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1.
Oncol Lett ; 28(1): 336, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38846430

RESUMO

The present study compared the differences in effectiveness and safety between segmentectomy (ST) and wedge resection (WR) in patients with operable non-small cell lung cancer (NSCLC). The PubMed, EMBASE, Cochrane Library and Web of Science databases were searched for papers published from inception until July 2023. The inclusion criteria were based on the population, intervention, comparator, outcomes and study designs. ROBINS-I was selected to assess the risk of bias and quality of evidence in the included non-randomised studies. Appropriate effect sizes were selected, and subgroup analyses, heterogeneity tests, sensitivity analyses and publication bias were applied. A total of 18 retrospective studies were included, involving 19,381 patients with operable NSCLC. The 5-year overall survival rate [hazard ratio (HR), 0.19; 95% confidence interval (CI), 0.04, 0.34; P=0.014; I2=76.3%], lung cancer-specific survival rate (HR, 0.3; 95% CI, 0.21, 0.38; P<0.01; I2=13.8%) and metastasis rate [odds ratio (OR), 1.56; 95% CI, 1.03, 2.38; P=0.037] in patients with operable NSCLC treated with WR were worse than those in patients treated with ST. The incidence of postoperative complications (OR, 0.44; 95% CI, 0.23, 0.82) in the WR group was lower than in the ST treatment group. There was no difference in postoperative recurrence (OR, 2.15; 95% CI, 0.97, 4.74; P=0.058) and mortality (risk difference, 0.04; 95% CI, -0.03, 0.11; P=0.287) between groups. Based on current evidence, patients with NSCLC treated with ST surgery have better postoperative survival but more complications than those patients treated with WT, while the effect of WR and ST on the recurrence rate and distant metastasis rate remains controversial.

2.
Diabetes ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38857114

RESUMO

Insulin replacement therapy is indispensable in the treatment of type 1 and advanced type 2 diabetes. However, insulin's clinical application is challenging due to its narrow therapeutic index. To mitigate acute and chronic risks of glucose excursions, glucose-responsive insulin (GRI) has long been pursued for clinical application. By integrating with glucose-sensitive elements, GRI is capable of releasing or activating insulin in response to plasma or interstitial glucose levels without external monitoring, therefore improving glycemic control and reducing hypoglycemic risk. In this perspective, first we introduce the history of GRI development, followed by a review of major glucose-responsive components which can be leveraged to control insulin delivery. Subsequently, we highlight the recent advances in glucose-responsive insulin delivery carriers and insulin analogs. Finally, we provide a look to the future and the challenges of clinical application of GRI.

3.
Sci Total Environ ; : 173923, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880144

RESUMO

Rhizobium inoculation has been widely applied to alleviate heavy metal (HM) stress in legumes grown in contaminated soils, but it has generated inconsistent results with regard to HM accumulation in plant tissues. Here, we conducted a meta-analysis to assess the performance of Rhizobium inoculation for regulating HM in legumes and reveal the general influencing factors and processes. The meta-analysis showed that Rhizobium inoculation in legumes primarily increased the total HM uptake by stimulating plant biomass growth rather than HM phytoavailability. Inoculation had no significant effect on the average shoot HM concentration (p > 0.05); however, it significantly increased root HM uptake by 61 % and root HM concentration by 7 % (p < 0.05), indicating safe agricultural production while facilitating HM phytostabilisation. Inoculation decreased shoot HM concentrations and increased root HM uptake in Vicia, Medicago and Glycine, whereas it increased shoot HM concentrations in Sulla, Cicer and Vigna. The effects of inoculation on shoot biomass were suppressed by nitrogen fertiliser and native microorganisms, and the effect on shoot HM concentration was enhanced by high soil pH, organic matter content, and phosphorous content. Inoculation-boosted shoot nutrient concentration was positively correlated with increased shoot biomass, whereas the changes in pH and organic matter content were insufficient to significantly affect accumulation outcomes. Nitrogen content changes in the soil were positively correlated with changes in root HM concentration and uptake, whereas nitrogen translocation changes in the tissues were positively correlated with changes in HM translocation. Phosphorus solubilisation could improve HM phytoavailability at the expense of slight biomass promotion. These results suggest that the diverse growth-promoting characteristics of Rhizobia influence the trade-off between biomass-HM phytoavailability and HM translocation, impacting HM accumulation outcomes. Our findings can assist in optimising the utilisation of legume-Rhizobium systems in HM-contaminated soils.

4.
J Pharm Anal ; 14(5): 100929, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799234

RESUMO

Analyzing polysorbate 20 (PS20) composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance. The similar structures and polarities of PS20 components make accurate separation, identification, and quantification challenging. In this work, a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) to separate 18 key components with multiple esters. The separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) with an identical gradient as the HPLC-CAD analysis. The polysorbate compound database and library were expanded over 7-time compared to the commercial database. The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship. UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources. The method observed the impact of 4 degradation conditions on peak components, identifying stable components and their tendencies to change. HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences, distinguishing quasi products.

5.
Small Methods ; : e2400376, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801007

RESUMO

Ammonia borane (AB) has emerged as a promising chemical hydrogen storage material. The development of efficient, stable, and cost-effective catalysts for AB hydrolysis is the key to achieving hydrogen energy economy. Here, cobalt phosphide (CoP) is used to anchor single-atom Pt species, acting as robust catalysts for hydrogen generation from AB hydrolysis. Thanks to the high Pt utilization and the synergy between CoP and Pt species, the optimized Pt/CoP-100 catalyst exhibits an unprecedented hydrogen generation rate, giving a record turnover frequency (TOF) value of 39911 mo l H 2 mo l Pt - 1 mi n - 1 ${\mathrm{mo}}{{{\mathrm{l}}}_{{{{\mathrm{H}}}_{\mathrm{2}}}}}{\mathrm{\ mo}}{{{\mathrm{l}}}_{{\mathrm{Pt}}}}^{{\mathrm{ - 1}}}{\mathrm{\ mi}}{{{\mathrm{n}}}^{{\mathrm{ - 1}}}}$ and turnover number of 2926829 mo l H 2 mo l Pt - 1 ${\mathrm{mo}}{{{\mathrm{l}}}_{{{{\mathrm{H}}}_{\mathrm{2}}}}}{\mathrm{\ mo}}{{{\mathrm{l}}}_{{\mathrm{Pt}}}}^{{\mathrm{ - 1}}}$ at room temperature. These metrics surpass those of all existing state-of-the-art supported metal catalysts by an order of magnitude. Density functional theory calculations reveal that the integration of single-atom Pt onto the CoP substrate significantly enhances adsorption and dissociation processes for both water and AB molecules, thereby facilitating hydrogen production from AB hydrolysis. Interestingly, the TOF value is further elevated to 54878 mo l H 2 mo l Pt - 1 mi n - 1 ${\mathrm{mo}}{{{\mathrm{l}}}_{{{{\mathrm{H}}}_{\mathrm{2}}}}}{\mathrm{\ mo}}{{{\mathrm{l}}}_{{\mathrm{Pt}}}}^{{\mathrm{ - 1}}}{\mathrm{\ mi}}{{{\mathrm{n}}}^{{\mathrm{ - 1}}}}$ under UV-vis light irradiation, which can be attributed to the efficient separation and mobility of photogenerated carriers at the Pt-CoP interface. The findings underscore the effectiveness of CoP as a support for single-atom metals in hydrogen production, offering insights for designing high-performance catalysts for chemical hydrogen storage.

6.
Heliyon ; 10(10): e31097, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38807884

RESUMO

The Sustainable Development Goals (SDGs) reflect the shift in global economic conversation toward inclusive growth. The growth can promote inclusivity and widespread sharing of its advancements by concentrating on four key dimensions. (a) Equality of opportunity, (b) sharing prosperity, (3) environmental sustainability/climate adaptation, and (4) macroeconomic stability. We used the Kao cointegration test to study how certain variables are connected over a long period. The relationship between CO2 and GDP per capita, renewable energy and tourism, improved water and sanitation, and access to power all have a positive feedback effect on each other. Based on FMOLS's findings, a 1 % increase in Inclusive growth leads to a 0.342 % (Model 1) and 0.258 % (Model 3) increase in CO2 emissions. An increase of 1 percent in energy consumption per person resulted in a rise of 1.343 % in CO2 emissions in Case 1, 0.524 % in Case 2, and 0.618 % in Case 3. Increasing the tourism sector's proportion of total exports by just one percent will reduce CO2 emissions by 0.221 % (case 1) and 0.234 % (case 3). Based on CCR findings, a 1 % improvement in inclusive growth leads to a 0.403.

7.
Macromol Rapid Commun ; : e2400129, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778746

RESUMO

Biopolymeric implantable patches are popular scaffolds for myocardial regeneration applications. Besides being biocompatible, they can be tailored to have required properties and functionalities for this application. Recently, fibrillar biobased nanostructures prove to be valuable in the development of functional biomaterials for tissue regeneration applications. Here, periodate-oxidized nanofibrillated cellulose (OxNFC) is blended with lysozyme amyloid nanofibrils (LNFs) to prepare a self-crosslinkable patch for myocardial implantation. The OxNFC:LNFs patch shows superior wet mechanical properties (60 MPa for Young's modulus and 1.5 MPa for tensile stress at tensile strength), antioxidant activity (70% scavenging activity under 24 h), and bioresorbability ratio (80% under 91 days), when compared to the patches composed solely of NFC or OxNFC. These improvements are achieved while preserving the morphology, required thermal stability for sterilization, and biocompatibility toward rat cardiomyoblast cells. Additionally, both OxNFC and OxNFC:LNFs patches reveal the ability to act as efficient vehicles to deliver spermine modified acetalated dextran nanoparticles, loaded with small interfering RNA, with 80% of delivery after 5 days. This study highlights the value of simply blending OxNFC and LNFs, synergistically combining their key properties and functionalities, resulting in a biopolymeric patch that comprises valuable characteristics for myocardial regeneration applications.

8.
IEEE Trans Image Process ; 33: 3227-3241, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38691435

RESUMO

The statistical regularities of natural images, referred to as natural scene statistics, play an important role in no-reference image quality assessment. However, it has been widely acknowledged that screen content images (SCIs), which are typically computer generated, do not hold such statistics. Here we make the first attempt to learn the statistics of SCIs, based upon which the quality of SCIs can be effectively determined. The underlying mechanism of the proposed approach is based upon the mild assumption that the SCIs, which are not physically acquired, still obey certain statistics that could be understood in a learning fashion. We empirically show that the statistics deviation could be effectively leveraged in quality assessment, and the proposed method is superior when evaluated in different settings. Extensive experimental results demonstrate the Deep Feature Statistics based SCI Quality Assessment (DFSS-IQA) model delivers promising performance compared with existing NR-IQA models and shows a high generalization capability in the cross-dataset settings. The implementation of our method is publicly available at https://github.com/Baoliang93/DFSS-IQA.

9.
Angew Chem Int Ed Engl ; : e202405459, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711309

RESUMO

The hydrogen evolution and nitrite reduction reactions are key to producing green hydrogen and ammonia. Antenna-reactor nanoparticles hold promise to improve the performances of these transformations under visible-light excitation, by combining plasmonic and catalytic materials. However, current materials involve compromising either on the catalytic activity or the plasmonic enhancement and also lack control of reaction selectivity. Here, we demonstrate that ultralow loadings and non-uniform surface segregation of the catalytic component optimize catalytic activity and selectivity under visible-light irradiation. Taking Pt-Au as an example we find that fine-tuning the Pt content produces a 6-fold increase in the hydrogen evolution compared to commercial Pt/C as well as a 6.5-fold increase in the nitrite reduction and a 2.5-fold increase in the selectivity for producing ammonia under visible light excitation relative to dark conditions. Density functional theory suggests that the catalytic reactions are accelerated by the intimate contact between nanoscale Pt-rich and Au-rich regions at the surface, which facilitates the formation of electron-rich hot-carrier puddles associated with the Pt-based active sites. The results provide exciting opportunities to design new materials with improved photocatalytic performance for sustainable energy applications.

10.
J Pharm Biomed Anal ; 245: 116194, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38704878

RESUMO

A miniature mass spectrometer (mMS) based point-of-care testing (POCT) method was evaluated for on-site detecting the hypertension drugs, amlodipine and benazepril. The instrument parameters, including voltage, ISO1, ISO2, and CID, were optimized, under which the target compounds could be well detected in MS2. When these two drugs were injected simultaneously, the mutual ionization inhibition and mutual reduction between amlodipine and benazepril were evaluated. This phenomenon was severe on the precursor ions but had a small impact on the product ions, thus making this POCT method suitable for analysis using product ions. Finally, the method was validated and applied. The blood samples from patients were tested one hour after oral administration of the drugs (20 mg), and the benazepril was quantitatively analyzed using a standard curve, with detected concentrations ranging from 190.6 to 210 µg L-1 and a relative standard deviation (RSD) of 8.6 %. In summary, amlodipine has low sensitivity and can only be detected at higher concentrations, while benazepril has high sensitivity, good linearity, and even meets semi-quantitative requirements. The research results of this study are of great clinical significance for monitoring blood drug concentrations during hypertension medication, predicting drug efficacy, and customizing individualized medication plans.


Assuntos
Anlodipino , Anti-Hipertensivos , Benzazepinas , Anlodipino/sangue , Humanos , Benzazepinas/sangue , Anti-Hipertensivos/sangue , Anti-Hipertensivos/administração & dosagem , Espectrometria de Massas/métodos , Testes Imediatos , Reprodutibilidade dos Testes , Limite de Detecção , Sistemas Automatizados de Assistência Junto ao Leito
11.
Plant Biotechnol J ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816932

RESUMO

Many biotic or abiotic factors such as CPPU (N-(2-chloro-pyridin-4-yl)-N'-phenylurea), a growth regulator of numerous crops, can induce bitterness in cucurbits. In melon, cucurbitacin B is the major compound leading to bitterness. However, the molecular mechanism underlying CuB biosynthesis in response to different conditions remains unclear. Here, we identified a set of genes involved in CPPU-induced CuB biosynthesis in melon fruit and proposed CmBr gene as the major regulator. Using CRISPR/Cas9 gene editing, we confirmed CmBr's role in regulating CuB biosynthesis under CPPU treatment. We further discovered a CPPU-induced MYB-related transcription factor, CmRSM1, which specifically binds to the Myb motif within the CmBr promoter and activates its expression. Moreover, we developed an introgression line by introducing the mutated Cmbr gene into an elite variety and eliminated CPPU-induced bitterness, demonstrating its potential application in breeding. This study offers a valuable tool for breeding high-quality non-bitter melon varieties and provides new insights into the regulation of secondary metabolites under environmental stresses.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38615157

RESUMO

Cell-mediated nanoparticle delivery systems (CMNDDs) utilize cells as carriers to deliver the drug-loaded nanoparticles. Unlike the traditional nanoparticle drug delivery approaches, CMNDDs take the advantages of cell characteristics, such as the homing capabilities of stem cells, inflammatory chemotaxis of neutrophils, prolonged blood circulation of red blood cells, and internalization of macrophages. Subsequently, CMNDDs can easily prolong the blood circulation, cross biological barriers, such as the blood-brain barrier and the bone marrow-blood barrier, and rapidly arrive at the diseased areas. Such advantageous properties make CMNDDs promising delivery candidates for precision targeting. In this review, we summarize the recent advances in CMNDDs fabrication and biomedical applications. Specifically, ligand-receptor interactions, non-covalent interactions, covalent interactions, and internalization are commonly applied in constructing CMNDDs in vitro. By hitchhiking cells, such as macrophages, red blood cells, monocytes, neutrophils, and platelets, nanoparticles can be internalized or attached to cells to construct CMNDDs in vivo. Then we highlight the recent application of CMNDDs in treating different diseases, such as cancer, central nervous system disorders, lung diseases, and cardiovascular diseases, with a brief discussion about challenges and future perspectives in the end.

13.
J Hazard Mater ; 470: 134140, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38574658

RESUMO

The backfill mining of coal-based solid waste in goaf poses a potential risk of heavy metal pollution to the groundwater environment, and the migration behavior of heavy metals differs significantly under the disturbance of backfill mining in close-distance multi-layer coal seams and single-layer coal seams. In this study, a migration model of heavy metals after solid backfilling in the goaf of shallow-buried close-distance thick coal seams was established, and the impact of the overburden damage and the layered distribution of the filling body on the long-term migration behavior of heavy metals were analyzed. The results show that the migration of heavy metals after close-distance coal seam backfill mining exhibits a higher risk of heavy metal pollution. The peak permeability of overburden after close-distance coal seam backfill mining is about 600 × 10-19 m2 higher than that after single-layer coal seam backfill mining. The migration distance of heavy metals in the floor after backfill mining of close-distance coal seams is 7.41 m farther than that of single-layer coal seam backfill mining, and its migration time of heavy metals to the surface is 27 a earlier than that of single-layer coal seam. This research provides theoretical and empirical support for the ecological risk assessment and heavy metal pollution control in close-distance coal seam backfill mining. ENVIRONMENTAL IMPLICATION: The main filling material of close-distance coal seams backfill mining is coal gangue. Heavy metal elements such as Mn and Cr will be released in the underground environment for a long time, and the migration behavior of heavy metal elements will have an impact on the groundwater environment for more than 1000 years. This research provides theoretical and empirical support for the ecological risk assessment of close-distance coal seam backfill mining and the mitigation of heavy metal pollution.

14.
Foods ; 13(8)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38672942

RESUMO

BACKGROUND: Dietary intervention is the preferred approach for the prevention and clinical management of gout. Nevertheless, the existing evidence regarding the influence of specific foods on gout is insufficient. METHODS: We used two-sample Mendelian randomization for genetic prediction to analyze the relationship between the intake of more than a dozen daily food items, such as pork, beef, cheese, and poultry, and dietary macronutrient intake (fat, protein, carbohydrates, and sugar) and the risk of developing gout and elevating the serum uric acid level. Inverse-variance weighted MR analyses were used as the main evaluation method, and the reliability of the results was tested by a sensitivity analysis. RESULTS: Cheese intake was associated with lower serum uric acid levels, and tea intake (OR = 0.523, [95%CI: 0.348~0.784], p = 0.002), coffee intake (OR = 0.449, [95%CI: 0.229~0.882], p = 0.020), and dried fruit intake (OR = 0.533, [95%CI: 0.286~0.992], p = 0.047) showed a preventive effect on the risk of gouty attacks. In contrast, non-oily fish intake (ß = 1.08, [95%CI: 0.24~1.92], p = 0.012) and sugar intake (ß = 0.34, [95%CI: 0.03~0.64], p = 0.030) were risk factors for elevated serum uric acid levels, and alcohol intake frequency (OR = 1.422, [95%CI: 1.079~1.873], p = 0.012) was a risk factors for gout predisposition. CONCLUSIONS: These results will significantly contribute to the formulation and refinement of nutritional strategies tailored to patients afflicted with gout.

15.
Mycoses ; 67(4): e13721, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570912

RESUMO

BACKGROUND: Psoriatic patients may experience the coexistence of onychomycosis (OM). However, the evaluation of OM in psoriatics has been hindered by potential clinical differences from OM in non-psoriatics. OBJECTIVE: To assess and compare dermoscopic features between toenail OM in psoriatic and in non-psoriatic patients. PATIENTS AND METHODS: Between September 2020 and September 2023, dermoscopy was conducted on 183 affected toenails by OM in psoriatics and 232 affected toenails by OM in non-psoriatics in two centres. The dermoscopic characteristics were compared using the Chi-squared test. RESULTS: Among toenail OM cases in psoriatic subjects, the most prevalent dermoscopic features included pitting (147/183, 80.33%) and subungual hyperkeratosis (118/183, 64.48%). Conversely, toenail OM in non-psoriatics was characterized by subungual hyperkeratosis (175/232, 75.43%) and nail spikes (139/232, 59.91%). Comparative analysis revealed a significantly higher occurrence of pitting (80.33% vs. 15.96%, p < .001), periungual telangiectasis (22.40% vs. 4.74%, p < .001), oil patches (12.57% vs. 0.43%,p < .001) and transverse grooves (43.72% vs. 28.45%,p < .01) in toenail OM in psoriatics. Furthermore, toenail OM in psoriatics exhibited a significantly lower frequency of yellow structureless area (13.11% vs. 42.67%, p < .001), nail spikes (43.17% vs. 59.91%, p < .01), ruin appearance of sulphur nugget (8.20% vs. 31.03%, p < .001), dotted/blocky haemorrhage (6.01% vs. 20.69%,p < .001) and partial onycholysis (32.79% vs. 46.98%, p < .01). CONCLUSIONS: Dermoscopic features of toenail OM in psoriatic and non-psoriatic patients exhibit notable differences. OM in psoriatics shows a higher frequency of pitting and periungual telangiectasis, while a lower frequency of yellow structureless areas and nail spikes under dermoscopy.


Assuntos
Ceratose , Doenças da Unha , Onicomicose , Telangiectasia , Humanos , Onicomicose/epidemiologia , Onicomicose/complicações , Unhas , Estudos Prospectivos , Ceratose/complicações , Telangiectasia/complicações
16.
Adv Sci (Weinh) ; 11(21): e2308910, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582507

RESUMO

Myocardial infarction (MI) is a critical global health challenge, with current treatments limited by the complex MI microenvironment, particularly the excessive oxidative stress and intense inflammatory responses that exacerbate cardiac dysfunction and MI progression. Herein, a mannan-based nanomedicine, Que@MOF/Man, is developed to target the inflammatory infarcted heart and deliver the antioxidative and anti-inflammatory agent quercetin (Que), thereby facilitating a beneficial myocardial microenvironment for cardiac repair. The presence of mannan on the nanoparticle surface enables selective internalization by macrophages rather than cardiomyocytes. Que@MOF/Man effectively neutralizes reactive oxygen species in macrophages to reduce oxidative stress and promote their differentiation into a reparative phenotype, reconciling the inflammatory response and enhancing cardiomyocyte survival through intercellular communication. Owing to the recruitment of macrophages into inflamed myocardium post-MI, in vivo, administration of Que@MOF/Man in MI rats revealed the specific distribution into the injured myocardium compared to free Que. Furthermore, Que@MOF/Man exhibited favorable results in resolving inflammation and protecting cardiomyocytes, thereby preventing further myocardial remodeling and improving cardiac function in MI rats. These findings collectively validate the rational design of an inflammation-targeted delivery strategy to mitigate oxidative stress and modulate the inflammation response in the injured heart, presenting a therapeutic avenue for MI treatment.


Assuntos
Modelos Animais de Doenças , Inflamação , Macrófagos , Infarto do Miocárdio , Nanomedicina , Estresse Oxidativo , Animais , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Ratos , Nanomedicina/métodos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Inflamação/metabolismo , Quercetina/farmacologia , Quercetina/administração & dosagem , Masculino , Ratos Sprague-Dawley , Nanopartículas , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Antioxidantes/farmacologia
17.
Viruses ; 16(4)2024 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-38675833

RESUMO

One of the major functions of the accessory protein Vif of human immunodeficiency virus type 1 (HIV-1) is to induce the degradation of APOBEC3 (A3) family proteins by recruiting a Cullin5-ElonginB/C-CBFß E3 ubiquitin ligase complex to facilitate viral replication. Therefore, the interactions between Vif and the E3 complex proteins are promising targets for the development of novel anti-HIV-1 drugs. Here, peptides are designed for the Vif-CBFß interaction based on the sequences of Vif mutants with higher affinity for CBFß screened by a yeast surface display platform. We identified two peptides, VMP-63 and VMP-108, that could reduce the infectivity of HIV-1 produced from A3G-positive cells with IC50 values of 49.4 µM and 55.1 µM, respectively. They protected intracellular A3G from Vif-mediated degradation in HEK293T cells, consequently increasing A3G encapsulation into the progeny virions. The peptides could rapidly enter cells after addition to HEK293T cells and competitively inhibit the binding of Vif to CBFß. Homology modeling analysis demonstrated the binding advantages of VMP-63 and VMP-108 with CBFß over their corresponding wild-type peptides. However, only VMP-108 effectively restricted long-term HIV-1 replication and protected A3 functions in non-permissive T lymphocytes. Our findings suggest that competitive Vif-derived peptides targeting the Vif-CBFß interaction are promising for the development of novel therapeutic strategies for acquired immune deficiency syndrome.


Assuntos
Fármacos Anti-HIV , Subunidade beta de Fator de Ligação ao Core , HIV-1 , Peptídeos , Ligação Proteica , Produtos do Gene vif do Vírus da Imunodeficiência Humana , Produtos do Gene vif do Vírus da Imunodeficiência Humana/metabolismo , Produtos do Gene vif do Vírus da Imunodeficiência Humana/genética , Humanos , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Células HEK293 , Subunidade beta de Fator de Ligação ao Core/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo , Peptídeos/química , Fármacos Anti-HIV/farmacologia , Replicação Viral/efeitos dos fármacos , Desenho de Fármacos , Infecções por HIV/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo
18.
Plant Sci ; 344: 112083, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38588982

RESUMO

Due to the extended generation cycle of trees, the breeding process for forest trees tends to be time-consuming. Genetic engineering has emerged as a viable approach to expedite the genetic breeding of forest trees. However, current genetic engineering techniques employed in forest trees often utilize continuous expression promoters such as CaMV 35S, which may result in unintended consequences by introducing genes into non-target tissues. Therefore, it is imperative to develop specific promoters for forest trees to facilitate targeted and precise design and breeding. In this study, we utilized single-cell RNA-Seq data and co-expression network analysis during wood formation to identify three vascular tissue-specific genes in poplar, PP2-A10, PXY, and VNS07, which are expressed in the phloem, cambium/expanding xylem, and mature xylem, respectively. Subsequently, we cloned the promoters of these three genes from '84K' poplar and constructed them into a vector containing the eyGFPuv visual selection marker, along with the 35S mini enhancer to drive GUS gene expression. Transgenic poplars expressing the ProPagPP2-A10::GUS, ProPagPXY::GUS, and ProPagVNS07::GUS constructs were obtained. To further elucidate the tissue specificity of these promoters, we employed qPCR, histochemical staining, and GUS enzyme activity. Our findings not only establish a solid foundation for the future utilization of these promoters to precisely express of specific functional genes in stems but also provide a novel perspective for the modular breeding of forest trees.


Assuntos
Populus , Regiões Promotoras Genéticas , Populus/genética , Populus/metabolismo , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética , Xilema/genética , Xilema/metabolismo , Floema/genética , Floema/metabolismo , Genes de Plantas
19.
Heliyon ; 10(7): e27925, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38633640

RESUMO

The restorative benefits of urban green spaces (UGSs) have been supported by many studies. Eight perceived sensory dimensions (PSDs) are regarded as a tool to classify green spaces based on perception. However, little attention has been given to the effects of landscape characteristics (LCs) on the perceived restorativeness (PR) of green spaces. Thus, this study aims to clarify this relationship using the eight PSDs. The research collected information, via video stimulus, from 30 participants on the restorative experiences of urban green parks, according to the eight kinds of PSDs. The skin conductance level obtained via biosensors was used to measure the PR. The subjective satisfaction evaluation of 10 LCs was further obtained using a 5-point Likert scale. The data were analyzed using correlation and regression analyses. The results show that the UGSs with dominant "serene," "open," and "sheltered" PSDs are rated highest for restoration. Furthermore, the findings identify the significant factors affecting the restoration of green spaces using different PSDs. In green spaces controlled by PSD, scene, vegetation, water features, and disturbances are more reliable predictors for restoration. The results indicate how different PSD spaces can be distributed in green urban planning and provide key points for designing each PSD for restoration. The use of physiological indexes rather than subjective feelings provides an alternative for demonstrating the restorative benefits of the environment. However, before it can officially be used by designers, more research is needed.

20.
Int Immunopharmacol ; 131: 111861, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38484665

RESUMO

Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Desacetilase 6 de Histona , Leucemia Mieloide Aguda , Animais , Humanos , Camundongos , Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Glutationa/metabolismo , Desacetilase 6 de Histona/antagonistas & inibidores , Leucemia Mieloide Aguda/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos
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