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1.
J Phys Condens Matter ; 32(8): 08LT01, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31675733

RESUMO

Due to losing out-of-surface symmetry and the induced built-in dipole, two-dimensional (2D) Janus structures were believed to have various potential applications in the fields of piezoelectric devices, photocatalysis and electrochemical catalysis. In this work, 2D gallium oxides and chalcogenides (GaX) derived Janus monolayers Ga2XY (X/Y = O, S, Se, and Te) were designed. Our first-principles calculations showed that apart from Ga2OTe, all the monolayers are thermodynamically, dynamically and mechanically stable. These monolayers are demonstrated to be semiconductors with the band gaps in a wide range of 1.00-3.24 eV. The calculated in-plane piezoelectric coefficients of Janus monolayers (d 11 = 3.09-5.67 pm V-1) are demonstrably enhanced with respect to the pristine monolayers (d 11 = 0.41-3.04 pm V-1). Meanwhile, the yielding additional out-of-plane piezoelectric coefficients range from 0.11 to 0.34 pm V-1. Interestingly, O-participated Janus monolayers display distinctive properties: dipole direction flipping from O to S/Se, high stabilities and moderate direct-band-gaps. Particularly, Ga2OSe monolayer was found to have the largest piezoelectric coefficient of 5.67 pm V-1, which can be ascribed to the highly imbalanced charge distribution on O and Se as well as the largest bond length differences between Ga-O and Ga-Se. Our study revealed that the Janus Ga2XY monolayers, especially O-related systems, could be pretty promising as candidates in optoelectronic, piezoelectric sensors and energy conversion devices.

5.
Am J Mens Health ; 13(5): 1557988319880764, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31672076

RESUMO

Previous studies have reported the clinical efficacy of avanafil for erectile dysfunction (ED), but these findings are controversial. This study aims to investigate the safety and efficacy of avanafil for ED. EMBASE, PubMed, and Cochrane Library were searched extensively to obtain eligible studies. Clinical outcomes including successful vaginal penetration (SVP), successful intercourse (SI), International Index of Erectile Function-Erectile Function domain (IIEF-EF) score and treatment adverse events (TAEs) were compared using RevMan v.5.3. Eight RCTs involving 3,709 patients were included. The analysis demonstrated that compared with placebo, the SVP (RR = 3.20, 95% CI [2.60, 3.95], p < .001), SI (RR = 2.53, 95% CI [2.19, 2.92], p < .001), change in IIEF-EF score (MD = 4.57, 95% CI [3.68, 5.46], p < .001) and TAEs (RR = 1.78, 95% CI [1.38, 2.31], p < .0001) were significantly higher in the avanafil. In addition, avanafil 200 mg were higher than avanafil 100 mg in SI (RR = 0.86, 95% CI [0.75, 0.99], p = .03) and change in IIEF-EF score (MD = -1.34, 95% CI [-1.67, -1.01], p < .001), but there were no obvious differences in SVP (RR = 0.89; 95% CI [0.74, 1.08], p = .23) and TAEs (RR = 0.97, 95% CI [0.83, 1.14], p = .74) between the two doses. The present evidence suggests that avanafil (especially 200 mg) has the potential to be the drug of choice for ED, but more strict and larger sample size RCTs are need to validate the findings.

