatalytic and photo-enhanced piezocatalytic H production. It is revealed that the anomalous piezoelectricity in g-C N originates from the strong in-plane polarization along the a-axis, contributed by the superimposed polar tri-s-triazine units and flexoelectric effect derived from the structured triangular cavities, which provides powerful electrochemical driving force for the water reduction reaction. Furthermore, the photo-enhanced charge transfer enables g-C N nanosheets to reserve more energized polarization charges to fully participate in the reaction at the surface reactive sites enriched by strain-induced carbon vacancies. Without any cocatalysts, an exceptional photo-piezocatalytic H evolution rate of 12.16 mmol g h is delivered by the g-C N nanosheets, far exceeding that of previously reported piezocatalysts and g-C N photocatalysts. Further, high pure-water-splitting performance with production of the value-added oxidation product H O via photo-piezocatalysis is also disclosed. This work not only exposes the potential of g-C N as a piezo-semiconductor for catalytic H evolution, but also breaks a new ground for the conversion of solar and mechanical energy by photomediated piezocatalytic reaction.
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http://dx.doi.org/10.1002/adma.202101751DOI Listing
May 2021

MondoA-TXNIP axis maintains regulatory T cell identity and function in colorectal cancer microenvironment.

Gastroenterology 2021 Apr 23. Epub 2021 Apr 23.

Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai 200025, China. Electronic address:

Background & Aims: The metabolic features and function of intratumoral Tregs are ambiguous in colorectal cancer. Tumor-infiltrating Tregs are reprogrammed to exhibit high glucose-depleting properties and adapt to the glucose-restricted microenvironment. The glucose-responsive transcription factor MondoA is highly expressed in Tregs. However, the role of MondoA in colorectal cancer-infiltrating Tregs in response to glucose limitation remains to be elucidated.

Methods: We performed studies using mice in which MondoA was conditionally deleted in Tregs and human colorectal cancer tissues. Seahorse and other metabolic assays were used to assess Treg metabolism. To study the role of Tregs in anti-tumor immunity, we used a subcutaneous MC38 colorectal cancer model and induced colitis-associated colorectal cancer in mice by azoxymethane (AOM) and dextran sodium sulfate (DSS).

Results: Here we analyzed single-cell RNA-seq data of colorectal cancer patients and revealed that intratumoral Tregs featured low activity of MondoA-TXNIP axis and increased glucose uptake. Although MondoA-deficient Tregs were less immune suppressive and selectively promoted Th1 responses in a subcutaneous MC38 tumor model, Treg-specific MondoA knockout mice were more susceptible to AOM-DSS-induced colorectal cancer. Mechanistically, suppression of MondoA-TXNIP axis promoted glucose uptake and glycolysis, induced hyper-glycolytic Th17-like Tregs, which facilitated Th17 inflammation, promoted IL-17A-induced of CD8 T cell exhaustion and drove colorectal carcinogenesis. Blockade of IL-17A reduced tumor progression and minimized the susceptibility of MondoA-deficient mice to colorectal carcinogenesis.

Conclusions: The MondoA-TXNIP axis is a critical metabolic regulator of Treg identity and function in colorectal cancer microenvironment and a promising target for cancer therapy.
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http://dx.doi.org/10.1053/j.gastro.2021.04.041DOI Listing
April 2021

Erratum: Urine-derived stem cells accelerate the recovery of injured mouse hepatic tissue.

Am J Transl Res 2021 15;13(3):1904. Epub 2021 Mar 15.

Stem Cell Biology and Therapy Laboratory, Children's Hospital of Chongqing Medical University Chongqing, P. R. China.

[This corrects the article on p. 5131 in vol. 12, PMID: 33042410.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014404PMC
March 2021

ERα down-regulates carbohydrate responsive element binding protein and decreases aerobic glycolysis in liver cancer cells.

J Cell Mol Med 2021 Apr 3;25(7):3427-3436. Epub 2021 Mar 3.

Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Deregulated metabolism is one of the characteristics of hepatocellular carcinoma. Sex hormone receptor signalling has been involved in the marked gender dimorphism of hepatocellular carcinoma pathogenesis. Oestrogen receptor (ER) has been reported to reduce the incidence of liver cancer. However, it remains unclear how oestrogen and ER regulate metabolic alterations in liver tumour cells. Our previous work revealed that ERα interacted with carbohydrate responsive element binding protein (ChREBP), which is a transcription factor promoting aerobic glycolysis and proliferation of hepatoma cells. Here, the data showed that ERα overexpression with E2 treatment reduced aerobic glycolysis and cell proliferation of hepatoma cells. In addition to modestly down-regulating ChREBP transcription, ERα promoted ChREBP degradation. ERα co-immunoprecipitated with both ChREBP-α and ChREBP-β, the two known subtypes of ChREBP. Although E2 promoted ERα to translocate to the nucleus, it did not change subcellular localization of ChREBP. In addition to interacting with ChREBP-β and promoting its degradation, ERα decreased ChREBP-α-induced ChREBP-β transcription. Taken together, we confirmed an original role of ERα in suppressing aerobic glycolysis in liver cancer cells and elucidated the mechanism by which ERα and ChREBP-α together regulated ChREBP-β expression.
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http://dx.doi.org/10.1111/jcmm.16421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034478PMC
April 2021

Knockdown of nrf2 Exacerbates TNF--Induced Proliferation and Invasion of Rheumatoid Arthritis Fibroblast-Like Synoviocytes through Activating JNK Pathway.

