RESUMO
ConspectusOver the past two decades, terahertz (THz) technology has undergone rapid development, driven by advancements and the growing demand for THz applications across various scientific and technological domains. As the cornerstone of THz technology, strong THz-matter interactions, especially realized as high THz intrinsic absorption in nanometer-thick materials, play a highly important role in various applications including but not limited to THz absorption/shielding, detection, etc. The rigorous electromagnetic theory has posited a maximum intrinsic absorption of 50% for electromagnetic waves by thin films, and the succinct impedance matching condition has also been formulated to guide the design of highly intrinsically absorbing materials. However, these theories face challenges when applied to the THz spectrum with an ultrabroad bandwidth. Existing thin films typically achieve a maximum intrinsic absorption within a narrow frequency range, significantly limiting the performance of THz absorbers and detectors. To date, both theoretical frameworks and experimental solutions are lacking in overcoming the challenge of achieving broadband maximum intrinsic absorption in the THz regime.In this Account, we describe how two-dimensional (2D) transition-metal carbide and/or nitride (MXene) films with nanometer thickness can realize the maximum intrinsic absorption in the ultrabroad THz band, which successfully addresses the forementioned longstanding issue. Surprisingly, traditional DC impedance matching theory fails to explain this phenomenon, while we instead propose a novel theory of AC impedance matching to provide a satisfactory explanation. By delving into the microscopic transport behavior of free electrons in MXene, we discover that intraflake transport dominates terahertz conductivity under THz wave excitation, while interflake transport primarily dictates DC conductivity. This not only elucidates the significant disparities between DC and AC impedance in MXenes but also underscores the suitability of AC impedance matching for achieving broadband THz absorption limits. Furthermore, we identify a high electron concentration and short relaxation time as crucial factors for achieving broadband maximum absorption in the THz regime. Although approaching the THz intrinsic absorbing limits, it still faces hurdles to the use of MXene in practical applications. First, diverse and uncontrollable terminations exist on the surface of MXene stemming from the synthesis process, which largely influence the electron structure and THz absorbing property of MXene. Second, MXene suffers from poor stability in the presence of oxygen and water. To address the above issues, we have undertaken distinctive works to precisely control the terminations and suppress the oxidation of MXene even at high temperature through surface and interface chemistry, such as low-temperature Lewis basic halide treatment and building a Ti3C2Tx/extracted bentonite (EB) interface. For practical application consideration, we proposed a copolymer-polyacrylic latex (PAL)-based MXene waterborne paint (MWP) with a strong intermolecular polar interaction between MWP and the substrate provided by the cyano group in PAL. This not only has strong THz EMI shielding/absorption efficiency but also can easily adhere to various substrates that are commonly used in the THz band. These studies may have significant implications for future applications of MXene nanofilms in THz optoelectronic devices.
RESUMO
Ligand modulation of transition-metal catalysts to achieve optimal reactivity and selectivity in alkene hydrofunctionalization is a fundamental challenge in synthetic organic chemistry. Hydroaminoalkylation, an atom-economical approach for alkylating amines using alkenes, is particularly significant for amine synthesis in the pharmaceutical, agrochemical, and fine chemical industries. However, the existing methods usually require specific substrate combinations to achieve precise regio- and stereoselectivity, which limits their practical utility. Protocols allowing for regiodivergent hydroaminoalkylation from the same starting materials, controlling both regiochemical and stereochemical outcomes, are currently absent. Herein, we report a ligand-controlled, regiodivergent nickel-catalyzed hydroaminoalkylation of unactivated alkenes with N-sulfonyl amines. The reaction initiates with amine dehydrogenation and involves aza-nickelacycle intermediates. Tritert-butylphosphine promotes branched regioselectivity and syn diastereoselectivity, whereas ethyldiphenylphosphine enables linear selectivity, yielding regioisomers with inverse orientation. Systematic evaluation of diverse monodentate phosphine ligands reveals distinct regioselectivity cliffs, and % Vbur (min), a ligand steric descriptor, was established as a predictive parameter correlating ligand structure to regioselectivity. Computational investigations supported experimental findings, offering mechanistic insights into the origins of regioselectivity. Our method provides an efficient and predictable route for amine synthesis, demonstrating broad substrate scope, excellent tolerance toward various functional groups, and practical advantages. These include the use of readily available starting materials and cost-effective nickel(II) salts as precatalysts.
RESUMO
Controlling the site-selectivity of C-H functionalization is of significant importance and a formidable undertaking in synthetic organic chemistry, motivating the continuing development of efficient and sustainable technologies for activating C-H bonds. However, methods that control the site-selectivity for double C-H functionalization are rare. We herein report a conceptually new method to achieve highly site-selective C-H functionalization by implementing a radical single-out strategy. Leveraging the steric hindrance-sensitive CO-insertion as the radical differentiation process, a site-selective and stereoselective carbonylative formal [2 + 2] cycloaddition of imines and alkenes by sequential double allylic C-H bond activation was established without special and complicated HAT-reagents. This reaction was compatible with a wide range of alkenes and imines with diverse skeletons to deliver allylic ß-lactams that are of synthetic and medicinal interest.
RESUMO
Two-electron oxidative addition is one of the most important elementary reactions for d-block transition metals but it is uncommon for f-block elements. Here, we report the first examples of intermolecular oxidative addition of E-H (E=C, N) bonds to uranium(II) centers. The transient U(II) species was formed in-situ by reducing a heterometallic cluster featuring U(IV)-Pd(0) bonds with potassium-graphite (KC8). Oxidative addition of C-H or N-H bonds to the U(II) centers was observed when this transient U(II) species was treated with benzene, carbazole or 1-adamantylamine, respectively. The U(II) centers could also react with tetracene, biphenylene or N2O, leading to the formation of arene reduced U(IV) products and uranyl(VI) species via two- or four-electron processes. This study demonstrates that the intermolecular two-electron oxidative addition reactions are viable for actinide elements.
RESUMO
We present the first enantioselective nickel-catalyzed borylative coupling of 1,3-dienes with aldehydes, providing an efficient route to highly valuable homoallylic alcohols in a single step. The reaction involves the 1,4-carboboration of dienes, leading to the formation of C-C and C-B bonds accompanied by the construction of two continuous stereogenic centers. Enabled by a chiral spiro phosphine-oxazoline nickel complex, this transformation yields products with exceptional diastereoselectivity, E-selectivity, and enantioselectivity. The diastereoselectivity of the reaction can be controlled by employing either (Z)-1,3-dienes or (E)-1,3-dienes.
RESUMO
The movement of plant viruses is a complex process that requires support by the virus-encoded movement protein and multiple host factors. The unfolded protein response (UPR) plays important roles in plant virus infection, while how UPR regulates viral infection remains to be elucidated. Here, we show that rice stripe virus (RSV) elicits the UPR in Nicotiana benthamiana. The RSV-induced UPR activates the host autophagy pathway by which the RSV-encoded movement protein, NSvc4, is targeted for autophagic degradation. As a counteract, we revealed that NSvc4 hijacks UPR-activated type-I J-domain proteins, NbMIP1s, to protect itself from autophagic degradation. Unexpectedly, we found NbMIP1 stabilizes NSvc4 in a non-canonical HSP70-independent manner. Silencing NbMIP1 family genes in N. benthamiana, delays RSV infection, while over-expressing NbMIP1.4b promotes viral cell-to-cell movement. Moreover, OsDjA5, the homologue of NbMIP1 family in rice, behaves in a similar manner toward facilitating RSV infection. This study exemplifies an arms race between RSV and the host plant, and reveals the dual roles of the UPR in RSV infection though fine-tuning the accumulation of viral movement protein.
Assuntos
Nicotiana/virologia , Doenças das Plantas/genética , Proteínas de Plantas/metabolismo , Tenuivirus/metabolismo , Inativação Gênica , Oryza/genética , Oryza/metabolismo , Resposta a Proteínas não Dobradas/genética , Resposta a Proteínas não Dobradas/fisiologiaRESUMO
The catalytic C(sp3 )-C(sp3 ) coupling of alkyl halides and tertiary amines offers a promising tool for the rapid decoration of amine skeletons. However, this approach has not been well established, partially due to the challenges in precisely distinguishing and controlling the reactivity of amine-coupling partners and their product homologues. Herein, we developed a metal-free photocatalytic system for the aminomethylation of alkyl halides through radical-involved C(sp3 )-C(sp3 ) bond formation, allowing for the synthesis of sterically congested tertiary amines that are of interest in organic synthesis but not easily prepared by other methods. Mechanistic studies disclosed that sterically hindered N-substituents are key to activate the amine coupling partners by tuning their redox potentials to drive the reaction forward.
RESUMO
Wheat plants showing yellowing and mosaic in leaves and stunting were collected from wheat fields in Henan Province, China. Analysis of these plants by transmission electron microscopy showed that they contained two types of filamentous virus-like particles with a length of 200-500 nm and 1000-1300 nm, respectively. RNA-seq revealed a coinfection with wheat yellow mosaic virus (WYMV) and an unknown wheat-infecting virus. The genome of the unknown virus is 8,410 nucleotides long, excluding its 3' poly(A) tail. It has six open reading frames (ORFs). ORF1 encodes a putative viral replication-associated protein (Rep), and ORFs 2, 3, and 4 encode the triple gene block (TGB) proteins. ORFs 5 and 6 encode the capsid protein (CP) and a protein with unknown function, respectively. Phylogenetic analysis showed that this novel virus is evolutionarily related to members of the subfamily Quinvirinae, family Betaflexiviridae. It is, however, distinct from the viruses in the currently established genera. Based on the species and genus demarcation criteria set by the International Committee on Taxonomy of Viruses (ICTV), we tentatively name this novel virus "wheat yellow stunt-associated betaflexivirus" (WYSaBV), and we propose it to be a member of a new genus in the family Betaflexiviridae.
Assuntos
Flexiviridae/genética , Triticum/virologia , China , Flexiviridae/classificação , Flexiviridae/patogenicidade , Flexiviridae/ultraestrutura , Genoma Viral/genética , Fases de Leitura Aberta/genética , Filogenia , Doenças das Plantas/virologia , Folhas de Planta/virologia , RNA Viral/genética , Especificidade da Espécie , Proteínas Virais/genética , Vírion/ultraestruturaRESUMO
A supramolecular brush polymer Poly(P5-OXD) was constructed through the self-assembly of an A1/A2 disubstituted pillar[5]arene P5-OXD with a 1,3,4-oxadiazole unit and a cyanobutoxy group, exhibiting external stimuli responsiveness towards Cu2+ ions with an ON/OFF fluorescence signal output.
RESUMO
Proteins are subject to spontaneous rearrangements of their backbones. Most prominently, asparagine and aspartate residues isomerize to their ß-linked isomer, isoaspartate (isoAsp), on time scales ranging from days to centuries. Such modifications are typically considered "molecular wear-and-tear", destroying protein function. However, the observation that some proteins, including the essential bacterial enzyme MurA, harbor stoichiometric amounts of isoAsp suggests that this modification can confer advantageous properties. Here, we demonstrate that nature exploits an isoAsp residue within a hairpin to stabilize MurA. We found that isoAsp formation in MurA is unusually rapid and critically dependent on folding status. Moreover, perturbation of the isoAsp-containing hairpin via site-directed mutagenesis causes aggregation of MurA variants. Structural mass spectrometry revealed that this effect is caused by local protein unfolding in MurA mutants. Our findings demonstrate that MurA evolved to "mature" via a spontaneous post-translational incorporation of a ß-amino acid, which raises the possibility that isoAsp-containing hairpins may serve as a structural motif of biological importance.
Assuntos
Alquil e Aril Transferases/química , Proteínas de Bactérias/química , Enterobacter cloacae/enzimologia , Ácido Isoaspártico/química , Enterobacter cloacae/química , Estabilidade Enzimática , Isomerismo , Modelos Moleculares , Agregados Proteicos , Conformação Proteica , Dobramento de ProteínaRESUMO
The mitochondrial complexes are prone to sirtuin (Sirt)3-mediated deacetylation modification, which may determine cellular response to stimuli, such as oxidative stress. In this study, we show that the cytochrome c oxidase (COX)-1, a core catalytic subunit of mitochondrial complex IV, was acetylated and deactivated both in 2,2'-azobis(2-amidinopropane) dihydrochloride-treated NIH/3T3 cells and hydrogen peroxide-treated primary neuronal cells, correlating with apoptotic cell death induction by oxidative stress. Inhibition of Sirt3 by small interfering RNA or the inhibitor nicotinamide induced accumulation of acetylation of COX-1, reduced mitochondrial membrane potential, and increased cell apoptosis. In contrast, overexpression of Sirt3 enhanced deacetylation of COX-1 and inhibited oxidative stress-induced apoptotic cell death. Significantly, rats treated with ischemia/reperfusion injury, a typical oxidative stress-related disease, presented an inhibition of Sirt3-induced hyperacetylation of COX-1 in the brain tissues. Furthermore, K13, K264, K319, and K481 were identified as the acetylation sits of COX-1 in response to oxidative stress. In conclusion, COX-1 was discovered as a new deacetylation target of Sirt3, indicating that the Sirt3/COX-1 axis is a promising therapy target of stress-related diseases.-Tu, L.-F., Cao, L.-F., Zhang, Y.-H., Guo, Y.-L., Zhou, Y.-F., Lu, W.-Q., Zhang, T.-Z., Zhang, T., Zhang, G.-X., Kurihara, H., Li, Y.-F., He, R.-R. Sirt3-dependent deacetylation of COX-1 counteracts oxidative stress-induced cell apoptosis.
Assuntos
Isquemia Encefálica , Ciclo-Oxigenase 1/metabolismo , Proteínas de Membrana/metabolismo , Traumatismo por Reperfusão , Sirtuína 3/metabolismo , Sirtuínas/metabolismo , Amidinas/farmacologia , Animais , Ciclo-Oxigenase 1/genética , Regulação da Expressão Gênica , Peróxido de Hidrogênio , Proteínas de Membrana/genética , Camundongos , Células NIH 3T3 , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Sirtuína 3/genética , Sirtuínas/genética , Organismos Livres de Patógenos EspecíficosRESUMO
BACKGROUND: The expression of miR-125 is regulated by an single-nucleotide polymorphism (SNP), rs12976445, which may be involved in the risk of pneumonitis among non-small-cell lung carcinoma patients undergoing the radiotherapy. We investigated this hypothesis via clinical data analysis and in vitro experiments. METHODS: An online microRNA (miRNA) database (www.mirdb.org) and luciferase reporter assays were used to confirm the role of transforming growth factor-ß1 (TGFB1) as a target gene of miR-125a. Quantification by real-time PCR and Western blot analysis were used to measure the expression of miRNA-125a and TGFB1 among different groups (carrying CC, CT, and TT genotypes of rs12976445) or cells transfected with a scramble control, miR-125a mimics, TGFB1 siRNA, or miR-125a inhibitors. RESULTS: We evaluated 699 NSCLC patients and found that the patients carrying the TT or CT genotype of rs12976445 had a higher risk of radiotherapy-induced pneumonitis. Computational analysis and luciferase assays validated that TGFB1 is a target gene of miR-125a. The expression level of miR-125a mRNA was significantly downregulated in the CT and TT groups, while the expression levels of TGFB1 and SMAD2 were significantly upregulated in the CC group. The expression of TGFB1 and SMAD2 was regulated by miR-125a in A549 cells. CONCLUSION: The rs12976445 SNP in miR-125a is associated with the risk of pneumonitis after in lung cancer patients undergoing the radiotherapy by regulating the expression of miR-125a and TGFB1.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Neoplasias Pulmonares , MicroRNAs , Polimorfismo de Nucleotídeo Único , RNA Neoplásico , Pneumonite por Radiação , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , MicroRNAs/biossíntese , MicroRNAs/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Pneumonite por Radiação/genética , Pneumonite por Radiação/metabolismo , Pneumonite por Radiação/patologiaRESUMO
Recent evidence suggests that adipokines are involved in the regulation of bone metabolism. Ctrp4 is a newly discovered member of the adipokine CTRP family. Studies have shown that Ctrp4 is involved in the regulation of tumor cell inflammatory signaling pathways and acts on the hypothalamus to regulate food intake, but its role in osteoblasts is not yet clear. In this study, we found that the expression of Ctrp4 in bone tissue was significantly decreased in the tail-suspended mouse, while that in ovariectomized-simulated osteoporosis mice decreased similarly, indicating that Ctrp4 was involved in osteogenesis regulation. We further isolated Alp-positive osteoblasts from the femur of tail-suspended rats and confirmed that the expression of Ctrp4, Bglap and Alp was down-regulated in the process of bone loss caused by tail suspension. In the process of inducing osteoblastic differentiation in vitro, Ctrp4 interfering significantly inhibited the expression of Alp and Bglap. In addition, inhibition of Ctrp4 resulted in decreased alkaline phosphatase expression and less alizarin red staining, indicating that Ctrp4 promoted osteogenic differentiation and osteoblasts mineralization. In conclusion, our results suggest that Ctrp4 is involved in bone metabolism regulation and promotes osteoblast differentiation, which may become a potential target for future intervention in bone metabolic diseases.
Assuntos
Adipocinas/metabolismo , Osteoblastos/citologia , Osteogênese , Adipocinas/análise , Animais , Diferenciação Celular , Células Cultivadas , Feminino , Masculino , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoporose/metabolismo , Osteoporose/patologiaRESUMO
BACKGROUND: TGF-ß promotes tumor invasion and metastasis through inducing epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in human cancers. However, whether and how circRNAs contribute to TGF-ß-induced EMT and metastasis in NSCLC remain vague. Here, we investigated the regulation and function of Circular RNA hsa_circ_0008305 (circPTK2) in TGF-ß-induced EMT and tumor metastasis, as well as a link between circPTK2 and transcriptional intermediary factor 1 γ (TIF1γ) in NSCLC. METHODS: Circular RNAs were determined by human circRNA Array analysis, real-time quantitative reverse transcriptase PCR and northern blot. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were employed to test the interaction between circPTK2 and miR-429/miR-200b-3p. Ectopic overexpression and siRNA-mediated knockdown of circPTK2, TGF-ß-induced EMT, Transwell migration and invasion in vitro, and in vivo experiment of metastasis were used to evaluate the function of circPTK2. Transcription and prognosis analyses were done in public databases. RESULTS: CircPTK2 and TIF1γ were significantly down-regulated in NSCLC cells undergoing EMT induced by TGF-ß. CircPTK2 overexpression augmented TIF1γ expression, inhibited TGF-ß-induced EMT and NSCLC cell invasion, whereas circPTK2 knockdown had the opposite effects. CircPTK2 functions as a sponge of miR-429/miR-200b-3p, and miR-429/miR-200b-3p promote TGF-ß-induced EMT and NSCLC cell invasion by targeting TIF1γ. CircPTK2 overexpression inhibited the invasion-promoting phenotype of endogenous miR-429/miR-200b-3p in NSCLC cells in response to TGF-ß. CircPTK2 overexpression significantly decreased the expression of Snail, an important downstream transcriptional activator of TGF-ß/Smad signaling. In an in vivo experiment of metastasis, circPTK2 overexpression suppressed NSCLC cell metastasis. Moreover, circPTK2 expression was dramatically down-regulated and positively correlated with TIF1γ expression in human NSCLC tissues. Especially, circPTK2 was significantly lower in metastatic NSCLC tissues than non-metastatic counterparts. CONCLUSION: Our findings show that circPTK2 (hsa_circ_0008305) inhibits TGF-ß-induced EMT and metastasis by controlling TIF1γ in NSCLC, revealing a novel mechanism by which circRNA regulates TGF-ß-induced EMT and tumor metastasis, and suggesting that circPTK2 overexpression could provide a therapeutic strategy for advanced NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Transição Epitelial-Mesenquimal/genética , Quinase 1 de Adesão Focal/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , RNA , Fatores de Transcrição/genética , Regiões 3' não Traduzidas , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , MicroRNAs/genética , Metástase Neoplásica , Interferência de RNA , RNA Circular , Fator de Crescimento Transformador beta/farmacologiaRESUMO
BACKGROUND: Healthcare providers generate a huge amount of biomedical data stored in either legacy system (paper-based) format or electronic medical records (EMR) around the world, which are collectively referred to as big biomedical data (BBD). To realize the promise of BBD for clinical use and research, it is an essential step to extract key data elements from unstructured medical records into patient-centered electronic health records with computable data elements. Our objective is to introduce a novel solution, known as a double-reading/entry system (DRESS), for extracting clinical data from unstructured medical records (MR) and creating a semi-structured electronic health record database, as well as to demonstrate its reproducibility empirically. METHODS: Utilizing the modern cloud-based technologies, we have developed a comprehensive system that includes multiple subsystems, from capturing MRs in clinics, to securely transferring MRs, storing and managing cloud-based MRs, to facilitating both machine learning and manual reading, and to performing iterative quality control before committing the semi-structured data into the desired database. To evaluate the reproducibility of extracted medical data elements by DRESS, we conduct a blinded reproducibility study, with 100 MRs from patients who have undergone surgical treatment of lung cancer in China. The study uses Kappa statistic to measure concordance of discrete variables, and uses correlation coefficient to measure reproducibility of continuous variables. RESULTS: Using the DRESS, we have demonstrated the feasibility of extracting clinical data from unstructured MRs to create semi-structured and patient-centered electronic health record database. The reproducibility study with 100 patient's MRs has shown an overall high reproducibility of 98 %, and varies across six modules (pathology, Radio/chemo therapy, clinical examination, surgery information, medical image and general patient information). CONCLUSIONS: DRESS uses a double-reading, double-entry, and an independent adjudication, to manually curate structured data elements from unstructured clinical data. Further, through distributed computing strategies, DRESS protects data privacy by dividing MR data into de-identified modules. Finally, through internet-based computing cloud, DRESS enables many data specialists to work in a virtual environment to achieve the necessary scale of processing thousands MRs within days. This hybrid system represents probably a workable solution to solve the big medical data challenge.
Assuntos
Sistemas de Apoio a Decisões Clínicas , Registros Eletrônicos de Saúde , Pesquisa sobre Serviços de Saúde , Armazenamento e Recuperação da Informação/métodos , Neoplasias Pulmonares , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Oxidative stress is a causal factor and key promoter of a variety of cardiovascular diseases associated with apoptotic cell death by causing deregulation of related genes. Though carvedilol, a ß-adrenergic blocker, has been shown to produce cytoprotective effects against cardiomyocyte apoptosis, the mechanisms are not fully understood. The present study was designed to investigate whether the beneficial effects of carvedilol are related to microRNAs which have emerged as critical players in cardiovascular pathophysiology via post-transcriptional regulation of protein-coding genes. In vivo, we demonstrated that carvedilol ameliorated impaired cardiac function of infarct rats and restored miR-133 expression. In vitro, carvedilol protected cardiomyocytes from H2O2 induced apoptosis detected by TUNEL staining and MTT assays, and increased miR-133 expression in cardiomyocytes. Overexpression of miR-133, a recognized anti-apoptotic miRNA, produced similar effects to carvedilol: reduction of reactive oxygen species (ROS) and malondialdehyde (MDA) content and increment of superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) level, so as to protect cardiomyocytes from apoptosis by downregulating caspase-9 and caspase-3 expression in the presence of H2O2. Transfection with AMO-133 (antisense inhibitor oligodeoxyribonucleotides) alone abolished the beneficial effects of carvedilol. Caspase-9-specific inhibitor z-LEHD-fmk, caspase-3-specific inhibitor z-DEVD-fmk, caspase-9 siRNA and caspase-3 siRNA were used to establish caspase-3 as a downstream target of miR-133. In conclusion, our data indicated that carvedilol protected cardiomyocytes by increasing miR-133 expression and suppressing caspase-9 and subsequent apoptotic pathways.
Assuntos
Apoptose/efeitos dos fármacos , Carbazóis/farmacologia , Citoproteção/efeitos dos fármacos , MicroRNAs/genética , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Propanolaminas/farmacologia , Regulação para Cima/efeitos dos fármacos , Antagonistas Adrenérgicos beta/farmacologia , Animais , Apoptose/genética , Carbazóis/uso terapêutico , Cardiotônicos/farmacologia , Carvedilol , Caspase 9/metabolismo , Técnicas de Silenciamento de Genes , Testes de Função Cardíaca , Peróxido de Hidrogênio/toxicidade , Masculino , MicroRNAs/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , Propanolaminas/uso terapêutico , Ratos WistarRESUMO
Background: SLC30A5, a member of the solute transporter protein family, is implicated in tumorigenesis and cancer progression. This study aimed to explore the expression and prognostic significance of SLC30A family genes in pan-cancer, with a specific emphasis on SLC30A5 in hepatocellular carcinoma (HCC). Methods: Expression patterns and prognostic implications of SLC30A family genes were assessed across 33 cancer types, especially HCC. Co-expression analysis explored the relationship between SLC30A5 and immune cell infiltration, immune checkpoints, pathway molecules related to tumor angiogenesis and epithelial-mesenchymal transition (EMT). The role of SLC30A5 in HCC was evaluated through in vitro and in vivo assays, including CCK8 viability assay, EdU cell proliferation assay, colony formation assay, apoptosis assay, wound healing assay, transwell migration assay, and xenograft mouse model assay using Huh7 cells with targeted knockdown of SLC30A5. Results: SLC30A family genes exhibited overexpression in various tumors. In HCC, upregulation of SLC30A5 expression correlated with adverse prognosis. Significant associations were observed between SLC30A5 expression and immune cell infiltration, immune checkpoints, molecules involved in angiogenesis, and EMT. SLC30A5 overexpression was associated with advanced disease stages, higher histological grades, and vascular invasion. Single-cell RNA sequencing data (GSE112271) revealed notable SLC30A5 expression in malignant cells. In vitro and in vivo assays demonstrated that SLC30A5 knockdown in Huh7 cells reduced proliferation, migration, and invasion while promoting apoptosis. Conclusions: This study highlights the clinical relevance of SLC30A5 in HCC, emphasizing its role in cell proliferation and migration. SLC30A5 emerges as a promising candidate for a prognostic marker and a potential target in HCC.
RESUMO
The main purpose of this study was to study the changes in growth, root system, and tissue anatomical structure of Pinus sylvestris var. mongolica under soil drought conditions. In this study, the growth indexes and photosynthesis of P. sylvestris var. mongolica seedlings under soil drought stress were studied by pot cultivation. Continuous pot water control experiment of the indoor culture of P. sylvestris var. mongolica was carried out, ensuring that the soil water content of each treatment reached 80%, 40%, and 20% of the field moisture capacity as control, moderate drought and severe drought, respectively. The submicroscopic structures of the needles and roots were observed using a scanning electron microscope and a transmission electron microscope. The response of soil roots to drought stress was studied by root scanning. Moderate drought stress increased needle stomatal density, while under severe drought stress, stomatal density decreased. At the same time, the total number of root tips, total root length, root surface area, and root volume of seedlings decreased with the deepening of the drought. Furthermore, moderate drought and severe drought stress significantly reduced the chlorophyll a and chlorophyll b content in P. sylvestris var. mongolica seedlings compared to the control group. The needle cells were deformed and damaged, and chloroplasts and mitochondria were damaged, gradually disintegrated, and the number of osmiophiles increased. There was also an increase in nuclear vacuolation.
Assuntos
Pinus sylvestris , Solo , Clorofila A , Secas , Plântula/fisiologia , ÁguaRESUMO
Since the discovery of Ti3 C2 Tx in 2011, 2D transition metal carbides, nitrides, and carbonitrides, known as MXenes, have been attracting great attention as the emerging member of 2D materials. The surface terminations, intercalants, and the interfaces between MXenes and other substances are of importance for tuning the properties of MXenes. For instance, surface termination of MXenes can change the density of states at the Fermi levels to make MXenes electronically tunable. Different terminations can lead to band opening and changes in behavior from metallic to semiconducting, as well as dramatic changes in the work function of MXenes. On the other hand, electron transfer occurring at the interface between MXenes and other substances due to the physical interaction/chemical bonding, changes the electron configuration of MXenes and realizes the functionalization. In this review, the most up-to-date progress of the surface and interface regulation of MXenes is comprehensively summarized, introducing the effect of various synthesis methods on the surface and interface chemistry, the routes on tuning the surface and interface chemistry, and the related potential applications. Finally, the perspective of the future research directions and challenges on surface and interface regulation is outlined.
RESUMO
As an important organic photofunctional material, spirooxazine (SO) usually does not exhibit photochromism in the solid state since the intermolecular π-π stacking impedes photoisomerization. Developing photochromic SO in the solid state is crucial for practical applications but is still full of challenges. Here, a series of spirooxazine derivatives (SO1-SO4) with bulky aromatic substituents at the 4- and 7-positions of the skeleton, which provide them with a large volume with which to undergo solid-state photochromism under mild conditions, is designed and synthesized. All the compounds SO1-SO4 exhibit tunable solid photochromism without ground colors, excellent fatigue resistance, and high thermal stability. Notably, it takes only 15 s for SO4 to reach the saturation of absorption intensity, thought to represent the fastest solid-state photoresponse of spirooxazines. X-ray crystal structures of the intermediate compound SO0 and the products SO1-SO2 as well as computational studies suggest that the bulky aromatic groups can lead to a hypochromic effect, allowing for the photochromism of SO in the solid state. The ideal photochromic properties of these spirooxazines open a new avenue for their applications in UV printing, quick response code, and related fields.