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Self-propelled nanomotors possess strong propulsion and penetration abilities, which can increase the efficiency of cellular uptake of nanoparticles and enhance their cytotoxicity against tumor cells, opening a new path for treating major diseases. In this study, the concept of driving nanomotors by alternately stretching and contracting a temperature-sensitive polymer (TS-P) chain is proposed. The TS-Ps are successfully linked to one side of Cu2-xSe@Au (CS@Au) nanoparticles to form a Janus structure, which is designated as Cu2-xSe@Au-polymer (CS@Au-P) nanomotors. Under near-infrared (NIR) light irradiation, Cu2-xSe nanoparticles generate photothermal effects that change the system temperature, triggering the alternation of the TS-P structure to generate a mechanical force that propels the motion of CS@Au-P nanomotors. The nanomotor significantly improved the cellular uptake of nanoparticles and enhanced their penetration and accumulation in tumor. Furthermore, the exceptional photothermal conversion efficiency of CS@Au-P nanomotors suggests their potential as nanomaterials for photothermal therapy (PTT). The prepared material exhibited good biocompatibility and anti-tumor effects both in vivo and in vitro, providing new research insights into the design and application of nanomotors in tumor therapy.
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Quasi-two-dimensional perovskites have attracted widespread interest in developing low-cost high-quality small lasers. The nano cavity based on topologically protected valley edge states can be robust against special defects. Here, we report a high-quality two-dimensional perovskite topological photonic crystal laser based on the quantum valley Hall effect. By adjusting the position of the air holes relative to the pillar, radiation leakage in topological edge states is reduced to a large extent, electric field distribution becomes more uniform and the quality factor can be as high as 3.6 × 104. Our findings could provide opportunities for the development of high-power, stable perovskite lasers with topological protection.
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Natural redox-regulated channel proteins often utilize disulfide bonds as redox sensors for adaptive regulation of channel conformations in response to diverse physiological environments. In this study, we developed novel synthetic ion channels capable of reversibly switching their ion-transport capabilities by incorporating multiple disulfide bonds into artificial systems. X-ray structural analysis and electrophysiological experiments demonstrated that these disulfide-bridged molecules possess well-defined tubular cavities and can be efficiently inserted into lipid bilayers to form artificial ion channels. More importantly, the disulfide bonds in these molecules serve as redox-tunable switches to regulate the formation and disruption of ion-permeation pathways, thereby achieving a transition in the transmembrane transport process between the ON and OFF states.
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Disulfuros , Canales Iónicos , Transporte Iónico , Oxidación-Reducción , Disulfuros/química , Canales Iónicos/metabolismo , Canales Iónicos/química , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/metabolismo , Modelos Moleculares , Cristalografía por Rayos XRESUMEN
The development of new methods for regio- and stereoselective activation of C-O bonds in ethers holds significant promise for synthetic chemistry, offering advantages in terms of environmental sustainability and economic efficiency. Moreover, the C-N atropisomers represent a fascinating and crucial chiral system, extensively found in natural products, pharmaceutical leads, and the frameworks of advanced materials. In this work, we have introduced a nickel-catalyzed regio- and enantioselective carbon-oxygen arylation reaction for atroposelective synthesis of N-arylisoquinoline-1,3(2H,4H)-diones. The high regioselectivity of C-O cleavage benefits from the high stability of the inâ situ formed (amido)ethenolate via oxidative addition. Additionally, the self-activation of the aryl C-O bond facilitates the reaction under mild conditions, leading to outstanding enantioselectivities. The diverse post-functionalizations of the axially chiral isoquinoline-1,3(2H,4H)-diones further highlighted the utility of this protocol in preparing valuable C-N atropisomers, including the chiral phosphine ligands.
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The systematic treatment of colorectal cancer (CRC) still has room for improvement. The efficacy of chemotherapy, that of anti-vascular therapy, and that of immunotherapy have been unsatisfactory. In recent years, nanomaterials have been used as carriers to improve the bioavailability of anticancer drugs. For the treatment of colorectal cancer, nanodrugs increase the possibility of more precise targeted delivery. However, the actual benefits may cover more aspects. Nanocarriers can produce synergistic effects with anticancer drugs, including the scavenging of reactive oxygen species and co-delivery of a variety of drugs. Currently, immunotherapy has very limited clinical applications in CRC. Modified nanocarriers can activate the immune microenvironment, which can be used for staging antigen recognition or the immune response. Cancer vaccines based on nanomaterials and modified immune checkpoint inhibitors have shown therapeutic potential in animal models. Considering the direct or indirect relationship between the intestinal microflora and CRC, a variety of nanodrugs that regulate microbial function have been explored as an anticancer strategy, and the special structure of microorganisms can also be used as a basis for improving the delivery of traditional nanoparticles (NPs). This review summarizes recent research performed on nanocarriers in in vivo and in vitro models and the synergistic anticancer effects of nanocarriers, focusing on the interaction between NPs and the body, resulting in enhanced efficacy and immune activation. Furthermore, this review describes the current trend of NPs used in the treatment of CRC.
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Antineoplásicos , Neoplasias Colorrectales , Nanopartículas , Animales , Nanomedicina , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Inmunoterapia/métodos , Nanopartículas/química , Neoplasias Colorrectales/tratamiento farmacológico , Microambiente TumoralRESUMEN
BACKGROUND: The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS (125I/131I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with 131I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with 18 F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin. RESULTS: SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when 131I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg 131I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism. CONCLUSION: The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials.
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Fibroínas , Nanopartículas del Metal , Animales , Ratones , Conejos , Ratas , Oro , Tomografía Computarizada por Tomografía de Emisión de Positrones , Arterias , Doxorrubicina/farmacologíaRESUMEN
Gut microbiota dysbiosis plays a crucial role in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD), which may be influenced by nutritional supplementation. Quinoa, a type of pseudocereal, has gained prominence due to its high nutritional value and diverse applications. This study aimed to determine whether yogurt containing quinoa can ameliorate NAFLD and alleviate metabolic disorders by protecting against the divergence of gut microbiota. Our findings suggested that quinoa yogurt could significantly reduce the body weight gain and fat tissue weight of high-fat diet (HFD)-fed obese mice. In addition, quinoa yogurt significantly reduced liver steatosis and enhanced glucose homeostasis and insulin sensitivity. Additional research indicates that quinoa yogurt can reduce the levels of proinflammatory cytokines (i.e., tumor necrosis factor α, IL-1ß, and IL-6) and inhibit endotoxemia and systemic inflammation. The characteristics of the gut microbiota were then determined by analyzing 16S rRNA. In addition, we discovered that the gut microbiota was disturbed by HFD consumption. Particularly, intestinal probiotics and beneficial intestinal secretions were increased, leading to the expression of glucagon-like peptide-1 in the colon, contributing to NAFLD. Furthermore, endotoxemia and systemic inflammation in HFD-fed mice were restored to the level of control mice when they were fed yogurt and quinoa. Therefore, yogurt containing quinoa can effectively alleviate NAFLD symptoms and may exert its effects via microbiome-gut-liver axis mechanisms. According to some research, the role of the enteric-liver axis may also influence metabolic disorders to reduce the development of NAFLD.
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Chenopodium quinoa , Endotoxemia , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/veterinaria , Dieta Alta en Grasa , Endotoxemia/veterinaria , Yogur , ARN Ribosómico 16S/metabolismo , Hígado/metabolismo , Inflamación/metabolismo , Inflamación/veterinaria , Ratones Endogámicos C57BLRESUMEN
Oxygen homeostasis is an important organizing principle for understanding development, physiology, disease, and evolution. Under various physiological and pathological states, organisms experience oxygen deficiency or hypoxia. FoxO4 has been recognized as an important transcriptional regulator involved in a variety of cellular functions, including proliferation, apoptosis, differentiation, and stress resistance, but its role in hypoxia adaptation mechanisms in animals is not so clear. To explore the role of foxO4 in the hypoxia response, we detected the expression of foxO4 and the regulatory relationship between Hif1α and foxO4 under hypoxic conditions. It was found that the expression of foxO4 was up-regulated in ZF4 cells and zebrafish tissues after hypoxia treatment, and Hif1α could directly target the HRE of the foxO4 promoter to regulate foxO4 transcription, indicating that foxO4 was involved in the hypoxia response by the Hif1α-mediated pathway. Furthermore, we obtained foxO4 knockout zebrafish and found that the disruption of foxO4 increased the tolerance to hypoxia. Further research found that the oxygen consumption and locomotor activity of foxO4-/- zebrafish were lower than those of WT zebrafish, as was true for NADH content, NADH/NAD+ rate, and expression of mitochondrial respiratory chain complex-related genes. This suggests that disruption of foxO4 reduced the oxygen demand threshold of the organism, which explained why the foxO4-/- zebrafish were more tolerant to hypoxia than WT zebrafish. These results will provide a theoretical basis for further study of the role of foxO4 in the hypoxia response.
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NAD , Pez Cebra , Animales , Pez Cebra/metabolismo , NAD/metabolismo , Hipoxia/genética , Hipoxia/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Oxígeno/metabolismoRESUMEN
Forming pyridine salts to construct covalent organic cages is an effective strategy for constructing covalent cage compounds. Covalent organic cages based on pyridine salt structures are prone to form water-soluble supramolecular compounds. Herein, we designed and synthesized a triangular prism-shaped hexagonal cage with a larger cavity and relatively flexible conformation. The supramolecular cage structure was also applied to the encapsulation of pyrene and information encryption.