J Immunol Res 2020 22;2020:6670464. Epub 2020 Dec 22.

Department of Rheumatology & Immunology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Fibroblast-like synoviocytes (FLS) in the synovial tissue of rheumatoid arthritis (RA) exhibit over-proliferative and aggressive phenotypes, which participate in the pathophysiology of RA. In RA, little is known about the nonantioxidant effect of nuclear factor erythroid 2-related factor 2 (nrf2), the master regulator of redox homeostasis. In this study, we aimed to explore the expression and upstream regulatory factors of nrf2 and revealed its functions in modulating the proliferation and invasion in RA-FLS. FLS were isolated from RA and osteoarthritis patients. Expression of nrf2 in the synovial tissues and FLS was analyzed by immunohistochemistry, real-time PCR, Western blotting, and immunofluorescence staining. Cell proliferation was examined by Cell Counting Kit-8. Cell invasion was tested by transwell assay. Phosphorylation of JNK was determined by Western blotting. The results showed that nrf2 expression in the RA synovial tissues was upregulated. TNF- promoted expression and nuclear translocation of nrf2 in RA-FLS and increased the intracellular reactive oxygen species (ROS) level. Nrf2 nuclear translocation was blocked by ROS inhibitor N-acetylcysteine. Both knockdown of nrf2 by siRNA and inhibition of nrf2 by ML385 significantly promoted the TNF--induced proliferation and invasion of RA-FLS. Activation of nrf2 by sulforaphane (SFN) profoundly inhibited the TNF--induced proliferation and invasion of RA-FLS. Knockdown of nrf2 also enhanced the TNF--induced matrix metalloproteinases (MMPs) expression and phosphorylation of JNK in RA-FLS. Proliferation and invasion of RA-FLS incubated with TNF- and nrf2 siRNA were inhibited by pretreatment with JNK inhibitor SP600125. In conclusion, nrf2 is overexpressed in synovial tissues of RA patients, which may be promoted by TNF- and ROS levels. Activation of nrf2 may suppress TNF--induced proliferation, invasion, and MMPs expression in RA-FLS by inhibiting JNK activation, indicating that nrf2 plays a protective role in relieving the severity of synovitis in RA. Our results might provide novel insights into the treatment of RA.
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http://dx.doi.org/10.1155/2020/6670464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772017PMC
December 2020

Increased Muscle Activity Accompanying With Decreased Complexity as Spasticity Appears: High-Density EMG-Based Case Studies on Stroke Patients.

Front Bioeng Biotechnol 2020 16;8:589321. Epub 2020 Nov 16.

Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, China.

Spasticity is a major contributor to pain, disabilities and many secondary complications after stroke. Investigating the effect of spasticity on neuromuscular function in stroke patients may facilitate the development of its clinical treatment, while the underlying mechanism of spasticity still remains unclear. The aim of this study is to explore the difference in the neuromuscular response to passive stretch between healthy subjects and stroke patients with spasticity. Five healthy subjects and three stroke patients with spastic elbow flexor were recruited to complete the passive stretch at four angular velocities (10°/s, 60°/s, 120°/s, and 180°/s) performed by an isokinetic dynamometer. Meanwhile, the 64-channel electromyography (EMG) signals from biceps brachii muscle were recorded. The root mean square (RMS) and fuzzy entropy (FuzzyEn) of EMG recordings of each channel were calculated, and the relationship between the average value of RMS and FuzzyEn over 64-channel was examined. The two groups showed similar performance from results that RMS increased and FuzzyEn decreased with the increment of stretch velocity, and the RMS was negatively correlated with FuzzyEn. The difference is that stroke patients showed higher RMS and lower FuzzyEn during quick stretch than the healthy group. Furthermore, compared with the healthy group, distinct variations of spatial distribution within the spastic muscle were found in the EMG activity of stroke patients. These results suggested that a large number of motor units were recruited synchronously in the presence of spasticity, and this recruitment pattern was non-uniform in the whole muscle. Using a combination of RMS and FuzzyEn calculated from high-density EMG (HD-EMG) recordings can provide an innovative insight into the physiological mechanism underlying spasticity, and FuzzyEn could potentially be used as a new indicator for spasticity, which would be beneficial to clinical intervention and further research on spasticity.
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http://dx.doi.org/10.3389/fbioe.2020.589321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703112PMC
November 2020

[Duration of automated auditory brainstem response test for the initial hearing screening and influencing factors for the duration in neonates].

Zhongguo Dang Dai Er Ke Za Zhi 2020 Oct;22(10):1085-1091

Children's Medical Center, Qilu Hospital of Shandong University, Jinan 250012, China.

Objective: To study the duration of automated auditory brainstem response (AABR) test for initial hearing screening and the factors influencing the duration in neonates.

Methods: A total of 472 neonates who were admitted to the neonatal intensive care unit (NICU) were enrolled as the study group and 182 healthy neonates were enrolled as the healthy control group. The influence of the duration of AABR test on the initial screening results was observed in the two groups. The influencing factors for the AABR test duration were analyzed.

