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1.
Sensors (Basel) ; 24(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38794003

RESUMO

With the rapid development of the intelligent driving technology, achieving accurate path planning for unmanned vehicles has become increasingly crucial. However, path planning algorithms face challenges when dealing with complex and ever-changing road conditions. In this paper, aiming at improving the accuracy and robustness of the generated path, a global programming algorithm based on optimization is proposed, while maintaining the efficiency of the traditional A* algorithm. Firstly, turning penalty function and obstacle raster coefficient are integrated into the search cost function to increase the adaptability and directionality of the search path to the map. Secondly, an efficient search strategy is proposed to solve the problem that trajectories will pass through sparse obstacles while reducing spatial complexity. Thirdly, a redundant node elimination strategy based on discrete smoothing optimization effectively reduces the total length of control points and paths, and greatly reduces the difficulty of subsequent trajectory optimization. Finally, the simulation results, based on real map rasterization, highlight the advanced performance of the path planning and the comparison among the baselines and the proposed strategy showcases that the optimized A* algorithm significantly enhances the security and rationality of the planned path. Notably, it reduces the number of traversed nodes by 84%, the total turning angle by 39%, and shortens the overall path length to a certain extent.

2.
Sensors (Basel) ; 24(10)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38793935

RESUMO

During the braking process of electric vehicles, both the regenerative braking system (RBS) and anti-lock braking system (ABS) modulate the hydraulic braking force, leading to control conflict that impacts the effectiveness and real-time capability of coordinated control. Aiming to enhance the coordinated control effectiveness of RBS and ABS within the electro-hydraulic composite braking system, this paper proposes a coordinated control strategy based on explicit model predictive control (eMPC-CCS). Initially, a comprehensive braking control framework is established, combining offline adaptive control law generation, online optimized control law application, and state compensation to effectively coordinate braking force through the electro-hydraulic system. During offline processing, eMPC generates a real-time-oriented state feedback control law based on real-world micro trip segments, improving the adaptiveness of the braking strategy across different driving conditions. In the online implementation, the developed three-dimensional eMPC control laws, corresponding to current driving conditions, are invoked, thereby enhancing the potential for real-time braking strategy implementation. Moreover, the state error compensator is integrated into eMPC-CCS, yielding a state gain matrix that optimizes the vehicle braking status and ensures robustness across diverse braking conditions. Lastly, simulation evaluation and hardware-in-the-loop (HIL) testing manifest that the proposed eMPC-CCS effectively coordinates the regenerative and hydraulic braking systems, outperforming other CCSs in terms of braking energy recovery and real-time capability.

3.
Small ; 19(50): e2205078, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36587991

RESUMO

Three-dimensional (3D) bioprinting is driving significant innovations in biomedicine over recent years. Under certain scenarios such as in intraoperative bioprinting, the bioinks used should exhibit not only cyto/biocompatibility but also adhesiveness in wet conditions. Herein, an adhesive bioink composed of gelatin methacryloyl, gelatin, methacrylated hyaluronic acid, and skin secretion of Andrias davidianus is designed. The bioink exhibits favorable cohesion to allow faithful extrusion bioprinting in wet conditions, while simultaneously showing good adhesion to a variety of surfaces of different chemical properties, possibly achieved through the diverse bonds presented in the bioink formulation. As such, this bioink is able to fabricate sophisticated planar and volumetric constructs using extrusion bioprinting, where the dexterity is further enhanced using ergonomic handheld bioprinters to realize in situ bioprinting. In vitro experiments reveal that cells maintain high viability; further in vivo studies demonstrate good integration and immediate injury sealing. The characteristics of the bioink indicate its potential widespread utility in extrusion bioprinting and will likely broaden the applications of bioprinting toward situations such as in situ dressing and minimally invasive tissue regeneration.


