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1.
Plant J ; 115(3): 724-741, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37095638

RESUMO

Carotenoids are major accessory pigments in the chloroplast, and they also act as phytohormones and volatile compound precursors to influence plant development and confer characteristic colours, affecting both the aesthetic and nutritional value of fruits. Carotenoid pigmentation in ripening fruits is highly dependent on developmental trajectories. Transcription factors incorporate developmental and phytohormone signalling to regulate the biosynthesis process. By contrast to the well-established pathways regulating ripening-related carotenoid biosynthesis in climacteric fruit, carotenoid regulation in non-climacteric fruit is poorly understood. Capsanthin is the primary carotenoid of non-climacteric pepper (Capsicum) fruit; its biosynthesis is tightly associated with fruit ripening, and it confers red pigmentation to the ripening fruit. In the present study, using a coexpression analysis, we identified an R-R-type MYB transcription factor, DIVARICATA1, and demonstrated its role in capsanthin biosynthesis. DIVARICATA1 encodes a nucleus-localised protein that functions primarily as a transcriptional activator. Functional analyses showed that DIVARICATA1 positively regulates carotenoid biosynthetic gene (CBG) transcript levels and capsanthin levels by directly binding to and activating CBG promoter transcription. Furthermore, an association analysis revealed a significant positive association between DIVARICATA1 transcription level and capsanthin content. ABA promotes capsanthin biosynthesis in a DIVARICATA1-dependent manner. Comparative transcriptomic analysis of DIVARICATA1 in Solanaceae plants showed that its function likely differs among species. Moreover, the pepper DIVARICATA1 gene could be regulated by the ripening regulator MADS-RIN. The present study illustrates the transcriptional regulation of capsanthin biosynthesis and offers a target for breeding peppers with high red colour intensity.


Assuntos
Capsicum , Fatores de Transcrição/metabolismo , Carotenoides/metabolismo , Pigmentos Biológicos/metabolismo , Capsicum/genética , Capsicum/metabolismo , Cor , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Transativadores/genética , Filogenia
2.
Nutr Metab Cardiovasc Dis ; 34(7): 1660-1669, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38555240

RESUMO

BACKGROUND AND AIMS: Personalized antihypertensive drug selection is essential for optimizing hypertension management. The study aimed to develop a machine learning (ML) model to predict individual blood pressure (BP) responses to different antihypertensive medications. METHODS AND RESULTS: We used data from a pragmatic, cluster-randomized trial on hypertension management in China. Each patient's multiple visit records were included, and two consecutive visits were paired as the index and subsequent visits. The least absolute shrinkage and selection operator method was used to select index visit variables for predicting subsequent BP. The dataset was randomly divided into training and test sets in a 7:3 ratio. Model performance was evaluated using mean absolute error (MAE) and R-square in the test set. A total of 19,013 hypertension management visit records (6282 patients) were included. The mean age of the study population was 63.9 years, and 2657 (42.3%) were females. A total of 12 phenotypical features (age, sex, smoking within seven days, body mass index, waist circumference, index visit systolic BP, diastolic BP, heart rate, comorbidities of diabetes, dyslipidemia, coronary heart disease, and stroke), together with currently taking any prescribed antihypertensive medication regimens and visits time interval were selected to build the model. The Extreme Gradient Boost model performed best among all candidate algorithms, with an MAE of 8.57 mmHg and an R2 = 0.28 in the test set. CONCLUSION: The ML techniques exhibit significant potential for predicting individual responses to antihypertensive treatments, thereby aiding clinicians in achieving optimal BP control safely and efficiently. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03636334. Registered July 3, 2018, https://clinicaltrials.gov/study/NCT03636334.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Hipertensão , Aprendizado de Máquina , Valor Preditivo dos Testes , Humanos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Feminino , Masculino , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertensão/diagnóstico , Pessoa de Meia-Idade , Pressão Sanguínea/efeitos dos fármacos , Idoso , China/epidemiologia , Resultado do Tratamento , Medicina de Precisão , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
3.
J Biopharm Stat ; : 1-11, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557411

RESUMO

The incorporation of real-world data (RWD) into medical product development and evaluation has exhibited consistent growth. However, there is no universally adopted method of how much information to borrow from external data. This paper proposes a study design methodology called Tree-based Monte Carlo (TMC) that dynamically integrates patients from various RWD sources to calculate the treatment effect based on the similarity between clinical trial and RWD. Initially, a propensity score is developed to gauge the resemblance between clinical trial data and each real-world dataset. Utilizing this similarity metric, we construct a hierarchical clustering tree that delineates varying degrees of similarity between each RWD source and the clinical trial data. Ultimately, a Gaussian process methodology is employed across this hierarchical clustering framework to synthesize the projected treatment effects of the external group. Simulation result shows that our clustering tree could successfully identify similarity. Data sources exhibiting greater similarity with clinical trial are accorded higher weights in treatment estimation process, while less congruent sources receive comparatively lower emphasis. Compared with another Bayesian method, meta-analytic predictive prior (MAP), our proposed method's estimator is closer to the true value and has smaller bias.

4.
Angew Chem Int Ed Engl ; 63(3): e202316295, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38057496

RESUMO

Oligomer acceptors in organic solar cells (OSCs) have garnered substantial attention owing to their impressive power conversion efficiency (PCE) and long-term stability. However, the simple and efficient synthesis of oligomer acceptors with higher glass transition temperatures (Tg ) remains a formidable challenge. In this study, we propose an innovative strategy for the synthesis of tetramers, denoted as Tet-n, with elevated Tg s, achieved through only two consecutive Stille coupling reactions. Importantly, our strategy significantly reduces the redundancy in reaction steps compared to conventional methods for linear tetramer synthesis, thereby improving both reaction efficiency and yield. Furthermore, the OSC based on PM6:Tet-1 attains a high PCE of 17.32 %, and the PM6:L8-BO:Tet-1 ternary device achieves an even more higher PCE of 19.31 %. Remarkably, the binary device based on the Tet-1 tetramer demonstrates outstanding operational stability, retaining 80 % of the initial efficiency (T80 ) even after 1706 h of continuous illumination, which is primarily attributed to the enhanced Tg (247 °C) and lower diffusion coefficient (1.56×10-27  cm2 s-1 ). This work demonstrates the effectiveness of our proposed approach in the straightforward and efficient synthesis of tetramers materials with higher Tg s, thus offering a viable pathway for developing high-efficiency and stable OSCs.

5.
Angew Chem Int Ed Engl ; 63(22): e202404297, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38526996

RESUMO

The development of high-efficiency organic solar cells (OSCs) processed from non-halogenated solvents is crucially important for their scale-up industry production. However, owing to the difficulty of regulating molecular aggregation, there is a huge efficiency gap between non-halogenated and halogenated solvent processed OSCs. Herein, we fabricate o-xylene processed OSCs with approaching 20 % efficiency by incorporating a trimeric guest acceptor named Tri-V into the PM6:L8-BO-X host blend. The incorporation of Tri-V effectively restricts the excessive aggregation of L8-BO-X, regulates the molecular packing and optimizes the phase-separation morphology, which leads to mitigated trap density states, reduced energy loss and suppressed charge recombination. Consequently, the PM6:L8-BO-X:Tri-V-based device achieves an efficiency of 19.82 %, representing the highest efficiency for non-halogenated solvent-processed OSCs reported to date. Noticeably, with the addition of Tri-V, the ternary device shows an improved photostability than binary PM6:L8-BO-X-based device, and maintains 80 % of the initial efficiency after continuous illumination for 1380 h. This work provides a feasible approach for fabricating high-efficiency, stable, eco-friendly OSCs, and sheds new light on the large-scale industrial production of OSCs.