Results: In the AABR screening of 180, 360, and 540 seconds, the study group had a failure rate of 41.5%, 28.4%, and 24.4% respectively, while the healthy control group had a failure rate of 31.3%, 19.8%, and 15.4% respectively, showing a decreasing trend with the extension of test time in both groups (P<0.05). In the two groups, the screening results of 180-second testing were moderately consistent with those of 360- or 540-second testing (Kappa<0.75, P<0.05), and the screening results of 360-second testing were highly consistent with those of 540-second testing (Kappa>0.75, P<0.05). In the study group, the median duration of AABR test was 108 seconds (95%CI: 97-120 seconds), which was significantly longer than the duration of 75 seconds (95%CI: 65-85 seconds) in the healthy control group (P<0.05). The Cox regression analysis showed that maternal age ≥35 years, anemia, and electrolyte disturbance (RR<1, P<0.05) were independent risk factors for prolonged AABR test duration, while the prolonged continuous positive airway pressure-assisted ventilation was a protective factor (RR>1, P<0.05).

Conclusions: The AABR test time of 360-540 seconds for initial hearing screening helps to reduce false positive results due to environmental and risk factors in neonates. It may be useful to reduce the false positive results of AABR screening before discharge by taking corresponding intervention measures for NICU neonates with high risk factors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568999PMC
October 2020

Urine-derived stem cells accelerate the recovery of injured mouse hepatic tissue.

Am J Transl Res 2020 15;12(9):5131-5150. Epub 2020 Sep 15.

Stem Cell Biology and Therapy Laboratory, Children's Hospital of Chongqing Medical University Chongqing, P. R. China.

Urine-derived stem cells (USCs) are autologous stem cells that exhibit self-renewal ability and multi-lineage differentiation potential. These characteristics make USCs an ideal cell source for hepatocellular transplantation. Here, we investigated the biological characteristics of USCs and their potential use for the treatment of chronic liver injury. We characterized the cell-surface marker profile of USCs by flow cytometry and determined the osteogenic, adipogenic, and hepatic differentiation capacities of USCs using histology. We established a chronic liver-injury model by intraperitoneally injecting carbon tetrachloride into nude mice. USCs were then transplanted via tail vein injection. To determine liver function and histopathology following chronic liver injury, we calculated the liver index, measured serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and performed histological staining. USCs were small, adherent cells expressing mesenchymal but not hematopoietic stem-cell markers. Some induced USCs underwent osteogenic and adipogenic differentiation. When co-cultured with hepatic progenitor cells, about 10% of USCs underwent hepatic differentiation. The ALT and AST levels of the USC-transplanted group were lower than that of the chronic liver-injury model group, and there were no significant differences between the two USC-transplanted groups. However, hepatocyte degeneration and liver fibrosis substantially improved in the hypoxia-pretreated USC-transplanted group compared with the normoxia USC-transplanted group. Taken together, USCs display desirable proliferation and differentiation characteristics, and USC transplantation partially improves abnormal liver function and pathology associated with chronic liver injury. Furthermore, hypoxia pretreatment promotes cell proliferation, migration, and colony formation by inducing autophagy, leading to USC-elicited liver tissue recovery following injury .
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540109PMC
September 2020

[Identification of Gastrodia elata and its hybrid by polymerase chain reaction].

Zhongguo Zhong Yao Za Zhi 2020 Aug;45(15):3666-3671

Aademician Workstation, Jiangxi University of Traditional Chinese Medicine Nanchang 330004, China State Key Laboratory of Dao-di Herbs, National Resource Center for Chinese Materia Medica,China Academy of Chinese Medical Sciences Beijing 100700, China.

Gastrodia elata is a kind of traditional Chinese medicinal materials and has good medicinal value. G. elata is divided into five varieties, which includes G. elata f. elata(proto variant), G. elata f. glauca, G. elata f. viridis, G. elata f. flavid and G. elata f. alba. Among them, G. elata f. elata and G. elata f. glauca have excellent characteristics and higher contents of gastrodin and polysaccharides. The hybrid of G. elata f. elata and G. elata f. glauca is present in markets, but the characteristics between hybrid and parent are not obvious and distinguished quickly and accurately. The aim of this study is to establish a PCR specific PCR identification method, which can identify G. elata f. elata, G. elata f. glauca and their hybrid. Based on the re-sequencing results of G. elata, we screened for the single nucleotide polymorphism(SNP) variation sites, and designed two pairs of specific primers(W291-F/W291-R and H255-F/H255-R). We further collected G. elata f. elata, G. elata f. glauca and their hybrid samples from different regions, established and optimized PCR method, and investigated and verified their tolerance and applicability. The results showed that when the annealing temperature was 48 ℃ and the number of cycles was 33, 255 bp specific band were obtained from G. elata f. glauca and hybrid by using specific primers W291-F/W291-R. When the annealing temperature was 51 ℃ and the number of cycles was 33, 291 bp specific band were obtained from G. elata f. elata and hybrid by using specific primers H255-F/H255-R. Our method could be used as a promising method to identify G. elata f. elata, G. elata f. glauca and their hybrid.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200527.102DOI Listing
August 2020

GSK-3β activation accelerates early-stage consumption of Hippocampal Neurogenesis in senescent mice.

Theranostics 2020 1;10(21):9674-9685. Epub 2020 Aug 1.

Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Adult hippocampal neurogenesis (AHN) deficits contribute to the progression of cognitive impairments during accelerated senescence, with the mechanistic causes poorly understood. Glycogen synthase kinase-3β (GSK-3β) is a critical regulator in prenatal neurodevelopment. The present study aims to study whether and how GSK-3β regulates AHN during the accelerated senescence. AHN and AHN-dependent cognition and GSK-3β were evaluated in 3- and 6-month senescence-accelerated mice prone 8 (SAM-P8) and senescence resistant 1 (SAM-R1) mice, respectively. GSK-3β was selectively overexpressed in wild-type mice using adeno-associated virus, or knocked-out by crossbreeding with GSK-3β floxed mice in the neural stem cells (NSCs) of Nestin-Cre mice, or pharmacologically inhibited with SB216763 in SAM-P8 mice. AHN was evaluated by BrdU-, DCX-staining and retrovirus-labeling. AHN transiently increased at 3-month, but dramatically dropped at 6-month of age in SAM-P8 mice with a simultaneous activation of GSK-3β at 3-month. Selective overexpression of GSK-3β in hippocampal NSCs of wildtype mice induced long-term AHN deficits due to an accelerated depletion of NSC pool, although it transiently increased the proliferation and survival of the newborn neurons. Pharmacologically inhibiting GSK-3β by SB216763 efficiently preserved AHN and improved contextual memory in 6-month SAM-P8 mice, while conditional knock-out of GSK-3β in NSCs impaired AHN. Early-stage activation of GSK-3β in NSCs impairs AHN by accelerating the depletion of NSC pool, and pharmacological inhibition of GSK-3β is efficient to preserve AHN during the accelerated aging. These results reveal novel mechanisms underlying the AHN impairments during accelerated senescence and provide new targets for pro-neurogenic therapies for related diseases.
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http://dx.doi.org/10.7150/thno.43829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449917PMC
May 2021

Diffusion tensor imaging study of brain precentral gyrus and postcentral gyrus during normal brain aging process.

Brain Behav 2020 10 25;10(10):e01758. Epub 2020 Aug 25.

Department of CT, The Fifth People's Hospital of Hengshui, Hengshui, Hebei, China.

Objective: To study the changes of white matter tracts in precentral gyrus and postcentral gyrus during normal brain aging process by analyzing fractional anisotropy (FA) values obtained from diffusion tensor imaging (DTI) technology.

Methods: Magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were conducted on 120 healthy right-handed subjects. The subjects were separated into four age groups, namely Young Male/Female (<45 years old) and Senior Male/Female (>45 years old). Each subject undertakes routine MRI and DTI scans. Left/right precentral and left/right postcentral gyrus are automatically detected on the image. The area for region of interest (ROI) is set to be 18 ± 2 mm .

Results: For each age group, the FA values of white matter in precentral gyrus and postcentral gyrus are statistically different (p < .05) in both left and right sides of the brain across different age groups and genders. Additionally, the FA values are statistically different (p < .05) between two young and senior age groups across different genders, brain regions, and hemispheres.

Conclusion: The FA values of precentral gyrus and postcentral gyrus are statistically different across genders, age groups, and hemispheres. Additionally, the FA values of both precentral gyrus and postcentral gyrus decrease over time, which is a strong indication of aging.
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http://dx.doi.org/10.1002/brb3.1758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559610PMC
October 2020

Cutting Edge: Inhibition of Glycogen Synthase Kinase 3 Activity Induces the Generation and Enhanced Suppressive Function of Human IL-10 FOXP3-Induced Regulatory T Cells.

J Immunol 2020 09 19;205(6):1497-1502. Epub 2020 Aug 19.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;

IL-10 is critical for Foxp3 regulatory T cell (Tregs)-mediated immune suppression, but how to efficiently upregulate IL-10 production in Tregs remains unclear. In this article, we show that human IL-10 FOXP3-induced regulatory T cell (iTreg) generation can be dramatically promoted by inhibiting GSK3 activity. IL-10 FOXP3 iTregs induced by GSK3 inhibition exhibit classical features of immune-suppressive T cells. We further demonstrate that IL-10 iTregs exhibit enhanced suppressive function in both IL-10-dependent and -independent manners. The enhanced suppressive function of IL-10 Tregs is not due to a single factor such as IL-10, although IL-10 may mediate this enhanced suppressive function to some extent. Mechanistically, the increased transcriptional activity of IL-10 promoter and the enhanced expression of C-Maf and BLIMP1 coordinately facilitate IL-10 expression in human iTregs under GSK3 inhibition. Our study provides a new strategy to generate human immune-suppressive IL-10 FOXP3 Tregs for immunotherapies.
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http://dx.doi.org/10.4049/jimmunol.2000136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477744PMC
September 2020

Photocatalysis Enhanced by External Fields.

Angew Chem Int Ed Engl 2020 Aug 7. Epub 2020 Aug 7.

Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes, School of Materials Science and Technology, China University of Geosciences, Beijing, 100083, P. R. China.

The efficient conversion of solar energy by means of photocatalysis shows huge potential to relieve the ongoing energy crisis and increasing environmental pollution. However, unsatisfactory conversion efficiency still hinders its practical application. The introduction of external fields can remarkably enhance the photocatalytic performance of semiconductors from the inside out. This review focuses on recent advances in the application of diverse external fields, including microwaves, mechanical stress, temperature gradient, electric field, magnetic field, and coupled fields, to boost photocatalytic reactions, for applications in, for example, contaminant degradation, water splitting, CO reduction, and bacterial inactivation. The relevant reinforcement mechanisms of photoabsorption, the transport and separation of photoinduced charges, and adsorption of reagents by the external fields are highlighted. Finally, the challenges and outlook for the development of external-field-enhanced photocatalysis are presented.
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http://dx.doi.org/10.1002/anie.202009518DOI Listing
August 2020

Mitochondrial GRIM-19 deficiency facilitates gastric cancer metastasis through oncogenic ROS-NRF2-HO-1 axis via a NRF2-HO-1 loop.