Assuntos
Bioimpressão , Alicerces Teciduais , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Adesivos , Gelatina/química , Pele , Cicatrização , Impressão Tridimensional , Hidrogéis/química , Bioimpressão/métodos
4.
BMC Geriatr ; 23(1): 716, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37924002

RESUMO

BACKGROUND: Frailty is common and not limited to older age group. Serum α-Klotho works as a biomarker of anti-aging effect. However, there is limited research about the relationship between them in middle-aged and older people and controversy still exists. METHODS: Based on data from National Health and Nutrition Examination Survey (NHANES) 2007-2016, we constructed weighted logistic regression models and conducted sensitivity tests to investigate the correlation between frailty and α-Klotho among people aged 40 to 79. And then their relationship was visualized by Restricted Cubic Spline (RCS). Finally, the stratified analyses and interaction tests of covariables was presented in the forest plot. RESULTS: A total of 7052 individuals were involved in this study, with mean age of 62.76 ± 0.18 years and females accounting for 51.05%. 2554 of them were in "frailty". After adjustment for relevant covariables, weighted logistic regression models showed that the odds ratio and 95% confidence interval [ORs (95%CI)] of correlation between frailty and Natural Logarithm(ln)-transformed α- Klotho[ln(α-Klotho)] was 0.63 (0.50, 0.79); we then performed a sensitivity analysis and found that the results remained stable. In model 3, individuals in quartiles 2, 3, and 4 showed statistical differences compared with the lowest ln(α-Klotho) quartiles, ORs (95% CI) were 0.74 (0.59, 0.93), 0.72 (0.57, 0.91), 0.71 (0.57, 0.87), respectively. Subsequently, non-linear associations were exhibited by RCS (p<0.001). The turning point for α-Klotho and ln(α-Klotho) were 785.7(pg/ml) and 6.67, respectively. Finally, analysis of the relationship between different levels of ln(α-Klotho) and frailty in different populations revealed differences between groups. The results of the interaction test showed that no other covariables had significant interaction with serum α-Klotho in our study. CONCLUSION: The L-shaped and negative correlation was found between α-Klotho and frailty among people aged 40 to 79 in the NHANES from 2007 to 2016.


Assuntos
Fragilidade , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Inquéritos Nutricionais , Envelhecimento , Biomarcadores , Modelos Logísticos
5.
Cancer Cell Int ; 22(1): 417, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36572921

RESUMO

BACKGROUND: Pancreatic cancer is one of the most aggressive malignancies without effective targeted therapies. MUC1 has emerged as a potential common target for cancer therapy because it is overexpressed in a variety of different cancers including the majority of pancreatic cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1 have been reported. Recently, we generated a humanized MUC1 antibody (HzMUC1) specific to the interaction region between MUC1-N and MUC1-C. In this study, we generated the antibody drug conjugate (ADC) by conjugating HzMUC1 with monomethyl auristatin (MMAE), and examined the efficacy of HzMUC1-MMAE against the MUC1-positive pancreatic cancer in vitro and in vivo. METHODS: Western blot and immunoprecipitation were used to detect MUC1 in pancreatic cancer cells. MUC1 localization in pancreatic cancer cells was determined by confocal microscopy. HzMUC1 was conjugated with the monomethyl auristatin (MMAE), generating the HzMUC1-MMAE ADC. Colony formation assay and flow cytometry were used to assess the effects of the HzMUC1-MMAE cell viability, cell cycle progression and apoptosis. Capan-2 and CFPAC-1 xenograft model were used to test the efficacy of HzMUC1-MMAE against pancreatic cancer. RESULTS: HzMUC1 antibody binds to MUC1 on the cell surface of pancreatic cancer cells. HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in pancreatic cancer cells. Importantly, HzMUC1-MMAE significantly reduced the growth of pancreatic xenograft tumors by inhibiting cell proliferation and enhancing cell death. CONCLUSION: Our results indicate that HzMUC1-ADC is a promising novel targeted therapy for pancreatic cancer. HzMUC1-ADC should also be an effective drug for the treatment of different MUC1-positive cancers.

