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1.
Opt Lett ; 45(3): 726-729, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32004295

RESUMO

We propose and demonstrate parallel structured optical fiber in-line Fabry-Perot interferometers for high temperature sensing. The device consists of three Fabry-Perot cavities in parallel connection, which allows three independent fringe patterns superimposed at its output, and, as a result, a number of dominant fringe peaks/dips appear, thus enabling unambiguous measurement in a large range. The device is featured with compact size, robust structure, and excellent high temperature sustainability, which makes it promising in extreme environment monitoring.

2.
Chin J Traumatol ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-32005413

RESUMO

PURPOSE: To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury. METHODS: Twenty female healthy goats were randomly divided into three groups by different driving pressures: 4.0 MPa group (n = 4), 4.5 MPa group (n = 12) and 5.0 MPa group (n = 4). The severe blast lung injury model of goats was established using a BST-I bio-shock tube. Vital signs (respiration, heart rate and blood pressure), lung ultrasound score (LUS), PO2/FiO2 and extravascular lung water (EVLW) were measured before injury (0 h) and at 0.5 h, 3 h, 6 h, 9 h, 12 h after injury. CT scanning was performed before injury (0 h) and at 12 h after injury for dynamic monitoring of blast lung injury and measurement of lung volume. The correlation of LUS with PaO2/FiO2, EVLW, and lung injury ratio (lesion volume/total lung volume*100%) was analyzed. All animals were sacrificed at 12 h after injury for gross observation of lung injury and histopathological examination. Statistical analysis was performed by the SPSS 22.0 software. The measurement data were expressed as mean ± standard deviation. The means of two samples were compared using independent-sample t-test. Pearson correlation analysis was conducted. RESULTS: (1) At 12 h after injury, the mortality of goats was 0, 41.67% and 100% in the 4.0 Mpa group, 4.5 MPa group and 5.0 MPa group, respectively; the area of pulmonary hemorrhage was 20.00% ± 13.14% in the 4.0 Mpa group and 42.14% ± 15.33% in the 4.5 MPa group. A severe lung shock injury model was established under the driving pressure of 4.5 MPa (2) The respiratory rate, heart rate, LUS and EVLW were significantly increased, while PaO2/FiO2 was significantly reduced immediately after injury, and then they gradually recovered and became stabilized at 3 h after injury. (3) LUS was positively correlated with EVLW (3 h: r = 0.597, 6 h: r = 0.698, 9 h: r = 0.729; p < 0.05) and lung injury ratio (12 h: r = 0.884, p < 0.05), negatively correlated with PaO2/FiO2 (3 h: r = -0.871, 6 h: r = -0.637, 9 h: r = -0.658; p < 0.05). CONCLUSION: We established a severe blast lung injury model of goats using the BST-I bio-shock tube under the driving pressure of 4.5 MPa and confirmed that ultrasound can be used for quick evaluation and dynamic monitoring of blast lung injury.

3.
Anal Chem ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027489

RESUMO

A total of 15 representative organophosphorus pesticides (OPPs), a class of water pollutants causing serious global concerns, have been sensitively quantified by internal extractive electrospray ionization mass spectrometry (iEESI-MS) after enrichment with innovatively fabricated Fe3O4-ZrO2 synthesized in our lab by a co-precipitation method in one step. For the premium enrichment, the amounts of Fe3O4-ZrO2, pH value, adsorption time, type and volume of desorption solvent, shaking time of desorption were systematically optimized. Under optimized conditions, the proposed method provided low limit of detections (LODs) of 0.14-16.39 ng L-1 with the relative standard deviations (RSDs) less than 8.7%. A wide linear responding range about 4 orders was achieved with the linear coefficients R2=0.9921-0.9999 for all the analytes tested. The present method also provided good recoveries (85.4-105.9%) with acceptable precision (RSDs<7.2%) in spiked environmental water samples. Furthermore, multiple analytes including dimethoate, omethoate, etc. were simultaneously detected in a single sample run, which was accomplished within 1 min, resulting in significantly improved analytical throughput for quantitative analysis of bulk amounts of samples. The experimental results demonstrated that Fe3O4-ZrO2-iEESI-MS provided the advantages including high sensitivity, high speed and reasonable selectivity for the detection of OPPs, showing potential applications in environmental water sample analysis and environmental science.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32030889

