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1.
Anal Chim Acta ; 1082: 116-125, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472700

RESUMO

A novel six-membered rhodamine-based fluorescent probe (6G-ClO) was developed from 2-formyl rhodamine (6G-CHO) and used for hypochlorite detection in water and HUVEC cells. Different from planar penta cycle of rhodamine spirolactam, there was a twist six-membered spirocyclic hydrazone in 6G-ClO optimized by Gaussian software at DFT/B3LYP/6-31G(d) level. The high selectivity, high sensitivity and fast response of 6G-ClO towards ClO- would be attributed to the twist six-membered spirocycle. Test-strip prepared with 6G-ClO was successfully used to semi-quantitatively indicate the concentration of ClO- in water. 6G-ClO can also quantitatively detect the concentration of ClO- in tap water and swimming pool water. The detection limit of 6G-ClO was as low as 12 nM. The co-localization staining of HUVEC cells further verified that 6G-ClO could specifically accumulate in lysosomes and capture exogenous/endogenous ClO- in living lysosomes. 6G-ClO would be a practical probe for real-time monitoring of ClO- in the biological and real water samples.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(4): 452-456, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31484605

RESUMO

To analyze the clinical features and prognosis of ulcerative colitis(UC)complicated with acute massive lower gastrointestinal bleeding(LGIB). Methods Eleven patients hospitalized in Peking Union Medical College Hospital from January 2006 to December 2017 for treatment of UC,suffering from acute massive LGIB,were enrolled and descriptively analyzed. Results The proportion of UC patients with acute massive LGIB was 0.7% among all 1486 UC patients hospitalized during the study period.The disease was moderately or severely active in these 11 patients,among whom 9 patients(81.8%)had chronic relapsing pancolitis.Cytomegalovirus infection was present in 5 patients,among whom 4 patients received antiviral treatments.All the 11 patients received treatments including food and water fasting,rehydration,blood transfusion,and use of somatostatin.Four patients received emergency surgical treatment after the first episode of massive bleeding,and 3 of them suffered from re-bleeding after the surgery.Among the remaining seven patients,two underwent emergency total colectomy+subtotal rectectomy+ileostomy and three received elective total resection of colon and rectum or total colectomy+subtotal rectectomy+ileostomy.Thus,9 patients underwent emergency surgery,1 patient did not receive surgey during follow-up,and 1 patient was lost to follow-up. Conclusions Acute massive LGIB is a manifestation of active UC and can be associated with poor prognosis.Optimized perioperative management is important for improving the outcomes of such patients.

3.
Eur J Neurosci ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31491043

RESUMO

The role of the fibroblast growth factor (FGF) system in depression has received considerable attention in recent years. To understand the role of this system, it is important to identify the specific members of the FGF family that have been implicated and the various mechanisms that they modulated. Here, we review the role of FGFs in depression and integrate evidence from clinical and basic research. These data suggest that changes in the FGF family are involved in depression and possibly in a wider range of psychiatric disorders. We analyze the abnormalities of FGF family members in depression and their roles in modulating depression-related molecules. The role of the FGF family in depression and related disorders needs to be studied in more detail. This article is protected by copyright. All rights reserved.

4.
J Gen Physiol ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481514

RESUMO

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open more easily when cAMP or cGMP bind to a domain in the intracellular C-terminus in each of four identical subunits. How sensitivity of the channels to these ligands is determined is not well understood. Here, we apply a mathematical model, which incorporates negative cooperativity, to gating and mutagenesis data available in the literature and combine the results with binding data collected using isothermal titration calorimetry. This model recapitulates the concentration-response data for the effects of cAMP and cGMP on wild-type HCN2 channel opening and, remarkably, predicts the concentration-response data for a subset of mutants with single-point amino acid substitutions in the binding site. Our results suggest that ligand sensitivity is determined by negative cooperativity and asymmetric effects on structure and channel opening, which are tuned by ligand-specific interactions and residues within the binding site.

5.
Brain Behav ; : e01363, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483562

RESUMO

INTRODUCTION: The increasing use of large sample sizes for population and personalized medicine requires high-throughput tools for imaging processing that can handle large amounts of data with diverse image modalities, perform a biologically meaningful information reduction, and result in comprehensive quantification. Exploring the reproducibility of these tools reveals the specific strengths and weaknesses that heavily influence the interpretation of results, contributing to transparence in science. METHODS: We tested-retested the reproducibility of MRICloud, a free automated method for whole-brain, multimodal MRI segmentation and quantification, on two public, independent datasets of healthy adults. RESULTS: The reproducibility was extremely high for T1-volumetric analysis, high for diffusion tensor images (DTI) (however, regionally variable), and low for resting-state fMRI. CONCLUSION: In general, the reproducibility of the different modalities was slightly superior to that of widely used software. This analysis serves as a normative reference for planning samples and for the interpretation of structure-based MRI studies.