6.
Blood ; 131(20): 2247-2255, 2018 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29615403

RESUMO

Mantle cell lymphoma (MCL) is characterized by increased B-cell receptor (BCR) signaling, and BTK inhibition is an effective therapeutic intervention in MCL patients. The mechanisms leading to increased BCR signaling in MCL are poorly understood, as mutations in upstream regulators of BCR signaling such as CD79A, commonly observed in other lymphomas, are rare in MCL. The transcription factor SOX11 is overexpressed in the majority (78% to 93%) of MCL patients and is considered an MCL-specific oncogene. So far, attempts to understand SOX11 function in vivo have been hampered by the lack of appropriate animal models, because germline deletion of SOX11 is embryonically lethal. We have developed a transgenic mouse model (Eµ-SOX11-EGFP) in the C57BL/6 background expressing murine SOX11 and EGFP under the control of a B-cell-specific IgH-Eµ enhancer. The overexpression of SOX11 exclusively in B cells exhibits oligoclonal B-cell hyperplasia in the spleen, bone marrow, and peripheral blood, with an immunophenotype (CD5+CD19+CD23-) identical to human MCL. Furthermore, phosphocytometric time-of-flight analysis of the splenocytes from these mice shows hyperactivation of pBTK and other molecules in the BCR signaling pathway, and serial bone marrow transplant from transgenic donors produces lethality with decreasing latency. We report here that overexpression of SOX11 in B cells promotes BCR signaling and a disease phenotype that mimics human MCL.


Assuntos
Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/patologia , Receptores de Antígenos de Linfócitos B/metabolismo , Fatores de Transcrição SOXC/metabolismo , Transdução de Sinais , Microambiente Tumoral , Animais , Linfócitos B/metabolismo , Linfócitos B/patologia , Biomarcadores , Linhagem Celular Tumoral , Evolução Clonal , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cadeias Pesadas de Imunoglobulinas , Linfoma de Célula do Manto/genética , Camundongos , Camundongos Transgênicos , Fenótipo , Fatores de Transcrição SOXC/genética
7.
J Environ Manage ; 271: 111029, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32778309

RESUMO

Biochar has been widely applied to paddy fields to improve soil fertility, crop productivity and carbon sequestration, thereby leading to variations in the CO2 exchange between the paddy fields under flooding irrigation and the atmosphere, as indicated by many previous reports. However, few relevant reports have focused on paddy fields under water-saving irrigation. This study conducted a field experiment to investigate the effects of three biochar addition rates (0, 20 and 40 t ha-1) on the CO2 exchange between paddy fields under controlled irrigation (CI, a water-saving irrigation technique) and the atmosphere in the Taihu Lake region of Southeast China. Our results showed that biochar addition increased the paddy field ecosystem respiration (Reco) and the soil respiration rate (Rs) in the CI paddy fields. And biochar application increased the total CO2 emissions and the total soil CO2 emissions, especially at a rate of 40 t ha-1. In contrast, gross primary productivity (GPP) was decreased and the net ecosystem exchange of CO2 (NEE) was increased with biochar addition. However, biochar addition at a rate of 20 t ha-1 significantly increased the total CO2 absorption and the net CO2 absorption of the CI paddy fields (p < 0.05), whereas biochar addition at a rate of 40 t ha-1 had no effect on the total CO2 absorption and decreased the total net CO2 absorption. At the same time, biochar addition significantly increased soil catalase, invertase and urease activities and contributed substantially to the increase in soil invertase activity. In addition, the soil bacterial, fungal and actinomycetal abundances were evidently increased with biochar addition, of which the soil fungal abundance showed the greatest increase. A high correlation was observed between soil catalase and invertase activities and soil microbial abundance. Reco was highly correlated with air and soil temperatures and soil enzyme activity. A significant quadratic polynomial correlation was observed between GPP and leaf area index (p < 0.01). The combination of biochar addition at a rate of 20 t ha-1 and water-saving irrigation has the potential to increase the size of the carbon sink and promote soil enzyme and microbial activities in paddy field ecosystems.


Assuntos
Oryza , Água , Agricultura , Dióxido de Carbono/análise , Carvão Vegetal , China , Ecossistema , Solo
8.
J Xray Sci Technol ; 28(1): 147-155, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31771087

RESUMO

OBJECTIVE: To evaluate the accuracy of a novel guidance method of pedicle screw implantation determined by spinal stress. METHODS: We retrospectively analyzed patients underwent pedicle screw internal fixation between January 2015 and August 2018 in our hospital. Patients were divided into two groups according to the methods of pedicle screw implantation namely, the conventional nail placement and novel guidance method of pedicle screw implantation determined by spinal stress. Accuracy of spinal pedicle screw placements was evaluated using intraoperative and postoperative X-ray computed tomography (CT) examination and intraoperative touch of nerve root dissection pedicle bone. The success rate of intraoperative one-time screw placement was calculated according to Heary classification I. RESULTS: A total of 785 patients underwent pedicle screw internal fixation were retrospectively analyzed. Among them 384 patients were treated using conventional nail placement (Group A) and 401 patients were treated using the technique according to analysis of spinal stress (Group B). There was no significant difference in terms of the characteristics between two groups. There were significant differences in terms of the success rate of total of screw placement (88.7% vs. 96.2%, P < 0.001) including thoracic screw placement (87.8% vs. 94.5%, P = 0.003) and lumbar screw placement (88.8% vs. 96.5%, P = 0.001) for Group A and Group B, respectively. CONCLUSIONS: Using the novel guidance method of pedicle screw implantation determined by spinal stress might improve the accuracy of pedicle screw implantation.


Assuntos
Parafusos Pediculares , Implantação de Prótese/métodos , Radiografia/métodos , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/fisiopatologia , Estresse Fisiológico/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
9.
Environ Pollut ; 342: 123026, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38012968

RESUMO

The addition of biochar in paddies under the condition of water-saving irrigation can simultaneously achieve soil improvement and water conservation, but little is known about the role of these two regulations in mediating the fate of antibiotic resistome in paddy soils. Here, metagenomic analysis was conducted to investigate the effects and intrinsic mechanisms of biochar application and irrigation patterns on propagation of antibiotic resistance genes (ARGs) in paddy soils. The addition of biochar in paddy soil resulted in a reduction of approximately 1.32%-8.01% in the total absolute abundance of ARGs and 0.60%-22.09% in the numbers of ARG subtype. Compared with flooding irrigation, the numbers of detected ARG subtype were reduced by 1.60%-22.90%, but the total absolute abundance of ARGs increased by 0.06%-5.79% in water-saving irrigation paddy soils. Moreover, the combined treatments of flooding irrigation and biochar could significantly reduce the abundance of ARGs in paddy soils. The incremental antibiotic resistance in soil induced by water-saving irrigation was likewise mitigated by the addition of biochar. Correlation analyses indicated that, the differences in soil physicochemical properties under biochar addition or irrigation treatments contributed to the corresponding changes in the abundance of ARGs. Moreover, the variations of microbial community diversity, multidrug efflux abundance and transport system-related genes in paddy soil were also important for mediating the corresponding differences in the abundance of ARGs under the conditions of biochar addition or irrigation treatments. The findings of this study demonstrated the effectiveness of biochar application in mitigating antibiotic resistance in paddy soils. However, it also highlighted a potential concern relating to the elevated antibiotic resistance associated with water-saving irrigation in paddy fields. Consequently, these results contribute to a deeper comprehension of the environmental risks posed by ARGs in paddy soils.


Assuntos
Carvão Vegetal , Rizosfera , Solo , Solo/química , Antibacterianos/farmacologia , Antibacterianos/análise , Água/análise , Genes Bacterianos , Microbiologia do Solo
10.
Int J Pharm ; 655: 124016, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38503397

RESUMO

Triple negative breast cancer (TNBC) presents a formidable challenge due to its low sensitivity to many chemotherapeutic drugs and a relatively low overall survival rate in clinical practice. Photothermal therapy has recently garnered substantial interest in cancer treatment, owing to its swift therapeutic effectiveness and minimal impact on normal cells. Metal-polyphenol nanostructures have recently garnered significant attention as photothermal transduction agents due to their facile preparation and favorable photothermal properties. In this study, we employed a coordinated approach involving Fe3+ and apigenin, a polyphenol compound, to construct the nanostructure (nFeAPG), with the assistance of ß-CD and DSPE-PEG facilitating the formation of the complex nanostructure. In vitro research demonstrated that the formed nFeAPG could induce cell death by elevating intracellular oxidative stress, inhibiting antioxidative system, and promoting apoptosis and ferroptosis, and near infrared spectrum irradiation further strengthen the therapeutic outcome. In 4T1 tumor bearing mice, nFeAPG could effectively accumulate into tumor site and exhibit commendable control over tumor growth. Futher analysis demonstrated that nFeAPG ameliorated the suppressed immune microenvironment by augmenting the response of DC cells and T cells. This study underscores that nFeAPG encompasses a multifaceted capacity to combat TNBC, holding promise as a compelling therapeutic strategy for TNBC treatment.


Assuntos
Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Terapia Fototérmica , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Apigenina , Ferro , Linhagem Celular Tumoral , Polifenóis , Microambiente Tumoral
11.
Environ Sci Pollut Res Int ; 30(3): 7770-7785, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36044151

RESUMO

Growing evidence points to the controlled irrigation (CI) and biochar application (BA) having agricultural economic value and ecological benefits, but their synergistic effect and microbial mechanism of nitrogen conversion remain unknown in paddy fields. The effects of different BA (0, 20, 40 t/hm2) on the soil nitrogen functional transformation microbial genes (nifH, AOA-amoA, AOB-amoA) in different irrigation (CI, flooding irrigation) were clarified. After one seasonal growth of paddy, the correlation between the abundance of functional genes OUT and soil nitrogen transformation environment factors during the typical growth period was analyzed. High-throughput sequencing results illustrated that the application of CC (40 t/hm2 biochar) increased the nifH genes bacterial community abundance; the abundance of dominant microorganism increased by 79.68~86.19%. Because biochar can potentially control the rates of N cycling in soil systems by adsorbing ammonia and increasing NH4+ storage, it increased soil NH4+-N and NO3--N content by 60.77% and 26.14%, improving microbial nitrogen fixation. Rare species Nitrosopumilus, Nitrosococcus, and Methylocystis appeared in biochar treatments group, which increased the diversity of microbial in paddy. The combined use of CI and BA affected soil inorganic nitrogen content, temperature (T), pH, Eh, etc., which affected urease, urea hydrolysis, and nitrogen functional transformation microorganism genes. Correlation analysis shows that soil NH4+-N, T, and Eh, respectively, are significant factors for the formation of nifH, AOA-amoA, and AOB-amoA soil bacterial communities, respectively. This study suggests that to maintain the biodiversity of soil and realize the sustainable development of rice cultivation, CI is of great importance in combination with BA.


Assuntos
Nitrogênio , Solo , Solo/química , Bactérias/genética , Archaea/genética , Genes Microbianos , China , Microbiologia do Solo , Amônia
12.
Colloids Surf B Biointerfaces ; 228: 113438, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37421763

RESUMO

Cancer, a disease notorious for its difficult therapy regimen, has long puzzled researchers. Despite attempts to cure cancer using surgery, chemotherapy, radiotherapy, and immunotherapy, their effectiveness is limited. Recently, photothermal therapy (PTT), a rising strategy, has gained attention. PTT can increase the surrounding temperature of cancer tissues and cause damage to them. Fe is widely used in PTT nanostructures due to its strong chelating ability, good biocompatibility, and the potential to induce ferroptosis. In recent years, many nanostructures incorporating Fe3+ have been developed. In this article, we summarize PTT nanostructures containing Fe and introduce their synthesis and therapy strategy. However, PTT nanostructures containing Fe are still in their infancy, and more effort must be devoted to improving their effectiveness so that they can eventually be used in clinics.


Assuntos
Hipertermia Induzida , Nanopartículas , Nanoestruturas , Neoplasias , Humanos , Terapia Fototérmica , Nanoestruturas/química , Fototerapia , Neoplasias/tratamento farmacológico
13.
Front Plant Sci ; 14: 1143462, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37351200

RESUMO

Cotton is widely used in textile, decoration, and industry, but it is also threatened by soil salinization. Drip irrigation plays an important role in improving water and fertilization utilization efficiency and ensuring crop production in arid areas. Accurate prediction of soil salinity and crop evapotranspiration under drip irrigation is essential to guide water management practices in arid and saline areas. However, traditional hydrological models such as Hydrus require more variety of input parameters and user expertise, which limits its application in practice, and machine learning (ML) provides a potential alternative. Based on a global dataset collected from 134 pieces of literature, we proposed a method to comprehensively simulate soil salinity, evapotranspiration (ET) and cotton yield. Results showed that it was recommended to predict soil salinity, crop evapotranspiration and cotton yield based on soil data (bulk density), meteorological factors, irrigation data and other data. Among them, meteorological factors include annual average temperature, total precipitation, year. Irrigation data include salinity in irrigation water, soil matric potential and irrigation water volume, while other data include soil depth, distance from dripper, days after sowing (for EC and soil salinity), fertilization rate (for yield and ET). The accuracy of the model has reached a satisfactory level, R2 in 0.78-0.99. The performance of stacking ensemble ML was better than that of a single model, i.e., gradient boosting decision tree (GBDT); random forest (RF); extreme gradient boosting regression (XGBR), with R2 increased by 0.02%-19.31%. In all input combinations, other data have a greater impact on the model accuracy, while the RMSE of the S1 scenario (input without meteorological factors) without meteorological data has little difference, which is -34.22%~19.20% higher than that of full input. Given the wide application of drip irrigation in cotton, we recommend the application of ensemble ML to predict soil salinity and crop evapotranspiration, thus serving as the basis for adjusting the irrigation schedule.

14.
Adv Healthc Mater ; 12(13): e2203397, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36690435

RESUMO

Psoriasis is an immune-mediated chronic inflammatory skin disorder characterized by epidermal hyperplasia and infiltration of inflammatory cells. Even though the pathogenesis remains unclear, T helper 17 (Th17) cells-mediated inflammation and keratinocyte-involved proliferation are considered to play key roles during the occurrence and the development of psoriasis. Therefore, suppressing the infiltration/function of Th17 and the abnormal hyperplasia of keratinocytes can be a rational strategy for ameliorating and treating psoriasis. In this study, a self-assembly nanoparticle (BVn) is developed with bilirubin (an endogenous antioxidant) and V9302 (a blocker of ASCT2, an amino acid transporter mediating glutamine influx for providing energy and activating mammalian target of rapamycin [mTOR] pathway) to intervene the local metabolism and alleviate oxidative stress for psoriasis treatment. BVn effectively suppresses inflammatory keratinocyte proliferation and scavenges excess reactive oxygen species (ROS). In the in vivo psoriasis mouse model, BVn shows increased permeation and delayed retention in the psoriatic lesion and reverses the psoriasis-related symptoms, evidenced by the normalized keratinocyte condition and decreased Th17 infiltration/activation. Mechanism study indicates that BVn not only cut off the energy supply but also suppressed cell proliferation or lymph cell expansion by deactivating mTOR pathway, besides alleviated oxidative stress. BVn-based glutamine metabolism modulation strategy offers a promising strategy for psoriasis therapy.


Assuntos
Nanopartículas , Psoríase , Camundongos , Animais , Glutamina/metabolismo , Bilirrubina/metabolismo , Hiperplasia/metabolismo , Hiperplasia/patologia , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Psoríase/patologia , Queratinócitos/metabolismo , Estresse Oxidativo , Serina-Treonina Quinases TOR/metabolismo , Mamíferos/metabolismo
15.
Adv Healthc Mater ; 12(24): e2300571, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37236618

RESUMO

Acute liver failure (ALF) is a severe liver disease caused by many reasons. One of them is the overdosed acetaminophen (APAP), which is metabolized into N-acetyl-p-benzoquinone imine (NAPQI), an excessive toxic metabolite, by CYP2E1, resulting in excessive reactive oxygen species (ROS), exhausted glutathione (GSH), and thereafter hepatocyte necrosis. N-acetylcysteine is the Food and Drug Administration-approved drug for detoxification of APAP, but it has limited clinical application due to the short therapeutic time window and concentration-related adverse effects. In this study, a carrier-free and bilirubin dotted nanoparticle (B/BG@N) is developed, which is formed using bilirubin and 18ß-Glycyrrhetinic acid, and bovine serum albumin (BSA) is then adsorbed to mimic the in vivo behavior of the conjugated bilirubin for hitchhiking. The results demonstrate that B/BG@N can effectively reduce the production of NAPQI as well as exhibit antioxidant effects against intracellular oxidative stress via regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signal axis and reducing the production of inflammatory factors. In vivo study shows that B/BG@N can effectively improve the clinical symptom of the mice model. This study suggests that B/BG@N own increases circulation half-life, improves accumulation in the liver, and dual detoxification, providing a promising strategy for clinical ALF treatment.


Assuntos
Acetaminofen , Falência Hepática Aguda , Animais , Camundongos , Acetaminofen/efeitos adversos , Acetaminofen/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP2E1/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Biomimética , Fígado/metabolismo , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Glutationa/metabolismo , Bilirrubina/metabolismo , Bilirrubina/farmacologia
16.
J Control Release ; 362: 468-478, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37666304

RESUMO

Psoriasis is a multifactorial immuno-inflammatory skin disease, characterized by keratinocyte hyperproliferation and aberrant immune activation. Although the pathogenesis is complex, the interactions among inflammation, Th17-mediated immune activation, and keratinocyte hyperplasia are considered to play a crucial role in the occurrence and development of psoriasis. Therefore, pharmacological interventions on the "inflammation-Th17-keratinocyte" vicious cycle may be a potential strategy for psoriasis treatment. In this study, JPH203 (a specific inhibitor of LAT1, which engulfs leucine to activate mTOR signaling)-loaded, ultraviolet B (UVB) radiation-induced, keratinocyte-derived extracellular vesicles (J@EV) were prepared for psoriasis therapy. The EVs led to increased interleukin 1 receptor antagonist (IL-1RA) content due to UVB irradiation, therefore not only acting as a carrier for JPH203 but also functioning through inhibiting the IL-1-mediated inflammation cascade. J@EV effectively restrained the proliferation of inflamed keratinocytes via suppressing mTOR-signaling and NF-κB pathway in vitro. In an imiquimod-induced psoriatic model, J@EV significantly ameliorated the related symptoms as well as suppressed the over-activated immune reaction, evidenced by the decreased keratinocyte hyperplasia, Th17 expansion, and IL17 release. This study shows that J@EV exerts therapeutic efficacy for psoriasis by suppressing LAT1-mTOR involved keratinocyte hyperproliferation and Th17 expansion, as well as inhibiting IL-1-NF-κB mediated inflammation, representing a novel and promising strategy for psoriasis therapy.

17.
Antimicrob Agents Chemother ; 56(1): 552-4, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22005995

RESUMO

We investigated the utility of radioimmunotherapy (RIT) in early and established cryptococcal infection in immunocompetent mice. RIT with (213)Bi-18B7 antibody completely eliminated fungus from mouse lungs and brains for early infection, while (188)Re-18B7 significantly reduced CFU in the lungs or both lungs and brains during early and established infection, respectively. The results point to the independence of RIT of the immune status of the host, which is encouraging for translation of this strategy into the clinic.


Assuntos
Anticorpos Antifúngicos/administração & dosagem , Criptococose/radioterapia , Cryptococcus neoformans/efeitos dos fármacos , Imunoconjugados/uso terapêutico , Pulmão/efeitos dos fármacos , Radioimunoterapia/métodos , Animais , Anticorpos Monoclonais/administração & dosagem , Bismuto/toxicidade , Criptococose/microbiologia , Cryptococcus neoformans/imunologia , Feminino , Imunocompetência , Imunoconjugados/administração & dosagem , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Radioisótopos , Rênio/toxicidade
18.
Plants (Basel) ; 11(13)2022 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-35807642

RESUMO

Irrigation and nitrogen fertilizer application are two important factors affecting yield and nitrogen loss in rice fields; however, the interaction effects of different irrigation schedules and combined management of nitrogen fertilizer application on yield and nitrogen loss in rice fields remain unknown. Therefore, we collected 327 sets of data on rice yield and 437 sets of data on nitrogen loss in rice fields from 2000 to 2021 and investigated the effects of different water-saving irrigation schedules, nitrogen application levels, and water-nitrogen couplings on rice yield, nitrogen use efficiency, and nitrogen loss (N2O emissions, nitrogen runoff, nitrogen leaching, and ammonia volatilization) by meta-analysis using conventional flooding irrigation and no nitrogen treatment as controls. The results showed that alternate wet and dry irrigation and controlled irrigation had increasing effects on rice yield. Alternate wet and dry irrigation had a significant yield-increasing effect (average 2.57% increase) and dry cultivation significantly reduced rice yield with an average 21.25% yield reduction. Water-saving irrigation reduces nitrogen runoff and leaching losses from rice fields but increases N2O emissions, and alternate wet and dry irrigation has a significant effect on increasing N2O emissions, with an average increase of 67.77%. Most water-saving irrigation can increase nitrogen use efficiency. Among water-saving irrigation methods, the effect of controlled irrigation on increasing nitrogen use efficiency is 1.06%. Rice yield and nitrogen use efficiency both showed a trend of increasing then decreasing with nitrogen fertilizer application, and nitrogen loss gradually increased with the amount of nitrogen fertilizer input. Water-nitrogen coupling management can significantly reduce nitrogen loss in rice fields while saving water and increasing yield. Based on the analysis of the data in this study, when the irrigation amount was 300~350 mm and the nitrogen application amount was 200~250 kg/ha, the rice yield and nitrogen fertilizer use efficiency were at a high level, which corresponded to the irrigation schedule of controlled irrigation or alternating wet and dry irrigation in the literature. However, different rice-growing areas are affected by rainfall and land capability, etc. Further optimization and correction of the adapted water and fertilizer management system for paddy fields are needed. The optimal water-nitrogen pattern of this study can achieve high rice yield and reduce nitrogen loss.

19.
Environ Sci Pollut Res Int ; 29(3): 3587-3599, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34392484

RESUMO

To reveal the comprehensive impacts of controlled release urea (CRU) on rice production, nitrogen (N) loss, and greenhouse gas (GHG) emissions, a research based on global meta-analysis and machine learning (ML) was conducted. The results revealed that the CRU application instead of conventional fertilizer can increase rice yield, N use efficiency (NUE), and net benefits by 5.24%, 20.18%, and 9.30%, respectively, under the same amount of N. Furthermore, the emission of N2O and CH4, global warming potential (GWP), the loss of N leaching, and NH3 volatilization were respectively reduced by 25.64%, 18.33%, 21.10%, 14.90%, and 35.88%. The enhancing effects of CRU on rice yield and NUE were greater when the nitrogen application rate was 150 kg N ha-1. Nevertheless, the reducing effects of CRU on GHG emission reduction, nitrogen leaching, and NH3 volatilization was greater at high nitrogen application rate (≥150 kg ha-1). Mitigating effects of CRU on N2O and CH4 emission were significant when soil pH ≥ 6, while CRU posed a measurable effect on reducing nitrogen leaching and NH3 volatilization in paddy fields with soil organic carbon lower than 15 g kg-1 and pH lower than 6. Based on the data collected from meta-analysis, the results of ML demonstrated that it was feasible to use soil data and N application rate to predict N losses in rice fields under CRU. The performance of random forest is better than multilayer perceptron regression in predicting N losses from paddy fields. Thus, it is necessary to promote the application of CRU in paddy fields, especially in coarse soil, in which scenario the environmental pollution would be decreased and the rice yields, NUE, and net benefits would be increased. Meanwhile, machine learning models can be used to predict N losses in CRU paddy fields.


Assuntos
Oryza , Agricultura , Carbono , Preparações de Ação Retardada , Poluição Ambiental , Fertilizantes/análise , Aprendizado de Máquina , Nitrogênio , Óxido Nitroso/análise , Solo , Ureia
20.
Sci Total Environ ; 809: 152246, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-34896144

RESUMO

Growing evidence points to the pivotal roles of salt accumulation in mediating antibiotic resistance genes (ARGs) spread in soil, whereas how salt mediates ARGs dissemination remains unknown. Herein, the effects of neutral or alkaline (Ne/Al) salt at low, moderate and high levels (Ne/Al-L, Ne/Al-M, Ne/Al-H) on the dissemination of ten typical ARGs in soils were explored, by simultaneously considering the roles of salinity stress and response strategies of microbes. In the soils amended with Ne/Al-L and Al-M salt, the dissemination of ARGs was negligible and the relative abundances of ARGs and mobile genetic elements (MGEs) were decreased. However, Ne-M and Al-H salt contributed to the dissemination of ARGs in soils, with the significantly increased absolute and relative abundances of ARGs and MGEs. In Ne-H soil, although the absolute abundance of ARGs declined drastically due to serious oxidative damage, their relative abundances were promoted. The facilitated ARGs transfer was potentially related to the excessive generation of intracellular reactive oxygen species and increased activities of DNA repair enzymes involved in SOS system. In addition, the activated intracellular protective response including quorum sensing and energy metabolism largely provided essential factors for ARGs dissemination. The co-occurrence of ARGs and over-expressed salt-tolerant genes in specific halotolerant bacteria further suggested the selection of salt stress on ARGs. Moreover, less disturbance of alkaline salt than neutral salt on ARGs evolution was observed, due to the lower abiotic stress and selective pressure on microbes. This study highlights that soil salinity-sodicity could dose-dependently reshape the dissemination of ARGs and community structure of microbes, which may increase the ecological risks of ARGs in agricultural environment.


Assuntos
Antibacterianos , Solo , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Estresse Salino , Sais , Microbiologia do Solo
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