Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.095
Filtrar
1.
Front Immunol ; 11: 282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32153586

RESUMO

The emerging concept of microbiota contributing to local mucosal homeostasis has fueled investigation into its specific role in immunology. Gut microbiota is mostly responsible for maintaining the balance between host defense and immune tolerance. Dysbiosis of gut microbiota has been shown to be related to various alterations of the immune system. This review focuses on the reciprocal relationship between gut microbiota and innate immunity compartment, with emphasis on gut-associated lymphoid tissue, innate lymphoid cells, and phagocytes. From a clinical perspective, the review gives a possible explanation of how the "gut microbiota-innate immunity" axis might contribute to the pathogenesis of autoimmune diseases like rheumatoid arthritis, spondyloarthritis, and systemic lupus erythematosus.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32166332

RESUMO

CONTEXT: Higher blood glucose level during gestational periods has been consistently associated with increased risk of adverse birth outcomes. Evidence on the association between higher HbA1c within the normal range and adverse birth outcomes is limited. OBJECTIVE: We aimed to examine the association between HbA1c within the normal range and the risk of adverse birth outcomes. DESIGN AND SETTING: The data were abstracted from the Information System of Guangdong Women and Children Hospital, China, from September 2014 to March 2018. PATIENTS: A total of 5,658 pregnant women with normal gestational HbA1c were included in this analysis. MAIN OUTCOME MEASURES: The adverse birth outcomes include preterm birth, macrosomia, and large for gestational age (LGA). RESULTS: Among 5,658 subjects, the rates of preterm birth, macrosomia, and large for gestational age (LGA) were 4.6% (261/5,658), 3.5% (200/5,658) and 5.7% (325/5,658) respectively. The results of multivariate logistic regression model showed that each 1% increase in maternal HbA1c was positively associated with increased risks of preterm birth (OR: 1.58, 95% CI: 1.08 - 2.31), macrosomia (OR: 1.70, 95% CI: 1.10 - 2.64), and LGA (OR: 1.38, 95% CI: 0.98 - 1.96). The association between gestational HbA1c and preterm birth was more evident among women with pre-pregnancy body mass index (BMI) ≤ 24 kg/m². CONCLUSIONS: Gestational higher HbA1c level within the normal range is an independent risk factor for preterm birth, macrosomia, and LGA. Intervention for reducing HbAc1 may help to prevent adverse birth outcomes.

3.
Int J Med Sci ; 17(3): 403-413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32132875

RESUMO

Heparanase cleaves the extracellular matrix by degrading heparan sulfate that ultimately leads to cell invasion and metastasis; a condition that causes high mortality among cancer patients. Many of the anticancer drugs available today are natural products of plant origin, such as hinokitiol. In the previous report, it was revealed that hinokitiol plays an essential role in anti-inflammatory and anti-oxidation processes and promote apoptosis or autophagy resulting to the inhibition of tumor growth and differentiation. Therefore, this study explored the effects of hinokitiol on the cancer-promoting pathway in mouse melanoma (B16F10) and breast (4T1) cancer cells, with emphasis on heparanase expression. We detected whether hinokitiol can elicit anti-metastatic effects on cancer cells via wound healing and Transwell assays. Besides, mice experiment was conducted to observe the impact of hinokitiol in vivo. Our results show that hinokitiol can inhibit the expression of heparanase by reducing the phosphorylation of protein kinase B (Akt) and extracellular regulated protein kinase (ERK). Furthermore, in vitro cell migration assay showed that heparanase downregulation by hinokitiol led to a decrease in metastatic activity which is consistent with the findings in the in vivo experiment.

4.
J Clin Lab Anal ; : e23281, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157743

RESUMO

BACKGROUND: Detection of hepatitis B virus (HBV) is vital for the diagnosis of hepatitis B infection. A novel test loop-mediated isothermal amplification (LAMP) has been successfully applied to detect various pathogens. However, the accuracy of LAMP in diagnosing HBV remains unclear. Therefore, in the present study, the accuracy of LAMP for HBV detection was evaluated systematically. METHODS: Embase, Cochrane Library, and PubMed databases were searched for studies using LAMP to detect HBV. Then, two researchers extracted data and assessed the quality of literature using the QUADAS-2 tool independently. I2 statistic and chi-square test were analyzed to investigate the heterogeneity, and Deek's funnel plot assessed the publication bias. The pooled sensitivity (SEN), specificity (SPE), positive LR (PLR), negative LR (NLR), diagnostic odds ratio (DOR), and 95% confidence intervals were displayed in forest plots. We calculated the area under the curve (AUC) to assess the overall efficiency of LAMP for HBV detection. RESULTS: A total of nine studies with 1298 samples were finally included in this evaluation. The pooled sensitivity and specificity of HBV detection were 0.91 (95% CI: 0.89 ~ 0.92) and 0.97 (95% CI: 0.94 ~ 0.99), respectively. The PLR, NLR, and DOR were 16.93 (95% CI: 6.15 ~ 46.55), 0.08 (95% CI: 0.05 ~ 0.14), and 397.57 (95% CI: 145.41 ~ 1087.07). Besides, the AUC was 0.9872, and Deek's plot suggested that there existed publication bias in the studies. CONCLUSION: Compared with PCR, LAMP is a simple, rapid, and effective assay to diagnose HBV. However, additional evidence is essential to confirm that LAMP can replace other methods in diagnosing HBV infection.

5.
J Am Chem Soc ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32118412

RESUMO

The discovery of low-cost, less toxic, and earth-abundant thermoelectric materials is a great challenge. Herein, with the aid of a unique and safe boron-chalcogen method, we discover the new tetragonal α-CsCu5Se3, featuring a previously unrecognized structure in the ternary family of Cs/Cu/Se. The structure is constructed by a Chinese-knot-like Cu8Se8 building unit that is further linked into a 3D network. α-CsCu5Se3 exhibits thermal stability that is superior to that of the recently established thermoelectric materials Cu2-xSe and CsAg5Te3 suffering unfavorable phase transitions. Distinct from the liquidlike migration in Cu2-xSe, α-CsCu5Se3 obeys a typical crystalline solid thermal transport behavior dominated by Umklapp scattering. In compariosn to the isostructural CsAg5Te3, α-CsCu5Se3 shows a 30% volume decrease that leads to stronger orbital overlapping that markedly decreases the band effective mass (m*). With a smaller m* and a softer Cu-Se bond, α-CsCu5Se3 eventually realizes a 200% increase in the power factor (8.17 µW/(cm K2), the highest among the copper-rich alkali-metal chalcogenides) and a figure of merit (ZT) of 1.03 at 980 K. Further, the doping in α-Cs(Cu0.96Sb0.04)5Se3 boosts the lattice anharmonicity by the lone pairs that, via intensifying the Umklapp scattering and slowing the phonon velocity, ensures a low lattice thermal conductivity (0.40 W/(m K)), and finally leads to a ZTmax value of 1.30 at 980 K. Our discovery represents a step toward low-cost, earth-abundant, and high-performance chalcogenide materials that will shed useful light on future exploration in the related fields.

6.
J Orthop Res ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129514

RESUMO

Animal osteoarthritis (OA) models have been developed to understand OA progression and evaluate new OA therapies. However, individual variations in joint lesions remain a critical problem in most current OA models. We established a novel rabbit model by creating a longitudinal tear in the medial meniscus body that was reproducible and similar to posttraumatic biomechanical disturbances in human OA. New Zealand rabbits underwent surgery and were assessed for 9 weeks. The rabbits were randomized into the sham control, medial meniscal tear (MMT), and anterior cruciate ligament transection (ACLT) groups. The animals were sacrificed at 4, 6, and 9 weeks posttreatment. The knee joints were harvested for histological and gene expression assessments. Both the MMT and ACLT procedures led to time-dependent degenerative changes in the femoral condyle cartilage. At each time point, the MMT group cartilage showed more severe degenerative changes than did the ACLT group cartilage. Consistently, inflammatory cytokine and catabolic gene expression were significantly higher, and anabolic gene expression was significantly lower in the MMT group than in the ACLT group. MMT treatment caused more severe structural damage to the cartilage and higher catabolic gene expression levels than the ACLT model at each time point. The MMT model may be highly beneficial in investigating posttraumatic OA (PTOA) development, especially PTOA from a meniscal injury. The MMT model replicated key features of human PTOA, including meniscal lesions, inflammatory responses, and the progression to osteoarthritic cartilage degeneration, thereby providing an exciting new avenue for translating promising treatments to clinical practice.

7.
JCI Insight ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32213710

RESUMO

Monocyte-derived dendritic cells (moDCs) have been implicated in the pathogenesis of autoimmunity, but the molecular pathways determining the differentiation potential of these cells remain unclear. In this paper, we report that microRNA (miR)-148a serves as a critical regulator for moDC differentiation. Firstly, miR-148a deficiency impaired the moDC development in vitro and in vivo. Following mechanism study manifested that MAFB, a transcription factor that hampers moDC differentiation, was a direct target of miR-148a. In addition, promoter study further identified that miR-148a could be transcriptionally induced by PU.1, which is crucial for moDC generation. MiR-148a ablation eliminated the inhibition of PU.1 on MAFB. Furthermore, we found that miR-148a increased in monocytes from psoriasis patients, and miR-148a deficiency or intradermal injection of antagomir-148a immensely alleviated the development of psoriasis-like symptoms in a psoriasis-like mouse model. Therefore, these results identify a pivotal role for PU.1-miR-148a-MAFB circuit in moDC differentiation and suggest a potential therapeutic avenue for autoimmunity.

8.
PeerJ ; 8: e8682, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219020

RESUMO

Background: Alzheimer's disease (AD) is a prevalent progressive neurodegenerative human disease whose cause remains unclear. Numerous initially highly hopeful anti-AD drugs based on the amyloid-ß (Aß) hypothesis of AD have failed recent late-phase tests. Natural aging (AG) is a high-risk factor for AD. Here, we aim to gain insights in AD that may lead to its novel therapeutic treatment through conducting meta-analyses of gene expression microarray data from AG and AD-affected brain. Methods: Five sets of gene expression microarray data from different regions of AD (hereafter, ALZ when referring to data)-affected brain, and one set from AG, were analyzed by means of the application of the methods of differentially expressed genes and differentially co-expressed gene pairs for the identification of putatively disrupted biological pathways and associated abnormal molecular contents. Results: Brain-region specificity among ALZ cases and AG-ALZ differences in gene expression and in KEGG pathway disruption were identified. Strong heterogeneity in AD signatures among the five brain regions was observed: HC/PC/SFG showed clear and pronounced AD signatures, MTG moderately so, and EC showed essentially none. There were stark differences between ALZ and AG. OXPHOS and Proteasome were the most disrupted pathways in HC/PC/SFG, while AG showed no OXPHOS disruption and relatively weak Proteasome disruption in AG. Metabolic related pathways including TCA cycle and Pyruvate metabolism were disrupted in ALZ but not in AG. Three pathogenic infection related pathways were disrupted in ALZ. Many cancer and signaling related pathways were shown to be disrupted AG but far less so in ALZ, and not at all in HC. We identified 54 "ALZ-only" differentially expressed genes, all down-regulated and which, when used to augment the gene list of the KEGG AD pathway, made it significantly more AD-specific.

9.
J Subst Abuse Treat ; 112S: 56-62, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32220412

RESUMO

BACKGROUND: Healthcare data from electronic health records (EHRs) and related health information technology (IT) tools are critical data sources for pragmatic clinical trials and observational studies aimed at producing real-world evidence. To unlock the full potential of such data to advance science, the data must be complete and in structured formats to facilitate research use. METHODS: A Health IT survey was conducted within the National Drug Abuse Treatment Clinical Trials Network (CTN) to explore information related to data completeness and presence of unstructured data (e.g., clinical notes, free text) for conducting the EHR-based research for substance use disorders (SUDs). The analysis was based on 36 participants from 36 facilities located in 14 states and affiliated with the CTN. RESULTS: The mean age of the participants (n = 34) was 48.0 years (SD = 9.8). Of the participants enrolled, 50.0% were female and 82.4% were white. Participants' facilities were from four census-defined regions (South 35.3%, Northeast 29.4%, West 20.6%, Midwest 11.8%, Missing 2.9%) and represented diverse settings. The EHR was used by all surveyed facilities including 17 different kinds of EHR platforms or vendors, and 17.6% (n = 6) of surveyed facilities also used a separate EHR for behavioral health care (e.g., SUD care). Paper records were also used by 76.5% of surveyed facilities for clinical care (e.g., for health risk appraisal questionnaires, substance use screening or assessment, check-in screening, substance use specific intervention/treatment or referral, or labs/testing). The prevalence of using a patient portal, practice management system, and mHealth for patient care was 76.5%, 50.0%, and 29.4%, respectively. CONCLUSION: While results are descriptive in nature, they reveal the heterogeneity in the existing EHRs and frequent use of paper records to document patient care tasks, especially for SUD care. The use of a separate EHR for behavioral healthcare also suggests the challenge of obtaining complete EHR data to support research for SUDs. Much EHR development, integration, and standardization needs to be done especially in regard to SUD treatment to facilitate research across disparate healthcare systems.

10.
J Hazard Mater ; 393: 122405, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32120220

RESUMO

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) have attracted global attention due to their chemical durability, wide distribution, biotoxicity and bioaccumulative properties. Persulfate is a promising alternative to H2O2 for advanced oxidation processes and effective for organic removal. In this review, persulfate activation methods and operational factors in persulfate-based PFOA / PFOS degradation are analyzed and summarized. Moreover, the decomposing mechanisms of PFOA and PFOS are outlined in terms of molecular structures based a series of proposed pathways. PFOS could be converted to PFOA with the attack of SO4- and OH. And then PFOA defluorination occurs with one CF2 unit missing in each round and the similar procedure would occur continuously with sufficient SO4- and OH until entire decomposition. In addition, several knowledge gaps and research needs for further in-depth studies are identified. This review provides an overview for better understanding of the mechanisms and prospects in persulfate-based degradation of PFOA and PFOS.

11.
J Ethnopharmacol ; 255: 112760, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32173427

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese herbal medicine Qing-Dai (also known as Indigo naturalis) extracted from indigo-bearing plants including Baphicacanthus cusia (Ness) Bremek was previously reported to exhibit anti-psoriatic effects in topical treatment. TH17 was later established as a key player in the pathogenesis of psoriasis. We investigated the anti-TH17 effect of Indigo naturalis and its active compounds. The aim of this study is to evaluate the toxicity of Indigo naturalis (IN) and its derivatives on five cell types involved in psoriasis, and to study the anti-inflammatory mechanism for the toxicity. MATERIALS AND METHODS: Following the fingerprint and quantity analysis of indirubin, indigo, and tryptanthrin in IN extract, we used MTS kits to measure the anti-proliferative effect of IN and three active compounds on five different cell types identified in psoriatic lesions. Quantitative RT-PCR analysis was used to measure the expression of various genes identified in the activated keratinocytes and TH17 polarized gene expression in RORγt-expressing T cells. RESULTS: We showed that IN differentially inhibited the proliferation of keratinocytes and endothelial cells but not monocytes, fibroblasts nor Jurkat T cells. Among three active compounds identified in IN, tryptanthrin was the most potent compound to reduce their proliferation. In addition to differentially reducing IL6 and IL8 expression, both IN and tryptanthrin also potently decreased the expression of anti-microbial S100A9 peptide, CCL20 chemokine, IL1B and TNFA cytokines, independent of NF-κB-p65-activation. Their attenuating effect was also detected on the expression of signature cytokines or chemokines induced during RORγT-induced TH17 polarization. CONCLUSIONS: We were the first to confirm a direct anti-TH17 effect of both IN herbal extract and tryptanthrin.

12.
J Ethnopharmacol ; 254: 112717, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32114166

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Amygdalin is commonly distributed in plants of the Rosaceae, such as peach, plum, loquat, apple and bayberry, but most notably in the seeds (kernels) of apricot almonds. As a naturally aromatic cyanogenic compound, it has long been used in Asia, Europe and other regions for the treatment of various diseases including cough, asthma, nausea, leprosy and leukoderma. Importantly, in recent years, an increasing attention has been paid to its antitumor effect. AIM OF THE STUDY: The paper aims to review the pharmacological activities and toxicological effects of amygdalin and provide a reference and perspective for its further investigation. METHODS: Electronic databases including the Web of Science, Cochrane Library, PubMed, EMBASE, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang database and VIP information database were searched up to November 2019 to identify eligible studies. A meticulous review was performed, an in-depth analysis on the pharmacological activity and toxicology of amygdalin was conducted, and perspectives for future research were also discussed. RESULTS: A total of 110 papers about in vitro/in vivo studies on amygdalin have been reviewed. Analysis on the data suggested that this compound presented pharmacological activities of anti-tumor, anti-fibrotic, anti-inflammatory, analgesic, immunomodulatory, anti-atherosclerosis, ameliorating digestive system and reproductive system, improving neurodegeneration and myocardial hypertrophy, as well as reducing blood glucose. In addition, studies revealed that amygdalin's toxicity was caused by its poisonous decomposite product of benzaldehyde and hydrogen cyanide after oral ingestion, toxicity of intravenous administration route was far less than the oral route, and it can be avoidable with an oral dose ranging from 0.6 to 1 g per day. CONCLUSION: This paper has systematically reviewed the pharmacology and toxicology of amygdalin and provided comprehensive information on this compound. We hope this review highlights some perspectives for the future research and development of amygdalin.

13.
Anal Chem ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32141288

RESUMO

Distinguishing the delicate structural differences among molecules is a critical and challenging task in biological/chemical analysis. A molecular decoding strategy has recently become promising to differentiate similar molecules, which is advantageous over the common sensing methods mostly used for detecting a single target. However, the design of an ideal molecular decoder is still strictly hindered by the tailored preparation of probes for particular molecules and the severe lack of widespread feasibility. We herein for the first time proposed to use single bimetallic lanthanide-based metal-organic frameworks (Ln-MOFs) as a powerful, versatile probe for fast and facile decoding of homologues, isomers, enantiomers, and even deuterated isotopomers, based on the unique host-guest interaction of a specific target with the Ln-MOF which could provide an according visual output based on the modulated energy transfer process.

14.
Acta Otolaryngol ; : 1-7, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186224

RESUMO

Background: Neoadjuvant chemotherapy is important for advanced laryngeal and hypopharyngeal carcinoma (LHC).Aims/objectives: To determine the efficacy and toxicity of the combination of docetaxel, nedaplatin, and 5-fluorouracil in induction treatment of advanced LHC.Material and methods: A total of 157 cancer patients were included. The primary endpoints of this study were overall response rate, pathological complete response rate, the safety of induction treatment, progression-free survival (PFS), and overall survival (OS).Results: After two-cycle induction treatment, 17(10.8%) patients experienced complete remission, 76 (48.4%) experienced partial remission, 47 (30.0%) had stable disease, and 17 (10.8%) had progressive disease. The TNM stage decreased by two or more in 17 cases, decreased by one in 71 cases, increased in 15 cases, and did not change in 54 cases after induction treatment. Most of the adverse chemotherapy responses were alleviated by symptomatic management. After the induction treatment, 29 patients continued receiving chemotherapy followed by radiotherapy, and 112 underwent surgical management depending on tumor site followed by radiotherapy. The median PFS was 13.00 ± 2.10 months and the median OS was 14.20 ± 0.29 months.Conclusions and significance: Combination of docetaxel, nedaplatin, and 5-fluorouracil plays an important role in the comprehensive treatment of advanced LHC.

15.
Sci Rep ; 10(1): 4475, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161271

RESUMO

Patients with chronic kidney disease (CKD) are at high risk of infection, but whether the risks are attenuated in different patient groups remains unclear. This study enrolled participants with CKD stages 1-3 in the New Taipei City Health Screening Program between 2005 and 2008. A proportional hazard regression model was employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for infection-related hospitalization and mortality in younger (<50-year-old) and older (≥50-year-old) CKD patients. Of 119,871 adults, there were 14,207 cases of first hospitalization for infection during a median follow-up of 8.14 years; 45.5% of these cases were younger patients. Unlike CKD stage 1 and 2 patients, the risk of infection-related hospitalization in younger CKD stage 3 patients is as high as for older CKD stage 3 patients. Proteinuria increases the risk of infection-related hospitalization independent of estimated glomerular filtration rate (eGFR) levels in older CKD patients but this relationship is weak in their younger counterparts. In conclusion, the risk of infection-related hospitalization is high in subgroups of CKD patients. Prevention and treatment of infections in these patients merit more attention.

16.
Stem Cell Res Ther ; 11(1): 110, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143712

RESUMO

BACKGROUND: Although dental pulp stem cells (DPSCs) isolated from periodontally compromised teeth (P-DPSCs) have been demonstrated to retain pluripotency and regenerative potential, their use as therapeutics remains largely unexplored. In this study, we investigated the proangiogenic effects of extracellular vesicles (EVs) secreted by P-DPSCs using in vitro and in vivo testing models. METHODS: Patient-matched DPSCs derived from periodontally healthy teeth (H-DPSCs) were used as the control for P-DPSCs. Conditioned media (CMs) derived from H-DPSCs and P-DPSCs (H-CM and P-CM), CMs derived from both cell types pretreated with the EV secretion blocker GW4869 (H-GW and P-GW), and EVs secreted by H-DPSCs and P-DPSCs (H-EVs and P-EVs) were prepared to test their proangiogenic effects on endothelial cells (ECs). Cell proliferation, migration, and tube formation were assessed using the Cell Counting Kit-8 (CCK-8), transwell/scratch wound healing, and Matrigel assays, respectively. Specifically, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blot analysis were used to examine the expression levels of angiogenesis-related genes/proteins in ECs in response to EV-based incubation. Finally, a full-thickness skin defect model was applied to test the effects of EVs on wound healing and new vessel formation. RESULTS: Both H-CM and P-CM promoted EC angiogenesis, but the proangiogenic effects were compromised when ECs were incubated in H-GW and P-GW, wherein the EV secretion was blocked by pretreatment with GW4869. In EV-based incubations, although both H-EVs and P-EVs were found to enhance the angiogenesis-related activities of ECs, P-EVs exerted a more robust potential to stimulate EC proliferation, migration, and tube formation. In addition, P-EVs led to higher expression levels of angiogenesis-related genes/proteins in ECs than H-EVs. Similarly, both P-EVs and H-EVs were found to accelerate wound healing and promote vascularization across skin defects in mice, but wounds treated with P-EVs resulted in a quicker healing outcome and enhanced new vessel formation. CONCLUSIONS: The findings of the present study provide additional evidence that P-DPSCs derived from periodontally diseased teeth represent a potential source of cells for research and therapeutic use. Particularly, the proangiogenic effects of P-EVs suggest that P-DPSCs may be used to promote new vessel formation in cellular therapy and regenerative medicine.

17.
J Am Chem Soc ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32160462

RESUMO

Interest on the nonlinear optical (NLO) switches that turn on/off the second-harmonic generation (SHG) triggered by the external stimulus (such as heat) have continuously grown, especially on the solid-state NLO switches showing superior stability, reversibility, and reproducibility. Herein, we discover (NH4)2PO3F, as an entirely new solid-state NLO switch showing outstanding switch contrast and reversibility as well as strong SHG intensity (1.1 × KH2PO4 (KDP)) and high laser-induced damage threshold (2.0 × KDP), undergoes a unique first-order phase transition that originates from a reversible hydrogen-bond rearrangement and needs to overcome an energy barrier. Accordingly, we put forward a strategy to continuously modify such an energy barrier by reducing the number of hydrogen bonds per unit cell via an isoelectronic replacement of NH4+ by K+ with a similar size yet incapability of providing any hydrogen bond. Consequently, Kx(NH4)2-xPO3F (x = 0-0.3) exhibiting excellent switching performance are obtained. Remarkably, Kx(NH4)2-xPO3F not only realizes a continuously tunable Tc spanning from 270 to 150 K, representing the widest NLO switching temperature range ever known but also indicates the first solid-state NLO switch example with continuous Tc. Intrinsically, such a Tc decline depends on the weakening degree of the hydrogen-bonding interactions in the unit cell. These new insights will shed useful light on the future material design and open new application possibilities.

18.
BMC Psychiatry ; 20(1): 124, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171290

RESUMO

BACKGROUND: Previous studies have shown escitalopram is related to sleep quality. However, effects of escitalopram on dynamics of electroencephalogram (EEG) features especially during different sleep stages have not been reported. This study may help to reveal pharmacological mechanism underlying escitalopram treatment. METHODS: The spatial and temporal responses of patients with major depressive disorder (MDD) to escitalopram treatment were analyzed in this study. Eleven MDD patients and eleven healthy control subjects who completed eight weeks' treatment of escitalopram were included in the final statistics. Six-channel sleep EEG signals were acquired during sleep. Power spectrum and nonlinear dynamics were used to analyze the spatio-temporal dynamics features of the sleep EEG after escitalopram treatment. RESULTS: For temporal dynamics: after treatment, there was a significant increase in the relative energy (RE) of Î´1 band (0.5 - 2 Hz), accompanied by a significant decrease in the RE of ß2 band (20 - 30 Hz). Lempel-Ziv complexity and Co - complexity values were significantly lower. EEG changes at different sleep stages also showed the same regulation as throughout the night sleep. For spatio dynamics: after treatment, the EEG response of the left and right hemisphere showed asymmetry. Regarding band-specific EEG complexity estimations, δ1 and ß2 in stage-1 and δ1 in stage-2 sleep stage in frontal cortex is found to be much more sensitive to escitalopram treatment in comparison to central and occipital cortices. CONCLUSIONS: The sleep quality of MDD patients improved, EEG response occurred asymmetry in left and right hemispheres due to escitalopram treatment, and frontal cortex is found to be much more sensitive to escitalopram treatment. These findings may contribute to a comprehensive understanding of the pharmacological mechanism of escitalopram in the treatment of depression.

19.
Chin Med J (Engl) ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32187053

RESUMO

BACKGROUND: Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patient-assessed) and proportions of treatment cost to household income. METHODS: This was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (<10%, 10-30%, 31-50%, and >50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients' treatment satisfaction. RESULTS: When considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P < 0.001). Effectiveness, side effects, and convenience scores were higher in the <10% subgroup compared to those in the >50% subgroup (all P < 0.05). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 13.183, P = 0.004). For biological disease-modifying anti-rheumatic drugs, effectiveness and convenience scores were lower in the severe RA subgroup than those in the extremely mild RA subgroup (both P < 0.05). Convenience score was higher in the <10% subgroup compared to that in the 31% to 50% and >50% subgroups (F = 12.646, P = 0.005). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 8.794, P = 0.032). CONCLUSION: Higher disease severity and higher financial burden were associated with lower patient satisfaction.

20.
J Biol Chem ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188694

RESUMO

The protein tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstream of growth factor receptors.Mutations in the SHP2gene have beenlinked to many different types of human diseases, including developmental disorders, leukemia and solid tumors.Unlike most SHP2-activating mutations, the T507K substitution in SHP2 is unique in that it exhibits oncogenic Ras-like transforming activity. However, the biochemical basis of how the SHP2/T507K variant elicits transformation remains unclear. By combining kinetic and biophysical methods, X-ray crystallography and molecular modeling, as well as using cell biology approaches, here we uncovered that the T507K substitution alters both SHP2 substrate specificity and its allosteric regulatory mechanism. We found that although SHP2/T507K exists in the closed, autoinhibited conformation similar to the wild-type enzyme, the interactions between its N-SH2 and PTP domains are weakened such that SHP2/T507K possesses a higher affinity for the scaffolding protein Grb2-associated binding protein 1 (Gab1). We also discovered that the T507K substitution alters the structure of the SHP2 active site, resulting in a change in SHP2 substrate preference for Sprouty1, a known negative regulator of Ras signaling and potential tumor suppressor. Our results suggest that SHP2/T507K's shift in substrate specificity coupled with its preferential association of SHP2/T507K with Gab1 enables the mutant SHP2 to more efficiently dephosphorylate Sprouty1 at pTyr53. This dephosphorylation hyperactivates Ras signaling, which is likely responsible for SHP2/T507K's Ras-like transforming activity.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA