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1.
Virol J ; 18(1): 75, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849599

RESUMO

BACKGROUND: H9N2 influenza virus, a subtype of influenza A virus, can spread across different species and induce the respiratory infectious disease in humans, leading to a severe public health risk and a huge economic loss to poultry production. Increasing studies have shown that polymerase acidic (PA) subunit of RNA polymerase in ribonucleoproteins complex of H9N2 virus involves in crossing the host species barriers, the replication and airborne transmission of H9N2 virus. METHODS: Here, to further investigate the role of PA subunit during the infection of H9N2 influenza virus, we employed mass spectrometry (MS) to search the potential binding proteins of PA subunit of H9N2 virus. Our MS results showed that programmed cell death protein 7 (PDCD7) is a binding target of PA subunit. Co-immunoprecipitation and pull-down assays further confirmed the interaction between PDCD7 and PA subunit. Overexpression of PA subunit in A549 lung cells greatly increased the levels of PDCD7 in the nuclear and induced cell death assayed by MTT assay. RESULTS: Flow cytometry analysis and Western blot results showed that PA subunit overexpression significantly increased the expression of pro-apoptotic protein, bax and caspase 3, and induced cell apoptosis. However, knockout of PDCD7 effectively attenuated the effects of PA overexpression in cell apoptosis. CONCLUSIONS: In conclusion, the PA subunit of H9N2 virus bind with PDCD7 and regulated cell apoptosis, which provide new insights in the role of PA subunit during H9N2 influenza virus infection.

2.
Biol Reprod ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33899080

RESUMO

Upon fertilization, extensive chromatin reprogramming occurs during preimplantation development. Growing evidence reveals species-dependent regulations of this process in mammals. ATP-dependent chromatin remodeling factor SMARCA5 (also known as SNF2H) is required for peri-implantation development in mice. However, the specific functional role of SMARCA5 in preimplantation development and if it is conserved among species remain unclear. Herein, comparative analysis of public RNA-seq datasets reveals that SMARCA5 is universally expressed during oocyte maturation and preimplantation development in mice, cattle, humans and pigs with species-specific patterns. Immunostaining analysis further describes the temporal and spatial changes of SMARCA5 in both mouse and bovine models. siRNA-mediated SMARCA5 depletion reduces the developmental capability and compromises the specification and differentiation of inner cell mass in mouse preimplantation embryos. Indeed, OCT4 is not restricted into the inner cell mass and the formation of epiblast and primitive endoderm disturbed with reduced NANOG and SOX17 in SMARCA5-deficient blastocysts. RNA-seq analysis shows SMARCA5 depletion causes limited effects on the transcriptomics at the morula stage, however, dysregulates 402 genes, including genes involved in transcription regulation and cell proliferation at the blastocyst stage in mice. By comparison, SMARCA5 depletion does not affect the development through the blastocyst stage but significantly compromises the blastocyst quality in cattle. Primitive endoderm formation is greatly disrupted with reduced GATA6 in bovine blastocysts. Overall, our studies demonstrate the importance of SMARCA5 in fostering the preimplantation development in mice and cattle while there are species-specific effects.

3.
J Colloid Interface Sci ; 597: 334-344, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33894544

RESUMO

Reducing cobalt dependency has attracted great interest for lithium batteries manufacturing due to limited cobalt resources and high prices. A highly promising LiNi0.6Co0.05Mn0.35O2 (NCM60535) high-nickel low cobalt lithium layered oxide cathode material is successfully prepared by systematically examining the two key synthesis conditions of pH and annealing temperature. The obtained materials exhibit a uniform size distribution, good spherical morphology, clear structure, and homogeneous element distribution. NCM60535 shows competitive electrochemical properties: when compared with the LiNi1/3Co1/3Mn1/3O2, with a higher output specific capacity and cycling stability at 4.3 V low voltage; when compared with the LiNi0.8Co0.1Mn0.1O2, with a comparable discharge capacity but relatively poor cycling stability at 4.5 V high voltage. A new type of electrolyte that combines high lithium salt concentration, EC-free solvent system, and VC and LiPO2F2 functional additives is designed and greatly improves the electrochemical properties of the material under high voltage. Moreover, it also delivers superior electrochemical properties in high voltage lithium full battery (270 Wh Kg-1). And we suggest that NCM60535 is expected to become a substitute for the currently widely commercialized LiNi1/3Co1/3Mn1/3O2 (NCM333), LiNi0.5Co0.2Mn0.3O2 (NCM523), LiNi0.6Co0.2Mn0.2O2 (NCM622), and LiNi0.8Co0.1Mn0.1O2 (NCM811) due to its relatively low production cost and competitive electrochemical properties.

4.
Water Sci Technol ; 83(8): 1878-1892, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33905359

RESUMO

Textile wastewater has been recognized as one of the most difficult to treat environmental problems. Aiming to acquire an excellent treatment effect that could meet the stringent discharge regulations, a series of Cu- and Fe-doped Al-MCM-41 heterogeneous Fenton catalysts with different metal contents (1.21-3.45 wt%) were successfully synthesized by co-precipitation method to degrade Rhodamine B. Their physicochemical properties were analysed by X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, nitrogen physisorption and scanning electron microscopy. The incorporation of metal did not alter MCM-41's mesostructure, but increasing the contents of metal would decrease the order of MCM-41s' structure. The effects of temperature, pH, H2O2 dosage, dye concentration and the dosage of catalysts on Rhodamine B degradation were also investigated. It was found that M2 with 2.71 wt% of active metals performed best on Rhodamine B degradation. For the high concentration of Rhodamine B (400 mg/L), the decolorization efficiency could reach 96.0% using only 40 mM H2O2 within 50 min at 60 °C. Further adding 40 mM of H2O2, the chemical oxygen demand removal reached 75.1% after 100 min. M2 showed excellent stability and could be reused at least three times without any obvious deterioration in catalytic activity. M2 fitted well with the Freundlich isotherms and the first-order rate model.


Assuntos
Peróxido de Hidrogênio , Dióxido de Silício , Catálise , Rodaminas
5.
Biol Reprod ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33763686

RESUMO

The NOTCH signaling pathway plays an important role in regulating various biological processes, including lineage specification and apoptosis. Multiple components of the NOTCH pathway have been identified in mammalian preimplantation embryos. However, the precise role of the NOTCH pathway in early embryonic development is poorly understood, especially in large animals. Here, we show that the expression of genes encoding key transcripts of the NOTCH pathway is dynamic throughout early embryonic development. We also confirm the presence of active NOTCH1 and RBPJ. By using pharmacological and RNAi tools, we demonstrate that the NOTCH pathway is required for the proper development of bovine early embryos. This functional consequence could be partly attributed to the major transcriptional mediator-RBPJ, whose deficiency also compromised the embryo quality. Indeed, both NOTCH1 and RBPJ knockdown cause a significant increase of histone H3 serine 10 phosphorylation (pH3S10, a mitosis marker) positive blastomeres, suggesting a cell cycle arrest at mitosis. Importantly, RNA-seq analyses reveal that either NOTCH1 or RBPJ depletion triggers a reduction in H1FOO that encodes the oocyte-specific linker histone H1 variant. Interestingly, depleting H1FOO results in detrimental effects on the developmental competence of early embryos, similar with NOTCH1 inhibition. Overall, our results reveal a crucial role for NOTCH pathway in regulating bovine preimplantation development, likely by controlling cell proliferation and maintaining H1FOO expression.

6.
Explore (NY) ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33712360

RESUMO

The main clinical manifestations of pleural effusion are exertional dyspnea, predominantly dry cough, and pleuritic chest pain. To treat pleural effusion appropriately, it is important to determine its etiology; which however, remains unclear in nearly 20% of cases.A 73-year-old man with a history of invasive pulmonary tuberculosis (TB), had been experiencing chest congestion and dyspnea with undiagnosed pleural effusion for six years. After a series of clinical examination and laboratory tests, there was still no clear diagnosis. Despite administering diuretics and intermittent draining, the patient's condition aggravated progressively. He sought further treatment at Dongzhimen Hospital Respiratory Outpatient Clinic. The patient was treated with Zanthoxylum and Trichosanthes Decoction (Jiao Mu Gua Lou Tang). After one and a half years, his symptoms greatly improved and ultrasound revealed that the pleural effusion had apparently absorbed.It is suggested that TCM herbal formulas can play a critical role in preventing the progression of complicated, undiagnosed pleural effusion, especially in cases of poor response to conventional therapy and thoracentesis. Additional studies on the functions and mechanisms of the medicinals are warranted.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33646538

RESUMO

Urban air pollution with PM2.5 as the main pollutant has become increasingly prominent in China since 2010. Scholars have conducted many studies on how urbanization affects PM2.5, but few concerns about the relationship between construction land (CL) expansion and PM2.5 at different scales from the perspective of expansion rate. Therefore, this study takes CL and PM2.5 data in China to describe the spatiotemporal progress of atmospheric environmental pollution and then adopts the overall and spatial coupling models to quantitatively reveal the dynamic relationship between them. The results indicate that the growth rate of PM2.5-polluted area in China was found to increase rapidly for 2000-2010 time period, followed by a continuous decline afterward. The annual average growth rates of CL area and PM2.5-polluted area within 15 years were 4.43% and 2.46%, respectively. Moreover, the barycenter distance between PM2.5 concentration and CL decreased gradually, and the two barycenters approached closer. Also, the spatial coupling coordination of CL and PM2.5 enhanced in Central, West, and East China but weakened in Northeast. Cities with a "very strong" coupling type are mainly located in the "Chongqing-Beijing" belt and the lower-middle reaches of the Yangtze River. Finally, the spatial coupling model results show that a low PM2.5 concentration is closely related to CL expansion. This study will provide a basis for cross-regional joint air pollution control and the management of heavily polluted areas in China.

8.
Med Oncol ; 38(4): 32, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33609219

RESUMO

Melanoma is a high-grade malignant subtype of human skin cancer with the highest mortality rate. Here we perform a bioinformatics analysis concerning human melanoma tissues by the Gene Expression Omnibus (GEO) database and Gene Expression Profiling Interactive Analysis (GEPIA) platform. We found that lncRNA LINC01550 was significantly down-regulated in the melanoma tissues as compared to the normal tissues. The low expression of LINC01550 was tightly associated with shorter overall survival and disease-free survival of patients with melanoma. LINC01550 expression is negatively associated with tumor cell proliferation and invasion abilities in melanoma as evidenced by the single-cell RNA sequencing (scRNA-seq) databases. LINC01550-overexpressing vectors were transferred into melanoma cells (WM35 and WM451). Up-regulation of LINC01550 significantly inhibited proliferation and invasion abilities, as well as induced cell apoptosis and G1 and S phase arrest of the melanoma cells. In conclusion, overexpression of LINC01550 may serve as a potential therapeutic target for melanoma.

9.
J Pharm Biomed Anal ; 197: 113959, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33626444

RESUMO

Acquired estrogen receptor 1 (ESR1) mutation is being promoted as a key mechanism of resistance to endocrine therapies in breast cancers. It is significative to monitor ESR1 mutations in real time, which provide an opportunity to alter therapy as these mutations emerge. Previous assays based on next-generation sequencing (NGS) and digital PCR (dPCR) usually due to high costs and complicated workflows hampered their clinical adoption in general medical institutions. Here, we proposed a new strategy using base-specific invasive reaction assisted qPCR measure for ESR1 mutations in cfDNA. Two pivotal steps involved in this strategy are target-specific signal generation and the quantification without adding any internal reference or making standard calibration curves. The strategy enabled a high specificity of 0.1% (better than traditional NGS-based method) and a minimum sensitivity of 0.1 copies µL-1. As validation, with the strategy, cfDNA from endocrine therapy-resistant breast cancers and untreated ones were successfully analyzed (20% mutation rate (2/10) with mutation abundance of 0.54-1.65% vs. 0% mutation rate (0/5)). By virtue of cost-effective, highly flexible and precise, the strategy could be readily implemented in general laboratory, showing promising application perspectives in analysis of other types of mutations.

10.
Int J Mol Med ; 47(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537821

RESUMO

Endothelial dysfunction and diabetic vascular disease induced by chronic hyperglycemia involve complex interactions among high glucose, long non­coding RNAs (lncRNAs), microRNAs (miRNAs or miRs) and the Ser/Thr kinase AKT. However, the molecular mechanisms underlying the regulatory crosstalk between these have not yet been completely elucidated. Thus, the present study aimed to explore the molecular mechanisms whereby high glucose (HG)­induced lncRNA MIR181A2HG modulates human umbilical vein endothelial cell (HUVEC) proliferation and migration by regulating AKT2 expression. The persistent exposure of HUVECs to HG resulted in MIR181A2HG downregulation and thus reduced its ability to sponge miR­6832­5p, miR­6842­5p and miR­8056, subsequently leading to an increase in miR­6832­5p, miR­6842­5p and miR­8056 levels. Mechanistically, miR­6832­5p, miR­6842­5p and miR­8056 were found to target the 3'UTR of AKT2 mRNA in HUVECs, and the increase in their levels led to a decreased expression of AKT2. Thus, this also led to the suppression of HUVEC proliferation and migration, and the formation of capillary­like structures. Moreover, the suppression of HUVEC proliferation and migration induced by MIR181A2HG downregulation was accompanied by changes in glucose metabolism. On the whole, the present study demonstrates that the downregulation of lncRNA MIR181A2HG by HG impairs HUVEC proliferation and migration by dysregulating the miRNA/AKT2 axis. The MIR181A2HG/miRNA/AKT2 regulatory axis may thus be a potential therapeutic target for HG­induced endothelial dysfunction.


Assuntos
Movimento Celular/efeitos dos fármacos , Regulação para Baixo/genética , Glucose/toxicidade , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , Regiões 3' não Traduzidas/genética , Sequência de Bases , Capilares/efeitos dos fármacos , Capilares/crescimento & desenvolvimento , Proliferação de Células/efeitos dos fármacos , Glucose/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Modelos Biológicos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo
11.
Sci Total Environ ; 775: 145836, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-33631578

RESUMO

Rapid urbanisation causes large urban conversions of natural and agricultural land to non-agricultural use. Research on urban expansion has typically disregarded gradient characteristics. The current study uses slope data calculated based on the Shuttle Radar Topography Mission Digital Elevation Model data set and multi-period land cover data derived from China's Multi-Period Land Use Land Cover Remote Sensing Monitoring data set to reveal the evolution of spatiotemporal patterns of vertical urban expansion in China from 1990 to 2015. A built-up land climbing index is specifically defined to measure the increasing use of land with slopes. A slope-climbing phenomenon has become increasingly apparent over time. Although built-up land with slopes below 5° accounts for over 85% of the total, this proportion has declined steadily from 89.53% in 1990 to 86.61% in 2015. The number of cities where built-up land was developed on high slopes (over 5°) increased from 150 to 238. Slope-climbing intensity spatially increased from north to south, and showed a "low-high-low" pattern from west to east. In addition, built-up land showed evident slope-climbing trend in areas with high variation in slope. Slope-climbing intensity was high for cities located in mountains and ethnic autonomous prefectures. Lastly, cities going uphill are subjected to the combined effects of natural environmental conditions and social factors. The average slope and population growth have significantly positive impact on slope-climbing intensity.

12.
Acta Cytol ; : 1-7, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535203

RESUMO

INTRODUCTION: We intend to determine the diagnostic power of fine needle aspiration biopsy (FNAB) for differentiation between malignant and benign lesions on axillary masses and draw the physicians' attention to the benefits of FNAB cytology in the diagnosis of axillary masses. METHODS: In this study, 1,328 patients with an axillary mass diagnosed by FNAB were retrospectively reviewed. These cases were registered at the affiliated hospital of Southwest Medical University (China), July 2014 to June 2017. Cytological results were verified either by histopathology following surgical resection or clinical follow-up. RESULTS: Of the 1,328 patients affected by axillary masses, 987 (74.3%) cases were female, and 341 (25.7%) cases were male. The highest incidence of patients was in the age group of 41-50 years (375, 28.2%). There were 1,129 (85.0%) patients with benign lesions and 199 (15.0%) with malignant lesions. Of the 199 malignant lesions cases, 21 cases were lymphomas, 2 cases were accessory breast cancers, and 176 cases were lymph node metastatic tumors. Under lymph node metastases, the most frequent primary tumors were breast cancer (141, 80.1%), followed by lung cancer (21, 11.9%). According to the study, the characters of 1,328 cases showed statistically significant difference (χ2 = 4.534, p = 0.033), and the incidence of females with axillary mass was significantly higher than that of males. There was a statistically significant difference in the distribution of benign and malignant cases in the patient age groups (χ2 = 1.129, p = 0.000), and the incidence of patients of 41-50 years of age was significantly higher than that of other patients. The diagnostic accuracy of FNAB in axillary masses was analyzed with the results of 95.98% of sensitivity, 99.56% of specificity, 97.45% of positive predictive value, and 99.29% of negative predictive value. CONCLUSION: Our results confirm that FNAB is a valuable initial screening method regarding pathologic diagnosis of axillary mass, in particular with respect to malignancy in 41- to 50-year-old female patients.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33389988

RESUMO

The nucleation and growth of spherical Ni0.6Co0.2Mn0.2(OH)2 agglomerates using the hydroxide coprecipitation (HCP) method in the presence of ammonia is investigated through chemical equilibrium calculations and experiments. In the nucleation stage, the transition metal ions in the salt solution gradually complete the nucleation reaction in the diffusion process from pH 5.4 to 11 after dropping into the continuously stirred tank reactor, and then Me(NH3)n2+ and Me(OH)2(s) (Me: Ni, Co, and Mn) reach a dynamic precipitation dissolution equilibrium. In the growth stage, the concentration ratio of Me(NH3)n2+ and OH- (complexation and precipitation, Rc/p) in the solution has an important influence on obtaining high-quality materials, which is further confirmed using the first principles density functional theory calculations on surface energy and adsorption energy. Then, the HCP reaction could be divided into three parts through experiments: incomplete precipitation area (Rc/p > 10.1); time-dependent area (Rc/p = 0.1-10.1); and hard-to-control area (Rc/p <0.1). According to the optimal ratio (Rc/p = 3.4), a prediction formula for the optimal synthesis conditions of the materials is proposed (y = 0.7731 × ln(x + 0.0312) + 11.6708, the optimal pH value (y) corresponds to different ammonia concentrations (x)). The results obtained for the growth reaction mechanism and the prediction scheme would help the modification research of the materials and obtain the desired lithium-layered transition metal oxide cathode material with excellent performance in the shortest time.

14.
Biochim Biophys Acta Mol Basis Dis ; 1867(1): 165995, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33141063

RESUMO

The progression of cardiovascular research is often impeded by the lack of reliable disease models that fully recapitulate the pathogenesis in humans. These limitations apply to both in vitro models such as cell-based cultures and in vivo animal models which invariably are limited to simulate the complexity of cardiovascular disease in humans. Implementing human heart tissue in cardiovascular research complements our research strategy using preclinical models. We established the Human Explanted Heart Program (HELP) which integrates clinical, tissue and molecular phenotyping thereby providing a comprehensive evaluation into human heart disease. Our collection and storage of biospecimens allow them to retain key pathogenic findings while providing novel insights into human heart failure. The use of human non-failing control explanted hearts provides a valuable comparison group for the diseased explanted hearts. Using HELP we have been able to create a tissue repository which have been used for genetic, molecular, cellular, and histological studies. This review describes the process of collection and use of explanted human heart specimens encompassing a spectrum of pediatric and adult heart diseases, while highlighting the role of these invaluable specimens in translational research. Furthermore, we highlight the efficient procurement and bio-preservation approaches ensuring analytical quality of heart specimens acquired in the context of heart donation and transplantation.


Assuntos
Pesquisa Biomédica , Insuficiência Cardíaca , Miocárdio , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Humanos
15.
J Cell Physiol ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33184863

RESUMO

Prolonged endoplasmic reticulum (ER) stress is the key driving force behind diabetic cardiomyopathy (DCM). Autophagy is extensively implicated in adaptive mechanisms for cell survival. Interleukin-33 (IL-33) is known to be a potent cardiac protector, but its roles in DCM, ER stress, and autophagy are currently unknown. We aimed to explore the effects of IL-33 on DCM and characterize the roles that ER stress and autophagy play in DCM. The effects of IL-33 on DCM, ER stress, and autophagy were characterized both in db/db mice and in palmitic acid (PA)-treated cardiomyocytes. The manipulators of ER stress and autophagy were used to clarify their roles in DCM remittance conferred by IL-33. Gene expression analysis was used to identify IL-33-dependent regulators of ER stress and autophagy. Both db/db mice and PA-treated cells presented with enhanced levels of ER stress, apoptosis, and lipid deposition, as well as impaired autophagy, all of which could be reversed by IL-33. Treatment with IL-33 improved the cardiac diastolic function of diabetic mice. Nonselective autophagy inhibitors, such as 3-methyladenine (3-MA) or wortmannin, abolished the protective effects of IL-33, resulting in an increase in both ER stress and apoptosis. Strikingly, insulin-like growth factor-binding protein 3 (IGFBP3) was identified as the gene most significantly differentially expressed between IL-33 and control groups. Knockdown of IGFBP3 expression, similar to the effect of nonselective autophagy inhibitors, resulted in high levels of ER stress, impaired autophagy, and apoptosis that were not rescued upon treatment with IL-33. IL-33 abates DCM by alleviating ER stress and promoting autophagy. IGFBP3 is essential for IL-33-induced ER stress resolution and autophagic enhancement during DCM.