RESUMO

AIM: The aim of this study was to evaluate the clinical and molecular characteristics of myelodysplastic syndrome (MDS) patients with monosomal karyotype (MK). METHODS: Eighty MDS patients with MK diagnosed between January 2010 and December 2018 were included in the retrospective study. Seventy-three had complex karyotype (CK) and 46 had very CK (vCK, ≥ 5 abnormalities). Clinical information was collected, and a panel of 37 genes, on which mutations have been previously reported to be associated with MDS patients, was analyzed by next-generation sequencing. Genetic and biological features and their association with survival were evaluated. RESULTS: Monosomy 5, 7, and 17 were the most frequent and mainly occurred in patients with vCK. While median overall survival (OS) for all patients was 12.8 months with 95% CI 9.1-16.5, patients with vCK had shorter OS (8.4 months with 95% CI 3.9-12.8) than those with non-vCK (16.1 months with 95% CI 11.5-20.8) (P = .02). At least one gene mutation was detected in 76 patients (95%), TP53 mutations were detected in 57 patients, and their median OS was significantly shorter than those without TP53 mutations (9.5 months with 95% CI 7.5-11.5 vs 26.1 months with 95% CI 8.0-44.2, P < .01). In 34 patients who received treatment with decitabine, 25 with TP53 mutations had higher overall response rate than those with wild-type TP53 (60% vs 22.2%, P = .03). However, OS was still significantly shorter in those with TP53 mutations (10.1 vs 26.1 months, P = .03). Multivariate analysis confirmed that TP53 mutations was an independent poor prognostic factor on OS. CONCLUSIONS: CK and vCK overlap in most of the MDS patients with MK. TP53 mutations occur more frequently in MDS patients with vCK, and both TP53 mutations and vCK are adverse prognostic factors.

5.
Life Sci ; 246: 117366, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32001266

RESUMO

BACKGROUND: Hydroxychloroquine exhibits synergistic anticancer properties as an adjuvant. However, the role and molecular mechanisms underlying of HCQ as monotherapy for lung adenocarcinoma (LUAD) have yet to be elucidated. METHODS: We assessed the antitumor effects of HCQ in LUAD cells through a series of in vitro and in vivo assays. GEO database and R packages were used to predict molecular mechanisms of HCQ in the treatment of lung adenocarcinoma, followed by verification of gene expression and subcellular localization via immunoblotting, immunofluorescent and immunohistochemistry assays. RESULTS: We showed the phenotypic effects that HCQ inhibited cell growth, induced apoptosis and cell cycle arrest at G1/S transition in A549 and PC-9 cells, which was associated with inhibition of CDK2, CDK4, CyclinD1 and CyclinE, but up-regulation of p21 and p27Kip1. Bioinformatic analysis predicted that 63 targets related to HCQ and LUAD were mainly enriched in JAK-STAT and FoxO pathways. Then, we observed that HCQ decreased the phosphorylation of STAT3, but increased the expression of FoxO3a and its accumulation in the nucleus. The specific STAT3 inhibitor cryptotanshinon augmented the HCQ-induced upregulation and nuclear translocation of FoxO3a. In addition, HCQ increased the expression of p27Kip1, which was impaired by FoxO3a blockade with siRNA. Finally, ablation of p27Kip1 expression abrogated the cytotoxicity of HCQ. More importantly, similar results were further confirmed in vivo. CONCLUSIONS: Taken together, this study suggests that STAT3/FoxO3a/p27Kip1 signaling pathway is involved in the anticancer effects of HCQ, and provides preliminary evidence for therapeutic prospects of HCQ alone in LUAD.

6.
Thorac Cancer ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32061027

RESUMO

BACKGROUND: The prognostic value of platelet distribution width (PDW) is different in various malignancies. The purpose of this study was to identify the relationship between preoperative PDW and survival in patients with non-small cell lung cancer (NSCLC). METHODS: Optimal cutoff values of PDW were confirmed using a receiver operating characteristic (ROC) curve. The Kaplan-Meier method and log-rank test were used to estimate disease-free survival (DFS) and overall survival (OS). Univariate and multivariate Cox regression models were used for prognostic analysis. The likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare two models of the TNM staging system and the PDW-TNM staging system (combination of PDW and the TNM staging system). RESULTS: Survival analysis indicated that the disease-free survival (DFS) and overall survival (OS) of patients with PDW > 12.65 were both significantly longer than those of patients with PDW ≤ 12.65. Multivariate analysis showed that PDW was an independent prognostic factor for DFS and OS. After the two prediction models were established, further LRT analysis showed that the PDW-TNM model had a better ability to assess patient prognosis. CONCLUSIONS: PDW might act as an independent risk factor to predict progression and prognosis. Preoperative PDW combined with the TNM staging system showed a better ability to assess the prognosis of NSCLC patients. KEY POINTS: Our study focused on the prognostic value of preoperative PDW in 750 patients with NSCLC. We also analyzed preoperative PDW in different stages and histological subtypes systematically. A model built by preoperative PDW combined with the TNM staging system had a better prognostic ability. LRT was used to calculate values of the goodness of fit between the model and the TNM staging system.

7.
Int J Biol Macromol ; 150: 102-113, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044370

RESUMO

Auricularia mushrooms are known for their bioactive compounds, mostly polysaccharides, which have numerous biological activities, such as antioxidant, antitumor, immunomodulatory, hyperlipidemic, antidiabetic, anticoagulant and hepatoprotective effects. Over the past decades, there has been a consistent focus on the isolation, chemical properties and bioactivities of polysaccharides from Auricularia. This review will cover what is known about Auricularia polysaccharides (AP) especially for several common species, including A. auricula-judae, A. auricula, A. polytricha, and A. cornea var. Li. The isolation and purifications, structural characterizations, chemical modifications, and biological activities of these AP and their derivatives will be discussed, thus to provide a foundation for the further investigation, production, and application of AP as functional foods and therapeutic agents.

8.
Neoplasia ; 22(3): 142-153, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32062068

RESUMO

The BCL6 proto-oncogene encodes a transcriptional repressor, which is required for germinal centers (GCs) formation and lymphomagenesis. Previous studies have been reported that the constitutive expression of BCL6 leads to diffuse large B cell lymphoma (DLBCL) through activation-induced cytidine deaminase (AID) mediated chromosomal translocations and mutations. However, other DLBCLs (45%) without structural variants were characterized by abnormally high level of BCL6 expression through an unknown mechanism. Herein, we report that deficiency in AID or methyltransferase 1 (DNMT1) triggers high level of BCL6 expression. AID-DNMT1 complex binds to -0.4 kb -0 kb region of BCL6 promoter and contributes to generate BCL6 methylation which results in inhibition of BCL6 expression. The proteasome pathway inhibitor MG132 induces accumulation of AID and DNMT1, causes decreased BCL6 expression, and leads to cell apoptosis and tumor growth inhibition in DLBCL cell xenograft mice. These findings propose mechanistic insight into an alternative cofactor role of AID in assisting DNMT1 to maintain BCL6 methylation, thus suppress BCL6 transcription in DLBCL. This novel mechanism will provide a new drug selection in the therapeutic approach to DLBCL in the future.

