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1.
Heliyon ; 10(9): e29874, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38694094

RESUMO

Ischemia‒reperfusion (I/R) injury is a frequently observed complication after flap surgery, and it affects skin flap survival and patient prognosis. Currently, there are no proven safe and effective treatment options to treat skin flap I/R injury. Herein, the potential efficacies of the bioactive peptide from maggots (BPM), as well as its underlying mechanisms, were explored in a rat model of skin flap I/R injury and LPS- or H2O2-elicited RAW 264.7 cells. We demonstrated that BPM significantly ameliorated the area of flap survival, and histological changes in skin tissue in vivo. Furthermore, BPM could markedly restore or enhance Nrf2 and HO-1 levels, and suppress the expression of pro-inflammatory cytokines, including TLR4, p-IκB, NFκB p65, p-p65, IL-6, and TNF-α in I/R-injured skin flaps. In addition, BPM treatment exhibited excellent biocompatibility with an adequate safety profile, while it exhibited superior ROS-scavenging ability and the upregulation of antioxidant enzymes in vitro. Mechanistically, the above benefits related to BPM involved the activation of Nrf2/HO-1 and suppression of TLR4/NF-κB pathway. Taken together, this study may provide a scientific basis for the potential therapeutic effect of BPM in the prevention of skin flap I/R injury and other related diseases.

3.
Nanomicro Lett ; 16(1): 205, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819522

RESUMO

Metal halide perovskites, particularly the quasi-two-dimensional perovskite subclass, have exhibited considerable potential for next-generation electroluminescent materials for lighting and display. Nevertheless, the presence of defects within these perovskites has a substantial influence on the emission efficiency and durability of the devices. In this study, we revealed a synergistic passivation mechanism on perovskite films by using a dual-functional compound of potassium bromide. The dual functional potassium bromide on the one hand can passivate the defects of halide vacancies with bromine anions and, on the other hand, can screen the charged defects at the grain boundaries with potassium cations. This approach effectively reduces the probability of carriers quenching resulting from charged defects capture and consequently enhances the radiative recombination efficiency of perovskite thin films, leading to a significant enhancement of photoluminescence quantum yield to near-unity values (95%). Meanwhile, the potassium bromide treatment promoted the growth of homogeneous and smooth film, facilitating the charge carrier injection in the devices. Consequently, the perovskite light-emitting diodes based on this strategy achieve a maximum external quantum efficiency of ~ 21% and maximum luminance of ~ 60,000 cd m-2. This work provides a deeper insight into the passivation mechanism of ionic compound additives in perovskite with the solution method.

4.
Nat Commun ; 15(1): 4186, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760336

RESUMO

Arylamines, serving as crucial building blocks in natural products and finding applications in multifunctional materials, are synthesized on a large scale via an electrophilic nitration/reduction sequence. However, the current methods for aromatic C-H amination have not yet attained the same level of versatility as electrophilic nitration. Here we show an extensively investigated transition metal-free and regioselective strategy for the amination of nitrobenzenes, enabling the synthesis of 4-nitro-N-arylamines through C(sp2)-H/N-H cross-coupling between electron-deficient nitroarenes and amines. Mechanistic studies have elucidated that the crucial aspects of these reactions encompass the generation of nitrogen radicals and recombination of nitrobenzene complex radicals. The C(sp2)-N bond formation is demonstrated to be highly effective for primary and secondary arylamines as well as aliphatic amines under mild conditions, exhibiting exceptional tolerance towards diverse functional groups in both nitroarenes and amines (>100 examples with yields up to 96%). Notably, this C(sp2)-H/N-H cross-coupling exhibits exclusive para-selectivity.

5.
Sci Total Environ ; 937: 173182, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740192

RESUMO

Organophosphate flame retardants (OPFRs) are widely used as alternatives to brominated flame retardants in a variety of consumer products and their consumption has continuously increased in recent years. However, their concentrations and human exposures in indoor microenvironments, particularly in a university environment, have received limited attention. In this study, the concentrations and seasonal variations of 15 OPFRs were assessed in typical microenvironments of two universities, including dormitories, offices, public microenvironments (PMEs: classroom, dining hall, gymnasium and library), and laboratories on the northern coast of China. Analysis of the OPFRs in both air and dust samples indicated widespread distribution in college campuses. The average concentration of ∑15OPFRs in the winter (12,774.4 ng/g and 5.3 ng/m3 for dust and air, respectively) was higher than in the summer (2460.4 ng/g and 4.6 ng/m3 for dust and air, respectively). The dust and air samples collected from PMEs and laboratories exhibited higher concentrations of OPFRs, followed by offices and dormitories. An equilibrium was reached between dust and air in all collected microenvironments. The daily intakes of OPFRs were significantly lower than the reference dose. Dust ingestion was the primary intake pathway in the winter, while inhalation and dust ingestion were the main intake pathways in the summer. The non-carcinogenic hazard quotients fell within the range of 10-7-10-3 in both the summer and winter, which are below the theoretical risk threshold. For the carcinogenic risk, the LCR values ranged from 10-10 to 10-8, indicating no elevated carcinogenic risk due to TnBP, TCEP, and TDCP in indoor dust and air.

6.
J Proteome Res ; 23(4): 1495-1505, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38576392

RESUMO

Triple-negative breast cancer (TNBC) is known for its aggressive nature, and TNBC management is currently challenging due to the lack of effective targets. Despite the importance of histone post-translational modifications (hPTMs) in breast cancer, their associations with molecular subtypes of breast cancer, especially TNBC, are poorly understood. In this study, a combination of untargeted and targeted proteomics approaches, supplemented by a derivatization method, was applied to breast cancer cells and tissue samples. Untargeted proteomics of eight breast cancer cell lines belonging to different molecular subtypes revealed 36 modified peptides with 12 lysine modification sites in histone H3, and the most frequently reported top 5 histone H3 methylation and acetylation sites were covered. Then, targeted proteomics was carried out to quantify the total 20 target hPTMs at the covered modification sites (i.e., mono-, di-, trimethylation, and acetylation for each site), indicating the difficulty in distinguishing TNBC cells from normal cells. Subsequently, the analysis in TNBC patients revealed significant expression differences in 4 specific hPTMs (H3K14ac, H3K27me1, H3K36me2, and H3K36me3) between TNBC and adjacent normal tissue samples. These unique hPTM patterns allowed for the differentiation of TNBC from normal cases. This finding provides promising implications for advancing targeted treatment strategies for TNBC in the future.


Assuntos
Histonas , Neoplasias de Mama Triplo Negativas , Humanos , Histonas/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Proteômica/métodos , Linhagem Celular Tumoral , Espectrometria de Massas , Processamento de Proteína Pós-Traducional
7.
Physiol Plant ; 176(2): e14287, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606719

RESUMO

Salt stress substantially leads to flowering delay. The regulation of salt-induced late flowering has been studied at the transcriptional and protein levels; however, the involvement of secondary metabolites has rarely been investigated. Here, we report that FMOGS-OXs (EC 1.14.13.237), the enzymes that catalyze the biosynthesis of glucosinolates (GSLs), promote flowering transition in Arabidopsis thaliana. It has been reported that WRKY75 is a positive regulator, and MAF4 is a negative regulator of flowering transition. The products of FMOGS-OXs, methylsulfinylalkyl GSLs (MS GSLs), facilitate flowering by inducing WRKY75 and repressing the MAS-MAF4 module. We further show that the degradation of MS GSLs is involved in salt-induced late flowering and salt tolerance. Salt stress induces the expression of myrosinase genes, resulting in the degradation of MS GSLs, thereby relieving the promotion of WRKY75 and inhibition of MAF4, leading to delayed flowering. In addition, the degradation products derived from MS GSLs enhance salt tolerance. Previous studies have revealed that FMOGS-OXs exhibit alternative catalytic activity to form trimethylamine N-oxide (TMAO) under salt stress, which activates multiple stress-related genes to promote salt tolerance. Therefore, FMOGS-OXs integrate flowering transition and salt tolerance in various ways. Our study shed light on the functional diversity of GSLs and established a connection between flowering transition, salt resistance, and GSL metabolism.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Oxigenases , Arabidopsis/metabolismo , Tolerância ao Sal , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Glucosinolatos
8.
J Am Chem Soc ; 146(18): 12601-12608, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38687243

RESUMO

The burgeoning necessity to discover new methodologies for the synthesis of long-chain hydrocarbons and oxygenates, independent of traditional reliance on high-temperature, high-pressure, and fossil fuel-based carbon, is increasingly urgent. In this context, we introduce a nonthermal plasma-based strategy for the initiation and propagation of long-chain carbon growth from biogas constituents (CO2 and CH4). Utilizing a plasma reactor operating at atmospheric room temperature, our approach facilitates hydrocarbon chain growth up to C40 in the solid state (including oxygenated products), predominantly when CH4 exceeds CO2 in the feedstock. This synthesis is driven by the hydrogenation of CO2 and/or amalgamation of CHx radicals. Global plasma chemistry modeling underscores the pivotal role of electron temperature and CHx radical genesis, contingent upon varying CO2/CH4 ratios in the plasma system. Concomitant with long-chain hydrocarbon production, the system also yields gaseous products, primarily syngas (H2 and CO), as well as liquid-phase alcohols and acids. Our finding demonstrates the feasibility of atmospheric room-temperature synthesis of long-chain hydrocarbons, with the potential for tuning the chain length based on the feed gas composition.

9.
Cancer Immunol Immunother ; 73(4): 68, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430269

RESUMO

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response. RESULTS: The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1-6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15-45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively. CONCLUSION: Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.


Assuntos
Criocirurgia , Neoplasias Hepáticas , Melanoma , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Melanoma/patologia , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos
10.
Sci Total Environ ; 926: 171885, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38527540

RESUMO

Organic contaminants, notorious for their complexity and resistance to degradation, are prevalent in aquatic environments, posing severe threats to ecosystems. Sulfate radical-based advanced oxidation processes (SR-AOPs), known for their stability and high effectiveness, have become a common choice for treating organic wastewater. Metal-organic framework materials (MOFs) have garnered substantial attention due to their facile chemical manipulation, unique structural configurations, and other favorable properties. Therefore, this article critically reviews recent advances in research involving the utilization of Fe-based MOFs (Fe-MOFs) and their derivatives in SR-AOPs. Specifically, it highlights the manipulation of influencing factors within the system to enhance the degradation of organic pollutants. The mechanisms and applications underlying the degradation of organic pollutants in the SR-AOPs system are also elucidated.

11.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474320

RESUMO

Recent mechanistic studies have indicated that combinations of radiotherapy (RT) plus immunotherapy (via CSF-1R inhibition) can serve as a strategy to overcome RT resistance and improve the survival of glioma mice. Given the high mortality rate for glioma, including low-grade glioma (LGG) patients, it is of critical importance to investigate the mechanism of the combination of RT and immunotherapy and further translate the mechanism from mouse studies to improve survival of RT-treated human glioma patients. Using the RNA-seq data from a glioma mouse study, 874 differentially expressed genes (DEGs) between the group of RT-treated mice at glioma recurrence and the group of mice with combination treatment (RT plus CSF-1R inhibition) were translated to the human genome to identify significant molecular pathways using the KEGG enrichment analysis. The enrichment analysis yields statistically significant signaling pathways, including the phosphoinositide 3-kinase (PI3K)/AKT pathway, Hippo pathway, and Notch pathway. Within each pathway, a candidate gene set was selected by Cox regression models as genetic biomarkers for resistance to RT and response to the combination of RT plus immunotherapies. Each Cox model is trained using a cohort of 295 RT-treated LGG patients from The Cancer Genome Atlas (TCGA) database and validated using a cohort of 127 RT-treated LGG patients from the Chinese Glioma Genome Atlas (CGGA) database. A four-DEG signature (ITGB8, COL9A3, TGFB2, JAG1) was identified from the significant genes within the three pathways and yielded the area under time-dependent ROC curve AUC = 0.86 for 5-year survival in the validation set, which indicates that the selected DEGs have strong prognostic value and are potential intervention targets for combination therapies. These findings may facilitate future trial designs for developing combination therapies for glioma patients.


Assuntos
Neoplasias Encefálicas , Glioma , Radioterapia (Especialidade) , Humanos , Animais , Camundongos , Fosfatidilinositol 3-Quinases , Fosfatidilinositol 3-Quinase , Imunoterapia
13.
Nano Lett ; 24(12): 3661-3669, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38408021

RESUMO

The lack of stability of red perovskite nanocrystals (PeNCs) remains the main problem that restricts their patterning application. In this work, the dual-ligand passivation strategy was introduced to stabilize PeNCs and inhibit their halogen ion migration during high-voltage electrohydrodynamic (EHD) inkjet printing. The as-printed red arrays exhibit the highest emisson intensity and least blue shift compared with samples with other passivation strategies under a high electric field during EHD inkjet printing. Combining with blue and green PeNC inks, single-color and tricolor color conversion layer arrays were successfully printed, with minimum pixel size of 5 µm and the highest spatial resolution of 2540 dpi. The color coordinate of CsPbBrI2 NCs arrays are located close to the red point, with a color gumat of 97.28% of Rec. 2020 standard. All of these show great potential in the application of color conversion layers in a near-eye micro-LED display.

14.
Arch Phys Med Rehabil ; 105(6): 1124-1132, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38307318

RESUMO

OBJECTIVE: To investigate the parallel-forms reliability, minimal detectable change with 95% confidence interval (MDC95), and feasibility of the 4 telerehabilitation version mobility-related function scales: Fugl-Meyer Assessment-lower extremity subscale (Tele-FMA-LE), Berg Balance Scale (Tele-BBS), Tinetti Performance Oriented Mobility Assessment-Gait subscale (Tele-POMA-G), and Rivermead Mobility Index (Tele-RMI). DESIGN: Reliability and agreement study and cross-sectional study. SETTING: Medical center. PARTICIPANTS: Stroke survivors' ability to independently walk 3 meters with assistive devices, age of ≥18 years for participants and their partners, stable physical condition, and absence of cognitive impairment (N=60). INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Parallel-forms reliability and MDC95 of Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI. RESULTS: No significant differences (P>.05) were observed among the mean scores of the telerehabilitation version and face-to-face version mobility-related function scales. Intraclass correlation coefficients (ICCs) indicated good reliability for most scales, with Tele-FMA-LE, Tele-BBS, and Tele-RMI scores achieving values of 0.81, 0.78, and 0.84. Tele-POMA-G scores demonstrated moderate reliability (ICC=0.72). Weighted kappa (κw) showed good-to-excellent reliability for most individual items (κw>0.60). The MDCs of the Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI were 5.84, 8.10, 2.74, and 1.31, respectively. Bland-Altman analysis showed adequate agreement between tele-assessment and face-to-face assessment for all scales. The 5 dimensions affirm the robust feasibility of tele-assessment: assessment time, subjective fatigue perception, overall preference, participant satisfaction, and system usability. CONCLUSIONS: The study demonstrates good parallel-forms reliability, MDC, and promising feasibility of the 4 telerehabilitation version mobility-related function scales (Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI) in survivors of stroke.


Assuntos
Avaliação da Deficiência , Reabilitação do Acidente Vascular Cerebral , Telerreabilitação , Humanos , Masculino , Feminino , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Reabilitação do Acidente Vascular Cerebral/métodos , Estudos Transversais , Idoso , Adulto , Limitação da Mobilidade , Equilíbrio Postural/fisiologia , Sobreviventes
15.
Opt Express ; 32(2): 1851-1863, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297728

RESUMO

We demonstrate a bidirectional mode-locked erbium-doped fiber laser by incorporating gold nanofilm as a saturable absorber (SA). The gold nanofilm SA has the advantages of high stability and high optical damage threshold. Besides, the SA exhibits a large modulation depth of 26% and a low saturation intensity of 1.22 MW/cm2 at 1.56 µm wavelength band, facilitating the mode-locking of bidirectional propagating solitons within a single laser cavity. Bidirectional mode-locked solitons are achieved, with the clockwise pulse centered at 1568.35 nm and the counter-clockwise one at 1568.6 nm, resulting in a slight repetition rate difference of 19 Hz. Moreover, numerical simulations are performed to reveal the counter-propagating dynamics of the two solitons, showing good agreement with the experimental results. The asymmetric cavity configuration gives rise to distinct buildup and evolution dynamics of the two counter-propagating pulses. These findings highlight the advantage of the gold nanofilm SA in constructing bidirectional mode-locked fiber lasers and provide insights for understanding the bidirectional pulse propagation dynamics.

16.
World J Gastroenterol ; 30(4): 318-331, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38313229

RESUMO

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma (uHCC). HAIC-based treatment showed great potential for treating uHCC. However, large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking. AIM: To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors, programmed cell death of protein 1 (PD-1) and its ligand (PD-L1) blockers (triple therapy) under real-world conditions. METHODS: Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis. Study-level pooled analyses of hazard ratios (HRs) and odds ratios (ORs) were performed. This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades (AIPB) at Sun Yat-sen University Cancer Center from January 2018 to April 2023. Propensity score matching (PSM) was performed to balance the bias between the groups. The Kaplan-Meier method and cox regression were used to analyse the survival data, and the log-rank test was used to compare the suvival time between the groups. RESULTS: A total of 13 randomized controlled trials were included. HAIC alone and in combination with sorafenib were found to be effective treatments (P values for ORs: HAIC, 0.95; for HRs: HAIC + sorafenib, 0.04). After PSM, 176 HCC patients were included in the analysis. The triple therapy group (n = 88) had a longer median overall survival than the AIPB group (n = 88) (31.6 months vs 14.6 months, P < 0.001) and a greater incidence of adverse events (94.3% vs 75.4%, P < 0.001). CONCLUSION: This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC. Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Antígeno B7-H1 , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos , Sorafenibe/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
J Food Prot ; 87(3): 100235, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38301956

RESUMO

Polychlorinated biphenyls (PCBs) are synthetic organic contaminants that are widespread in the environment. There are 209 PCB congeners. Fish oil produced from marine fish is widely used as a health supplement. PCB contamination of fish oil is of concern. We determined the concentrations of all 209 PCB congeners in commercially available fish oil supplements from Japan and estimated PCB intakes for humans consuming the supplements. We determined the concentrations of non-dioxin-like PCBs separately. The total PCB concentrations in 37 fish oil supplements purchased in Japan were 0.024-19 ng/g whole weight, and the non-dioxin-like PCB concentration range was also 0.024-19 ng/g whole weight. The total PCB intakes calculated for a 50 kg human consuming the supplements were 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)) and the non-dioxin-like PCB intake range was also 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)). The total PCB intakes were much lower than the tolerable daily intake of 20 ng/(kg body weight per day) recommended by the WHO. The results indicated that PCBs in the fish oil supplements pose acceptable risks to humans consuming the fish oil supplements daily.


Assuntos
Bifenilos Policlorados , Humanos , Bifenilos Policlorados/análise , Óleos de Peixe , Japão , Suplementos Nutricionais/análise , Peso Corporal , Contaminação de Alimentos/análise
18.
Proc Natl Acad Sci U S A ; 121(3): e2319335121, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38198526

RESUMO

The phytohormone cytokinin has various roles in plant development, including meristem maintenance, vascular differentiation, leaf senescence, and regeneration. Prior investigations have revealed that cytokinin acts via a phosphorelay similar to the two-component system by which bacteria sense and respond to external stimuli. The eventual targets of this phosphorelay are type-B ARABIDOPSIS RESPONSE REGULATORS (B-ARRs), containing the conserved N-terminal receiver domain (RD), middle DNA binding domain (DBD), and C-terminal transactivation domain. While it has been established for two decades that the phosphoryl transfer from a specific histidyl residue in ARABIDOPSIS HIS PHOSPHOTRANSFER PROTEINS (AHPs) to an aspartyl residue in the RD of B-ARRs results in a rapid transcriptional response to cytokinin, the underlying molecular basis remains unclear. In this work, we determine the crystal structures of the RD-DBD of ARR1 (ARR1RD-DBD) as well as the ARR1DBD-DNA complex from Arabidopsis. Analyses of the ARR1DBD-DNA complex have revealed the structural basis for sequence-specific recognition of the GAT trinucleotide by ARR1. In particular, comparing the ARR1RD-DBD and ARR1DBD-DNA structures reveals that unphosphorylated ARR1RD-DBD exists in a closed conformation with extensive contacts between the RD and DBD. In vitro and vivo functional assays have further suggested that phosphorylation of the RD weakens its interaction with DBD, subsequently permits the DNA binding capacity of DBD, and promotes the transcriptional activity of ARR1. Our findings thus provide mechanistic insights into phosphorelay activation of gene transcription in response to cytokinin.


Assuntos
Arabidopsis , Citocininas , Ativação Transcricional , Arabidopsis/genética , Reguladores de Crescimento de Plantas , DNA
19.
Discov Oncol ; 15(1): 11, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236337

RESUMO

Adipocytes play a significant role in breast cancer due to the unique histological structure of the breast. These have not only been detected adjacent to breast cancer cells but they have also been implicated in cancer development. Adipocytes in obese individuals and tumor microenvironment (TME) have a common feature, that is, hypoxia. The increased expression of hypoxia-inducible factor (HIF)-1α is known to alter the metabolism and functions of adipocytes. In this study, we described the mechanism linking the hypoxia-sensing pathway manifested by HIF to adipocytes and breast cancer and discussed the mechanism underlying the role of hypoxic adipocytes in breast cancer development from the perspective of metabolic remodeling. The processes and pathways in hypoxic adipocytes could be a promising target in breast cancer therapy.

20.
ACS Nano ; 18(4): 2685-2707, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38241491

RESUMO

Optical metasurfaces, capable of manipulating the properties of light with a thickness at the subwavelength scale, have been the subject of extensive investigation in recent decades. This research has been mainly driven by their potential to overcome the limitations of traditional, bulky optical devices. However, most existing optical metasurfaces are confined to planar and rigid designs, functions, and technologies, which greatly impede their evolution toward practical applications that often involve complex surfaces. The disconnect between two-dimensional (2D) planar structures and three-dimensional (3D) curved surfaces is becoming increasingly pronounced. In the past two decades, the emergence of flexible electronics has ushered in an emerging era for metasurfaces. This review delves into this cutting-edge field, with a focus on both flexible and conformal design and fabrication techniques. Initially, we reflect on the milestones and trajectories in modern research of optical metasurfaces, complemented by a brief overview of their theoretical underpinnings and primary classifications. We then showcase four advanced applications of optical metasurfaces, emphasizing their promising prospects and relevance in areas such as imaging, biosensing, cloaking, and multifunctionality. Subsequently, we explore three key trends in optical metasurfaces, including mechanically reconfigurable metasurfaces, digitally controlled metasurfaces, and conformal metasurfaces. Finally, we summarize our insights on the ongoing challenges and opportunities in this field.

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