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Climate warming induces shifts from snow to rain in cold regions1, altering snowpack dynamics with consequent impacts on streamflow that raise challenges to many aspects of ecosystem services2-4. A straightforward conceptual model states that as the fraction of precipitation falling as snow (snowfall fraction) declines, less solid water is stored over the winter and both snowmelt and streamflow shift earlier in season. Yet the responses of streamflow patterns to shifts in snowfall fraction remain uncertain5-9. Here we show that as snowfall fraction declines, the timing of the centre of streamflow mass may be advanced or delayed. Our results, based on analysis of 1950-2020 streamflow measurements across 3,049 snow-affected catchments over the Northern Hemisphere, show that mean snowfall fraction modulates the seasonal response to reductions in snowfall fraction. Specifically, temporal changes in streamflow timing with declining snowfall fraction reveal a gradient from earlier streamflow in snow-rich catchments to delayed streamflow in less snowy catchments. Furthermore, interannual variability of streamflow timing and seasonal variation increase as snowfall fraction decreases across both space and time. Our findings revise the 'less snow equals earlier streamflow' heuristic and instead point towards a complex evolution of seasonal streamflow regimes in a snow-dwindling world.
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Aquecimento Global , Chuva , Estações do Ano , Neve , Ecossistema , Rios , Fatores de Tempo , Movimentos da Água , Aquecimento Global/estatística & dados numéricos , Análise Espaço-TemporalRESUMO
Autophagy, a process of degradation that occurs via the lysosomal pathway, has an essential role in multiple aspects of immunity, including immune system development, regulation of innate and adaptive immune and inflammatory responses, selective degradation of intracellular microorganisms, and host protection against infectious diseases1,2. Autophagy is known to be induced by stimuli such as nutrient deprivation and suppression of mTOR, but little is known about how autophagosomal biogenesis is initiated in mammalian cells in response to viral infection. Here, using genome-wide short interfering RNA screens, we find that the endosomal protein sorting nexin 5 (SNX5)3,4 is essential for virus-induced, but not for basal, stress- or endosome-induced, autophagy. We show that SNX5 deletion increases cellular susceptibility to viral infection in vitro, and that Snx5 knockout in mice enhances lethality after infection with several human viruses. Mechanistically, SNX5 interacts with beclin 1 and ATG14-containing class III phosphatidylinositol-3-kinase (PI3KC3) complex 1 (PI3KC3-C1), increases the lipid kinase activity of purified PI3KC3-C1, and is required for endosomal generation of phosphatidylinositol-3-phosphate (PtdIns(3)P) and recruitment of the PtdIns(3)P-binding protein WIPI2 to virion-containing endosomes. These findings identify a context- and organelle-specific mechanism-SNX5-dependent PI3KC3-C1 activation at endosomes-for initiation of autophagy during viral infection.
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Autofagia/imunologia , Nexinas de Classificação/metabolismo , Vírus/imunologia , Animais , Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Linhagem Celular , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Endossomos/metabolismo , Feminino , Humanos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética , Nexinas de Classificação/deficiência , Nexinas de Classificação/genética , Proteínas de Transporte Vesicular/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, ranking fourth in frequency. The relationship between metabolic reprogramming and immune infiltration has been identified as having a crucial impact on HCC progression. However, a deeper understanding of the interplay between the immune system and metabolism in the HCC microenvironment is required. In this study, we used a proteomic dataset to identify three immune subtypes (IM1-IM3) in HCC, each of which has distinctive clinical, immune, and metabolic characteristics. Among these subtypes, IM3 was found to have the poorest prognosis, with the highest levels of immune infiltration and T-cell exhaustion. Furthermore, IM3 showed elevated glycolysis and reduced bile acid metabolism, which was strongly correlated with CD8 T cell exhaustion and regulatory T cell accumulation. Our study presents the proteomic immune stratification of HCC, revealing the possible link between immune cells and reprogramming of HCC glycolysis and bile acid metabolism, which may be a viable therapeutic strategy to improve HCC immunotherapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteoma , Proteômica , Microambiente Tumoral , Ácidos e Sais BiliaresRESUMO
SignificanceThe detection of low-abundance molecular biomarkers is key to the liquid-biopsy-based disease diagnosis. Existing methods are limited by the affinity and specificity of recognition probes and the mass transportation of analyte molecules onto the sensor surfaces, resulting in insufficient sensitivity and long assay time. This work establishes a rapid and ultrasensitive approach by actively tuning binding kinetics and accelerating the mass transportation via nanoparticle micromanipulations. This is significant because it permits extremely sensitive measurements within clinically acceptable assay time. It is incubation-free, washing-free, and compatible with low- and high-affinity probes.
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Imagem Individual de Molécula/métodos , Sítios de Ligação , Biomarcadores/metabolismo , Cinética , Limite de Detecção , TermodinâmicaRESUMO
Interference from nonspecific binding imposes a fundamental limit in the sensitivity of biosensors that is dependent on the affinity and specificity of the available sensing probes. The dynamic single-molecule sensing (DSMS) strategy allows ultrasensitive detection of biomarkers at the femtomolar level by identifying specific binding according to molecular binding traces. However, the accuracy in classifying binding traces is not sufficient from separate features, such as the bound lifetime. Here, we establish a DSMS workflow to improve the sensitivity and linearity by classifying molecular binding traces in surface plasmon resonance microscopy with multiple kinetic features. The improvement is achieved by correlation analysis to select key features of binding traces, followed by unsupervised k-clustering. The results show that this unsupervised classification approach improves the sensitivity and linearity in microRNA (hsa-miR155-5p, hsa-miR21-5p, and hsa-miR362-5p) detection to achieve a limit of detection at the subfemtomolar level.
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Técnicas Biossensoriais , MicroRNAs , MicroRNAs/genética , Técnicas Biossensoriais/métodos , Ressonância de Plasmônio de Superfície , Nanotecnologia , BiomarcadoresRESUMO
Osteosarcoma (OS) is the most prevalent primary tumor of bones, often diagnosed late with a poor prognosis. Currently, few effective biomarkers or diagnostic methods have been developed for early OS detection with high confidence, especially for metastatic OS. Tumor-derived extracellular vesicles (EVs) are emerging as promising biomarkers for early cancer diagnosis through liquid biopsy. Here, we report a plasmonic imaging-based biosensing technique, termed subpopulation protein analysis by single EV counting (SPASEC), for size-dependent EV subpopulation analysis. In our SPASEC platform, EVs are accurately sized and counted on plasmonic sensor chips coated with OS-specific antibodies. Subsequently, EVs are categorized into distinct subpopulations based on their sizes, and the membrane proteins of each size-dependent subpopulation are profiled. We measured the heterogeneous expression levels of the EV markers (CD63, BMP2, GD2, and N-cadherin) in each of the EV subsets from both OS cell lines and clinical plasma samples. Using the linear discriminant analysis (LDA) model, the combination of four markers is applied to classify the healthy donors (n = 37), nonmetastatic OS patients (n = 13), and metastatic patients (n = 12) with an area under the curve of 0.95, 0.92, and 0.99, respectively. SPASEC provides accurate EV sensing technology for early OS diagnosis.
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Biomarcadores Tumorais , Neoplasias Ósseas , Vesículas Extracelulares , Osteossarcoma , Humanos , Osteossarcoma/patologia , Osteossarcoma/diagnóstico , Vesículas Extracelulares/química , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Técnicas Biossensoriais , Análise DiscriminanteRESUMO
Lithium-sulfur (Li-S) batteries hold the superiority of eminent theoretical energy density (2600 Wh kg-1 ). However, the ponderous sulfur reduction reaction and the issue of polysulfide shuttling pose significant obstacles to achieving the practical wide-temperature operation of Li-S batteries. Herein, a covalent organic nanosheet-wrapped carbon nanotubes (denoted CON/CNT) composite is synthesized as an electrocatalyst for wide-temperature Li-S batteries. The design incorporates the CON skeleton, which contains imide and triazine functional units capable of chemically adsorbing polysulfides, and the underlaid CNTs facilitate the conversion of captured polysulfides enabled by enhanced conductivity. The electrocatalytic behavior and chemical interplay between polysulfides and the CON/CNT interlayer are elucidated by in situ X-ray diffraction detections and theoretical calculations. Resultantly, the CON/CNT-modified cells demonstrate upgraded performances, including wide-temperature operation ranging from 0 to 65 °C, high-rate performance (625 mAh g-1 at 5.0 C), exceptional high-rate cyclability (1000 cycles at 5.0 C), and stable operation under high sulfur loading (4.0 mg cm-2 ) and limited electrolyte (5 µL mgs -1 ). These findings might guide the development of advanced Li-S batteries.
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It has been well-established that light-matter interactions, as manifested by diverse linear and nonlinear optical (NLO) processes, are mediated by real and virtual particles, such as electrons, phonons, and excitons. Polarons, often regarded as electrons dressed by phonons, are known to contribute to exotic behaviors of solids, from superconductivity to photocatalysis, while their role in materials' NLO response remains largely unexplored. Here, the NLO response mediated by polarons supported by a model ionic metal oxide, TiO2, is examined. It is observed that the formation of polaronic states within the bandgap results in a dramatic enhancement of NLO absorption coefficient by over 130 times for photon energies in the sub-bandgap regions, characterized by a 100 fs scale ultrafast response that is typical for thermalized electrons in metals. The ultrafast polaronic NLO response is then exploited for the development of all-optical switches for ultrafast pulse generation in near-infrared (NIR) fiber lasers and modulation of optical signal in the telecommunication band based on evanescent interaction on a planar waveguide chip. These results suggest that the polarons supported by dielectric ionic oxides can fill the gaps left by dielectric and metallic materials and serve as a novel platform for nonlinear photonic applications.
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Bamboo, a renewable resource with rapid growth and an impressive height-to-diameter ratio, faces mechanical instability due to its slender structure. Despite this, bamboo maintains its posture without breaking in its battle against environmental and gravitational forces. But what drives this motor function in bamboo? This study subjected Moso bamboo (Phyllostachys edulis) to gravitational stimulation, compelling it to grow at a 45° angle instead of upright. Remarkably, the artificially inclined bamboo exhibited astonishing shape control and adjustment capabilities. The growth strain was detected at both macroscopic and microscopic levels, providing evidence for the presence of internal stress, namely growth stress. The high longitudinal tensile stress on the upper side, along with a significant asymmetry in stress distribution in tilted bamboo, plays a pivotal role in maintaining its mechanical stability. Drawing upon experimental findings, it can be deduced that the growth stress primarily originates from the broad layers of fiber cells. Bamboo could potentially regulate the magnitude of growth stress by modifying the number of fiber cell layers during its maturation process. Additionally, the microfibril angle and lignin disposition may decisively influence the generation of growth stress.
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Thin-film polarizing beam splitters (PBSs) fulfill a pivotal role in laser beam splitting, modulation, shaping and isolation. In this study, a high-reliability infrared broadband thin-film PBS was developed. To correct for tensile stress in Ge/YbF3 multilayer coatings, ZnSe compensation layers were incorporated in the multilayer design. The effects of different symmetrical periods on the spectral properties of the infrared PBS were systematically discussed. The infrared PBS operated at 45° and in the long-wave infrared (LWIR) band. Using the percent of optical extrema monitoring (POEM) strategy combined with the high-temperature optical constants (HTOC) of Ge film, the infrared PBS was precisely fabricated on ZnSe substrates. Subsequently, the spectral performance and film reliability of the infrared PBS were carefully characterized. Specifically, the transmittance of p-polarization surpassed 96%, while the extinction ratio exceeded 100:1 within the 10.6 ± 0.15â µm band. The infrared PBS demonstrated commendable environmental reliability, in addition to exhibiting excellent spectral characteristics.
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Photonic topological insulators with topologically protected edge states featuring one-way, robustness and backscattering-immunity possess extraordinary abilities to steer and manipulate light. In this work, we construct a topological heterostructure (TH) consisting of a domain of nontrivial pseudospin-type topological photonic crystals (PCs) sandwiched between two domains of trivial PCs based on two-dimensional all-dielectric core-shell PCs in triangle lattice. We consider three THs with different number of layers in the middle nontrivial domain (i.e., one-layer, two-layer, three-layer) and demonstrate that the projected band diagrams of the three THs host interesting topological waveguide states (TWSs) with properties of one-way, large-area, broad-bandwidth and robustness due to coupling effect of the helical edge states associated with the two domain-wall interfaces. Moreover, taking advantage of the tunable bandgap between the TWSs by the layer number of the middle domain due to the coupling effect, a topological Y-splitter with functionality of wavelength division multiplexing is explicitly demonstrated exploiting the unique feature of the dispersion curves of TWSs in the three THs. Our work not only offers a new method to realize pseudospin-polarized large-area TWSs with tunable mode-width, but also could provide new opportunities for practical applications in on-chip multifunctional (i.e., wavelength division multiplexing) photonic devices with topological protection and information processing with pseudospin-dependent transport.
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Plant viruses exist in a broader ecological community, with key components include non-vector herbivores that can impact vector abundance, behavior, and virus transmission within shared host plants. However, little is known about the effects of non-vector herbivores infestation on the virus transmission by vector insects on the neighboring plants through inter-plant airborne chemicals. In this study, we investigated how volatiles emitted from tomato plants infested with the two-spotted spider mite (Tetranychus urticae) affect the infection of Tomato yellow leaf curl virus (TYLCV) transmitted by the whitefly (Bemisia tabaci) in the neighboring plants. Exposure of neighboring tomato plants to volatiles released from T. urticae-infested tomato plants reduced subsequent herbivory as well as TYLCV transmission and infection, and JA signaling pathway was essential for generation of the inter-plant defense signals. We also demonstrated that (E)-ß-Ocimene and MeSA were two volatiles induced by T. urticae that synergistically attenuated TYLCV transmission and infection in tomato. Thus, our findings suggest that plant-plant communication via volatiles likely represents a widespread defensive mechanism that substantially contributes to plant fitness. Understanding such phenomena may help us to predict the occurrence and epidemic of multiple herbivores and viruses in the agroecosystem, ultimately to manage pest and virus outbreaks.
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Arenobufagin (ArBu) is a natural monomer extracted and isolated from the secretion of the Chinese toad, also known as toad venom. This compound exerts anti-tumor effects by promoting apoptosis in tumor cells, inhibiting tumor angiogenesis, and preventing the invasion and migration of tumor cells. However, their impact on ferroptosis in tumor cells has yet to be fully confirmed. In this study, we established a subcutaneous transplant tumor model in nude mice to investigate the inhibitory effect of ArBu on gastric cancer cells (MGC-803) and the safety of drug delivery. in vitro experiments, we screened the most sensitive cancer cell lines using the MTT method and determined the response of ArBu to cell death. Use flow cytometry to measure cytoplasmic and lipid reactive oxygen species (ROS) levels. Determine the expression levels of ferritin-related proteins through Western blot experiments. In addition, a MGC-803 cell model overexpressing Nrf2 was created using lentiviral transfection to investigate the role of ArBu in inducing ferroptosis in cancer cells. Our research findings indicate that ArBu inhibits the proliferation of MGC-803 cells and is linked to ferroptosis. In summary, our research findings indicate that ArBu is a potential anti-gastric cancer drug that can induce ferroptosis in human cancer cells through the Nrf2/SLC7A11/GPX4 pathway.
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Bufanolídeos , Ferroptose , Neoplasias Gástricas , Humanos , Animais , Camundongos , Neoplasias Gástricas/tratamento farmacológico , Fator 2 Relacionado a NF-E2/genética , Camundongos Nus , Espécies Reativas de OxigênioRESUMO
Dark photons have emerged as promising candidates for dark matter, and their search is a top priority in particle physics, astrophysics, and cosmology. We report the first use of a tunable niobium superconducting radio-frequency cavity for a scan search of dark photon dark matter with innovative data analysis techniques. We mechanically adjusted the resonant frequency of a cavity submerged in liquid helium at a temperature of 2 K, and scanned the dark photon mass over a frequency range of 1.37 MHz centered at 1.3 GHz. Our study leveraged the superconducting radio-frequency cavity's remarkably high quality factors of approximately 10^{10}, resulting in the most stringent constraints to date on a substantial portion of the exclusion parameter space on the kinetic mixing coefficient ε between dark photons and electromagnetic photons, yielding a value of ε<2.2×10^{-16}.
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Constructing organic composite materials through molecular recognition has emerged as an important theme in materials science. Here we report an ion-pair recognition system involving the use of a propoxylated pillar[5]arene (PrP5) to modulate the solid-state photophysical properties of dye trans-4'-(dimethylamino)-N-methyl-4-stilbazolium hexafluorophosphate (DMASP). Single crystal X-ray diffraction analysis reveals that the dye guest DMASP is encapsulated by PrP5 to form a 2:1 host-guest complex 2PrP5⸧DMASP in the crystalline state. The macrocyclic skeleton of PrP5 imposes restrictions on the intramolecular motions of the dye guest, leading to a significant enhancement of its fluorescence emission. Additionally, within the 2PrP5⸧DMASP complex crystal structure, DMASP molecules are found to display two possible opposite orientations in the one-dimensional channels formed by PrP5 molecules. This arrangement is believed to alter the overall solid-state packing structure of DMASP, thereby activating its nonlinear optical activity. This work not only reports a novel ion-pair molecular recognition system based on pillararenes but also provides valuable insights into the modulation of the crystalline state photophysical properties of organic dyes via cocrystal engineering.
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BACKGROUND: Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes. METHODS: Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram. RESULTS: This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance. CONCLUSION: Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.
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Biomarcadores Tumorais , Neoplasias Colorretais , Progressão da Doença , Instabilidade de Microssatélites , Fosfopiruvato Hidratase , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Prognóstico , Feminino , Masculino , Regulação Neoplásica da Expressão Gênica , Transição Epitelial-Mesenquimal/genética , Pessoa de Meia-Idade , Nomogramas , Análise de Célula Única , Variações do Número de Cópias de DNARESUMO
Changes in the intestinal microbiota have been observed in patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE). However, whether and how the intestinal microbiota is involved in the pathogenesis of NMDARE susceptibility needs to be demonstrated. Here, we first showed that germ-free (GF) mice that underwent fecal microbiota transplantation (FMT) from NMDARE patients, whose fecal microbiota exhibited low short-chain fatty acid content, decreased abundance of Lachnospiraceae, and increased abundance of Verrucomicrobiota, Akkermansia, Parabacteroides, Oscillospirales, showed significant behavioral deficits. Then, these FMT mice were actively immunized with an amino terminal domain peptide from the GluN1 subunit (GluN1356-385) to mimic the pathogenic process of NMDARE. We found that FMT mice showed an increased susceptibility to an encephalitis-like phenotype characterized by more clinical symptoms, greater pentazole (PTZ)-induced susceptibility to seizures, and higher levels of T2 weighted image (T2WI) hyperintensities following immunization. Furthermore, mice with dysbiotic microbiota had impaired blood-brain barrier integrity and a proinflammatory condition. In NMDARE-microbiota recipient mice, the levels of Evan's blue (EB) dye extravasation increased, ZO-1 and claudin-5 expression decreased, and the levels of proinflammatory cytokines (IL-1, IL-6, IL-17, TNF-α and LPS) increased. Finally, significant brain inflammation, mainly in hippocampal and cortical regions, with modest neuroinflammation, immune cell infiltration, and reduced expression of NMDA receptors were observed in NMDARE microbiota recipient mice following immunization. Overall, our findings demonstrated that intestinal dysbiosis increased NMDARE susceptibility, suggesting a new target for limiting the occurrence of the severe phenotype of NMDARE.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Humanos , Camundongos , Animais , Barreira Hematoencefálica , Disbiose , Homeostase , PermeabilidadeRESUMO
Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.
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Aterosclerose , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3 , Fator de Transcrição STAT3/metabolismo , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Camundongos , Masculino , Dieta Hiperlipídica/efeitos adversos , Humanos , Células RAW 264.7 , Camundongos Knockout , Ligação Proteica , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismoRESUMO
BACKGROUND: Periodontitis is a chronic destructive inflammatory disease exacerbated by osteoblast dysfunction. Ferroptosis has emerged as a significant factor that could contribute to the pathological changes observed in periodontitis. However, the impact of ferroptosis on osteogenic differentiation and gene expression patterns of primary osteoblasts remain elusive. METHODS: In this study, osteoblasts were osteogenically induced for specific durations with and without the ferroptosis inducer erastin. Subsequently, cell proliferation, ferroptosis-related molecules, and osteogenic differentiation capacity were assessed. Furthermore, the differences in transcriptome expression following erastin treatment were analyzed by RNA sequencing. RESULTS: The results demonstrated that erastin treatment induced ferroptosis, resulting in suppressed cell proliferation and impaired osteogenic differentiation. Transcriptomic analysis revealed significant alterations in processes such as hydrogen peroxide catabolism, response to lipid peroxidation, and metal iron binding, as well as BMP receptor activity and collagen type XI trimer. CONCLUSION: The ferroptosis inducer erastin inhibited osteoblast proliferation and differentiation. Our study provides novel insights into the effect of ferroptosis on osteogenesis, suggesting that targeting ferroptosis may present a promising approach in the treatment of periodontitis.
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Diferenciação Celular , Proliferação de Células , Ferroptose , Osteoblastos , Osteogênese , Piperazinas , Ferroptose/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Animais , Piperazinas/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos , Células CultivadasRESUMO
In this paper, the synthesis, photophysics, electrochemistry, and intramolecular energy transfer of two series of dinuclear and tetranuclear metallic complexes [(bpy)2M1LxM2(bpy)2]4+ (x = 1, 2; M1 = Ru, M2 = Ru/Os; M1 = Os, M2 = Ru) and {[Ru(bpy)2(Lx)]3Ru}8+ based on new heteroditopic bridging ligands (L1 = 6-phenyl-4-Hpip-2-2'-bipyridine, L2 = 6-Hpip-2-2'-bipyridine, Hpip = 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline) are reported. The dimetallic and tetrametallic complexes exhibit rich redox properties with successive reversible metal-centered oxidation and ligand-centered reduction couples. All complexes display intense absorption in the entire ultraviolet-visible spectral regions. The mononuclear [LxRu(bpy)2]2+ and homodinuclear [(bpy)2RuLxRu(bpy)2]4+ complexes display strong Ru-based characteristic emission at room temperature. Interestingly, the optical studies of heterodinuclear complexes reveal almost complete quenching of the RuII-based emission and efficient photoinduced energy transfer, resulting in an OsII-based emission in the near-infrared region. As a result of the intramolecular energy transfer from the center to the periphery and steric hindrance quenching of the peripheral RuII-centered emissive triplet metal-to-ligand charge transfer states, the tetranuclear complexes exhibit weak RuII-based emission with a short lifetime. Since the light absorbed by several chromophores is efficiently directed to the subunit with the lowest-energy excited state, the present multinuclear complexes can be used as well-visible-light-absorption antennas.