Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.799
Filtrar
1.
Adv Mater ; : e1906015, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027058

RESUMO

Developing low-cost, highly efficient, and durable electrocatalysts for oxygen evolution reaction (OER) is essential for the practical application of electrochemical water splitting. Herein, it is discovered that organic small molecule (hexabromobenzene, HBB) can activate commercial transition metal (Ni, Fe, and NiFe) foam by directly evolving metal nanomeshes embedded in graphene-like films (M-NM@G) through a facile Br-induced solid-phase migration process. Systematic investigations indicate that HBB can conformally generate graphene-like network on bulk metal foam substrate via the cleavage of CBr bonds and the formation of CC linkage. Simultaneously, the cleaved CBr fragments can efficiently extract metal atoms from bulk substrate, in situ producing transition metal nanomeshes embedded in the graphene-like films. As a result, such functional nanostructure can serve as an efficient OER electrocatalyst with a low overpotential and excellent long-term stability. Specifically, the overpotential at 100 mA cm-2 is only 208 mV for NiFe-NM@G, ranking the top-tier OER electrocatalysts. This work demonstrates an intriguing general strategy for directly transforming bulk transition metals into nanostructured functional electrocatalysts via the interaction with organic small molecules, opening up opportunities for bridging the application of organic small molecules in energy technologies.

2.
Clin Cancer Res ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071116

RESUMO

The unprecedented benefits of immunotherapy in advanced malignancies have resulted in increased interests in exploiting immune stimulatory agents in earlier stage solid tumors in the neoadjuvant setting. However, systemic delivery of immunotherapies may cause severe immune-related side-effects and hamper the development of combination treatments. Intratumoral delivery of neoadjuvant immunotherapy provides a promising strategy in harnessing the power of immunotherapy while minimizing off-target toxicities. The direct injection of immune stimulating agents into the tumor primes the local tumor-specific immunity to generate a systemic, durable clinical response. Intratumoral immunotherapy is a highly active area of investigation resulting in a plethora of agents, e.g. immune receptor agonists, non-oncolytic and oncolytic viral therapies, being tested in preclinical and clinical settings. Currently, more than 20 neoadjuvant clinical trials exploring distinct intratumoral immune stimulatory agents and their combinations are ongoing. Practical considerations including appropriate timing and optimal local delivery of immune stimulatory agents play an important role in safety and efficacy of this approach. Here we discuss promising approaches in drug delivery technologies and opportunity for combining intratumoral immunotherapy with other cancer treatments and summarize the recent preclinical and clinical evidences that highlighted its promise as a part of routine oncologic care.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32077347

RESUMO

OBJECTIVE: This study was performed to evaluate the efficacy and safety of parecoxib for early postoperative cognitive dysfunction (POCD) in elderly patients. METHODS: Comprehensive literature search based on six electronic databases was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane's Tool was applied to evaluate the methodological quality of included studies. RevMan 5.3 was used to perform meta-analysis. RESULTS: 8 RCTs comprising a total of 1106 subjects that prepared for orthopedic surgical operation were selected. All the identified RCTs were conducted in China. The methodological qualities of included studies were judged to be medium to high. The integrated data showed that perioperative intravenous parecoxib could remarkably reduce the incidence of POCD with improved MMSE score. Parecoxib could significantly reduce the concentrations of IL-6 but results regarding the changes in TNF-α, CRP, and S100ß levels remained inconsistent. CONCLUSION: Perioperative parecoxib administration is effective in reducing the incidence of POCD and improving MMSE score compared with control. However, the beneficial effect of parecoxib has been tested only in Chinese population. Future RCTs in western countries with larger-scale and more comprehensive neurological tests are needed.

4.
Gene ; 736: 144417, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32006593

RESUMO

Sphingosine 1-phosphate receptor 1 (S1PR1) plays a pivotal role in mediating trafficking and migration of immune cells. Previous reports also identify S1PR1 as an important susceptibility gene of asthma and other autoimmune disorders. However, little has been known about the regulatory mechanism of S1PR1 expression. Thus we systematically investigated the transcriptional regulation of S1PR1 in this study. Promoter activity of S1PR1 gene was carefully screened using series of pGL3-Basic reporter vectors, containing full length (range from transcription start site to upstream -1 kb region) or several truncated fragments of S1PR1 promoter. We identified an area (from -29 to -12 bp) of the S1PR1 promoter as the minimal promoter region. Bioinformatics prediction results showed that several transcription factors were recruited to these sites. EMSA and ChIP assays demonstrated the transcriptional factor STAT1 could bind to the region. We also found that the level of S1PR1 level was significantly reduced when STAT1 was knocked-down. Consistent with the reduction of S1PR1 caused by depletion of STAT1, overexpression of STAT1 resulted in up-regulation of S1PR1. In addition, both mRNA and protein levels of S1PR1 were increased when STAT1 was activated by IFN-γ, and decreased when STAT1 was inhibited by fludarabine. Besides, the levels of STAT1 and S1PR1 expression were positively correlated in peripheral blood leukocytes derived from 41 healthy individuals. Our study showed that transcription factor STAT1 could bind to upstream region of -29 bp to -12 bp of the S1PR1 promoter and stimulate the expression of S1PR1.

5.
Chemosphere ; 250: 126128, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32088613

RESUMO

This work aimed to quantify the contribution of electrocoagulation(EC) mechanisms on emulsified oil removal from polymer-flooding sewage (PFS), and also to quantitatively compare the performance of EC, anode-electrocoagulation(AEC) and chemical coagulation(CC) on PFS treatment. An apparatus which introduced the salt bridge was proposed to help separate the anode and cathode. To quantify the contribution of coagulation and oxidation individually, the EDTA, a chemical addictive which can inhibit the ability of Al3+ was added to shield the effect of coagulation. The experimental results show that in the PFS treatment by EC method, about 80% of emulsified oil in anode zone was removed by coagulation while only 11%-13% was oxidized; In cathode zone, about 13%-14% of the oil was removed by flotation. Besides, the results suggest that the separation of anode and cathode not only result in the low demulsification efficiency but also generated the fragile flocs. During the comparison and contrast of purification performance of EC, AEC and CC, the effects of treatment time and current densities(aluminum doses) on oil removal was investigated, the pH and absorption spectra evolution over time were also analyzed. The results showed that under all conditions studied, the EC performance outperforms AEC and far beyond CC.

6.
Oxid Med Cell Longev ; 2020: 7912763, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089779

RESUMO

Acute kidney injury (AKI) is a common clinical problem, characterized by a sudden loss of renal function, a high risk of death, and the eventual development of renal fibrosis and renal failure. Cordyceps cicadae is a traditional Chinese medicine with the potential function of kidney protection. We analyze two sputum extracts, a water extract (WCC), and an ethanol extract (ECC), to assess the potential of treating AKI in an animal model of kidney injury induced by cisplatin. A nephrotoxic mouse model was first established by intraperitoneal injection of cisplatin. Subsequently, WCC and ECC were orally administered in these mice. The results show that WCC and ECC significantly alleviated cisplatin-induced AKI renal histological changes, serum creatinine (CRE) and blood urea nitrogen (BUN) production, and the levels of NO, TNF-α, IL-1ß, and IL-6. The levels of malondialdehyde (MDA) and glutathione (GSH) were suppressed by administration of WCC and ECC. However, WCC treatment prevented these changes significantly better than ECC treatment. In addition, Western blot data showed that WCC attenuated the cisplatin-induced protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), as well as inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in the kidney tissues. Furthermore, WCC greatly inhibited the expression of Toll-like receptor 4 (TLR4) and cisplatin-induced NF-κB activation, as well as dramatically increasing the production of antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1)), silent information regulator T1 (Sirt1), and p-AMP-activated protein kinase (AMPK) in the kidney tissues. In addition, we found that WCC increased the expression levels of the autophagy-related proteins LC3B and Beclin-1; proapoptotic proteins, including cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) 1; and organic anion transporters 1 (OAT1) and 3 (OAT3) in the kidney tissues. Finally, WCC, ECC, and two bioactive compounds-adenosine and N6-(2-hydroxyethyl) adenosine (HEA)-inhibited the production of nitrite oxide (NO) and intracellular reactive oxygen species (ROS) triggered by lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophages in vitro. Collectively, WCC could provide a potential therapeutic candidate for the prevention of cisplatin-induced kidney injury through the inhibition of oxidative stress and inflammation.