6.
Neurobiol Dis ; 185: 106244, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37524211

RESUMO

Lysosomes are acidic intracellular organelles with autophagic functions that are critical for protein degradation and mitochondrial homeostasis, while abnormalities in lysosomal physiological functions are closely associated with neurological disorders. Transmembrane protein 175 (TMEM175), an ion channel in the lysosomal membrane that is essential for maintaining lysosomal acidity, has been proven to coordinate with V-ATPase to modulate the luminal pH of the lysosome to assist the digestion of abnormal proteins and organelles. However, there is considerable controversy about the characteristics of TMEM175. In this review, we introduce the research progress on the structural, modulatory, and functional properties of TMEM175, followed by evidence of its relevance for neurological disorders. Finally, we discuss the potential value of TMEM175 as a therapeutic target in the hope of providing new directions for the treatment of neurodegenerative diseases.


Assuntos
Canais Iônicos , Doenças Neurodegenerativas , Humanos , Canais Iônicos/análise , Canais Iônicos/metabolismo , Doenças Neurodegenerativas/metabolismo , Lisossomos/metabolismo , Autofagia , Canais de Potássio/química
7.
Nat Mater ; 21(6): 656-663, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35513501

RESUMO

In organic photovoltaics, morphological control of donor and acceptor domains on the nanoscale is the key for enabling efficient exciton diffusion and dissociation, carrier transport and suppression of recombination losses. To realize this, here, we demonstrated a double-fibril network based on a ternary donor-acceptor morphology with multi-length scales constructed by combining ancillary conjugated polymer crystallizers and a non-fullerene acceptor filament assembly. Using this approach, we achieved an average power conversion efficiency of 19.3% (certified 19.2%). The success lies in the good match between the photoelectric parameters and the morphological characteristic lengths, which utilizes the excitons and free charges efficiently. This strategy leads to an enhanced exciton diffusion length and a reduced recombination rate, hence minimizing photon-to-electron losses in the ternary devices as compared to their binary counterparts. The double-fibril network morphology strategy minimizes losses and maximizes the power output, offering the possibility of 20% power conversion efficiencies in single-junction organic photovoltaics.

8.
Ann Surg Oncol ; 30(9): 5912-5922, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37389655

RESUMO

BACKGROUND: Small pulmonary nodules (<3 cm) can sometimes be unrecognizable and nonpalpable in video-assisted thoracoscopic surgery (VATS). Near-infrared fluorescence (NIF) VATS after indocyanine green (ICG) inhalation may effectively guide surgeons to locate the nodules. OBJECTIVE: This study aimed to investigate the safety, feasibility, and efficacy of ICG inhalation-based NIF imaging for guiding small pulmonary nodule resections. METHODS: Between February and May 2021, the first-stage, non-randomized trial enrolled 21 patients with different nodule depth, ICG inhalation doses, post-inhalation surgery times, and nodule types at a tertiary referral hospital. Between May 2021 and May 2022, the second-stage randomized trial enrolled 56 patients, who were randomly assigned to the fluorescence VATS (FLVATS) or the white-light VATS (WLVATS) group. The ratio of effective guidance and the time consumption for nodule localization were compared. RESULTS: The first-stage trial proved this new method is safe and feasible, and established a standardized protocol with optimized nodule depth (≤1 cm), ICG dose (0.20-0.25 mg/kg), and surgery window (50-90 min after ICG inhalation). In the second-stage trial, the FLVATS achieved 87.1% helpful nodule localization guidance, which was significantly higher than the WLVATS (59.1%, p < 0.05). The mean nodule locating time (standard deviation) was 1.8 [0.9] and 3.3 [2.3] min, respectively. Surgeons adopting FLVATS were significantly faster (p < 0.01), especially when locating small ground-glass opacities (1.3 [0.6] min vs. 7.0 [3.5] min, p < 0.05). Five of 31 nodules (16.1%) were only detectable by FLVATS, whereas both white light and palpation failed. CONCLUSIONS: This new method is safe and feasible for small pulmonary nodule resection. It significantly improves nodule localization rates with less time consumption, and hence is highly worthy for clinical promotion. Clinical Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2100047326.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Verde de Indocianina , Cirurgia Torácica Vídeoassistida/métodos , Neoplasias Pulmonares/cirurgia , Tomografia Computadorizada por Raios X/métodos , Pulmão , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia
9.
Mol Pharm ; 20(9): 4743-4757, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37579048