Gastric Cancer 2021 Jan 8;24(1):117-132. Epub 2020 Aug 8.

Chongqing Key Laboratory of Child Infection and Immunity, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, No. 136 Zhongshan Erd Road, Yuzhong District, Chongqing, 400014, China.

Background: NRF2, a prime target of cellular defense against oxidative stress, has shown a dark side profile in cancer progression. GRIM-19, an essential subunit of the mitochondrial MRC complex I, was recently identified as a suppressive role in tumorigenesis of human gastric cancer (GC). However, little information is available on the role of GRIM-19 and its cross-talk with NRF2 in GC metastasis.

Methods: Online GC database was used to investigate DNA methylation and survival outcomes of GRIM-19. CRISPR/Cas9 lentivirus-mediated gene editing, metastasis mice models and pharmacological intervention were applied to investigate the role of GRIM-19 deficiency in GC metastasis. Quantitative RT-PCR, FACS, Western blot, IHC, IF and reporter gene assay were performed to explore underlying mechanisms.

Results: Low GRIM-19 is correlated with poor survival outcome of GC patients while DNA hypermethylation is associated with GRIM-19 downregulation. GRIM-19 deficiency facilitates GC metastasis and triggers aberrant oxidative stress as well as ROS-dependent NRF2-HO-1 activation. Experimental interventions of specific ROS, NRF2 or HO-1 inhibitor significantly abrogate GRIM-19 deficiency-driven GC metastasis in vitro and in vivo. Moreover, HO-1 inhibition not only reverses GRIM-19 deficiency-driven NRF2 activation, but also feedback blocks NRF2 activator-induced NRF2 signaling, resulting in decreased metastasis-associated genes.

Conclusions: Our data suggest that GRIM-19 deficiency accelerates GC metastasis through the oncogenic ROS-NRF2-HO-1 axis via a positive-feedback NRF2-HO-1 loop. Therefore, this study not only offers novel insights into the role of oncogenic NRF2 in tumor progression, but also provides new strategies to alleviate the dark side of NRF2 by targeting HO-1.
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http://dx.doi.org/10.1007/s10120-020-01111-2DOI Listing
January 2021

Anti-CD40 monoclonal antibody ameliorates experimental autoimmune uveoretinitis in mice.

Vet Ophthalmol 2020 Sep 3;23(5):797-805. Epub 2020 Jul 3.

Chongqing Medical University, Chongqing, P. R. China.

Objective: To investigate the effects of CD40 on ocular inflammation in experimental autoimmune uveoretinitis (EAU) in B10.RIII mice.

Animals Studied: EAU-susceptible B10.RIII mice were subcutaneously immunized with interphotoreceptor retinoid-binding protein (IRBP) 161-180 in complete Freund's adjuvant and evaluated clinically and pathologically on days 7, 14, 21, 28, and 35 postimmunization. Anti-CD40 antibody was intraperitoneally injected into mice every other day from days 7 to 14 postimmunization. Phosphate-buffered saline (PBS)-injected EAU mice were used as the controls.

Procedures: The frequencies of CD11c CD40 dendritic cells (DCs), CD11c MHC-II DCs, and CD11c CD40 MHC-II DCs in splenocytes were evaluated by flow cytometry on days 0, 7, 14, and 21 after immunization. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 production in CD11c DCs was assessed by ELISA. IRBP-specific lymphocyte proliferation was assessed using a modified MTT cell proliferation assay.

Results: The number of CD11c CD40 DCs, CD11c MHC-II DCs, and CD11c CD40 MHC-II DCs increased at the onset of EAU, peaked at the height of disease severity, and was sustained at a high level until day 21. Treatment with anti-CD40 antibody significantly alleviated clinical and pathological activities related to EAU. Compared with the control mice, antibody-treated EAU mice showed few CD11c CD40 DC and CD11c CD40 MHC-II DC frequencies in splenocytes. The anti-CD40 antibody significantly suppressed IRBP-specific lymphocyte proliferation and TNF-α and IL-6 production by DCs in EAU mice.

Conclusions: The increased expression of CD40 and major histocompatibility complex (MHC) class II molecules in the splenocytes of EAU mice were correlated with inflammatory activity. Anti-CD40 treatment can significantly attenuate EAU activity by inhibiting systemic IRBP-specific immune responses.
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http://dx.doi.org/10.1111/vop.12799DOI Listing
September 2020

Bioimpedance Guided Fluid Management in Peritoneal Dialysis: A Randomized Controlled Trial.

Clin J Am Soc Nephrol 2020 05;15(5):685-694

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

Background And Objectives: Bioelectrical impedance analysis (BIA) devices can help assess volume overload in patients receiving maintenance peritoneal dialysis. However, the effects of BIA on the short-term hard end points of peritoneal dialysis lack consistency. This study aimed to test whether BIA-guided fluid management could improve short-term outcomes in patients on peritoneal dialysis.

Design, Setting, Participants, & Measurements: A single-center, open-labeled, randomized, controlled trial was conducted. Patients on prevalent peritoneal dialysis with volume overload were recruited from July 1, 2013 to March 30, 2014 and followed for 1 year in the initial protocol. All participants with volume overload were 1:1 randomized to the BIA-guided arm (BIA and traditional clinical methods) and control arm (only traditional clinical methods). The primary end point was all-cause mortality and secondary end points were cardiovascular disease mortality and technique survival.

Results: A total of 240 patients (mean age, 49 years; men, 51%; diabetic, 21%, 120 per group) were enrolled. After 1-year follow-up, 11(5%) patients died (three in BIA versus eight in control) and 21 patients were permanently transferred to hemodialysis (eight in BIA versus 13 in control). The rate of extracellular water/total body water decline in the BIA group was significantly higher than that in the control group. The 1-year patient survival rates were 96% and 92% in BIA and control groups, respectively. No significant statistical differences were found between patients randomized to the BIA-guided or control arm in terms of patient survival, cardiovascular disease mortality, and technique survival (>0.05).

Conclusions: Although BIA-guided fluid management improved the fluid overload status better than the traditional clinical method, no significant effect was found on 1-year patient survival and technique survival in patients on peritoneal dialysis.
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http://dx.doi.org/10.2215/CJN.06480619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269207PMC
May 2020

Genome-Wide Identification and Characterization of UTR-Introns of .

Int J Mol Sci 2020 Apr 27;21(9). Epub 2020 Apr 27.

College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

Introns exist not only in coding sequences (CDSs) but also in untranslated regions (UTRs) of a gene. Recent studies in animals and model plants such as have revealed that the UTR-introns (UIs) are widely presented in most genomes and involved in regulation of gene expression or RNA stability. In the present study, we identified introns at both 5'UTRs (5UIs) and 3'UTRs (3UIs) of sweet orange genes, investigated their size and nucleotide distribution characteristics, and explored the distribution of -elements in the UI sequences. Functional category of genes with predicted UIs were further analyzed using GO, KEGG, and PageMan enrichment. In addition, the organ-dependent splicing and abundance of selected UI-containing genes in root, leaf, and stem were experimentally determined. Totally, we identified 825 UI- and 570 3UI-containing transcripts, corresponding to 617 and 469 genes, respectively. Among them, 74 genes contain both 5UI and 3UI. Nucleotide distribution analysis showed that 5UI distribution is biased at both ends of 5'UTR whiles 3UI distribution is biased close to the start site of 3'UTR. elements analysis revealed that 5UI and 3UI sequences were rich of promoter-enhancing related elements, indicating that they might function in regulating the expression through them. Function enrichment analysis revealed that genes containing 5UI are significantly enriched in the RNA transport pathway. While, genes containing 3UI are significantly enriched in splicesome. Notably, many and the were identified to be 3UI-containing. RT-PCR result confirmed the existence of UIs in the eight selected gene transcripts whereas alternative splicing events were found in some of them. Meanwhile, qRT-PCR result showed that UIs were differentially expressed among organs, and significant correlation was found between some genes and their UIs, for example: The expression of and its 3UI was significantly negative correlated. This is the first report about the UIs in sweet orange from genome-wide level, which could provide evidence for further understanding of the role of UIs in gene expression regulation.
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http://dx.doi.org/10.3390/ijms21093088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247714PMC
April 2020

Optimization of food deprivation and sucrose preference test in SD rat model undergoing chronic unpredictable mild stress.

Animal Model Exp Med 2020 Mar 31;3(1):69-78. Epub 2020 Mar 31.

Laboratory Animal Center Chongqing Medical University Chongqing China.

Background: The chronic unpredictable mild stress (CUMS) model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression. However, there are no widely recognised standards for strategies for modeling and for behavioral testing. The present study aimed to optimize the protocols for food deprivation and the sucrose preference test (SPT) for the CUMS model.

Methods: We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley (SD) rats by testing food deprivation for 24 hours (8:00-8:00), food deprivation for 12 hours during the daytime (8:00-20:00) and food deprivation for 12 hours at night (20:00-8:00). Next, we established a SD rat CUMS model with 15 different stimulations, and used body weight measurement, SPT, forced swim test (FST), open field test (OFT) and Morris water maze (MWM) test to verify the success of the modeling. In the SPT, consumption of sucrose and pure water within 1 and 12 hours was measured.

Results: Twelve hours of food deprivation during the daytime (8:00-20:00) had no effect on body weight, while 12 hours of food deprivation at night (20:00-8:00) and 24 hours of food deprivation (8:00-8:00) significantly reduced the mean body weight of the SD rats. When SPT was used to verify the successful establishment of the CUMS rat model, sucrose consumption measured within 12 hours was less variable than that measured within 1 hour.

Conclusions: Twelve hours of food deprivation in the daytime (8:00-20:00) may be considered a mild stimulus for the establishment of a CUMS rat model. Measuring sucrose consumption over 12 hours is recommended for SPT.
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http://dx.doi.org/10.1002/ame2.12107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167236PMC
March 2020

Transketolase Deficiency in Adipose Tissues Protects Mice From Diet-Induced Obesity by Promoting Lipolysis.

Diabetes 2020 07 15;69(7):1355-1367. Epub 2020 Apr 15.

Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Obesity has recently become a prevalent health threat worldwide. Although emerging evidence has suggested a strong link between the pentose phosphate pathway (PPP) and obesity, the role of transketolase (TKT), an enzyme in the nonoxidative branch of the PPP that connects PPP and glycolysis, remains obscure in adipose tissues. In this study, we specifically deleted TKT in mouse adipocytes and found no obvious phenotype upon normal diet feeding. However, adipocyte TKT abrogation attenuated high-fat diet-induced obesity, reduced hepatic steatosis, improved glucose tolerance, alleviated insulin resistance, and increased energy expenditure. Mechanistically, TKT deficiency accumulated nonoxidative PPP metabolites and decreased glycolysis and pyruvate input into the mitochondria, leading to increased lipolytic enzyme gene expression and enhanced lipolysis, fatty acid oxidation, and mitochondrial respiration. Therefore, our data not only identify a novel role of TKT in regulating lipolysis and obesity but also suggest that limiting glucose-derived carbon into the mitochondria induces lipid catabolism and energy expenditure.
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http://dx.doi.org/10.2337/db19-1087DOI Listing
July 2020

[DNA fingerprinting identification of bile power(bile)medicines].

Zhongguo Zhong Yao Za Zhi 2020 Mar;45(5):1064-1069

College of Traditional Chinese Medicine, Guangdong Pharmaceutical University Guangzhou 510006, China State Key Laboratory of Dao-di Herbs Breeding Base, National Resource Center for Chinese Materia Medica,China Academy of Chinese Medical Sciences Beijing 100700, China.

The pig bile powder, bovine bile powder, snake bile, sheep bile, goose bile powder, and bear bile powder were contained by the Chinese Pharmacopoeia. The bile power medicine has a long history in traditional Chinese medicine and definite effect. However, the medicine of bile powder(bile) are similar in morphology. Besides, many medicine lack specific microscopic identification characteristics and chemical characteristics. There is a risk of adulteration, especially when the fake medicine were mixed in authentic medicine, it is difficult to detection. The key to control the quality and ensures the clinical efficacy is the good or bad, true or false of the bile power medicine. The STR typing technology is a method that according to differential typing of PCR amplified lengths to compare and identify individual organisms. Based on the principle of STR typing, the easily, rapid DNA fingerprinting method to identify the bile power and adulteration was established.The original animal or bile powder of pigs, cattle, sheep, chickens, ducks, geese, snakes, bears, fish were collected, the 12 S-L1091/12 S-H1478 and 16 S-L3428/16 S-H3667 was obtained by sifted, the DNA fingerprinting of the bile power and adulteration was obtained by STR typing. Every species has different STR fingerprints, so different species can be identified. Besides, the fingerprints have both the authentic and fake's information, the adulteration of authentic and fake can be identified. Therefore, the method to identify the bile power and adulteration was achieved through the combination of two primers. The DNA fingerprinting method established in this study can also be used for other animal medicine.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200105.106DOI Listing
March 2020

Chloromethyl-modified Ru(ii) complexes enabling large pH jumps at low concentrations through photoinduced hydrolysis.

Chem Sci 2019 Nov 24;10(43):9949-9953. Epub 2019 Oct 24.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials , Technical Institute of Physics and Chemistry , Chinese Academy of Sciences , Beijing 100190 , P. R. China . Email: ; Email:

Photoacid generators (PAGs) are finding increasing applications in spatial and temporal modulation of biological events and . In these applications, large pH jumps at low PAG concentrations are of great importance to achieve maximal expected manipulation but minimal unwanted interference. To this end, both high photoacid quantum yield and capacity are essential, where the capacity refers to the proton number that a PAG molecule can release. Up to now, most PAGs only produce one proton for each molecule. In this work, the hydrolysis reaction of benzyl chlorides was successfully leveraged to develop a novel type of PAG. Upon visible light irradiation, Ru(ii) polypyridyl complexes modified with chloromethyl groups can undergo full hydrolysis with photoacid quantum yield as high as 0.6. Depending on the number of the chloromethyl groups, the examined Ru(ii) complexes can release multiple protons per molecule, leading to large pH jumps at very low PAG concentrations, a feature particularly favorable for bio-related applications.
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http://dx.doi.org/10.1039/c9sc03957kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066672PMC
November 2019

Long-term study on the osteogenetic capability and mechanical behavior of a new resorbable biocomposite anchor in a canine model.

J Orthop Translat 2020 Mar 14;21:81-90. Epub 2020 Jan 14.

School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China.

Background: Biodegradable suture anchors are commonly used for repairing torn rotator cuffs, but these biodegradable materials still suffer from low mechanical strength, poor osteointegration, and the generation of acidic degradation byproducts.

Method: The purpose of this study was to evaluate the long-term mechanical behavior and osteogenetic capabilities of a biocomposite anchor injection molded with 30% β-tricalcium phosphate microparticles blended with 70% poly (L-lactide-co-glycolide) (85/15). This study investigated degradation and bone formation in a canine model. The initial mechanical behavior, mechanical strength retention with degradation time, and degradation features were investigated.

Results: The results showed that the biocomposite anchor had sufficient initial mechanical stability confirmed by comparing the initial shear load on the anchor with the minimum shear load borne by an ankle fracture fixation screw, which is considered a worst-case implantation site for mechanical loading. The maximum shear load retention of the biocomposite anchor was 83% at 12 weeks, which is desirable, as it aligns with the rate of bone healing. The β-tricalcium phosphate fillers were evenly dispersed in the polymeric matrix and acted to slow the degradation rate and improve the mechanical strength of the anchor. The interface characteristics between the β-tricalcium phosphate particles and the polymeric matrix changed the degradation behavior of the biocomposite. Phosphate buffer saline was shown to diffuse through the interface into the biocomposite to inhibit the core accelerated degradation rate. , the addition of β-tricalcium phosphate induced new bone formation. The biocomposite material developed in this study demonstrated improved osteogenesis in comparison to a plain poly (L-lactide-co-glycolide) material. Neither anchor produced adverse tissue reactions, indicating that the biocomposite had favorable biocompatibility following long-term implantation.

Conclusion: In summary, the new biocomposite anchor presented in this study had favorable osteogenetic capability, mechanical property, and controlled degradation rate for bone fixation.

Translational Potential Of This Article: The new biocomposite anchor had sufficient initial and long-term fixation stability and bone formation capability in the canine model. It is indicated that the new biocomposite anchor has a ​potential for orthopedic application.
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http://dx.doi.org/10.1016/j.jot.2019.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033359PMC
March 2020

Hyperactive PI3Kδ predisposes naive T cells to activation via aerobic glycolysis programs.

Cell Mol Immunol 2020 Feb 25. Epub 2020 Feb 25.

National Clinical Research for Child Health and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal-dominant combined immunodeficiency disorder resulting from pathogenic gain-of-function (GOF) mutations in the PIK3CD gene. Patients with APDS display abnormal T cell homeostasis. However, the mechanisms by which PIK3CD GOF contributes to this feature remain unknown. Here, with a cohort of children with PIK3CD GOF mutations from multiple regions of China and a corresponding CRISPR/Cas9 gene-edited mouse model, we reported that hyperactive PI3Kδ disrupted T cell homeostasis in the periphery by intrinsically promoting the growth, proliferation, and activation of T cells. Our results showed that PIK3CD GOF resulted in loss of the quiescence-associated gene expression profile in naive T cells and promoted naive T cells to overgrow, hyperproliferate and acquire an activated functional status. Naive PIK3CD GOF T cells exhibited an enhanced glycolytic capacity and reduced mitochondrial respiration in the resting or activated state. Blocking glycolysis abrogated the abnormal splenic T cell pool and reversed the overactivated phenotype induced by PIK3CD GOF in vivo and in vitro. These results suggest that enhanced aerobic glycolysis is required for PIK3CD GOF-induced overactivation of naive T cells and provide a potential therapeutic approach for targeting glycolysis to treat patients with APDS as well as other immune disorders.
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http://dx.doi.org/10.1038/s41423-020-0379-xDOI Listing
February 2020

Z-scheme g-CN/BiO[BO(OH)] heterojunction for enhanced photocatalytic CO reduction.

J Colloid Interface Sci 2020 May 11;568:139-147. Epub 2020 Feb 11.

Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid Wastes, National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing 100083, China.

Construction of Z-scheme heterojunction photocatalyst for CO photoreduction shows great significance as it holds strong redox ability and high charge separation efficiency. In this work, we developed a Z-scheme heterojunction photocatalyst graphitic carbon nitride (g-CN)/basic bismuth borate (BiO[BO(OH)]) by a simple high-energy ball milling method. The structure, surface element distribution and morphology of the composite samples were systematically analyzed. The photocatalytic performance of the samples was surveyed by CO reduction experiment under the simulated solar light irradiation. Almost all the g-CN/BiO[BO(OH)] composites show enhanced photocatalytic activity for converting CO into CO, and the highest CO production rate observed for g-CN/BiO[BO(OH)] (CNBB-3) among all the samples was determined to be approximately 6.09 µmol g h, which is 2.78 times higher that of pristine g-CN. The largely strengthened photocatalytic CO reduction activity mainly originates from the formation of Z-scheme band structures between g-CN and BiO[BO(OH)] benefiting for the efficient charge separation, which was confirmed by the photoeletrochemical, photoluminescence and ESR spectra. This study provides a new reference for fabrication of high-performance Z-scheme photocatalysts for CO reduction.
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http://dx.doi.org/10.1016/j.jcis.2020.02.025DOI Listing
May 2020

GABA consumption during early pregnancy impairs endometrial receptivity and embryo development in mice.

J Biochem Mol Toxicol 2020 May 11;34(5):e22473. Epub 2020 Feb 11.

Laboratory Animal Center, Chongqing Medical University, Chongqing, China.

γ-Aminobutyrate (GABA) is commonly used as a food supplement and a health care product by young females, due to its positive roles in relieving stress, alleviating anxiety, and improving sleep. However, its recommended daily dose in different products varies widely. Besides, it is unknown whether, and how, GABA consumption during early pregnancy influences pregnancy establishment. In this study, we found that when pregnant mice were treated with a high (12.5 mg/g) dose of GABA (orally) during preimplantation, there was a reduction in the number of implantation sites on day 5 of pregnancy. Also, among these unimplanted embryos, most exhibited morphological degeneration and developmental retardation, and only a few of them developed into blastocysts but could not implant into the uterus. Moreover, the expression of uterine receptivity-related factors-LIF, E-cadherin, and HOXA10-were all downregulated, while the number of uterine glands was reduced in the high GABA dose group. Finally, in vitro results demonstrated that GABA (ranging from 10 to 50 μg/μL) markedly inhibited preimplantation embryo development in a dose-response manner. However, this inhibitory effect was not observed when the embryos were pretreated with 40 μΜ 2-hydroxysaclofen, a GABA antagonist, indicating that GABA exerts its inhibitory effects via its B-type receptor. Our results suggest that exposure to certain GABA concentrations, during early pregnancy, can impair preimplantation embryo development via its B-type receptor, and endometrial receptivity, which greatly disturbs early embryo implantation in mice. These findings could raise concerns about GABA consumption during the early stages of pregnancy.
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http://dx.doi.org/10.1002/jbt.22473DOI Listing
May 2020