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1.
Biomed Pharmacother ; 175: 116703, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38713948

RESUMO

The distinctive role of Yes-associated protein (YAP) in the nervous system has attracted widespread attention. This comprehensive review strategically uses the retina as a vantage point, embarking on an extensive exploration of YAP's multifaceted impact from the retina to the brain in development and pathology. Initially, we explore the crucial roles of YAP in embryonic and cerebral development. Our focus then shifts to retinal development, examining in detail YAP's regulatory influence on the development of retinal pigment epithelium (RPE) and retinal progenitor cells (RPCs), and its significant effects on the hierarchical structure and functionality of the retina. We also investigate the essential contributions of YAP in maintaining retinal homeostasis, highlighting its precise regulation of retinal cell proliferation and survival. In terms of retinal-related diseases, we explore the epigenetic connections and pathophysiological regulation of YAP in diabetic retinopathy (DR), glaucoma, and proliferative vitreoretinopathy (PVR). Lastly, we broaden our exploration from the retina to the brain, emphasizing the research paradigm of "retina: a window to the brain." Special focus is given to the emerging studies on YAP in brain disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), underlining its potential therapeutic value in neurodegenerative disorders and neuroinflammation.

2.
Chem Commun (Camb) ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743417

RESUMO

Two anionic tetrahedral cages were self-assembled as the only observable products in weakly basic water via imine condensation. The success of the high-yielding formation of the cages in water relies on (i) multivalency enhancing the stability of the imine bond and affording these cages water compatibility and (ii) a guest template with a complementary size and geometry that provides a hydrophobic driving force by occupying the corresponding cage cavity. When all four precursors, namely two trisaldehydes and two trisamines, were combined in water, narcissistic self-sorting occurred when both guest templates were present. In organic media where the hydrophobic effect is absent, narcissistic self-sorting did not occur in the analogous cage systems, confirming the importance of guest templates.

3.
Diabetes Metab Syndr ; 18(5): 103037, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38744090

RESUMO

AIM: To evaluate the potential of the combined individual vascular histopathological lesion and serum 25-hydroxy vitamin D [25(OH)D] level as predictors of outcomes in patients with diabetes and chronic kidney disease. METHODS: A total of 190 patients with type 2 diabetes and kidney disease stages 1-4 were retrospectively included. Kaplan-Meier analysis and the log-rank test were performed to assess renal survival differences. And the time-dependent receiver operating characteristic analyses were used to characterize the predictive accuracy. Hazard ratios for vascular lesion scores and 25(OH)D levels with renal outcomes were estimated using Cox proportional hazards regression models with follow-up time. RESULTS: Over a median follow-up of 23.78 (12.61, 37.14) months, 71 patients (37.4 %) experienced the renal outcomes. Enrolled patients with more severe vascular lesions had worse kidney function, heavier proteinuria, lower serum 25(OH)D levels, and higher prevalence of composite kidney outcomes. Baseline serum 25(OH)D was a significant independent risk factor for vascular lesion scores. The effect of serum 25(OH)D level on kidney prognosis was more pronounced in males and those with more exacerbated vascular lesions (score 2). The severity of vascular lesions and serum 25(OH)D levels were associated with unfavorable kidney outcomes. Accordingly, further time-dependent receiver operating characteristic curves confirmed that combined 25(OH)D level and vascular lesion score had a stable and reliable performance in renal outcomes prediction at short and long-term follow-up times. CONCLUSIONS: 25(OH)D level and vascular lesion scores in kidney histopathology could serve as a useful risk-stratification tool for predicting renal progression in patients with type 2 diabetes.

4.
J Med Chem ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718180

RESUMO

Faced with increasingly serious fungal infections and drug resistance issues, three different series of novel dual-target (programmed death ligand 1/14 α-demethylase) compounds were constructed through the fragment combination pathway in the study. Their chemical structures were synthesized, characterized, and evaluated. Among them, preferred compounds 10c-1, 17b-1, and 18b-2 could efficiently exert their antifungal and antidrug-resistant fungal ability through blocking ergosterol biosynthesis, inducing the upregulation of reactive oxygen species level, and triggering apoptosis. Especially, compound 18b-2 exhibited the synergistic function of fungal inhibition and immune activation. Moreover, the covalent organic framework carrier was also generated based on the acidic microenvironment of fungal infection to improve the bioavailability and targeting of preferred compounds; this finally accelerated the body's recovery rate.

