Publications by authors named "Na Lv"

112 Publications

Genetic features and efficacy of decitabine-based chemotherapy in elderly patients with acute myeloid leukemia.

Hematology 2021 Dec;26(1):371-379

Department of Hematology, Chinese PLA General Hospital, Beijing, People's Republic of China.

Objectives: The outcome of elderly acute myeloid leukemia (AML) patients is poor, which was traditionally attributed to patient- and leukemia-related factors. However, studies about the genetic features of these elderly patients have not been integrated and the genetic mechanism of their poor outcome is less known.

Methods: Here, we used next generation sequencing (NGS) to identify the genetic features of elderly AML patients and confirmed the efficacy of chemotherapy based on molecular aberrations. Mutations in 111 genes relevant to hematological malignancy was analysed by virtue of NGS and the genetic differences were compared between elderly (n=52) and young (n=161) AML patients. Furthermore, the outcome of decitabine-based chemotherapy was identified in elderly patients.

Results: Frequencies of adverse genetic alterations, such as and secondary-type mutations (, 2 and ), were much higher in elderly patients, while the frequency of mutations was much lower. Moreover, epigenetic mutations such as , , and , were also more common in elderly patients. Furthermore, there were 39 elderly patients receiving the decitabine-based chemotherapy, and the results showed that the overall response rate (ORR) and complete remission rate (CR) were 76.9% and 71.8%, respectively. The median overall survival (OS) for those older patients was 12 months, and the 2-year OS probability was 20.5%.

Discussion: Our study provides deep understanding into the molecular mechanisms of the poor outcome of elderly AML patients.

Conclusion: Epigenetic mutations play an important role, and decitabine-based regimen can be used as alternative first-line chemotherapy for elderly patients.
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http://dx.doi.org/10.1080/16078454.2021.1921434DOI Listing
December 2021

Unveiling structural, electronic properties and chemical bonding of (VH) (n=10-30) nanoclusters: DFT investigation.

J Mol Graph Model 2021 Mar 24;106:107907. Epub 2021 Mar 24.

State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing, 100029, China. Electronic address:

The geometries, electronic properties, and chemical bonding of (VH) (n=10-30) nanoclusters are systematically investigated by a combination of artificial bee colony optimization with density functional theory calculations. Structure analysis indicates that the structures of (VH) nanoclusters tend to be a disorder, where the hydrogen atoms prefer to occupy the hollow sites among different V atoms, binding three V atoms to form the HV moieties. The bond length suggests that the average V-V bond lengths are about 2.60 Å, and the average V-H bond lengths are near 1.86 Å, which close to the experimental values of 2.77 Å and 1.79 Å for the V-V and V-H of bulk vanadium hydride, respectively. Interestingly, the coordination numbers of V-H fluctuate around 5.50 in the nanoclusters, and the corresponding value of H-V is estimated at 3.00. Moreover, the electronic properties and chemical bonding analyses indicate that d orbitals of V atoms and s orbitals of H atoms have a relatively large overlap to form sigma bonds. Specifically, the σ molecular orbital of H can donate electronic density to the d orbital of V atom, exhibiting the Kubas interaction in VH and VH nanoclusters. Kubas interaction results in a longer bond between the hydrogen molecule and the V atom.
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http://dx.doi.org/10.1016/j.jmgm.2021.107907DOI Listing
March 2021

Profiling of somatic mutations and fusion genes in acute myeloid leukemia patients with FLT3-ITD or FLT3-TKD mutation at diagnosis reveals distinct evolutionary patterns.

Exp Hematol Oncol 2021 Apr 9;10(1):27. Epub 2021 Apr 9.

Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.

Background: The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML).

Methods: We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients.

Results: FLT3-ITD mutations were positive in 58 patients (28%), and FLT3-TKD mutations were positive in 20 patients (9.7%). FLT3-ITD was associated with a higher white blood cell count (WBC, mean 72.9 × 10/L vs. 24.2 × 10/L, P = 0.000), higher bone marrow blasts (mean 65.9% vs. 56.0%, P = 0.024), and NK-AML (normal karyotype) (64.8% vs. 48.4%, P = 0.043). NPM1 and DNMT3A mutations were enriched in FLT3-ITD (53.5% vs. 15.3%, P = 0.000; 34.6% vs. 13%, P = 0.003). However, the mutations of CEBPA were excluded in FLT3-AML (3.8% vs. 0% vs. 19.8%, P = 0.005). Mutations of Ras and TP53 were unlikely associated with FLT3-ITD (1.9% vs. 20.6%, P = 0.006; 0% vs. 6.1%, P = 0.04). The common fusion genes (> 10%) in FLT3-ITD had MLL-rearrangement and NUP98-rearrangement, while the common fusion genes in FLT3-TKD had AML1-ETO and MLL-rearrangement. Two novel fusion genes PRDM16-SKI and EFAN2-ZNF238 were identified in FLT3-ITD patients. Gene fusions and NPM1 mutation were mutually excluded in FLT3-ITD and FLT3-TKD patients. Their patterns of mutual exclusivity and cooperation among mutated genes suggest that additional driver genetic alterations are required and reveal two evolutionary patterns of FLT3 pathogenesis. Patients with FLT3-ITD had a lower CR (complete remission) rate, lower 3-year OS (overall survival), DFS (disease-free survival), and EFS (event-free survival) compared to FLT3AML. NK-AML with FLT3-ITD had a lower 3-year OS, DFS, and EFS than those without, while FLT3-TKD did not influence the survival in whole cohort and NK-AML. Besides, we found that FLT3-ITD/TET2 bimutation defined a poor prognostic subgroup.

Conclusions: Our study offers deep insights into the molecular pathogenesis and biology of AML with FLT3-ITD and FLT3-TKD by providing the profiles of concurrent molecular alterations and the clinical impact of FLT3-ITD and FLT3-TKD on AML patients.
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http://dx.doi.org/10.1186/s40164-021-00207-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033687PMC
April 2021

Discovery of novel Staphylococcus aureus penicillin binding protein 2a inhibitors by multistep virtual screening and biological evaluation.

