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1.
Anal Chem ; 96(29): 11923-11931, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38989922

RESUMO

The pH and humidity of the crop environment are essential indicators for monitoring crop growth status. This study reports a lead-free perovskite/polyvinylidene fluoride-hexafluoropropylene composite (LPPC) to enhance the stability and reliability of in situ plant pH and humidity monitoring. The mesh composite membrane of LPPC illustrates a hydrophobic contact angle of 101.982°, a tensile strain of 800%, and an opposing surface potential of less than -184.9 mV, which ensures fast response, high sensitivity, and stability of the sensor during long-term plant monitoring. The LPPC-coated pH electrode possesses a sensitivity of -63.90 mV/pH, which provides a fast response within 5 s and is inert to environmental temperature interference. The LPPC-coated humidity sensor obtains a sensitivity of -145.7 Ω/% RH, responds in 28 s, and works well under varying light conditions. The flexible multimodal sensor coated with an LPPC membrane completed real-time in situ monitoring of soilless strawberries for 17 consecutive days. Satisfactory consistency and accuracy performance are observed. The study provides a simple solution for developing reliable, flexible wearable multiparameter sensors for in situ monitoring of multiple parameters of crop environments.

2.
Sensors (Basel) ; 23(18)2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37765733

RESUMO

In order to enhance the precision and speed of control for electronic throttle valves (ETVs) in the face of disturbance and parameter uncertainties, an adaptive second-order fixed-time sliding mode (ASOFxTSM) controller is developed, along with disturbance observer compensation techniques. Initially, a control-oriented model specifically considering lumped disturbances within the ETV is established. Secondly, to address the contradiction between fast response and heavy chattering of conventional fixed-time sliding mode, a hierarchical sliding surface approach is introduced. This approach proficiently alleviates chattering effects while preserving the fixed convergence properties of the controller. Furthermore, to enhance the anti-disturbance performance of the ETV control system, an innovative fixed-time sliding mode observer is incorporated to estimate lumped disturbances and apply them as a feed-forward compensation term to the ASOFxTSM controller output. Building upon this, a parameter adaptive mechanism is introduced to optimize control gains. Subsequently, a rigorous stability proof is conducted, accompanied by the derivation of the expression for system convergence time. Finally, a comparison is drawn between the proposed controller and fixed-time sliding mode and super-twisting controllers through simulations and experiments. The results demonstrate the superiority of the proposed method in terms of chattering suppression, rapid dynamic response, and disturbance rejection capability.

3.
BMC Med Imaging ; 21(1): 189, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34879818

RESUMO

PURPOSE: The objective of this study is to construct a computer aided diagnosis system for normal people and pneumoconiosis using X-raysand deep learning algorithms. MATERIALS AND METHODS: 1760 anonymous digital X-ray images of real patients between January 2017 and June 2020 were collected for this experiment. In order to concentrate the feature extraction ability of the model more on the lung region and restrain the influence of external background factors, a two-stage pipeline from coarse to fine was established. First, the U-Net model was used to extract the lung regions on each sides of the collection images. Second, the ResNet-34 model with transfer learning strategy was implemented to learn the image features extracted in the lung region to achieve accurate classification of pneumoconiosis patients and normal people. RESULTS: Among the 1760 cases collected, the accuracy and the area under curve of the classification model were 92.46% and 89% respectively. CONCLUSION: The successful application of deep learning in the diagnosis of pneumoconiosis further demonstrates the potential of medical artificial intelligence and proves the effectiveness of our proposed algorithm. However, when we further classified pneumoconiosis patients and normal subjects into four categories, we found that the overall accuracy decreased to 70.1%. We will use the CT modality in future studies to provide more details of lung regions.


Assuntos
Aprendizado Profundo , Diagnóstico por Computador , Pneumoconiose/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Raios X
4.
J Struct Biol ; 212(1): 107573, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32679070

RESUMO

DciA is a newly discovered bacterial protein involved in loading the replicative helicase DnaB onto DNA at the initiation step of chromosome replication. Its three-dimensional structure is composed of a folded N-terminal domain (residues 1-111) resembling K Homology domains and a long disordered C-terminal tail (residues 112-157) which structure-activity relationship remains to be elucidated. In the present study on Vibrio cholerae DciA, we emphasize the importance of its disordered region to load DnaB onto DNA using surface plasmon resonance (SPR) and isothermal titration microcalorimetry (ITC). Then we characterize the conformational ensemble of the full-length protein using a combination of circular dichroism (CD), small angle X-ray scattering (SAXS), and molecular dynamics (MD) simulations. The atomic-level structural ensemble generated by MD simulations is in very good agreement with SAXS data. From initial conformations of the C-terminal tail without any secondary structure, our simulations bring to light several transient helical structures in this segment, which might be molecular recognition features (MoRFs) for the binding to DnaB and its recruitment and loading onto DNA.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , DNA/metabolismo , DnaB Helicases/química , DnaB Helicases/metabolismo , Simulação de Dinâmica Molecular , Estrutura Secundária de Proteína , Espalhamento a Baixo Ângulo , Relação Estrutura-Atividade , Vibrio cholerae/metabolismo , Difração de Raios X/métodos
5.
Biophys J ; 116(7): 1216-1227, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30878202

RESUMO

Because of their large conformational heterogeneity, structural characterization of intrinsically disordered proteins (IDPs) is very challenging using classical experimental methods alone. In this study, we use NMR and small-angle x-ray scattering (SAXS) data with multiple molecular dynamics (MD) simulations to describe the conformational ensemble of the fully disordered verprolin homology domain of the neural Aldrich syndrome protein involved in the regulation of actin polymerization. First, we studied several back-calculation software of SAXS scattering intensity and optimized the adjustable parameters to accurately calculate the SAXS intensity from an atomic structure. We also identified the most appropriate force fields for MD simulations of this IDP. Then, we analyzed four conformational ensembles of neural Aldrich syndrome protein verprolin homology domain, two generated with the program flexible-meccano with or without NMR-derived information as input and two others generated by MD simulations with two different force fields. These four conformational ensembles were compared to available NMR and SAXS data for validation. We found that MD simulations with the AMBER-03w force field and the TIP4P/2005s water model are able to correctly describe the conformational ensemble of this 67-residue IDP at both local and global level.


Assuntos
Proteínas Intrinsicamente Desordenadas/química , Proteína da Síndrome de Wiskott-Aldrich/química , Humanos , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Domínios Proteicos , Espalhamento a Baixo Ângulo , Difração de Raios X
6.
J Chem Inf Model ; 59(5): 1743-1758, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-30840442

RESUMO

The concept of intrinsically disordered proteins (IDPs) has emerged relatively slowly, but over the past 20 years, it has become an intense research area in structural biology. Indeed, because of their considerable flexibility and structural heterogeneity, the determination of IDP conformational ensemble is particularly challenging and often requires a combination of experimental measurements and computational approaches. With the improved accuracy of all-atom force fields and the increasing computing performances, molecular dynamics (MD) simulations have become more and more reliable to generate realistic conformational ensembles. And the combination of MD simulations with experimental approaches, such as nuclear magnetic resonance (NMR) and/or small-angle X-ray scattering (SAXS) allows one to converge toward a more accurate and exhaustive description of IDP structures. In this Review, we discuss the state of the art of MD simulations of IDP conformational ensembles, with a special focus on studies that back-calculated and directly compared theoretical and experimental NMR or SAXS observables, such as chemical shifts (CS), 3J-couplings (3Jc), residual dipolar couplings (RDC), or SAXS intensities. We organize the review in three parts. In the first section, we discuss the studies which used NMR and/or SAXS data to test and validate the development of force fields or enhanced sampling techniques. In the second part, we explore different methods for the refinement of MD-derived structural ensembles, such as NMR or SAXS data-restrained MD simulations or ensemble reweighting to better fit experiments. Finally, we survey some recent studies combining MD simulations with NMR and/or SAXS measurements to investigate the relationship between IDP conformational ensemble and biological activity, as well as their implication in human diseases. From this review, we noticed that quite a few studies compared MD-generated conformational ensembles with both NMR and SAXS measurements to validate IDP structures at both local and global levels. Yet, beside the IDP propensity to form local secondary structures, their dynamic extension or compactness also appears important for their activity. Thus, we believe that a close synergy between MD simulations, NMR, and SAXS experiments would be greatly appropriate to address the challenges of characterizing the disordered structures of proteins and their complexes, relative to their biological functions.


Assuntos
Proteínas Intrinsicamente Desordenadas/química , Simulação de Dinâmica Molecular , Peptídeos/química , Proteínas Amiloidogênicas/química , Animais , Humanos , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , Espalhamento a Baixo Ângulo , Proteínas Virais/química , Difração de Raios X
7.
J Clin Pharm Ther ; 44(6): 875-882, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31529525

RESUMO

WHAT IS KNOWN AND OBJECTIVES: The etoposide, doxorubicin hydrochloride, vincristine sulphate, cyclophosphamide and prednisone (EPOCH) chemotherapy regimen is effective in patients with relapsed or refractory non-Hodgkin's lymphoma. However, vincristine and doxorubicin hydrochloride are relatively toxic, leading to neurovirulence and cardiotoxicity, respectively. In this study, we replaced these drugs with vindesine and epirubicin hydrochloride to reduce the cardiotoxicity and evaluated admixtures containing these drugs along with etoposide in a single infusion bag in vitro. METHODS: The appearance and pH of the admixtures were evaluated, and the number of particles was detected. High-performance liquid chromatography was used to measure the concentration and degradation rates of etoposide, epirubicin hydrochloride and vindesine sulphate in each admixture. RESULTS AND DISCUSSION: No precipitation occurred when mixing clinically relevant concentrations of etoposide, epirubicin hydrochloride and vindesine sulphate in a 0.9% NaCl injection solution. Furthermore, the delta pH of the admixtures was ≤0.12 throughout the experiment, and the number of particles (≥10 and ≥25 µm) in the solutions over the 24 hours post-preparation period met USP standards. Etoposide, epirubicin hydrochloride and vindesine sulphate were retained at >96% of their initial concentrations in the admixtures at 25°C over the course of the experiment. Etoposide, epirubicin hydrochloride and vindesine sulphate are compatible when mixed in a 0.9% NaCl injection solution, and the admixtures are stable for at least 24 hours when stored in infusion bags. WHAT IS NEW AND CONCLUSION: This in vitro analysis indicates the suitability of our novel admixtures containing less toxic drug equivalents in a single infusion bag for clinical application.


Assuntos
Epirubicina/administração & dosagem , Etoposídeo/administração & dosagem , Vindesina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Estabilidade de Medicamentos , Humanos , Bombas de Infusão , Linfoma não Hodgkin/tratamento farmacológico , Prednisona/administração & dosagem , Vincristina/administração & dosagem
8.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514372

RESUMO

Cellular regulation or signaling processes are mediated by many proteins which often have one or several intrinsically disordered regions (IDRs). These IDRs generally serve as binders to different proteins with high specificity. In many cases, IDRs undergo a disorder-to-order transition upon binding, following a mechanism between two possible pathways, the induced fit or the conformational selection. Since these mechanisms contribute differently to the kinetics of IDR associations, it is important to investigate them in order to gain insight into the physical factors that determine the biomolecular recognition process. The verprolin homology domain (V) of the Neural Wiskott-Aldrich Syndrome Protein (N-WASP), involved in the regulation of actin polymerization, is a typical example of IDR. It is composed of two WH2 motifs, each being able to bind one actin molecule. In this study, we investigated the early steps of the recognition process of actin by the WH2 motifs of N-WASP domain V. Using docking calculations and molecular dynamics simulations, our study shows that actin is first recognized by the N-WASP domain V regions which have the highest propensity to form transient α -helices. The WH2 motif consensus sequences "LKKV" subsequently bind to actin through large conformational changes of the disordered domain V.


Assuntos
Actinas/metabolismo , Proteína da Síndrome de Wiskott-Aldrich/química , Proteína da Síndrome de Wiskott-Aldrich/metabolismo , Actinas/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Probabilidade , Domínios Proteicos , Multimerização Proteica , Fatores de Tempo
9.
Zhonghua Nan Ke Xue ; 24(9): 844-850, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32212466

RESUMO

Cell apoptosis is an active process of the self-destruction of biological cells, which is an important mechanism of multicellular organisms regulating the development of the body, controlling cell senescence, and maintaining the stability of the internal and external environment of the body. As a basic biological process of keeping the balance in the body, cell apoptosis also plays an important role in cell differentiation and sperm maturation and survival in the testis. In spermatogenesis, any change may affect cell apoptosis and consequently upset the balance between the survival and death of germ cells. Current studies have shown that the mitochondrial pathway, cell death receptor pathway and endoplasmic reticulum pathway are essential for the apoptosis of germ cells in the testis and the factors in the three pathways interact with one another, forming a complex network for the regulation of cell apoptosis. This review focuses on the mechanisms of the three pathways regulating the apoptosis of testicular germ cells.

10.
Biomed Environ Sci ; 30(2): 150-155, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28292355

RESUMO

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity.


Assuntos
Doença de Kashin-Bek/diagnóstico , Doença de Kashin-Bek/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Doença de Kashin-Bek/classificação , Doença de Kashin-Bek/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Biomacromolecules ; 16(4): 1119-30, 2015 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-25686200

RESUMO

RNA-based delivery system for cancer therapy remains a challenge. In this study, a stearyl-peptide (SHR) was synthesized using arginine, histidine, cysteine, and stearyl moieties. Further, the stearyl-peptides were cross-linked by disulfide bonds to obtain cross-linked polypeptides (SHRss) with different molecular weight (SHRss1, SHRss2, SHRss3, SHRss4). The SHRss could effectively condense small interfering RNA (siRNA) into polyplexes with a hydrodynamic size of 100-300 nm and zeta potential of 20-40 mV. Flow cytometry and confocal laser scanning microscope studies revealed high cellular uptake and rapid dissociation behavior of SHRss2/siRNA complexes. Long-lasting high concentration of siRNA in cytoplasm was observed even at 24 h after SHRss2/Cy3-siRNA transfection. Compared with SHR, the SHRss showed much improved siRNA interference efficiency targeting luciferase on Luc-Hela cells. Moreover, SHRss2 exhibited higher interference efficiency and slower decay rate on Luc-Hela cells than Lipofectamine 2000 and SHR. In addition, much weaker expression of red fluorescence protein was also observed on SHRss2/simCh-treated mCherry-HEK293 cells than Lipofectamine 2000 and SHR. The SHRss did not induce cytotoxicity at siRNA concentrations of 25-200 nM under transfection. The in vivo studies demonstrated the gene interference efficiency of SHRss2/siRNA complexes. Our studies indicated that the SHRss are promising and efficient nonviral vectors for siRNA delivery.


Assuntos
Peptídeos Penetradores de Células/química , Dissulfetos/química , Lipopeptídeos/química , RNA Interferente Pequeno/administração & dosagem , Ácidos Esteáricos/química , Animais , Peptídeos Penetradores de Células/farmacocinética , Feminino , Células HEK293 , Células HeLa , Humanos , Lipopeptídeos/farmacocinética , Camundongos , Camundongos Endogâmicos BALB C , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Terapêutica com RNAi/métodos
12.
ACS Appl Mater Interfaces ; 16(10): 13326-13334, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480983

RESUMO

Flexible sensors for application in various industries, including biomedicine and wearable electronics, are frequently made using silver nanoparticle (AgNP) inks and inkjet printing (IJP) technology. Inkjet-printed flexible electronic devices are made up of many printed lines that run parallel to each other, and the surface morphology of the printed lines and the interline state directly impact the electrical conductivity of the electronic devices. This paper describes the experimental setup for IJP, the definition of print line characteristics, and common unavoidable defects. Conductivity and physical defects are considered in defining the print line quality assessment. In addition, two prediction models of flexible sensors before batch printing and a model for detecting defects after printing are provided. The predictive models can guide actions, leading to a print success rate of over 80%. We build the defect detection model using a neural architecture search because manually fine-tuning neural networks for reference is challenging. Finally, a target detection model with a mAP@0.5 of 81.2% is built in just 0.77 graphics processing unit (GPU) days. The model takes only 4.6 ms to detect an image, satisfying the real-time monitoring needs. At the same time, an accuracy of 95.5% can be achieved in the test data set. This work provides a new idea for the high-volume preparation of flexible sensors.

13.
Sci Total Environ ; 947: 174334, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38955279

RESUMO

High-precision rainfall erosivity mapping is crucial for accurately evaluating regional soil erosion on the Tibetan Plateau (TP) under the backdrop of climate warming and humidification. Although high spatiotemporal resolution gridded precipitation data provides the foundation for rainfall erosivity mapping, the increasing spatial heterogeneity of rainfall with decreasing temporal granularity can lead to greater errors when directly computing rainfall erosivity from gridded precipitation data. In this study, a site-scale conversion coefficient was established so that rainfall erosivity calculated using hourly data can be converted to rainfall erosivity calculated using per-minute data. A revised model was established for calculating the rainfall erosivity based on high-resolution hourly precipitation data from the Third Pole gridded precipitation dataset (TPHiPr). The results revealed a notable underestimation in the original calculation results obtained using the TPHiPr, but strong correlation was observed between the two sets of results. There was a significant improvement in the Nash-Sutcliffe coefficient of efficiency (from -0.39 to 0.80) and the Percent Bias (from -63.95 % to 0.37 %) after model revision. The TPHiPr effectively depict the spatial characteristics of rainfall erosivity on the TP. It accurately reflected the rain shadow area on the northern flank of the Himalayas and the dry-hot valley in the Hengduan Mountains. It also showed high rainfall erosivity values in the tropical rainforest area on the southern flank of the eastern Himalayas. The overall trend of rainfall erosivity has increased on the TP during the period 1981 to 2020, with 65.91 % of the regions exhibiting an increasing trend and 22.25 % showing significant increases, indicating an intensified risk of water erosion. These findings suggest that the 40-year-high spatial resolution rainfall erosivity dataset can provide accurate data support for a quantitative understanding of soil erosion on the TP.

14.
Clin Cosmet Investig Dermatol ; 17: 1049-1058, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737946

RESUMO

Introduction: Angiotensin (1-7) (Ang-(1-7)) is an emerging component of the renin-angiotensin system (RAS) with effective anti-fibrosis properties and has been shown to interfere with epithelial-mesenchymal transition (EMT) by numerous studies. In recent years, EMT has been proposed as a new therapeutic target for skin fibrotic diseases such as keloids. However, the effect of Ang-(1-7) on EMT in skin is still unclear. Hence, the purpose of this study was to explore the effect of Ang-(1-7) on Transforming growth factor-ß1(TGF-ß1)-induced EMT of human immortalized keratinocytes HaCaT in vitro. Methods: The study involved the use of the human immortalized keratinocyte cell line (HaCaT). The cells were cultured in high-glucose DMEM medium with 10% fetal bovine serum and 1% penicillin-streptomycin. Four groups were created for experimentation: control group (Group C), TGF-ß1-treated group (Group T), Ang-(1-7)-treated group (Group A), and a group treated with both TGF-ß1 and Ang-(1-7) (Group A + T). Various assays were conducted, including a cell proliferation assay using CCK-8 solution, a scratch wound healing assay to evaluate cell migration, and Western blotting to detect protein expressions related to cell characteristics. Additionally, quantitative real-time polymerase chain reaction (PCR) was performed to analyze epithelial-mesenchymal transition (EMT) related gene expression levels. The study aimed to investigate the effects of TGF-ß1 and Ang-(1-7) on HaCaT cells. Results: We found that Ang-(1-7) not only reduced the migration of HaCaT cells induced by TGF-ß1 in vitro but also reduced the expression of α-SMA and vimentin, and restored the protein expression of E-cadherin and claudin-1. Mechanistically, Ang-(1-7) inhibits the phosphorylation levels of Smad2 and Smad3 in the TGF-ß1 canonical pathway, and suppresses the expression of EMT-related transcription factors (EMT-TFs) such as SNAI2, TWIST1, and ZEB1. Discussion: Taken together, our findings suggest that Ang-(1-7) inhibits TGF-ß1-induced EMT in HaCaT cells in vitro by disrupting the TGF-ß1-Smad canonical signaling pathway. These results may be helpful in the treatment of EMT in skin fibrotic diseases such as keloids.

15.
J Hazard Mater ; 468: 133844, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394900

RESUMO

Androgen receptor (AR) agonists have strong endocrine disrupting effects in fish. Most studies mainly investigate AR binding capacity using human AR in vitro. However, there is still few methods to rapidly predict AR agonists in aquatic organisms. This study aimed to screen AR agonists of fish species using machine learning and molecular models in water-relevant list from NORMAN, a network of reference laboratories for monitoring contaminants of emerging concern in the environment. In this study, machine learning approaches (e.g., Deep Forest (DF)), Random Forests and artificial neural networks) were applied to predict AR agonists. Zebrafish, fathead minnow, mosquitofish, medaka fish and grass carp are all important aquatic model organisms widely used to evaluate the toxicity of new pollutants, and the molecular models of ARs from these five fish species were constructed to further screen AR agonists using AlphaFold2. The DF method showed the best performances with 0.99 accuracy, 0.97 sensitivity and 1 precision. The Asn705, Gln711, Arg752, and Thr877 residues in human AR and the corresponding sites in ARs from the five fish species were responsible for agonist binding. Overall, 245 substances were predicted as suspect AR agonists in the five fish species, including, certain glucocorticoids, cholesterol metabolites, and cardiovascular drugs in the NORMAN list. Using machine learning and molecular modeling hybrid methods rapidly and accurately screened AR agonists in fish species, and helping evaluate their ecological risk in fish populations.


Assuntos
Androgênios , Disruptores Endócrinos , Peixes , Receptores Androgênicos , Animais , Humanos , Androgênios/química , Androgênios/toxicidade , Cyprinidae , Aprendizado de Máquina , Modelos Moleculares , Peixe-Zebra , Disruptores Endócrinos/química , Disruptores Endócrinos/toxicidade
16.
Nicotine Tob Res ; 15(2): 320-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22614545

RESUMO

INTRODUCTION: Bupropion is a first-line pharmacological aid for smoking cessation; however, no clinical trials have been conducted in a Chinese population. METHODS: We enrolled 248 smokers in a hospital-based, randomized, smoking cessation trial conducted at four outpatient centers in Beijing. A total of 123 participants received an 8-week course of sustained-release bupropion (Bup-SR) and 125 participants received 8 weeks of placebo. All participants received brief education and counseling on smoking cessation. We determined rates of abstinence and smoking reduction based on chemical verification and self-report at 8 and 12 weeks. RESULTS: At the end of the medication treatment (8 weeks) and at the end of the trial (12 weeks), the abstinence rates for Bup-SR were 29.3% and 39.8%, respectively, and 10.4% and 8.0% for placebo, respectively (both p < .001). Bup-SR was also superior to placebo in reducing cigarettes per day and urinary cotinine levels. CONCLUSION: Bup-SR is efficacious for smoking cessation in healthy Chinese patients treated in the outpatient setting. It is well tolerated with a few mild side effects.


Assuntos
Bupropiona/uso terapêutico , Abandono do Hábito de Fumar , Adulto , China , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento
17.
MedComm (2020) ; 4(5): e352, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37638339

RESUMO

Enhanced P53 signaling may lead to hematopoietic disorders, yet an effective therapeutic strategy is still lacking. Our study, along with previous research, suggests that P53 overactivation and hematopoietic defects are major consequences of zinc deficiency. However, the relationship between these two pathological processes remains unclear. In this study, we observed a severe reduction in the number of hematopoietic stem cells (HSCs) and multi-lineage progenitor cells in zebrafish treated with the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine and showed the indispensable role of P53 signaling in the process. Next, we took advantage of HSCs-labeled transgenic zebrafish and conducted a highly efficient phenotypic screening for small molecules against P53-dependent hematopoietic disorders. Hydroxysafflor yellow A (HSYA), a natural chalcone glycoside, exhibited potent protection against hematopoietic failure in zinc-deficient zebrafish and strongly inhibited the P53 pathway. We confirmed the protective effect of HSYA in zinc-deficient mice bone marrow nucleated cells, which showed a significant suppression of P53 signaling and oxidative stress. Furthermore, the hematopoietic-protective activity of HSYA was validated using a mice model of myelotoxicity induced by 5-FU. In summary, our work provides an effective phenotypic screening strategy for identifying hematopoietic-protective agents and reveals the novel role of HSYA as a promising lead compound in rescuing hematopoietic disorders associated with P53 overactivation.

18.
Acta Histochem ; 125(4): 152042, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37137202

RESUMO

This study aimed to investigate the effect of hypoxia on the anti-inflammatory effect of adipose-derived mesenchymal stem cells (AMSCs) in vitro and its possible mechanism. AMSCs were cultured in vitro in a hypoxic environment with 3% O2, and a normoxic (21% O2) environment was used as the control. The cells were identified by in vitro adipogenic and osteogenic differentiation and cell surface antigen detection, and the cell viability were detected. The effect of hypoxic AMSCs on macrophage inflammation was analyzed by co-culture. The results showed that under hypoxia, AMSCs had better viability, significantly downregulated the expression of inflammatory factors, alleviated macrophage inflammation, and activated the PI3K/AKT/HIF-1α pathway.


Assuntos
Células-Tronco Mesenquimais , Proteínas Proto-Oncogênicas c-akt , Humanos , Hipóxia Celular/fisiologia , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/metabolismo , Obesidade/metabolismo , Osteogênese , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
19.
Front Physiol ; 14: 1284981, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089479

RESUMO

Poor wound healing and pathological healing have been pressing issues in recent years, as they impact human quality of life and pose risks of long-term complications. The study of neovascularization has emerged as a prominent research focus to address these problems. During the process of repair and regeneration, the establishment of a new vascular system is an indispensable stage for complete healing. It provides favorable conditions for nutrient delivery, oxygen supply, and creates an inflammatory environment. Moreover, it is a key manifestation of the proliferative phase of wound healing, bridging the inflammatory and remodeling phases. These three stages are closely interconnected and inseparable. This paper comprehensively integrates the regulatory mechanisms of new blood vessel formation in wound healing, focusing on the proliferation and migration of endothelial cells and the release of angiogenesis-related factors under different healing outcomes. Additionally, the hidden link between the inflammatory environment and angiogenesis in wound healing is explored.

20.
Sci Total Environ ; 879: 163090, 2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37003178

RESUMO

The sediment transport capacity by overland flow (Tc) is a key parameter in process-based soil erosion models and Tc variation is sensitive to changes in soil properties. This study was undertaken to investigate Tc variations with respect to soil properties and establish a universal relationship to predict Tc. The test soils were collected from typical agricultural regions (Guanzhong basin-Yangling (YL), Weibei Dry plateau-Chunhua (CH), Hilly and gully region-Ansai (AS), Ago-pastoral transition zone along the Great Wall-Yuyang (YY), and Weiriver floodplain-Weicheng (WC)) of the Loess Plateau, and subjected to 36 different combinations of slope gradients (S, 5.24-44.52 %) and flow discharge (q, 0.00033-0.00125 m2 s-1) in a hydraulic flume. The results showed that the mean Tc values for WC were 2.15, 1.38, 1.32, and 1.16 times greater than those for YL, CH, AS, and YY, respectively. Tc significantly decreased with clay content (C), mean weight diameter (MWD), and soil organic matter content (SOM). Tc for different soil types increased with S and q as a binary power function, and Tc variation was more sensitive to S than to q. Stream power (w) was the most appropriate hydraulic variable to express Tc for different soils. Tc for different soil types could be satisfactorily simulated using a quaternary power function of S, q, C, and MWD (R2 = 0.94; NSE = 0.94) or a ternary power function of w, C, and MWD (R2 = 0.94; NSE = 0.94). The new Tc equation can reflect the effect of soil properties on it and facilitate the development of a process-based soil erosion model.

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