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Electrocatalytic nitrogen reduction is a challenging process that requires achieving high ammonia yield rate and reasonable faradaic efficiency. To address this issue, this study developed a catalyst by in situ anchoring interfacial intergrown ultrafine MoO2 nanograins on N-doped carbon fibers. By optimizing the thermal treatment conditions, an abundant number of grain boundaries were generated between MoO2 nanograins, which led to an increased fraction of oxygen vacancies. This, in turn, improved the transfer of electrons, resulting in the creation of highly active reactive sites and efficient nitrogen trapping. The resulting optimal catalyst, MoO2/C700, outperformed commercial MoO2 and state-of-the-art N2 reduction catalysts, with NH3 yield and Faradic efficiency of 173.7 µg h-1 mg-1cat and 27.6%, respectively, under - 0.7 V vs. RHE in 1 M KOH electrolyte. In situ X-ray photoelectron spectroscopy characterization and density functional theory calculation validated the electronic structure effect and advantage of N2 adsorption over oxygen vacancy, revealing the dominant interplay of N2 and oxygen vacancy and generating electronic transfer between nitrogen and Mo(IV). The study also unveiled the origin of improved activity by correlating with the interfacial effect, demonstrating the big potential for practical N2 reduction applications as the obtained optimal catalyst exhibited appreciable catalytic stability during 60 h of continuous electrolysis. This work demonstrates the feasibility of enhancing electrocatalytic nitrogen reduction by engineering grain boundaries to promote oxygen vacancies, offering a promising avenue for efficient and sustainable ammonia production.
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GPR34 is a functional G-protein-coupled receptor of Lysophosphatidylserine (LysoPS), and has pathogenic roles in numerous diseases, yet remains poorly targeted. We herein report a cryo-electron microscopy (cryo-EM) structure of GPR34 bound with LysoPS (18:1) and Gi protein, revealing a unique ligand recognition mode with the negatively charged head group of LysoPS occupying a polar cavity formed by TM3, 6 and 7, and the hydrophobic tail of LysoPS residing in a lateral open hydrophobic groove formed by TM3-5. Virtual screening and subsequent structural optimization led to the identification of a highly potent and selective antagonist (YL-365). Design of fusion proteins allowed successful determination of the challenging cryo-EM structure of the inactive GPR34 complexed with YL-365, which revealed the competitive binding of YL-365 in a portion of the orthosteric binding pocket of GPR34 and the antagonist-binding-induced allostery in the receptor, implicating the inhibition mechanism of YL-365. Moreover, YL-365 displayed excellent activity in a neuropathic pain model without obvious toxicity. Collectively, this study offers mechanistic insights into the endogenous agonist recognition and antagonist inhibition of GPR34, and provides proof of concept that targeting GPR34 represents a promising strategy for disease treatment.
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Inibição Psicológica , Neuralgia , Humanos , Microscopia Crioeletrônica , Ligação CompetitivaRESUMO
Nanoparticle sintering has long been a major challenge in developing catalytic systems for use at elevated temperatures. Here we report an in situ electron microscopy study of the extraordinary sinter resistance of a catalytic system comprised of sub-2 nm Pt nanoparticles on a Se-decorated carbon support. When heated to 700 °C, the average size of the Pt nanoparticles only increased from 1.6 to 2.2 nm, while the crystal structure, together with the {111} and {100} facets, of the Pt nanoparticles was well retained. Our electron microscopy analyses suggested that the superior resistance against sintering originated from the Pt-Se interaction. Confirmed by energy-dispersive X-ray elemental mapping and electron energy loss spectra, the Se atoms surrounding the Pt nanoparticles could survive the heating. This work not only offers an understanding of the physics behind the thermal behavior of this catalytic material but also sheds light on the future development of sinter-resistant catalytic systems.
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Cuproptosis, a copper-dependent cell death process, has been confirmed to further activate the immune response and mediate the immune resistance. However, hypoxic tumor microenvironment hampers cuproptosis sensitivity and suppresses the body's antitumor immune response. Herein, we have successfully immobilized and functionalized catalase (CAT) with long single-stranded DNA containing polyvalent CpG sequences through rolling circle amplification (RCA) techniques, obtaining an enzyme-cored spherical nucleic acid nanoplatform (CAT-ecSNA-Cu) to deliver copper ions for cuproptosis. The presence of long-stranded DNA-protected CAT enhances mitochondrial respiration by catalyzing the conversion of H2O2 to O2, thereby sensitizing cuproptosis. Meanwhile, increased tumor oxygenation suppresses the expression of the hypoxia-inducible factor-1 (HIF-1) protein, resulting in the alleviation of the immunosuppressive tumor microenvironment. Of note, cuproptosis induces immunogenic cell death (ICD), which facilitates dendritic cell (DC) maturation and enhances antigen presentation through polyCpG-supported Toll-like receptor 9 (TLR9) activation. Furthermore, cuproptosis-induced PD-L1 upregulation in tumor cells complements checkpoint blockers (αPD-L1), enhancing antitumor immunity. The strategy of enhancing cuproptosis-mediated antitumor immune responses by alleviating hypoxia effectively promotes the activation and proliferation of effector T cells, ultimately leading to long-term immunity against cancer.
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Catalase , Cobre , Hipóxia Tumoral , Hipóxia Tumoral/efeitos dos fármacos , Animais , Cobre/química , Catalase/metabolismo , Catalase/química , Camundongos , Microambiente Tumoral/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Morte Celular Imunogênica/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacosRESUMO
Excessive sulfite usage in food and pharmaceutical production causes respiratory and neurological diseases, underscoring the need for a sensitive and rapid quantification strategy. The portable sensing platform based on a luminescent hydrogel sensor is a powerful tool for the on-site, real-time detection of sulfite ions. However, the lack of recyclability in almost all reaction-based hydrogel sensors increases the application cost. This study constructed a reversible and upconversion nanoprobe combining upconversion nanoparticles (UCNPs) and pararosaniline (PAR) for sulfite detection. The upconversion nanoprobe was further encapsulated in a three-dimensional polyacrylamide hydrogel matrix to create a background-free, reversible hydrogel sensor. The near-infrared excitation of UCNPs avoids the autofluorescence in the hydrogel and real samples. Meanwhile, PAR serves as a specific recognition unit for sulfite ions. After the addition of sulfites, a specific reaction occurs between PAR and sulfites, leading to the recovery of characteristic emission at 540 nm, achieving sensitive detection of sulfite ions. Importantly, this specific reaction is reversible under thermal treatment, allowing the hydrogel sensor to return to its initial state and thus enabling reversible detection of sulfite ions. Furthermore, a portable sensing platform is developed to realize point-of-care, real-time quantitative detection of sulfite ions. The proposed upconversion reversible hydrogel sensor provides a new sensing strategy for the detection of hazardous substances in food and offers new insights into the preparation of reversible, highly sensitive hydrogel sensors.
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Hidrogéis , Nanopartículas , Corantes de Rosanilina , Toluidinas , Alimentos , Luminescência , SulfitosRESUMO
The synthesis of stable polynitrogen compounds with high-energy density has long been a major challenge. The cyclo-pentazolate anion (cyclo-N5 -) is successfully converted into aromatic and structurally symmetric bipentazole (N10) via electrochemical synthesis using highly conductive multi-walled carbon nanotubes (MWCNTs) as the substrate and sodium pentazolate hydrate ([Na(H2O)(N5)]·2H2O) as the raw material. Attenuated total refraction Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and density functional theory calculations confirmed the structure and homogeneous distribution of N10 in the sidewalls of the MWCNTs (named MWCNT-N10-n m). The MWCNT-N10-2.0 m is further used as a catalyst for electrochemical oxygen reduction to synthesize hydrogen peroxide from oxygen with a two-electron selectivity of up to 95%.
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Under the high current density, the excessive strong adsorption of H* intermediates and H2 accumulation the catalysts are the major obstacle to the industrial application of hydrogen evolation reaction (HER) catalysts. Herein, through experimental exploration, it is found that the superaerophobic Nitrogen (N)-doped carbon material can promote the rapid release of H2 and provide H* desorption site for the hydrogen spillover process, which makes it have great potential as the catalysts support for hydrogen spillover. Based on this discovery, this work develops the hydrogen spillover catalyst with electron-rich Pt sites loaded on N-doped carbon nanocage (N-CNC) with adjustable work function. Through a series of comprehensive electrochemical tests, the existence of hydrogen spillover effort has been proved. Moreover, the in situ tests showed that pyrrolic-N can activate adjacent carbon sites as the desorption sites for hydrogen spillover. The Pt@N-1-CNC with the minimum work function difference (ΔΦ) between Pt NPs and support shows superior hydrogen evolution performance, only needs overpotential of 12.2 mV to reach current density of 10 mA cm-2 , outstanding turnover frequency (TOF) (44.7 s-1 @100 mV) and superior durability under the 360 h durability tests at current density of 50 mA cm-2 .
