RESUMEN
Double-sided planetary grinding (DSPG) with a fixed abrasive is widely used in sapphire substrate processing. Compared with conventional free abrasive grinding, it has the advantages of high precision, high efficiency, and environmental protection. In this study, we propose a material removal rate (MRR) model specific to the fixed-abrasive DSPG process for sapphire substrates, grounded in the trajectory length of abrasive particles. In this paper, the material removal rate model is obtained after focusing on the theoretical analysis of the effective number of abrasive grains, the indentation depth of a single abrasive grain, the length of the abrasive grain trajectory, and the groove repetition rate. To validate this model, experiments were conducted on sapphire substrates using a DSPG machine. Theoretical predictions of the material removal rate were then juxtaposed with experimental outcomes across varying grinding pressures and rotational speeds. The trends between theoretical and experimental values showed remarkable consistency, with deviations ranging between 0.2% and 39.2%, thereby substantiating the model's validity. Moreover, leveraging the insights from this model, we optimized the disparity in the material removal rate between two surfaces of the substrate, thereby enhancing the uniformity of the machining process across both surfaces.
RESUMEN
Lunar-based equipment plays a vital role in the exploration of the moon because it undertakes the tasks of moving, transporting, digging, and so on. In order to control the gait of lunar-based equipment more precisely and guarantee mobile stability, the contact mechanism between its foot and lunar soil is worthy of in-depth study. In this paper, a contact model is proposed to predict the stress, strain, and displacement both on the contact surface and in the lunar soil when the foot is under vertical load. The axial stress in the proposed contact model is verified through the experiment and its accuracy in the lunar equipment is verified through simulation. The error is in a reasonable range and the influence depth of load conforms to the experiment results. This paper provides a relatively accurate model to describe the contact force between the lunar-based equipment's foot and the lunar soil and will promote the research of lunar exploration.
RESUMEN
The 8-16-4 graphyne, a recently identified two-dimensional carbon allotrope, exhibits distinctive mechanical and electrical properties, making it a candidate material for flexible electronic applications. This study endeavors to enhance our comprehension of the fracture behavior and mechanical properties of 8-16-4 graphyne. The mechanical properties of 8-16-4 graphyne were evaluated through molecular dynamics simulations, examining the impact of boundary conditions, temperature, and strain rate, as well as the coupled interactions between temperature, vacancy defects, and microcracks. The findings reveal that 8-16-4 graphyne undergoes fracture via the cleavage of ethylene bonds at a critical strain value of approximately 0.29. Variations in boundary conditions and strain rate influence the fidelity of tensile simulation outcomes. Temperature, vacancy concentration, and the presence of microcracks markedly affect the mechanical properties of 8-16-4 graphyne. In contrast to other carbon allotropes, 8-16-4 graphyne exhibits a diminished sensitivity to vacancy defects in its mechanical performance. However, carbon vacancies at particular sites are more prone to initiating cracks. Furthermore, pre-existing microcracks within the material can potentially alter the fracture mode.
RESUMEN
Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.
Asunto(s)
COVID-19 , Microbioma Gastrointestinal , Trombosis , Humanos , Ratones , Animales , Integrina alfa2beta1/genética , Integrina alfa2beta1/metabolismo , Colágeno/metabolismo , Plaquetas/metabolismo , COVID-19/metabolismoRESUMEN
Colorectal cancer (CRC), which shows a high degree of heterogeneity, is the third most deadly cancer worldwide. Mutational activation of KRASG12D occurs in approximately 10-12% of CRC cases, but the susceptibility of KRASG12D-mutated CRC to the recently discovered KRASG12D inhibitor MRTX1133 has not been fully defined. Here, we report that MRTX1133 treatment caused reversible growth arrest in KRASG12D-mutated CRC cells, accompanied by partial reactivation of RAS effector signaling. Through a drug-anchored synthetic lethality screen, we discovered that epidermal growth factor receptor (EGFR) inhibition was synthetic lethal with MRTX1133. Mechanistically, MRTX1133 treatment downregulated the expression of ERBB receptor feedback inhibitor 1 (ERRFI1), a crucial negative regulator of EGFR, thereby causing EGFR feedback activation. Notably, wild-type isoforms of RAS, including H-RAS and N-RAS, but not oncogenic K-RAS, mediated signaling downstream of activated EGFR, leading to RAS effector signaling rebound and reduced MRTX1133 efficacy. Blockade of activated EGFR with clinically used antibodies or kinase inhibitors suppressed the EGFR/wild-type RAS signaling axis, sensitized MRTX1133 monotherapy, and caused the regression of KRASG12D-mutant CRC organoids and cell line-derived xenografts. Overall, this study uncovers feedback activation of EGFR as a prominent molecular event that restricts KRASG12D inhibitor efficacy and establishes a potential combination therapy consisting of KRASG12D and EGFR inhibitors for patients with KRASG12D-mutated CRC.
Asunto(s)
Neoplasias Colorrectales , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Receptores ErbB/metabolismo , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Retroalimentación FisiológicaRESUMEN
The vast majority of existing sub-Nyquist sampling wideband spectrum sensing (WSS) methods default to a sparse spectrum. However, research data suggests that in the near future, the wideband spectrum will no longer be sparse. This article proposes a sub-Nyquist sampling WSS algorithm that can adapt well to non-sparse spectrum scenarios. The algorithm continues to implement the idea of our previously proposed "no reconstruction (NoR) of spectrum" algorithm, thus having low computational complexity. The new one is actually an advanced version of the NoR algorithm, so it is called AdNoR. The key to its advancement lies in the establishment of a folded time-frequency (TF) spectrum model with the same special structure as in the fold spectrum model of the NoR algorithm. For this purpose, we have designed a comprehensive sampling technique which consists of multicoset sampling, digital fractional delay, and TF transform. It is verified by simulation that the AdNoR algorithm maintains a good sensing performance with low computational complexity in the non-sparse scenario.
Asunto(s)
Algoritmos , Simulación por ComputadorRESUMEN
Despite timely immunization programs, and efficacious vaccines conveying protection against SARS-CoV-2 infection, breakthrough infections in vaccinated individuals have been reported. The Delta variant of concern (VOC) outbreak in Guangzhou resulted in local transmission in vaccinated and non-vaccinated residents, providing a unique opportunity to study the protective effects of the inactivated vaccines in breakthrough infection. Here, we find that the 2-dose vaccinated group has similar peak viral titers and comparable speeds of viral RNA clearance to the non-vaccinated group but accelerated viral suppression in the middle course of the disease. We quantitatively demonstrate that peak viral pneumonia is significantly mitigated in the 2-dose vaccine group (median 0.298%) compared with the non-vaccinated (5.77%) and 1-dose vaccine (3.34%) groups. Pneumonia absorbance is approximately 6 days ahead in the 2-dose group (median 10 days) than in the non-vaccinated group (16 days) (p = 0.003). We also observe reduced cytokine inflammation and markedly undisturbed gene transcription profiles of peripheral blood mononuclear cells (PBMCs) in the 2-dose group. In short, our study demonstrates that prior vaccination substantially restrains pneumonia development, reduces cytokine storms, and facilitates clinical recovery.
Asunto(s)
COVID-19 , Vacunas Virales , COVID-19/prevención & control , Humanos , Leucocitos Mononucleares , SARS-CoV-2 , VacunaciónRESUMEN
Single-crystal silicon carbide (SiC) is widely used because of its excellent properties. However, SiC is a typical hard and brittle material, and there are many challenges in realizing its high efficiency and high-precision machining. Grinding is the main method used to achieve the high-efficiency processing of SiC, but the contradiction between processing quality and processing efficiency is prominent. Vibration-assisted grinding is an effective method to realize high-efficiency and precision machining of SiC. To reveal the vibration-assisted grinding mechanism of SiC, the vibration-assisted nano-scratch process is studied using the molecular dynamics method, and the material removal process and damage formation mechanism in the vibration-assisted scratch are analyzed. Aiming at the three main structural crystal types, 3C-, 4H- and 6H-SiC, scratch simulations were carried out. The vibration-assisted scratch characteristics of SiC polytypes were evaluated from the perspectives of scratch force and the amorphous layer. It was found that the effects of vibration-assisted scratch on different crystal structures of SiC differ, and 3C-SiC is quite different from 4H- and 6H-SiC. Through vibration-assisted scratch simulations under different scratch conditions and vibration characteristics, the influence laws for machining parameters and vibration characteristic parameters were explored. It was found that increasing the frequency and amplitude was beneficial for improving the machining effect. This provides a basis for vibration-assisted grinding technology to be used in the high-efficiency precision machining of SiC.
RESUMEN
Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.
Asunto(s)
COVID-19/sangre , Hiperglucemia/sangre , Resistencia a la Insulina , Metabolismo de los Lípidos , Lípidos/sangre , SARS-CoV-2/metabolismo , Adulto , Anciano , Biomarcadores/sangre , COVID-19/complicaciones , Femenino , Humanos , Hiperglucemia/etiología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Since April 2021, the SARS-CoV-2 (B.1.167) Delta variant has been rampant worldwide. Recently, this variant has spread in Guangzhou, China. Our objective was to characterize the clinical features and risk factors of severe cases of the Delta variant in Guangzhou. METHODS: A total of 144 patients with the Delta variant were enrolled, and the data between the severe and non-severe groups were compared. Logistic regression methods and Cox multivariate regression analysis were used to investigate the risk factors of severe cases. RESULTS: The severity of the Delta variant was 11.1%. Each 1-year increase in age (OR, 1.089; 95% CI, 1.035-1.147; P = 0.001) and each 1-µmol/L increase in total bilirubin (OR, 1.198; 95% CI, 1.021-1.406; P = 0.039) were risk factors for severe cases. Moreover, the risk of progression to severe cases increased 13.444-fold and 3.922-fold when the age was greater than 58.5 years (HR, 13.444; 95% CI, 2.989-60.480; P = 0.001) or the total bilirubin level was greater than 7.23 µmol/L (HR, 3.922; 95% CI, 1.260-12.207; P = 0.018), respectively. CONCLUSION: Older age and elevated total bilirubin were independent risk factors for severe cases of the Delta variant in Guangzhou, especially if the age was greater than 58.5 years or the total bilirubin level was greater than 7.23 µmol/L.
Asunto(s)
COVID-19/terapia , SARS-CoV-2/aislamiento & purificación , Adulto , COVID-19/diagnóstico , COVID-19/mortalidad , COVID-19/prevención & control , Vacunas contra la COVID-19 , Enfermedades Cardiovasculares/epidemiología , China/epidemiología , Comorbilidad , Tos/etiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Fiebre/etiología , Mortalidad Hospitalaria , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2/genética , Índice de Severidad de la EnfermedadAsunto(s)
COVID-19/sangre , COVID-19/genética , COVID-19/terapia , Pruebas de Neutralización , SARS-CoV-2/genética , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/inmunología , China , Variación Genética , Humanos , Inmunidad Humoral , Inmunización Pasiva , Persona de Mediana Edad , Mutación , Glicoproteína de la Espiga del Coronavirus , Adulto Joven , Sueroterapia para COVID-19RESUMEN
OBJECTIVE: The aim of this study was to present the clinical characteristics and dynamic changes in laboratory parameters of the coronavirus disease 2019 (COVID-19) in Guangzhou, and explore the probable early warning indicators of disease progression. METHOD: We enrolled all the patients diagnosed with COVID-19 in the Guangzhou No. 8 People's Hospital. The patients' demographic and epidemiologic data were collected, including chief complaints, lab results, and imaging examination findings. RESULTS: The characteristics of the patients in Guangzhou are different from those in Wuhan. The patients were younger in age, predominately female, and their condition was not commonly combined with other diseases. A total of 75% of patients suffered fever on admission, followed by cough occurring in 62% patients. Comparing the mild/normal and severe/critical patients, being male, of older age, combined with hypertension, abnormal blood routine test results, raised creatine kinase, glutamic oxaloacetic transaminase, lactate dehydrogenase, C-reactive protein, procalcitonin, D-dimer, fibrinogen, activated partial thromboplastin time, and positive proteinuria were early warning indicators of severe disease. CONCLUSION: The patients outside epidemic areas showed different characteristics from those in Wuhan. The abnormal laboratory parameters were markedly changed 4 weeks after admission, and also were different between the mild and severe patients. More evidence is needed to confirm highly specific and sensitive potential early warning indicators of severe disease.
RESUMEN
We report a comprehensive experimental and theoretical study of the lower-wavenumber vibrational modes in the surface-enhanced hyper-Raman scattering (SEHRS) of Rhodamine 6G (R6G) and its isotopologue R6G-d4. Measurements acquired on-resonance with two different electronic states, S1 and S2, are compared to the time-dependent density functional theory computations of the resonance hyper-Raman spectra and electrodynamics-quantum mechanical computations of the SEHRS spectra on-resonance with S1 and S2. After accounting for surface orientation, we find excellent agreement between experiment and theory for both R6G and its isotopologue. We then present a detailed analysis of the complex vibronic coupling effects in R6G and the importance of surface orientation for characterizing the system. This combination of theory and experiment allows, for the first time, an unambiguous assignment of lower-wavenumber vibrational modes of R6G and its isotopologue R6G-d4.
RESUMEN
Severe patients of the coronavirus disease 2019 (COVID-19) may progress rapidly to critical stage. This study aimed to identify factors useful for predicting the progress. 33 severe COVID-19 patients at the intensive care unit were included in this study. During treatment, 13 patients deteriorated and required further treatment for supporting organ function. The remaining 20 patients alleviated and were transferred to the general wards. The multivariate COX regression analyses showed that hypoproteinemia was an independent risk factor associated with deterioration of severe patients (HR, 0.763; 95% CI, 0.596 to 0.978; p = 0.033). The restricted cubic spline indicated that when HR = 1, the corresponding value of albumin is 29.6 g/L. We used the cutoff of 29.6 g/L to divide these patients. Kaplan-Meier curves showed that the survival rate of the high-albumin group was higher than that of the low-albumin group. Therefore, hypoalbuminemia may be an independent risk factor to evaluate poor prognosis of severely patients with COVID-19, especially when albumin levels were below 29.6 g/L.
RESUMEN
OBJECTIVE: Coronavirus disease 2019 (COVID-19) outbreak is a major challenge all over the world, without acknowledged treatment. Intravenous immunoglobulin (IVIG) has been recommended to treat critical coronavirus disease 2019 (COVID-19) patients in a few reviews, but the clinical study evidence on its efficacy in COVID-19 patients was lacking. METHODS: 325 patients with laboratory-confirmed critical COVID-19 were enrolled from 4 government-designated COVID-19 treatment centres in southern China from December 2019 to March 2020. The primary outcomes were 28- and 60-day mortality, and the secondary outcomes were the total length of in-hospital and the total duration of the disease. Subgroup analysis was carried out according to clinical classification of COVID-19, IVIG dosage and timing. RESULTS: In the enrolled 325 patients, 174 cases used IVIG and 151 cases did not. The 28-day mortality was improved with IVIG after adjusting confounding in overall cohort (P = 0.0014), and the in-hospital and the total duration of disease were longer in the IVIG group (P < 0.001). Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28-day mortality, decrease the inflammatory response and improve some organ functions (all P < 0.05); the application of IVIG in the early stage (admission ≤ 7 days) with a high dose (> 15 g per day) exhibited significant reduction in 60-day mortality in the critical-type patients. CONCLUSION: Early administration of IVIG with high dose improves the prognosis of critical-type patients with COVID-19. This study provides important information on clinical application of IVIG in the treatment of SARS-CoV-2 infection, including patient selection and administration dosage and timing.
RESUMEN
Continuous wave (cw) photon stimulated electron energy loss and gain spectroscopy (sEELS and sEEGS) is used to image the near field of optically stimulated localized surface plasmon resonance (LSPR) modes in nanorod antennas. An optical delivery system equipped with a nanomanipulator and a fiber-coupled laser diode is used to simultaneously irradiate plasmonic nanostructures in a (scanning) transmission electron microscope. The nanorod length is varied such that the m = 1, 2, and 3 LSPR modes are resonant with the laser energy and the optically stimulated near field spectra and images of these modes are measured. Various nanorod orientations are also investigated to explore retardation effects. Optical and electron beam simulations are used to rationalize the observed patterns. As expected, the odd modes are optically bright and result in observed sEEG responses. The m = 2 dark mode does not produce a sEEG response, however, when tilted such that retardation effects are operative, the sEEG signal emerges. Thus, we demonstrate that cw sEEGS is an effective tool in imaging the near field of the full set of nanorod plasmon modes of either parity.
RESUMEN
The ability to control and manipulate temperature at nanoscale dimensions has the potential to impact applications including heat-assisted magnetic recording, photothermal therapies, and temperature-driven reactivity. One challenge with controlling temperature at nanometer dimensions is the need to mitigate heat diffusion, such that the temperature only changes in well-defined nanoscopic regions of the sample. Here we demonstrate the ability to use far-field laser excitation to actively shape the thermal near-field in individual gold nanorod heterodimers by resonantly pumping either the in-phase or out-of-phase hybridized dipole plasmon modes. Using single-particle photothermal heterodyne imaging, we demonstrate localization bias in the photothermal intensity due to preferential heating of one of the nanorods within the pair. Theoretical modeling and numerical simulation make explicit how the resulting photothermal images encode wavelength-dependent temperature biases between each nanorod within a heterodimer, demonstrating the ability to actively manage the thermal near-field by simply tuning the color of incident light.
RESUMEN
Tip-enhanced Raman spectroscopy (TERS) exhibits new selection rule and sub-nanometer spatial resolution, which is attributed to the plasmonic near-field confinement. Despite recent advances in simulations of TERS spectra under highly confined fields, a simply physical mechanism has remained elusive. In this work we show that single-molecule TERS images can be explained by local sub-molecular density changes induced by the confined near-field during the Raman process. The local sub-molecular density changes determine the spatial resolution in TERS and the gradient-based selection rule. Using this approach we find that the four-fold symmetry of meso-tetrakis(3,5-di-tert-butylphenyl)porphyrin (H2TBPP) TERS images observed in experiments arises from the combination of degenerate normal modes localized in the functional side groups rather than the porphyrin ring as previously considered. As an illustration of the potential of the method, we demonstrate how this new theory can be applied to microscopic structure characterization.