9.
Cancer Med ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068352

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) has become the second most common tumor type that contributes to cancer-related death worldwide. The study aimed to establish a robust immune-related gene pair (IRGP) signature for predicting the prognosis of HCC patients. METHODS: Two RNA-seq datasets (The Cancer Genome Atlas Program and International Cancer Genome Consortium) and one microarray dataset (GSE14520) were included in this study. We used a series of immune-related genes from the ImmPort database to construct gene pairs. Lasso penalized Cox proportional hazards regression was employed to develop the best prognostic signature. We assigned patients into two groups with low immune risk and high immune risk. Then, the prognostic ability of the signature was evaluated by a log-rank test and a Cox proportional hazards regression model. RESULTS: After 1000 iterations, the 33-immune gene pair model obtained the highest frequency. As a result, we chose the 33 immune gene pairs to establish the immune-related prognostic signature. As we expected, the immune-related signature accurately predicted the prognosis of HCC patients, and high-risk groups showed poor prognosis in the training datasets and testing datasets as well as in the validation datasets. Furthermore, the immune-related gene pair (IRGP) signature also showed higher predictive accuracy than three existing prognostic signatures. CONCLUSION: Our prognostic signature, which reflects the link between the immune microenvironment and HCC patient outcome, is promising for prognosis prediction in HCC.

10.
Nanoscale ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016240

RESUMO

The continuous exploration of advanced electrode materials is of remarkable significance to revolutionize next-generation high-performance energy storage devices towards a green future. Benefiting from their electrochemically active sites and abundant redox centers, bimetallic selenides with desirable nanostructures recently have emerged as promising electrode alternatives for battery-supercapacitor hybrid (BSH) devices which demonstrate enormous potential in bridging the gap between electrochemical properties with high power densities (supercapacitors) and energy densities (batteries). Herein, employing the hydrothermal approach with solid Ni-Co spheres as precursors followed by the selenization process, selenide-rich bimetallic selenide spheres with a core-shell nanostructure were rationally designed and synthesized for use as the cathode electrode in superior BSH devices. The as-obtained (NiCo)9Se8/(NiCo)0.85Se (Ni-Co-Se) exhibits a high specific capacity of 164.44 mA h g-1 at a current density of 1 A g-1 with 85.72% capacity retention even after 5000 cycles at a current density of as high as 8 A g-1, suggesting its great promise in practical applications for BSH devices. By integrating activated carbon as the anode with the as-obtained bimetallic selenides as the cathode, an alkaline aqueous BSH device is fabricated and delivers a high energy density of 37.54 W h kg-1 at a high power density of 842.7 W kg-1. It is found that the excellent electrochemical performances can be ascribed to facile ion and electron transport pathways, high electrical conductivity and reliable structural robustness of the prepared selenides. Moreover, the synthetic strategy presented in this paper opens up an avenue to guide the synthesis of various anion doped bimetallic compounds towards high-performance energy conversion and storage devices.

