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This study investigated the role of O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation hierarchy and heterogeneity in grade 2-3 gliomas, focusing on variations in chemotherapy benefits and resection dependency. A cohort of 668 newly diagnosed grade 2-3 gliomas, with comprehensive clinical, radiological, and molecular data, formed the basis of this analysis. The extent of resection was categorized into gross total resection (GTR ≥100%), subtotal resection (STR >90%), and partial resection (PR ≤90%). MGMTp methylation levels were examined using quantitative pyrosequencing. Our findings highlighted the critical role of GTR in improving the prognosis for astrocytomas (IDH1/2-mutant and 1p/19q non-codeleted), contrasting with its lesser significance for oligodendrogliomas (IDH1/2 mutation and 1p/19q codeletion). Oligodendrogliomas demonstrated the highest average MGMTp methylation levels (median: 28%), with a predominant percentage of methylated cases (average methylation levels >20%). Astrocytomas were more common in the low-methylated group (10%-20%), while IDH wild-type gliomas were mostly unmethylated (<10%). Spatial distribution analysis revealed a decrement in frontal lobe involvement from methylated, low-methylated to unmethylated cases (72.8%, 59.3%, and 47.8%, respectively). In contrast, low-methylated and unmethylated cases were more likely to invade the temporal-insular region (19.7%, 34.3%, and 40.4%, respectively). Astrocytomas with intermediate MGMTp methylation were notably associated with temporal-insular involvement, potentially indicating a moderate response to temozolomide and underscoring the importance of aggressive resection strategies. In conclusion, our study elucidates the complex interplay of MGMTp methylation hierarchy and heterogeneity among grade 2-3 gliomas, providing insights into why astrocytomas and IDH wild-type lower-grade glioma might derive less benefit from chemotherapy.
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Ultrafast electron diffraction using MeV energy beams(MeV-UED) has enabled unprecedented scientific opportunities in the study of ultrafast structural dynamics in a variety of gas, liquid and solid state systems. Broad scientific applications usually pose different requirements for electron probe properties. Due to the complex, nonlinear and correlated nature of accelerator systems, electron beam property optimization is a time-taking process and often relies on extensive hand-tuning by experienced human operators. Algorithm based efficient online tuning strategies are highly desired. Here, we demonstrate multi-objective Bayesian active learning for speeding up online beam tuning at the SLAC MeV-UED facility. The multi-objective Bayesian optimization algorithm was used for efficiently searching the parameter space and mapping out the Pareto Fronts which give the trade-offs between key beam properties. Such scheme enables an unprecedented overview of the global behavior of the experimental system and takes a significantly smaller number of measurements compared with traditional methods such as a grid scan. This methodology can be applied in other experimental scenarios that require simultaneously optimizing multiple objectives by explorations in high dimensional, nonlinear and correlated systems.
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Manipulating the polarization of light at the nanoscale is key to the development of next-generation optoelectronic devices. This is typically done via waveplates using optically anisotropic crystals, with thicknesses on the order of the wavelength. Here, using a novel ultrafast electron-beam-based technique sensitive to transient near fields at THz frequencies, we observe a giant anisotropy in the linear optical response in the semimetal WTe2 and demonstrate that one can tune the THz polarization using a 50 nm thick film, acting as a broadband wave plate with thickness 3 orders of magnitude smaller than the wavelength. The observed circular deflections of the electron beam are consistent with simulations tracking the trajectory of the electron beam in the near field of the THz pulse. This finding offers a promising approach to enable atomically thin THz polarization control using anisotropic semimetals and defines new approaches for characterizing THz near-field optical response at far-subwavelength length scales.
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We present an experimental demonstration of ultrafast electron diffraction (UED) with THz-driven electron bunch compression and time-stamping that enables UED probes with improved temporal resolution. Through THz-driven longitudinal bunch compression, a compression factor of approximately four is achieved. Moreover, the time-of-arrival jitter between the compressed electron bunch and a pump laser pulse is suppressed by a factor of three. Simultaneously, the THz interaction imparts a transverse spatiotemporal correlation on the electron distribution, which we utilize to further enhance the precision of time-resolved UED measurements. We use this technique to probe single-crystal gold nanofilms and reveal transient oscillations in the THz near fields with a temporal resolution down to 50 fs. These oscillations were previously beyond reach in the absence of THz compression and time-stamping.
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Phonon scattering in metals is one of the most fundamental processes in materials science. However, understanding such processes has remained challenging and requires detailed information on interactions between phonons and electrons. We use an ultrafast electron diffuse scattering technique to resolve the nonequilibrium phonon dynamics in femtosecond-laser-excited tungsten in both time and momentum. We determine transient populations of phonon modes which show strong momentum dependence initiated by electron-phonon coupling. For phonons near Brillouin zone border, we observe a transient rise in their population on a timescale of approximately 1 picosecond driven by the strong electron-phonon coupling, followed by a slow decay on a timescale of approximately 8 picosecond governed by the weaker phonon-phonon relaxation process. We find that the exceptional harmonicity of tungsten is needed for isolating the two processes, resulting in long-lived nonequilibrium phonons in a pure metal. Our finding highlights that electron-phonon scattering can be the determinant factor in the phonon thermal transport of metals.
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Identifying multiple rival reaction products and transient species formed during ultrafast photochemical reactions and determining their time-evolving relative populations are key steps toward understanding and predicting photochemical outcomes. Yet, most contemporary ultrafast studies struggle with clearly identifying and quantifying competing molecular structures/species among the emerging reaction products. Here, we show that mega-electronvolt ultrafast electron diffraction in combination with ab initio molecular dynamics calculations offer a powerful route to determining time-resolved populations of the various isomeric products formed after UV (266 nm) excitation of the five-membered heterocyclic molecule 2(5H)-thiophenone. This strategy provides experimental validation of the predicted high (â¼50%) yield of an episulfide isomer containing a strained three-membered ring within â¼1 ps of photoexcitation and highlights the rapidity of interconversion between the rival highly vibrationally excited photoproducts in their ground electronic state.
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Understanding the origin of electron-phonon coupling in lead halide perovskites is key to interpreting and leveraging their optical and electronic properties. Here we show that photoexcitation drives a reduction of the lead-halide-lead bond angles, a result of deformation potential coupling to low-energy optical phonons. We accomplish this by performing femtosecond-resolved, optical-pump-electron-diffraction-probe measurements to quantify the lattice reorganization occurring as a result of photoexcitation in nanocrystals of FAPbBr3. Our results indicate a stronger coupling in FAPbBr3 than CsPbBr3. We attribute the enhanced coupling in FAPbBr3 to its disordered crystal structure, which persists down to cryogenic temperatures. We find the reorganizations induced by each exciton in a multi-excitonic state constructively interfere, giving rise to a coupling strength that scales quadratically with the exciton number. This superlinear scaling induces phonon-mediated attractive interactions between excitations in lead halide perovskites.
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Molecular ions are ubiquitous and play pivotal roles1-3 in many reactions, particularly in the context of atmospheric and interstellar chemistry4-6. However, their structures and conformational transitions7,8, particularly in the gas phase, are less explored than those of neutral molecules owing to experimental difficulties. A case in point is the halonium ions9-11, whose highly reactive nature and ring strain make them short-lived intermediates that are readily attacked even by weak nucleophiles and thus challenging to isolate or capture before they undergo further reaction. Here we show that mega-electronvolt ultrafast electron diffraction (MeV-UED)12-14, used in conjunction with resonance-enhanced multiphoton ionization, can monitor the formation of 1,3-dibromopropane (DBP) cations and their subsequent structural dynamics forming a halonium ion. We find that the DBP+ cation remains for a substantial duration of 3.6 ps in aptly named 'dark states' that are structurally indistinguishable from the DBP electronic ground state. The structural data, supported by surface-hopping simulations15 and ab initio calculations16, reveal that the cation subsequently decays to iso-DBP+, an unusual intermediate with a four-membered ring containing a loosely bound17,18 bromine atom, and eventually loses the bromine atom and forms a bromonium ion with a three-membered-ring structure19. We anticipate that the approach used here can also be applied to examine the structural dynamics of other molecular ions and thereby deepen our understanding of ion chemistry.
