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1.
Sci Total Environ ; : 173422, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38796019

RESUMO

Tamarix hispida is highly tolerant to salt, drought and heavy metal stress and is a potential material for the remediation of cadmium (Cd)-contaminated soil under harsh conditions. In this study, T. hispida growth and chlorophyll content decreased, whereas flavonoid and carotenoid contents increased under long-term Cd stress (25 d). The aboveground components of T. hispida were collected for RNA-seq to investigate the mechanism of Cd accumulation. GO and KEGG enrichment analyses revealed that the differentially expressed genes (DEGs) were significantly enriched in plant hormone-related pathways. Exogenous hormone treatment and determination of Cd2+ levels showed that ethylene (ETH) and abscisic acid (ABA) antagonists regulate Cd accumulation in T. hispida. Twenty-five transcription factors were identified as upstream regulators of hormone-related pathways. ThDRE1A, which was previously identified as an important regulatory factor, was selected for further analysis. The results indicated that ThABAH2.5 and ThACCO3.1 were direct target genes of ThDRE1A. The determination of Cd2+, ABA, and ETH levels indicated that ThDRE1A plays an important role in Cd accumulation through the antagonistic regulation of ABA and ethylene. In conclusion, these results reveal the molecular mechanism underlying Cd accumulation in plants and identify candidate genes for further research.

2.
J Insect Physiol ; 155: 104651, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38763360

RESUMO

Hemolin, a member of the immunoglobulin superfamily, plays a crucial role in the immune responses of insects against pathogens. However, the innate immune response of Hemolin to baculovirus infection varies among different insects, and the antiviral effects of Hemolin in Hyphantria cunea (HcHemolin) remain poorly understood. Our results showed that HcHemolin was expressed throughout all developmental stages, with higher expressions observed during pupal and adult stages of H. cunea. Additionally, HcHemolin was expressed in reproductive and digestive organs. The expression levels of the HcHemolin were induced significantly following H. cunea nucleopolyhedrovirus (HcNPV) infection. The susceptibility of H. cunea larvae to HcNPV decreased upon silencing of HcHemolin, resulting in a 40% reduction in median lifespan compared to the control group. The relative growth rate (RGR), the relative efficiency of consumption rate (RCR), the efficiency of the conversion of ingested food (ECI), and efficiency of the conversion of digested food (ECD) of silenced H. cunea larvae were significantly lower than those of the control group. Immune challenge assays showed that the median lifespan of treated H. cunea larvae was two-fold longer than the control group after HcNPV and HcHemolin protein co-injection. Therefore, we propose that HcHemolin plays a crucial role in regulating the growth, development, and food utilization of H. cunea, as well as in the antiviral immune response against HcNPV. These findings provide implications for the development of targeted nucleic acid pesticides and novel strategies for pollution-free biological control synergists for HcNPV.

3.
Microorganisms ; 12(5)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38792750

RESUMO

Bacillus velezensis is well known as a plant growth-promoting rhizobacteria (PGPR) and biocontrol agent. Nevertheless, there are very few reports on the study of B. velezensis on tomato early blight, especially the biocontrol effects among different inoculation concentrations. In this study, an IAA-producing strain, Bacillus velezensis YXDHD1-7 was isolated from the tomato rhizosphere soil, which had the strongest inhibitory effect against Alternaria solani. Inoculation with bacterial suspensions of this strain promoted the growth of tomato seedlings effectively. Furthermore, inoculations at 106, 107, and 108 cfu/mL resulted in control efficacies of 100%, 83.15%, and 69.90%, respectively. Genome sequencing showed that it possesses 22 gene clusters associated with the synthesis of antimicrobial metabolites and genes that are involved in the production of IAA. Furthermore, it may be able to produce spermidine and volatile compounds that also enhance plant growth and defense responses. Our results suggest that strain YXDHD1-7 prevents early blight disease by promoting growth and enhancing the defense enzyme activities in tomato plants. This strain is a promising candidate for an excellent microbial inoculant that can be used to enhance tomato production.

4.
Molecules ; 29(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731459

RESUMO

Terpenoid alkaloids are recognized as a class of compounds with limited numbers but potent biological activities, primarily derived from plants, with a minor proportion originating from animals and microorganisms. These alkaloids are synthesized from the same prenyl unit that forms the terpene skeleton, with the nitrogen atom introduced through ß-aminoethanol, ethylamine, or methylamine, leading to a range of complex and diverse structures. Based on their skeleton type, they can be categorized into monoterpenes, sesquiterpenes, diterpenes, and triterpene alkaloids. To date, 289 natural terpenoid alkaloids, excluding triterpene alkaloids, have been identified in studies published between 2019 and 2024. These compounds demonstrate a spectrum of biological activities, including anti-inflammatory, antitumor, antibacterial, analgesic, and cardioprotective effects, making them promising candidates for further development. This review provides an overview of the sources, chemical structures, and biological activities of natural terpenoid alkaloids, serving as a reference for future research and applications in this area.


Assuntos
Alcaloides , Terpenos , Alcaloides/química , Alcaloides/farmacologia , Terpenos/química , Terpenos/farmacologia , Humanos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Estrutura Molecular
5.
Materials (Basel) ; 17(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38793475

RESUMO

The hot deformation behavior and mechanism of Ti65 alloy with a bimodal microstructure were investigated by isothermal compression experiments conducted on the Thermecmastor-Z simulator equipment at temperatures ranging from 950 to 1110 °C and strain rates ranging from 0.01 to 10.0 s-1. The Arrhenius constitutive model, based on strain compensation, and Grey Wolf optimization-neural network with back propagation model (GWO-BP), were both established. The differences between the experimental and predicted value of flow stress were compared and analyzed using the two models. The results show that the prediction accuracy of GWO-BP in the two-phase region is higher than that of Arrhenius model. In the single-phase region, both methods demonstrated high prediction accuracy. Compared to the single-phase region, the flow stress of Ti65 alloy shows a higher degree of softening in the two-phase region. During deformation in the two-phase region, the initial lamellar α phase transformed from a kinked and elongated morphology to a globularized topography as the strain rate decreased. Boundary-splitting was the primary mechanism leading to the spheroidization process. The degree of recrystallization increased with the increase in strain rate during the deformation in the single-phase region, while dynamic recovery and strain-induced grain boundary migration were the main deformation mechanisms at a lower strain rate. Discontinuous dynamic recrystallization may be the dominant recrystallization mechanism under a high strain rate of 10 s-1.

6.
Drug Metab Dispos ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38772712

RESUMO

This study investigated an association between the cytochrome P450 (CYP) 2C8*3 polymorphism with asthma symptom control in children and changes in lipid metabolism and pro-inflammatory signaling by human bronchial epithelial cells (HBECs) treated with cigarette smoke condensate (CSC). CYP genes are inherently variable in sequence and while such variations are known to produce clinically relevant effects on drug pharmacokinetics and pharmacodynamics, the effects on endogenous substrate metabolism and associated physiological processes are less understood. In this study, CYP2C8*3 was associated with improved asthma symptom control among children: Mean asthma control scores were 3.68 [n=207] for patients with one or more copies of the CYP2C8*3 allele vs. 4.42 [n=965] for CYP2C8*1/*1 (p=0.0133). In vitro, CYP2C8*3 was associated with an increase in montelukast 36-hydroxylation and a decrease in linoleic acid (LA) metabolism despite lower mRNA and protein expression. Additionally, CYP2C8*3 was associated with reduced mRNA expression of interleukin-6 (IL-6) and C-X-C motif chemokine ligand 8 (CXCL-8) by HBECs in response to CSC, which was replicated using the soluble epoxide hydrolase inhibitor, AUDA. Interestingly, 9(10)- and 12(13)-DiHOME, the hydrolyzed metabolites of 9(10)- and 12(13)-EpOME, increased the expression of IL-6 and CXCL-8 mRNA by HBECs. This study reveals previously undocumented effects of the CYP2C8*3 variant on the response of HBECs to exogenous stimuli. Significance Statement These findings suggest a role for CYP2C8 in regulating the EpOME:DiHOME ratio leading to a change in cellular inflammatory responses elicited by environmental stimuli that exacerbate asthma.

7.
Phys Rev Lett ; 132(16): 165002, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38701476

RESUMO

We report the experimental measurement of millijoule terahertz (THz) radiation emitted in the backward direction from laser wakefields driven by a femtosecond laser pulse of few joules interacting with a gas target. By utilizing frequency-resolved energy measurement, it is found that the THz spectrum exhibits two peaks located at about 4.5 and 9.0 THz, respectively. In particular, the high frequency component emerges when the drive laser energy exceeds 1.26 J, at which electron acceleration in the forward direction is detected simultaneously. Theoretical analysis and particle-in-cell simulations indicate that the THz radiation is generated via mode conversion from the laser wakefields excited in plasma with an up-ramp profile, where radiations both at the local electron plasma frequency and its harmonics are produced. Such intense THz sources may find many applications in ultrafast science, e.g., manipulating the transient states of matter.

8.
Molecules ; 29(7)2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38611928

RESUMO

Diterpenes represent one of the most diverse and structurally complex families of natural products. Among the myriad of diterpenoids, grayanane diterpenes are particularly notable. These terpenes are characterized by their unique 5/7/6/5 tetracyclic system and are exclusive to the Ericaceae family of plants. Renowned for their complex structures and broad spectrum of bioactivities, grayanane diterpenes have become a primary focus in extensive phytochemical and pharmacological research. Recent studies, spanning from 2018 to January 2024, have reported a series of new grayanane diterpenes with unprecedented carbon skeletons. These compounds exhibit various biological properties, including analgesic, antifeedant, anti-inflammatory, and inhibition of protein tyrosine phosphatase 1B (PTP1B). This paper delves into the discovery of 193 newly identified grayanoids, representing 15 distinct carbon skeletons within the Ericaceae family. The study of grayanane diterpenes is not only a deep dive into the complexities of natural product chemistry but also an investigation into potential therapeutic applications. Their unique structures and diverse biological actions make them promising candidates for drug discovery and medicinal applications. The review encompasses their occurrence, distribution, structural features, and biological activities, providing invaluable insights for future pharmacological explorations and research.


Assuntos
Produtos Biológicos , Diterpenos , Ericaceae , Diterpenos/farmacologia , Terpenos , Produtos Biológicos/farmacologia , Carbono
9.
J Clin Nurs ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572996

RESUMO

BACKGROUND: Older hospitalised patients have low levels of physical activity and multiple impairing factors. AIMS: To systematically evaluate the perceived barriers to physical activity among older patients during hospitalisation, and provide reference for future intervention programs. DESIGN: Following ENTREQ, do a systematic evaluation and synthesis of qualitative investigations. METHODS: An exhaustive exploration was conducted across the CNKI, Wanfang Database, VIP Database, China Biomedical Literature Database, PubMed, Embase, Cochrane Library and Web of Science from their inception until August, 2023 to identify qualitative research on obstacles to physical activity among older hospital patients. The quality of the literature was evaluated using the Joanna Briggs Institute's critical appraisal tool for qualitative research. Meta-synthesis method was used to integrate the results. RESULTS: In total, 8 literatures were included, 43 themes were extracted, and analogous research results were amalgamated to generate 10 categories and 3 syntheses: individual level, interpersonal influencing factors and hospital environment and resources level. CONCLUSION: Older inpatients are faced with multiple barriers to physical activity. Medical staff should pay attention to changes in physical activity during hospitalisation, identify barriers to physical activity in older inpatients and provide references for promoting physical activity programs for the older. NO PATIENT OR PUBLIC CONTRIBUTION: This study is a meta-synthesis and does not require relevant contributions from patients or the public. WHAT IS ALREADY KNOWN: Older patients are at low physical activity levels during hospitalisation. Older inpatients are faced with multiple barriers to physical activity. WHAT THIS PAPER ADDS: Factors of physical activity impairment in hospitalised older patients should be considered in the context of health status, psychological factors, motivation and social support. Disease-induced psychological fallout has a greater impact on physical activity in the older.

10.
BMC Pediatr ; 24(1): 291, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689221

RESUMO

BACKGROUND: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the Bruton tyrosine kinase (BTK) gene. Individuals diagnosed with XLA are at an increased risk of developing autoimmune diseases. However, renal involvement are rare in cases of XLA. CASE PRESENTATION: In this report, we discussed a specific case involving a 6-year-old boy with XLA who experienced recurrent upper respiratory tract infections since the age of one. He presented with symptoms of hematuria and proteinuria, and renal pathology confirmed the presence of immunoglobulin (Ig) A nephropathy. Treatment comprised glucocorticoids, mycophenolate mofetil, and intermittent intravenous immunoglobulin replacement therapy. Consequently, there was a remission of proteinuria and a partial improvement in hematuria. CONCLUSIONS: In this study, we describe the first case of IgA nephropathy associated with XLA. This is an interesting phenotype found in XLA, and it provides valuable insights into the process of autoimmunity and the regulation of immune function in individuals with XLA. Based on our findings, we recommend the evaluation of immunoglobulin levels in patients diagnosed with IgA nephropathy.


Assuntos
Agamaglobulinemia , Doenças Genéticas Ligadas ao Cromossomo X , Glomerulonefrite por IGA , Humanos , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/genética , Masculino , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Criança , Imunoglobulinas Intravenosas/uso terapêutico , Glucocorticoides/uso terapêutico , Ácido Micofenólico/uso terapêutico , Imunossupressores/uso terapêutico
11.
Pharmaceuticals (Basel) ; 17(4)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38675431

RESUMO

Sepsis-induced acute lung injury (ALI), characterized by widespread lung dysfunction, is associated with significant morbidity and mortality due to the lack of effective pharmacological treatments available clinically. Small-molecule compounds derived from natural products represent an innovative source and have demonstrated therapeutic potential against sepsis-induced ALI. These natural small molecules may provide a promising alternative treatment option for sepsis-induced ALI. This review aims to summarize the pathogenesis of sepsis and potential therapeutic targets. It assembles critical updates (from 2014 to 2024) on natural small molecules with therapeutic potential against sepsis-induced ALI, detailing their sources, structures, effects, and mechanisms of action.

12.
Am J Transl Res ; 16(2): 415-431, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463586

RESUMO

Primary hepatocellular carcinoma (HCC) affects people all over the world. Circular RNAs are involved in the growth and development of several malignancies and regulate a number of biological processes. However, the roles of has-circ-0009158 in HCC remain unknown. This study explored the expression and associated miRNA-mRNA network of has-circ-0009158 in HCC. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-circ-0009158 in the HCC tissues of 143 patients and four human HCC cell lines. Then, the potential relationship of hsa-circ-0009158 expression with clinical characteristics and prognosis of patients was analyzed using the GO and KEGG databases. Correlated miRNA-mRNA networks were forecasted using the TCGA database and Cytoscape software. The hsa-circ-0009158 expression was significantly upregulated in HCC tissues and cell lines (P<0.001). The multivariate Cox analysis revealed that HCC patients were associated with high hsa-circ-0009158 expression. The bioinformatics analysis screened 1 miRNA, and 248 mRNAs associated with the circRNA in HCC. A pathway analysis suggested that the differentially expressed genes (DEGs) may be linked to the development and growth of HCC tumors. Ten hub genes (MELK, NCAPG, BUB1B, BIRC5, CDCA8, CENPF, BUB1, CDK1, TTK, TPX2) were identified from the PPI network based on the 248 genes. Additionally, the 10 hub genes that were verified had an association between high expression levels and low overall survival rates. As a result, the high expression of hsa-circ-0009158 was found to be a separate risk factor for recurrence and a poor prognosis in HCC patients.

13.
Neurology ; 102(7): e209217, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38489544

RESUMO

BACKGROUND AND OBJECTIVES: Acute stent thrombosis (AST) is not uncommon and even catastrophic during intracranial stenting angioplasty in patients with symptomatic high-grade intracranial atherosclerotic stenosis (ICAS). The purpose of this study was to investigate whether adjuvant intravenous tirofiban before stenting could reduce the risk of AST and periprocedural ischemic stroke in patients receiving stent angioplasty for symptomatic ICAS. METHODS: A prospective, multicenter, open-label, randomized clinical trial was conducted from September 9, 2020, to February 18, 2022, at 10 medical centers in China. Patients intended to receive stent angioplasty for symptomatic high-grade ICAS were enrolled and randomly assigned to receive intravenous tirofiban or not before stenting in a 1:1 ratio. The primary outcomes included the incidence of AST within 30 minutes after stenting, periprocedural new-onset ischemic stroke, and symptomatic intracranial hemorrhage. The outcomes were analyzed using logistic regression analysis to obtain an odds ratio and 95% confidence interval. RESULTS: A total of 200 participants (122 men [61.0%]; median [interquartile ranges] age, 57 [52-66] years) were included in the analysis, with 100 participants randomly assigned to the tirofiban group and 100 participants to the control (no tirofiban) group. The AST incidence was lower in the tirofiban group than that in the control group (4.0% vs 14.0%; adjusted odds ratio, 0.25; 95% CI 0.08-0.82; p = 0.02). No significant difference was observed in the incidence of periprocedural ischemic stroke (7.0% vs 8.0%; p = 0.98) or symptomatic intracranial hemorrhage between the 2 groups. DISCUSSION: This study suggests that adjuvant intravenous tirofiban before stenting could lower the risk of AST during stent angioplasty in patients with symptomatic high-grade ICAS. TRIAL REGISTRATION INFORMATION: URL: chictr.org.cn; Unique identifier: ChiCTR2000031935. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with symptomatic high-grade ICAS, pretreatment with tirofiban decreases the incidence of acute stent thrombosis. This study is Class II due to the unequal distribution of involved arteries between the 2 groups.


Assuntos
Arteriosclerose Intracraniana , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Masculino , Humanos , Pessoa de Meia-Idade , Tirofibana/uso terapêutico , Acidente Vascular Cerebral/etiologia , Estudos Prospectivos , Constrição Patológica/complicações , Stents/efeitos adversos , AVC Isquêmico/complicações , Hemorragias Intracranianas/complicações , Trombose/complicações , Arteriosclerose Intracraniana/tratamento farmacológico , Arteriosclerose Intracraniana/cirurgia , Resultado do Tratamento
14.
Methods Appl Fluoresc ; 12(3)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38537297

RESUMO

The alignment of chromophores plays a crucial role in determining the optoelectronic properties of materials. Such alignment can make interpretation of fluorescence anisotropy microscopy (FAM) images somewhat ambiguous. The time-resolved emission behaviour can also influence the fluorescence anisotropy. This is particularly the case when probing excitation energy migration between chromophores in a condensed phase. Ideally information concerning the chromophoric alignment, emission decay kinetics and fluorescence anisotropy can be recorded and correlated. We report on the use of polarised transmission imaging (PTI) coupled with both steady-state and time-resolved FAM to enable accurate identification of chromophoric alignment and morphology in thin films of a conjugated polydiarylfluorene. We show that the combination of these three imaging modes presents a comprehensive methodology for investigating the alignment and morphology of chromophores in thin films, particularly for accurately mapping the distribution of amorphous and crystalline phases within the thin films, offering valuable insights for the design and optimization of materials with enhanced optoelectronic performance.

15.
J Mater Chem B ; 12(12): 3129-3143, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38451208

RESUMO

Nasopharyngeal carcinoma (NPC) is one of the most common tumors in South China and Southeast Asia and is thought to be associated with Epstein-Barr virus (EBV) infection. Downregulation of latent membrane protein 1 (LMP1) encoded by EBV can reduce the expression of NF-κB and PI3K, induce apoptosis, and inhibit the growth of EBV-related NPC. For targeted cleavage of the Lmp1 oncogene via the CRISPR/Cas9 gene editing system, a post cross-linked ROS-responsive poly(ß-amino ester) (PBAE) polymeric vector was developed for the delivery of CRISPR/Cas9 plasmids both in vitro and in vivo. After composition optimization, the resultant polymer-plasmid polyplex nanoparticles (NPs) showed a diameter of ∼230 nm and a zeta potential of 22.3 mV with good stability. Compared with the non-cross-linked system, the cross-linked NPs exhibited efficient and quick cell uptake, higher transfection efficiency in EBV-positive C666-1 cells (53.5% vs. 40.6%), more efficient gene editing ability against the Mucin2 model gene (Muc2) (17.9% vs. 15.4%) and Lmp1 (8.5% vs. 5.6%), and lower intracellular reactive oxygen species (ROS) levels. The NPs achieved good tumor penetration and tumor growth inhibition in the C666-1 xenograft tumor model via Lmp1 cleavage, indicating their potential for gene therapy of EBV-related NPC.


Assuntos
Carcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Polímeros , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/terapia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/terapia , Infecções por Vírus Epstein-Barr/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/terapia , Terapia Genética
16.
Iran J Immunol ; 21(1): 81-88, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347674

RESUMO

Background: Human adenovirus (HAdV) is an enveloped icosahedral DNA virus. HAdV infection can lead to immune system damage, resulting in decreased numbers and compromised function of T cells and B cells. It can also cause an imbalanced Th1/Th2 ratio and dysregulation of pro-inflammatory and anti-inflammatory cytokines. Objective: To investigate the serum levels of interleukin (IL)-13 and IL-17A in children with HAdV pneumonia. Methods: Pediatric patients diagnosed with HAdV pneumonia were divided into a non-severe group or a severe group based on the severity of their condition. Patients in the severe group were further classified into good and poor prognosis subgroups. We collected 2-2.5 mL of venous blood from each patient, which was then centrifuged. Using an ELISA detection kit, we determined the concentrations of IL-13 and IL-17A. Results: Patients with a severe condition exhibited significantly higher serum concentrations of IL-13 and IL-17A than the non-severe cases. Out of 50 severe cases, 32 had good prognoses, while 18 cases showed poor prognoses. Patients with poor prognoses showed significantly higher serum concentrations of IL-13 compared to those with good prognoses. Conclusion: Serum concentrations of IL-13 and IL-17A are potential diagnostic markers for pediatric patients with severe HAdV pneumonia. Additionally, they demonstrate good predictive value for a poor prognosis in severe pneumonia cases.


Assuntos
Interleucina-13 , Pneumonia , Humanos , Criança , Interleucina-17 , Pneumonia/diagnóstico , Citocinas , Adenoviridae
17.
Cancer Cell Int ; 24(1): 79, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374035

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) cells usually show strong resistance to chemotherapy, which not only reduces the efficacy of chemotherapy but also increases the side effects. Regulation of autophagy plays an important role in tumor treatment. Cell senescence is also an important anti-cancer mechanism, which has become an important target for tumor treatment. Therefore, it is of great clinical significance to find anti-HCC drugs that act through this new mechanism. Platycodin D2 (PD2) is a new saponin compound extracted from the traditional Chinese medicine Platycodon grandiflorum. PURPOSE: Our study aimed to explore the effects of PD2 on HCC and identify the underlying mechanisms. METHODS: First, the CCK8 assay was used to detect the inhibitory effect of PD2 on HCC cells. Then, different pathways of programmed cell death and cell cycle regulators were measured. In addition, we assessed the effects of PD2 on the autophagy and senescence of HCC cells by flow cytometry, immunofluorescence staining, and Western blotting. Finally, we studied the in vivo effect of PD2 on HCC cells by using a mouse tumor-bearing model. RESULTS: Studies have shown that PD2 has a good anti-tumor effect, but the specific molecular mechanism has not been clarified. In this study, we found that PD2 has no obvious toxic effect on normal hepatocytes, but it can significantly inhibit the proliferation of HCC cells, induce mitochondrial dysfunction, enhance autophagy and cell senescence, upregulate NIX and P21, and downregulate CyclinA2. Gene silencing and overexpression indicated that PD2 induced mitophagy in HCC cells through NIX, thereby activating the P21/CyclinA2 pathway and promoting cell senescence. CONCLUSIONS: These results indicate that PD2 induces HCC cell death through autophagy and aging. Our findings provide a new strategy for treating HCC.

18.
Bioact Mater ; 35: 208-227, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38327823

RESUMO

Repair of large bone defects caused by severe trauma, non-union fractures, or tumor resection remains challenging because of limited regenerative ability. Typically, these defects heal through mixed routines, including intramembranous ossification (IMO) and endochondral ossification (ECO), with ECO considered more efficient. Current strategies to promote large bone healing via ECO are unstable and require high-dose growth factors or complex cell therapy that cause side effects and raise expense while providing only limited benefit. Herein, we report a bio-integrated scaffold capable of initiating an early hypoxia microenvironment with controllable release of low-dose recombinant bone morphogenetic protein-2 (rhBMP-2), aiming to induce ECO-dominated repair. Specifically, we apply a mesoporous structure to accelerate iron chelation, this promoting early chondrogenesis via deferoxamine (DFO)-induced hypoxia-inducible factor-1α (HIF-1α). Through the delicate segmentation of click-crosslinked PEGylated Poly (glycerol sebacate) (PEGS) layers, we achieve programmed release of low-dose rhBMP-2, which can facilitate cartilage-to-bone transformation while reducing side effect risks. We demonstrate this system can strengthen the ECO healing and convert mixed or mixed or IMO-guided routes to ECO-dominated approach in large-size models with clinical relevance. Collectively, these findings demonstrate a biomaterial-based strategy for driving ECO-dominated healing, paving a promising pave towards its clinical use in addressing large bone defects.

19.
Adv Mater ; 36(19): e2307605, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38349697

RESUMO

Emerging printed large-area polymer light-emitting diodes (PLEDs) are essential for manufacturing flat-panel displays and solid lighting devices. However, it is challenging to obtain large-area and stable ultradeep-blue PLEDs because of the lack of light-emitting conjugated polymers (LCPs) with robust deep-blue emissions, excellent morphological stabilities, and high charging abilities. Here, a novel unsymmetrically substituted polydiarylfluorene (POPSAF) is obtained with stable narrowband emission for large-area printed displays via triphenylamine (TPA) spirofunctionalization of LCPs. POPSAF films show narrowband and stable ultradeep-blue emission with a full width at half maximum (FWHM) of 36 nm, associated with their intrachain excitonic behavior without obvious polaron formation. Compared to controlled poly[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]-co-[5-(octyloxy)-9,9-diphenylfluoren-2,7-diyl] (PODPF), excellent charge transport is observed in the POPSAF films because of the intrinsic hole transport ability of the TPA units. Large-area PLEDs are fabricated via blade-coating with an emission area of 9 cm2, which exhibit uniform ultradeep-blue emission with an FWHM of 36 nm and corresponding Commission internationale de l'éclairage (CIE) coordinates of (0.155, 0.072). These findings are attributed to the synergistic effects of robust emission, stable morphology, and printing capacity. Finally, preliminary printed passive matrix (PM) PLED displays with 20 × 20 pixels monochromes are fabricated, confirmed the effectiveness of spirofunctionalization in optoelectronics.

20.
Phys Chem Chem Phys ; 26(4): 2951-2962, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38214187

RESUMO

Catechol, which has a high toxicity and low degradability, poses significant risks to both human health and the environment. Tracking of catechol residues is essential to protect human health and to assess the safety of the environment. We constructed sensing platforms to detect catechol based on the conductive metal-organic frameworks [Ni3(HITP)2] and their nanosilver composites. The reduction process of catechol at the Ni3(HITP)2/AgNP electrode is chemically irreversible as a result of the difference in compatibility of the oxidation stability and conductivity between the Ni3(HITP)2/AgNS and Ni3(HITP)2/AgNP electrodes. The electrochemical results show that the Ni3(HITP)2/AgNS electrode presents a lower detection limit of 0.053 µM and better sensitivity, reproducibility and repeatability than the Ni3(HITP)2/AgNP electrode. The kinetic mechanism of the catechol electrooxidation at the surface of the electrode is controlled by diffusion through a 2H+/2e- process. The transfer coefficient is the key factor used to illustrate this process. During the electrochemical conversion of phenol to ketone, more than half of ΔG is used to change the activation energy. We also studied the stability, anti-interference and reproducibility of these electrode systems.

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