11.
Acc Chem Res ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031367

RESUMO

The rational design of highly efficient catalysts relies on understanding their structure-activity relationships and reaction mechanisms at a molecular level. Such an understanding can be obtained by in situ monitoring of dynamic reaction processes using surface-sensitive techniques. Surface-enhanced Raman spectroscopy (SERS) can provide rich structural information with ultrahigh surface sensitivity, even down to the single-molecule level, which makes it a promising tool for the in situ study of catalysis. However, only a few metals (like Au, Ag, and Cu) with particular nanostructures can generate strong SERS effects. Thus, it is almost impossible to employ SERS to study transition metals (like Pt, Pd, Ru, etc.) and other nonmetal materials that are usually used in catalysis (material limitation). Furthermore, SERS is also unable to study model single crystals with atomically flat surface structures or practical nanocatalysts (morphology limitation). These limitations have significantly hindered the applications of SERS in catalysis over the past four decades since its discovery, preventing SERS from becoming a widely used technique in catalysis. In this Account, we summarize the extensive efforts done by our group since the 1980s, particularly in the past decade, to overcome the material and morphology limitations in SERS. Particular attention has been paid to the work using core-shell nanostructures as SERS substrates, because they provide high Raman enhancement and are highly versatile for application on different catalytic materials. Different SERS methodologies for catalysis developed by our group, including the "borrowing" strategy, shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), and SHINERS-satellite strategy, are discussed in this account, with an emphasis on their principles and applications. These methodologies have successfully overcome the long-standing limitations of traditional SERS, enabling in situ tracking of catalysis at model single-crystal surfaces and practical nanocatalysts that can hardly be studied by SERS. Using these methodologies, we systematically studied a series of fundamentally important reactions, such as oxygen reduction reaction, hydrogen evolution reaction, electrooxidation, CO oxidation, and selective hydrogenation. As such, direct spectroscopic evidence of key intermediates that can hardly be detected by other traditional techniques was obtained. Combined with density functional theory and other in situ techniques, the reaction mechanisms and structure-activity relationships of these catalytic reactions were revealed at a molecular level. Furthermore, the future of SERS in catalysis has also been proposed in this work, which we believe should be focused on the in situ dynamic studies at the single-molecule, or even single-atom, level using techniques with ultrahigh sensitivity or spatial resolution, for example, single-molecule SERS or tip-enhanced Raman spectroscopy. In summary, core-shell nanostructure-enhanced Raman spectroscopies are shown to greatly boost the application of SERS in catalysis, from model systems like single-crystal surfaces to practical nanocatalysts, liquid-solid interfaces to gas-solid interfaces, and electrocatalysis to heterogeneous catalysis to photocatalysis. Thus, we believe this Account would attract increasing attention to SERS in catalysis and opens new avenues for catalytic studies.

12.
J Org Chem ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031379

RESUMO

Two highly rearranged daphniphyllum alkaloids, daphnillonins A (1) and B (2), were isolated from Daphniphyllum longeracemosum and structurally characterized by a combination of diverse methods, including the calculation of electronic circular dichroism (ECD). Compound 1 possesses an unprecedented carbon architecture with a very unique 8-methyl-6-azabicyclo[3.2.1]octane moiety, and compound 2 represents a new carbon skeleton with an uncommon 7/6/5/7/5/5-fused ring system. The biosynthetic pathways for the two alkaloids were proposed with the concurrent major alkaloids as the precursors.

13.
PLoS One ; 15(2): e0228223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32032386

RESUMO

To better understand the agricultural resources and environmental problems of the provinces along The Belt and Road in China, it is critical to investigate their agricultural carbon emission efficiency and evolutionary trends. Based on the panel data of 18 key provinces and cities between 2006 and 2015, this paper evaluated the agricultural carbon emission efficiency with the data envelopment analysis-Malmquist model and further explored their dynamic evolutionary trends. There were several main findings. First, the efficiency levels of agricultural carbon emissions showed significant regional differentiation among the areas, with that along the 21st-Century Maritime Silk Road being much higher than that along the Silk Road Economic Belt. Second, technical efficiency was the key factor that restricted the improvement of the comprehensive efficiency of agricultural carbon. Third, most provinces invested in too many redundant and unreasonably allocated resources, showing a trend of diminishing returns to scale. Last, According to dynamic evolution analysis, the total productivity still demonstrated a diminishing trend. This paper provides some suggestions for effectively improve the efficiency of agricultural carbon emissions in China, such as optimize the agricultural industrial structure, increasing the investment of carbon emission reduction technology, and implementing a carbon emission quota clearing system. This paper contributes to the improvement of the environment in China.

14.
Adv Mater ; : e1902964, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32026507

RESUMO

Various kinds of amorphous materials, such as transition metal dichalcogenides, metal oxides, and metal phosphates, have demonstrated superior electrocatalytic performance compared with their crystalline counterparts. Compared to other materials for electrocatalysis, noble metals exhibit intrinsically high activity and excellent durability. However, it is still very challenging to prepare amorphous noble-metal nanomaterials due to the strong interatomic metallic bonding. Herein, the discovery of a unique thiol molecule is reported, namely bismuthiol I, which can induce the transformation of Pd nanomaterials from face-centered-cubic (fcc) phase into amorphous phase without destroying their integrity. This ligand-induced amorphization is realized by post-synthetic ligand exchange under ambient conditions, and is applicable to fcc Pd nanomaterials with different capping ligands. Importantly, the obtained amorphous Pd nanoparticles exhibit remarkably enhanced activity and excellent stability toward electrocatalytic hydrogen evolution in acidic solution. This work provides a facile and effective method for preparing amorphous Pd nanomaterials, and demonstrates their promising electrocatalytic application.

15.
J Appl Microbiol ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027450

RESUMO

AIM: To screen a Lactic acid bacteria (LAB) strain for good adaption in alfalfa ensiling and to evaluate its effects on alfalfa ensiling. METHODS AND RESULTS: Lactobacillus plantarum (LP) strain ZZU203 was selected due to its superior ability to acidify structural carbohydrate metabolite and alfalfa powder. Alfalfa was ensiled with LP FG1 (from a commercial inoculant), LP ZZU203, or a no-additive control (CK) for 60 d. The two silages with LP additives significantly (P < 0.05) increased lactic acid (LA) and acetic acid (AA) concentrations compared to CK silage. The pH, ammonia nitrogen (NH3 -N), and cellulose concentrations, and the numbers of bacilli, coliform, aerobic bacteria, and Clostridium decreased significantly (P < 0.05). The dry matter, LA, AA, and water-soluble carbohydrate concentrations of ZZU203 silage were significantly (P < 0.05) higher, whereas the NH3 -N and the neutral detergent fiber (NDF) concentrations, and the aerobic bacterial and Clostridium counts were significantly (P < 0.05) lower than in FG1 silage. CONCLUSION: ZZU203 obtained by the screening method of this study can improve the quality of alfalfa silage. SIGNIFICANCE AND IMPACT OF THE STUDY: The screening method designed for alfalfa silage conditions can effectively screen out LAB with potential application value in alfalfa silage.

16.
Molecules ; 25(3)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32046013

RESUMO

Histone deacetylases (HDACs) have been proved to be promising targets for the treatment of cancer, and five histone deacetylase inhibitors (HDACis) have been approved on the market for the treatment of different lymphomas. In our previous work, we designed a series of novel coumarin-containing hydroxamate HDACis, among which compounds 6 and 7 displayed promising activities against tumor growth. Based on a molecular docking study, we further developed 26 additional analogues with the aim to improve activity of designed compounds. Several of these new derivatives not only showed excellent HDAC1 inhibitory effects, but also displayed significant growth inhibitory activities against four human cancer cell lines. Representative compounds, 13a and 13c, showed potent anti-proliferative activities against solid tumor cell lines with IC50 values of 0.36-2.91 M and low cytotoxicity against Beas-2B and L-02 normal cells. Immunoblot analysis revealed that 13a and 13c dose-dependently increased the acetylation of histone H3 and H4. Importantly, the two compounds displayed much better anti-metastatic effects than SAHA against the MDA-MB-231 cell line. Moreover, 13a and 13c arrested MDA-MB-231 cells at G2/M phase and induced MDA-MB-231 cell apoptosis. Finally, the molecular docking study rationalized the high potency of compound 13c.

17.
Reprod Sci ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-32046443

RESUMO

Embryo implantation is a complex process which involves biochemical and physiological interactions between an implantation-competent blastocyst and a receptive uterus. However, the exact biochemical changes of uterine fluid, uterus, and plasma during peri-implantation remain unclear. This study aims to characterize the biochemical and metabolic changes that occur during the peri-implantation period of early pregnancy, using mice as an animal model. Gas chromatography-mass spectrometry was used to analyze the metabolite profiles of the uterus, uterine fluid, and maternal plasma at pre-implantation and implantation. The multivariate analyses, ANOVA and Tukey's HSD test, were applied to detect significant changes in metabolites and metabolic pathways. The metabolic networks were reconstructed in silico based on the identified metabolites and KEGG metabolic framework. Between pre-implantation day 1 and day 4, dramatic metabolic changes were observed in the uterine fluid that could be important for blastocyst development and protection against the harsh uterine environment. Palmitoleic acid, fumaric acid, and glutaric acid changed levels at day 4 in the uterus, suggesting that they may be associated with endometrial receptivity. Both the uterus and maternal plasma showed profound changes in cellular metabolism at the early implantation period, including upregulation of branched-chain amino acids and intermediates of one-carbon metabolism, an upregulation of glyoxylate and dicarboxylate metabolism, and downregulation of aerobic respiration; all of which could be involved in the regulation of the maternal-fetal interface, alternative nutrient utilization, and energy preservation for implantation as well as later placentation and fetal development to ensure successful embryo implantation.

18.
J Thorac Oncol ; 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32018053

RESUMO

Small cell lung cancer patient outcomes have not yet been significantly impacted by the revolution in precision oncology, primarily due to a paucity of genetic alterations in actionable driver oncogenes. Nevertheless, systemic therapies that include immunotherapy are beginning to show promise in the clinic. While these results are encouraging, many patients do not respond to or rapidly recur after current regimens, necessitating alternative or complementary therapeutic strategies. In this review, we discuss ongoing investigations into the pathobiology of this recalcitrant cancer and the therapeutic vulnerabilities that are exposed by the disease state. Included within this discussion is a snapshot of the current biomarker and clinical trial landscapes for small cell lung cancer. Finally, we identify key knowledge gaps that should be addressed in order to advance the field in pursuit of reduced small cell lung cancer mortality. This review largely summarizes work presented at the Third Biennial IASLC Small Cell Lung Cancer Meeting.

19.
Mil Med Res ; 7(1): 4, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029004

RESUMO

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

20.
FASEB J ; 34(1): 807-821, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914636

RESUMO

Kv4 pore-forming subunits co-assemble with ß-subunits including KChIP2 and DPP6 and the resultant complexes conduct cardiac transient outward K+ current (Ito). Compound NS5806 has been shown to potentate Ito in canine cardiomyocytes; however, its effects on Ito in other species yet to be determined. We found that NS5806 inhibited native Ito in a concentration-dependent manner (0.1~30 µM) in both mouse ventricular cardiomyocytes and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), but potentiated Ito in the canine cardiomyocytes. In HEK293 cells co-transfected with cloned Kv4.3 (or Kv4.2) and ß-subunit KChIP2, NS5806 significantly increased the peak current amplitude and slowed the inactivation. In contrast, NS5806 suppressed the current and accelerated inactivation of the channels when cells were co-transfected with Kv4.3 (or Kv4.2), KChIP2 and another ß-subunit, DPP6-L (long isoform). Western blot analysis showed that DPP6-L was dominantly expressed in both mouse ventricular myocardium and hiPSC-CMs, while it was almost undetectable in canine ventricular myocardium. In addition, low level of DPP6-S expression was found in canine heart, whereas levels of KChIP2 expression were comparable among all three species. siRNA knockdown of DPP6 antagonized the Ito inhibition by NS5806 in hiPSC-CMs. Molecular docking simulation suggested that DPP6-L may associate with KChIP2 subunits. Mutations of putative KChIP2-interacting residues of DPP6-L reversed the inhibitory effect of NS5806 into potentiation of the current. We conclude that a pharmacological modulator can elicit opposite regulatory effects on Kv4 channel complex among different species, depending on the presence of distinct ß-subunits. These findings provide novel insight into the molecular design and regulation of cardiac Ito. Since Ito is a potential therapeutic target for treatment of multiple cardiovascular diseases, our data will facilitate the development of new therapeutic Ito modulators.

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