7.
Structure ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32049031

RESUMO

Members of the family Reoviridae package several copies of the viral polymerase complex into their capsid to carry out replication and transcription within viral particles. Classical single-particle reconstruction encounters difficulties resolving structures such as the intraparticle polymerase complex because refinement can converge to an incorrect map and because the map could depict a nonrepresentative subset of particles or an average of heterogeneous particles. Using the nine-segmented Fako virus, we tested hypotheses for the arrangement and number of polymerase complexes within the virion by measuring how well each hypothesis describes the set of cryoelectron microscopy images of individual viral particles. We find that the polymerase complex in Fako virus binds at ten possible sites despite having only nine genome segments. A single asymmetric configuration describes the arrangement of these complexes in both virions and genome-free capsids. Similarities between the arrangements of Reoviridae with 9, 10, and 11 segments indicate the generalizability of this architecture.

8.
Anal Chem ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32066231

RESUMO

Liver fibrosis is a major stage in the development of liver diseases and it is important to investigate its pathogenesis for early intervene or even reversing. Recent studies have found that intestinal disease can aggravate liver fibrosis through the role of the "gut-liver axis". Hypoxia is considered to be a typical characteristic of many diseases including ulcerative colitis and liver fibrosis. However, there is no fluorescent probe for hypoxia detection to investigate "gut-liver axis". Herein, we design and synthesize a turn-on fluorescent probe termed Cy-AP, which displays high sensitivity and selectivity to hypoxia given by sodium dithionite (Na2S2O4) in vitro with near-infrared (NIR) emission (735 nm). And the possible response mechanism of Cy-AP towards hypoxia is given and proved by HPLC, MS and theory calculation. Moreover, on the basis of low cell cytotoxicity, the probe is successfully applied in visualizing hypoxia in four cell lines (HepG2, HCT116, HeLa and MCF-7 cells) by fluorescence imaging, flow cytometry and 3D imaging. Furthermore, due to its NIR emission, Cy-AP can monitor the hypoxia condition in vivo such as liver fibrosis mice and ulcerative colitis mice model. In particular, the probe can validate the existence and mechanism of "gut-liver axis" in vivo by monitoring hypoxia. To the best of our knowledge, this is the first report to describe a strategy for study "gut-liver axis" by a NIR hypoxia-sensitive fluorescent probe, which will provide some powerful support for delaying the progression of liver fibrosis and thus promoting the treatment of liver disease.

9.
Int J Mol Sci ; 21(4)2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32075272

RESUMO

Non-invasively monitoring allogeneic graft rejection with a specific marker is of great importance for prognosis of patients. Recently, data revealed that IL-27Rα was up-regulated in alloreactive CD4+ T cells and participated in inflammatory diseases. Here, we evaluated whether IL-27Rα could be used in monitoring allogeneic graft rejection both in vitro and in vivo. Allogeneic (C57BL/6 donor to BALB/c recipient) and syngeneic (BALB/c both as donor and recipient) skin grafted mouse models were established. The expression of IL-27Rα in grafts was detected. The radio-probe, 125I-anti-IL-27Rα mAb, was prepared. Dynamic whole-body phosphor-autoradiography, ex vivo biodistribution and immunofluorescence staining were performed. The results showed that the highest expression of IL-27Rα was detected in allogeneic grafts on day 10 post transplantation (top period of allorejection). 125I-anti-IL-27Rα mAb was successfully prepared with higher specificity and affinity. Whole-body phosphor-autoradiography showed higher radioactivity accumulation in allogeneic grafts than syngeneic grafts on day 10. The uptake of 125I-anti-IL-27Rα mAb in allogeneic grafts could be almost totally blocked by pre-injection with excess unlabeled anti-IL-27Rα mAb. Interestingly, we found that 125I-anti-IL-27Rα mAb accumulated in allogeneic grafts, along with weaker inflammation earlier on day 6. The high uptake of 125I-anti-IL-27Rα mAb was correlated with the higher infiltrated IL-27Rα positive cells (CD3+/CD68+) in allogeneic grafts. In conclusion, IL-27Rα may be a novel molecular imaging marker to predict allorejection.

10.
Chem Commun (Camb) ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31998888

RESUMO

It is unprecedentedly found that ethylamine hydrochloride (EaCl) and phenol (PhOH) can form a new type of deep eutectic solvent (DES) with quite low viscosity. The strong hydrogen-bond donating abilities of EaCl and PhOH provide two active sites for robust interaction with NH3. Thus, the capacities of EaCl + PhOH DESs for NH3 absorption are notably high even at low pressures.

11.
J Biomed Nanotechnol ; 16(1): 125-135, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31996291

RESUMO

Theranostic nanosystems encompassing imaging reagents and therapeutic genes are promising for concurrent tumor diagnosis and gene therapy. In this work, we developed bioresponsive gadolinium (Gd)-based nanopolyplexes (denoted as Gdplexes) for in vivo tumor theranostic applications. Gdplexes were generated by a hierarchical assembly method involving the neutralization of DNA with a Gd-chelated bioreducible cationic polyurethane (termed as GdCPUA), which was followed by condensation of DNA with a cationic dextran conjugate (DP800). By adjusting GdCPUA/DP800 ratios, the resultant Gdplexes had GdCPUA/DNA complex as an inner core and a dextran outer shell; thus, Gdplexes exhibit an improved colloidal stability under physiological conditions and perform active gene release in an intracellular reductive environment. In vitro tests against cancer cells revealed that optimized Gdplexes afforded comparable transfection efficiency to that of the 25 kDa branched polyethylenimine used as a positive control. Additionally, the Gdplexes could robustly transfer small hairpin RNA plasmids to silence vascular endothelial growth factor expression in SKOV-3 cells. In vivo, the Gdplexes loaded with plasmid were practical for systemic gene delivery via intravenous administration, yielding marked growth repression of an SKOV-3 tumor xenograft in a BALB/c nude mouse model. The tumor could be visualized by T1-weighted magnetic resonance (MR) imaging. Such efficient gene therapy had no adverse effects on hepatorenal functions and weight gain in the mouse. This work highlights Gdplexes as biosafe and robust nanocarriers for tumor theranostic applications in vivo.


Assuntos
Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Terapia Genética , Imagem por Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Fator A de Crescimento do Endotélio Vascular
12.
ACS Nano ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31939662

RESUMO

Radiotherapy remains a major treatment modality for cancer types such as non-small cell lung carcinoma (or NSCLC). To enhance treatment efficacy at a given radiation dose, radiosensitizers are often used during radiotherapy. Herein, we report a nanoparticle agent that can selectively sensitize cancer cells to radiotherapy. Specifically, we nitrosylated maytansinoid DM1 and then loaded the resulting prodrug, DM1-NO, onto poly(lactide-co-glycolic)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles. The toxicity of DM1 is suppressed by nanoparticle encapsulation and nitrosylation, allowing the drug to be delivered to tumors through the enhanced permeability and retention effect. Under irradiation to tumors, the oxidative stress is elevated, leading to the cleavage of the S-N bond and the release of DM1 and nitric oxide (NO). DM1 inhibits microtubule polymerization and enriches cells at the G2/M phase, which is more radiosensitive. NO under irradiation forms highly toxic radicals such as peroxynitrites, which also contribute to tumor suppression. The two components work synergistically to enhance radiotherapy outcomes, which was confirmed in vitro by clonogenic assays and in vivo with H1299 tumor-bearing mice. Our studies suggest the great promise of DM1-NO PLGA nanoparticles in enhancing radiotherapy against NSCLC and potentially other tumor types.

13.
Molecules ; 25(2)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963527

RESUMO

Aromatic heterocycles are ubiquitous building blocks in bioactive natural products, pharmaceutical and agrochemical industries. Accordingly, the carborane-fused heterocycles would be potential candidates in drug discovery, nanomaterials, metallacarboranes, as well as photoluminescent materials. In recent years, the transition metal catalyzed B-H activation has been proved to be an effective protocol for selective functionalization of B-H bond of o-carboranes, which has been further extended for the synthesis of polyhedral borane cluster-fused heterocycles via cascade B-H functionalization/annulation process. This article summarizes the recent progress in construction of polyhedral borane cluster-fused heterocycles via B-H activation.

14.
Oncol Rep ; 43(2): 562-570, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894335

RESUMO

Psoriasin, otherwise known as S100A7, is a member of the S100 protein family. With the key function of binding calcium, it is able to regulate a range of cellular functions. Altered Psoriasin expression is associated with poor clinical outcomes in several solid cancers. The present study aimed to examine the implication of Psoriasin in bladder cancer (BC). Expression of Psoriasin was examined in BC cell lines using PCR. Immunohistochemical (IHC) staining of Psoriasin was performed on a bladder disease spectrum tissue array. Plasmids were constructed to effectively knockdown and overexpress Psoriasin in BC cells and further utilized for in vitro BC cellular function assays. Association between Psoriasin expression and survival of patients with BC was evaluated using Kaplan­Meier survival analysis. Psoriasin was revealed to be expressed by both bladder epithelia and cancer cells as determined by IHC. Increased expression of Psoriasin was significantly correlated with a poor overall BC patient survival. Overexpression of Psoriasin in the EJ138 cell line increased cellular proliferation, adhesion and invasion, whereas knockdown exhibited the opposite effect on cellular functions in RT112 cells. Matrix metalloprotease (MMP)9 appeared to be the most affected of the three MMPs examined in these two BC cell lines. The analysis revealed a positive correlation in BC tumours between Psoriasin and MMP9. Overall, high Psoriasin expression was correlated with poor overall survival in BC patients and promoted invasiveness of BC cells via upregulation of MMPs. Psoriasin possesses certain prognostic and therapeutic potential in BC which requires further exploration.

15.
Oncogene ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996785

RESUMO

Aurora B is a serine/threonine kinase that has been implicated in regulating cell proliferation in distinct cancers, including breast cancer. Here we show that Aurora B expression is elevated in basal-like breast cancer (BLBC) compared with other breast cancer subtypes. This high level of expression seems to correlate with poor metastasis-free survival and relapse-free survival in affected patients. Mechanistically, we show that elevated Aurora B expression in breast cancer cells activates AKT/GSK3ß to stabilize Snail1 protein, a master regulator of epithelial-mesenchymal transition (EMT), leading to EMT induction in a kinase-dependent manner. Conversely, Aurora B knock down by short-hairpin RNAs (shRNAs) suppresses AKT/GSK3ß/Snail1 signaling, reverses EMT and reduces breast cancer metastatic potential in vitro and in vivo. Finally, we identified a specific OCT4 phosphorylation site (T343) responsible for mediating Aurora B-induced AKT/GSK3ß/Snail1 signaling and EMT that could be attenuated by Aurora B kinase inhibitor treatment. These findings support that Aurora B induces EMT to promote breast cancer metastasis via OCT4/AKT/GSK3ß/Snail1 signaling. Pharmacologic Aurora B inhibition might be a potential effective treatment for breast cancer patients with metastatic disease.