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OBJECTIVE: To investigate the effect of intramedullary nail fixation (IMN) and minimally invasive percutaneous plate internal fixation (MIPPO) techniques on tibiofibular fractures and their effect on platelet activation and serum transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-2 (BMP-2). METHODS: Total of 105 patients with tibiofibular fractures from February 2019 to February 2020 were selected and divided into 53 cases in the MIPPO group and 52 cases in the IMN group. There were 29 males and 24 females with an average age of (41.74±6.05) years old in MIPPO group;in IMN group, 31 males and 21 females with an average age of (40.59±5.26) years old. The perioperative surgical indexes, postoperative complications, ankle function recovery at 12 months postoperatively, platelet activation indexes at 3 and 7 days preoperatively and postoperatively, and serum TGF-ß1 and BMP-2 levels at 4 and 8 weeks preoperatively and postoperatively were compared between the two groups. RESULTS: The operating time and fracture healing time in the MIPPO group were shorter than those in the IMN group(P<0.05); Compared with the preoperative period, the levels of GMP-140, PAC-1, CD63, and CD61 increased in both groups at 3 and 7 days after surgery, but were lower in the MIPPO group than in the IMN group(P<0.05);the levels of serum TGF-ß1 and BMP-2 increased in both groups at 4 and 8 weeks after surgery compared with the preoperative period, and the postoperative complication rate in the MIPPO group was lower than that in the IMN group(P<0.05);the difference was not statistically significant in the excellent rate of ankle function recovery at 12 months follow-up after surgery between two groups(P>0.05). CONCLUSION: Both intramedullary nail fixation and MIPO technique for treatment of tibia and fibula fractures can improve ankle joint function, but the latter has the advantages of short operation time, fast fracture healing, fewer complications, and light platelet activation. Serum TGF-ß1, BMP-2 level improves quickly.
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Fijación Intramedular de Fracturas , Fracturas Múltiples , Fracturas de la Tibia , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Tibia/cirugía , Tibia/lesiones , Factor de Crecimiento Transformador beta1 , Fijación Intramedular de Fracturas/métodos , Fracturas de la Tibia/cirugía , Fijación Interna de Fracturas/métodos , Placas Óseas , Curación de Fractura , Complicaciones Posoperatorias , Resultado del Tratamiento , Proteínas Morfogenéticas Óseas , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Despite the release of updated metrics for Life's Essential 8 (LE8), key indicators for assessing cardiovascular health (CVH) status, there is currently no report on their distribution among Chinese children. OBJECTIVE: This study aimed to assess the nationwide distribution of CVH in Chinese school-aged children using LE8 scores and analyze temporal changes in these scores over time. METHODS: Participants aged 7 to 19 years from 11 waves (between 1989 and 2018) of the China Health and Nutrition Survey were included in this study. LE8 components were grouped into 2 domains of health behaviors (diet, physical activity, nicotine exposure, sleep) and health factors (BMI, blood lipids, blood glucose, blood pressure). Scores of overall CVH and each LE8 metric were calculated individually. Temporal changes were assessed with joint point regression models by rural and urban living residence. The causal relationships between health behaviors and health factors that changed the most over time were built with cross-lagged panel models. RESULTS: A total of 21,921 participants, 52.6% (n=11,537) of whom were male, who had data for at least 4 CVH components were included in the analysis. The mean age was 13 (SD 3.6) years. The overall CVH score remained stable in most regions, with the lowest found in Shandong from East China, which had a mean between 67 (SD 10.9) and 67.2 (SD 12.4). In contrast, the highest score was found in Guizhou from Southwest China, with a mean between 71.4 (SD 10.8) and 74.3 (SD 10.3). In rural areas, the diet score decreased significantly from 1997 onward with a speed of 0.18 (95% CI: 0.15-0.21; P<.001) per year, and the BMI score decreased significantly from 2005 onward with a speed of 0.56 (95% CI 0.44-0.68; P<.001) per year. In urban areas, the diet score decreased from 1994 onward with a speed of 0.03 (95% CI: 0.001-0.07; P=.04) per year, and the BMI score decreased from 2002 onward with a speed of 0.63 (95% CI 0.47-0.79; P<.001) per year. The sleep score dropped constantly in both urban and rural areas, with a speed of 0.69 (95% CI 0.58-0.80; P<.001) and 0.69 (95% CI: 0.52-0.86; P<.001) per year, respectively. A decline in the diet score led to a decline in the BMI score with a coefficient of 0.190 (95% CI 0.030-0.351; P=.02), while a decline in the BMI score led to a decline in sleep health with a coefficient of 0.089 (95% CI 0.010-0.168; P=.03). CONCLUSIONS: Chinese school-aged children and adolescents were generally of moderate CVH status, but mutual influences existed between CVH metrics. Dietary interventions should be prioritized for promoting overall CVH in the future.
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Enfermedades Cardiovasculares , Pueblos del Este de Asia , Estado de Salud , Adolescente , Niño , Femenino , Humanos , Masculino , Enfermedades Cardiovasculares/epidemiología , Estudios Transversales , Pueblos del Este de Asia/estadística & datos numéricos , Conductas Relacionadas con la Salud , Adulto Joven , Dieta Saludable/estadística & datos numéricos , Dieta Saludable/tendenciasRESUMEN
Directly imaging structural dynamics involving hydrogen atoms by ultrafast diffraction methods is complicated by their low scattering cross sections. Here we demonstrate that megaelectronvolt ultrafast electron diffraction is sufficiently sensitive to follow hydrogen dynamics in isolated molecules. In a study of the photodissociation of gas phase ammonia, we simultaneously observe signatures of the nuclear and corresponding electronic structure changes resulting from the dissociation dynamics in the time-dependent diffraction. Both assignments are confirmed by ab initio simulations of the photochemical dynamics and the resulting diffraction observable. While the temporal resolution of the experiment is insufficient to resolve the dissociation in time, our results represent an important step towards the observation of proton dynamics in real space and time.
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Dendrimers are a family of polymers with highly branched structure, well-defined composition, and extensive functional groups, which have attracted great attention in biomedical applications. Micelles formed by dendrimers are ideal nanocarriers for delivering anticancer agents due to the explicit study of their characteristics of particle size, charge, and biological properties such as toxicity, blood circulation time, biodistribution, and cellular internalization. Here, the classification, preparation, and structure of dendrimer micelles are reviewed, and the specific functional groups modified on the surface of dendrimers for tumor active targeting, stimuli-responsive drug release, reduced toxicity, and prolonged blood circulation time are discussed. In addition, their applications are summarized as various platforms for biomedical applications related to cancer therapy including drug delivery, gene transfection, nano-contrast for imaging, and combined therapy. Other applications such as tissue engineering and biosensor are also involved. Finally, the possible challenges and perspectives of dendrimer micelles for their further applications are discussed.
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Dendrímeros , Neoplasias , Humanos , Micelas , Dendrímeros/química , Distribución Tisular , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Portadores de Fármacos/químicaRESUMEN
Understanding how microscopic spin configuration gives rise to exotic properties at the macroscopic length scale has long been pursued in magnetic materials1-5. One seminal example is the Einstein-de Haas effect in ferromagnets1,6,7, in which angular momentum of spins can be converted into mechanical rotation of an entire object. However, for antiferromagnets without net magnetic moment, how spin ordering couples to macroscopic movement remains elusive. Here we observed a seesaw-like rotation of reciprocal lattice peaks of an antiferromagnetic nanolayer film, whose gigahertz structural resonance exhibits more than an order-of-magnitude amplification after cooling below the Néel temperature. Using a suite of ultrafast diffraction and microscopy techniques, we directly visualize this spin-driven rotation in reciprocal space at the nanoscale. This motion corresponds to interlayer shear in real space, in which individual micro-patches of the film behave as coherent oscillators that are phase-locked and shear along the same in-plane axis. Using time-resolved optical polarimetry, we further show that the enhanced mechanical response strongly correlates with ultrafast demagnetization, which releases elastic energy stored in local strain gradients to drive the oscillators. Our work not only offers the first microscopic view of spin-mediated mechanical motion of an antiferromagnet but it also identifies a new route towards realizing high-frequency resonators8,9 up to the millimetre band, so the capability of controlling magnetic states on the ultrafast timescale10-13 can be readily transferred to engineering the mechanical properties of nanodevices.
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OBJECTIVES: The long-term trends of cognitive function and its associations with physical performance remain unclear, particularly in Asian populations. The study objectives were to determine cognitive trajectories in middle-aged and elderly Chinese individuals, as well as to examine differences in physical performance across cognitive trajectory groups. METHODS: Data were extracted from the China Health and Retirement Longitudinal Study. A total of 5,701 participants (47.7% male) with a mean age of 57.8 (standard deviation, 8.4) years at enrollment were included. A group-based trajectory model was used to identify cognitive trajectory groups for each sex. Grip strength, repeated chair stand, and standing balance tests were used to evaluate physical performance. An ordered logistic regression model was employed to analyze differences in physical performance across cognitive trajectory groups. RESULTS: Three cognitive trajectory groups were identified for each sex: low, middle, and high. For both sexes, higher cognitive trajectory groups exhibited smaller declines with age. In the fully adjusted model, relative to the low trajectory group, the odds ratios (ORs) of better physical performance in the middle cognitive group were 1.37 (95% confidence interval [CI], 1.17 to 1.59; p<0.001) during follow-up and 1.40 (95% CI, 1.20 to 1.64; p<0.001) at the endpoint. The ORs in the high trajectory group were 1.94 (95% CI, 1.61 to 2.32; p<0.001) during follow-up and 2.04 (95% CI, 1.69 to 2.45; p<0.001) at the endpoint. CONCLUSIONS: Cognitive function was better preserved in male participants and individuals with higher baseline cognitive function. A higher cognitive trajectory was associated with better physical performance over time.
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Cognición , Jubilación , Anciano , Persona de Mediana Edad , Femenino , Humanos , Masculino , Estudios Longitudinales , Fuerza de la Mano , China/epidemiologíaRESUMEN
Malignant transformation (MT) of low-grade gliomas (LGGs) to a higher-grade variant seems inevitable, yet it remains unclear which LGG patients will progress to grade 3 or even directly to grade 4 after receiving a long course of treatment. To elucidate this, we conducted a retrospective cohort study based on 229 adults with recurrent LGG. Our study aimed to disclose the characteristics of different MT patterns and to build predictive models for patients with LGG. Patients were allocated into group 2-2 (n = 81, 35.4%), group 2-3 (n = 91, 39.7%), and group 2-4 (n = 57, 24.9%), based on their MT patterns. Patients who underwent MT showed lower Karnofsky performance scale (KPS) scores, larger tumor sizes, smaller extents of resection (EOR), higher Ki-67 indices, lower rates of 1p/19q codeletion, but higher rates of subventricular involvement, radiotherapy, chemotherapy, astrocytoma, and post-progression enhancement (PPE) compared with those in group 2-2 (p < 0.01). On multivariate logistic regression, 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score were independently associated with MT (p < 0.05). Survival analyses demonstrated that patients in group 2-2 had the longest survival, followed by group 2-3 and then group 2-4 (p < 0.0001). Based on these independent parameters, we constructed a nomogram model that exhibited superior potential (sensitivity: 0.864, specificity: 0.814, and accuracy: 0.843) compared with PPE in early prediction of MT. Combining the factors of 1p/19q codeletion, Ki-67 index, radiotherapy, EOR, and KPS score that were presented at initial diagnosis could precisely forecast the subsequent MT patterns of patients with LGG.
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Glioma , Glioma/diagnóstico , Glioma/patología , Humanos , Estudios Retrospectivos , Adulto , Clasificación del Tumor , Progresión de la Enfermedad , Modelos Teóricos , Neuroimagen , Masculino , Femenino , Adolescente , Adulto Joven , Persona de Mediana EdadRESUMEN
BACKGROUND: Recent evidence has revealed that circulating coagulation factor prekallikrein (PK), an important part of the kallikrein-kinin system, regulates cholesterol metabolism, but the association between serum PK and lipid levels is unclear. METHODS: This cross-sectional study included 256 subjects (aged from 1 month to 90 years) who underwent physical examinations at the First People's Hospital of Huaihua, China. After overnight fasting, serum was collected for PK and lipid testing. Spearman correlation analysis and multivariable logistic regression analysis were used to analyze the association of PK level with lipid levels and the likelihood risk of hyperlipidemia. The possible threshold value of PK was calculated according to the receiver operating characteristic (ROC) curve. RESULTS: The median serum PK level was 280.9 µg/mL (IQR 168.0, 377.0), and this level changed with age but not sex. The serum PK level was positively correlated with the serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. A nonlinear relationship was observed between serum PK and high-density lipoprotein cholesterol (HDL-C) levels. The serum PK level was positively correlated with HDL-C when its level was lower than 240 µg/mL and negatively correlated with HDL-C when its level was higher than 240 µg/mL. The regression analysis demonstrated that an elevated serum PK level was significantly associated with the likelihood risk of hypercholesterolemia and hypertriglyceridemia. The ROC curve showed that the possible threshold values of serum PK for hypercholesterolemia and hypertriglyceridemia occurrences were 344.9 µg/mL and 305.7 µg/mL, respectively. CONCLUSIONS: Elevated serum PK levels were significantly associated with the likelihood of hypercholesterolemia and hypertriglyceridemia, and the possible threshold values of PK levels were 344.9 µg/mL and 305.70 µg/mL, respectively, suggesting that higher PK levels may be a risk factor for cardiovascular diseases.
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Pueblos del Este de Asia , Hiperlipidemias , Precalicreína , Humanos , HDL-Colesterol , Estudios Transversales , Hipercolesterolemia/sangre , Hiperlipidemias/sangre , Hipertrigliceridemia/sangre , Precalicreína/análisis , Triglicéridos , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
Understanding the driving mechanisms behind metal-insulator transitions (MITs) is a critical step toward controlling material's properties. Since the proposal of charge order-induced MIT in magnetite Fe3O4 in 1939 by Verwey, the nature of the charge order and its role in the transition have remained elusive. Recently, a trimeron order was found in the low-temperature structure of Fe3O4; however, the expected transition entropy change in forming trimeron is greater than the observed value, which arises a reexamination of the ground state in the high-temperature phase. Here, we use electron diffraction to unveil that a nematic charge order on particular Fe sites emerges in the high-temperature structure of bulk Fe3O4 and that, upon cooling, a competitive intertwining of charge and lattice orders arouses the Verwey transition. Our findings discover an unconventional type of electronic nematicity in correlated materials and offer innovative insights into the transition mechanism in Fe3O4 via the electron-phonon coupling.
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Electrones , Fonones , Frío , Electrónica , EntropíaRESUMEN
A pyrrolodithiin-derived box-like cyclophane (ProBox), featuring an adaptive geometry with stimuli-responsiveness, was designed and successfully constructed. The dynamic and foldable dithiin subunit endowed the cyclophane with a compressible cavity which can transform from a hex-nut geometry to a nearly rectangular box upon complexing guests with various sizes and shapes. The resulting pseudorotaxane complexes could be dethreaded via electrochemical oxidation. Such an adaptive cavity along with redox-switchable host-guest binding of ProBox could enable further applications in complex molecular switches and machines.
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Strong coupling between light and mechanical strain forms the foundation for next-generation optical micro- and nano-electromechanical systems. Such optomechanical responses in two-dimensional materials present novel types of functionalities arising from the weak van der Waals bond between atomic layers. Here, by using structure-sensitive megaelectronvolt ultrafast electron diffraction, we report the experimental observation of optically driven ultrafast in-plane strain in the layered group IV monochalcogenide germanium sulfide (GeS). Surprisingly, the photoinduced structural deformation exhibits strain amplitudes of order 0.1% with a 10 ps fast response time and a significant in-plane anisotropy between zigzag and armchair crystallographic directions. Rather than arising due to heating, experimental and theoretical investigations suggest deformation potentials caused by electronic density redistribution and converse piezoelectric effects generated by photoinduced electric fields are the dominant contributors to the observed dynamic anisotropic strains. Our observations define new avenues for ultrafast optomechanical control and strain engineering within functional devices.