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BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant tumor known for its hypoxic environment, which contributes to resistance against the anticancer drug Sorafenib (SF). Addressing SF resistance in HCC requires innovative strategies to improve tumor oxygenation and effectively deliver therapeutics. RESULTS: In our study, we explored the role of KPNA4 in mediating hypoxia-induced SF resistance in HCC. We developed hemoglobin nanoclusters (Hb-NCs) capable of carrying oxygen, loaded with indocyanine green (ICG) and SF, named HPRG@SF. In vitro, HPRG@SF targeted HCC cells, alleviated hypoxia, suppressed KPNA4 expression, and enhanced the cytotoxicity of PDT against hypoxic, SF-resistant HCC cells. In vivo experiments supported these findings, showing that HPRG@SF effectively improved the oxygenation within the tumor microenvironment and countered SF resistance through combined photodynamic therapy (PDT). CONCLUSION: The combination of Hb-NCs with ICG and SF, forming HPRG@SF, presents a potent strategy to overcome drug resistance in hepatocellular carcinoma by improving hypoxia and employing PDT. This approach not only targets the hypoxic conditions that underlie resistance but also provides a synergistic anticancer effect, highlighting its potential for clinical applications in treating resistant HCC.
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Carcinoma Hepatocelular , Hemoglobinas , Verde de Indocianina , Neoplasias Hepáticas , Fotoquimioterapia , Sorafenibe , Microambiente Tumoral , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Humanos , Fotoquimioterapia/métodos , Animais , Hemoglobinas/farmacologia , Linhagem Celular Tumoral , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Camundongos , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Verde de Indocianina/uso terapêutico , Camundongos Nus , Camundongos Endogâmicos BALB C , Antineoplásicos/farmacologia , Antineoplásicos/química , alfa Carioferinas/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas/químicaRESUMO
Breast cancer is a common malignancy in women with poor prognosis. This study aimed to investigate the molecular mechanism of microRNA-944 (miR-944) mediated secreted phosphoprotein-1 (SPP1) in breast cancer progression and its regulatory effect on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Differential gene analysis was performed to identify key genes associated with breast cancer development by screening breast cancer-related microarray data. The expression of miR-944 and SPP1 and their relationship were determined in clinical samples and cells. sh-SPP1, oe-SPP1, LY294002 or miR-944 mimic were transfected into MCF-7 cells to investigate the role of miR-944 mediated SPP1 in breast cancer development and its regulatory effect on the PI3K/Akt pathway. Finally, the tumorigenicity of breast cancer cells was observed in nude mice. Through bioinformatics analysis, we identified SPP1 as a key gene in breast cancer, and miR-944 as an upstream miRNA of SPP1. In breast cancer tissues and cells, the expression of miR-944 was decreased while that of SPP1 was increased. miR-944 negatively regulated the expression of SPP1. In breast cancer cells, SPP1 activated the PI3K/Akt pathway to promote cell proliferation and inhibit apoptosis. In vitro cell experiments showed that the downregulation of miR-944 promoted the high expression of SPP1, which then activated the PI3K/Akt signaling pathway, promoting breast cancer cell proliferation. In vivo experiments further confirmed the anti-cancer role of miR-944 mediated SPP1 in breast cancer. Our study highlights the role of miR-944 mediated SPP1 in inhibiting breast cancer progression by blocking the PI3K/Akt pathway.
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Neoplasias da Mama , MicroRNAs , Camundongos , Animais , Humanos , Feminino , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias da Mama/genética , Camundongos Nus , Apoptose/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular , Osteopontina/genética , Osteopontina/metabolismoRESUMO
Many natural materials possess built-in structural variation, endowing them with superior performance. However, it is challenging to realize programmable structural variation in self-assembled synthetic materials since self-assembly processes usually generate uniform and ordered structures. Here, we report the formation of asymmetric microribbons composed of directionally self-assembled two-dimensional nanoflakes in a polymeric matrix during three-dimensional direct-ink printing. The printed ribbons with embedded structural variations show site-specific variance in their mechanical properties. Remarkably, the ribbons can spontaneously transform into ultrastretchable springs with controllable helical architecture upon stimulation. Such springs also exhibit superior nanoscale transport behavior as nanofluidic ionic conductors under even ultralarge tensile strains (>1,000%). Furthermore, to show possible real-world uses of such materials, we demonstrate in vivo neural recording and stimulation using such springs in a bullfrog animal model. Thus, such springs can be used as neural electrodes compatible with soft and dynamic biological tissues.