6.
Stem Cell Res ; 40: 101545, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31472451

RESUMO

Here we describe the generation and characterization of the human induced pluripotent stem cell (iPSC) lines from urine-derived cells (UCs) from two patients with unbalanced chromosomal translocation t(3,22)(q28;q13.3). The iPSC lines retain the original chromosome abnormality, express pluripotency markers and bear differentiation potential.

7.
Mol Ther Nucleic Acids ; 18: 24-33, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31479922

RESUMO

The aim of this study is to explore the roles of circular RNA (circRNA) Cdr1as on cisplatin resistance in ovarian cancer and explore the underlying mechanisms. We investigated the expression of circRNAs in five paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The quantitative real-time PCR analysis was to investigate the expression pattern of Cdr1as in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then, the effects of Cdr1as on cisplatin resistance, cell proliferation, and apoptosis were assessed in ovarian cancer cells. In this study, Cdr1as was observed to be downregulated in cisplatin-resistant patient tissues and cell lines. Overexpression of Cdr1as inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed Cdr1as promoted the miR-1270 expression, and miR-1270 could bind to the predicted binding site of Cdr1as. Furthermore, we found that miR-1270 displayed its role via modulating the Suppressor of Cancer Cell Invasion (SCAI) expression. Importantly, we demonstrated that Cdr1as was downregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that Cdr1as sensitizes ovarian cancer to cisplatin by regulating the miR-1270/SCAI signaling pathway.

8.
BMC Surg ; 19(1): 128, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488117

RESUMO

BACKGROUND: The aim of the study was to develop a scoring system for the prediction of postoperative complications of open hepatectomy. METHOD: All consecutive patients receiving open hepatectomy from 2015 to 2017 were included in the study. Univariate and multivariate analyses were used to confirm the risk factors for postoperative complications. Afterwards, a novel scoring system was developed to predict the postoperative complications. RESULTS: The study included a total of 207 patients. For the test dataset, multivariate analysis indicated that diabetes, scale of surgery, serum potassium, and blood loss versus body weight were independent risk factors of the postoperative complications. The area under the curve (AUC) of the novel scoring system we proposed for prediction of postoperative complications of hepatectomy was 0.803, which is comparable with the AUCs of previous scoring systems. Furthermore, in the validation dataset, the corresponding AUC of the new scoring system was 0.717. CONCLUSION: This novel and simplified scoring system can effectively predict the postoperative complications of open hepatectomy and could help identify patients who are at high risk of postoperative complications.

9.
J Orthop Surg Res ; 14(1): 299, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488174

RESUMO

PURPOSE: Our purpose was to combine intravoxel incoherent motion diffusion-weighted MR imaging (IVIM-DWI) and magnetic resonance spectroscopy (MRS) to differentiate osteoporotic fractures from osteolytic metastatic vertebral compression fractures (VCFs). METHODS: A total of 70 patients with VCFs were included and divided into two groups, according to their causes of fractures based on pathological findings or clinical follow-up. All patients underwent conventional sagittal T1WI, T2WI, STIR, IVIM-DWI, and single-voxel MRS. The diffusion coefficient (D), pseudo diffusion (D*), and perfusion fraction (f) parameters from IVIM-DWI and the lipid water ratio (LWR) and fat fraction (FF) parameters from MRS were obtained and compared among groups. Furthermore, the diagnostic performance of MRS, IVIM-DWI, and IVIM-DWI combined with MRS for differentiation between osteoporotic and osteolytic metastatic VCFs was assessed by using receiver operating characteristic (ROC) curve analysis. RESULTS: Compared with the osteoporotic group, the metastatic group had significantly lower values for f, D, and FF, but higher D* (all P < 0.05). The area under the receiver operating characteristic (ROC) curve of MRS, IVIM-DWI, and IVIM-DWI combined with MRS were 0.73, 0.88, and 0.94, respectively. Among these, the IVIM-DWI combined with MRS showed the highest sensitivity, specificity, and accuracy, which are 90.63% (29/32), 97.37 % (37/38), and 94.29% (66/70), respectively. CONCLUSIONS: IVIM-DWI combined with MRS can be more accurate and efficient for differentiation between osteoporotic and osteolytic metastatic VCFs than single MRS or IVIM-DWI.

10.
Stem Cell Res ; 40: 101557, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31505389

RESUMO

An induced pluripotent stem cell (iPSC) line was generated from human urine-derived cells of a 4 year-old boy with autism spectrum disorder(ASD) and developmental delay (DD) carrying a 830 kb de novo deletion at chromosome 7q11.22 disrupting the first exon and promoter region of AUTS2. The iPSC retained the original deletion of AUTS2, and had a normal karyotype, express pluripotency markers and bear differentiation potential in vitro.

11.
J Med Chem ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513410

RESUMO

Short peptide-based inhibition of fusion remains an attractive goal in anti-human immunodeficiency virus (HIV) research based on its potential for the development of technically and economically desirable antiviral agents. Herein, we report use of the dithiol bis-alkylation reaction to generate a series of m-xylene thioether-stapled 22-residue α-helical peptides that have been identified as fusion inhibitors targeting HIV-1 glycoprotein 41 (gp41). The peptide sequence is based on the helix-zone binding domain (HBD) of the gp41 C-terminal heptad repeat (CHR) region. We found that one of these stapled peptides, named hCS6ERE, showed promising inhibitory potency against HIV-1 Env-mediated cell-cell fusion and viral replication at a level comparable to the clinically used 36-mer peptide T20. Furthermore, combining hCS6ERE with a fusion inhibitor having a different target site, such as HP23, produced synergistic anti-HIV-1 activity. Collectively, our study offers new insight into the design of anti-HIV peptides with short sequences.

12.
Nat Commun ; 10(1): 4132, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511516

RESUMO

Near-zero-index (NZI) media, a medium with near zero permittivity and/or permeability, exhibits unique wave phenomena and exciting potential for multiple applications. However, previous proof-of-concept realizations of NZI media based on bulky and expensive platforms are not easily compatible with low-cost and miniaturization demands. Here, we propose the method of substrate-integrated (SI) photonic doping, enabling the implementation of NZI media within a printed circuit board (PCB) integrated design. Additionally, the profile of the NZI device is reduced by half by using symmetries. We validate the concept experimentally by demonstrating NZI supercoupling in straight and curve substrate integrated waveguides, also validating properties of position-independent photonic doping, zero-phase advance and finite group delay. Based on this platform, we propose design of three NZI devices: a high-sensitivity dielectric sensor, an efficient acousto-microwave modulator, and an arbitrarily-curved 'electric fiber'. Our results represent an important step forward in the development of NZI technologies for microwave/terahertz applications.

13.
Nucleic Acids Res ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31504793

RESUMO

HMCES and yedK were recently identified as sensors of abasic sites in ssDNA. In this study, we present multiple crystal structures captured in the apo-, nonspecific-substrate-binding, specific-substrate-binding, and product-binding states of yedK. In combination with biochemical data, we unveil the molecular basis of AP site sensing in ssDNA by yedK. Our results indicate that yedK has a strong preference for AP site-containing ssDNA over native ssDNA and that the conserved Glu105 residue is important for identifying AP sites in ssDNA. Moreover, our results reveal that a thiazolidine linkage is formed between yedK and AP sites in ssDNA, with the residues that stabilize the thiazolidine linkage important for the formation of DNA-protein crosslinks between yedK and the AP sites. We propose that our findings offer a unique platform to develop yedK and other SRAP domain-containing proteins as tools for detecting abasic sites in vitro and in vivo.

