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Semiconducting graphene plays an important part in graphene nanoelectronics because of the lack of an intrinsic bandgap in graphene1. In the past two decades, attempts to modify the bandgap either by quantum confinement or by chemical functionalization failed to produce viable semiconducting graphene. Here we demonstrate that semiconducting epigraphene (SEG) on single-crystal silicon carbide substrates has a band gap of 0.6 eV and room temperature mobilities exceeding 5,000 cm2 V-1 s-1, which is 10 times larger than that of silicon and 20 times larger than that of the other two-dimensional semiconductors. It is well known that when silicon evaporates from silicon carbide crystal surfaces, the carbon-rich surface crystallizes to produce graphene multilayers2. The first graphitic layer to form on the silicon-terminated face of SiC is an insulating epigraphene layer that is partially covalently bonded to the SiC surface3. Spectroscopic measurements of this buffer layer4 demonstrated semiconducting signatures4, but the mobilities of this layer were limited because of disorder5. Here we demonstrate a quasi-equilibrium annealing method that produces SEG (that is, a well-ordered buffer layer) on macroscopic atomically flat terraces. The SEG lattice is aligned with the SiC substrate. It is chemically, mechanically and thermally robust and can be patterned and seamlessly connected to semimetallic epigraphene using conventional semiconductor fabrication techniques. These essential properties make SEG suitable for nanoelectronics.
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Most structural and evolutionary properties of galaxies strongly rely on the stellar initial mass function (IMF), namely the distribution of the stellar mass formed in each episode of star formation1-4. The IMF shapes the stellar population in all stellar systems, and so has become one of the most fundamental concepts of modern astronomy. Both constant and variable IMFs across different environments have been claimed despite a large number of theoretical5-7 and observational efforts8-15. However, the measurement of the IMF in Galactic stellar populations has been limited by the relatively small number of photometrically observed stars, leading to high uncertainties12-16. Here we report a star-counting result based on approximately 93,000 spectroscopically observed M-dwarf stars, an order of magnitude more than previous studies, in the 100-300 parsec solar neighbourhood. We find unambiguous evidence of a variable IMF that depends on both metallicity and stellar age. Specifically, the stellar population formed at early times contains fewer low-mass stars compared with the canonical IMF, independent of stellar metallicities. In more recent times, however, the proportion of low-mass stars increases with stellar metallicity. The variable abundance of low-mass stars in our Milky Way establishes a powerful benchmark for models of star formation and can heavily affect results in Galactic chemical-enrichment modelling, mass estimation of galaxies and planet-formation efficiency.
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Peracetic acid (PAA) is emerging as a versatile agent for generating long-lived and selectively oxidative organic radicals (R-Oâ¢). Currently, the conventional transition metal-based activation strategies still suffer from metal ion leaching, undesirable by-products formation, and uncontrolled reactive species production. To address these challenges, we present a method employing BiOI with a unique electron structure as a PAA activator, thereby predominantly generating CH3C(O)O⢠radicals. The specificity of CH3C(O)O⢠generation ensured the superior performance of the BiOI/PAA system across a wide pH range (2.0 to 11.0), even in the presence of complex interfering substances such as humic acids, chloride ions, bicarbonate ions, and real-world water matrices. Unlike conventional catalytic oxidative methods, the BiOI/PAA system degrades sulfonamides without producing any toxic by-products. Our findings demonstrate the advantages of CH3C(O)O⢠in water decontamination and pave the way for the development of eco-friendly water decontaminations based on organic peroxides.
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Transparent piezoelectrics are highly desirable for numerous hybrid ultrasound-optical devices ranging from photoacoustic imaging transducers to transparent actuators for haptic applications1-7. However, it is challenging to achieve high piezoelectricity and perfect transparency simultaneously because most high-performance piezoelectrics are ferroelectrics that contain high-density light-scattering domain walls. Here, through a combination of phase-field simulations and experiments, we demonstrate a relatively simple method of using an alternating-current electric field to engineer the domain structures of originally opaque rhombohedral Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) crystals to simultaneously generate near-perfect transparency, an ultrahigh piezoelectric coefficient d33 (greater than 2,100 picocoulombs per newton), an excellent electromechanical coupling factor k33 (about 94 per cent) and a large electro-optical coefficient γ33 (approximately 220 picometres per volt), which is far beyond the performance of the commonly used transparent ferroelectric crystal LiNbO3. We find that increasing the domain size leads to a higher d33 value for the [001]-oriented rhombohedral PMN-PT crystals, challenging the conventional wisdom that decreasing the domain size always results in higher piezoelectricity8-10. This work presents a paradigm for achieving high transparency and piezoelectricity by ferroelectric domain engineering, and we expect the transparent ferroelectric crystals reported here to provide a route to a wide range of hybrid device applications, such as medical imaging, self-energy-harvesting touch screens and invisible robotic devices.