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Neuroestimuladores Implantáveis , Microtecnologia/instrumentação , Nanoestruturas , Impressão Tridimensional , Animais , Anuros , Elasticidade , Grafite/química , Íons/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Neurofisiologia/instrumentação , Nervo Isquiático/fisiologiaRESUMO
Phototheranostic offers a regional-focused tumor treatment upon photoirradiation. However, it is difficult to completely eradicate solid tumors using a conventional phototheranostic owing to the residual tumor cells outside the laser irradiation range. Herein, we fabricated a metallopolysaccharide-based smart nanotheranostic (Fe-dHA) via a nanoassembly-driven method, in which Fe3+ ions were coordinated to dopamine-modified biopolysaccharide hyaluronic acid (dHA). Taking advantage of the structural backbone and intrinsic dual-information-related functions of HA as well as the bi-functional Fe(III)-coordination centers, Fe-dHA can efficiently target tumor cells for phototheranostic. Additionally, it can be activated by endogenous overexpressed hyaluronidase to achieve sequential ferroptosis in tumor cells. The precise imaging and effective tumor inhibition using this metallopolysaccharide-based nanotheranostic were significantly demonstrated in vivo and in vitro. Thus, this rationally designed Fe-dHA provided a simple metallopolysaccharide strategy to develop an "all-in-one" smart nanotheranostic to synergize different therapeutic modalities for improving cancer therapy.
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Ferroptose , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Compostos Férricos , Humanos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fototerapia , Nanomedicina TeranósticaRESUMO
Photodynamic therapy (PDT) is a treatment procedure that relies on cytotoxic reactive oxygen species (ROS) generated by the light activation of a photosensitizer. The photophysical and biological properties of photosensitizers are vital for the therapeutic outcome of PDT. In this work a 2D rhomboidal metallacycle and a 3D octahedral metallacage were designed and synthesized via the coordination-driven self-assembly of a Ru(II)-based photosensitizer and complementary Pt(II)-based building blocks. The metallacage showed deep-red luminescence, a large 2-photon absorption cross-section, and highly efficient ROS generation. The metallacage was encapsulated into an amphiphilic block copolymer to form nanoparticles to encourage cell uptake and localization. Upon internalization into cells, the nanoparticles selectively accumulate in the lysosomes, a favorable location for PDT. The nanoparticles are almost nontoxic in the dark, and can efficiently destroy tumor cells via the generation of ROS in the lysosomes under 2-photon near-infrared light irradiation. The superb PDT efficacy of the metallacage-containing nanoparticles was further validated by studies on 3D multicellular spheroids (MCS) and in vivo studies on A549 tumor-bearing mice.
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Nanopartículas Metálicas , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Compostos de Platina , Compostos de Rutênio , Células A549 , Animais , Desenvolvimento de Medicamentos , Humanos , Lisossomos , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Fármacos Fotossensibilizantes/químicaRESUMO
DNA methylation, as one of the major means of epigenesis change, makes a large difference in the spatial structure of chromatin, transposable element activity and, fundamentally, gene transcription. It has been confirmed that DNA methylation is closely related to innate immune responses. Decitabine, the most efficient available DNA methyltransferase inhibitor, has demonstrated exhilarating immune activation and antiviral effects on multiple viruses, including HIV, HBV, HCV, HPV and EHV1. This review considers the role of decitabine in regulating innate immune responses and antiviral ability. Understanding the complex transcriptional and immune regulation of decitabine could help to identify and validate therapeutic methods to reduce pathogen infection-associated morbidity, especially virus infection-induced morbidity and mortality.
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Antivirais , Imunomodulação , Antivirais/farmacologia , Antivirais/uso terapêutico , Cognição , Decitabina/farmacologia , Imunidade InataRESUMO
Posttranslational modification (PTM) and regulation of protein stability are crucial to various biological processes. Histone deacetylase 6 (HDAC6), a unique histone deacetylase with two functional catalytic domains (DD1 and DD2) and a ZnF-UBP domain (ubiquitin binding domain, BUZ), regulates a number of biological processes, including gene expression, cell motility, immune response, and the degradation of misfolded proteins. In addition to the deacetylation of histones, other nonhistone proteins have been identified as substrates for HDAC6. Hsp90, a molecular chaperone that is a critical modulator of cell signaling, is one of the lysine deacetylase substrates of HDAC6. Intriguingly, as one of the best-characterized regulators of Hsp90 acetylation, HDAC6 is the client protein of Hsp90. In addition to regulating Hsp90 at the post-translational modification level, HDAC6 also regulates Hsp90 at the gene transcription level. HDAC6 mainly regulates the Hsp90-HSF1 complex through the ZnF-UBP domain, thereby promoting the HSF1 entry into the nucleus and activating gene transcription. The mutual interaction between HDAC6 and Hsp90 plays an important role in the regulation of protein stability, cell migration, apoptosis and other functions. Plenty of of studies have indicated that blocking HDAC6/Hsp90 has a vital regulatory role in multifarious diseases, mainly in cancers. Therefore, developing inhibitors or drugs against HDAC6/Hsp90 becomes a promising development direction. Herein, we review the current knowledge on molecular regulatory mechanisms based on the interaction of HDAC6 and Hsp90 and inhibition of HDAC6 and/or Hsp90 in oncogenesis and progression, antiviral and immune-related diseases and other vital biological processes.
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Proteínas de Choque Térmico HSP90/metabolismo , Desacetilase 6 de Histona/metabolismo , Processamento de Proteína Pós-Traducional , Acetilação , Animais , Desenvolvimento de Medicamentos , Descoberta de Drogas , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/genética , Desacetilase 6 de Histona/antagonistas & inibidores , Desacetilase 6 de Histona/genética , Histonas/metabolismo , Humanos , Isoenzimas , Ligação Proteica , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Biomass-derived carbon materials (BCMs) are encountering the most flourishing moment because of their versatile properties and wide potential applications. Numerous BCMs, including 0D carbon spheres and dots, 1D carbon fibers and tubes, 2D carbon sheets, 3D carbon aerogel, and hierarchical carbon materials have been prepared. At the same time, their structure-property relationship and applications have been widely studied. This paper aims to present a review on the recent advances in the controllable preparation and potential applications of BCMs, providing a reference for future work. First, the chemical compositions of typical biomass and their thermal degradation mechanisms are presented. Then, the typical preparation methods of BCMs are summarized and the relevant structural management rules are discussed. Besides, the strategies for improving the structural diversity of BCMs are also presented and discussed. Furthermore, the applications of BCMs in energy, sensing, environment, and other areas are reviewed. Finally, the remaining challenges and opportunities in the field of BCMs are discussed.
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Carbono , BiomassaRESUMO
SARS-CoV-2 infection poses a global challenge to human health. Upon viral infection, host cells initiate the innate antiviral response, which primarily involves type I interferons (I-IFNs), to enable rapid elimination of the invading virus. Previous studies revealed that SARS-CoV-2 infection limits the expression of I-IFNs in vitro and in vivo, but the underlying mechanism remains incompletely elucidated. In the present study, we performed data mining and longitudinal data analysis using SARS-CoV-2-infected normal human bronchial epithelial (NHBE) cells and ferrets, and the results confirmed the strong inhibitory effect of SARS-CoV-2 on the induction of I-IFNs. Moreover, we identified genes that are negatively correlated with IFNB1 expression in vitro and in vivo based on Pearson correlation analysis. We found that SARS-CoV-2 activates numerous intrinsic pathways, such as the circadian rhythm, phosphatidylinositol signaling system, peroxisome, and TNF signaling pathways, to inhibit I-IFNs. These intrinsic inhibitory pathways jointly facilitate the successful immune evasion of SARS-CoV-2. Our study elucidates the underlying mechanism by which SARS-CoV-2 evades the host innate antiviral response in vitro and in vivo, providing theoretical evidence for targeting these immune evasion-associated pathways to combat SARS-CoV-2 infection.
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COVID-19/imunologia , Interações Hospedeiro-Patógeno/imunologia , Interferon gama/metabolismo , SARS-CoV-2/imunologia , Animais , Brônquios/citologia , COVID-19/virologia , Linhagem Celular , Conjuntos de Dados como Assunto , Modelos Animais de Doenças , Células Epiteliais , Furões , Regulação da Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata , Interferon gama/imunologia , RNA-Seq , Mucosa Respiratória/citologia , Transdução de Sinais/genética , Transdução de Sinais/imunologiaRESUMO
Herpes simplex virus type 1 (HSV-1) is an important human pathogenic virus. It is urgent to develop novel antiviral targets because of the limited treatment options and the emergence of drug resistant strains. In this study, we tested the antiviral activity of lupeol, a triterpenoid compound, against HSV-1 and acyclovir (ACV) resistant strains. Lupeol significantly inhibited HSV-1 (F strain) and ACV-resistant strains including HSV-1/106, HSV-1/153, and HSV-1/Blue. Lupeol activity of the HSV-1α0 and α4 promoters, therefore down regulating the expression of the α0, α4, and α27 genes. Collectively, lupeol showed strong antiviral activity against HSV-1 and ACV-resistant strains, and could be a promising therapeutic candidate for HSV-1 pathogenesis. Keywords: herpes simplex virus 1; lupeol; ACV-resistant strains; promoter.
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Herpes Simples , Herpesvirus Humano 1 , Aciclovir , Antivirais/farmacologia , Antivirais/uso terapêutico , Farmacorresistência Viral , Genes Precoces , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/genética , Humanos , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/uso terapêuticoRESUMO
Organic cages are fascinating because of their well-defined 3D cavities, excellent stability, and accessible post-modification. However, the synthesis is normally realized by fragment coupling approach in low yields. Herein, we report one-pot, gram-scale and shape-controlled synthesis of two covalent organic cages (box-shaped [4]cage and triangular prism-shaped [2]cage) in yields of 46 % and 52 %, involving direct condensation of triangular 1,3,5-tris(2,4-dimethoxyphenyl)benzene monomer with paraformaldehyde and isobutyraldehyde, respectively. The cages can convert into high-yielding per-hydroxylated analogues. The [2]cage can be utilized as gas chromatographic stationary phase for high-resolution separation of benzene/cyclohexane and toluene/methylcyclohexane. By changing the central moiety of the triangular monomer and/or aldehyde, this synthetic method would have the potential to be a general strategy to access diverse cages with tunable shape, size, and electronic properties.
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Hierarchical self-assembly of discrete organoplatinum(II) metallacycles has attracted considerable attention. However, the exact assembly mechanism involving non-covalent interactions has limited the formation and application of self-assembly due to the dynamics of platinum metallacycles. Herein, we report the hierarchical self-assembly of a pyrene-based discrete organoplatinum(II) double-metallacycle that takes advantage of heteroligation-coordination-driven self-assembly and triflate anions' hydrogen bonding, which is extended into a 3-D supramolecular framework by the hydrogen-bonding interactions involving triflate anions. Furthermore, the assembled system displays tunable fluorescence emission and enhanced solid emission. The studies herein disclosed pave the way to prepare platinum(II) metallacycle-based supramolecular functional materials.
Assuntos
Fluorescência , Compostos Organoplatínicos/química , Pirenos/química , Ânions/química , Ligação de Hidrogênio , Estrutura Molecular , Compostos Organoplatínicos/síntese química , Espectrometria de FluorescênciaRESUMO
TaS2 nanolayers with reduced dimensionality show interesting physics, such as a gate-tunable phase transition and enhanced superconductivity, among others. Here, a solution-based strategy to fabricate a large-area foil of hybrid TaS2 /organic superlattice, where [TaS2 ] monolayers and organic molecules alternatively stack in atomic scale, is proposed. The [TaS2 ] layers are spatially isolated with remarkably weakened interlayer bonding, resulting in lattice vibration close to that of TaS2 monolayers. The foil also shows excellent mechanical flexibility together with a large electrical conductivity of 1.2 × 103 S cm-1 and an electromagnetic interference of 31 dB, among the highest values for solution-processed thin films of graphene and inorganic graphene analogs. The solution-based strategy reported herein can add a new dimension to manipulate the structure and properties of 2D materials and provide new opportunities for flexible nanoelectronic devices.
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Alzheimer's disease (AD) is a multifactorial disease triggered by environmental factors in combination with genetic predisposition. Infectious agents, in particular herpes simplex virus type 1 (HSV-1), are gradually being recognised as important factors affecting the development of AD. However, the mechanism linking HSV-1 and AD remains unknown. Of note, HSV-1 manipulates the activity of cofilin-1 to ensure their efficient infection in neuron cells. Cofilin-1, the main regulator of actin cytoskeleton reorganization, is implicating for the plastic of dendritic spines and axon regeneration of neuronal cells. Moreover, dysfunction of cofilin-1 is observed in most AD patients, as well as in mice with AD and ageing. Further, inhibition of cofilin-1 activity ameliorates the host cognitive impairment in an animal model of AD. Together, dysregulation of cofilin-1 led by HSV-1 infection is a potential link between HSV-1 and AD. Herein, we critically summarize the role of cofilin-1-mediated actin dynamics in both HSV-1 infection and AD, respectively. We also propose several hypotheses regarding the connecting roles of cofilin-1 dysregulation in HSV-1 infection and AD. Our review provides a foundation for future studies targeting individuals carrying HSV-1 in combination with cofilin-1 to promote a more individualised approach for treatment and prevention of AD.
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Doença de Alzheimer/metabolismo , Doença de Alzheimer/virologia , Cofilina 1/metabolismo , Herpes Simples/metabolismo , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Doença de Alzheimer/genética , Animais , Axônios/metabolismo , Axônios/virologia , Cofilina 1/genética , Herpes Simples/genética , Herpesvirus Humano 1/genética , Humanos , Neurônios/metabolismo , Neurônios/virologiaRESUMO
Following publication of the original article [1], we have been notified that there is a typo in the title of this article.
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BACKGROUND: Herpes simplex virus 1, an enveloped DNA virus belonging to the Herpesviridae family, spreads to neurons and causes pathological changes in the central nervous system. The purpose of this study was to investigate the potency and mechanism of antiviral activity of Aspergillipeptide D, a cyclic pentapeptide isolated from a culture broth of marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501, At present, there are many studies on the anti-tumor, anti-clotting, anti-oxidant and immunoinflammatory effects of Aspergillipeptide D, but little research has been done on the anti-HSV-1 activity of Aspergillipeptide D. METHODS: The anti-HSV-1 activity of Aspergillipeptide D was evaluated by plaque reduction assay. The mechanism of action against HSV-1 was determined from the effective stage. Then we assayed the viral DNA replication, viral RNA synthesis and protein expression, respectively. We also identified the proteins that interact with gB by mass spectrometry, and assayed the effect of Aspergillipeptide D on the interaction between the virus gB protein and cell proteins. RESULTS: Plaque reduction experiments showed that Aspergillipeptide D did not affect HSV-1 early infection events, including viral inactivation, attachment and penetration. Interestingly, Aspergillipeptide D dramatically reduced both the gene and protein levels of viral late protein gB, and suppressed its location in the endoplasmic reticulum and Golgi apparatus. In contrast, overexpression of gB restored viral production. Finally, proteomic analysis revealed that the numbers of cellular proteins that interacted with gB protein was largely decreased by Aspergillipeptide D. These results suggested that Aspergillipeptide D inhibited gB function to affect HSV-1 intercellular spread. CONCLUSIONS: Our results indicated that Aspergillipeptide D might be a potential candidate for HSV-1 therapy, especially for ACV-resistant strains.
Assuntos
Antivirais/farmacologia , Aspergillus/química , Herpesvirus Humano 1/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Animais , Antivirais/isolamento & purificação , Chlorocebus aethiops , Meios de Cultura , Herpesvirus Humano 1/fisiologia , Humanos , Inibidores da Síntese de Ácido Nucleico/isolamento & purificação , Inibidores da Síntese de Ácido Nucleico/farmacologia , Peptídeos Cíclicos/isolamento & purificação , Proteômica , RNA Viral/biossíntese , Células Vero , Inativação de Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
The outbreak of pneumonia caused by SARS-CoV-2 posed a great threat to global human health, which urgently requires us to understand comprehensively the mechanism of SARS-CoV-2 infection. Angiotensin-converting enzyme 2 (ACE2) was identified as a functional receptor for SARS-CoV-2, distribution of which may indicate the risk of different human organs vulnerable to SARS-CoV-2 infection. Previous studies investigating the distribution of ACE2 mRNA in human tissues only involved a limited size of the samples and a lack of determination for ACE2 protein. Given the heterogeneity among humans, the datasets covering more tissues with a larger size of samples should be analyzed. Indeed, ACE2 is a membrane and secreted protein, while the expression of ACE2 in blood and common blood cells remains unknown. Herein, the proteomic data in HIPED and the antibody-based immunochemistry result in HPA were collected to analyze the distribution of ACE2 protein in human tissues. The bulk RNA-seq profiles from three separate public datasets including HPA tissue Atlas, GTEx, and FANTOM5 CAGE were also obtained to determine the expression of ACE2 in human tissues. Moreover, the abundance of ACE2 in human blood and blood cells was determined by analyzing the data in the PeptideAtlas and the HPA Blood Atlas. We found that the mRNA expression cannot reflect the abundance of ACE2 factor due to the strong differences between mRNA and protein quantities of ACE2 within and across tissues. Our results suggested that ACE2 protein is mainly expressed in the small intestine, kidney, gallbladder, and testis, while the abundance of which in brain-associated tissues and blood common cells is low. HIPED revealed enrichment of ACE2 protein in the placenta and ovary despite a low mRNA level. Further, human secretome shows that the average concentration of ACE2 protein in the plasma of males is higher than those in females. Our research will be beneficial for understanding the transmission routes and sex-based differences in susceptibility of SARS-CoV-2 infection.
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Infecções por Coronavirus/metabolismo , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/metabolismo , Receptores Virais/metabolismo , Enzima de Conversão de Angiotensina 2 , Betacoronavirus , COVID-19 , Bases de Dados de Proteínas , Feminino , Humanos , Imuno-Histoquímica , Masculino , Espectrometria de Massas , Pandemias , Proteômica , RNA Mensageiro/metabolismo , RNA-Seq , SARS-CoV-2 , Distribuição Tecidual , TranscriptomaRESUMO
Conformational exchanges of synthetic macrocyclic acceptors are rather fast, which is rarely studied in the absence of guests. Here, we report multiple stimuli-responsive conformational exchanges between two preexisting conformations of 2,2',4,4'-tetramethoxyl biphen[3]arene (MeBP3) macrocycle. Structures of these two conformations are both observed in solid state, and characterized by 1H NMR, 13C NMR and 2D NMR in solution. In particular, conformational exchanges can respond to solvents, temperatures, guest binding and acid/base addition. The current system may have a role to play in the construction of molecular switches and other stimuli-responsive systems.
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Compostos Macrocíclicos/química , Modelos Moleculares , Conformação Molecular , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Solventes , TemperaturaRESUMO
Microglia, as brain-resident macrophages, are the first line of defense against brain invading pathogens. Further, their dysfunction has been recognized to be closely associated with mounting CNS diseases. Of note, chronic HSV-1 infection leads to the persistent activation of microglia, which elicit a comprehensive response by generating certain factors with neurotoxic and neuroprotective effects. CNS infection with HSV-1 results in herpes simplex encephalitis and herpes simplex keratitis. Microglial immune response plays a crucial role in the development of these diseases. Moreover, HSV-1 infection is strongly associated with several CNS diseases, especially Alzheimer's disease and schizophrenia. These CNS diseases can be effectively ameliorated by eliciting an appropriate immune response, such as inhibition of microglial proliferation and activation. Therefore, it is crucial to reassess the positive and negative roles of microglia in HSV-1 CNS infection for a more comprehensive and detailed understanding of the relationship between microglia and CNS diseases. Hence, the present review focuses on the dual roles of microglia in mediating HSV-1 CNS infection, as well as on the strategy of targeting microglia to ameliorate CNS diseases. Further research in this field can help comprehensively elucidate the dual role of the microglial immune response in HSV-1 CNS infection, providing a theoretical basis for identifying therapeutic targets against overactive microglia in CNS diseases and HSV-1 infection.
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Encefalite por Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Microglia/imunologia , Animais , Encefalite por Herpes Simples/imunologia , Herpesvirus Humano 1/genética , Humanos , Microglia/virologiaRESUMO
Reported here is the highly efficient separation of industrially important cis- and trans-1,2-dichloroethene (cis-DCE and trans-DCE) isomers by activated crystalline 2,2',4,4'-tetramethoxyl biphen[3]arene (MeBP3) materials, MeBP3α. MeBP3 can be synthesized in excellent yield (99 %), and a cyclic pentamer is also obtained when using 1,2-dichloroethane as the solvent. The structure of MeBP3 in the CH3 CN@MeBP3 crystal displays a triangle-shape topology, forming 1D channels through window-to-window packing. Desolvated crystalline MeBP3 materials, MeBP3α, preferentially adsorb cis-DCE vapors over its trans isomer. MeBP3α is able to separate cis-DCE from a 50:50 (v/v) cis/trans-isomer mixture, yielding cis-DCE with a purity of 96.4 % in a single adsorption cycle. Single-crystal structures and powder X-ray diffraction patterns indicate that the uptake of cis-DCE triggers a solid-state structural transformation of MeBP3, suggesting the adaptivity of MeBP3α materials during the sorption process. Moreover, the separation can be performed over multiple cycles without loss of separation selectivity and capacity.