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Histone modifications (HMs) play various roles in growth, development, and resistance to abiotic stress. However, HMs have been systematically identified in a few plants, and identification of HMs in medicinal plants is very rare. Aquilaria sinensis is a typical stress-induced medicinal plant, in which HMs remain unexplored. We conducted a comprehensive study to identify HMs and obtained 123 HMs. To conduct evolutionary analysis, we constructed phylogenetic trees and analyzed gene structures. To conduct functional analysis, we performed promoter, GO, and KEGG analyses and ortholog analyses against AtHMs. Based on the expression profiles of different tissues and different layers of Agar-Wit, some HMs of A. sinensis (AsHMs) were predicted to be involved in the formation of agarwood, and their response to MeJA and NaCl stress was tested by qRT-PCR analysis. By analyzing the enrichment of H3K4me3, H3K27me3, and H4K5ac in the promoter regions of two key sesquiterpene synthase genes, AsTPS13/18, we hypothesized that AsHMs play important roles in the synthesis of agarwood sesquiterpenes. We confirmed this hypothesis by conducting RNAi transgenic interference experiments. This study provided valuable information and important biological theories for studying epigenetic regulation in the formation of agarwood. It also provided a framework for conducting further studies on the biological functions of HMs.
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This study aimed to investigate the effects and possible mechanisms of adenylate cyclase 1 (ADCY1) on pirarubicin-induced cardiomyocyte injury. HL-1 cells were treated with pirarubicin (THP) to induce intracellular toxicity, and the extent of damage to mouse cardiomyocytes was assessed using CCK-8, Edu, flow cytometry, ROS, ELISA, RT-qPCR and western blotting. THP treatment reduced the viability of HL-1 cells, inhibited proliferation, induced apoptosis and triggered oxidative stress. In addition, the RT-qPCR results revealed that ADCY1 expression was significantly elevated in HL-1 cells, and molecular docking showed a direct interaction between ADCY1 and THP. Western blotting showed that ADCY1, phospho-protein kinase A and GRIN2D expression were also significantly elevated. Knockdown of ADCY1 attenuated THP-induced cardiotoxicity, possibly by regulating the ADCY1/PKA/GRIN2D pathway.
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Adenilil Ciclases , Cardiotoxicidade , Doxorrubicina , Técnicas de Silenciamento de Genes , Miócitos Cardíacos , Adenilil Ciclases/metabolismo , Adenilil Ciclases/genética , Animais , Camundongos , Cardiotoxicidade/genética , Doxorrubicina/toxicidade , Doxorrubicina/farmacologia , Doxorrubicina/análogos & derivados , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Linhagem Celular , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Simulação de Acoplamento Molecular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/toxicidadeRESUMO
Risk evaluation is ubiquitous in decisions. Deep brain stimulation of the subthalamic nucleus is effective for Parkinson's disease and obsessive-compulsive disorder, and can be associated with impulsivity and hypomania. Subthalamic stimulation has seemingly contrasting effects on impulsivity enhancing conflict-induced impulsivity but decreasing risk taking. Here, using a card gambling task paired with intracranial recordings (n = 25) and within-subject case control acute stimulation (n = 15) of the right subthalamic nucleus, we dissociated objective risk and uncertainty and subjective physiological markers of risk. Acute stimulation decreased risk taking (P = 0.010, Cohen's d = 0.72) and increased subthalamic theta activity (P < 0.001, Cohen's d = 0.72). Critically, stimulation negatively shifted the relationship between subthalamic physiology and a measure of evidence accumulation similar to observations with stimulation-induced conflict processing. This highlights the phenotypic and physiological heterogeneity of impulsivity, yet linking mechanisms underlying stimulation-induced conflict and risk. Finally, stimulation-induced risk seeking implicates the ventral subthalamic nucleus and dissociating anatomical and functional connectivity with the mesial prefrontal cortex. Our findings have implications for conceptualizations of impulsivity, and clinical relevance for neuropsychiatric disorders.
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PURPOSE: In clinical practice, the success of preimplantation genetic testing for monogenic diseases (PGT-M) for thalassemia was hindered by the absence of probands, incomplete family members, or failure in detecting embryonic gene mutation sites. This study aimed to address these issues. METHODS: This retrospective study included 342 couples undergoing PGT-M for α- or ß-thalassemia at three reproductive medicine centers from 2019 to 2022. Various methods were used to construct parental haplotypes. A total of 1778 embryos were analyzed and selected for transfer based on chromosomal ploidy and PGT-M results. Follow-up involved amniocentesis results and clinical outcomes. RESULTS: Haplotypes were established using DNA samples from probands or parents, as well as sibling blood samples, single sperm, and affected embryos, achieving an overall success rate was 99.4% (340/342). For α-thalassemia and ß-thalassemia, the concordance between embryo single nucleotide polymorphism (SNP) haplotype analysis results and mutation loci detection results was 93.8% (1011/1078) and 98.2% (538/548), respectively. Multiple annealing and looping-based amplification cycles (MALBAC) showed a higher whole genome amplification success rate than multiple displacement amplification (MDA) (98.8% (1031/1044) vs. 96.2% (703/731), p < 0.001). Amniocentesis confirmed PGT-M outcomes in 100% of cases followed up (99/99). CONCLUSION: This study summarizes feasible solutions to various challenging scenarios encountered in PGT-M for thalassemia, providing valuable insights to enhance success rate of PGT-M in clinical practice.
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Houttuynia cordata Thunb., commonly known as yuxingcao in China, is known for its characteristic fishy smell and is widely recognized as an important herb and vegetable in many parts of Asia. However, the lack of genomic information on H. cordata limits the understanding of its population structure, genetic diversity, and biosynthesis of medicinal compounds. Here we used single-molecule sequencing, Illumina paired-end sequencing, and chromosome conformation capture technology to construct the first chromosome-scale decaploid H. cordata reference genome. The genome assembly was 2.63 Gb in size, with 1348 contigs and a contig N50 of 21.94 Mb further clustered and ordered into 88 pseudochromosomes based on Hi-C analysis. The results of genome evolution analysis showed that H. cordata underwent a whole-genome duplication (WGD) event ~17 million years ago, and an additional WGD event occurred 3.3 million years ago, which may be the main factor leading to the high abundance of multiple copies of orthologous genes. Here, transcriptome sequencing across five different tissues revealed significant expansion and distinct expression patterns of key gene families, such as l-amino acid/l-tryptophan decarboxylase and strictosidine synthase, which are essential for the biosynthesis of isoquinoline and indole alkaloids, along with the identification of genes such as TTM3, which is critical for root development. This study constructed the first decaploid medicinal plant genome and revealed the genome evolution and polyploidization events of H. cordata .
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Perovskite quantum dots (PQDs) photoresists are promising building blocks for photolithographically patterned devices. However, their complex synthesis and combination processes limit their optical properties and potential patterning applications. Here, we present an exceptionally simple strategy for the synthesis of PQDs photoresist. Unlike traditional approaches that involve centrifugation, separation, and combination processes, our direct synthesis technique using polymerizable acrylic monomer as solvent to fabricate PQDs photoresists without complex post-synthesis process. We demonstrate that the change in solubility of the precursors is the main reason for the formation of PQDs in the polymerizable monomer. By direct photolithography, colorful PQD patterns with high photoluminescence quantum yields and excellent fluorescence uniformity are successfully demonstrated. This work opens a new avenue for the direct synthesis of PQDs photoresist, expanding their applications in various integrated applications, such as photonic, energy harvesting, and optoelectronic devices.
