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1.
Phytochemistry ; 184: 112681, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548771

RESUMO

Seven undescribed (valejatadoids A-G) and 26 known iridoids were obtained from the roots and rhizomes of Valeriana jatamansi. Their structures were determined based on extensive spectroscopic data, especially 1D and 2D NMR, along with HRESIMS. Valejatadoid B is a monoene-type iridoid with a unique double bond between C-4 and C-5. Valejatadoids D-G, jatamanin U, jatamanin O, jatamanvaltrate E, valeriotetrate C, IVHD-valtrate, 10-isovaleroxy-valtrathydrin, jatamanvaltrate Q, valeriandoid F, jatamanvaltrate K, jatamanvaltrate W and isovaltrate were more potent than the positive control when evaluated for inhibition of NO production. Among them, valeriandoid F and jatamanvaltrate K exhibited the most significant inhibitory effects with IC50 values of 0.88 and 0.62 µM, respectively. In addition, valeriandoid F selectively inhibited the proliferation of human glioma stem cell lines, GSC-3# and GSC-18#, with IC50 values of 7.16 and 5.75 µM, respectively.

2.
Support Care Cancer ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33527226

RESUMO

PURPOSE: This study aimed to examine the prevalence of psychological distress and the corresponding risk factors among patients with breast cancer affected by the outbreak of coronavirus disease 2019 (COVID-19). METHODS: This cross-sectional, survey-based, region-stratified study was conducted from March 14 to March 21, 2020. An online survey was used to collect the basic characteristics of patients with breast cancer. The degree of depression, anxiety, and insomnia symptoms were assessed using the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder (GAD-7), and the Insomnia Severity Index (ISI) questionnaires, respectively. Multivariate logistic analysis was performed to identify factors associated with psychological distress outcomes. RESULTS: Among the 834 patients with breast cancer included in the study, the prevalence of depression, anxiety, and insomnia was 21.6%, 15.5%, and 14.7%, respectively. No statistically significant difference in the prevalence of these symptoms was observed between patients in Wuhan and those outside Wuhan. Multivariate logistic regression analyses revealed that comorbidity, living alone, deterioration of breast cancer, and affected treatment plan were risk factors for psychological distress including depression, anxiety, and insomnia. When stratified by location, living alone was associated with depression and insomnia only among patients in Wuhan, but not those outside Wuhan. CONCLUSIONS: This study shows an elevated prevalence of depression, anxiety, and insomnia among patients with breast cancer during part of the COVID-19 pandemic. Patients with comorbidity, living alone, deterioration of breast cancer, and whose treatment plan was affected should be paid more attention to prevent mental disorders.

3.
Sci Total Environ ; 771: 144654, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33545459

RESUMO

Soil saline-alkaline stress and flooding extremes have been projected to be the main factors influencing the degradation of marsh plants in wetlands worldwide, which would affect their ecological functions (i.e. food source for migrating birds). Plants cope with flooding either by escaping from below water through shoot elongation or by remaining quiescent until water subsides. However, little is known about the adaptive strategies of Phragmites australis and Bolboschoenus planiculmis to flooding combined with salinity-alkalinity, which are the key environmental filters in Western Songnen Plain, China. Accordingly, this study investigated the adaptive strategies of P. australis and B. planiculmis subjected to the interacting effects of flooding and soil ion stress under field and greenhouse conditions. Results showed that the two species adopted different strategies to survive flooding. P. australis exhibited an escape strategy because of leaf and shoot elongation with increasing flooding depth whereas B. planiculmis became quiescent with no or deceased leaf and shoot elongation and biomass accumulation. High soil ion stress changed the flooding adaptive strategy of P. australis to a quiescence strategy, whereas B. planiculmis remained quiescent with increasing flooding depth at each soil ion content. The strategies of the two species were changed by alkaline ion stress but not by saline ion stress, and they exhibited different adaptive responses. High alkaline ion stress induced P. australis to remain quiescent with increasing flooding depth, whereas low alkaline ion stress promoted B. planicumis to escape from below water, probably due to the buffer effect of low alkaline ion contents outside the roots probably. Hence, P. australis and B. planicumis might adopt the quiescence strategy with increasing degree of soil salinization and alkalization under high greenhouse gas emissions scenarios in Western Songnen Plain, which may lead to severe degradation of the two kinds of marshes in the future.

4.
Am J Hematol ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606900

RESUMO

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from Jan 2008 to Aug 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation. This article is protected by copyright. All rights reserved.

5.
Chemosphere ; 269: 129395, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33385669

RESUMO

The main purpose of this work was to quantify and characterize chemically and morphologically the emission of soot particles from the open burning of several common solid waste including paperboard, wood, peel, chemical fiber, polyethylene (PE) and polyvinyl chloride (PVC). The experiment was conducted in a laboratory-scale open-burning combustor with a dilution sampling system to obtain soot particles. The thermogravimetric profiles (TGA) showed an increasing order of oxidation reactivity: PE > PVC > fiber > paper ≈ peel > wood. High resolution transmission electron microscopy (HRTEM) images revealed more detailed information about the morphology and the particle size of soot aggregates. Subsequent quantification of nanostructure by fringe analysis showed that plastics generated soot particles with the looser carbon layers with higher tortuosity compared to the three kind of biomass. Raman spectroscopy further confirms the observed differences. In addition, wood soot exhibited the highest content of C-OH group (17.5%) among the six samples (X-Ray photoelectron spectroscopy, XPS), whereas PE and PVC soot exhibited the highest absorption peaks of aliphatic C-H groups (Fourier transform infrared spectroscopy, FTIR). Comparative analysis revealed that the interlayer distance was more important on the evaluation of reactivity than soot morphologies. The present work concluded that the physiochemical characteristics of soot particles releasing during open burning are strongly depending on waste composition and provided new data for the understanding of soot emissions from open burning.


Assuntos
Nanoestruturas , Fuligem , Tamanho da Partícula , Resíduos Sólidos , Madeira
6.
Reprod Domest Anim ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33492695

RESUMO

The microenvironment in the seminiferous tubules of buffalo changes with age, which affects the self-renewal and growth of spermatogonial stem cells (SSCs) and the process of spermatogenesis, but the mechanism remains to be elucidated. RNA-seq was performed to compare the transcript profiles of pre-pubertal buffalo (PUB) and adult buffalo (ADU) seminiferous tubules. In total, 17299 genes from PUB and ADU seminiferous tubules identified through RNA-seq, among which 12271 were expressed in PUB and ADU seminiferous tubules, 4027 were expressed in only ADU seminiferous tubules, and 956 were expressed in only PUB seminiferous tubules. Of the 17299 genes, we identified 13714 genes that had significant differences in expression levels between PUB and ADU through GO enrichment analysis. Among these genes, 5342 were significantly upregulated and possibly related to the formation or identity of the surface antigen on SSCs during self-renewal; 7832 genes were significantly downregulated, indicating that genes in PUB seminiferous tubules do not participate in the biological processes of sperm differentiation or formation in this phase compared with those in ADU seminiferous tubules. Subsequently, through the combination with KEGG analysis, we detected enrichment in a number of genes related to the development of spermatogonial stem cells, providing a reference for study of the development mechanism of buffalo spermatogonial stem cells in the future. In conclusion, our data provide detailed information on the mRNA transcriptomes in PUB and ADU seminiferous tubules, revealing the crucial factors involved in maintaining the microenvironment and providing a reference for further in vitro cultivation of SSCs.