5.
Adv Sci (Weinh) ; : e2402756, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38696647

RESUMO

Colloidal quantum dots (CQDs) are promising optoelectronic materials for solution-processed thin film optoelectronic devices. However, the large surface area with abundant surface defects of CQDs and trap-assisted non-radiative recombination losses at the interface between CQDs and charge-transport layer limit their optoelectronic performance. To address this issue, an interface heterojunction strategy is proposed to protect the CQDs interface by incorporating a thin layer of polyethyleneimine (PEIE) to suppress trap-assisted non-radiative recombination losses. This thin layer not only acts as a protective barrier but also modulates carrier recombination and extraction dynamics by forming heterojunctions at the buried interface between CQDs and charge-transport layer, thereby enhancing the interface charge extraction efficiency. This enhancement is demonstrated by the shortened lifetime of carrier extraction from 0.72 to 0.46 ps. As a result, the resultant PbS CQD solar cells achieve a power-conversion-efficiency (PCE) of 13.4% compared to 12.2% without the heterojunction.

6.
Front Endocrinol (Lausanne) ; 15: 1365350, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628586

RESUMO

Background: Thyroid-associated ophthalmopathy (TAO) is the most prevalent autoimmune orbital condition, significantly impacting patients' appearance and quality of life. Early and accurate identification of active TAO along with timely treatment can enhance prognosis and reduce the occurrence of severe cases. Although the Clinical Activity Score (CAS) serves as an effective assessment system for TAO, it is susceptible to assessor experience bias. This study aimed to develop an ensemble deep learning system that combines anterior segment slit-lamp photographs of patients with facial images to simulate expert assessment of TAO. Method: The study included 156 patients with TAO who underwent detailed diagnosis and treatment at Shanxi Eye Hospital Affiliated to Shanxi Medical University from May 2020 to September 2023. Anterior segment slit-lamp photographs and facial images were used as different modalities and analyzed from multiple perspectives. Two ophthalmologists with more than 10 years of clinical experience independently determined the reference CAS for each image. An ensemble deep learning model based on the residual network was constructed under supervised learning to predict five key inflammatory signs (redness of the eyelids and conjunctiva, and swelling of the eyelids, conjunctiva, and caruncle or plica) associated with TAO, and to integrate these objective signs with two subjective symptoms (spontaneous retrobulbar pain and pain on attempted upward or downward gaze) in order to assess TAO activity. Results: The proposed model achieved 0.906 accuracy, 0.833 specificity, 0.906 precision, 0.906 recall, and 0.906 F1-score in active TAO diagnosis, demonstrating advanced performance in predicting CAS and TAO activity signs compared to conventional single-view unimodal approaches. The integration of multiple views and modalities, encompassing both anterior segment slit-lamp photographs and facial images, significantly improved the prediction accuracy of the model for TAO activity and CAS. Conclusion: The ensemble multi-view multimodal deep learning system developed in this study can more accurately assess the clinical activity of TAO than traditional methods that solely rely on facial images. This innovative approach is intended to enhance the efficiency of TAO activity assessment, providing a novel means for its comprehensive, early, and precise evaluation.


Assuntos
Aprendizado Profundo , Oftalmopatia de Graves , Humanos , Oftalmopatia de Graves/diagnóstico por imagem , Qualidade de Vida , Órbita , Dor
7.
Exp Appl Acarol ; 92(4): 871-883, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38656472

RESUMO

The growing concern about migratory birds potentially spreading ticks due to global warming has become a significant issue. The city of Nantong in this study is situated along the East Asia-Australasian Flyway (EAAF), with numerous wetlands serving as roosting sites for migratory birds. We conducted an investigation of hard ticks and determined the phylogenetic characteristics of tick species in this city. We utilized three different genes for our study: the mitochondrial cytochrome oxidase subunit 1 (COX1) gene, the second internal transcribed spacer (ITS2), and the mitochondrial small subunit rRNA (12 S rRNA) gene. The predominant tick species were Haemaphysalis flava (H. flava) and Haemaphysalis longicornis (H. longicornis). Additionally, specimens of Haemaphysalis campanulata (H. campanulata) and Rhipicephalus sanguineus (R. sanguineus) were collected. The H. flava specimens in this study showed a close genetic relationship with those from inland provinces of China, as well as South Korea and Japan. Furthermore, samples of H. longicornis exhibited a close genetic relationship with those from South Korea, Japan, Australia, and the USA, as well as specific provinces in China. Furthermore, R. sanguineus specimens captured in Nantong showed genetic similarities with specimens from Egypt, Nigeria, and Argentina.


Assuntos
Migração Animal , Aves , Complexo IV da Cadeia de Transporte de Elétrons , Ixodidae , Filogenia , Animais , China , Ixodidae/genética , Ixodidae/classificação , Ixodidae/fisiologia , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/análise , RNA Ribossômico/genética , RNA Ribossômico/análise , Ninfa/crescimento & desenvolvimento , Ninfa/classificação , Ninfa/genética , Ninfa/fisiologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/análise , DNA Espaçador Ribossômico/análise
8.
Chem Commun (Camb) ; 60(40): 5294-5297, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38659410

RESUMO

We developed a triazatruxene-based hole transport material (HTM), 3Ka-DBT-3Ka, aiming to enhance band alignment and augment charge generation and collection in devices, as an alternative for 1,2-ethanedithiol (EDT). The PbS CQD solar cells employing 3Ka-DBT-3Ka as the HTM achieve a peak efficiency of 11.4%, surpassing devices employing the conventional PbS-EDT HTM (8.9%).

9.
J Nanobiotechnology ; 22(1): 200, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654299

RESUMO

The glymphatic system plays an important role in the transportation of cerebrospinal fluid (CSF) and the clearance of metabolite waste in brain. However, current imaging modalities for studying the glymphatic system are limited. Herein, we apply NIR-II nanoprobes with non-invasive and high-contrast advantages to comprehensively explore the function of glymphatic system in mice under anesthesia and cerebral ischemia-reperfusion injury conditions. Our results show that the supplement drug dexmedetomidine (Dex) enhances CSF influx in the brain, decreases its outflow to mandibular lymph nodes, and leads to significant differences in CSF accumulation pattern in the spine compared to isoflurane (ISO) alone, while both ISO and Dex do not affect the clearance of tracer-filled CSF into blood circulation. Notably, we confirm the compromised glymphatic function after cerebral ischemia-reperfusion injury, leading to impaired glymphatic influx and reduced glymphatic efflux. This technique has great potential to elucidate the underlying mechanisms between the glymphatic system and central nervous system diseases.


Assuntos
Sistema Glinfático , Traumatismo por Reperfusão , Animais , Sistema Glinfático/metabolismo , Camundongos , Traumatismo por Reperfusão/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Encéfalo/metabolismo , Dexmedetomidina/farmacologia , Acidente Vascular Cerebral , Anestesia , Isoflurano/farmacologia , Nanopartículas/química , Líquido Cefalorraquidiano/metabolismo , Líquido Cefalorraquidiano/química
10.
BMC Ophthalmol ; 24(1): 172, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627651

RESUMO

PURPOSE: To assess the efficacy and safety of various intraocular lenses (IOLs), including standard monofocal, bifocal, trifocal, extended depth of focus (EDOF), and enhanced monofocal IOLs, post-cataract surgery through a network meta-analysis. METHODS: A systematic search of PubMed, Cochrane Library, and Web of Science was conducted to identify relevant studies from the past 5 years. Parameters such as binocular visual acuities, spectacle independence, contrast sensitivity (CS), and optical quality were used to evaluate efficacy and safety. Data from the selected studies were analyzed using Review Manager 5.4 and STATA 17.0 software. RESULTS: Twenty-eight Randomized Controlled Trials (RCTs) comprising 2465 subjects were included. Trifocal IOLs exhibited superior uncorrected near visual acuity (UNVA) compared to monofocal IOLs (MD: -0.35; 95% CI: -0.48, -0.22). Both trifocal (AcrySof IQ PanOptix IOLs group MD: -0.13; 95% CI: -0.21, -0.06) and EDOF IOLs (MD: -0.13; 95% CI: -0.17, -0.09) showed better uncorrected intermediate visual acuity (UIVA) than monofocal IOLs. Trifocal IOLs ranked highest in spectacle independence at various distances (AT LISAtri 839MP group: SUCRA 97.5% for distance, 80.7% for intermediate; AcrySof IQ PanOptix group: SUCRA 83.0% for near). CONCLUSIONS: For cataract patients who want to treat presbyopia, trifocal IOLs demonstrated better visual acuity and spectacle independence at near distances. Different types of trifocal IOL characteristics differ. EDOF and enhanced monofocal IOLs have improved visual quality at intermediate distances.Therefore, It is very important to select the appropriate IOLs based on the lens characteristics and patient needs.


Assuntos
Catarata , Lentes Intraoculares , Facoemulsificação , Presbiopia , Humanos , Implante de Lente Intraocular , Presbiopia/cirurgia , Refração Ocular , Satisfação do Paciente , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Front Mol Neurosci ; 17: 1366855, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38685914

RESUMO

As wireless communication devices gain popularity, concerns about the potential risks of environmental exposure to complex frequency electromagnetic radiation (EMR) on mental health have become a public health issue. Historically, EMR research has predominantly focused on single- frequency electromagnetic waves, neglecting the study of multi-frequency electromagnetic waves, which more accurately represent everyday life. To address these concerns, our study compared the emotional effects of single-frequency and dual-frequency EMR while exploring potential molecular mechanisms and intervention targets. Our results revealed that single-frequency EMR at 2.65 or 0.8 GHz did not induce anxiety-like behavior in mice. However, exposure to dual-frequency EMR at 2.65/0.8 GHz significantly led to anxiety-like behavior in mice. Further analysis of mouse sera revealed substantial increases in corticosterone and corticotrophin releasing hormone levels following exposure to 2.65/0.8 GHz EMR. Transcriptome sequencing indicated a significant decrease in the expression of Cnr1, encoding cannabinoid receptor 1 Type (CB1R), in the cerebral. This finding was consistently verified through western blot analysis, revealing a substantial reduction in CB1R content. Additionally, a significant decrease in the endocannabinoid 2-arachidonoylglycerol was observed in the cerebral cortex. Remarkably, administering the cannabinoid receptor agonist Win55-212-2 significantly alleviated the anxiety-like behavior, and the cannabinoid receptor antagonist AM251 effectively counteracted the anti-anxiety effects of Win55-212-2. In summary, our research confirmed that dual-frequency EMR is more likely to induce anxiety-like behavior in mice than single-frequency EMR, with implications for the hypothalamic-pituitary-adrenal axis and the endocannabinoid system. Furthermore, our findings suggest that Win55-212-2 may represent a novel avenue for researching and developing anti-EMR drugs.

12.
Molecules ; 29(8)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38675707

RESUMO

Wastewater containing organic dyes has become one of the important challenges in water treatment due to its high salt content and resistance to natural degradation. In this work, a novelty adsorbent, PEI-SMA, was prepared by grafting polyethyleneimine (PEI) onto styrene-maleic anhydride copolymer (SMA) through an amidation reaction. The various factors, such as pH, adsorbent dosage, contact time, dye concentration, and temperature, which may affect the adsorption of PEI-SMA for Reactive Black 5 (RB5), were systematically investigated by static adsorption experiments. The adsorption process of PEI-SMA for RB5 was more consistent with the Langmuir isotherm model and the pseudo-second-order model, suggesting a single-layer chemisorption. PEI-SMA exhibits excellent adsorption performance for RB5 dye, with a maximum adsorption capacity of 1749.19 mg g-1 at pH = 2. Additionally, PEI-SMA exhibited highly efficient RB5 competitive adsorption against coexisting Cl- and SO42- ions and cationic dyes. The adsorption mechanism was explored, and it can be explained as the synergistic effect of electrostatic interaction, hydrogen bonding and π-π interaction. This study demonstrates that PEI-SMA could act as a high performance and promising candidate for the effective adsorption of anionic dyes from aqueous solutions.

13.
J Med Chem ; 67(9): 7176-7196, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38679872

RESUMO

Peroxiredoxin (PRDX1) is a tumor-overexpressed antioxidant enzyme for eliminating excessive reactive oxygen species (ROS) to protect tumor cells from oxidative damage. Herein, a series of celastrol urea derivatives were developed based on its cocrystal structure with PRDX1, with the aim of pursuing a PRDX1-specific inhibitor. Among them, derivative 15 displayed potent anti-PRDX1 activity (IC50 = 0.35 µM) and antiproliferative potency against colon cancer cells. It covalently bound to Cys-173 of PRDX1 (KD = 0.37 µM), which was secured by the cocrystal structure of PRDX1 with an analogue of 15 while exhibiting weak inhibitory effects on PRDX2-PRDX6 (IC50 > 50 µM), indicating excellent PRDX1 selectivity. Treatment with 15 dose-dependently decreased the mitochondria membrane potential of SW620 cells, probably due to ROS induced by PRDX1 inhibition, leading to cell apoptosis. In colorectal cancer cell xenograft model, it displayed potent antitumor efficacy with superior safety to celastrol. Collectively, 15 represents a promising PRDX1 selective inhibitor for the development of anticolorectal cancer agents.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Triterpenos Pentacíclicos , Peroxirredoxinas , Ureia , Humanos , Peroxirredoxinas/antagonistas & inibidores , Peroxirredoxinas/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ureia/análogos & derivados , Ureia/farmacologia , Ureia/química , Linhagem Celular Tumoral , Camundongos , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Relação Estrutura-Atividade , Camundongos Nus , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Camundongos Endogâmicos BALB C , Triterpenos/farmacologia , Triterpenos/química , Triterpenos/síntese química , Espécies Reativas de Oxigênio/metabolismo , Descoberta de Drogas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Ensaios de Seleção de Medicamentos Antitumorais
14.
J Environ Manage ; 358: 120798, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38603851

RESUMO

Adopting energy-saving and noise-reducing technologies in vehicle transportation has the potential to mitigate urban traffic pollution and promote sustainable urban mobility. However, a universal analytical framework for obtaining the combined energy savings and noise reduction patterns in vehicles is still lacking. This study addresses this gap by integrating a fundamental traffic noise model with a vehicle energy conservation equation. A theoretical framework was constructed that establishes the relationship between vehicle noise and energy consumption, with the theoretical origins of this framework explained. By summarizing a substantial body of classical literature, the typical model's properties are analyzed through the principle of optimality, and the noise interval for combined vehicle energy-saving and noise-reducing is determined. Subsequently, a rigorous vehicle experiment was conducted to validate the proposed framework's effectiveness, utilizing synchronized data on energy consumption and noise. The findings indicate that vehicles can achieve unconstrained combined energy-saving and noise-reducing in four driving states and conditional combined energy-saving and noise-reducing in five driving states. The Recall index demonstrates a verification rate exceeding 0.62 for the combined energy-saving and noise-reducing rules. This research provides valuable insights to support energy-saving and noise-reducing measures in urban traffic.


Assuntos
Ruído dos Transportes , Meios de Transporte , Ruído dos Transportes/prevenção & controle , Ruído/prevenção & controle , Modelos Teóricos , Cidades , Veículos Automotores
15.
Anal Chem ; 96(17): 6774-6783, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38634427

RESUMO

The identification of a specific tumor cell is crucial for the early diagnosis and treatment of cancer. However, it remains a challenge due to the limited sensitivity and accuracy, long response time, and low contrast of the recent approaches. In this study, we develop a dual miRNA-triggered DNA walker (DMTDW) assisted by APE1 for the specific recognition of tumor cells. miR-10b and miR-155 were selected as the research models. Without miR-10b and miR-155 presence, the DNA walker remains inactive as its walking strand of W is locked by L1 and L2. After miR-10b and miR-155 are input, the DNA walker is triggered as miR-10b and miR-155 bind to L1 and L2 of W-L1-L2, respectively, unlocking W. The DNA walker is driven by endogenous APE1 that is highly catalytic and is highly expressed in the cytoplasm of tumor cells but barely expressed in normal cells, ensuring high contrast and reaction efficiency for specific recognition of tumor cells. Dual miRNA input is required to trigger the DNA walker, making this strategy with a high accuracy. The DMTDW strategy exhibited high sensitivity for miRNA analysis with a detection limit of 44.05 pM. Living cell-imaging experiments confirmed that the DMTDW could effectively respond to the fluctuation of miRNA and specifically identified MDA-MB-231 cells from different cell lines. The proposed DMTDW is sensitive, rapid, and accurate for specific tumor cell recognition. We believe that the DMTDW strategy can become a powerful diagnostic tool for the specific recognition of tumor cells.


Assuntos
DNA Liase (Sítios Apurínicos ou Apirimidínicos) , MicroRNAs , MicroRNAs/análise , MicroRNAs/metabolismo , MicroRNAs/genética , Humanos , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , DNA/química , Linhagem Celular Tumoral
16.
J Plant Physiol ; 296: 154218, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490054

RESUMO

Jasmonates (JAs) are among the main phytohormones, regulating plant growth and development, stress responses, and secondary metabolism. As the major regulator of the JA signaling pathway, MYC2 also plays an important role in plant secondary metabolite synthesis and accumulation. In this study, we performed a comparative transcriptome analysis of Lycoris aurea seedlings subjected to methyl jasmonate (MeJA) at different treatment times. A total of 31,193 differentially expressed genes (DEGs) were identified by RNA sequencing. Among them, 732 differentially expressed transcription factors (TFs) comprising 51 TF families were characterized. The most abundant TF family was WRKY proteins (80), followed by AP2/ERF-EFR (67), MYB (59), bHLH (52), and NAC protein (49) families. Subsequently, by calculating the Pearson's correlation coefficient (PCC) between the expression level of TF DEGs and the lycorine contents, 41 potential TF genes (|PCC| >0.8) involved in lycorine accumulation were identified, including 36 positive regulators and 5 negative regulators. Moreover, a MeJA-inducible MYC2 gene (namely LaMYC2) was cloned on the basis of transcriptome sequencing. Bioinformatic analyses revealed that LaMYC2 proteins contain the bHLH-MYC_N domain and bHLH-AtAIB_like motif. LaMYC2 protein is localized in the cell nucleus, and can partly rescue the MYC2 mutant in Arabidopsis thaliana. LaMYC2 protein could interact with most LaJAZs (especially LaJAZ3 and LaJAZ4) identified previously. Transient overexpression of LaMYC2 increased lycorine contents in L. aurea petals, which might be associated with the activation of the transcript levels of tyrosine decarboxylase (TYDC) and phenylalanine ammonia lyase (PAL) genes. By isolating the 887-bp-length promoter fragment upstream of the start codon (ATG) of LaTYDC, we found several different types of E-box motifs (CANNTG) in the promoter of LaTYDC. Further study demonstrated that LaMYC2 was indeed able to bind the E-box (CACATG) present in the LaTYDC promoter, verifying that the pathway genes involved in lycorine biosynthesis could be regulated by LaMYC2, and that LaMYC2 has positive roles in the regulation of lycorine biosynthesis. These findings demonstrate that LaMYC2 is a positive regulator of lycorine biosynthesis and may facilitate further functional research of the LaMYC2 gene, especially its potential regulatory roles in Amaryllidaceae alkaloid accumulation in L. aurea.


Assuntos
Acetatos , Alcaloides de Amaryllidaceae , Arabidopsis , Lycoris , Fenantridinas , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Alcaloides de Amaryllidaceae/metabolismo , Lycoris/genética , Lycoris/metabolismo , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo , Oxilipinas/farmacologia , Oxilipinas/metabolismo , Transcriptoma , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas
17.
Apoptosis ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498249

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy is highly effective for treating blood cancers such as B-cell malignancies, however, its effectiveness as an approach to treat solid tumors remains to be further explored. Here, we focused on the development of CAR-T cell therapies targeting tropomyosin-related kinase receptor B (TRKB), a highly expressed protein that is significantly associated with tumor progression, malignancy, and drug resistance in multiple forms of aggressive solid tumors. To achieve this, we screened brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NTF4) ligand-based CAR-T cells for their efficiency in targeting the TRKB receptor in the context of solid tumors, particularly hepatocellular carcinoma and pancreatic cancer. We demonstrated that TRKB is overexpressed not only in hepatocellular carcinoma and pancreatic carcinoma cell lines but also in cancer stem-like cells (CSCs). Notably, BDNF-CAR T and NTF4-CAR T cells could not only effectively target and kill TRKB-expressing pan-cancer cell lines in a dose-dependent manner but also effectively kill CSCs. We also performed in vivo studies to show that NTF4-CAR T cells have a better potential to inhibit the tumor growth of hepatocellular carcinoma xenografts in mice, compared with BDNF-CAR T cells. Taken together, our findings suggest that CAR-T targeting TRKB may be a promising approach for developing novel therapies to treat solid cancers.

18.
J Sleep Res ; : e14191, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499503

RESUMO

Maternal sleep is closely related to subsequent gestational diabetes mellitus (GDM) in natural pregnancies. However, whether this connection exists in pregnant women conceiving with the help of assisted reproductive technology (ART) has not been confirmed. Hence, in this study, we evaluated whether early pregnancy sleep duration or sleep quality is associated with gestational diabetes mellitus in ART-pregnant women, as well as the influence of maternal age on this association. This prospective birth cohort study included 856 pregnant women who successfully conceived with the help of ART treatment. The sleep parameters of ART-pregnant women were assessed using the Pittsburgh Sleep Quality Index (PSQI) in early pregnancy. We explored the association between sleep and the risk of gestational diabetes mellitus using an unconditional binary logistic regression model. Different models were constructed to examine the robustness of the estimation by incorporating different confounding factors. Multivariable logistic regression revealed that sleep duration of more than 10 h among ART-pregnant women was significantly associated with the risk of GDM, and the association between sleep duration and gestational diabetes mellitus varied by maternal age. We found an increased risk of subsequent gestational diabetes mellitus with increasing sleep duration only in pregnant women aged <35 years. Additionally, no statistically significant association between sleep quality and gestational diabetes mellitus was found in this study. In conclusion, excessive sleep duration (≥10 h) is associated with a high risk of gestational diabetes mellitus in pregnant women who conceived with the help of assisted reproductive technology, and maternal age may modify this effect.

19.
J Affect Disord ; 354: 232-238, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38461901

RESUMO

BACKGROUND: Sleep disturbance may exacerbate the risk of suicide among youth with depression, but whether this association is independent of psychopathology requires further study. METHODS: This cross-sectional study included 576 youths (13-25 years old) recruited from January 2022 to May 2023. The patients were first divided into two groups by the presence of suicidal ideation according to the Columbia-Suicide Severity Scale (C-SSRS). Sleep quality was assessed by the Athens Insomnia Scale (AIS) and mental health with the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA). Logistic regression was conducted to analyze the association between sleep disturbance and suicidal ideation, adjusted for depressive symptoms severity. RESULTS: The suicidal ideation group exhibited more severe sleep disturbances, anxiety symptoms, and depressive symptoms than the non-suicidal ideation group. Pearson correlation showed that sleep disturbance (AIS) was significantly correlated with the severity of anxiety symptoms, depressive symptoms, and suicidal ideation. Logistic regression analysis revealed that the AIS factor "daytime dysfunction" (ß = 0.145; OR = 1.156, 95 % CI: 1.02, 1.309; p = 0.023) was significantly associated with suicidal ideation after adjusting for demographic characteristics and depressive symptoms severity. LIMITATIONS: Due to the cross-sectional nature of the data, no causal inference can be made regarding the observed associations between sleep disturbance and suicidal ideation. CONCLUSION: Sleep disturbance, particularly in the realm of daytime dysfunction, is associated with increased suicidal ideation among depressed youth. Clinicians need to assess and manage sleep disturbance in the context of suicidal ideation for young depression patients.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Suicídio , Humanos , Adolescente , Adulto Jovem , Adulto , Ideação Suicida , Depressão/epidemiologia , Depressão/psicologia , Estudos Transversais , Suicídio/psicologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/psicologia , Sono
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 313: 124061, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38479226

RESUMO

Hydrogen peroxide(H2O2), as a reliable signaling biomolecule for oxidative stress, its accurate detection during agent-stimulated oxidative stress plays a vital role in pathological and physiological mechanism exploration for disease theranostics. It's necessary to develop an efficient method for their detection. In view of the advantages of fluorescent probes, we rationally constructed a novel fluorescent probe Compound 2 based on 4-(Bromomethyl)benzeneboronic acid pinacol ester_Herein, a small molecule fluorescent probe was fabricated using isoflore nitrile as fluorescent group, phenylboronic acid pinacol ester as the response group, to detect H2O2. The probe Compound 2 has a strong fluorescence intensity at 575 nm, indicating that the structure of the probe molecule is reasonably designed, and the Stokes shift is up to 172 nm. While the detection time is as low as 30 s and the LOD of the probe for H2O2 is as low as 3.7 µmol/L,the quantum yield is Φ = 40.31 %. It has been successfully used for imaging detection of H2O2 in HepG2 cells and zebrafish for its low toxicity. It can be found that this small molecule fluorescent probe can identify H2O2 in tumor cells significantly and efficiently, which would realize the early diagnosis of tumor.


Assuntos
Ácidos Borônicos , Corantes Fluorescentes , Glicóis , Peróxido de Hidrogênio , Humanos , Animais , Corantes Fluorescentes/toxicidade , Corantes Fluorescentes/química , Peixe-Zebra , Estresse Oxidativo , Células HeLa , Ésteres
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