RESUMO

Currently, the low survival rate and poor prognosis of patients with nasopharyngeal carcinoma are ascribed to the lack of early and accurate diagnosis and resistance to radiotherapy. In parallel, the integration of imaging-guided diagnosis and precise treatment has gained much attention in the field of theranostic nanotechnology. However, constructing dual-modal imaging-guided nanotheranostics with desired imaging performance as well as great biocompatibility remains challenging. Therefore, we developed a simple but multifunctional nanotheranostic GdCPP for the early and accurate diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC), which combined fluorescence imaging and magnetic resonance imaging (MRI) onto a single nanoplatform for imaging-guided subsequent photodynamic therapy (PDT). GdCPP had an appropriate particle size (81.93 ± 0.69 nm) and was highly stable, resulting in sufficient tumor accumulation, which along with massive reactive oxygen species (ROS) generation upon irradiation further significantly killed tumor cells. Moreover, GdCPP owned much stronger r1 relaxivity (9.396 mM-1 s-1) compared to clinically used Gd-DTPA (5.034 mM-1 s-1) and exhibited better T1WI MRI performance. Under dual-modal imaging-guided PDT, GdCPP achieved efficient therapeutic outcomes without causing any noticeable tissue damage. The results of in vitro and in vivo studies indicated that GdCPP may be a suitable candidate for dual-modal imaging-guided precision tumor therapy.


Assuntos
Nanopartículas , Neoplasias Nasofaríngeas , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Nanomedicina Teranóstica/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Linhagem Celular Tumoral
10.
Behav Res Methods ; 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38082115

RESUMO

Driving requires vision, yet there is little empirical data about how vision and cognition support safe driving. It is difficult to study perception during natural driving because the experimental rigor required would be dangerous and unethical to implement on the road. The driving environment is complex, dynamic, and immensely variable, making it extremely challenging to accurately replicate in simulation. Our proposed solution is to study vision using stimuli which reflect this inherent complexity by using footage of real driving situations. To this end, we curated a set of 750 crowd-sourced video clips (434 hazard and 316 no-hazard clips), which have been spatially, temporally, and categorically annotated. These annotations describe where the hazard appears, what it is, and when it occurs. In addition, perceived dangerousness changes from moment to moment and is not a simple binary detection judgement. To capture this more granular aspect of our stimuli, we asked 48 observers to rate the perceived hazardousness of 1356 brief video clips taken from these 750 source clips on a continuous scale. These ratings span the entire scale, have high interrater agreement, and are robust to driving history. This novel stimulus set is not only useful for understanding drivers' ability to detect hazards, but is also a tool for studying dynamic scene perception and other aspects of visual function. While this stimulus set was originally designed for behavioral studies, researchers interested in other areas such as traffic safety or computer vision may also find this dataset a useful resource.

11.
Angew Chem Int Ed Engl ; 62(40): e202308595, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37551967

RESUMO

Oligomer acceptors have recently emerged as promising photovoltaic materials for achieving high power conversion efficiency (PCE) and long-term stability in organic solar cells (OSCs). However, the limited availability of diverse acceptors, resulting from the sole synthetic approach, has hindered their potential for future industrialization. In this study, we present a facile and effective stepwise approach that utilizes two consecutive Stille coupling reactions for the synthesis of oligomer acceptors. To demonstrate the feasibility of the novel approach, we successfully synthesize a trimer acceptor, Tri-Y6-OD, and further systematically investigate the impact of oligomerization on device performance and stability. The results reveal that this approach has significant advantages compared to the conventional method, including reduced formation of unwanted by-products and lower difficulties in purification. Remarkably, the OSC based on PM6 : Tri-Y6-OD achieves an impressive PCE of 18.03 % and maintains 80 % of the initial PCE (T80 ) for 1523 h under illumination, surpassing the performance of the corresponding small molecule acceptor Y6-OD-based device. Furthermore, the versatility of the synthetic strategy in obtaining diverse acceptors is further demonstrated. Overall, our findings provide a facile, versatile and stepwise way for synthesizing oligomer acceptors, thereby facilitating the development of stable and efficient OSCs.

12.
Br J Cancer ; 127(6): 1014-1025, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35715638

RESUMO

BACKGROUND: Fibroblast growth factor receptor (FGFR) signaling influenced tumour occurrence and development. Overexpression of FGFR had been observed in many types of cancers, including colon cancer. FGFR inhibitor is considered to be effective in treating colon cancer patients. METHODS: First, the kinase inhibition rate was determined. MTT, western blotting, colony formation, EdU and comet assays were performed to evaluate the anti-tumour effects of F1-7 in vitro. RNA-seq and bioinformatics analysis were used for further verification. Additionally, a xenograft model was generated to investigate the anti-tumour effect of F1-7. RESULTS: F1-7 can inhibit the proliferation of colon cancer cells in vitro. It could significantly inhibit FGFR phosphorylation and its downstream signaling pathway. Whole-genome RNA-seq analysis found that the changed genes were not only functionally focused on MAPK signaling pathway but also related to cell apoptosis and ferroptosis. Experimental evidence demonstrated that F1-7 can directly increase the level of cellular DNA damage. The occurrence of DNA damage led to cell cycle arrest and inhibition of cell metastasis and cell apoptosis. Mouse model experiments also confirmed that F1-7 could inhibit tumour growth by inhibiting the FGFR pathway. CONCLUSIONS: F1-7 exhibits anti-tumour activity by inhibiting the FGFR pathway. It could be a novel therapeutic agent for targeting colon cancer cells.


Assuntos
Neoplasias do Colo , Inibidores de Proteínas Quinases , Animais , Morte Celular , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Dano ao DNA , Humanos , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Receptores de Fatores de Crescimento de Fibroblastos/genética
13.
BMC Plant Biol ; 21(1): 262, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098881

RESUMO

BACKGROUND: The basic helix-loop-helix (bHLH) transcription factors (TFs) serve crucial roles in regulating plant growth and development and typically participate in biological processes by interacting with other TFs. Capsorubin and capsaicinoids are found only in Capsicum, which has high nutritional and economic value. However, whether bHLH family genes regulate capsorubin and capsaicinoid biosynthesis and participate in these processes by interacting with other TFs remains unknown. RESULTS: In this study, a total of 107 CabHLHs were identified from the Capsicum annuum genome. Phylogenetic tree analysis revealed that these CabHLH proteins were classified into 15 groups by comparing the CabHLH proteins with Arabidopsis thaliana bHLH proteins. The analysis showed that the expression profiles of CabHLH009, CabHLH032, CabHLH048, CabHLH095 and CabHLH100 found in clusters C1, C2, and C3 were similar to the profile of carotenoid biosynthesis in pericarp, including zeaxanthin, lutein and capsorubin, whereas the expression profiles of CabHLH007, CabHLH009, CabHLH026, CabHLH063 and CabHLH086 found in clusters L5, L6 and L9 were consistent with the profile of capsaicinoid accumulation in the placenta. Moreover, CabHLH007, CabHLH009, CabHLH026 and CabHLH086 also might be involved in temperature-mediated capsaicinoid biosynthesis. Yeast two-hybrid (Y2H) assays demonstrated that CabHLH007, CabHLH009, CabHLH026, CabHLH063 and CabHLH086 could interact with MYB31, a master regulator of capsaicinoid biosynthesis. CONCLUSIONS: The comprehensive and systematic analysis of CabHLH TFs provides useful information that contributes to further investigation of CabHLHs in carotenoid and capsaicinoid biosynthesis.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Capsicum/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Capsicum/metabolismo , Genes de Plantas , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo
14.
J Vis ; 21(10): 8, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34495294

RESUMO

Previous research suggests that peripheral target detection is modulated by viewing distance and distance simulated by pictorial cues and optic flow. In the latter case, it is unclear what cues contribute to the effect of distance. The current study evaluated the effect of distance on peripheral detection in a virtual three-dimensional environment. Experiments 1-3 used a continuous, dynamic central task that simulated observers traveling either actively or passively through a virtual environment following a car. Peripheral targets were flashed on checkerboard-covered walls to the left and right of the path of motion, at a near and a far distance from the observer. The retinal characteristics of the targets were identical across distances. Experiment 1 found more accurate and faster detection for near targets compared to far targets, especially for larger eccentricities. Experiment 2 equated the predictability of target onset across distances and found the near advantage for larger eccentricities in accuracy but a much smaller effect in reaction time (RT). Experiment 3 removed the checkerboard background implemented in Experiments 1 and 2, and Experiment 4 manipulated several static, monocular cues. Experiments 3 and 4 found that the variation in the density of the checkerboard backgrounds could explain the main effect of distance on accuracy but could not completely account for the interaction between target distance and eccentricity. These results suggest that attention is modulated by target distance, but the effect is small. Finally, there were consistent divided attention costs in the central car-following task but not the peripheral detection task.


Assuntos
Atenção , Sinais (Psicologia) , Percepção de Distância , Humanos , Tempo de Reação
15.
Molecules ; 26(24)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34946556

RESUMO

Drug-target interaction (DTIs) prediction plays a vital role in probing new targets for breast cancer research. Considering the multifaceted challenges associated with experimental methods identifying DTIs, the in silico prediction of such interactions merits exploration. In this study, we develop a feature-based method to infer unknown DTIs, called PsePDC-DTIs, which fuses information regarding protein sequences extracted by pseudo-position specific scoring matrix (PsePSSM), detrended cross-correlation analysis coefficient (DCCA coefficient), and an FP2 format molecular fingerprint descriptor of drug compounds. In addition, the synthetic minority oversampling technique (SMOTE) is employed for dealing with the imbalanced data after Lasso dimensionality reduction. Then, the processed feature vectors are put into a random forest classifier to perform DTIs predictions on four gold standard datasets, including nuclear receptors (NR), G-protein-coupled receptors (GPCR), ion channels (IC), and enzymes (E). Furthermore, we explore new targets for breast cancer treatment using its risk genes identified from large-scale genome-wide genetic studies using PsePDC-DTIs. Through five-fold cross-validation, the average values of accuracy in NR, GPCR, IC, and E datasets are 95.28%, 96.19%, 96.74%, and 98.22%, respectively. The PsePDC-DTIs model provides us with 10 potential DTIs for breast cancer treatment, among which erlotinib (DB00530) and FGFR2 (hsa2263), caffeine (DB00201) and KCNN4 (hsa3783), as well as afatinib (DB08916) and FGFR2 (hsa2263) are found with direct or inferred evidence. The PsePDC-DTIs model has achieved good prediction results, establishing the validity and superiority of the proposed method.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Descoberta de Drogas , Algoritmos , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Enzimas/genética , Enzimas/metabolismo , Feminino , Humanos , Canais Iônicos/antagonistas & inibidores , Canais Iônicos/genética , Canais Iônicos/metabolismo , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
16.
J Integr Plant Biol ; 63(12): 2150-2163, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34647689

RESUMO

Grain size is determined by the size and number of cells in the grain. The regulation of grain size is crucial for improving crop yield; however, the genes and molecular mechanisms that control grain size remain elusive. Here, we report that a member of the detoxification efflux carrier /Multidrug and Toxic Compound Extrusion (DTX/MATE) family transporters, BIG RICE GRAIN 1 (BIRG1), negatively influences grain size in rice (Oryza sativa L.). BIRG1 is highly expressed in reproductive organs and roots. In birg1 grain, the outer parenchyma layer cells of spikelet hulls are larger than in wild-type (WT) grains, but the cell number is unaltered. When expressed in Xenopus laevis oocytes, BIRG1 exhibits chloride efflux activity. Consistent with this role of BIRG1, the birg1 mutant shows reduced tolerance to salt stress at a toxic chloride level. Moreover, grains from birg1 plants contain a higher level of chloride than those of WT plants when grown under normal paddy field conditions, and the roots of birg1 accumulate more chloride than those of WT under saline conditions. Collectively, the data suggest that BIRG1 in rice functions as a chloride efflux transporter that is involved in mediating grain size and salt tolerance by controlling chloride homeostasis.


Assuntos
Oryza , Tolerância ao Sal , Cloretos , Grão Comestível/genética , Grão Comestível/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Tolerância ao Sal/genética
17.
BMC Genomics ; 21(1): 573, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831011

RESUMO

BACKGROUND: ERF transcription factors (TFs) belong to the Apetala2/Ethylene responsive Factor (AP2/ERF) TF family and play a vital role in plant growth and development processes. Capsorubin and capsaicinoids have relatively high economic and nutritional value, and they are specifically found in Capsicum. However, there is little understanding of how ERFs participate in the regulatory networks of capsorubin and capsaicinoids biosynthesis. RESULTS: In this study, a total of 142 ERFs were identified in the Capsicum annuum genome. Subsequent phylogenetic analysis allowed us to divide ERFs into DREB (dehydration responsive element binding proteins) and ERF subfamilies, and further classify them into 11 groups with several subgroups. Expression analysis of biosynthetic pathway genes and CaERFs facilitated the identification of candidate genes related to the regulation of capsorubin and capsaicinoids biosynthesis; the candidates were focused in cluster C9 and cluster C10, as well as cluster L3 and cluster L4, respectively. The expression patterns of CaERF82, CaERF97, CaERF66, CaERF107 and CaERF101, which were found in cluster C9 and cluster C10, were consistent with those of accumulating of carotenoids (ß-carotene, zeaxanthin and capsorubin) in the pericarp. In cluster L3 and cluster L4, the expression patterns of CaERF102, CaERF53, CaERF111 and CaERF92 were similar to those of the accumulating capsaicinoids. Furthermore, CaERF92, CaERF102 and CaERF111 were found to be potentially involved in temperature-mediated capsaicinoids biosynthesis. CONCLUSION: This study will provide an extremely useful foundation for the study of candidate ERFs in the regulation of carotenoids and capsaicinoids biosynthesis in peppers.


Assuntos
Capsicum , Fatores de Transcrição , Capsicum/genética , Capsicum/metabolismo , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Bioorg Med Chem Lett ; 30(17): 127373, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738985

RESUMO

In this study, a series of compounds with 1,2,4-oxadiazole core was designed and synthesized for the optimization of JC01, an anti-inflammatory hit identified from our in-house compound library using NF-κB pathway luciferase assay and NO production assay. All the synthetic compounds 1-29 have been screened for their anti-inflammatory effects by evaluating their inhibition against LPS-induced NO release, and compound 17 exhibited the highest activity. Western blotting and immunofluorescence analysis revealed that 17 prominently inhibited LPS-induced activation of NF-κB in RAW264.7 cells and blocked the phosphorylation of p65. Consistent with these results, it was found that 17 prevented the nuclear translocation of NF-κB induced by LPS. These data highlighted 17 as a promising anti-inflammatory agent by inhibiting NF-κB activity.


Assuntos
Anti-Inflamatórios/farmacologia , Oxidiazóis/química , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/síntese química , Sobrevivência Celular , Desenho de Fármacos , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Oxidiazóis/síntese química , Oxidiazóis/farmacologia , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
19.
Proc Natl Acad Sci U S A ; 114(10): E2036-E2045, 2017 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-28202726

RESUMO

The central vacuole in a plant cell occupies the majority of the cellular volume and plays a key role in turgor regulation. The vacuolar membrane (tonoplast) contains a large number of transporters that mediate fluxes of solutes and water, thereby adjusting cell turgor in response to developmental and environmental signals. We report that two tonoplast Detoxification efflux carrier (DTX)/Multidrug and Toxic Compound Extrusion (MATE) transporters, DTX33 and DTX35, function as chloride channels essential for turgor regulation in Arabidopsis Ectopic expression of each transporter in Nicotiana benthamiana mesophyll cells elicited a large voltage-dependent inward chloride current across the tonoplast, showing that DTX33 and DTX35 each constitute a functional channel. Both channels are highly expressed in Arabidopsis tissues, including root hairs and guard cells that experience rapid turgor changes during root-hair elongation and stomatal movements. Disruption of these two genes, either in single or double mutants, resulted in shorter root hairs and smaller stomatal aperture, with double mutants showing more severe defects, suggesting that these two channels function additively to facilitate anion influx into the vacuole during cell expansion. In addition, dtx35 single mutant showed lower fertility as a result of a defect in pollen-tube growth. Indeed, patch-clamp recording of isolated vacuoles indicated that the inward chloride channel activity across the tonoplast was impaired in the double mutant. Because MATE proteins are widely known transporters of organic compounds, finding MATE members as chloride channels expands the functional definition of this large family of transporters.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Canais de Cloreto/genética , Regulação da Expressão Gênica de Plantas , Membranas Intracelulares/metabolismo , Proteínas de Membrana Transportadoras/genética , Raízes de Plantas/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Canais de Cloreto/metabolismo , Membranas Intracelulares/ultraestrutura , Potenciais da Membrana/fisiologia , Proteínas de Membrana Transportadoras/metabolismo , Mutação , Pressão Osmótica , Técnicas de Patch-Clamp , Células Vegetais/metabolismo , Células Vegetais/ultraestrutura , Raízes de Plantas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transdução de Sinais , Nicotiana/genética , Nicotiana/metabolismo , Vacúolos/metabolismo , Vacúolos/ultraestrutura
20.
Ecotoxicol Environ Saf ; 191: 110001, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31812281

RESUMO

The interference of toxic heavy metals in the process of microbial aerobic denitrification is a hot issue in industry wastewater treatment in recent years. In this study, a multifunctional aerobic denitrifying bacterium - Pseudomonas aeruginosa G12 isolated from sewage sludge was used to explore the simultaneous removal ability to NO3--N and Cr(VI) in wastewater by a series of batch experiments. The results showed that G12 could effectively remove NO3--N (500 mg L-1) and Cr(VI) (10 mg L-1) by 98% and 93%, respectively. Meanwhile, the study found that the strain G12 had the potential to adapt to the complex external environment, including different carbon resources, nitrogen sources, and the coexisting heavy metals (Mn2+ and Cu2+). The strain G12 also had the considerable tolerance to initial NO3--N (100-700 mg L-1) and Cr(VI) (1-20 mg L-1) concentrations. The instrument analysis methods-Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD), from the molecular level, further confirmed that the strain G12 could remove NO3--N by aerobic denitrification, and the reduced functional groups (amino group, amide group, hydroxyl group and carboxyl group) on the surface of bacteria could transform Cr(VI) to Cr(III) (mainly CrCl3). This study will offer a promising new microbial resource for nitrogen and Cr(VI) removal in industry wastewater treatment.


Assuntos
Cromo/metabolismo , Nitratos/metabolismo , Pseudomonas aeruginosa/metabolismo , Águas Residuárias/química , Poluentes Químicos da Água/metabolismo , Desnitrificação , Metais Pesados/metabolismo , Nitratos/química , Óxidos de Nitrogênio/metabolismo , Esgotos/microbiologia
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