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Pirenos , Piridinas , Cloruro de Sodio , AguaRESUMEN
Fluorescent chemosensors are powerful imaging tools used in a broad range of biomedical fields. However, the application of fluorescent dyes in bioimaging still remains challenging, with small Stokes shifts, interfering signals, background noise, and self-quenching on current microscope configurations. In this work, we reported a supramolecular cage (CA) by coordination-driven self-assembly of benzothiadiazole derivatives and Eu(OTf)3. The CA exhibited high fluorescence with a quantum yield (QY) of 38.57%, good photoluminescence (PL) stability, and a large Stokes shift (153 nm). Furthermore, the CCK-8 assay against U87 glioblastoma cells verified the low cytotoxicity of CA. We revealed that the designed probes could be used as U87 cells targeting bioimaging.
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Colorantes Fluorescentes , MicroscopíaRESUMEN
As an emerging subset of organic complexes, metal complexes have garnered considerable attention owing to their outstanding structures, properties, and applications. In this content, metal-organic cages (MOCs) with defined shapes and sizes provide internal spaces to isolate water for guest molecules, which can be selectively captured, isolated, and released to achieve control over chemical reactions. Complex supramolecules are constructed by simulating the self-assembly behavior of the molecules or structures in nature. For this purpose, massive amounts of cavity-containing supramolecules, such as metal-organic cages (MOCs), have been extensively explored for a large variety of reactions with a high degree of reactivity and selectivity. Because sunlight and water are necessary for the process of photosynthesis, water-soluble metal-organic cages (WSMOCs) are ideal platforms for photo-responsive stimulation and photo-mediated transformation by simulating photosynthesis due to their defined sizes, shapes, and high modularization of metal centers and ligands. Therefore, the design and synthesis of WSMOCs with uncommon geometries embedded with functional building units is of immense importance for artificial photo-responsive stimulation and photo-mediated transformation. In this review, we introduce the general synthetic strategies of WSMOCs and their applications in this sparking field.
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BACKGROUND: There is an ongoing debate if weekend admissions of critically ill patients are associated with higher mortality rates. The current review aimed to specifically assess this effect in sepsis and septic shock patients by comparing mortality rates with weekend versus weekday admissions. METHODS: PubMed, CENTRAL, Scopus, Web of Science, and Embase were searched up to 20th February 2023 with an additional search of Google Scholar for gray literature. RESULTS: Nine studies were eligible. Meta-analysis of all nine studies with data from 1,134,417 patients demonstrated that sepsis or septic shock patients admitted on weekends don't have higher mortality as compared to those admitted on weekdays (OR: 1.04; 95% CI: 1.00, 1.09; p = 0.05; I2 = 93%). On subgroup analysis based on sample size (>2000 or <2000 patients) and timing of mortality, we noted no difference in the significance of the results. However, there was a small significant increased risk of mortality with weekend admission noted in studies on the Asian population and including septic shock patients. CONCLUSION: Weekend admission does not have an adverse impact on mortality rates of sepsis and septic shock patients. Results must be interpreted with caution owing to high interstudy heterogeneity and variation in confounders adjusted by individual studies.
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Sepsis , Choque Séptico , Humanos , Choque Séptico/terapia , Admisión del Paciente , Mortalidad Hospitalaria , Factores de TiempoRESUMEN
Improving the directionality of surface radiation is the key to increase the output power and the differential quantum efficiency of grating-coupled surface-emitting distributed feedback lasers. We proposed a scheme to realize the high directionality of surface radiation. In the structure, the second-order grating is fabricated on the p-side of the epitaxial wafer. A SiO2/Si3N4 multilayer reflector arranged above the grating is used to redirect the upward-diffracted beam. The design of the intermediate layer between the grating and the reflector is an important part of achieving high directionality, because the adjustment of its thickness can be used to phase the redirected light with the downward-diffracted light. The calculation results show that the directionality of this structural scheme can reach more than 98% which meets the device requirements. This design provides a reference for surface-emitting distributed feedback lasers with high performance and high stability.
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A novel, to the best of our knowledge, broad-area distributed feedback laser with high-order surface curved gratings has been fabricated based on standard near ultraviolet lithography. The characteristics of increasing output power and mode selection are achieved simultaneously by using a broad-area ridge as well as an unstable cavity structure composed of curved gratings and a high-reflectivity coated rear facet. Suppression of high-order lateral modes is realized by setting current injection/non-injection regions and asymmetric waveguides. This DFB laser emitting around 1070â nm has achieved a spectral width of 0.138â nm and a maximum output power of 915â mW kink-free optical power. The threshold current and side-mode suppression ratio of the device are 370â mA and 33â dB, respectively. The simple manufacturing process and stable performance give this high-power laser broad application prospects in the fields of light detection and ranging, laser pumps, optical disk access, etc.
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Herein, we report a novel strategy for diversity-oriented lysine modification of cyclic peptides based on the orthogonal alkylation of the lysine residues. All steps can be achieved in the solid phase with satisfying conversions. Notably, we demonstrated that the tether modification could help to improve the cellular uptake of peptides.
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Lisina , Péptidos Cíclicos , Lisina/química , Péptidos/química , Péptidos Cíclicos/químicaRESUMEN
High-order surface grating distributed feedback lasers are known to operate with a fundamental mode, narrow linewidth, high power, and high slope efficiency. The adoption of high-order surface gratings can avoid epitaxial re-growth necessary for the fabrication of conventional buried gratings, which simplifies the fabrication process and reduces device cost. It is essential for the design and optimization of device structure to clarify the influence of the change of grating structure parameters on grating characteristics (coupling and loss). Based on Lumerical's Mode Solutions and multiple grating samples, we evaluated the coupling and loss coefficients of surface gratings as a function of duty cycle, order, and V-groove topography. As the order increases, the duty cycle corresponding to the peak value of the grating coupling coefficient increases gradually and approaches one. The grating coupling coefficient decreases with increasing order but increases at some specific orders. At high duty cycles, the width of the grating groove corresponding to the peak of the coupling coefficient remains substantially in the range of 100-150 nm, which is close to the length of a quarter-wavelength in the grating groove filling material. Regarding the grating groove morphology, the fabrication difficulty of the V-shaped groove grating is obviously less than that of the rectangular groove grating, but its coupling coefficient is slightly smaller than that of the rectangular shaped groove grating of the same depth. The larger the V-shaped groove width, the smaller the peak coupling coefficient and the corresponding sidewall inclination will be. Losses decrease with increasing duty cycle and decreasing sidewall inclination of the V-groove.
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A self-powered ultraviolet (UV) photodetector (PD) with a position-controlled array based on zinc oxide (ZnO) nanoclusters (NCs) has been proposed. The structure of the special array makes it possible to reduce the light loss and improve the light trap. The PD innovatively modifies the structure of ZnO PDs, which is distinguished from other traditional devices. The results demonstrate that the ZnO NC array can spontaneously generate the carrier and successfully achieve the detection at zero bias under the radiation of UV light. In this study, the structure is fabricated with two different substrates of silicon (Si) and GaN. At zero bias voltage, the Si-based PD under 365 nm shows the responsivity and external quantum efficiency (EQE) reaching up to 14.1 mA/W and 4.79%, respectively, and the responsivity of the GaN-based detector can be obtained up to 59.9 mA/W; its parameter of EQE is 20.04%, the photocurrent is 10-5A, and the on/off ratio is 174. Our findings indicate that this structure of the device has potential for applications that require detection of light.
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In recent years, incredible endeavors have been devoted to the design and self-assembly of discrete metal-organic cages (MOCs) with expanding intricacy and functionality. The controlled synthesis of metal-organic supramolecular cages with large branched chains remains an interesting and challenging work in supramolecular chemistry. Herein, a tetrahedral metal-organic supramolecular cage (ZnII4L4) containing 12 dendritic carbazole arms is unprecedentedly constructed through coordination-driven subcomponent self-assembly and characterized in different ways. Interestingly, tetrahedral supramolecular Cage-1 exhibited the potential for aggregation-induced emission (AIE) performance and stimulus-responsive luminescence features, and it achieved color-tunable photoluminescence due to the introduction of dendritic carbazole arms. Crucially, owing to the great photophysical properties of Cage-1 in solution, Cage-1 was enabled to act as a fluorescent ink for the vapor-responsive recording and wiping of information.
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Carbazoles , Colorantes , Gases , Luminiscencia , MetalesRESUMEN
We report that the pincer nickel complexes display prostate cancer antitumor properties through inhibition of cell proliferation. Notably, they display better antitumor properties than cisplatin. Mechanistic studies reveal that these pincer nickel complexes trigger cell apoptosis, most likely due to cell cycle arrest. Interestingly, these complexes also inhibit androgen receptor (AR) and prostate-specific antigen (PSA) signaling, which are critical for prostate cancer survival and progression. Our study reveals a novel function of pincer nickel complexes as potential therapeutic drugs in prostate cancer.
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Antineoplásicos , Neoplasias de la Próstata , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Humanos , Masculino , Níquel , Pelvis/patología , Neoplasias de la Próstata/patologíaRESUMEN
A NaOH-mediated sustainable synthesis of functionalized quinoxalines is disclosed via redox condensation of o-nitroamines with diols and α-hydroxy ketones. Under optimized conditions, various o-nitroamines and alcohols are well tolerated to generate the desired products in 44-99% yields without transition metals and external redox additives.