6.
Biomater Sci ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31761913

RESUMO

Three SAP (self-assembling peptide)-tagged fluorinases (FLAs), namely, FLA-ELK16, FLA-L6KD and FLA-18A (named after the SAP used for tagging FLA) were successfully engineered. All three SAP-tagged FLAs could be highly over-expressed using engineered E. coli host cells despite being in the form of aggregates (inclusion bodies). It was noted that all three SAP-tagged FLAs exhibited enzymatic activity. It was also observed that all three SAP-tagged FLAs were capable of self-assembly to form nano-sized particles with different dimensions in aqueous solutions. Strikingly, one of the SAP-tagged FLA (FLA-L6KD) displayed improved enzyme activity, thermostability and reusability, which is potentially ideal for bio-transformation. FLA is an exotic enzyme that is capable of catalysing the formation of C-F bonds using inorganic fluorine ions as substrates. This significant feature enables it to incorporate [18F]-fluoride into different small molecules to generate radiopharmaceuticals in PET (positron emission tomography) labeling. In addition, fluorinase is greatly valuable in synthetic biology for incorporating the fluorine element into building blocks to produce non-natural organofluorines or as a biocatalyst for transforming non-native substrates. Our method would be a further step in making FLA-based biocatalysis even 'greener' by enhancing the enzymatic activity, thermostability and reusability of FLA through the introduction of nano-sized aggregates. Enzymes are such nontrivial biomaterials, which can be manifested in different scenarios. Our research expands their reach and tunes their properties by tagging SAP partners. Thus, this methodology can be put into the 'toolbox' of enzymologists, which can be further explored and generalised for others.

7.
Chin Med Sci J ; 34(3): 211-220, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601304

RESUMO

We review the representatives literatures on chronic osteomyelitis, sum up the new insights in recent years into diagnostic options and treatment regimens, analyze the advantages and disadvantages of various diagnostic approaches and treatment strategies, and propose areas of interest to make current diagnostic and treatment strategies more specific.

8.
Theriogenology ; 142: 26-33, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31574397

RESUMO

Asiatic acid is a pentacyclic triterpene enriched in the medicinal herb Centella asiatica, and it has been suggested to possess free radical scavenging and anti-apoptotic properties. The purpose of the current study was to explore the effects of asiatic acid on porcine early-stage embryonic development and the potential mechanisms for any observed effects. The results showed that 10 µM asiatic acid supplementation during the in vitro culture period dramatically improved developmental competence in porcine embryos derived from parthenogenetic activation (PA), somatic cell nuclear transfer (SCNT) and in vitro fertilization (IVF). Further analysis revealed that asiatic acid attenuated H2O2-induced intracellular reactive oxygen species (ROS) generation. Notably, asiatic acid not only enhanced intracellular GSH levels but also attenuated mitochondrial dysfunction. Gene expression analysis revealed that asiatic acid upregulated expression of the antioxidant-related gene Sod-1 and the blastocyst formation related gene Cox-2, while downregulating expression of the apoptosis-related gene Caspase-9 in SCNT blastocysts. These results suggest that asiatic acid exerts beneficial effects on early embryonic development in porcine embryos and that asiatic acid may be useful for improving the in vitro production of porcine embryos.

9.
ACS Appl Mater Interfaces ; 11(46): 43751-43765, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31659888

RESUMO

In view of the increasing serious water environmental and human health issues caused by oily wastewater, functional superwetting materials with controllable wettability, high durability, and scale preparation methods are highly desired for efficient oil/water separation. In this respect, a pH-responsive multifunctional fabric with switchable surface wettability, favorable mechanical durability, and self-repairing property has been developed via decorating the modified TiO2 nanoparticles of special surface compositions onto the fabric surface. By virtue of the intelligent surface wettability, the resulted superwettable fabric can be used for controllable separation of multiple oil/water mixtures, particularly the complicated oil/water/oil ternary mixtures, showing excellent separation efficiency and high filtration flux even under extreme pH conditions, which is comparable to most of the commercial and currently reported functionalized membranes. Simultaneously, the negative pressure-driven, continuous, high-speed, and highly efficient in situ purification of large volumes of oily wastewater is successfully achieved based on the resulted superwettable fabric. More importantly, with the as-prepared superwettable fabric as the filtration membrane, the continuous in situ separation of the synthetic oily product from the corresponding chemical reaction systems is well performed without interruption of the reaction, demonstrating outstanding merits of simplifying procedures, saving operation time, and increasing product yield. In addition, it is worth noting that the alkali-treated superhydrophilic fabric presents superior photocatalysis self-cleaning performance for various water-soluble organic pollutants. These unique advantages of the functionalized smart superwettable fabric ensure that it can be competent in multifarious relevant challenging settings, indicating a broad prospect for diverse practical applications, especially the oily wastewater treatment and multiple industrial operation optimizations.