16.
Pediatrics ; 146(6)2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33177168

RESUMO

Crohn disease (CD) is a chronic inflammatory disease, and its incidence in children is rising. Despite extensive reports and investigations, the pathogenesis of CD has not been clearly elucidated, particularly in regard to triggering factors. A genetic predisposition is considered important when investigating the mechanism leading to CD, and the discovery of new CD-associated genes has increased our understanding of its immunopathogenesis and improved the efficacy of its treatment of CD. Early detection and treatment (eg, as children) with gene-based precision therapy can effectively prevent complications related to CD. In this case, a Chinese Han boy with CD associated with a mutation of tumor necrosis factor α-induced protein 3 was treated with recombinant human tumor necrosis factor-a receptor II:IgG Fc fusion protein. We suspected the boy had CD because of chronic abdominal pain, aphthous stomatitis, moderate anemia, a high erythrocyte sedimentation rate (36-79 mm/h), multiple intestinal ulcers, knee joint swelling, and a tumor necrosis factor α-induced protein 3 mutation. After total enteral nutrition and hormone therapy for 5 months, his abdominal pain and joint symptoms did not improve, so we started gene-based precision therapy with recombinant human tumor necrosis factor-a receptor II: IgG Fc fusion protein, which may play an important role in restricting TNF-α-induced NF-κB signaling. After 3 weeks, inflammation indicators were within the normal range, and multiple ulcers and joint symptoms were relieved. The present case demonstrates a safe therapeutic schedule that leads to rapid improvements in the clinical and biochemical status of patients with CD.

17.
Front Neurosci ; 14: 743, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013281

RESUMO

Background: Low-density lipoprotein receptor-related protein 1 (LRP1) is involved in cerebral glucose metabolism and amyloid-ß clearance. This study aimed to investigate the pathogenetic roles of LRP1 and its rs1799986 polymorphism in mild cognitive impairment (MCI) among patients with type 2 diabetes mellitus (T2DM). Methods: A total of 166 Chinese patients with T2DM were enrolled and divided into two groups according to Montreal Cognitive Assessment (MoCA) scores. Neuropsychological tests were performed. Soluble LRP1 (sLRP1) levels were assessed using enzyme-linked immunosorbent assay, and the genotype of LRP1 rs1799986 was detected using the Sequenom method. Results: Diabetic patients with MCI (n = 60) exhibited significantly lower plasma sLRP1 levels (p = 0.033) and worse glucose control (p = 0.009) than the healthy cognition controls (n = 106). Multivariate regression analysis revealed plasma sLRP1 levels [odds ratio (OR) = 0.971, p = 0.005] and HbA1c (OR = 1.298, p = 0.003) as a risk factor for MCI in diabetic patients, in addition to insulin use and hypertension. However, there was no association between plasma sLRP1 levels and HbA1c. After adjusting for age, sex, and education level, plasma sLRP1 levels in the MCI group were negatively correlated with Stroop Color Word Test B number (r = -0.335, p = 0.011), which represents selective attention, cognitive flexibility, and processing speed. Additionally, patients with T2DM carrying the T allele of LRP1 rs1799986 showed higher Auditory Verbal Learning Test (AVLT) delayed recall scores (p = 0.025). Conclusion: Decreased plasma sLRP1 levels are associated with MCI, particularly with attention dysfunction, in patients with T2DM. Moreover, the T allele of LRP1 rs1799986 may decrease susceptibility to MCI. Further studies with large cohorts should be designed to elucidate the roles of LRP1 in hyperglycemia-induced cognitive decline.