7.
Environ Pollut ; 272: 116416, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433341

RESUMO

Prior human studies have explored effects of phthalate exposures on thyroid function, but the underlying biological mechanisms remain poorly unclear. We aimed to explore the associations between phthalate exposures and thyroid function among a potentially susceptible population such as patients with thyroid nodules, and further to assess the mediating role of oxidative stress. We measured eight phthalate metabolites, three oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine and three thyroid function biomarkers [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4)] in serum among 214 patients with thyroid nodules. Multivariate regression models were applied to assess the associations among urinary phthalate metabolites, oxidative stress and thyroid function biomarkers. The potential mediating role of oxidative stress was explored by mediation analysis. We observed that multiple urinary phthalate metabolites were associated with altered FT4 and increased oxidative stress biomarkers (all FDR-adjusted P ≤ 0.05). Meanwhile, we found that 8-isoPGF2α was negatively associated with FT3/FT4 among patients with benign thyroid nodules (FDR-adjusted P = 0.08). The mediation analysis indicated that 8-isoPGF2α mediated the associations of urinary MEHHP and %MEHP with FT3/FT4, with 55.6% and 32.6% proportion of the mediating effects, respectively. Our data suggest that lipid peroxidation may be an intermediate mechanism involved in the effects of certain phthalate exposures on altered thyroid function among patients with benign thyroid nodules.


Assuntos
Ácidos Ftálicos , Nódulo da Glândula Tireoide , Biomarcadores , Humanos , Estresse Oxidativo , Ácidos Ftálicos/toxicidade
8.
Curr Opin Biotechnol ; 69: 103-111, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33422913

RESUMO

Polyketide natural products are valuable sources of bioactive molecules such as nutraceuticals and pharmaceuticals. The tremendous development of the genome sequence database revealed that the majority of the biosynthetic gene clusters (BGCs) are cryptic. Activation of these cryptic BGCs and identification of the related products is essential for finding more lead compounds for pharmaceuticals. On the other hand, 99% of microbes in nature cannot be cultured in regular conditions, which greatly hinders the efforts to explore their biosynthetic potentials. Expression of polyketide BGCs in heterologous hosts with better growth, good genetic characteristics, and amenable molecular tools is a robust approach to identify new polyketides and characterize their biosynthesis. This review outlines the challenges in the heterologous production of polyketide BGCs of bacterial origins.

9.
Transbound Emerg Dis ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33406318

RESUMO

Infectious bursal disease (IBD) is one of the most economically important infectious diseases. Currently, vaccination is the most effective method to prevent IBD. Medium-virulence vaccines can damage the bursa of Fabricius and result in immunosuppression. Therefore, it is essential to develop a safe and effective vaccine against infectious bursal disease virus (IBDV). In this study, the five neutralizing epitopes of the IBDV VP2 protein were confirmed by neutralizing single chain variable fragment antibodies. Then, the neutralizing epitopes antigen (NEA) protein was constructed with five neutralizing epitopes and expressed by pET-27b. Furthermore, the immune effect and protective immunity of the NEA protein with the following adjuvants were evaluated in specific-pathogen-free chickens: oil emulsion adjuvant (OEA), double emulsion adjuvant (DEA), granulocyte-macrophage colony-stimulating factor (GM-CSF) adjuvant and complete Freund's adjuvant (CFA). The experimental results demonstrated that chickens immunized with NEA vaccines elicited stronger humoral and/or cellular immune responses and inflammatory responses than those in the NEA protein group. Chickens were protected in OEA, CFA and GM-CSF adjuvant groups, which were challenged with virulent IBDV BC6/85. Furthermore, IBDV RNA was not measured, and there appeared to be little apoptosis in the bursa of Fabricius based on TUNEL histology and the expression of Bax and Bcl-2 in the OEA, CFA and GM-CSF adjuvant groups. Based on the experimental results, the advantages and disadvantages of adjuvants and industrial production methods, GM-CSF was found to be the optimal adjuvant. Therefore, NEA with GM-CSF adjuvant is a promising vaccine candidate against IBDV, and it provides a framework for developing other vaccines against infectious viral diseases.

10.
J Hematol Oncol ; 14(1): 12, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436023

RESUMO

BACKGROUND: Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. METHODS: We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. RESULTS: Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30-22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2-51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. CONCLUSIONS: In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. TRIAL REGISTRATION: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.

11.
J Nanosci Nanotechnol ; 21(2): 1054-1060, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33183443

RESUMO

This article explores the role of lysin nanocarriers in inducing apoptosis of human hepatocellular carcinoma cells and the possible molecular mechanisms. Cytotoxicity tests were performed in human fibroblast cell line MRC-5. Anti-cancer activity was tested in liver cancer cell lines HepG2 and HCCLM3. The results show that nanocarriers have a targeting effect on cancer cells, have high safety, and are good delivery vehicles for drugs. In this paper, the stability of lycopene and its degradation in aqueous solutions at different temperatures were studied, and the structure and mechanism of degradation products were determined. A new type of mesoporous silica nanocarrier was synthesized as a delivery carrier of lysin and its derivatives, which has a targeting effect on cancer cells and has a slow-release effect. Surface modification can improve circulation time and stability for future resistance in vivo. The cancer experiment laid the foundation. The results showed that the lysin nanocarriers inhibited the proliferation of HepG2 and HCCLM3 human liver cancer cells in a dependent manner. After the lysin nanocarriers acted on HepG2 human hepatocellular carcinoma cells for 48 h, the cell apoptosis rate was significantly increased by flow cytometry analysis. The carrier can significantly increase the levels of reactive oxygen species and malondialdehyde, and reduce the content of reduced glutathione and superoxide dismutase. At the same time, the lysin nanocarrier can down-regulate the expression of Nrf2 and HO-1 proteins, and inhibit the occurrence of Nrf2 Nuclear displacement. The lycopene nanocarrier inhibits the proliferation of HepG2, HCCLM3 human liver cancer cells, induces apoptosis, regulates the oxidative stress response in the cell, and regulates the Nrf2/AREE antioxidant signaling pathway, thereby promoting tumor cell apoptosis.

12.
Huan Jing Ke Xue ; 42(1): 9-18, 2021 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-33372452

RESUMO

Pollution occurs in the boundary layer, and the thermal and dynamic vertical structure of the boundary layer has a significant influence on the formation of heavy pollution episodes. Based on unmanned aerial vehicle (UAV) sounding, ground-based remote sensing and numerical modeling, this paper analyzes the vertical structure of the boundary layer and the causes of pollution during the heavy pollution episode in Tianjin from January 10 to 15, 2019, with a view to strengthening the understanding of the influence law of boundary layer processes on heavy pollution in northern coastal cities and improving the accuracy of weather forecasts and heavy pollution warnings. The results show that atmospheric temperature stratification had a significant influence on the formation, persistence, and dissipation of heavy pollution episodes. During an episode, accompanied by the development and dissipation of the inversion layer, a high PM2.5 concentration area developed to the upper atmosphere with a height of over 300 m in the daytime and compressed to the ground at night with a height about 100 m. When fog appeared and continued in the daytime, the vertical structure characteristics of the boundary layer changed. A temperature inversion above the fog restrained the diffusion of pollutants to the upper air and made the contribution of turbulence vertical mixing process decrease significantly in the daytime, leading to the persistence and development of heavy pollution near the surface. Regional pollution transport accounted for 66.6% during the episode, which was closely related to regional pollution transport. Regional pollution transport mainly appeared at the top of the boundary layer and above the fog inversion layer where high wind speeds occurred. Pollutants were transported to the ground by a sinking motion as the boundary layer and fog height changed. This is how regional pollution transport occurred when Tianjin was controlled by a weak high pressure field in the north. The vertical structure of the boundary layer also affected the improvement of air quality by cold air. The strong temperature inversion at the top of the fog resulted in the failure of the cold air to transmit to the ground through turbulent shear stress in the S3 stage. There was an obvious difference in wind speed between the upper and lower air. The influence of cold air on the ground was delayed, and the effect of it was weakened. Thus, the heavy pollution episode could not be alleviated completely.

13.
J Orthop Surg Res ; 15(1): 591, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298106

RESUMO

PURPOSE: To evaluate the operation and early clinical effect in primary total knee arthroplasty (TKA) about the novel combination of CT-based patient-specific three-dimensional (3D) preoperative design and conventional osteotomy instruments, compared with the conventional method. METHODS: After a 1:1 propensity score-matching (PSM), patients were matched to the novel technique group and the conventional group, 109 cases in each group. The conventional group adopted a preoperative design based on a full-length radiograph (FLX) and received TKA with conventional osteotomy instruments. The novel technique group used a CT-based patient-specific 3D preoperative design combined with conventional osteotomy instruments; during the surgery, the femoral entry point, femoral valgus osteotomy angle, the fix point of tibial plateau extramedullary guide pin, and the position of tibial extramedullary positioning rod were accurately selected according to the preoperative 3D design to ensure accurate intraoperative implementation. The lower limb alignment, component position, operation time, tourniquet time, hospital stay, blood loss volume, incidence of postoperative complications, visual analog scale (Vas) score, and New Knee Society Score System (NEW-KSS) at 1 day before operation and 1, 6, and 12 months after operation were recorded and compared. RESULTS: The novel technique group was significantly better than the conventional group in controlling lateral tibial component angle (LTC) (P < 0.001), and the novel technique group had lower percentages of hip-knee-ankle angle (HKA) outliers (P < 0.001) and overcorrection (P = 0.003). The operation time, tourniquet time, and hospital stay of the novel technique group was shorter (P < 0.05). In 1 month after the operation, the novel technique group achieved a significantly better VAS score (P < 0.05), but a similar NEW-KSS score (P > 0.05) when compared with the conventional group. But in 6 and 12 months after surgery, no statistical differences were seen in the above two scores (P > 0.05). CONCLUSION: The novel technique of CT-based patient-specific 3D preoperative design combined with conventional instruments can improve the accuracy of osteotomy in primary total knee arthroplasty, with benefits of significantly reducing pain and rapid recovery during the early postoperative period, but having no obvious effect on outcome after a 1-year follow-up.

14.
J Inorg Biochem ; 215: 111318, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33301985

RESUMO

On the one hand, to obtain a novel next-generation anticancer metal agent; on the other hand, to improve the targeting ability and decrease side effects of metal agent, we proposed to design active-targeting human serum albumin (HSA) nanoparticles (NPs) to achieve the end. Thus, we not only designed and synthesized two ruthenium (Ru) thiosemicarbazone compounds (C1 and C2) but also succeeded in constructing active Biotin-HSA NPs for Ru(III) compounds. Importantly, Biotin-HSA-C2 NPs not only possessed a stronger capacity for killing MCF-7 cells and inhibiting their migration versusC2 alone but also increased accumulation compared to non-malignant WI-38 cells. Additionally, C2 and Biotin-HSA-C2 NPs act against MCF-7 cells by the following potential mechanism: 1) arresting the cell cycle in the S phase by regulating cyclin and cyclin-dependent kinases; 2) inducing apoptosis by releasing cytochrome c to activate caspase-9/3; 3) inhibiting the expression of p-EGFR and regulating its neighboring cellular pathways, followed by the inactivation of PI3K/Akt and activation of p38 MAPK signaling pathways.

15.
Neurosci Bull ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33355900

RESUMO

Trigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca2+ concentration, induced the activation of ERK and p38, and increased the expression of pro-inflammatory cytokines in the TG. These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation. Targeting TLR8 signaling may be effective for the treatment of TNP.

16.
J Clin Invest ; 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33373331

RESUMO

Previous studies have shown that nitric oxide (NO) supplements may prevent bone loss and fractures in preclinical models of estrogen deficiency. However, the mechanisms by which NO modulates bone anabolism remain largely unclear. Argininosuccinate lyase (ASL) is the only mammalian enzyme capable of synthesizing arginine, the sole precursor for nitric oxide synthase (NOS)-dependent NO synthesis. Moreover, ASL is also required for channeling extracellular arginine to NOS for NO production. ASL deficiency (ASLD) is thus a model to study cell-autonomous, NOS-dependent NO deficiency. Here, we report that loss of ASL led to decreased NO production and impairment of osteoblast differentiation. Mechanistically, the bone phenotype was at least in part driven by the loss of NO-mediated activation of the glycolysis pathway in osteoblasts that led to decreased osteoblast differentiation and function. Heterozygous deletion of Caveolin-1, a negative regulator of NO synthesis, restored NO production, osteoblast differentiation, glycolysis, and bone mass in a hypomorphic mouse model of ASLD. The translational significance of these preclinical studies was further reiterated by studies conducted in induced pluripotent stem cells (iPSCs) from an individual with ASLD. Taken together, our findings suggest that ASLD is a unique genetic model for studying NO-dependent osteoblast function and that the NO-glycolysis pathway may be a new target to modulate bone anabolism.

17.
J Med Chem ; 63(22): 13695-13708, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33185442

RESUMO

Effective delivery of anticancer agents across the blood-brain barrier (BBB) required innovative strategies to achieve glioma regression. To resolve this problem, we proposed to develop a metal agent that target and treat glioma based on the unique property of apoferritin (AFt) nanoparticles (NPs). Thus, we synthesized a series of Au(III) 3-(4-metyl piperidine)thiosemicarbazides compounds and analyzed their structure-activity relationships, obtaining a Au agent (C6) with remarkable cytotoxicity in glioma. Moreover, we confirmed that C6 kills glioma cells by inducing lethal autophagy and apoptosis. Importantly, our results revealed that the successfully constructed apoferritin-C6 NPs (AFt-C6 NPs) can effectively cross the BBB, inhibit glioma growth, and selectively accumulate in tumors.

18.
Phys Rev Lett ; 125(17): 177203, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33156649

RESUMO

We show that a conical magnetic field H=(1,1,1)H can be used to tune the topological order and hence, anyon excitations of the Z_{2} quantum spin liquid in the isotropic antiferromagnetic Kitaev model. A novel topological order, featured with Chern number C=4 and Abelian anyon excitations, is induced in a narrow range of intermediate fields H_{c1}≤H≤H_{c2}. On the other hand, the C=1 Ising-topological order with non-Abelian anyon excitations, as previously known to be present at small fields, is found here to survive up to H_{c1}. The results are obtained by developing and applying a Z_{2} mean field theory that works at finite fields and is asymptotically exact in the zero field limit and the associated variational quantum Monte Carlo.

19.
Medicine (Baltimore) ; 99(45): e22980, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157941

RESUMO

Coronavirus disease 2019 (COVID-19) has spread worldwide, causing significant stress on the medical system. We explored the risk factors for condition changes in COVID-19 pneumonia patients after admission.The patients diagnosed with COVID-19 pneumonia at 2 medical centers in Hunan Province were studied, and those whose conditions changed after admission were compared. Their clinical characteristics and experimental indicators were compared using SPSS software and R language to build a disease risk prediction model.Patients with condition changes after admission were older and had more blood cell abnormalities and impaired organ function (decreased albumin, elevated D-dimer) than normal patients. We found that age, neutrophil ratio, D-dimer, chest Computed tomograpgy (CT) changes, and glucocorticoid use were risk factors for COVID-19 pneumonia after admission.Elderly patients are more susceptible to disease changes after COVID-19 pneumonia; COVID-19 pneumonia patients who develop disease changes after admission have higher neutrophil ratios, increased D-dimer levels, chest imaging changes, and glucocorticoid usage. Additional research is needed.


Assuntos
Infecções por Coronavirus/diagnóstico , Hospitalização , Pneumonia Viral/diagnóstico , Adulto , Fatores Etários , Idoso , Betacoronavirus , China , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Pandemias , Radiografia Torácica , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
20.
JMIR Mhealth Uhealth ; 8(12): e22098, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33170801

RESUMO

We evaluate a Bluetooth-based mobile contact-confirming app, COVID-19 Contact-Confirming Application (COCOA), which is being used in Japan to contain the spread of COVID-19, the disease caused by the novel virus termed SARS-COV-2. The app prioritizes the protection of users' privacy from a variety of parties (eg, other users, potential attackers, and public authorities), enhances the capacity to balance the current load of excessive pressure on health care systems (eg, local triage of exposure risk and reduction of in-person hospital visits), increases the speed of responses to the pandemic (eg, automated recording of close contact based on proximity), and reduces operation errors and population mobility. The peer-to-peer framework of COCOA is intended to provide the public with dynamic and credible updates on the COVID-19 pandemic without sacrificing the privacy of their information. However, cautions must be exercised to address critical concerns, such as the rate of participation and delays in data sharing. The results of a simulation imply that the participation rate in Japan needs to be close 90% to effectively control the spread of COVID-19.

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