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In solid backfill coal mining, recycled coal gangue aggregate (RCGA) is subject to the combined effects of overlying strata stress and leaching by mine water in the goaf. This process causes heavy metals to be leached and released from RCGA, which can lead to groundwater contamination. In this study, the release patterns of heavy metals in RCGA under the coupled effects of stress, solution pH, and solution flow rate were investigated, and the interactions between RCGA and the surrounding environment were explored. The findings indicate that: (1) The combined action of effective stress and mine water promotes the leaching of heavy metals. Specifically, the leaching of Pb, Zn, and Mn of RCGA is primarily influenced by the pH value of the leaching solution, while the leaching of Cu and Cr of RCGA is more closely related to the stress level; (2) Acidic environments accelerate the release of carbonate-bound fraction (CAR) in elements, facilitating the transformation of Fe/Mn oxide-bound fraction (XXI) into soluble forms; (3) The leaching ratios (Lr) of heavy metals follow the order: LrZn> LrPb> LrMn> LrCu> LrCr. This research provides guidance for the safe application of RCGA in solid backfill coal mining.
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The Krebs cycle byproduct itaconate has recently emerged as an important metabolite regulating macrophage immune functions, but its role in tumor cells remains unknown. Here, we show that increased tumor-intrinsic cis-aconitate decarboxylase (ACOD1 or CAD, encoded by immune-responsive gene 1, Irg1) expression and itaconate production promote tumor immunogenicity and anti-tumor immune responses. Furthermore, we identify thimerosal, a vaccine preservative, as a specific inducer of IRG1 expression in tumor cells but not in macrophages, thereby enhancing tumor immunogenicity. Mechanistically, thimerosal induces itaconate production through a ROS-RIPK3-IRF1 signaling axis in tumor cells. Further, increased IRG1/itaconate upregulates antigen presentation-related gene expression via promoting TFEB nuclear translocation. Intratumoral injection of thimerosal induced itaconate production, activated the tumor immune microenvironment, and inhibited tumor growth in a T cell-dependent manner. Importantly, IRG1 deficiency markedly impaired tumor response to thimerosal treatment. Furthermore, itaconate induction by thimerosal potentiates the anti-tumor efficacy of adoptive T-cell therapy and anti-PD1 therapy in a mouse lymphoma model. Hence, our findings identify a new role for tumor intrinsic IRG1/itaconate in promoting tumor immunogenicity and provide a translational means to increase immunotherapy efficacy.
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ATAD2 (ATPase Family AAA Domain-Containing 2) is highly expressed across varies tumor types, yet its common roles in tumor progression and immune interaction remain unclear. We analyzed the expression and alteration profiles of ATAD2, along with its diagnostic and prognostic role in pan-cancer, utilizing TCGA, GTEx, CPTAC, HPA, and cBioPortal databases. Furthermore, we examined the relationship between ATAD2 and immune infiltration utilizing single-cell sequencing data and TCGA database. Additionally, the expression and oncogenic functions of ATAD2 were verified in papillary thyroid carcinoma (PTC) through MTT, wound-healing, transwell, and flow cytometry assays. Our results revealed significant overexpression of ATAD2 in most cancers, strongly associated with poor prognosis. Amplification was the most frequent alteration type of ATAD2, with its mutation correlating with improved overall survival. ATAD2 was positively correlated with multiple inhibitory immune checkpoints and closely associated with the immunosuppressive microenvironment, particularly in PTC. In vitro experiments demonstrated that ATAD2 promoted the proliferation, migration, and invasion of PTC cells by activating the PI3K-AKT pathway and modulating the G1/S cell cycle checkpoint. Collectively, ATAD2 holds promise as a biomarker for pan-cancer diagnosis and prognosis, as well as a predictor of immunotherapeutic responsiveness and a therapeutic target to enhance the efficacy of existing anti-tumor immune therapies.
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ATPases Associadas a Diversas Atividades Celulares , Proteínas de Ligação a DNA , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/imunologia , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/metabolismo , ATPases Associadas a Diversas Atividades Celulares/metabolismo , ATPases Associadas a Diversas Atividades Celulares/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Prognóstico , Proliferação de Células , Linhagem Celular Tumoral , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mutação , Masculino , FemininoRESUMO
The monoclonal antibody rituximab improves clinical outcome in the treatment of CD20-positive lymphomatous neoplasms, and it is an established drug for treatment of these cancers. Successful mRNA COVID-19 (SARS-CoV-2) vaccination is extremely important for lymphoma patients because they tend to be elderly with comorbidities which leaves them at increased risk of poor outcomes once infected by Coronavirus. Anti-CD20 therapies such as rituximab, deplete B-cell populations and can affect vaccine efficacy. Therefore, a knowledge of the effect of COVID-19 vaccination in this group is critical. We followed a cohort of 28 patients with CD20-positive lymphomatous malignancies treated with rituximab that started prior to their course of COVID-19 vaccination, including boosters. We assayed for vaccine "take" in the humoral (IgG and IgA) and cellular compartment. Here, we show that short-term and long-term development of IgG and IgA antibodies directed toward COVID-19 spike protein are reduced in these patients compared to healthy controls. Conversely, the robustness and breath of underlying T-cell response is equal to healthy controls. This response is not limited to specific parts of the spike protein but spans the spike region, including response to the conserved Receptor Binding Domain (RBD). Our data informs on rational vaccine design and bodes well for future vaccination strategies that require strong induction of T-cell responses in these patients.
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Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Linfoma , Rituximab , SARS-CoV-2 , Humanos , Rituximab/uso terapêutico , COVID-19/imunologia , COVID-19/prevenção & controle , Feminino , Masculino , Idoso , SARS-CoV-2/imunologia , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Linfoma/imunologia , Linfoma/tratamento farmacológico , Linfoma/terapia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Imunoglobulina A/imunologia , Imunoglobulina A/sangue , Antígenos CD20/imunologia , Idoso de 80 Anos ou mais , Vacinação , Vacinas de mRNARESUMO
OBJECTIVES: Supplemental parenteral nutrition (SPN) is recommended to add when enteral nutrition alone is not sufficient. This research aims to evaluate the effect of preoperative SPN in patients with gastric cancer. METHODS: A total of 180 patients with gastric cancer were divided into three groups (60 patients per group) according to different nutritional support scheme. The primary endpoint was the changes in nutrition and inflammatory, while the secondary endpoint included the changes in prognosis. RESULTS: Compared with the control group, there were significant differences in nutrition and inflammation related indicators in the oral nutrition supplement (ONS) group and the SPN + ONS group (P < 0.05). Compared with the ONS group, the SPN + ONS group showed significant differences in the above indicators (P < 0.05). However, no significant changes were observed in the incidence of complications, the postoperative exhaust time, and the hospitalization time. CONCLUSIONS: Preoperative SPN had a positive effect on nutrition and inflammation of gastric cancer patients undergoing surgery, but had no significant effect on their prognosis.
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Due to their pivotal roles in regulating energy metabolism and apoptosis, mitochondria in cancer cells have been considered a vulnerable and feasible target. Many anticancer agents, e.g., metal-based compounds, are found to target and disturb mitochondria primarily, which may lead to the disturbance of energy metabolism and, more importantly, the initiation of apoptosis. In this work, a gold-based complex 7 (GC7) was synthesized and evaluated in a series of different cancer cell lines. The anticancer efficacies of GC7 on cell viability, apoptosis, and colony formation were determined. Cellular thioredoxin reductase (TrxR) activity, oxygen consumption rate (OCR), glucose uptake, and lactate production following GC7 treatment were evaluated and analyzed. The Jeko-1 and A549 xenograft models were used to assess GC7's tumor-suppressing effects. The results showed that GC7 possessed a broad-spectrum anticancer effect, with IC50 values ranging from 0.43 to 1.2 µM in multiple cancer cell lines, which was more potent than gold-based auranofin (â¼2-6 folds). GC7 (0.3 and 1 µM) efficiently induced apoptosis of Jeko-1, A549, and HCT116 cells, and it suppressed the sphere formation of cancer stem cells GSC11 and GSC23 cells at 0.1 µM, and it completely eliminated colony at 0.3 µM. The preliminary mechanistic study showed that GC7 inhibited cellular TrxR activity, suppressed mitochondrial OCR, reduced mitochondrial membrane potential (MMP), decreased glucose uptake, and possibly suppressed glycolysis to reduce lactate production. GC7 was predicted to have a similar yet slightly different pharmacokinetic profile as auranofin. Finally, GC7 (20 mg/kg, oral, 5/week, or 3 mg/kg, IP, 3/week) significantly inhibited tumor growth. In conclusion, GC7 showed great potential in suppressing cancer cell proliferation, probably via inhibiting TrxR and impacting mitochondria-mediated energy metabolism.
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Antineoplásicos , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Metabolismo Energético , Mitocôndrias , Humanos , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Metabolismo Energético/efeitos dos fármacos , Animais , Camundongos , Apoptose/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Ouro/química , Ouro/farmacologia , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Camundongos Nus , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Camundongos Endogâmicos BALB C , Compostos Organoáuricos/farmacologia , Compostos Organoáuricos/química , Compostos Organoáuricos/síntese químicaRESUMO
With the increasing age of the population worldwide, the incidence rate of Parkinson's disease (PD) is increasing annually. Currently, the treatment strategy for PD only improves clinical symptoms. No effective treatment strategy can slow down the progression of the disease. In the present study, whole transcriptome sequencing was used to obtain the mRNA and miRNA expression profiles in a PD mouse model, which revealed the pathogenesis of PD. The transcription factor RUNX3 upregulated the miR-186-3p expression in the PD model. Furthermore, the high miR-186-3p expression in PD can be targeted to inhibit the DAT expression, resulting in a decrease in the dopamine content of dopaminergic neurons. Moreover, miR-186-3p can be targeted to inhibit the IGF1R expression and prevent the activation of the IGF1R-P-PI3K-P-AKT pathway, thus increasing the apoptosis of dopaminergic neurons by regulating the cytochrome c-Bax-cleaved caspase-3 pathway. Our research showed that the RUNX3-miR-186-3p-DAT-IGF1R axis plays a key role in the pathogenesis of PD, and miR-186-3p is a potential target for the treatment of PD.
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Subunidade alfa 3 de Fator de Ligação ao Core , Modelos Animais de Doenças , MicroRNAs , Doença de Parkinson , Receptor IGF Tipo 1 , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 1/genética , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Camundongos Endogâmicos C57BL , Masculino , Apoptose/genética , Transdução de Sinais , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Camundongos , Sequência de BasesRESUMO
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death all over the world, and brings a heavy social economic burden especially in China. Several immuno-combination therapies have shown promising efficacy in the first-line treatment of unresectable HCC and are widely used in clinical practice. Nevertheless, which combination is the most affordable one is unknown. Our study assessed the cost-effectiveness of the immuno-combinations as first-line treatment for patients with unresectable HCC from the perspective of Chinese payers. METHODS: A Markov model was built according to five multicenter, phase III, open-label, randomized trials (Himalaya, IMbrave150, ORIENT-32, CARES-310, LEAP-002) to investigate the cost-effectiveness of tremelimumab plus durvalumab (STRIDE), atezolizumab plus bevacizumab (A + B), sintilimab plus bevacizumab biosimilar (IBI305) (S + B), camrelizumab plus rivoceranib (C + R), and pembrolizumab plus lenvatinib (P + L). Three disease states were included: progression free survival (PFS), progressive disease (PD) as well as death. Medical costs were searched from West China Hospital, published literatures or the Red Book. Cost-effectiveness ratios (CERs) and incremental cost-effectiveness ratios (ICERs) were evaluated to compare costs among different combinations. Sensitivity analyses were performed to assess the robust of the model. RESULTS: The total cost and quality-adjusted life years (QALYs) of C + R, S + B, P + L, A + B and STRIDE were $12,109.27 and 0.91, $26,961.60 and 1.12, $55,382.53 and 0.83, $70,985.06 and 0.90, $84,589.01 and 0.73, respectively, resulting in the most cost-effective strategy of C + R with CER of $13,306.89 per QALY followed by S + B with CER of $24,072.86 per QALY. Compared with C + R, the ICER of S + B strategy was $70,725.38 per QALY, which would become the most cost-effective when the willing-to-pay threshold exceeded $73,500/QALY. In the subgroup analysis, with the application of Asia results in Leap-002 trial, the model results were the same as global data. In the sensitivity analysis, with the variation of parameters, the results were robust. CONCLUSION: As one of the promising immuno-combination therapies in the first-line systemic treatment of HCC, camrelizumab plus rivoceranib demonstrated the potential to be the most cost-effective strategy, which warranted further studies to best inform the real-world clinical practices.
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Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Análise de Custo-Efetividade , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Humanos , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Bevacizumab/economia , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/economia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , China/epidemiologia , Ensaios Clínicos Fase III como Assunto , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/economia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/economia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Cadeias de Markov , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/economia , Intervalo Livre de Progressão , Anos de Vida Ajustados por Qualidade de Vida , Quinolinas/uso terapêutico , Quinolinas/economia , Quinolinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The constantly evolving environment imposes increasingly stringent demands on the mechanical qualities of materials employed for absorbing electromagnetic waves (EMWs). Therefore, there is an urgent need for advanced materials capable of efficiently absorbing EMWs and withstanding harsh electromagnetic conditions. In this study, the electrodeposition method was effectively used to synthesize nickel-cobalt layered double hydroxides (NiCo-LDHs) in a controlled manner on a composite structure of carbon nanotubes and carbon foam, creating an exquisite construction. The manipulation of the electrodeposition time facilitated the regulation of the density of the layered structure within the composite material, thereby significantly enhancing its polarization relaxation performance. Increased defect sites and interface polarization enhance impedance matching and the attenuation constant, resulting in greatly improved absorption performance. The optimized sample demonstrated exceptional wave-absorbing performance in comparative experimental analysis, attaining a maximum reflection loss of -58.18 dB. It also has an effective absorption bandwidth of 5.36 GHz at a wavelength of 2.28 mm. The exceptional isolation effect of LDH, coupled with the outstanding insulation ability of the porous carbon skeleton, confers remarkable corrosion resistance and thermal insulation performance on the composite material. Hence, this discovery offers novel insights into designing environmentally tolerant absorbent materials.
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Recent advancements in photoacoustic (PA) imaging have leveraged reversibly photoswitchable chromophores, known for their dual absorbance states, to enhance imaging sensitivity through differential techniques. Yet, their deployment in tumor imaging has faced obstacles in achieving targeted delivery with high efficiency and specificity. Addressing this challenge, we introduce innovative protein assemblies, DrBphP-CBD, by genetically fusing a photosensory module from Deinococcus radiodurans bacterial phytochrome (DrBphP) with a collagen-binding domain (CBD). These protein assemblies form sub-100-nanometer structures composed of 24 DrBphP dimers and 12 CBD trimers, presenting 24 protein subunits. Their affinity for collagens, combined with impressive photoswitching contrast, markedly improves PA imaging precision. In various tumor models, intravenous administration of DrBphP-CBD has demonstrated enhanced tumor targeting and retention, augmenting contrast in PA imaging by minimizing background noise. This strategy underscores the clinical potential of DrBphP-CBD as PA contrast agents, propelling photoswitchable chromoproteins to the forefront of precise cancer diagnosis.
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Colágeno , Deinococcus , Neoplasias , Técnicas Fotoacústicas , Fitocromo , Técnicas Fotoacústicas/métodos , Colágeno/química , Colágeno/metabolismo , Animais , Humanos , Camundongos , Fitocromo/química , Fitocromo/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Deinococcus/metabolismo , Deinococcus/química , Linhagem Celular Tumoral , Ligação Proteica , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genéticaRESUMO
Eggs are recognized for their rich nutrient profile, providing essential proteins and lipids with notable functional properties. This study examines the effects of incorporating Water Extract of Ampelopsis grossedentata (WEA) into poultry feed on egg quality, focusing on lipid content, choline, L-carnitine levels, and flavonoid compound deposition. Our results show significant increases in essential amino acids, flavonoids, and other bioactive compounds in eggs from WEA-treated hens, suggesting enhanced cardiovascular, antioxidant, and anti-inflammatory benefits. Additionally, we observed elevated levels of choline and betaine in egg yolks, alongside increased L-carnitine content, which may contribute to improved lipid metabolism and reduced cardiovascular disease risk. KEGG pathway analysis revealed upregulation of metabolites involved in critical metabolic pathways, enhancing the nutritional profile of eggs. Flavonoid compounds, traditionally associated with plant-based foods, were also significantly increased, with notable levels of 7, 4'-dihydroxyflavone, daidzein, and glycitein identified in WEA-treated eggs, indicating potential health benefits. These findings suggest that WEA supplementation can produce functional eggs with improved nutritional quality, offering a novel approach to enhancing egg production and meeting the growing demand for functional foods. Further research is needed to fully understand the bioavailability and health impacts of these enriched compounds.
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Ampelopsis , Ração Animal , Galinhas , Dieta , Suplementos Nutricionais , Gema de Ovo , Metaboloma , Extratos Vegetais , Animais , Gema de Ovo/química , Suplementos Nutricionais/análise , Ração Animal/análise , Metaboloma/efeitos dos fármacos , Dieta/veterinária , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Feminino , Ampelopsis/química , Clara de Ovo/químicaRESUMO
Herbal polysaccharides are extensively studied as vaccine adjuvants due to their safety and potent immunoenhancing activity. This study aimed to analyze the structure of Lagenaria siceraria (Molina) Standl polysaccharide (LSP50) and investigate its adjuvant activity for the H9N2 vaccine in broiler chickens. Structural analysis revealed that LSP50 primarily consisted of rhamnose, arabinose, xylose, mannose, glucose, and galactose with molar ratios of 23.12: 12.28: 10.87: 8.26: 2.64: 22.82 respectively. The adjuvant activity of LSP50 was evaluated, which showing significant enhancements compared to the H9N2 group. Parameters including the immune organ index, H9N2 specific IgG level, cytokines contents (IFN-γ, IL-2, IL-4, and IL-5), and the proportion of CD3e+CD8aT+cells were significantly increased in the LSP50 group (P < 0.05). Additionally, sequencing results showed that LSP50 modulates the immune response by regulating PLA2G12B and PTGDS genes involved in the arachidonic acid pathway. These findings were further validated through qPCR analysis to affirm the reliability of the sequencing data. In conclusion, our results demonstrate that LSP50 exhibits potent adjuvant activity, enhancing both cellular and humoral immunity.
Assuntos
Adjuvantes Imunológicos , Galinhas , Polissacarídeos , Animais , Galinhas/imunologia , Polissacarídeos/farmacologia , Polissacarídeos/química , Adjuvantes Imunológicos/farmacologia , Vírus da Influenza A Subtipo H9N2/efeitos dos fármacos , Cucurbitaceae/química , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/prevenção & controle , Ração Animal/análise , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
As histone modification enzymes, EZH2 mediates H3K27 trimethylation (H3K27me3), whereas LSD1 removes methyl groups from H3K4me1/2 and H3K9me1/2. Synergistic anticancer effects of combining inhibitors of these two enzymes are observed in leukemia and prostate cancer. Thus, a series of EZH2/LSD1 dual inhibitors are designed and synthesized to evaluate their anticancer activity. After the structure-activity study, one of the best compounds, ML234, displayed excellent antiproliferative capacity against prostate cancer cell lines LNCAP, PC3, and 22RV1. Enzymatic assays ascertained that the anticancer potency of ML234 was mediated through coinhibition of EZH2 and LSD1. Moreover, the accumulation of H3K4me2 and H3K9me2 and the decrease of H3K27me3 induced by ML234 were verified by Western blot analysis. More importantly, the compound remarkably suppressed the tumor growth and enhanced the therapeutic efficacy of clinical drug enzalutamide in the 22RV1 xenograft mouse model, indicating that it may have potential as an anticancer agent in prostate cancer.