10.
Angew Chem Int Ed Engl ; 58(48): 17199-17204, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31508869

RESUMO

A chiral Brønsted base catalyzed asymmetric annulation of ortho-alkynylanilines has been developed to access axially chiral naphthyl-C2-indoles via vinylidene ortho-quinone methide (VQM) intermediates. This strategy provides a unique organocatalytic atroposelective route to axially chiral aryl-C2-indole skeletons with excellent enantioselectivity and functional-group tolerance. This transformation was applicable to decagram-scale preparation (50.0 g) with perfect enantioselectivity through simple recrystallization. Moreover, the utility of this reaction was demonstrated by a variety of transformations towards chiral naphthyl-C2-indoles for a series of carbon-heteroatom bond formations. Furthermore, the prepared axially chiral naphthyl-C2-indoles were applied as a chiral skeleton for organocatalytic aza-Baylis-Hillman reaction and asymmetric formal [4+2] tandem cyclization to give the corresponding adducts in high yields with improved enantioselectivity and diastereoselectivity.

11.
Nat Biotechnol ; 37(11): 1302-1313, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31548728

RESUMO

Targeting membrane proteins could improve the efficacy of T cell-based immunotherapies. To facilitate the identification of T cell targets, we developed a hybrid genetic screening system where the Sleeping Beauty (SB) transposon and single guide RNA cassette are nested in an adeno-associated virus (AAV). SB-mediated genomic integration of the single guide RNA cassette enables efficient gene editing in primary murine T cells as well as a screen readout. We performed in vivo AAV-SB-CRISPR screens for membrane protein targets in CD8+ T cells in mouse models of glioblastoma (GBM). We validated screen hits by demonstrating that adoptive transfer of CD8+ T cells with Pdia3, Mgat5, Emp1 or Lag3 gene editing enhances the survival of GBM-bearing mice in both syngeneic and T-cell receptor transgenic models. Transcriptome profiling, single cell sequencing, cytokine assays and T cell signaling analysis showed that Pdia3 editing in T cells enhances effector functions. Engineered PDIA3 mutant EGFRvIII chimeric antigen T cells are more potent in antigen-specific killing of human GBM cells.

12.
J Virol ; 93(24)2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31554686

RESUMO

Outbreaks of severe diarrhea in neonatal piglets in Guangdong, China, in 2017 resulted in the isolation and discovery of a novel swine enteric alphacoronavirus (SeACoV) derived from the species Rhinolophus bat coronavirus HKU2 (Y. Pan, X. Tian, P. Qin, B. Wang, et al., Vet Microbiol 211:15-21, 2017). SeACoV was later referred to as swine acute diarrhea syndrome CoV (SADS-CoV) by another group (P. Zhou, H. Fan, T. Lan, X.-L. Yang, et al., Nature 556:255-258, 2018). The present study was set up to investigate the potential species barriers of SADS-CoV in vitro and in vivo We first demonstrated that SADS-CoV possesses a broad species tropism and is able to infect cell lines from diverse species, including bats, mice, rats, gerbils, hamsters, pigs, chickens, nonhuman primates, and humans. Trypsin contributes to but is not essential for SADS-CoV propagation in vitro Furthermore, C57BL/6J mice were inoculated with the virus via oral or intraperitoneal routes. Although the mice exhibited only subclinical infection, they supported viral replication and prolonged infection in the spleen. SADS-CoV nonstructural proteins and double-stranded RNA were detected in splenocytes of the marginal zone on the edge of lymphatic follicles, indicating active replication of SADS-CoV in the mouse model. We identified that splenic dendritic cells (DCs) are the major targets of virus infection by immunofluorescence and flow cytometry approaches. Finally, we demonstrated that SADS-CoV does not utilize known CoV receptors for cellular entry. The ability of SADS-CoV to replicate in various cells lines from a broad range of species and the unexpected tropism for murine DCs provide important insights into the biology of this bat-origin CoV, highlighting its possible ability to cross interspecies barriers.IMPORTANCE Infections with bat-origin coronaviruses (CoVs) (severe acute respiratory syndrome CoV [SARS-CoV] and Middle East respiratory syndrome CoV [MERS-CoV]) have caused severe illness in humans after "host jump" events. Recently, a novel bat-HKU2-like CoV named swine acute diarrhea syndrome CoV (SADS-CoV) has emerged in southern China, causing lethal diarrhea in newborn piglets. It is important to assess the species barriers of SADS-CoV infection since the animal hosts (other than pigs and bats) and zoonotic potential are still unknown. An in vitro susceptibility study revealed a broad species tropism of SADS-CoV, including various rodent and human cell lines. We established a mouse model of SADS-CoV infection, identifying its active replication in splenic dendritic cells, which suggests that SADS-CoV has the potential to infect rodents. These findings highlight the potential cross-species transmissibility of SADS-CoV, although further surveillance in other animal populations is needed to fully understand the ecology of this bat-HKU2-origin CoV.

13.
Med Sci Monit ; 25: 6649-6659, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31484919

RESUMO

BACKGROUND Chondrocyte dysfunction and apoptosis are 2 major features during the progression of osteoarthritis. Catalpol, an iridoid glycoside isolated from the root of Rehmannia, is a valuable medication with anti-inflammatory, anti-oxidative, and anti-apoptotic effects in various diseases. However, whether catalpol protects against osteoarthritis has not been investigated. MATERIAL AND METHODS To assess the role of catalpol in osteoarthritis and the potential mechanism of action, chondrocytes were treated with interleukin (IL)-1ß and various concentrations of catalpol. Catabolic metabolism, apoptotic level and relative signaling pathway were measured by western blot, real-time polymerase chain reaction and immunofluorescence staining. Meanwhile, we assess the cartilage degeneration in an experimental rat model using Safranin O fast green staining and cartilage was graded according to the Osteoarthritis Research Society International (OARSI) system. RESULTS The results showed that catalpol prevented chondrocyte apoptotic level triggered by IL-1ß, suppressed the release of catabolic enzymes, and inhibited the degradation of extracellular matrix induced by IL-1ß. Catalpol also inhibited the nuclear factor kappa B (NF-kappaB) pathway, reduced the production of inflammatory cytokines (IL-6, tumor necrosis factor-alpha) in IL-1ß-treated chondrocytes, and partially reversed cartilage degeneration in the knee joint in animal model of osteoarthritis. CONCLUSIONS Our work suggested that catalpol treatment attenuates IL-1ß-induced inflammatory response and catabolism in rat chondrocytes by inhibiting the NF-kappaB pathway, suggesting the therapeutic potential of catalpol for the treatment of osteoarthritis.

14.
Vet Microbiol ; 236: 108387, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500721

RESUMO

Given the highly contagious and acute nature of porcine epidemic diarrhea (PED), especially in piglets, there is an urgent need for the development of rapid and sensitive diagnostic assays. The diagnostic potentials of specific porcine epidemic diarrhea virus (PEDV) accessory and nonstructural proteins, if any, have not yet been investigated. In order to determine and compare which of the viral proteins may be useful as diagnostic antigens, whole virus (WV) particles and a panel of structural and nonstructural PEDV proteins [spike subunit 1 (S1), the C-terminal part of ORF3 (ORF3C), envelope (E), nonstructural protein 1 (Nsp1), Nsp2, Ac (acidic domain of Nsp3), and ADRP (ADP-ribose-1-monophosphatase domain of Nsp3), expressed individually in bacterial and/or mammalian cells] were tested for reactivity with sera from PEDV-infected pigs by ELISA and/or western blot analysis. According to western blots, serum antibody interactions with the S1 protein were relatively more sensitive and specific than ORF3C, E and Ac. Furthermore, a total of 851 serum samples from diarrheal pigs of different ages were analyzed by ELISA, with most showing immune-reactivity towards the WV, S1, ORF3C, and E proteins. The earliest IgG antibody response was observed in the one-week-old piglets, with similar antibody ontogeny and patterns of seroconversion for S1, ORF3C, E, and WV antigens. In addition, the pattern of neutralizing antibody was more similar to that of IgA in weaning piglets after PEDV infection. Collectively, these data provide more reliable information on the host immune response to different viral proteins, which will be useful for development of novel serological assays and for design of vaccines that better stimulate protective immunity.

15.
Medicine (Baltimore) ; 98(35): e16907, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464923

RESUMO

This study was to investigate the incidence and the risk factors of postpartum stress urinary incontinence (SUI), and the effect of comprehensive care and rehabilitation program (CCRP) on preventing postpartum SUI.In stage I, 479 puerperae were recruited within 1 week postpartum, then the postpartum SUI incidence at 8th week and its risk factors were investigated. In stage II, 240 vaginal delivery puerperae were enrolled within 1 week postpartum and randomly assigned to CCRP group or control group as 1:1 ratio. The postpartum SUI incidence and pelvic floor muscle function indexes were evaluated at 8th week.In stage I, the postpartum SUI incidence was 25.7%, and SUI puerperae presented with higher body mass index (BMI), vaginal delivery rate, newborn weight, and larger newborn head diameter compared with non-SUI puerperae. Besides, the vaginal delivery, the elevated age and BMI were independent risk factors for postpartum SUI. In stage II, the postpartum SUI incidence in CCRP group was decreased compared with control group, and the vaginal resting pressure, vaginal squeezing pressure, and vaginal contraction duration were increased in CCRP group compared to control group at 8th week postpartum.The incidence of postpartum SUI is 25.7%, and the vaginal delivery, increased age, and BMI are independent risk factors for postpartum SUI. More importantly, CCRP strengthens pelvic floor muscle functions and decreases postpartum SUI incidence in puerperae.


Assuntos
Assistência Integral à Saúde/métodos , Transtornos Puerperais/epidemiologia , Transtornos Puerperais/reabilitação , Incontinência Urinária por Estresse/epidemiologia , Incontinência Urinária por Estresse/reabilitação , Adulto , Índice de Massa Corporal , Cesárea/efeitos adversos , Parto Obstétrico/efeitos adversos , Feminino , Educação em Saúde/métodos , Humanos , Incidência , Idade Materna , Diafragma da Pelve/fisiopatologia , Período Pós-Parto , Gravidez , Distribuição Aleatória , Incontinência Urinária por Estresse/etiologia
16.
Virology ; 536: 110-118, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31419711

RESUMO

Swine enteric alphacoronavirus (SeACoV), also known as swine acute diarrhea syndrome coronavirus (SADS-CoV), belongs to the species Rhinolophus bat coronavirus HKU2. Herein, we report on the primary characterization of SeACoV in vitro. Four antibodies against the SeACoV spike, membrane, nucleocapsid and nonstructural protein 3 capable of reacting with viral antigens in SeACoV-infected Vero cells were generated. We established a DNA-launched SeACoV infectious clone based on the cell adapted passage-10 virus and rescued the recombinant virus with a unique genetic marker in cultured cells. Six subgenomic mRNAs containing the leader-body junction sites, including a bicistronic mRNA encoding the accessory NS7a and NS7b genes, were experimentally identified in SeACoV-infected cells. Cellular ultrastructural changes induced by SeACoV infection were visualized by electron microscopy. The availability of the SeACoV infectious clone and a panel of antibodies against different viral proteins will facilitate further studies on understanding the molecular mechanisms of SeACoV replication and pathogenesis.

17.
Neuropeptides ; 76: 101941, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31256921

RESUMO

Substance P (SP) is an undecapeptide encoding the tachykinin 1 (TAC1) gene and belongs to the tachykinin family. SP is widely distributed in the central nervous system and the peripheral nervous system. SP is also produced by nonneuronal cells, such as inflammatory cells and endothelial cells. The biological activities of SP are mainly regulated through the high-affinity neurokinin 1 receptor (NK-1R). The SP/NK-1R system plays an important role in the molecular bases of many human pathophysiologic processes, such as pain, infectious and inflammatory diseases, and cancer. In addition, this system has been implicated in fibrotic diseases and processes such as wound healing, myocardial fibrosis, bowel fibrosis, myelofibrosis, renal fibrosis, and lung fibrosis. Recently, studies have shown that SP plays an important role in liver fibrosis and that NK-1R antagonists can inhibit the progression of fibrosis. NK-1R receptor antagonists could provide clinical solutions for fibrotic diseases. This review summarizes the structure and function of SP and its involvement in fibrotic diseases.

18.
J Cell Biochem ; 120(10): 16408-16415, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31310357

RESUMO

Aging process in mammals is associated with a decline in amplitude and a long period of circadian behaviors which are regulated by a central circadian regulator in the suprachiasmatic nucleus (SCN) and local oscillators in peripheral tissues. It is unclear whether enhancing clock function can retard aging. Using fibroblasts expressing per2::lucSV and senescent cells, we revealed cycloastragenol (CAG), a natural aglycone derivative from astragaloside IV, as a clock amplitude enhancing small molecule. CAG could activate telomerase to antiaging, but no reports focused on its effects on circadian rhythm disorders in aging mice. Here we analyze the potential effects of CAG on d-galactose-induced aging mice on the circadian behavior and expression of clock genes. For this purpose, CAG (20 mg/kg orally), was administered daily to d-galactose (150 mg/kg, subcutaneous) mice model of aging for 6 weeks. An actogram analysis of free-running activity of these mice showed that CAG significantly enhances the locomotor activity. We further found that CAG increase expressions of per2 and bmal1 genes in liver and kidney of aging mouse. Furthermore, CAG enhanced clock protein BMAL1 and PER2 levels in aging mouse liver and SCN. Our results indicated that the CAG could restore the behavior of circadian rhythm in aging mice induced by d-galactose. These data of present study suggested that CAG could be used as a novel therapeutic strategy for the treatment of age-related circadian rhythm disruption.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31240625

RESUMO

To investigate the drug release and anti-adhesion effects of a TET (tetrandrine)-loaded PDLLA (poly-DL-lactide) film. Detection of TET release in vitro was carried out by high-performance liquid chromatography (HPLC) every 2 days following immersion of the tetrandrine-loaded PDLLA film in simulated body fluid until the TET content of the eluate could not be detected. For the in vivo test, TET-loaded PDLLA films were implanted into animal laminectomy models and positive and blank control groups were also set up. Postoperative serum tests, and macroscopic and histological analyses at 1, 4, 8, and 12 weeks, were used to assess the effects of the film. Statistical analyses were performed by one-way ANOVA. The drug release of the tetrandrine-loaded PDLLA film in vitro showed two phases with a second release peak. Ultimately, the duration of continuous delivery was up to 66 days and the cumulative delivery rate was up to 93.18%. Scores for the proliferation of epidural scars or adhesion of the dura mater in the test group were much lower than those for the two control groups. Histological analysis revealed the test group had fewer inflammatory cells and fibroblasts, as well as fewer extracellular collagen fibers, and a lower histology score than those of the two control groups at all time points. Tetrandrine-loaded PDLLA film is a novel controlled drug release and anti-adhesion material in vitro and in vivo.

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