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High-speed actuation of laser frequency1 is critical in applications using lasers and frequency combs2,3, and is a prerequisite for phase locking, frequency stabilization and stability transfer among optical carriers. For example, high-bandwidth feedback control of frequency combs is used in optical-frequency synthesis4, frequency division5 and optical clocks6. Soliton microcombs7,8 have emerged as chip-scale frequency comb sources, and have been used in system-level demonstrations9,10. Yet integrated microcombs using thermal heaters have limited actuation bandwidths11,12 of up to 10 kilohertz. Consequently, megahertz-bandwidth actuation and locking of microcombs have only been achieved with off-chip bulk component modulators. Here we demonstrate high-speed soliton microcomb actuation using integrated piezoelectric components13. By monolithically integrating AlN actuators14 on ultralow-loss Si3N4 photonic circuits15, we demonstrate voltage-controlled soliton initiation, tuning and stabilization with megahertz bandwidth. The AlN actuators use 300 nanowatts of power and feature bidirectional tuning, high linearity and low hysteresis. They exhibit a flat actuation response up to 1 megahertz-substantially exceeding bulk piezo tuning bandwidth-that is extendable to higher frequencies by overcoming coupling to acoustic contour modes of the chip. Via synchronous tuning of the laser and the microresonator, we exploit this ability to frequency-shift the optical comb spectrum (that is, to change the comb's carrier-envelope offset frequency) and make excursions beyond the soliton existence range. This enables a massively parallel frequency-modulated engine16,17 for lidar (light detection and ranging), with increased frequency excursion, lower power and elimination of channel distortions resulting from the soliton Raman self-frequency shift. Moreover, by modulating at a rate matching the frequency of high-overtone bulk acoustic resonances18, resonant build-up of bulk acoustic energy allows a 14-fold reduction of the required driving voltage, making it compatible with CMOS (complementary metal-oxide-semiconductor) electronics. Our approach endows soliton microcombs with integrated, ultralow-power and fast actuation, expanding the repertoire of technological applications of microcombs.
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DNA Methylation is a significant epigenetic modification that can modulate chromosome states, but its role in orchestrating chromosome organization has not been well elucidated. Here we systematically assessed the effects of DNA Methylation on chromosome organization with a multi-omics strategy to capture DNA Methylation and high-order chromosome interaction simultaneously on mouse embryonic stem cells with DNA methylation dioxygenase Tet triple knock-out (Tet-TKO). Globally, upon Tet-TKO, we observed weakened compartmentalization, corresponding to decreased methylation differences between CpG island (CGI) rich and poor domains. Tet-TKO could also induce hypermethylation for the CTCF binding peaks in TAD boundaries and chromatin loop anchors. Accordingly, CTCF peak generally weakened upon Tet-TKO, which results in weakened TAD structure and depletion of long-range chromatin loops. Genes that lost enhancer-promoter looping upon Tet-TKO showed DNA hypermethylation in their gene bodies, which may compensate for the disruption of gene expression. We also observed distinct effects of Tet1 and Tet2 on chromatin organization and increased DNA methylation correlation on spatially interacted fragments upon Tet inactivation. Our work showed the broad effects of Tet inactivation and DNA methylation dynamics on chromosome organization.
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Cromatina , Islas de CpG , Metilación de ADN , Proteínas de Unión al ADN , Dioxigenasas , Proteínas Proto-Oncogénicas , Animales , Ratones , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Dioxigenasas/metabolismo , Dioxigenasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Cromatina/metabolismo , Cromatina/genética , Islas de CpG/genética , Células Madre Embrionarias de Ratones/metabolismo , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/genética , Epigénesis Genética , Regiones Promotoras Genéticas , Cromosomas/genéticaRESUMEN
Singlet oxygen (1O2) plays a pivotal role in numerous catalytic oxidation processes utilized in water purification and chemical synthesis. The spin-trapping method based on electron paramagnetic resonance (EPR) analysis is commonly employed for 1O2 detection. However, it is often limited to time-independent acquisition. Recent studies have raised questions about the reliability of the 1O2 trapper, 2,2,6,6-tetramethylpiperidine (TEMP), in various systems. In this study, we introduce a comprehensive, kinetic examination to monitor the spin-trapping process in EPR analysis. The EPR intensity of the trapping product was used as a quantitative measurement to evaluate the concentration of 1O2 in aqueous systems. This in situ kinetic study was successfully applied to a classical photocatalytic system with exceptional accuracy. Furthermore, we demonstrated the feasibility of our approach in more intricate 1O2-driven catalytic oxidation processes for water decontamination and elucidated the molecular mechanism of direct TEMP oxidation. This method can avoid the false-positive results associated with the conventional 2D 1O2 detection techniques, and provide insights into the reaction mechanisms in 1O2-dominated catalytic oxidation processes. This work underscores the necessity of kinetic studies for spin-trapping EPR analysis, presenting an avenue for a comprehensive exploration of the mechanisms governing catalytic oxidation processes.
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Synergistic drug combinations can improve the therapeutic effect and reduce the drug dosage to avoid toxicity. In previous years, an in vitro approach was utilized to screen synergistic drug combinations. However, the in vitro method is time-consuming and expensive. With the rapid growth of high-throughput data, computational methods are becoming efficient tools to predict potential synergistic drug combinations. Considering the limitations of the previous computational methods, we developed a new model named Siamese Network and Random Matrix Projection for AntiCancer Drug Combination prediction (SNRMPACDC). Firstly, the Siamese convolutional network and random matrix projection were used to process the features of the two drugs into drug combination features. Then, the features of the cancer cell line were processed through the convolutional network. Finally, the processed features were integrated and input into the multi-layer perceptron network to get the predicted score. Compared with the traditional method of splicing drug features into drug combination features, SNRMPACDC improved the interpretability of drug combination features to a certain extent. In addition, the introduction of convolutional networks can better extract the potential information in the features. SNRMPACDC achieved the root mean-squared error of 15.01 and the Pearson correlation coefficient of 0.75 in 5-fold cross-validation of regression prediction for response data. In addition, SNRMPACDC achieved the AUC of 0.91 ± 0.03 and the AUPR of 0.62 ± 0.05 in 5-fold cross-validation of classification prediction of synergistic or not. These results are almost better than all the previous models. SNRMPACDC would be an effective approach to infer potential anticancer synergistic drug combinations.
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Protocolos de Quimioterapia Combinada Antineoplásica , Biología Computacional , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sinergismo Farmacológico , Biología Computacional/métodos , Combinación de Medicamentos , Simulación por ComputadorRESUMEN
Zinc finger protein 471 (ZNF471) is a member of the Krüppel-related domain zinc finger protein family, and has recently attracted attention because of its anti-cancer effects. N-glycosylation regulates expression and functions of the protein. This study aimed to investigate the effects of ZNF471 N-glycosylation on the proliferation, invasion, and docetaxel sensitivity of tongue squamous cell carcinoma (TSCC). It analyzed the expression, function, and prognostic significance of ZNF471 in TSCC using bioinformatics techniques such as gene differential expression analysis, univariate Cox regression analysis, functional enrichment analysis, and gene set enrichment analysis. Using site-specific mutagenesis, this study generated three mutant sites for ZNF471 N-glycosylation to determine the effect of N-glycosylation on ZNF471 protein levels and function. Quantitative real-time PCR, Western blot analysis, and immunohistochemistry tests confirmed the down-regulation of ZNF471 expression in TSCC. Low expression of ZNF471 is associated with poor prognosis of patients with TSCC. Overexpression of ZNF471 in vitro retarded the proliferation of TSCC cells and suppressed cell invasion and migration ability. Asparagine 358 was identified as a N-glycosylation site of ZNF471. Suppressing N-glycosylation of ZNF471 enhanced the protein stability and promoted the translocation of protein to the cell nucleus. ZNF471 binding to c-Myc gene promoter suppressed oncogene c-Myc expression, thereby playing the anti-cancer effect and enhancing TSCC sensitivity to docetaxel. In all, N-glycosylation of ZNF471 affects the proliferation, invasion, and docetaxel sensitivity of TSCC via regulation of c-Myc.
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Proliferación Celular , Docetaxel , Invasividad Neoplásica , Proteínas Proto-Oncogénicas c-myc , Proteínas Represoras , Neoplasias de la Lengua , Femenino , Humanos , Masculino , Antineoplásicos/farmacología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Docetaxel/farmacología , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glicosilación/efectos de los fármacos , Pronóstico , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismoRESUMEN
Allostery refers to the biological process by which an effector modulator binds to a protein at a site distant from the active site, known as allosteric site. Identifying allosteric sites is essential for discovering allosteric process and is considered a critical factor in allosteric drug development. To facilitate related research, we developed PASSer (Protein Allosteric Sites Server) at https://passer.smu.edu, a web application for fast and accurate allosteric site prediction and visualization. The website hosts three trained and published machine learning models: (i) an ensemble learning model with extreme gradient boosting and graph convolutional neural network, (ii) an automated machine learning model with AutoGluon and (iii) a learning-to-rank model with LambdaMART. PASSer accepts protein entries directly from the Protein Data Bank (PDB) or user-uploaded PDB files, and can conduct predictions within seconds. The results are presented in an interactive window that displays protein and pockets' structures, as well as a table that summarizes predictions of the top three pockets with the highest probabilities/scores. To date, PASSer has been visited over 49 000 times in over 70 countries and has executed over 6 200 jobs.
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Proteínas , Programas Informáticos , Sitio Alostérico , Proteínas/química , Redes Neurales de la Computación , Aprendizaje Automático , Regulación AlostéricaRESUMEN
OBJECTIVE: Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome. DESIGN: We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified. RESULTS: Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion. CONCLUSION: Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.
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Microbioma Gastrointestinal , Aneurisma Intracraneal , Metabolómica , Metagenómica , Triptófano , Aneurisma Intracraneal/microbiología , Aneurisma Intracraneal/metabolismo , Microbioma Gastrointestinal/fisiología , Humanos , Animales , Masculino , Ratones , Femenino , Triptófano/metabolismo , Triptófano/sangre , Metabolómica/métodos , Metagenómica/métodos , Persona de Mediana Edad , Aneurisma Roto/microbiología , Aneurisma Roto/metabolismo , Indicán/metabolismo , Indicán/sangre , Biomarcadores/sangre , Biomarcadores/metabolismo , Heces/microbiología , Modelos Animales de Enfermedad , Anciano , Progresión de la EnfermedadRESUMEN
Selective activation of C-H bonds in light alkanes under mild conditions is challenging but holds the promise of efficient upgrading of abundant hydrocarbons. In this work, we report the conversion of propane to propylene with â¼95% selectivity on Cu(I)-ZSM-5 with O2 at room temperature and pressure. The intraporous Cu(I) species was oxidized to Cu(II) during the reaction but could be regenerated with H2 at 220 °C. Diffuse reflectance ultraviolet spectroscopy indicated the presence of both Cu+-O2 and Cu2(µ-O2)2+ species in the zeolite pores during the reaction, and electron paramagnetic resonance results showed that propane activation occurred via a radical-mediated pathway distinct from that with H2O2 as the oxidant. Correlation between spectroscopic and reactivity results on Cu(I)-ZSM-5 with different Cu loadings suggests that the isolated intraporous Cu(I) species is the main active species in propane activation.
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3D metal-organic frameworks (MOFs) have gained attention as heterogeneous photocatalysts due to their porosity and unique host-guest interactions. Despite their potential, MOFs face challenges, such as inefficient mass transport and limited light penetration in photoinduced energy transfer processes. Recent advancements in organic photocatalysis have uncovered a variety of photoactive cores, while their heterogenization remains an underexplored area with great potential to build MOFs. This gap is bridged by incorporating photoactive cores into 2D MOF nanosheets, a process that merges the realms of small-molecule photochemistry and MOF chemistry. This approach results in recyclable heterogeneous photocatalysts that exhibit an improved mass transfer efficiency. This research demonstrates a bottom-up synthetic method for embedding photoactive cores into 2D MOF nanosheets, successfully producing variants such as PCN-641-NS, PCN-643-NS, and PCN-644-NS. The synthetic conditions were systematically studied to optimize the crystallinity and morphology of these 2D MOF nanosheets. Enhanced host-guest interactions in these 2D structures were confirmed through various techniques, particularly solid-state NMR studies. Additionally, the efficiency of photoinduced energy transfer in these nanosheets was evidenced through photoborylation reactions and the generation of reactive oxygen species (ROS).
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BACKGROUND: Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear. METHODS: Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively. RESULTS: The tpCR rate in the PLR- group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], Pâ =â .032). The tpCR rate in the NLR- group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], Pâ =â .024). The tpCR rate of the PLR-NLR- (PLR- and NLR-) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; Pâ =â .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR- group (Pâ =â .028 for EFS; Pâ =â .047 for OS). Patients in the PLR-NLR- group had a longer EFS than those in the PLR+/NLR+ group (Pâ =â .002). CONCLUSION: PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis.
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Ciclobutanos , Terapia Neoadyuvante , Compuestos Organoplatinos , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/sangre , Neoplasias de la Mama Triple Negativas/mortalidad , Femenino , Terapia Neoadyuvante/métodos , Pronóstico , Persona de Mediana Edad , Ciclobutanos/farmacología , Ciclobutanos/uso terapéutico , Ciclobutanos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/farmacología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Anciano , Neutrófilos/metabolismo , Biomarcadores de Tumor/sangre , Linfocitos/metabolismo , Plaquetas/patología , Estudios RetrospectivosRESUMEN
Saline-sodic stress can limit the absorption of available zinc in rice, subsequently impacting the normal photosynthesis and carbohydrate metabolism of rice plants. To investigate the impact of exogenous zinc application on photosynthesis and carbohydrate metabolism in rice grown in saline-sodic soil, this study simulated saline-sodic stress conditions using two rice varieties, 'Changbai 9' and 'Tonghe 899', as experimental materials. Rice seedlings at 4 weeks of age underwent various treatments including control (CT), 2 µmol·L-1 zinc treatment alone (Z), 50 mmol·L-1 saline-sodic treatment (S), and 50 mmol·L-1 saline-sodic treatment with 2 µmol·L-1 zinc (Z + S). We utilized JIP-test to analyze the variations in excitation fluorescence and MR820 signal in rice leaves resulting from zinc supplementation under saline-sodic stress, and examined the impact of zinc supplementation on carbohydrate metabolism in both rice leaves and roots under saline-sodic stress. Research shows that zinc increased the chloroplast pigment content, specific energy flow, quantum yield, and performance of active PSII reaction centers (PIABS), as well as the oxidation (VOX) and reduction rate (Vred) of PSI in rice leaves under saline-sodic stress. Additionally, it decreased the relative variable fluorescence (WK and VJ) and quantum energy dissipation yield (φDO) of the rice. Meanwhile, zinc application can reduce the content of soluble sugars and starch in rice leaves and increasing the starch content in the roots. Therefore, the addition of zinc promotes electron and energy transfer in the rice photosystem under saline-sodic stress. It enhances rice carbohydrate metabolism, improving the rice plants' ability to withstand saline-sodic stress and ultimately promoting rice growth and development.
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Metabolismo de los Hidratos de Carbono , Clorofila , Oryza , Plantones , Zinc , Oryza/metabolismo , Oryza/efectos de los fármacos , Zinc/metabolismo , Plantones/metabolismo , Plantones/efectos de los fármacos , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Clorofila/metabolismo , Fluorescencia , Fotosíntesis/efectos de los fármacos , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacosRESUMEN
BACKGROUND: Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline. METHODS: We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (Pinteraction = 0.001, Pinteraction = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044). CONCLUSIONS: Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.
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Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclobutanos , Terapia Neoadyuvante , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclobutanos/administración & dosificación , Ciclobutanos/uso terapéutico , Antraciclinas/uso terapéutico , Antraciclinas/administración & dosificación , Anciano , Taxoides/uso terapéutico , Taxoides/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Resultado del Tratamiento , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Hidrocarburos Aromáticos con PuentesRESUMEN
Although chemotherapy has the potential to induce tumor immunotherapy via immunogenic cell death (ICD) effects, how to control the intensity of the immune responses still deserves further exploration. Herein, a controllable ultrasound (US)-triggered chemo-immunotherapy nanoagonist is successfully synthesized by utilizing the pH and reactive oxygen species (ROS) dual-responsive PEG-polyphenol to assemble sonosensitizer zinc oxide (ZnO) and doxorubicin (DOX). The PZnO@DOX nanoparticles have an intelligent disassembly to release DOX and zinc ions in acidic pH conditions. Notably, US irradiation generates ROS by sonodynamic therapy and accelerates the drug release process. Interestingly, after the PZnO@DOX+US treatment, the injured cells release double-stranded DNA (dsDNA) from the nucleus and mitochondria into the cytosol. Subsequently, both the dsDNA and zinc ions bind with cyclic GMP-AMP synthase and activate the stimulator of interferon genes (STING) pathway, resulting in the dendritic cell maturation, ultimately promoting DOX-induced ICD effects and antigen-specific T cell immunity. Therefore, chemotherapy-induced immune responses can be modulated by non-invasive control of US.
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Doxorrubicina , Muerte Celular Inmunogénica , Nanopartículas , Óxido de Zinc , Doxorrubicina/farmacología , Doxorrubicina/química , Muerte Celular Inmunogénica/efectos de los fármacos , Óxido de Zinc/química , Óxido de Zinc/farmacología , Animales , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Proteínas de la Membrana/metabolismo , Humanos , Ondas Ultrasónicas , Ratones , Concentración de Iones de Hidrógeno , Liberación de Fármacos , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , ADN/química , ADN/metabolismoRESUMEN
Silicon (Si) is considered a promising commercial material for the next-generation of high-energy density lithium-ion battery (LIB) due to its high theoretical capacity. However, the severe volume changes and the poor conductivity hinder the practical application of Si anode. Herein, a novel core-shell heterostructure, Si as the core and V3 O4 @C as the shell (Si@V3 O4 @C), is proposed by a facile solvothermal reaction. Theoretical simulations have shown that the in-situ-formed V3 O4 layer facilitates the rapid Li+ diffusion and lowers the energy barrier of Li transport from the carbon shell to the inner core. The 3D network structure constructed by amorphous carbon can effectively improve electronic conductivity and structural stability. Benefiting from the rationally designed structure, the optimized Si@V3 O4 @C electrode exhibits an excellent cycling stability of 1061.1 mAh g-1 at 0.5 A g-1 over 700 cycles (capacity retention of 70.0%) with an average Coulombic efficiency of 99.3%. In addition, the Si@V3 O4 @C||LiFePO4 full cell shows a superior capacity retention of 78.7% after 130 cycles at 0.5 C. This study opens a novel way for designing high-performance silicon anode for advanced LIBs.
RESUMEN
Current thrombolytic drugs exhibit suboptimal therapeutic outcomes and potential bleeding risks due to their limited circulation time, inadequate thrombus penetration, and off-target biodistribution. Herein, a photosensitizer-loaded, red cell membrane-encapsuled multiple magnetic nanoparticles aggregate is successfully developed for integrated mechanical/photothermal/photodynamic thrombolysis. Red cell membrane coating endows magnetic particles with prolonged blood circulation and superior biocompatibility. Under a preset rotating magnetic field (RMF), the aggregate with asymmetric magnetic distribution initiates rolling motion toward the blood clot interface, and because of magnetic dipole-dipole interactions, the aggregate tends to self-assemble into longer, flexible chain-like microrobotic swarm with powerful mechanical stir forces, thereby facilitating thrombus penetration and mechanical thrombolysis. Moreover, precise magnetic control enables targeted photosensitizer accumulation, allowing effective conversion of near-infrared (NIR) light into heat and reactive oxygen species (ROS) for thrombus phototherapy. In thrombolysis assays, the weight of thrombi is massively reduced by ≈90%. The work presents a safer and more promising combination of magnetic microrobotic technology and phototherapy for multi-modality thrombolysis.
RESUMEN
Developing multifunctional, stimuli-responsive nanomedicine is intriguing because it has the potential to effectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen-driven silicon-based nanomotor (Si-motor) loaded with MnO and CaO2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO2 and MnO. Under acidic TME, CaO2 reacts with acid to release Ca2+ to induce mitochondrial damage and simultaneously produces O2 and H2O2, when the loaded MnO exerts Fenton-like activity to produce ·OH and O2 based on the produced H2O2. The generated O2 drives Si-motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si-motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscaused by intracellular Ca2 + overloading, GSH depletion induced by Mn2+, and Mn2+ mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment.