RESUMEN
Nonlinear wave-matter interactions may give rise to solitons, phenomena that feature inherent stability in wave propagation and unusual spectral characteristics. Solitons have been created in a variety of physical systems and have had important roles in a broad range of applications, including communications, spectroscopy and metrology1-4. In recent years, the realization of dissipative Kerr optical solitons in microcavities has led to the generation of frequency combs in a chip-scale platform5-10. Within a cavity, photons can interact with mechanical modes. Cavity optomechanics has found applications for frequency conversion, such as microwave-to-optical or radio-frequency-to-optical11-13, of interest for communications and interfacing quantum systems operating at different frequencies. Here we report the observation of mechanical micro-solitons excited by optical fields in an optomechanical microresonator, expanding soliton generation in optical resonators to a different spectral window. The optical field circulating along the circumference of a whispering gallery mode resonator triggers a mechanical nonlinearity through optomechanical coupling, which in turn induces a time-varying periodic modulation on the propagating mechanical mode, leading to a tailored modal dispersion. Stable localized mechanical wave packets-mechanical solitons-can be realized when the mechanical loss is compensated by phonon gain and the optomechanical nonlinearity is balanced by the tailored modal dispersion. The realization of mechanical micro-solitons driven by light opens up new avenues for optomechanical technologies14 and may find applications in acoustic sensing, information processing, energy storage, communications and surface acoustic wave technology.
RESUMEN
The binding of tumor necrosis factor-like cytokine 1A (TL1A) to death receptor 3 (DR3) plays an important role in the interaction between dendritic cells (DCs) and T cells and contributes to intestinal inflammation development. However, the mechanism by which DCs expressing TL1A mediate helper T (Th) cell differentiation in the intestinal lamina propria (LP) during the pathogenesis of inflammatory bowel disease remains unclear. In this study, we found that TL1A/DR3 promoted Th1 and Th17 cell differentiation in T-T and DC-T cell interaction-dependent manners. TL1A-deficient CD4+ T cells failed to polarize into Th1/Th17 cells and did not cause colonic inflammation in a T cell transfer colitis model. Notably, TL1A was located in the cytoplasm and nuclei of DCs, positively regulated the DC-specific ICAM-grabbing nonintegrin/RAF1/nuclear factor κB signaling pathway, enhanced the antigen uptake ability of DCs, and promoted TLR4-mediated DC activation, inducing naive CD4+ T cell differentiation into Th1 and Th17 cells. Our work reveals that TL1A plays a regulatory role in inflammatory bowel disease pathogenesis.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Humanos , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/genética , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Miembro 25 de Receptores de Factores de Necrosis Tumoral/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Inflamación/metabolismo , Factor de Necrosis Tumoral alfaRESUMEN
The C-F bond is the strongest covalent single bond (126 kcal/mol) in carbon-centered bonds, in which the highest electronegativity of fluorine (χ = 4) gives rise to the shortest bond length (1.38 Å) and the smallest van der Waals radius (rw = 1.47 Å), resulting in enormous challenges for activation and transformation. Herein, C-F conversion was realized via photouranium-catalyzed hydroxylation of unactivated aryl fluorides using water as a hydroxyl source to deliver multifunctional phenols under ambient conditions. The activation featured cascade sequences of single electron transfer (SET)/hydrogen atom transfer (HAT)/oxygen atom transfer (OAT), highly integrated from the excited uranyl cation. The *UO22+ prompted water splitting under mild photoexcitation, caging the active oxygen in a peroxo-bridged manner for the critical OAT process and releasing hydrogen via the HAT process.
RESUMEN
Autism spectrum disorder (ASD) is a group of neurodevelopment disorders characterized by deficits in social interaction and communication, and repetitive or stereotyped behavior. Autistic children are more likely to have vision problems, and ASD is unusually common among blind people. However, the mechanisms behind the vision disorders in autism are unclear. Stabilizing WNT-targeted scaffold protein Axin2 by XAV939 during embryonic development causes overproduction of cortical neurons and leads to autistic-like behaviors in mice. In this study, we investigated the relationship between vision abnormality and autism using an XAV939-induced mouse model of autism. We found that the mice receiving XAV939 had decreased amplitude of bright light-adaptive ERG. The amplitudes and latency of flash visual evoked potential recorded from XAV939-treated mice were lower and longer, respectively than in the control mice, suggesting that XAV939 inhibits visual signal processing and conductance. Anatomically, the diameters of RGC axons were reduced when Axin2 was stabilized during the development, and the optic fibers had defective myelin sheaths and reduced oligodendrocytes. The results suggest that the WNT signaling pathway is crucial for optic nerve development. This study provides experimental evidence that conditions interfering with brain development may also lead to visual problems, which in turn might exaggerate the autistic features in humans.
Asunto(s)
Proteína Axina , Modelos Animales de Enfermedad , Potenciales Evocados Visuales , Nervio Óptico , Animales , Proteína Axina/metabolismo , Ratones , Potenciales Evocados Visuales/fisiología , Nervio Óptico/metabolismo , Nervio Óptico/patología , Electrorretinografía , Ratones Endogámicos C57BL , Axones/patología , Células Ganglionares de la Retina/patología , Células Ganglionares de la Retina/metabolismo , Masculino , Vía de Señalización Wnt/fisiología , Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/metabolismo , Trastorno Autístico/fisiopatología , Trastorno Autístico/metabolismoRESUMEN
The nanomaterialization of traditional Chinese medicine (TCM) has aroused widespread interest among researchers. Sanguinarine (SAN) is a kind of TCM with good antibacterial properties, which has important applications in anti-infection of wounds. Additionally, the combination of photothermal therapy and chemotherapy can overcome bacterial resistance, further improving bactericidal and wound healing efficiency. In this paper, we prepared an antibacterial agent by loading SAN on the zwitterion-modified MXene quantum dot nanocarrier (SAN@AHEP@Ta4C3), realizing pH/NIR controlled drug release and photothermal/chemotherapy synergistic antibacterial and wound healing. The particle size of SAN@AHEP@Ta4C3 is about 120 nm, and it has a good water solubility and stability. In addition, it also has excellent photothermal conversion performance (η = 39.2%), which can effectively convert light energy into heat energy under near-infrared (NIR) laser irradiation, further promoting drug release and achieving bactericidal effects by synergistic chemotherapy and photothermal therapy. The in vitro and in vivo experiments show that SAN@AHEP@Ta4C3 exhibits an excellent antibacterial effect against Staphylococcus aureus and Escherichia coli, and it can effectively promote the wound healing of mice. Moreover, the SAN@AHEP@Ta4C3 also has good biocompatibility and has no side effects on normal tissue and organs. This work introduces a multifunctional antibacterial agent based on TCM and hot-spot material MXene, which will have considerable application prospects in biomedical fields.
Asunto(s)
Antibacterianos , Benzofenantridinas , Portadores de Fármacos , Escherichia coli , Isoquinolinas , Puntos Cuánticos , Staphylococcus aureus , Cicatrización de Heridas , Antibacterianos/farmacología , Antibacterianos/química , Cicatrización de Heridas/efectos de los fármacos , Puntos Cuánticos/química , Staphylococcus aureus/efectos de los fármacos , Animales , Benzofenantridinas/química , Benzofenantridinas/farmacología , Escherichia coli/efectos de los fármacos , Ratones , Portadores de Fármacos/química , Isoquinolinas/química , Isoquinolinas/farmacología , Medicina Tradicional China , Terapia Fototérmica , Liberación de Fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
In recent years, nanocarrier-based pesticide delivery systems have provided new possibilities for the efficient utilization of pesticides. In this research, we developed a hydroxypropyl-ß-cyclodextrin-modified graphene oxide (GO-HP-ß-CD) nanocarrier for pyraclostrobin (Pyr) delivery and studied its application for tobacco target spot disease control. GO-HP-ß-CD has excellent pesticide-loading performance for Pyr (adsorption capacity of 1562.5 mg/g) and good water dispersibility and stability. Besides, GO-HP-ß-CD shows pH-responsive release performance. In addition, GO-HP-ß-CD also has better leaf affinity than Pyr, and it can effectively adhere to the leaf surface after simulated washing. The results of antifungal experiments indicate that GO-HP-ß-CD-Pyr has a good preventive effect on tobacco target spot disease, and its EC50 value is 0.384 mg/L, which is lower than Pyr. Specifically, this nanopesticide formulation does not contain toxic organic solvent or additive, so it has good environmental friendliness. Therefore, we believe that the GO-HP-ß-CD-Pyr nanopesticide has brilliant potential in the prevention and control of tobacco diseases.
Asunto(s)
Grafito , Nicotiana , Estrobilurinas , Grafito/química , Nicotiana/química , Estrobilurinas/química , Antifúngicos/química , Antifúngicos/farmacología , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiología , Carbamatos/química , Portadores de Fármacos/química , Plaguicidas/química , beta-Ciclodextrinas/química , Fungicidas Industriales/química , Fungicidas Industriales/farmacologíaRESUMEN
Pesticides play a crucial role in ensuring food production and food security. Conventional pesticide formulations can not meet the current needs of social and economic development, and they also can not meet the requirements of green agriculture. Therefore, there is an urgent need to develop efficient, stable, safe, and environmentally friendly pesticide formulations to gradually replace old formulations which have high pollution and low efficacy. The rise of nanotechnology provides new possibilities for innovation in pesticide formulations. Through reasonable design and construction of an environmentally friendly pesticide delivery system (PDS) based on multifunctional nanocarriers, the drawbacks of conventional pesticides can be effectively solved, realizing a water-based, nanosized, targeted, efficient, and safe pesticide system. In the past five years, researchers in chemistry, materials science, botany, entomology, plant protection, and other fields are paying close attention to the research of nanomaterials based PDSs and nanopesticide formulations and have made certain research achievements. These explorations provide useful references for promoting the innovation of nanopesticides and developing a new generation of green and environmentally friendly pesticide formulations. This Perspective summarizes the recent advances of nanomaterials in PDSs and nanopesticide innovation, aiming to provide useful guidance for carrier selection, surface engineering, controlled release conditions, and application in agriculture.
Asunto(s)
Agricultura , Nanoestructuras , Nanotecnología , Plaguicidas , Plaguicidas/química , Nanoestructuras/química , Nanotecnología/métodos , Agricultura/métodosRESUMEN
Polarization of optical fields is a crucial degree of freedom in the all-optical analogue of electromagnetically induced transparency (EIT). However, the physical origins of EIT and polarization-induced phenomena have not been well distinguished, which can lead to confusion in associated applications such as slow light and optical/quantum storage. Here we study the polarization effects in various optical EIT systems. We find that a polarization mismatch between whispering gallery modes in two indirectly coupled resonators can induce a narrow transparency window in the transmission spectrum resembling the EIT lineshape. However, such polarization-induced transparency (PIT) is distinct from EIT: It originates from strong polarization rotation effects and shows a unidirectional feature. The coexistence of PIT and EIT provides additional routes for the manipulation of light flow in optical resonator systems.
RESUMEN
As "chemical chameleons," organosulfones have been widely applied in various desulfonylative functionalization reactions. However, the desulfonylative functionalization of (hetero)arylsulfones through the cleavage of inert C(sp2)-SO2 bonds remains a challenging and underexplored task. Over the past twenty years, the use of (hetero)arylsulfones as arylation reagents has gradually gained attention in diverse cross-coupling reactions under specific catalytic conditions, especially in transition metal-catalysis and photocatalysis chemistry. In this review, we discuss the representative accomplishments and mechanistic insights achieved in desulfonylative reactions of inactive C(sp2)-SO2 bonds in (hetero)arylsulfones, including: (i) transition-metal-catalyzed desulfonylative cross-coupling reactions and (ii) photo-/electrocatalytic radical desulfonylative coupling reactions. We anticipate that this review will provide an overall perspective in this area to a general audience of researchers and stimulate further innovative strategies for desulfonylative functionalization of inert arylsulfones.
RESUMEN
Polysulfides are significant compounds in life science, pharmaceutical science, and materials science. Therefore, polysulfide construction is in great demand. The controllable sequential installation of groups on both ends of a S-S motif faces an enormous challenge owing to the reversible nature of the covalent S-S bond. A library was established with two divergent mask groups for bilateral unsymmetrical disulfurating reagents (R1O-SS-SO2R2). Sequential coupling with preferential activation of the S-SO2 bond (37.6â kcal/mol) and controllable activation of the S-O bond (54.8â kcal/mol) in the presence of the S-S bond (62.0â kcal/mol) enabled successive reactions at each end of the S-S motif to afford unsymmetrical disulfides and trisulfides, even for the cross-linkage of natural products, pharmaceuticals, peptides, and a protein (bovine serum albumin).
RESUMEN
Sulfur(VI)-fluoride exchange linkage as a next generation of click chemistry was introduced by Sharpless and coworkers in 2014. Distinguished from CuAAC, the SuFEx reaction proceeds under metal-free conditions, and the reactive linkers are variable, enabling access to a diverse class of linkage compounds. Therein, a series of SuFEx linkers emerged has been widely prevalent in diverse fields. The SVI -F bond in comparison to SVI -Cl bond features excellent stability and chemoselectivity. The linkage chemistry primarily involves the formation of S-O and S-N bonds via commercially available phenols and amines, yet less study on C-SuFEx linkage. This review will focus on three types of linkage for SuFEx linkers comprising S-O, S-N, and S-C bonds, and we hope to provide a practical guidance for SuFEx linkage chemistry.
Asunto(s)
Fluoruros , Fluoruros/química , Química Clic , Azufre/química , Polímeros/química , Nitrógeno/químicaRESUMEN
Nanoparticles with visual imaging capabilities and synergistic therapeutics have a bright future in antitumor applications. However, most of the current nanomaterials lack multiple imaging-guided therapeutic capabilities. In this study, a novel enhanced photothermal photodynamic antitumor nanoplatform with photothermal imaging, fluorescence (FL) imaging, and MRI-guided therapeutic capabilities was constructed by grafting gold, dihydroporphyrin Ce6, and Gd onto α-iron trioxide. This antitumor nanoplatform can convert NIR light into local hyperthermia at a temperature of up to 53 °C under NIR light irradiation, while Ce6 can generate singlet oxygen, which further synergizes the tumor-killing effect. At the same time, α-Fe2O3@Au-PEG-Ce6-Gd can also have significant photothermal imaging effect under light irradiation, which can guide to see the temperature change near the tumor tissue. It is worth noting that α-Fe2O3@Au-PEG-Ce6-Gd can have obvious MRI and FL imaging effects after tail vein injection in mice with blood circulation, realizing imaging-guided synergistic antitumor therapy. α-Fe2O3@Au-PEG-Ce6-Gd NPs provide a new solution for tumor imaging and treatment.
Asunto(s)
Nanopartículas , Fotoquimioterapia , Animales , Ratones , Línea Celular Tumoral , Peróxido de Hidrógeno , Imagen Multimodal , Oxigenadores , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes , Fototerapia/métodosRESUMEN
Background: Immunotherapy shows promise in treating cancer by leveraging the immune system to combat cancer cells. However, the influence of crotonylation metabolism on the prognosis and tumor environment in ccRCC patients is not fully understood. Methods: We conducted various systematic analyses, including prognosis and cluster analyses, to investigate the role of KAT2A in immunotherapy. We used qRT-PCR to compare KAT2A expression in cancer and adjacent tissues and among different cell lines. Additionally, we employed Cell Counting Kit-8, wound healing, and Transwell chamber assays to assess changes in the proliferative and metastatic ability of A498 and 786-O cells. Results: We identified three clusters related to crotonylation metabolism, each with distinct prognosis and immune characteristics in ccRCC. We categorized CT1 as immune-inflamed, CT2 as immune-excluded, and CR3 as immune-desert. A new system, CRS, emerged as an effective predictor of patient outcomes with differing immune characteristics. Moreover, qRT-PCR revealed elevated KAT2A levels in ccRCC tissues and cell lines. KAT2A was found to promote ccRCC and correlate significantly with immunosuppressive elements and checkpoints. Reducing KAT2A expression hindered ccRCC cell growth and metastasis. Conclusion: Our study highlights the critical role of crotonylation metabolism in cancer development and progression, particularly its link to poor prognosis. CRS proves to be an accurate predictor of patient outcomes and immune features in ccRCC. KAT2A shows strong associations with clinical factors and the immunosuppressive environment, suggesting potential for innovative immunotherapies in ccRCC treatment.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Inmunosupresores , Reacción en Cadena de la Polimerasa , PronósticoRESUMEN
AIM: Recurrent vulvovaginal candidiasis (RVVC) is a chronic, difficult to treat vaginal infection, caused by Candida species, which affects women of all ages and ethnic and social background. Most RVVC studies use animal models, and there is still a lack of observation on human tissue samples and effective therapy to reduce recurrence. MATERIALS AND METHODS: We observed CD163+ macrophages and NLRP3 expression by immunohistochemistry, also investigated bacteria and fungi co-invasion by fluorescence in situ hybridization from 144 human vaginal biopsy tissues (48 RVVC, 48 VVC, 48 healthy volunteers), and we also explored the effect of combining metronidazole in the treatment of RVVC. RESULTS: A large number of neutrophils, lymphocytes and plasma cells infiltrated the mucosa, basement membrane and submucosa, accompanied by significantly overexpressed NLRP3 inflammasome. While CD163+ macrophages often infiltrated under the basement membrane in patients with RVVC, 29.2% of cases were found Gardnerella and fungi jointly invaded the vaginal mucosas. RVVC vaginal mucosal histopathology revealed mucosal inflammatory responses dominated by neutrophils, which may involve activation of NLRP3 and immune tolerance of M2 macrophages (CD163+ ). Fluconazole combined with metronidazole can achieve higher efficiency (95.8% vs. 70.8%) and reduce the recurrence rate more (8.3% vs. 37.5%) at 6-month follow-up. CONCLUSION: Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in RVVC. The combined medication will need to further evaluate in future.
Asunto(s)
Candidiasis Vulvovaginal , Humanos , Femenino , Candidiasis Vulvovaginal/etiología , Metronidazol , Hibridación Fluorescente in Situ , Proteína con Dominio Pirina 3 de la Familia NLR , Membrana MucosaRESUMEN
Sulfur-containing compounds have attracted considerable interest due to their wide-ranging applications in pharmaceuticals, agriculture, natural products, and organic materials. The development of efficient and rapid methods for the construction and transformation of sulfur-containing compounds is of great importance. Since nickel is inexpensive and has a variety of valence states, strong nucleophilicity and low energy barriers for oxidative addition, the construction and transformation of sulfur-containing compounds by nickel-catalyzed cross-coupling have become important strategies. In addition, sulfur-containing compounds have also been playing increasingly important roles in the field of cross-coupling due to their thermodynamically stable but dynamic activity. This review will focus on nickel-catalyzed construction and transformation of various sulfide-containing compounds, such as sulfides, disulfides, and hypervalent sulfur-containing compounds.
Asunto(s)
Productos Biológicos , Níquel , Catálisis , Disulfuros , Níquel/química , Preparaciones Farmacéuticas , Sulfuros/química , Azufre/química , Compuestos de AzufreRESUMEN
Diesel vehicles have caused serious environmental problems in China. Hence, the Chinese government has launched serious actions against air pollution and imposed more stringent regulations on diesel vehicle emissions in the latest China VI standard. To fulfill this stringent legislation, two major technical routes, including the exhaust gas recirculation (EGR) and high-efficiency selective catalytic reduction (SCR) routes, have been developed for diesel engines. Moreover, complicated aftertreatment technologies have also been developed, including use of a diesel oxidation catalyst (DOC) for controlling carbon monoxide (CO) and hydrocarbon (HC) emissions, diesel particulate filter (DPF) for particle mass (PM) emission control, SCR for the control of NOx emission, and an ammonia slip catalyst (ASC) for the control of unreacted NH3. Due to the stringent requirements of the China VI standard, the aftertreatment system needs to be more deeply integrated with the engine system. In the future, aftertreatment technologies will need further upgrades to fulfill the requirements of the near-zero emission target for diesel vehicles.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Emisiones de Vehículos/prevención & control , Emisiones de Vehículos/análisis , Contaminación del Aire/prevención & control , Contaminación del Aire/análisis , Catálisis , China , Gasolina , Material Particulado/análisis , Vehículos a MotorRESUMEN
A disulfide click strategy is disclosed for stapling to enhance the metabolic stability and cellular permeability of therapeutic peptides. A 17-membered library of stapling reagents with adjustable lengths and angles was established for rapid double/triple click reactions, bridging S-terminal peptides from 3 to 18 amino acid residues to provide 18- to 48-membered macrocyclic peptides under biocompatible conditions. The constrained peptides exhibited enhanced anti-HCT-116 activity with a locked α-helical conformation (IC50 =6.81â µM vs. biological incompetence for acyclic linear peptides), which could be unstapled for rehabilitation of the native peptides under the assistance of tris(2-carboxyethyl)phosphine (TCEP). This protocol assembles linear peptides into cyclic peptides controllably to retain the diverse three-dimensional conformations, enabling their cellular uptake followed by release of the disulfides for peptide delivery.
Asunto(s)
Disulfuros , Péptidos , Disulfuros/química , Péptidos/química , Péptidos Cíclicos , Aminoácidos , Conformación MolecularRESUMEN
Thioamide peptides were synthesized in a straightforward one-pot process via the linkage of diverse natural amino acids in the presence of thiolphosphonate and trichlorosilane, wherein carbonyl groups were replaced with thiono compounds with minimal racemization. Experimental and computational mechanistic studies demonstrated that the trichlorosilane enables the activation of carboxylic acids via intense interactions with the Si-O bond, followed by coupling of the carboxylic acids with thiolphosphonate to obtain the key intermediate S-acyl dithiophosphate. Silyl-activated quadrangular metathesis transition states afforded the thioamide peptides. The potential applications of these thioamide peptides were further highlighted via late-stage linkages of diverse natural products and pharmaceutical drugs and the thioamide moiety.
Asunto(s)
Aminoácidos , Tioamidas , Tioamidas/química , Péptidos/química , Aminas , Ácidos CarboxílicosRESUMEN
Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus worldwide. However, whether and how HHV-6 infection influences the metabolic machinery of the host cell to provide the energy and biosynthetic resources for virus propagation remains unknown. In this study, we identified that HHV-6A infection promotes glucose metabolism in infected T cells, resulting in elevated glycolytic activity with an increase of glucose uptake, glucose consumption and lactate secretion. Furthermore, we explored the mechanisms involved in HHV-6A-mediated glycolytic activation in the infected T cells. We found increased expressions of the key glucose transporters and glycolytic enzymes in HHV-6A-infected T cells. In addition, HHV-6A infection dramatically activated AKT-mTORC1 signaling in the infected T cells and pharmacological inhibition of mTORC1 blocked HHV-6A-mediated glycolytic activation. We also found that direct inhibition of glycolysis by 2-Deoxy-D-glucose (2-DG) or inhibition of mTORC1 activity in HHV-6A-infected T cells effectively reduced HHV-6 DNA replication, protein synthesis and virion production. These results not only reveal the mechanism of how HHV-6 infection affects host cell metabolism, but also suggest that targeting the metabolic pathway could be a new avenue for HHV-6 therapy.