RESUMO
Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes.
Assuntos
Fator de Transcrição Associado à Microftalmia/metabolismo , NADP Trans-Hidrogenases/metabolismo , Pigmentação da Pele/efeitos da radiação , Raios Ultravioleta , Animais , Linhagem Celular , Estudos de Coortes , AMP Cíclico/metabolismo , Dano ao DNA , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Predisposição Genética para Doença , Humanos , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Melanossomas/efeitos dos fármacos , Melanossomas/metabolismo , Melanossomas/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , NADP Trans-Hidrogenases/antagonistas & inibidores , Oxirredução/efeitos dos fármacos , Oxirredução/efeitos da radiação , Polimorfismo de Nucleotídeo Único/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise/efeitos dos fármacos , Proteólise/efeitos da radiação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/genética , Ubiquitina/metabolismo , Peixe-ZebraRESUMO
Single-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex systems1. However, a comprehensive single-cell atlas has not been achieved for humans. Here we use single-cell mRNA sequencing to determine the cell-type composition of all major human organs and construct a scheme for the human cell landscape (HCL). We have uncovered a single-cell hierarchy for many tissues that have not been well characterized. We established a 'single-cell HCL analysis' pipeline that helps to define human cell identity. Finally, we performed a single-cell comparative analysis of landscapes from human and mouse to identify conserved genetic networks. We found that stem and progenitor cells exhibit strong transcriptomic stochasticity, whereas differentiated cells are more distinct. Our results provide a useful resource for the study of human biology.
Assuntos
Células/citologia , Células/metabolismo , Análise de Célula Única/métodos , Adulto , Animais , Povo Asiático , Diferenciação Celular , Linhagem Celular , Separação Celular , China , Bases de Dados Factuais , Corpos Embrioides/citologia , Corpos Embrioides/metabolismo , Etnicidade , Feto/citologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Imunidade , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Camundongos , Especificidade de Órgãos , RNA Mensageiro/análise , RNA Mensageiro/genética , Análise de Sequência de RNA , Análise de Célula Única/instrumentação , Processos EstocásticosRESUMO
BACKGROUND & AIMS: Despite the increasing number of treatment options available for liver cancer, only a small proportion of patients achieve long-term clinical benefits. Here, we aim to develop new therapeutic approaches for liver cancer. METHODS: A compound screen was conducted to identify inhibitors that could synergistically induce senescence when combined with cyclin-dependent kinase (CDK) 4/6 inhibitor. The combination effects of CDK4/6 inhibitor and exportin 1 (XPO1) inhibitor on cellular senescence were investigated in a panel of human liver cancer cell lines and multiple liver cancer models. A senolytic drug screen was performed to identify drugs that selectively killed senescent liver cancer cells. RESULTS: The combination of CDK4/6 inhibitor and XPO1 inhibitor synergistically induces senescence of liver cancer cells in vitro and in vivo. The XPO1 inhibitor acts by causing accumulation of RB1 in the nucleus, leading to decreased E2F signaling and promoting senescence induction by the CDK4/6 inhibitor. Through a senolytic drug screen, cereblon (CRBN)-based proteolysis targeting chimera (PROTAC) ARV-825 was identified as an agent that can selectively kill senescent liver cancer cells. Up-regulation of CRBN was a vulnerability of senescent liver cancer cells, making them sensitive to CRBN-based PROTAC drugs. Mechanistically, we find that ubiquitin specific peptidase 2 (USP2) directly interacts with CRBN, leading to the deubiquitination and stabilization of CRBN in senescent liver cancer cells. CONCLUSIONS: Our study demonstrates a striking synergy in senescence induction of liver cancer cells through the combination of CDK4/6 inhibitor and XPO1 inhibitor. These findings also shed light on the molecular processes underlying the vulnerability of senescent liver cancer cells to CRBN-based PROTAC therapy.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Senescência Celular , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Proteína Exportina 1 , Carioferinas , Neoplasias Hepáticas , Inibidores de Proteínas Quinases , Receptores Citoplasmáticos e Nucleares , Ubiquitina-Proteína Ligases , Humanos , Senescência Celular/efeitos dos fármacos , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/metabolismo , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/metabolismo , Carioferinas/antagonistas & inibidores , Carioferinas/metabolismo , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Animais , Proteínas de Ligação a Retinoblastoma/metabolismo , Proteínas de Ligação a Retinoblastoma/genética , Sinergismo Farmacológico , Senoterapia/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Transdução de Sinais/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Hidrazinas/farmacologia , Hidrazinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Células Hep G2 , Camundongos , Piperazinas , Piridinas , TriazóisRESUMO
Shape memory hydrogels provide a worldwide scope for functional soft materials. However, most shape memory hydrogels exhibit poor mechanical properties, leading to low actuation strength, which severely limits their applications in smart biomimetic devices. Herein, a strategy for muscle-inspired shape memory-oriented polyvinyl alcohol (PVA)-natural rubber latex (NRL) hydrogel (OPNH) with multiscale oriented structure is demonstrated. The shape memory function comes from the stretch-induced crystallization of natural rubber (NR), while PVA forms strong hydrogen bonding interactions with proteins and phospholipids on the surface of NRL particles. Meanwhile, the reconfigurable interactions of PVA and NR produce a multiscale-oriented structure during stretch-drying, improving the mechanical and shape memory properties. The resultant OPNH shows excellent interfacial compatibility, exhibiting outstanding mechanical performance (3.2 MPa), high shape fixity (≈80%) and shape recovery ratio (≈92%), high actuation strength (206 kPa), working capacity (105 kJ m- 3), extremely short response time (≈2 s), low response temperature (28 °C) and smart thermal responsiveness. It can even maintain muscle-like working capacity when lifting a load equivalent to 372 times its weight, providing a new class shape memory material for the application in smart biomimetic muscles and multistimulus responsive devices.
RESUMO
Due to the high surface area and uniform porosity of covalent organic frameworks (COFs), they exhibit superior properties in capturing and detecting even trace amounts of gases in the air. However, the COFs materials that possess dual detected functionality are still less reported. Here, an imine-based COF containing thiophene as a donor and triazine as an acceptor to form spatial-distribution-defined D-A structures was prepared. D-A system between thiophene and triazine facilitates the charge transfer process during the protonation process of the imine and the triazine units. The obtained COF exhibits simultaneous sensing ability toward both acidic and alkaline vapors with obvious colorimetric sensing functionality.
RESUMO
Toll-like receptors (TLRs) are one of the extensively studied pattern recognition receptors (PRRs) and play crucial roles in the immune responses of vertebrates and invertebrates. In this study, 14 TLR genes were identified from the genome-wide data of Octopus sinensis. Protein structural domain analysis showed that most TLR proteins had three main structural domains: extracellular leucine-rich repeats (LRR), transmembrane structural domains, and intracellular Toll/IL-1 receptor domain (TIR). The results of subcellular localization prediction showed that the TLRs of O. sinensis were mainly located on the plasma membrane. The results of quantitative real-time PCR (qPCR) showed that the detected TLR genes were differentially expressed in the hemolymph, white bodies, hepatopancreas, gills, gill heart, intestine, kidney, and salivary gland of O. sinensis. Furthermore, the present study investigated the expression changes of O. sinensis TLR genes in hemolymph, white bodies, gills, and hepatopancreas in different phases (6 h, 12 h, 24 h, 48 h) after stimulation with PGN, poly(I: C) and Vibrio parahaemolyticus. The expression of most of the TLR genes was upregulated at different time points after infection with pathogens or stimulation with PAMPs, a few genes were unchanged or even down-regulated, and many of the TLR genes were much higher after V. parahaemolyticus infection than after PGN and poly(I:C) stimulation. The results of this study contribute to a better understanding of the molecular immune mechanisms of O. sinensis TLRs genes in resistance to pathogen stimulation.
Assuntos
Regulação da Expressão Gênica , Imunidade Inata , Octopodiformes , Receptores Toll-Like , Vibrio parahaemolyticus , Animais , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Receptores Toll-Like/química , Vibrio parahaemolyticus/fisiologia , Octopodiformes/genética , Octopodiformes/imunologia , Imunidade Inata/genética , Regulação da Expressão Gênica/imunologia , Filogenia , Perfilação da Expressão Gênica/veterinária , Poli I-C/farmacologia , Peptidoglicano/farmacologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/química , Moléculas com Motivos Associados a Patógenos/farmacologiaRESUMO
Yogurt is popular as a natural and healthy food, but its flavor greatly affects acceptability by consumers. Flavor compounds of yogurt is generally produced by the metabolism of lactose, protein and fat, and the resulting flavors include carbonyls, acids, esters and alcohols, etc. Each flavor compounds could individually provide the corresponding flavor, or it can be combined with other compounds to form a new flavor. The flavor network was formed among the metabolites of milk components, and acetaldehyde, as the central compounds, played a role in connecting the whole network. The flavor compounds can be affected by many factors, such as the use of different raw milks, ways of homogenization, sterilization, fermentation, post ripening, storage condition and packaging materials, etc., which can affect the overall flavor of yogurt. This paper provides an overview of the volatile flavor compounds in yogurt, the pathways of production of the main flavor compounds during yogurt fermentation, and the factors that influence the flavor of yogurt including type of raw milk, processing, and storage. It also tries to provide theoretical guidance for the product of yogurt in ideal flavor, but further research is needed to provide a more comprehensive description of the flavor system of yogurt.
RESUMO
SAR imagery plays a crucial role in geological and environmental monitoring, particularly in highland mountainous regions. However, inherent geometric distortions in SAR images often undermine the precision of remote sensing analyses. Accurately identifying and classifying these distortions is key to analyzing their origins and enhancing the quality and accuracy of monitoring efforts. While the layover and shadow map (LSM) approach is commonly utilized to identify distortions, it falls short in classifying subtle ones. This study introduces a novel LSM ground-range slope (LG) method, tailored for the refined identification of minor distortions to augment the LSM approach. We implemented the LG method on Sentinel-1 SAR imagery from the tri-junction area where the Xiaojiang, Pudu, and Jinsha rivers converge at the Yunnan-Sichuan border. By comparing effective monitoring-point densities, we evaluated and validated traditional methods-LSM, R-Index, and P-NG-against the LG method. The LG method demonstrates superior performance in discriminating subtle distortions within complex terrains through its secondary classification process, which allows for precise and comprehensive recognition of geometric distortions. Furthermore, our research examines the impact of varying slope parameters during the classification process on the accuracy of distortion identification. This study addresses significant gaps in recognizing geometric distortions and lays a foundation for more precise SAR imagery analysis in complex geographic settings.
RESUMO
BACKGROUND: Chinese mugwort (Artemisia argyi) possesses extensive pharmacological activities associated with anti-tumour, antioxidative and anti-inflammatory effects. The present study aimed to investigate the antioxidant and anti-ageing effects of A. argyi extract (AAE) on the fruit fly (Drosophila melanogaster) ageing model by detecting antioxidant enzyme activities and the mRNA level of antioxidant genes. RESULTS: AAE could significantly lengthen the mean lifespan, 50% survival days, and maximum lifespan of D. melanogaster, especially when the amount of AAE added reached 6.68 mg mL-1, the mean lifespan of both female and male flies increased by 23.74% and 22.30%, respectively, indicating the effective life extension effect of AAE. At the same time, AAE could improve the climbing ability and tolerance to hydrogen peroxide in D. melanogaster. In addition, the addition of AAE effectively increased the activities of copper-zinc-containing superoxide dismutase, manganese-containing superoxide dismutase and catalase in D. melanogaster and reduced the contents of malondialdehyde. Moreover, when reared with diets containing AAE, the expression of antioxidant-related genes SOD1, SOD2 and CAT was up-regulated in D. melanogaster and down-regulated for MTH genes. CONCLUSION: The study indicates that AAE effectively enhances the antioxidant capacity of D. melanogaster and has potential applications as an antioxidant and anti-ageing agent in the nutraceutical industry. © 2024 Society of Chemical Industry.
Assuntos
Artemisia , Drosophila melanogaster , Masculino , Feminino , Animais , Drosophila melanogaster/genética , Antioxidantes/farmacologia , Longevidade , Envelhecimento , Suplementos NutricionaisRESUMO
Doping of polycyclic conjugated hydrocarbons (PCHs) with sulfur atoms is becoming more and more important as a means of creating unique functional materials. Recently, thiophene-containing multiple helicenes have garnered enormous attention due to their intriguing electronic and (chir)optical properties compared with carbohelicenes. However, the efficient synthesis of thiopyran-containing multiple helicenes and the underlying sulfur doping mechanisms are rather unexplored. Herein, the synthesis and structural analysis of a thiopyran-containing double [7]helicene 3 are reported. X-ray crystallographic analysis reveals 3 and its dication with C2-symmetric propeller-shape structure and compact p-p interaction in the solid state. 3 exhibits deep-red to near-infrared (NIR) fluorescence emission. Tunable aromaticity of the central benzene ring and thiopyran rings is found by chemical oxidation, which is further confirmed by nucleus-independent chemical shift (NICS), anisotropy of the induced current density (AICD) and harmonic oscillator model of aromaticity (HOMA) analysis. Furthermore, the chiral and photosensitizing characters of 3 are investigated. The excellent deep-red to NIR fluorescence, circularly polarized luminescence (CPL) and photosensitizing activities suggest that 3 can be used as an outstanding photosensitizer in photodynamic therapy (PDT) and bioimaging, especially paving the way for future CPL-PDT and CPL-bio-probe applications.
RESUMO
Lightweight porous hydrogels provide a worldwide scope for functional soft mateirals. However, most porous hydrogels have weak mechanical strength, high density (>1 g cm-3 ), and high heat absorption due to weak interfacial interactions and high solvent fill rates, which severely limit their application in wearable soft-electronic devices. Herein, an effective hybrid hydrogel-aerogel strategy to assemble ultralight, heat-insulated, and tough polyvinyl alcohol (PVA)/SiO2 @cellulose nanoclaws (CNCWs) hydrogels (PSCG) via strong interfacial interactions with hydrogen bonding and hydrophobic interaction is demonstrated. The resultant PSCG has an interesting hierarchical porous structure from bubble template (≈100 µm), PVA hydrogels networks introduced by ice crystals (≈10 µm), and hybrid SiO2 aerogels (<50 nm), respectively. PSCG shows unprecedented low density (0.27 g cm-3 ), high tensile strength (1.6 MPa) & compressive strength (1.5 MPa), excellent heat-insulated ability, and strain-sensitive conductivity. This lightweight porous and tough hydrogel with an ingenious design provides a new way for wearable soft-electronic devices.
RESUMO
Natural rubber (NR) composites containing bio-based chitin nanofibers (ChNFs) exhibit a wide range of mechanical properties - from rubber to plastic behavior - with increasing chitin contents. A constrained 3-dimensional network can be formed by mixing natural rubber latex and a modified zwitterionic rigid chitin counterpart. By inclusion of highly anisotropic chitin nanofibers (30 wt%), strain-induced NR crystallization occurs at a much lower strain of 50%. More intriguingly, 2D-WAXD results reveal that the strain-induced crystallization of NR/ChNFs composites show 3-dimensionally oriented crystallite formation behaving similar to "3D-single crystals orientation" when the content of ChNFs is over 5 wt%. It is suggested that not only c-axis (NR chains) orients along the stretching direction, but also the a- and b-axes deliberately arrange along the normal direction and transverse direction, respectively. Structure and morphology in 3-dimensional spaces after strain-induced crystallization of the NR/ChNFs30 composite are investigated in detail. Therefore, this study might pave a new way to enhance mechanical properties by incorporation of ChNFs, obtaining 3-dimensionally oriented crystallites of novel multifunctional NR/ChNFs composite with shape memory ability.
RESUMO
In order to utilize the synergistic effect between a conductive polymer and an inorganic semiconductor to efficaciously enhance charge transfer and solve the problem of unsatisfactory performance of a single photocatalyst, thiophene (Th) was polymerized on the Cd0.5Zn0.5S nanoparticle surface to prepare a conductive polymer-inorganic polythiophene/Cd0.5Zn0.5S (PTh/CZS) heterostructrue through a simple in situ oxidation polymerization for the first time. The as-prepared PTh/CZS heterostructures significantly improved photocatalytic TCH degradation and hydrogen production activities. Especially, the 15PTh/CZS sample exhibited the optimal hydrogen production rate (18.45 mmol g-1 h-1), which was 2.51 times higher than pure Cd0.5Zn0.5S nanoparticles. In addition, 15PTh/CZS also showed very fast and efficient photodegradation ability for degrading 88% of TCH in 25 min. Moreover, the degradation rate (0.06229 min-1) was five times more than that of Cd0.5Zn0.5S. The π-π* transition characteristics, high optical absorption coefficient, wide absorption wavelength of PTh, the tight contact interface, and synergistic effect of PTh and Cd0.5Zn0.5S efficiently boosted charge transfer rate and increased the light absorption of PTh/CZS photocatalysts, which greatly enhanced the photocatalytic abilities. Besides, the mechanism of improved photocatalytic activities for TCH degradation and H2 production was also carefully proposed. Undoubtedly, this work would provide new insights into coupling conductive polymers to inorganic photocatalysts for achieving multifunctional applications in the field of photocatalysis.
RESUMO
Immunotherapy has shown remarkable efficacy in various cancer treatments. However, enhanced T-cell immune surveillance can lead to aberrant immune responses, resulting in severe immune checkpoint inhibitor-related adverse events. This is a case report of a patient previously treated with immune checkpoint inhibitors who presented with ST-segment elevation without abnormal troponin and cardiac enzyme spectrum test results. Cardiac toxicity of immune checkpoint inhibitors mainly manifests as acute immune-mediated myocarditis. While Brugada phenocopy is commonly caused by fever, electrolyte abnormalities, tricyclic/tetracyclic antidepressants, and marijuana use, we suspect that it was induced by immune checkpoint inhibitors in the current case.
Assuntos
Inibidores de Checkpoint Imunológico , Miocardite , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Eletrocardiografia , Miocardite/induzido quimicamente , Miocardite/diagnóstico , Fenótipo , FebreRESUMO
BACKGROUND: To analyze the polymorphism distribution of low density lipoprotein receptor rs688, AvaII, NcoI gene in ischemic stroke, and explore the linkage disequilibrium among them. The correlation between the linkage disequilibrium and ischemic stroke was further analyzed. METHODS: The levels of serum lipid (triglyceride, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B) and rs688, AvaII, NcoI polymorphism of low density lipoprotein receptor gene were tested in patients with ischemic stroke (n = 140), healthy control (n = 129) and patients with other cerebrovascular diseases (n = 122). Chi-square test was used to compare the gene frequency and allele frequency of each group. Both the linkage disequilibrium of the three genes and the alleles correlated with ischemic stroke were analyzed. The correlation of linkage disequilibrium gene and ischemic stroke was analyzed with logistic binary regression. RESULTS: In the ischemic stroke group, significant difference was observed in frequencies and allelic frequencies of low density lipoprotein receptor (LDLR) rs688 and AvaII. No difference of NcoI was found. Linkage disequilibrium was found for rs688 and AvaII (D' = 0.927, R2 = 0.509). Allelic genes correlate with ischemic stroke included T of rs688 (X2 = 46.105, p < 0.001) and C of AvaII (X2 = 20.436, p < 0.001). CONCLUSIONS: Linkage disequilibrium existed between LDLR rs688 and AvaII genes. With the wild type gene (WT) (rs688/AvaII: CC/TT) as reference, rs688/AvaII: CT/TC, CT/CC and TT/CC increased the risk of ischemic stroke, which might be a genetic marker used for the screen of high-risk population contributing to the prevention of the disease.
Assuntos
AVC Isquêmico , Humanos , Frequência do Gene , Predisposição Genética para Doença , Desequilíbrio de Ligação , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Receptores de LDL/genéticaRESUMO
Spikelet number per panicle (SNP) is one of the most important yield components in rice. Rice ENHANCING BIOMASS AND SPIKELET NUMBER (OsEBS), a gene involved in improved SNP and yield, has been cloned from an accession of Dongxiang wild rice. However, the mechanism of OsEBS increasing rice SNP is poorly understood. In this study, the RNA-Seq technology was used to analyze the transcriptome of wildtype Guichao 2 and OsEBS over-expression line B102 at the heading stage, and analysis of the evolution of OsEBS was also conducted. A total of 5369 differentially expressed genes (DEGs) were identified between Guichao2 and B102, most of which were down-regulated in B102. Analysis of the expression of endogenous hormone-related genes revealed that 63 auxin-related genes were significantly down-regulated in B102. Gene Ontogeny (GO) enrichment analysis showed that the 63 DEGs were mainly enriched in eight GO terms, including auxin-activated signaling pathway, auxin polar transport, auxin transport, basipetal auxin transport, and amino acid transmembrane transport, most of which were directly or indirectly related to polar auxin transport. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis further verified that the down-regulated genes related to polar auxin transport had important effects on increased SNP. Analysis of the evolution of OsEBS found that OsEBS was involved in the differentiation of indica and japonica, and the differentiation of OsEBS supported the multi-origin model of rice domestication. Indica (XI) subspecies harbored higher nucleotide diversity than japonica (GJ) subspecies in the OsEBS region, and XI experienced strong balancing selection during evolution, while selection in GJ was neutral. The degree of genetic differentiation between GJ and Bas subspecies was the smallest, while it was the highest between GJ and Aus. Phylogenetic analysis of the Hsp70 family in O. sativa, Brachypodium distachyon, and Arabidopsis thaliana indicated that changes in the sequences of OsEBS were accelerated during evolution. Accelerated evolution and domain loss in OsEBS resulted in neofunctionalization. The results obtained from this study provide an important theoretical basis for high-yield rice breeding.
Assuntos
Oryza , RNA-Seq , Oryza/genética , Filogenia , Melhoramento Vegetal , Perfilação da Expressão Gênica , TranscriptomaRESUMO
Cancer is one of the deadliest diseases, having spurred researchers to explore effective therapeutic strategies for several centuries. Although efficacious, conventional chemotherapy usually introduces various side effects, such as cytotoxicity or multi-drug resistance. In recent decades, nanomaterials, possessing unique physical and chemical properties, have been used for the treatment of a wide range of cancers. Dynamic therapies, which can kill target cells using reactive oxygen species (ROS), are promising for tumor treatment, as they overcome the drawbacks of chemotherapy methods. Piezoelectric nanomaterials, featuring a unique property to convert ultrasound vibration energy into electrical energy, have also attracted increasing attention in biomedical research, as the piezoelectric effect can drive chemical reactions to generate ROS, leading to the newly emerging technique of ultrasound-driven tumor therapy. Piezoelectric materials are expected to bring a better solution for efficient and safe cancer treatment, as well as patient pain relief. In this review article, we highlight the most recent achievements of piezoelectric biomaterials for tumor therapy, including the mechanism of piezoelectric catalysis, conventional piezoelectric materials, modified piezoelectric materials and multifunctional piezoelectric materials for tumor treatment.
Assuntos
Nanoestruturas , Neoplasias , Humanos , Espécies Reativas de Oxigênio , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Materiais Biocompatíveis/uso terapêutico , UltrassonografiaRESUMO
The high prevalence of oral squamous cell carcinoma (OSCC) in South Asia is associated with habitual areca nut chewing. Arecoline, a primary active carcinogen within areca nut extract, is known to promote OSCC pathological development. Dysregulation of N6-methyladenosine (m6A) modification has begun to emerge as a significant contributor to cancer development and progression. However, the biological effects and molecular mechanisms of m6A modification in arecoline-promoted OSCC malignance remain elusive. We reveal that chronic arecoline exposure substantially induces upregulation of fat mass and obesity-associated protein (FTO), MYC, and programmed cell death-ligand 1 (PD-L1) in OSCC cells. Moreover, upregulation of PD-L1 is observed in OSCC cell lines and tissues and is associated with areca nut chewing in OSCC patients. We also demonstrate that arecoline-induced FTO promotes the stability and expression levels of PD-L1 transcripts through mediating m6A modification and MYC activity, respectively. PD-L1 upregulation confers superior cell proliferation, migration, and resistance to T-cell killing to OSCC cells. Blockage of PD-L1 by administration of anti-PD-L1 antibody shrinks tumor size and improves mouse survival by elevating T-cell-mediated tumor cell killing. Therefore, targeting PD-L1 might be a potential therapeutic strategy for treating PD-L1-positive OSCC patients, especially those with habitual areca nut chewing.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Apoptose , Areca/efeitos adversos , Areca/metabolismo , Arecolina/farmacologia , Carcinoma de Células Escamosas/patologia , Imunidade , Ligantes , Camundongos , Neoplasias Bucais/patologia , Obesidade/complicações , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
In the past decade, atomically dispersed Fe active sites (coordinated with nitrogen) on carbon materials (FeNC) have emerged rapidly as promising single-atom catalysts (SACs) for the oxygen reduction reaction (ORR) to substitute precious group metal (PGM) catalysts, owing to their earth abundance and low cost. Nonetheless, the production of highly active FeNC SACs is largely restricted by material cost, low product yield and difficulty of microstructure design. Herein, the authors demonstrate a facile in-situ xerogel (ISG) assisted synthetic strategy, using cheap materials, to construct FeNC SACs (ISG FeNC). The porous silica xerogel, formed in-situ with the FeNC precursors, encourages the emergence of enormous micropores/mesopores and homogeneous confinement/protection to the precursors during pyrolysis, benefiting to the formation of abundant accessible active sites (27.6 × 1019 sites g-1 ). Correspondingly, the ISG FeNC exhibits excellent ORR activity with a half-wave potential (E1/2 = 0.91 V) in alkaline medium. The Zn-air battery assembled using the ISG FeNC SACs as the bifunctional catalyst of air cathode, demonstrates commendable performance with high peak power density of 249.1 mW cm-2 and superior long-term stability (660 cycles with 220 h). This work offers an economic and efficient way to fabricate PGM-free SACs for diverse applications.
RESUMO
Plasmonic nanohybrids are promising photo energy conversion materials in photoelectronics and biomedicine, due to their unique surface plasmon resonance (SPR). Au and Cu2-x Sx nanostructures with strong SPR in the near-infrared (NIR) spectral region are classic plasmonic systems used to convert NIR photons into heat for photothermal therapy (PTT). The rational design of the Au/Cu2-x Sx nanohybrids is expected to induce better photothermal conversion; however, the construction of such hybrids via wet-chemistry methods with a well-controlled interfacial structure is still challenging. Here, the synthesis of an AuCu Star/Cu2-x Sx nanohybrid is reported, where the Cu2-x Sx components are selectively grown on the AuCu nanostar tips to form "caps". The spatial formation of the Cu2-x Sx caps on star tips is mainly governed by surfactant concentration, tip curvature, and experimental manipulation. The nanohybrids show low cytotoxicity and superior photothermal conversion efficiency, enabling robust PTT to kill cancer cells in the second NIR window. Numerical simulation reveals that the coupling of Cu2-x Sx on nanostar tips generates strong interfacial electric field, improving photothermal conversion. Moreover, the spatial separation structure favors the continuous flow of hot charge carriers to produce active radicals, further promoting the tumor treatment effect.