Bioorg Med Chem Lett 2021 Jun 1;41:128001. Epub 2021 Apr 1.

Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, China; Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui 230032, China. Electronic address:

Penicillin-binding protein 2a (PBP2a) is an essential protein involved in the resistance to β-lactam antibiotics acquired by methicillin-resistant Staphylococcus aureus (MRSA) and is a potential antibacterial target. In the current study, we employed a strategy that combined virtual screening with biological evaluation to discover novel inhibitors of PBP2a. In this investigation, a hybrid virtual screening method, consisting of drug-likeness evaluation (Lipinski's Rule of Five and ADMET) and rigid (LibDock) and semi-flexible (CDOCKER) docking-based virtual screenings, was used for retrieving novel PBP2a inhibitors from commercially available chemical databases. 11 compounds were selected from the final hits and subsequently shifted to experimental studies. Among them, Hit 2, Hit 3, and Hit 10 exhibited excellent anti-MRSA ATCC 33591 activity and weak toxicity in vitro. The affinity of the three compounds to bind to PBP2a was further confirmed by surface plasmon resonance (SPR) experiments and molecular dynamics (MD) simulation. An inter-complex interaction study showed that all hit compounds adapted well to the allosteric site of the PBP2a protein. In addition, Hit 2 (with best binding affinity to PBP2a, K = 1.29 × 10 M) significantly inhibits proliferation of MRSA clinical isolates. Together, the 3 hit compounds, especially Hit 2, may be potential non-β-lactam antibiotics against MRSA and the work will provide clues for the future development of specific compounds that block the interaction of PBP2a with their targets.
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http://dx.doi.org/10.1016/j.bmcl.2021.128001DOI Listing
June 2021

Light stimulates anoxic and oligotrophic growth of glacial Flavobacterium strains that produce zeaxanthin.

ISME J 2021 Jan 15. Epub 2021 Jan 15.

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichen West Road, Chaoyang District, Beijing, 100101, China.

Bacteria that inhabit glaciers usually produce carotenoids. Here, we report that a group of zeaxanthin-producing glacial Flavobacterium exhibited light-promoted growth. Of the tested 47 strains, 45 showed increased growths but two died under illumination at 50 μmol photon m s. Light stimulation occurred mainly in either anoxic or nutrient-poor cultures, while the same levels of light promotion were found for that grown at 14 and 7 °C. Pigment assays identified overrepresentative zeaxanthin but trace retinal in the light promoted 45 strains, while flexirubin was exclusively in the light-lethal two. Genomic analysis revealed the gene cluster for zeaxanthin synthesis in the 45 strains, in which 37 strains also harbored the proteorhodopsin gene prd. Transcriptomic analysis found that light-induced expressions of both the zeaxanthin synthesis and proteorhodopsin genes. Whereas, deletion of the prd gene in one strain did not diminish light promotion, inhibition of zeaxanthin synthesis did. In comparison, no light promotion was determined in a glacier Cryobacterium luteum that produced a non-zeaxanthin-type carotenoid. Therefore, light stimulation on the glacial Flavobacterium is mostly likely related to zeaxanthin, which could provide better photoprotection and sustain membrane integrity for the organisms living in cold environments.
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http://dx.doi.org/10.1038/s41396-020-00891-wDOI Listing
January 2021

Dual stimuli-responsive metal-organic framework-based nanosystem for synergistic photothermal/pharmacological antibacterial therapy.

Acta Biomater 2021 03 25;122:291-305. Epub 2020 Dec 25.

Department of Stomatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address:

The serious threat of drug-resistant bacterial pathogens has arisen through overuse of antibiotics. Photothermal therapy (PTT) has come to prominence as viable alternative strategy for antibacterial therapy. In this work, we report a NIR/pH dual stimuli-responsive antibacterial formulation based on zeolitic imidazolate frameworks-8 (ZIF-8) with strong antibacterial activity that combines photothermal heating with enhanced antibiotic delivery. ZIF-8 with polydopamine (PDA) surface modification was used to encapsulate the antibiotic vancomycin to construct a dual stimuli-responsive antimicrobial formulation (Van@ZIF-8@PDA). This treatment was tested against Gram-positive Mu50 (a vancomycin-intermediate S. aureus reference strain). Results showed that the PDA coating improved ZIF-8 stability and dispersion, while also conferring a high photothermal conversion efficiency. Hyperthermia activated by near-infrared (NIR) light irradiation, in conjunction with pH-dependent nanoparticle degradation to release vancomycin, enabled tight control of drug delivery that functioned synergistically in the elimination of both planktonic bacteria prior to biofilm formation and established biofilms. We found that this combined formulation compromises cell structure while also degrading bacterial DNA. Moreover, further investigation showed that the Van@ZIF-8@PDA nanoparticles exhibit good biocompatibility, with low toxicity toward host organs and tissues, while also reducing the antibiotic concentration needed for effective bacterial control. Finally, we treated Mu50 in a mouse model of skin abscess and found that Van@ZIF-8@PDA was effective and safe in vivo. Cumulatively, this study shows that this NIR/pH dual stimuli-responsive nanoparticle-based formulation offers a promising potential strategy for clinical application against bacterial infection that circumvents antibiotic resistance.
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http://dx.doi.org/10.1016/j.actbio.2020.12.045DOI Listing
March 2021

Effects of a preoperative forced-air warming system for patients undergoing video-assisted thoracic surgery: A randomized controlled trial.

Medicine (Baltimore) 2020 Nov;99(48):e23424

Department of Anaesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong, China.

Background: The incidence of intraoperative hypothermia is still high despite the proposal of different preventive measures during thoracoscopic surgery. This randomized control study evaluated the effects of 30-minute prewarming combined with a forced-air warming system during surgery to prevent intraoperative hypothermia in patients undergoing video-assisted thoracic surgery under general anesthesia combined with erector spinae nerve block.

Methods: Ninety-eight patients were randomly and equally allocated to prewarming or warming groups (n = 49 each). The primary outcome was the incidence of intraoperative hypothermia. Secondary outcomes were core temperature, irrigation and infused fluid, estimated blood loss, urine output, type of surgery, intraoperative anesthetic dosage, hemodynamics, recovery time, the incidence of postoperative shivering, thermal comfort, postoperative sufentanil consumption and pain intensity, patient satisfaction, and adverse events.

Results: The incidence of intraoperative hypothermia was significantly lower in the prewarming group than the warming group (12.24% vs 32.65%, P = .015). Core temperature showed the highest decrease 30 minutes after surgery start in both groups; however, the rate was lower in the prewarming than in the warming group (0.31 ± 0.04°C vs 0.42 ± 0.06°C, P < .05). Compared with the warming group, higher core temperatures were recorded for patients in the prewarming group from T1 to T6 (P < .05). Significantly fewer patients with mild hypothermia were in the prewarming group (5 vs 13, P = .037) and recovery time was significantly reduced in the prewarming group (P < .05). Although the incidence of postoperative shivering was lower in the prewarming group, it was not statistically significant (6.12% vs 18.37%, P = .064). Likewise, the shivering severity was similar for both groups. Thermal comfort was significantly increased in the prewarming group, although patient satisfaction was comparable between the 2 groups (P > .05). No adverse events occurred associated with the forced-air warming system. Both groups shared similar baseline demographics, type of surgery, total irrigation fluid, total infused fluid, estimated blood loss, urine output, intraoperative anesthetic dosage, hemodynamics, duration of anesthesia and operation time, postoperative sufentanil consumption, and pain intensity.

Conclusion: In patients undergoing video-assisted thoracic surgery, prewarming for 30 minutes before the induction of anesthesia combined with a forced-air warming system may improve perioperative core temperature and the thermal comfort, although the incidence of postoperative shivering and severity did not improve.
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http://dx.doi.org/10.1097/MD.0000000000023424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710179PMC
November 2020

Dominant subtype switch in avian influenza viruses during 2016-2019 in China.

Nat Commun 2020 11 20;11(1):5909. Epub 2020 Nov 20.

Federal Research Center of Fundamental and Translational Medicine, Federal State Budget Scientific Institution, Siberian Branch of Russian Academy of Sciences, Novosibirsk State University, Novosibirsk, Russia, 630090.

We have surveyed avian influenza virus (AIV) genomes from live poultry markets within China since 2014. Here we present a total of 16,091 samples that were collected from May 2016 to February 2019 in 23 provinces and municipalities in China. We identify 2048 AIV-positive samples and perform next generation sequencing. AIV-positive rates (12.73%) from samples had decreased substantially since 2016, compared to that during 2014-2016 (26.90%). Additionally, H9N2 has replaced H5N6 and H7N9 as the dominant AIV subtype in both chickens and ducks. Notably, novel reassortants and variants continually emerged and disseminated in avian populations, including H7N3, H9N9, H9N6 and H5N6 variants. Importantly, almost all of the H9 AIVs and many H7N9 and H6N2 strains prefer human-type receptors, posing an increased risk for human infections. In summary, our nation-wide surveillance highlights substantial changes in the circulation of AIVs since 2016, which greatly impacts the prevention and control of AIVs in China and worldwide.
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http://dx.doi.org/10.1038/s41467-020-19671-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679419PMC
November 2020

Microbiota-Derived Short-Chain Fatty Acids Promote LAMTOR2-Mediated Immune Responses in Macrophages.

mSystems 2020 Nov 3;5(6). Epub 2020 Nov 3.

Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

ABSRTACT is a common cause of human-pneumonia-derived sepsis with high morbidity and mortality. The microbiota promotes and maintains host immune homeostasis. The mechanisms by which the gut microbiota affects the host defenses in the respiratory system systematically, however, remain poorly understood. Here, we show that gut microbiota depletion increases susceptibility to extracellular infections in terms of increased bacterial burdens in lung and decreased survival rates. Oral supplementation with gut microbiota-derived short-chain fatty acids (SCFAs), subsequently activating G protein-coupled receptor 43 (GPCR43), enhances a macrophage's capacity to phagocytose invading Furthermore, SCFAs and GPR43 increase macrophage bacterial clearance by upregulating LAMTOR2, which is further identified as an antibacterial effector and elucidated to facilitate phagosome-lysosome fusion and extracellular signal-regulated kinase (ERK) phosphorylation. Lastly, conditional ablation of in macrophages decreases their antimicrobial activity, even though mice were pretreated with exogenous SCFA supplementation. These observations highlight that SCFAs promote macrophage elimination of via a LAMTOR2-dependent signal pathway and suggest that it is possible to intervene in pneumonia by targeting the gut microbiota.
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http://dx.doi.org/10.1128/mSystems.00587-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646525PMC
November 2020

Virulence-Related Gene Distribution Among Isolates in Anhui, China: The Association with Antimicrobial Resistance.

Infect Drug Resist 2020 19;13:3637-3647. Epub 2020 Oct 19.

Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.

Objective: The aim of this study was to investigate the antimicrobial resistance profiles and distribution of virulence-related genes (VRGs) among isolates in Anhui, China, and to identify the correlation between the VRGs and antimicrobial resistance.

Materials And Methods: A total of 525 non-duplicate isolates (449 , 68 , 3 , and 5 ) were collected in Anhui Province, China between September 2011 and September 2015. The antimicrobial resistance of the strains was determined by the agar dilution method according to CLSI guidelines. The presence of 16 VRGs, including , and , was evaluated using PCR amplification and sequencing.

Results: was the most abundant (85.5%), followed by (13.0%). The proportion of males with was higher than that of females (57% 43%; <0.0001). The most common resistance pattern was the combination of ampicillin, nalidixic acid, and tetracycline for (90.2%) and (94.1%). Resistance to ciprofloxacin and levofloxacin was more common among than among (49.7% .19.1%, <0.0001; 30.5% 10.3%, =0.001, respectively). All the isolates were positive for the gene, while the , and genes were not detected among the isolates. Except for and , resistance to chloramphenicol and ciprofloxacin was more common among VRG-positive than among VRG-negative (<0.05). Furthermore, resistance to ceftriaxone and ceftazidime was more frequently detected among and positive than among and negative (<0.05). However, gentamicin resistance was more prevalent among VRG-negative (, and ) than among VRG-positive (<0.05).

Conclusion: remains the predominant species in Anhui, China, and the resistance to fluoroquinolones was more widespread among than among strains harboring specific VRGs were associated with antimicrobial resistance. To the best of our knowledge, this is the first report of the correlation between the VRGs and antimicrobial resistance in Anhui, China.
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http://dx.doi.org/10.2147/IDR.S274862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585282PMC
October 2020

Near-Infrared-Controlled Nanoplatform Exploiting Photothermal Promotion of Peroxidase-like and OXD-like Activities for Potent Antibacterial and Anti-biofilm Therapies.

ACS Appl Mater Interfaces 2020 Nov 27;12(45):50260-50274. Epub 2020 Oct 27.

Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.

Nanozymes that mimic peroxidase (POD) activity can convert HO into bactericidal free radicals, which is referred to as chemodynamic therapy (CDT). High glutathione (GSH) levels in the infectious tissue severely limit the performance of CDT. Herein, we report a near-infrared-controlled antibacterial nanoplatform that is based on encapsulating tungsten sulfide quantum dots (WSQDs) and the antibiotic vancomycin in a thermal-sensitive liposome. The system exploits the photothermal sensitivity of the WSQDs to achieve selective liposome rupture for the targeted drug delivery. We determined that WSQDs show a strong POD-like activity under physiological conditions and the oxidase-like activity, which can oxidate GSH to further improve the CDT efficacy. Moreover, we found that increased temperature promotes multiple enzyme-mimicking activities of WSQDs. This platform exerts antibacterial effects against Gram-positive Mu50 (a vancomycin-intermediate reference strain) and Gram-negative and disrupts biofilms for improved penetration of therapeutic agents inside biofilms. studies with mice bearing Mu50-caused skin abscess revealed that this platform confers potent antibacterial activity without obvious toxicity. Accordingly, our work illustrates that the photothermal and nanozyme properties of WSQDs can be deployed alongside a conventional therapeutic to achieve synergistic chemodynamic/photothermal/pharmaco therapy for powerful antibacterial effects.
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http://dx.doi.org/10.1021/acsami.0c14451DOI Listing
November 2020

Cross-point calibration method for the Scheimpflug measurement system.

Appl Opt 2020 Oct;59(28):8618-8627

The Scheimpflug measurement system has broad application prospects in the fields of tomographic particle image velocimetry (PIV), ophthalmology, and three-dimensional reconstruction. Additionally, its special imaging structure makes the theoretical model of other traditional calibration methods no longer applicable. A cross-point calibration method in which the real-world coordinate system is transferred from an in-kind calibrator to displacement, achieving great improvements in the quantity and accuracy of the feature points, is proposed. This method, which makes up for the defects introduced by the distorted imaging plane, also in turn simplifies the calibration process. Finally, the proposed method is tested via both simulation and calibration experiments. The high calibration accuracy verifies that the method is feasible.
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http://dx.doi.org/10.1364/AO.401350DOI Listing
October 2020

Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice.

J Dev Orig Health Dis 2020 12 14;11(6):580-588. Epub 2020 Sep 14.

Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China.

Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.
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http://dx.doi.org/10.1017/S2040174420000768DOI Listing
December 2020

A novel TSC2 c.4511 T > C missense variant associated with tuberous sclerosis complex.

BMC Med Genet 2020 09 11;21(1):180. Epub 2020 Sep 11.

Electrocardiogram Room, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, P.R. China.

Background: Tuberous sclerosis complex (TSC) is an autosomal-dominant hereditary disease characterized by hamartomas of multiple organ systems, including the brain, skin, heart, kidney and lung. Genetically, TSC is caused by pathogenic variants in the TSC1 or TSC2 gene.

Case Presentation: We reported a sporadic case of a 32-year-old Han Chinese male diagnosed with TSC, whose spouse had a history of two spontaneous miscarriages and an induced abortion of a 30-week fetus identified with cardiac rhabdomyoma by ultrasound. A novel heterozygous missense variant in the TSC2 gene (Exon35:c.4511 T > C:p.L1504P) was identified in the male patient and the aborted fetus by next-generation sequencing, but not in his wife or both his parents. According to the ACMG/AMP criteria, this variant was classified as a "likely pathogenic" variant.

Conclusion: The novel TSC2:c.4511 T > C variant identified was highly likely associated with TSC and could potentially lead to adverse reproductive outcomes. IVF-ET and pre-implantation genetic diagnosis for TSC are recommended for this patient in the future to prevent fetal TSC.
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http://dx.doi.org/10.1186/s12881-020-01120-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488555PMC
September 2020

Alterations in the Gut Microbiome and Cecal Metabolome During -Induced Pneumosepsis.

Front Immunol 2020 31;11:1331. Epub 2020 Jul 31.

Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

(.) is a common cause of pneumonia-derived sepsis in human and is associated with high morbidity and mortality. The microbiota promotes and maintains host immune homeostasis during bacterial infections. However, the mechanisms by which the gut microbiota affects immune responses in the lung still remain poorly understood. Here, we performed cecal metabolomics sequencing and fecal 16s rRNA sequencing in -infected mice and uninfected controls and showed that infection led to profound alterations in the gut microbiome and thus the cecal metabolome. We observed that the levels of were significantly decreased in -infected mice. Spearman correlation analysis showed that alterations in the richness and composition of the gut microbiota were associated with profound changes in host metabolite concentrations. Further, short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, were detected in cecal contents and serum by gas chromatography-mass spectrometry (GC-MS). We observed that the concentrations of these three SCFAs were all lower in the infected groups than in the untreated controls. Lastly, oral supplementation with these three SCFAs reduced susceptibility to infections, as indicated by lower bacterial burdens in the lung and higher survival rates. Our data highlight the protective roles of gut microbiota and certain metabolites in -pneumonia and suggests that it is possible to intervene in this bacterial pneumonia by targeting the gut microbiota.
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http://dx.doi.org/10.3389/fimmu.2020.01331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411141PMC
April 2021

Development and Validation of a Model for Predicting the Risk of Death in Patients with Infection: A Retrospective Study.

Infect Drug Resist 2020 10;13:2761-2772. Epub 2020 Aug 10.

Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.

Purpose: This study aimed to develop and validate a personalized prediction model of death risk in patients with () infection and thus guide clinical research and support clinical decision-making.

Patients And Methods: The development group is comprised of 350 patients with infection admitted between January 2013 and December 2015 in The First Affiliated Hospital of Anhui Medical University. Further, 272 patients in the validation group were admitted between January 2016 and December 2018. The univariate and multivariate logistic regression analyses were used to determine the independent risk factors for death with infection. The nomogram prediction model was established based on the regression coefficients. The discrimination of the proposed prediction model was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curves and decision curve analysis (DCA). The calibration diagram was used to evaluate the calibration degree of this model.

Results: The infectious source, carbapenem-resistant (CRAB), hypoalbuminemia, Charlson comorbidity index (CCI), and mechanical ventilation (MV) were independent risk factors for death. The AUC of the ROC curve of the two groups was 0.768 and 0.792, respectively. The net income was higher when the probability was between 30% and 80%, showing a strong discrimination capacity of the proposed model. The calibration curve swung around the 45° oblique line, indicating a high degree of calibration.

Conclusion: The proposed model helped predict the risk of death from infection, improve the early identification of patients with a higher risk of death, and guide clinical treatment.
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http://dx.doi.org/10.2147/IDR.S253143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428379PMC
August 2020

Management of oral medicine emergencies during COVID-19: A study to develop practise guidelines.

J Dent Sci 2021 Jan 7;16(1):493-500. Epub 2020 Aug 7.

Department of Oral Diagnostic and Surgical Sciences, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.

Coronavirus disease (COVID-19) pandemic has become a significant global public health concern. Since the announcement of the Public Health Emergency of International Concern, many countries have implemented lockdown and restrictive quarantines; therefore, routine dentistry, as well as oral medicine practise, have been suspended in several countries. However, urgent oral cares and emergencies are still operated and delivered by on-call dental practitioners. The objective of this study was to investigate the management of oral medicine emergency during a viral pandemic such as COVID-19. During the lockdown period, digital technologies, such as video conferencing with Zoom, Google Meeting or WhatsApp, are useful and efficient tools that oral medicine practitioners could consider to use for patient triage, managing emergencies, reassure, and follow patients remotely. Oral medicine emergencies can be carefully evaluated and triaged via video conferencing and sometimes phone contact, to avoid life-threatening risks while realising the limitations by both patient and clinician.
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http://dx.doi.org/10.1016/j.jds.2020.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413161PMC
January 2021

Prevalence of Plasmid-Mediated Determinants With Decreased Susceptibility to Azithromycin Among Isolates in Anhui, China.

Front Microbiol 2020 30;11:1181. Epub 2020 Jun 30.

Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Objective: The aims of this study were to describe azithromycin (AZM) susceptibility patterns among isolates in Anhui, China and identify predictors of resistance with mobile element-mediated genes.

Methods: A total of 517 non-duplicate isolates (449 and 68 ) were collected in the Anhui Province of China from September 2011-September 2015, and screened for the plasmid-mediated genes of decreased susceptibility to AZM (DSA), using polymerase chain reaction amplification and sequencing. Conjugation experiments and pulsed-field gel electrophoresis were conducted for all positive DSA isolates.

Results: The DSA rate for 449 isolates was 33.6%, compared with 39.7% for 68 isolates. Among 161 DSA isolates, 93 (57.8%) carried the gene. Among 27 DSA isolates, 11 (40.7%) carried the gene. However, other plasmid-mediated DSA genes were not found in these isolates. A total of 89 transconjugants (95.7%) were obtained from 93 -positive isolates through conjugation, and 10 transconjugants (90.9%) were obtained from 11 -positive isolates. Furthermore, the minimum inhibitory concentrations (MICs) of AZM among 89 transconjugants ranged from 4 to 128 μg/mL, with an MIC of 8 μg/mL and MIC of 32 μg/mL. The MICs of AZM among 10 transconjugants ranged from 4 to 256 μg/mL, with an MIC of 8 μg/mL and MIC of 64 μg/mL. Thirteen clusters were found for -positive , and five clusters were found for -positive . Furthermore, 10 homologous isolates among 13 -positive isolates with high-level DSA were from Sixian county and were multidrug-resistant strains. Of the 10 homologous isolates, eight were from children (≤5 years old), and two from the elderly (>60 years old).

Conclusion: Our study demonstrates that the DSA for isolates was severe, and the plasmid-mediated gene was the most common macrolide resistance gene detected in isolates collected in Anhui, China. The -positive isolates with high-level DSA facilitated clonal spread in children and the elderly. This finding is noteworthy and warrants further study.
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http://dx.doi.org/10.3389/fmicb.2020.01181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338677PMC
June 2020

Increased repetitive self-grooming occurs in Pax2 mutant mice generated using CRISPR/Cas9.

Behav Brain Res 2020 09 9;393:112803. Epub 2020 Jul 9.

Nephrology Division, Shanxi Provincial People's Hospital, Affiliate of Shanxi Medical University, Taiyuan, China. Electronic address:

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive or restricted interest and behaviors. However, the specific pathogenesis of ASD is still unclear. It has been widely accepted that genetic and environmental risk factors are associated with the pathogenesis of ASD. Paired box2 (Pax2) gene encodes a transcription factor that plays an important role in the development of the central nervous system of humans and mice. In this study, we constructed Pax2 heterozygous gene knockout (Pax2) mice using CRISPR/Cas9 technology and performed several autistic-like behavioral assays, including self-grooming test, sociability approach, the elevated plus maze test and Y maze test. Results showed increased repetitive self-grooming and possible abnormal anxiety-like behavior occur in Pax2 mice. Furthermore, no changes were observed in the abilities of sociability and working memory in Pax2 mice compared to wild-type C57BL/6 J mice. Finally, we speculated that possible mechanism of abnormal autistic-like behaviors due to the deletion of Pax2 gene.
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http://dx.doi.org/10.1016/j.bbr.2020.112803DOI Listing
September 2020

Particulate Matter 2.5 Induced Developmental Cardiotoxicity in Chicken Embryo and Hatchling.

Front Pharmacol 2020 5;11:841. Epub 2020 Jun 5.

Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China.

Particulate matter poses health risk to developing organisms. To investigate particulate matters with a diameter smaller than 2.5 um (PM2.5)-induced developmental cardiotoxicity, fertile chicken eggs were exposed to PM2.5 air cell injection at doses of 0.05, 0.2, 0.5, 2, and 5 mg/egg kg. Morphological changes in the embryonic day four (ED4) and hatchling hearts were assessed with histological techniques. Heart rates of hatchling chickens were measured with electrocardiography. The protein expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-kb p65), inducible nitric oxide synthase (iNOS), and matrix metallopeptidase 9 (MMP9) were assessed with immunohistochemistry or western blotting in hatchling hearts. PM2.5 exposure elevated areas of heart in ED4 embryo, increased heart rate, and thickened right ventricular wall thickness in hatchling chickens. Immunohistochemistry revealed enhanced NF-kb p65 expression in hatchling hearts. Western blotting results indicated that both iNOS and MMP9 expression were enhanced by lower doses of PM2.5 exposure (0.2 and 0.5 mg/kg) but not 2 mg/kg. In summary, developmental exposure to PM2.5 induced developmental cardiotoxicity in chicken embryo and hatchling chickens, which is associated with NF-kb p65, iNOS, and MMP9.
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http://dx.doi.org/10.3389/fphar.2020.00841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289969PMC
June 2020

A rare case of accessory maxilla: a case report and literature review of Tessier no. 7 clefts.

J Int Med Res 2020 May;48(5):300060520925680

Department of Oral Diagnostic and Surgical Sciences, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.

Bilateral Tessier no. 7 clefts are rarely reported in the literature. Here, we describe the presence of accessory maxilla with supernumerary teeth in a patient who exhibited bilateral Tessier no. 7 clefts; the diagnosis was established based on the patient's history, clinical presentation, and computed tomography images. A review of the available literature revealed 24 patients with Tessier no. 7 clefts from 2000 to 2020, including our patient. The most common clinical manifestation in patients with Tessier no. 7 clefts comprises bilateral facial clefts. Additionally, Tessier no. 7 clefts are more frequently found in boys or men, rather than in girls or women. The presence of an accessory maxilla with supernumerary teeth in a patient with bilateral Tessier no. 7 clefts is extremely rare. Early detection of craniofacial abnormalities is important, because it may influence patient prognosis and management.
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http://dx.doi.org/10.1177/0300060520925680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243405PMC
May 2020

Minocycline and Fluconazole Have a Synergistic Effect Against Both and .

Front Microbiol 2020 5;11:836. Epub 2020 May 5.

Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

In recent decades, the incidence of infection, which causes cryptococcosis, has consistently increased. Fluconazole (FLU) is frequently used in the treatment of this disease, mainly in the immunocompromised population, and long-term therapy usually produces drug resistance. Research on antifungal sensitizers has gained attention as a possible means of overcoming this drug resistance. Minocycline (MINO) has an inhibitory effect on FLU-resistant , and the combination of MINO and FLU has a synergistic effect on FLU-resistant . A synergistic effect of MINO/FLU has been reported against , but this effect has not been evaluated on FLU-resistant isolates. This study aimed to investigate the interaction of MINO and FLU against FLU-resistant both and . We found that the combination of MINO and FLU had a synergistic effect on FLU-resistant . For all FLU-resistant strains, the minimum inhibitory concentration (MIC) of FLU decreased significantly when used in combination with MINO, dropping from >128 μg/ml down to 4-8 μg/ml. Additionally, MINO and FLU had a synergistic effect on both susceptible and resistant biofilms, in which the MIC of FLU decreased from >256 μg/ml down to 4-16 μg/ml. Compared with FLU alone, the combination of MINO with FLU prolonged the survival rate of larvae infected with FLU-resistant , and also significantly decreased the fungal burden of infected larvae and reduced the tissue damage and destruction caused by FLU-resistant . These findings will contribute to the discovery of antifungal agents and may yield a new approach for the treatment of cryptococcosis caused by FLU-resistant .
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http://dx.doi.org/10.3389/fmicb.2020.00836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214679PMC
May 2020

In ovo very early-in-life exposure to diesel exhaust induced cardiopulmonary toxicity in a hatchling chick model.

Environ Pollut 2020 Sep 3;264:114718. Epub 2020 May 3.

Department of Toxicology, School of Public Health, Qingdao University, Qingdao, 266021, China. Electronic address:

Diesel exhaust (DE) had been associated with cardiopulmonary toxicity and developmental toxicity. However, neonatal very early-in-life exposure had not been extensively studied previously. To investigate the potential effects of neonatal very early-in-life exposure to DE, a brand-new chicken embryo in ovo exposure model had been established, with which the cardiopulmonary effects of DE exposure via air cell infusion at embryonic day 18/19 (ED18/19) were assessed in hatchling chicks post-hatch 0-, 1-, or 2-weeks. Heart rates were assessed with electrocardiography. Cardiac and pulmonary morphologies were investigated with histopathological methods. Cardiopulmonary effects were explored with immunohistochemistry for alpha smooth muscle actin (alpha-SMA). In further investigations, the expression levels of phosphorylated AhR, serum levels of TGF-β1, phosphorylated SMAD2/3 and phosphorylated p38MAPK were assessed in the lung tissues. Significantly elevated heart rates, increased right ventricular wall thickness and cardiac collagen deposition were observed in the hearts of exposed hatchling chicks. Significantly increased collagen deposition as well as increased vascular alpha-SMA layer thickness/decreased cavity area were observed in exposed animal lungs. These effects persisted up to two weeks post-hatch. Mechanistic studies revealed elevated phosphorylated AhR expression levels in 0-week and 1-week chicken lungs, while phosphorylated SMAD2/3 levels significantly increased in 0-week chicken lungs but decreased in 2-week chicken lungs following DE exposure. Phosphorylation of p38MAPK did not remarkably increase until 2-week post-hatch. In summary, the novel chicken neonatal very early-in-life exposure model effectively exposed the chicken embryos during the neonatal initial breathing, resulting in cardiopulmonary toxicity, which is associated with AHR, TGF-β1 and MAPK signaling.
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http://dx.doi.org/10.1016/j.envpol.2020.114718DOI Listing
September 2020

Single‑cell RNA sequencing of t(8;21) acute myeloid leukemia for risk prediction.

Oncol Rep 2020 Apr 18;43(4):1278-1288. Epub 2020 Feb 18.

Department of Hematology and BMT Center, Chinese PLA General Hospital, Beijing 100853, P.R. China.

Single‑cell RNA sequencing (scRNA‑seq) of bone marrow or peripheral blood samples from patients with acute myeloid leukemia (AML) enables the characterization of heterogeneous malignant cells. A total of 87 cells from two patients with t(8;21) AML were analyzed using scRNA‑seq. Clustering methods were used to separate leukemia cells into different sub‑populations, and the expression patterns of specific marker genes were used to annotate these populations. Among the 31 differentially expressed genes in the cells of a patient who relapsed after hematopoietic stem cell transplantation, 13 genes were identified to be associated with leukemia. Furthermore, three genes, namely AT‑rich interaction domain 2, lysine methyltransferase 2A and synaptotagmin binding cytoplasmic RNA interacting protein were validated as possible prognostic biomarkers using two bulk expression datasets. Taking advantage of scRNA‑seq, the results of the present study may provide clinicians with several possible biomarkers to predict the prognostic outcomes of t(8;21) AML.
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http://dx.doi.org/10.3892/or.2020.7507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057921PMC
April 2020

Integrated metagenomic and metatranscriptomic profiling reveals differentially expressed resistomes in human, chicken, and pig gut microbiomes.

Environ Int 2020 05 19;138:105649. Epub 2020 Mar 19.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address:

Gut microbiota is a reservoir of antibiotic resistance genes (ARGs). Yet, limited information is available regarding the presence (metagenomic DNA level) and expression profiles (metatranscriptomic RNA level) of ARGs in gut microbiota. Here, we used both metagenomic and metatranscriptomic approaches to comprehensively reveal the abundance, diversity, and expression of ARGs in human, chicken, and pig gut microbiomes in China. Based on deep sequencing data and ARG databases, a total of 330 ARGs associated with 21 antibiotic classes were identified in 18 human, chicken, and pig fecal samples. Metatranscriptomic analysis revealed that 49.4, 66.5, and 56.6% of ARGs identified in human, chicken, and pig gut microbiota, respectively, were expressed, indicating that a large proportion of ARGs were not transcriptionally active. Further analysis demonstrated that transcript abundance of tetracycline, aminoglycoside, and beta-lactam resistance genes was mainly contributed by acquired ARGs. We also found that various biocide, chemical, and metal resistance genes were actively transcribed in human and animal guts. The combination of metagenomic and metatranscriptomic analysis in this study allowed us to specifically link ARGs to their transcripts, providing a comprehensive view of the prevalence and expression of ARGs in gut microbiota. Taken together, these data deepen our understanding of the distribution, evolution, and dissemination of ARGs and metal resistance genes in human, chicken, and pig gut microbiota.
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http://dx.doi.org/10.1016/j.envint.2020.105649DOI Listing
May 2020

Metagenomic analysis reveals the microbiome and resistome in migratory birds.

Microbiome 2020 03 2;8(1):26. Epub 2020 Mar 2.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Background: Antibiotic-resistant pathogens pose high risks to human and animal health worldwide. In recent years, the role of gut microbiota as a reservoir of antibiotic resistance genes (ARGs) in humans and animals has been increasingly investigated. However, the structure and function of the gut bacterial community, as well as the ARGs they carry in migratory birds remain unknown.

Results: Here, we collected samples from migratory bird species and their associated environments and characterized their gut microbiomes and resistomes using shotgun metagenomic sequencing. We found that migratory birds vary greatly in gut bacterial composition but are similar in their microbiome metabolism and function. Birds from the same environment tend to harbor similar bacterial communities. In total, 1030 different ARGs (202 resistance types) conferring resistance to tetracycline, aminoglycoside, β-lactam, sulphonamide, chloramphenicol, macrolide-lincosamide-streptogramin (MLS), and quinolone are identified. Procrustes analysis indicated that microbial community structure is not correlated with the resistome in migratory birds. Moreover, metagenomic assembly-based host tracking revealed that most of the ARG-carrying contigs originate from Proteobacteria. Co-occurrence patterns revealed by network analysis showed that emrD, emrY, ANT(6)-Ia, and tetO, the hubs of ARG type network, are indicators of other co-occurring ARG types. Compared with the microbiomes and resistomes in the environment, migratory birds harbor a lower phylogenetic diversity but have more antibiotic resistance proteins. Interestingly, we found that the mcr-1 resistance gene is widespread among different birds, accounting for 50% of the total samples. Meanwhile, a large number of novel β-lactamase genes are also reconstructed from bird metagenomic assemblies based on fARGene software.

Conclusions: Our study provides a comprehensive overview of the diversity and abundance of ARGs in migratory birds and highlights the possible role of migratory birds as ARG disseminators into the environment. Video abstract.
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http://dx.doi.org/10.1186/s40168-019-0781-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053137PMC
March 2020

Integrated analysis of miRNA and mRNA expression profiles in the brains of BTBR mice.

Int J Dev Neurosci 2020 May 9;80(3):221-233. Epub 2020 Mar 9.

Nephrology Division, Shanxi Provincial People's Hospital, Affiliate of Shanxi Medical University, Taiyuan, China.

The BTBR T  Itpr3 (BTBR) mouse has developmental disorders in brain and many aberrant neuroanatomical structures and brain dysfunction. However, identification of the pathological mechanisms underlying abnormal brain development in the brains of BTBR mice is still lacking. Increasingly evidence showed that epigenetics plays an important role in the processes of brain development. In this study, we analyzed microRNA (miRNA) and mRNA expression profiles in the cortical brain tissue from BTBR mice, using RNA sequencing. As compared to C57BL/6J (B6) mice, 1,271 differentially expressed genes (DEGs) and 36 known differentially expressed miRNAs (DEMs) were found in the brain from BTBR mice. The functional annotation and categories of DEGs and DEMs were analyzed. Integration analysis identified 103 known miRNA-mRNA interaction pairs. We further verified selected several genes and miRNAs which may be associated with brain development using quantitative RT-PCR (qRT-PCR). Finally, we speculate that reduced myelin-associated oligodendrocytic basic protein and transmembrane proteins 260 may be linked with abnormal brain development in BTBR mice.
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http://dx.doi.org/10.1002/jdn.10019DOI Listing
May 2020

The Genome Resequencing of TCR Loci in Revealed Their Distinct Evolutionary Features in Avians.

Immunohorizons 2020 01 28;4(1):33-46. Epub 2020 Jan 28.

Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;

The TCR is consisted of four chains: α (TCRα), β (TCRβ), γ (TCRγ), and δ (TCRδ) that are present in all jawed vertebrates. Birds are very important in terms of evolutionary aspects of the adaptive immune system, in which it bridges the evolutionary gap between mammals and other vertebrates. To gain better understanding into the genomic organization and complexity of birds' TCR loci, we applied cross-reference error-correction sequencing approach by using Illumina and single-molecule real-time sequencing technology to resequence genomic regions of chicken TCR loci based on 10 mapped bacterial artificial chromosome clones. We did de novo classification of V and J genes for all four chains of the TCR loci according to our sequencing results using the Immunogenetics nomenclature. In sum, we identified 85, 8, and 37 TCR V gene segments in the chicken , , and loci, respectively. The phylogenetic analysis showed the Vα 7 and Vα family 4 gene sequences shared greater sequence similarity with mammalian species, whereas the other Vα segment sequences are evolutionary closer with sequences from bony fishes. The organization of chicken TCRβ locus is more similar to fish TCRβ locus over mammalian species, as chicken TCRβ locus has a single translocon of its V-D-J-C and exhibits significantly fewer Vβ gene segments. In this study, we present a highly precise genomic map for chicken TCR loci and phylogenetic relationships of TCR variable gene segments against other animal species and verified the relative stability of the receptor structure during evolutional process.
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http://dx.doi.org/10.4049/immunohorizons.1900095DOI Listing
January 2020

Association of blood metal exposure with testosterone and hemoglobin: A cross-sectional study in Hangzhou Birth Cohort Study.

Environ Int 2020 03 7;136:105451. Epub 2020 Jan 7.

Department of Public Health, and Department of Reproductive Endocrinology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Bioelectromagnetics Laboratory, Institute of Environmental Health, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Background: Few epidemiological studies have investigated associations of exposure to multiple metals with testosterone homeostasis and erythropoiesis, especially for the pregnant women.

Methods: Among all the 1644 participants enrolled in Hangzhou Birth Cohort Study (HBCS) at baseline, a total of 918 pregnant women with complete data of interest were analyzed. The whole blood metals levels were examined by inductively coupled plasma mass spectrometry (ICP-MS), and serum testosterone level was evaluated by chemiluminescent microparticle immunoassay (CMIA), and erythropoietic parameters values were extracted from medical record. Multivariable linear regression models were applied to estimate the relationships between metals levels and testosterone level, and between metals levels and erythropoietic parameters, and potential confounders were adjusted.

Results: Single metal model analysis revealed a significant association of blood As, Mn and Pb level with serum testosterone level. After controlling for multiple testing, the dose-response trend with statistical significance (FDR-adjusted p trend <0.05) was observed across tertiles of Pb with testosterone. This association, when by stratified by gender, remained in pregnant women with a male fetus but did not reach significant in those with a female fetus. Furthermore, blood Pb level was positively associated with red blood cell counts, hemoglobin level and hematocrit. Serum testosterone level was positively associated with red blood cell counts, hemoglobin level and hematocrit. Mediation analyses indicated that testosterone might act as a mediator in the association between Pb exposure and erythropoietic parameters.

Conclusions: Serum testosterone level and hemoglobin level was positively related to blood Pb level among Chinese pregnant women, and testosterone might mediate the effect of Pb exposure on hemoglobin. Additional prospective studies are warranted to confirm the causality.
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http://dx.doi.org/10.1016/j.envint.2019.105451DOI Listing
March 2020

Acute myeloid leukemia immune escape by epigenetic CD48 silencing.

Clin Sci (Lond) 2020 Jan;134(2):261-271

Department of Hematology and Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen 518000, China.

Acute myeloid leukemia (AML) is a malignant disorder of hemopoietic stem cells. AML can escape immunosurveillance of natural killer (NK) by gene mutation, fusions and epigenetic modification. The mechanism of AML immune evasion is not clearly understood. Here we show that CD48 high expression is a favorable prognosis factor that is down-regulated in AML patients, which can help AML evade from NK cell recognition and killing. Furthermore, we demonstrate that CD48 expression is regulated by methylation and that a hypomethylating agent can increase the CD48 expression, which increases the NK cells killing in vitro. Finally, we show that CD48 high expression can reverse the AML immune evasion and activate NK cells function in vivo. The present study suggests that a combination the hypomethylating agent and NK cell infusion could be a new strategy to cure AML.
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http://dx.doi.org/10.1042/CS20191170DOI Listing
January 2020