18.
Essays Biochem ; 64(6): 947-954, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33034348

RESUMO

microRNAs (miRNAs) play essential roles in mouse embryonic stem cells (ESCs) and early embryo development. The exact mechanism by which miRNAs regulate cell fate transition during embryo development is still not clear. Recent studies have identified and captured various pluripotent stem cells (PSCs) that share similar characteristics with cells from different stages of pre- and post-implantation embryos. These PSCs provide valuable models to understand miRNA functions in early mammalian development. In this short review, we will summarize recent work towards understanding the function and mechanism of miRNAs in regulating the transition or conversion between different pluripotent states. In addition, we will highlight unresolved questions and key future directions related to miRNAs in pluripotent state transition. Studies in these areas will further our understanding of miRNA functions in early embryo development, and may lead to practical means to control human PSCs for clinical applications in regenerative medicine.

19.
J Safety Res ; 74: 17-25, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32951781

RESUMO

INTRODUCTION: Numerous studies have demonstrated the close relationship between alcohol availability and alcohol-related crashes. However, there is still a lack of spatial empirical analysis regarding this relationship, particularly in large cities of developing countries. Differences in alcohol outlets and drinking patterns in these cities may lead to quite different patterns of crash outcomes. METHOD: 3356 alcohol-related crashes were collected from the blood-alcohol test report of a forensic institution in Tianjin, China. Density of alcohol outlets such as retail locations, entertainment venues, restaurants, hotels, and companies were extracted based on 2114 Traffic Analysis Zones (TAZ) together with the residential and demographic characteristics. After applying the exploratory spatial data analysis, this research developed and compared the traditional Ordinary Least Square model (OLS), Spatial Lag Model (SLM), Spatial Error Model (SEM) and Spatial Durbin Model (SDM) to explore spatial effects of all the variables. RESULTS: The results of incremental spatial autocorrelation show that the most significant distance threshold of alcohol-related roadway traffic crashes is 3 km. The SDM is found to be the optimal spatial model to characterize the relationship between alcohol outlets and crashes. The number of alcohol-involved traffic crashes is positively related to population density and retail density, but negatively related to the company density, hotel density, and residential density within the same TAZ. Meanwhile, dense population and hotels have reverse spillover effects in adjacent zones. CONCLUSIONS: The significant spatial direct effect and spillover effect of alcohol outlet densities on drunk driving crashes should not be neglected. These findings could help improve transportation planning, traffic law enforcement and traffic management for large cities in developing countries.

20.
Cell Prolif ; 53(11): e12914, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32990380

RESUMO

OBJECTIVES: Mouse embryonic stem cell (mESC) culture contains various heterogeneous populations, which serve as excellent models to study gene regulation in early embryo development. The heterogeneity is typically defined by transcriptional activities, for example, the expression of Nanog or Rex1 mRNA. Our objectives were to identify mESC heterogeneity that are caused by mechanisms other than transcriptional control. MATERIALS AND METHODS: Klf3 mRNA and protein were analysed by RT-qPCR, Western blotting or immunofluorescence in mESCs, C2C12 cells, early mouse embryos and various mouse tissues. An ESC reporter line expressing KLF3-GFP fusion protein was made to study heterogeneity of KLF3 protein expression in ESCs. GFP-positive mESCs were sorted for further analysis including RT-qPCR and RNA-seq. RESULTS: In the majority of mESCs, KLF3 protein is actively degraded due to its proline-rich sequence and highly disordered structure. Interestingly, KLF3 protein is stabilized in a small subset of mESCs. Transcriptome analysis indicates that KLF3-positive mESCs upregulate genes that are initially activated in 8-cell embryos. Consistently, KLF3 protein but not mRNA is dramatically increased in 8-cell embryos. Forced expression of KLF3 protein in mESCs promotes the expression of 8-cell-embryo activated genes. CONCLUSIONS: Our study identifies previously unrecognized heterogeneity due to KLF3 protein expression in mESCs.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Fatores de Transcrição Kruppel-Like/genética , Células-Tronco Embrionárias Murinas/citologia , Animais , Diferenciação Celular , Linhagem Celular , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Mioblastos/citologia , Mioblastos/metabolismo , RNA Mensageiro/genética , Ativação Transcricional , Transcriptoma
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