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Perovskite oxides are proven as a striking platform for developing high-performance electrocatalysts. Nonetheless, a significant portion of them show CO2 electroreduction (CO2RR) inertness. Here a simple but effective strategy is reported to activate inert perovskite oxides (e.g., SrTiO3) for CO2RR through slight Cu2+ doping in B-sites. For the proof-of-concept catalysts of SrTi1-xCuxO3 (x = 0.025, 0.05, and 0.1), Cu2+ doping (even in trace amount, e.g., x = 0.025) can not only create active, stable CuO6 octahedra, increase electrochemical active surface area, and accelerate charge transfer, but also significantly regulate the electronic structure (e.g., up-shifted band center) to promote activation/adsorption of reaction intermediates. Benefiting from these merits, the stable SrTi1-xCuxO3 catalysts feature great improvements (at least an order of magnitude) in CO2RR activity and selectivity for high-order products (i.e., CH4 and C2+), compared to the SrTiO3 parent. This work provides a new avenue for the conversion of inert perovskite oxides into high-performance electrocatalysts toward CO2RR.
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Despite the intriguing potential, nano-socketed Cu/perovskite heterostructures for CO2 electroreduction (CO2RR) are still in their infancy and rational optimization of their CO2RR properties is lacking. Here, an effective strategy is reported to promote CO2-to-C2+ conversion over nano-socketed Cu/perovskite heterostructures by A-site-valence-controlled oxygen vacancies. For the proof-of-concept catalysts of Cu/La0.3-xSr0.6+xTiO3-δ (x from 0 to 0.3), their oxygen vacancy concentrations increase controllably with the decreased A-site valences (or the increased x values). In flow cells, their activity and selectivity for C2+ present positive correlations with the oxygen vacancy concentrations. Among them, the Cu/Sr0.9TiO3-δ with most oxygen vacancies shows the optimal activity and selectivity for C2+. And relative to the Cu/La0.3Sr0.6TiO3-δ with minimum oxygen vacancies, the Cu/Sr0.9TiO3-δ exhibits marked improvements (up to 2.4 folds) in activity and selectivity for C2+. The experiments and theoretical calculations suggest that the optimized performance can be attributed to the merits provided by oxygen vacancies, including the accelerated charge transfer, enhanced adsorption/activation of reaction species, and reduced energy barrier for CâC coupling. Moreover, when explored in a membrane-electrode assembly electrolyzer, the Cu/Sr0.9TiO3-δ catalyst shows excellent activity, selectivity (43.9%), and stability for C2H4 at industrial current densities, being the most effective perovskite-based catalyst for CO2-to-C2H4 conversion.
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BACKGROUND: Chelerythrine is an important alkaloid used in agriculture and medicine. However, its structural complexity and low abundance in nature hampers either bulk chemical synthesis or extraction from plants. Here, we reconstructed and optimized the complete biosynthesis pathway for chelerythrine from (S)-reticuline in Saccharomyces cerevisiae using genetic reprogramming. RESULTS: The first-generation strain Z4 capable of producing chelerythrine was obtained via heterologous expression of seven plant-derived enzymes (McoBBE, TfSMT, AmTDC, EcTNMT, PsMSH, EcP6H, and PsCPR) in S. cerevisiae W303-1 A. When this strain was cultured in the synthetic complete (SC) medium supplemented with 100 µM of (S)-reticuline for 10 days, it produced up to 0.34 µg/L chelerythrine. Furthermore, efficient metabolic engineering was performed by integrating multiple-copy rate-limiting genes (TfSMT, AmTDC, EcTNMT, PsMSH, EcP6H, PsCPR, INO2, and AtATR1), tailoring the heme and NADPH engineering, and engineering product trafficking by heterologous expression of MtABCG10 to enhance the metabolic flux of chelerythrine biosynthesis, leading to a nearly 900-fold increase in chelerythrine production. Combined with the cultivation process, chelerythrine was obtained at a titer of 12.61 mg per liter in a 0.5 L bioreactor, which is over 37,000-fold higher than that of the first-generation recombinant strain. CONCLUSIONS: This is the first heterologous reconstruction of the plant-derived pathway to produce chelerythrine in a yeast cell factory. Applying a combinatorial engineering strategy has significantly improved the chelerythrine yield in yeast and is a promising approach for synthesizing functional products using a microbial cell factory. This achievement underscores the potential of metabolic engineering and synthetic biology in revolutionizing natural product biosynthesis.
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Benzofenantridinas , Engenharia Metabólica , Saccharomyces cerevisiae , Engenharia Metabólica/métodos , Benzofenantridinas/metabolismo , Benzofenantridinas/biossíntese , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Vias BiossintéticasRESUMO
BACKGROUND: In clinical medicine, fetal heart rate (FHR) monitoring using cardiotocography (CTG) is one of the most commonly used methods for assessing fetal acidosis. However, as the visual interpretation of CTG depends on the subjective judgment of the clinician, this has led to high inter-observer and intra-observer variability, making it necessary to introduce automated diagnostic techniques. METHODS: In this study, we propose a computer-aided diagnostic algorithm (Hybrid-FHR) for fetal acidosis to assist physicians in making objective decisions and taking timely interventions. Hybrid-FHR uses multi-modal features, including one-dimensional FHR signals and three types of expert features designed based on prior knowledge (morphological time domain, frequency domain, and nonlinear). To extract the spatiotemporal feature representation of one-dimensional FHR signals, we designed a multi-scale squeeze and excitation temporal convolutional network (SE-TCN) backbone model based on dilated causal convolution, which can effectively capture the long-term dependence of FHR signals by expanding the receptive field of each layer's convolution kernel while maintaining a relatively small parameter size. In addition, we proposed a cross-modal feature fusion (CMFF) method that uses multi-head attention mechanisms to explore the relationships between different modalities, obtaining more informative feature representations and improving diagnostic accuracy. RESULTS: Our ablation experiments show that the Hybrid-FHR outperforms traditional previous methods, with average accuracy, specificity, sensitivity, precision, and F1 score of 96.8, 97.5, 96, 97.5, and 96.7%, respectively. CONCLUSIONS: Our algorithm enables automated CTG analysis, assisting healthcare professionals in the early identification of fetal acidosis and the prompt implementation of interventions.
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Acidose , Doenças Fetais , Feminino , Gravidez , Humanos , Acidose/diagnóstico , Algoritmos , Cardiotocografia , Tomada de Decisões , Inteligência ArtificialRESUMO
Waterborne acrylic coatings, the largest market share of predominant environmentally friendly coatings, face limitations in their extensive application due to their flammability. The flame-retardant properties of the coatings could be significantly enhanced by incorporate inorganic flame retardants. However, inorganic flame retardants tend to aggregate and unevenly disperse in waterborne acrylic coatings, causing a substantial decrease in flame retardancy. In this work, sodium silicate was utilized as a flame retardant, with urea and melamine serving as modifiers and synergistic agents. This combination resulted in the preparation of a sodium silicate/urea/melamine ternary synergistic waterborne acrylic flame-retardant coating. This coating was applied to the surface of poplar veneer to create flame-retardant poplar veneer. Subsequently, various instruments, including a scanning electron microscope (SEM), a limiting oxygen index meter (LOI), a thermogravimetric analyzer (TG), and a cone calorimeter (CONE), were employed to investigate the relevant properties and mechanisms of both the flame-retardant coating and poplar veneer. The results demonstrated that the sodium silicate/urea/melamine ternary synergistic flame retardant did not exhibit aggregation and could be uniformly dispersed in waterborne acrylic coatings. The physical and mechanical properties of the ternary synergistic flame-retardant poplar veneer coating were satisfactory. Melamine and urea, acting as modifiers, not only greatly enhanced the dispersibility of sodium silicate in waterborne acrylic coatings, but also assisted in the formation of a silicon-containing char layer through the generation of nitrogen, achieving ternary synergistic flame retardancy. In conclusion, this work explores a novel method to efficiently and uniformly disperse inorganic flame retardants in organic coatings. It significantly improves the dispersibility and uniformity of inorganic flame retardants in organic polymers, thereby substantially enhancing the flame-retardant performance of coatings. This work provides a theoretical basis for the research and application of new flame-retardant coatings in the field of chemistry and materials.
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The incompatibility between inorganic flame retardants and organic acrylic coatings represents a significant challenge that requires resolution. This work selected environmentally friendly organic aqueous acrylic coatings as the substrate, sodium silicate hydrate as the inorganic flame retardant, and melamine cyanurate (MCA) as the flame-retardant modifier and the flame-retardant co-modifier, with the objective of improving the dispersion and flame-retardant properties of sodium silicate hydrate in the aqueous acrylic coatings. Subsequently, the sodium silicate/MCA/waterborne acrylic acid flame-retardant coating was prepared. The flame-retardant treatment was then applied to poplar veneer in order to create a flame-retardant poplar veneer. The dispersion of the flame-retardant coating was characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDX), and X-ray diffractometry (XRD). Furthermore, the flame-retardant properties of the flame-retardant poplar veneer were analyzed by thermogravimetry (TG), limiting oxygen index (LOI), and cone calorimeter. The results demonstrated that the MCA-modified sodium silicate flame retardant was well dispersed in aqueous acrylic coatings. The results of the flame-retardant properties of the poplar veneer indicated that the ignition time of the 9% flame retardant-treated poplar veneer was increased by 122.7%, the limiting oxygen index value was increased by 43.0%, and the peak heat release rate (pHRR), the peak total heat release rate (pTHR), and the peak mass loss rate were decreased by 19.9%, 10.8%, and 27.2%, respectively, in comparison to the non-flame retardant-treated poplar veneer. Furthermore, the residual char mass increased by 14.4%, and the residual char exhibited enhanced thickness, density, and regularity. The results demonstrated that MCA was an effective promoter of sodium silicate dispersion in acrylic coatings. Furthermore, the sodium silicate/MCA/waterborne acrylic flame-retardant coating significantly enhance the flame retardancy of wood, and its flame retardant mechanism was consistent with the synergistic silicone-nitrogen expansion flame-retardant mechanism. This work presents a novel approach to enhancing the dispersion of inorganic flame retardants in organic coatings, offering a valuable contribution to the advancement of research and application in the domains of innovative flame retardant coatings and flame retardant wood.
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Electrochemical reduction reactions, as cathodic processes in many energy-related devices, significantly impact the overall efficiency determined mainly by the performance of electrocatalysts. Metal-organic frameworks (MOFs) derived carbon-supported metal materials have become one of star electrocatalysts due to their tunable structure and composition through ligand design and metal screening. However, for different electroreduction reactions, the required active metal species vary in phase component, electronic state, and catalytic center configuration, hence requiring effective customization. From this perspective, this review comprehensively analyzes the structural design principles, metal loading strategies, practical electroreduction performance, and complex catalytic mechanisms, thereby providing insights and guidance for the future rational design of such electroreduction catalysts.
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Recently, hydrogen spillover based binary (HSBB) catalysts have received widespread attention due to the sufficiently utilized reaction sites. However, the specific regulation mechanism of spillover intensity is still unclear. Herein, we have fabricated oxygen vacancies enriched Ru/NiMoO4-x to investigate the internal relationship between electron supply and mechanism of hydrogen spillover enhancement. The DFT calculations cooperate with in situ Raman spectrum to uncover that the H* spillover from NiMoO4-x to Ru. Meanwhile, oxygen vacancies weakened the electron supply from Ru to NiMoO4-x , which contributes to dilute the resistance of built-in electric field (BEF) for hydrogen spillover. In addition, the higher ion concentration in electrolyte will promote the H* adsorption step obviously, which is demonstrated by in situ EIS tests. As a result, the Ru/NiMoO4-x exhibits a low overpotential of 206â mV at 3.0â A cm-2 , a small Tafel slope of 28.8â mV dec-1 , and an excellent durability of 550â h at the current density of 0.5â A cm-2 for HER in 1.0â M KOH seawater.
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The gradual acceleration of the aging population in China has led to an increased demand for mobility aids, and the reliability of domestic wheeled walking-aid is one of their important attributes, but there is little research on the reliability of mobility aids. This paper conducts the failure mode, effects and criticality analysis on domestic wheeled walking-aid. By collecting, collating and analyzing the 26 failure modes, the key modules are the chassis and the lifting system. The key modules are obtained, and the failure data is analyzed to find out that the lifetime distribution model is log-normal and the 0.95 lower confidence limit for reliability life of product t 0.9 is 2489.4 hours. The study aims to provide ideas for the reliability analysis of other active medical devices and calls for the formation of a reliability study review point for the industry that meets the requirements of Chinese medical device regulations.
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Caminhada , Reprodutibilidade dos Testes , ChinaRESUMO
As one of the most typical bioorthogonal reactions, the Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC) reaction has received worldwide attention in intracellular transformation of prodrugs due to its high efficiency and selectivity. However, the exogenous Cu catalysts may disturb Cu homeostasis and cause side effects to normal tissues. What is more, the intratumoral Cu(I) is insufficient to efficiently catalyze the intracellular CuAAC reaction due to oncogene-induced labile Cu(I) deficiency. Herein, in order to boost the endogenous Cu(I) level for intracellular drug synthesis through the bioorthogonal reaction, a self-adaptive bioorthogonal catalysis system was constructed by encapsulating prodrugs and sodium ascorbate within adenosine triphosphate aptamer-functionalized metal-organic framework nanoparticles. The system presents specificity to tumor cells and does not require exogenous Cu catalysts, thereby leading to high anti-tumor efficacy and minimal side effects both in vitro and in vivo. This work will open up a new opportunity for developing biosafe and high-performance bioorthogonal catalysis systems.
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Estruturas Metalorgânicas , Pró-Fármacos , Cobre , Ácido Ascórbico , Catálise , Alcinos , Azidas , Reação de CicloadiçãoRESUMO
Pyroptosis is an inflammatory form of programmed cell death that holds great promise in cancer therapy. However, autophagy as the crucial pyroptosis checkpoint and the self-protective mechanism of cancer cells significantly weakens the therapeutic efficiency. Here, a bioorthogonal pyroptosis nanoregulator is constructed to induce pyroptosis and disrupt the checkpoint, enabling high-efficiency pyroptosis cancer therapy. The nanoregulator allows the in situ synthesis and accumulation of the photosensitizer PpIX in the mitochondria of cancer cells to directly produce mitochondrial ROS, thus triggering pyroptosis. Meanwhile, the in situ generated autophagy inhibitor via palladium-catalyzed bioorthogonal chemistry can disrupt the pyroptosis checkpoint to boost the pyroptosis efficacy. With the biomimetic cancer cell membrane coating, this platform for modulating pyroptosis presents specificity to cancer cells and poses no harm to normal tissue, resulting in a highly efficient and safe antitumor treatment. To our knowledge, this is the first report on a disrupting intrinsic protective mechanism of cancer cells for tumor pyroptosis therapy. This work highlights that autophagy as a checkpoint plays a key regulative role in pyroptosis therapy, which would motivate the future design of therapeutic regimens.
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Neoplasias , Piroptose , Apoptose , Autofagia , Biomimética , Membrana CelularRESUMO
Oocyte maturation defects are major phenotypes resulting in female infertility. Although many genetic factors have been found to be responsible for these phenotypes, the underlying pathogenic genes and variants remain to be identified. The anaphase promoting complex or cyclosome (APC/C) is known to be essential in the metaphase-to-anaphase transition. In this study, we identified two homozygous missense variants (c.986A > G, p.Y329C and c.988C > T, p.R330C) in CDC23 that are responsible for female infertility characterized by oocyte maturation defects in three infertile individuals. CDC23 (cell division cycle 23) is one of the core subunits of the APC/C. In vitro experiments showed that the variant c.986A > G (p.Y329C) led to a decrease in CDC23 protein level and the variant c.988C > T (p.R330C) changed the localization of CDC23 in HeLa cells and mouse oocytes. In vivo studies showed that Cdc23Y329C/Y329C mice successfully mimicked the patients' phenotype by causing low expression of CDC23 and APC4 and the accumulation of securin and cyclin B1 in oocytes. AZ3146 treatment was able to rescue the phenotype. Taken together, our findings reveal the important roles of CDC23 in human oocyte maturation and provide a new genetic marker for female infertility.
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Proteínas de Ciclo Celular , Infertilidade Feminina , Humanos , Feminino , Animais , Camundongos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Células HeLa , Infertilidade Feminina/genética , Ciclossomo-Complexo Promotor de Anáfase , OócitosRESUMO
Visual wearable devices can rapid intuitively monitor biomarkers in body fluids to indicate the human health status and provide valuable reference for further medical diagnosis. However, unavoidable interference factors such as skin color, natural light, and background luminescence can interfere with the visualization accuracy of flexible wearable devices, limiting their practical sensing application. Here, we designed a wearable sensing patch via an embedded upconversion optical probe in a 3D porous polyacrylamide hydrogel, exhibiting a multiplex chroma response to urea based on the inner filter effect, which overcomes the susceptibility to external conditions due to its near-infrared excited luminescence and improves the resolution and accuracy of visual sensing. Furthermore, a highly compatible portable sensing platform combined with a smartphone was designed to achieve in situ rapid quantitative analysis of urea. The limit of detection values of the upconversion optical probe and hydrogel sensor are as low as 1.4 and 30 µM respectively, exhibiting the practicality in different scenarios. The designed sensing patch provides a convenient and accurate sensing strategy for the detection of biomarkers in body fluids and has the potential to be developed into a point-of-care device to provide disease early warning and clinical diagnosis.