16.
J Affect Disord ; 265: 63-70, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31957693

RESUMO

OBJECTIVES: This is a meta-analysis of randomized double-blind controlled-placebo trials (RCTs) examining the effectiveness, tolerability, and safety of intranasal esketamine in treating major depressive disorder (MDD). METHODS: Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were calculated using RevMan version 5.3. RESULTS: Four RCTs with 7 active arms covering 708 patients with MDD on intranasal esketamine (n = 419) and placebo (n = 289) were included. Compared with placebo, adjunctive intranasal esketamine was associated with significantly greater study-defined response (RR=1.39, 95%CI: 1.18 to 1.64, P<0.0001) and remission (RR=1.42, 95%CI: 1.17 to 1.72, P = 0.0004) at endpoint assessment. Intranasal esketamine had greater study-defined response starting at 2 h (RR= 2.77, 95%CI: 1.62 to 4.76, P = 0.0002), peaking at 24 h (RR=5.42, 95%CI: 1.38 to 21.20, P = 0.02), and at least lasting for 28 days (RR=1.36, 95%CI: 1.16 to 1.58, P = 0.0001). Similarly, intranasal esketamine had significantly greater study-defined remission starting at 2 h (RR=7.71, 95%CI: 2.16 to 27.55, P = 0.002), peaking at 24 h (RR=6.87, 95%CI: 1.55 to 30.35, P = 0.01), and lasting for 28 days (RR=1.38, 95%CI: 1.11 to 1.72, P = 0.004). Intranasal esketamine had a significantly higher rate of discontinuation due to intolerability (RR=3.50, 95%CI: 1.38 to 8.86, P = 0.008). Discontinuation due to any reasons and inefficacy were similar between the two groups. CONCLUSION: Intranasal esketamine appears to have an ultra-rapid antidepressant effect for MDD, at least lasting for 28 days. The long-term therapeutic effect and safety of intranasal esketamine need to be further examined in large-scale RCTs.

17.
Inflammation ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907686

RESUMO

Disordered glucose and lipid metabolism contributes to the progression of several liver diseases, while the upregulation of phosphatase and tensin homology deleted on chromosome ten (PTEN), a well-known tumour suppressor gene, can improve the condition through metabolic programming. This study first characterized the metabolic profiles and the involvement of PTEN in the hepatic fibrosis induced by Schistosoma japonicum (S. japonicum) to provide a novel clue for metabolism-targeted treatment. Compared with control mice, infected mice showed infiltrated immune cells in their livers, increased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased glucose levels in their sera. The expression of key enzymes in the glycolytic pathway was significantly increased, and the expression of gluconeogenic genes was distinctly decreased. Moreover, the infection upregulated the hepatic expression of enzymes involved in fatty acid oxidation, which was consistent with the decreased number of lipid droplets in livers and the lowered levels of triglyceride in sera. Consistently, PTEN and its downstream signalling were significantly inhibited. In vitro, soluble egg antigen (SEA) downregulated the expression of PTEN in both the macrophage RAW264.7 cell line and the murine hepatocellular carcinoma HEP1-6 cell line, and induced a metabolic phenotype similar to the in vivo results. Overall, this study showed that S. japonicum infection induced the reprogramming of glucose and lipid metabolism in mice during the period of liver fibrosis and that SEA could act as a modulator to trigger such a metabolic switch in macrophages and hepatocytes. PTEN might play an essential role in mediating these metabolic reprogramming events.