14.
J Nutr Biochem ; 72: 108212, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31473513

RESUMO

Migration of vascular smooth muscle cell (VSMC) plays a critical role in the pathophysiology of hypertension and several other vascular diseases. Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a bioactive constituent from Curcuma longa, is commonly used as a spice, food additive or dietary pigment. It has several health benefits including antioxidant, anti-inflammatory and anticancer properties. This study examined the roles of curcumin in VSMC migration in hypertension and underlying mechanism. VSMC was isolated and prepared from thoracic aorta of Wistar-Kyoto rats and spontaneously hypertensive rats (SHR). VSMC migration was evaluated with Boyden chamber assay and wound-healing assay. Curcumin attenuated VSMC migration, inhibited nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) expression and reduced interleukin (IL)-1ß concentration in VSMC of SHR, which were similar to the effects of NLRP3 knockdown on IL-1ß concentration and VSMC migration. Curcumin inhibited NFκB activation in VSMC of SHR, which was similar to the effects of NFκB inhibitor BAY11-7082 on NFκB activation. In another in vitro model of rat VSMC migration, curcumin also inhibited angiotensin II-induced VSMC migration, NFκB activation, NLRP3 expression and IL-1ß production. Intragastric administration of curcumin in SHR attenuated hypertension and reduced NFκB activation, NLRP3 and matrix metalloproteinase-9 expressions and aortic media thickness. These results indicate that curcumin inhibits VSMC migration via inhibiting NFκB-mediated NLRP3 expression in VSMC of SHR or in angiotensin II-treated VSMC. Curcumin attenuates hypertension, vascular inflammation and vascular remodeling in SHR.

15.
Oncogene ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477833

RESUMO

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Currently, the prognosis of the patients with GBM is very poor and new molecular targets and treatment strategies are urgently needed to combat it. MicroRNA-148a (miR-148a) has been shown to be dysregulated in certain tumor types. However, the role of miR-148a in the pathogenesis of GBM is not fully understood. Here we comprehensively analyzed the roles of miR-148a, downstream DLGAP1, and their molecular pathways in GBM. We showed that miR-148a promote the proliferation and growth of GBM cells both in vitro and in vivo, and also induced the migration, invasion, and EMT (epithelial-mesenchymal transition) program of GBM cells by directly targeting DLGAP1. Furthermore, we identified 31 new miR-148a targets and found that miR-148a function was mainly involved in the cell adhesion signaling pathway and was associated with nervous system diseases. Our findings provide a new mechanism for miR-148a-mediated GBM cell invasion and reveal previously unreported targets of miR-148a as well as novel miR-148a-mediated regulatory networks in GBM. These results increase the understanding of the role of miR-148a in GBM and may lead to novel therapeutic strategies for GBM.

16.
Dev Cell ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31495692

RESUMO

Apical hook curvature is crucial for buried seedling survival and a superb model for dissecting differential cell growth. HOOKLESS1 (HLS1) is essential for apical hook formation, acting as a hub integrating various external and internal signals. However, its functional mechanism remains unclear. Here, we demonstrate that HLS1 protein is present as an oligomer in the nucleus of dark-grown seedlings. Oligomerization is required for HLS1 activation, as the mutated HLS1 protein abolishing self-association exists as nonfunctional monomers. Upon light exposure, photoreceptor phyB translocates into the nucleus and interacts with HLS1, disrupting the self-association and oligomerization of HLS1 to initiate hook unfolding. Remarkably, genetic expression of nuclear-localized phyB is sufficient to inactivate HLS1, resulting in compromised hook curvature in etiolated seedlings. Together, we conclude that HLS1 protein is active as oligomeric form in darkness and achieves allosteric photo-deactivation upon light, providing intriguing mechanistic insight into the molecular switch for developmental transition.

17.
Inorg Chem ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31497944

RESUMO

Presented herein is a group of highly stable Zr-based metal-organic frameworks with bowl-shaped dihydroanthracene-based tetratopic linkers as building blocks. Structural analysis reveals that these frameworks are all two-dimensional but comprise three distinct connectivities of Zr6 nodes. By using the steric hindrance of the nonplanar linker, the connectivity of Zr6 node can be tuned from 8-c to unusual 4-c. Further, through either one-pot synthesis or postsynthetic linker installation strategies, the connectivity of Zr6 node can be tuned from 8-c to 10-c by the insertion of a secondary linear dicarboxylate linker, from which not only the temperature-dependent flexibility of the structure can be effectively controlled with enhanced rigidity and thermal stability but also a scaffold for postsynthetic metalation of Pd(II) catalyst for Heck coupling reaction is offered.

18.
Pestic Biochem Physiol ; 159: 118-126, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400773

RESUMO

In the plant-insect arms race, plants synthesize toxic compounds to defend against herbivorous insects, whereas insects employ cytochrome P450 monooxygenases (P450s) to detoxify these phytotoxins. As ubiquitous environmental contaminants, heavy metals can be easily absorbed by plants and further accumulated in herbivorous insects through the food chains, resulting in tangible consequences for plant-insect interactions. However, whether heavy metals can influence P450 activities and thereby cause further effects on larval tolerance to phytotoxins remains unknown. In this study, we shown that prior exposure to copper (Cu) enhanced larval tolerance to xanthotoxin in Spodoptera litura, a major polyphagous pest of agriculture. P450 activities were induced in larvae exposed to Cu or xanthotoxin, and a midgut specific expressed P450 gene, CYP6B50 was cross-induced after exposure to these two toxic xenobiotics. Knocking down CYP6B50 by RNA interference (RNAi) rendered the larvae more sensitive to xanthotoxin. As defense against oxidative stress following metal exposure has been demonstrated to affect insecticide resistance, the reactive oxygen species (ROS) generation and antioxidant enzyme activities were assessed. Cu exposure caused the accumulation of hydrogen peroxide (H2O2) and enhanced the activities of superoxide dismutase (SOD) and peroxidase (POD) in larval midgut. In addition, two antioxidant response elements (AREs) were identified from the CYP6B50 promoter, indicating that Cu-induced CYP6B50 expression may be related to the ROS burst. Application of ROS scavenger N-acetylcysteine (NAC) effectively suppressed CYP6B50 expression, inhibited P450 activities and impaired larval tolerance to xanthotoxin that had been induced by Cu. These results indicate that the increase in CYP6B50 expression regulated by Cu-induced H2O2 generation contributed to the enhancement of larval tolerance to xanthotoxin in S. litura. Ingestion of heavy metals from their host plants can inadvertently boost the counter-defense system of herbivorous insects to protect themselves against plant defensive toxins.


Assuntos
Cobre/farmacologia , Peróxido de Hidrogênio/metabolismo , Metoxaleno/farmacologia , Spodoptera/efeitos dos fármacos , Spodoptera/metabolismo , Animais , Elementos de Resposta Antioxidante/genética , Elementos de Resposta Antioxidante/fisiologia , Sistema Enzimático do Citocromo P-450/metabolismo , Peroxidase/genética , Peroxidase/metabolismo , Interferência de RNA , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
19.
Work ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31450526

RESUMO

BACKGROUNDFalls are among the leading causes of occupational injuries for workers exposed to outdoor winter conditions such as Personal Support Workers (PSWs). Slip resistant footwear is known to reduce the risk of falls, however, it is difficult to predict how well a particular boot will perform prior to purchasing them. Our recently developed Maximum Achievable Angle (MAA) test can be used to rate footwear objectively to address this gap.OBJECTIVETo rate the slip resistance of a selection of winter footwear that meet the needs and preferences of PSWs.METHODSWe selected 40 representative types of footwear based on survey results from 677 PSWs and applied our MAA test to rate slip resistance.RESULTSComfort and slip resistance were rated the most important features for selecting winter footwear. Of the 40 types of footwear tested, six were found to have a good slip resistance on ice.CONCLUSIONThe vast majority of winter footwear that meet the needs and preferences of PSWs, perform poorly on ice. Therefore, PSWs should consult our website (ratemytreads.com) for selecting appropriate footwear that will keep them safe in the winter.

20.
Zygote ; : 1-8, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31452481

RESUMO

Endometrial injury is an important cause of intrauterine adhesion (IUA), amenorrhea and infertility in women, with limited effective therapies. Recently, stem cells have been used in animal experiments to repair and improve injured endometrium. To date, our understanding of adipose-derived stem cells (ADSCs) in endometrial injury repair and their further therapeutic mechanisms is incomplete. Here, we examined the benefit of ADSCs in restoration of injured endometrium by applying a rat endometrial injury model. The results revealed by immunofluorescence showed that green fluorescent protein (GFP)-labelled ADSCs can differentiate into endometrial epithelial cells in vivo. At 30 days after ADSCs transplantation, injured endometrium was significantly improved, with increased microvessel density, endometrial thickness and glands when compared with the model group. Furthermore, the fertility of rats with injured endometrium in ADSCs group was improved and had a higher conception rate (60% vs 20%, P = 0.014) compared with the control phosphate-buffered saline (PBS) group. However, there was no difference in the control group compared with the sham group. In addition, expression levels of the oestrogen receptor Eα/ß (ERα, ERß) and progesterone receptor (PR) detected by western blot and enzyme-linked immunosorbent assay (ELISA) were higher in the ADSCs group than in the PBS group. Taken together, these results suggested that ADSC transplantation could improve endometrial injury as a novel therapy for IUA.

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