18.
PLoS One ; 15(1): e0227787, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31986175

RESUMO

Prefabricated construction (PC) has attracted wide spread attention as a model of sustainable development for the construction industry of the future. Although the PC has many advantages, it is still at an initial stage in China. Based on the current conditions in China, this study focuses on the interrelationships of factors affecting PC promotion. Firstly, through a comprehensive review of relevant literatures and expert recommendations, 5 factors were identified: policy factor, technical factor, management factor, market factor and cost factor. Next, the data were collected through a questionnaire survey, and the questionnaire data were processed using SPSS 24.0 and AMOS 22.0. The overall relationships of each factor were quantitatively analyzed with Structural Equation Modeling (SEM). The results show that the policy factor plays a dominant role, while the management factor and market factors are also significant. This study also provides decision makers with relevant information about the factors involved, which will be helpful in devising appropriate strategies for the wider adoption of PC.

19.
Bioorg Med Chem ; 28(5): 115299, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31980361

RESUMO

Mitochondrial complex II and complex III are two promising targets for the development of numerous pharmaceuticals and pesticides. Although tremendous inhibitors of either complex II or complex III were identified, compounds which are capable of prohibiting the activities of both complexes have been rarely reported. Since multi-target drugs can interact with several drug targets simultaneously, we were keen on discovering new and potent dual-target inhibitors of both complex II and complex III. Therefore, a new series of structurally simplified sulfonamides bearing a diaryl ether scaffold were designed and synthesized in this paper. Afterwards, the biological activities of the newly synthesized compounds were evaluated. The results implied that several compounds demonstrated outstanding potency against succinate-cytochrome c reductase (SCR, a mixture of complex II and complex III). Further studies confirmed that N-(3,5-Dichloro-4-(2,4,6-trichlorophenoxy)phenyl)benzenesulfonamide (3f), a representative compound herein, was identified as a dual-target inhibitor of both complexes. Furthermore, computational simulations were also performed to have a better understanding about binding of 3f to the enzyme complexes, which concluded that 3f should bind to complex II and the Qo site of complex III. Consequently, we harbor the idea that this work can be beneficial for the synthesis and discovery of more dual- or multi-target inhibitors.

20.
Medicine (Baltimore) ; 99(4): e18584, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977849

RESUMO

To evaluate epidemiology and risk factors of severe adenovirus respiratory infection in hospitalized children in Guangzhou, China.A retrospective review study was conducted, and 542 children hospitalized for adenovirus respiratory infection, were included from January 2011 to December 2014. Patients were younger than 14 years. Disease severity was classified into severe and mild. Laboratory tests and clinical characteristics were analyzed for risk factors of adenovirus respiratory infection by multivariable logistic regression.Among these 542 children, 92.1% were aged < 6 years. Clinical diagnoses were upper respiratory infections in 11.6%, bronchiolitis in 16%, and mild pneumonia in 62.0% of children. Severe pneumonia rate was 10.3% (56/542) with a mortality rate of 0.9% (5/542). The cohort comprised 542 patients; 486 patients with mild adenovirus respiratory infection and 56 patients with severe adenovirus respiratory infection. Multivariable logistic regression was used to confirm associations between variables and adenovirus respiratory infection, after age and gender adjustment. Hospital stay, still significantly associated with adenovirus respiratory infection. Patients with longer hospital stay (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.13-1.28, P < .001), lower LYMPH (OR = 0.73 95% CI: 0.55-0.99, P = .039), and increased LDH (OR = 1.002, 95% CI: 1.001-1.003, P =  .001) had a higher risk of severe adenovirus respiratory infection.Adenovirus is a major pathogen in hospitalized children with respiratory infection. High serum LDH level and low lymphocyte count could be used as predictors of adenovirus respiratory infection severity in children.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Criança Hospitalizada/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Infecções por Adenovirus Humanos/mortalidade , Adolescente , Fatores Etários , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Tempo de Internação , Modelos Logísticos , Masculino , Pneumonia/epidemiologia , Infecções Respiratórias/mortalidade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA