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With the rapid development of Chinese transportation networks, such as the Sichuan-Tibet railway, numerous tunnels are under construction or planned in mountainous regions. Some of these tunnels must traverse or be situated near active fault zones, which could suffer damage from fault slip. In this study, the seismic response of a mountain tunnel subjected to coseismic faulting was analyzed using a fault-structure system in a two-step process. Firstly, a nonuniform slip model was proposed to calculate the ground deformations and internal displacements induced by a specific active fault on a geological scale, considering nonuniform slips on the fault plane. The 1989 Loma Prieta and 2022 Menyuan earthquakes were chosen as case studies to validate the proposed slip model. Secondly, the calculated displacement of the Menyuan earthquake was used as the input load for the discrete-continuous coupling analysis of the Daliang tunnel on an engineering scale. The simulated deformation of the Daliang tunnel aligned with the on-site damage observations following the Menyuan earthquake. Lastly, the effects of different fault conditions on the tunnel seismic response were investigated. The results indicate that the distribution of the peak longitudinal strain of the lining is governed by fault mechanisms, and the degree of fault slip significantly influences the response of the tunnel. A tunnel passing through an active fault with a wider fault fracture zone and smaller dip angle experience less damage.
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Frequency-scanning interferometry (FSI) utilizing external cavity diode lasers (ECDL) stands out as a potent technique for absolute distance measurement. Nevertheless, the inherent scanning nonlinearity of ECDL and phase noise pose a challenge, as it can compromise the accuracy of phase extraction from interference signals, thereby reducing the measurement accuracy of FSI. In this study, we propose a composite algorithm aimed at mitigating non-orthogonal errors by integrating the least-squares and Heydemann correction technique. Furthermore, we employ Kalman filtering for precise phase tracking. We introduce a parameter selection strategy based on the statistical distribution of instantaneous frequency to achieve the fusion estimation of phase observation values and theoretical models, which starts a new perspective for the application of multi-dimensional data fusion in FSI measurement. Through simulation and experimental validation, the efficacy of this approach is confirmed. The experimental results show promising outcomes: with an average phase error of 0.12%, a standard deviation of less than 1.7â µm in absolute distance measurement, and an average positioning accuracy error of 0.29â µm.
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UbiA-type prenyltransferases (PTases) are significant enzymes that lead to structurally diverse meroterpenoids. Herein, we report the identification and characterization of an undescribed UbiA-type PTase, FtaB, that is responsible for the farnesylation of indole-containing diketopiperazines (DKPs) through genome mining. Heterologous expression of the fta gene cluster and non-native pathways result in the production of a series of new C2-farnesylated DKPs. This study broadens the reaction scope of UbiA-type PTases and expands the chemical diversity of meroterpenoids.
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Dicetopiperazinas , Dimetilaliltranstransferasa , Prenilación , Dimetilaliltranstransferasa/metabolismo , Dimetilaliltranstransferasa/química , Dimetilaliltranstransferasa/genética , Dicetopiperazinas/química , Dicetopiperazinas/metabolismo , Estructura Molecular , Familia de MultigenesRESUMEN
Background: Cancer continues to be a prominent issue in the field of medicine, as demonstrated by recent studies emphasizing the significant role of autophagy in the development of cancer. Traditional Chinese Medicine (TCM) provides a variety of anti-tumor agents capable of regulating autophagy. However, the clinical application of autophagy-modulating compounds derived from TCM is impeded by their restricted water solubility and bioavailability. To overcome this challenge, the utilization of nanotechnology has been suggested as a potential solution. Nonetheless, the current body of literature on nanoparticles delivering TCM-derived autophagy-modulating anti-tumor compounds for cancer treatment is limited, lacking comprehensive summaries and detailed descriptions. Methods: Up to November 2023, a comprehensive research study was conducted to gather relevant data using a variety of databases, including PubMed, ScienceDirect, Springer Link, Web of Science, and CNKI. The keywords utilized in this investigation included "autophagy", "nanoparticles", "traditional Chinese medicine" and "anticancer". Results: This review provides a comprehensive analysis of the potential of nanotechnology in overcoming delivery challenges and enhancing the anti-cancer properties of autophagy-modulating compounds in TCM. The evaluation is based on a synthesis of different classes of autophagy-modulating compounds in TCM, their mechanisms of action in cancer treatment, and their potential benefits as reported in various scholarly sources. The findings indicate that nanotechnology shows potential in enhancing the availability of autophagy-modulating agents in TCM, thereby opening up a plethora of potential therapeutic avenues. Conclusion: Nanotechnology has the potential to enhance the anti-tumor efficacy of autophagy-modulating compounds in traditional TCM, through regulation of autophagy.
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Medicamentos Herbarios Chinos , Neoplasias , Humanos , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Nanotecnología , AutofagiaRESUMEN
BACKGROUND: Traditional Chinese medicinal formula (TCMF) has specific advantages in treating diseases. However, the pharmacological effects and mechanism of TCMF composed of traditional Chinese medicines (TCM) with unclear active components or targets have not yet been fully elucidated. OBJECTIVES: This research proposed a strategy for elucidating the pharmacological effects and mechanism to address this issue systematically. METHODS: With Guilin Xiguashuang (GLXGS) taken as a case, this study newly provided the multi-level assays, which decomposes TCMF into components, TCM, and TCMF levels. The main pharmacological effects were acquired through a comprehensive analysis based on the active components, pharmacological effects of TCM, and clinical efficacy of TCMF, respectively. The core targets and pathways were further identified and verified to elucidate the mechanism. RESULTS: The main pharmacological effects of GLXGS were anti-inflammatory, analgesic, antibacterial, immunoregulatory, and wound healing. Moreover, the mechanism analysis demonstrated that GLXGS was involved in the regulation of NF-κB and VEGF signaling pathways and core targets, such as IL-6 and TNF-α. Finally, unproven immunomodulatory and anti-inflammatory mechanism were verified using RAW264.7 and THP-1 cells. GLXGS was verified to down-regulate IL-6, IL-1ß, TNF-α, and CD86 in lipopolysaccharides-stimulated RAW264.7 cells, while enhancing polarization in both RAW264.7 and THP-1 cells, which were consistent with analysis results. CONCLUSION: The present research provides a systematic strategy for the pharmacological effect prediction and mechanism analysis of TCMF, which is of great significance for studying complex TCMF.
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Medicamentos Herbarios Chinos , Factor de Necrosis Tumoral alfa , Animales , Ratones , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , FN-kappa B/metabolismo , Antiinflamatorios/farmacología , Células RAW 264.7 , Antiinflamatorios no Esteroideos , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
Optical coherence tomography (OCT) is a label-free, non-invasive 3D imaging tool widely used in both biological research and clinical diagnosis. Conventional OCT modalities can only visualize specimen tomography without chemical information. Here, we report a bond-selective full-field OCT (BS-FF-OCT), in which a pulsed mid-infrared laser is used to modulate the OCT signal through the photothermal effect, achieving label-free bond-selective 3D sectioned imaging of highly scattering samples. We first demonstrate BS-FF-OCT imaging of 1â µm PMMA beads embedded in agarose gel. Next, we show 3D hyperspectral imaging of up to 75â µm of polypropylene fiber mattress from a standard surgical mask. We then demonstrate BS-FF-OCT imaging on biological samples, including cancer cell spheroids and C. elegans. Using an alternative pulse timing configuration, we finally demonstrate the capability of BS-FF-OCT on imaging a highly scattering myelinated axons region in a mouse brain tissue slice.
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Caenorhabditis elegans , Tomografía de Coherencia Óptica , Animales , Ratones , Tomografía de Coherencia Óptica/métodos , Imagenología TridimensionalRESUMEN
Cancer is the world's leading cause of human death today, and the treatment process of cancer is highly complex. Chemotherapy and targeted therapy are commonly used in cancer treatment, and the emergence of drug resistance is a significant problem in cancer treatment. Therefore, the mechanism of drug resistance during cancer treatment has become a hot issue in current research. A series of studies have found that lipid metabolism is closely related to cancer drug resistance. This paper details the changes of lipid metabolism in drug resistance and how lipid metabolism affects drug resistance. More importantly, most studies have reported that combination therapy may lead to changes in lipid-related metabolic pathways, which may reverse the development of cancer drug resistance and enhance or rescue the sensitivity to therapeutic drugs. This paper summarizes the progress of drug design targeting lipid metabolism in improving drug resistance, and providing new ideas and strategies for future tumor treatment. Therefore, this paper reviews the issues of combining medications with lipid metabolism and drug resistance.
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Point-based 3D detection approaches usually suffer from the severe point sampling imbalance problem between foreground and background. We observe that prior works have attempted to alleviate this imbalance by emphasizing foreground sampling. However, even adequate foreground sampling may be extremely unbalanced between nearby and distant objects, yielding unsatisfactory performance in detecting distant objects. To tackle this issue, this paper first proposes a novel method named Distant Object Augmented Set Abstraction and Regression (DO-SA&R) to enhance distant object detection, which is vital for the timely response of decision-making systems like autonomous driving. Technically, our approach first designs DO-SA with novel distant object augmented farthest point sampling (DO-FPS) to emphasize sampling on distant objects by leveraging both object-dependent and depth-dependent information. Then, we propose distant object augmented regression to reweight all the instance boxes for strengthening regression training on distant objects. In practice, the proposed DO-SA&R can be easily embedded into the existing modules, yielding consistent performance improvements, especially on detecting distant objects. Extensive experiments are conducted on the popular KITTI, nuScenes and Waymo datasets, and DO-SA&R demonstrates superior performance, especially for distant object detection. Our code is available at https://github.com/mikasa3lili/DO-SAR.
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Emotional eating has emerged as a significant disordered eating and public health concern among adolescents. Despite the widespread prevalence of social networking site (SNS) use among this population, research investigating the influence of SNS use on adolescent eating behaviors remains limited. This study is to examine the impact of SNS use on emotional eating among Chinese adolescents, with a specific focus on exploring the mediating role of negative social comparisons and the moderating effect of perspective-taking. Data were obtained through an online survey involving 778 middle school students in China. The findings indicate that SNS use exerts a positive influence on adolescents' engagement in emotional eating, with this association being mediated by the presence of negative social comparisons. Perspective-taking demonstrated a protective role in the context of adolescents' utilization of social media platforms. For individuals characterized by high levels of perspective-taking, the effects of SNS use on negative social comparisons are mitigated, subsequently reducing its impact on emotional eating.
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[This corrects the article DOI: 10.1021/acscentsci.3c00032.].
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Controlled incorporation of nitrogen into macromolecular skeletons is a long-standing challenge whose resolution would enable the preparation of soft materials with the scalability of man-made plastics and functionality of Nature's proteins. Nylons and polyurethanes notwithstanding, nitrogen-rich polymer backbones remain scarce, and their synthesis typically lacks precision. Here we report a strategy that begins to address this limitation founded on a mechanistic discovery: ring-opening metathesis polymerization (ROMP) of carbodiimides followed by carbodiimide derivatization. An iridium guanidinate complex was found to initiate and catalyze ROMP of N-aryl and N-alkyl cyclic carbodiimides. Nucleophilic addition to the resulting polycarbodiimides enabled the preparation of polyureas, polythioureas, and polyguanidinates with varied architectures. This work advances the foundations of metathesis chemistry and opens the door to systematic investigations of structure-folding-property relationships in nitrogen-rich macromolecules.
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In this study, polarization Raman spectra were collected for binary mixtures of formic acid/methanol and formic acid/acetonitrile with different volume fractions. The broad band of formic acid in the CîO vibration region was divided into four vibration peaks, corresponding to CîO symmetric and anti-symmetric stretching vibration from cyclic dimer, CîO stretching from open dimer, and CîO stretching from the free monomer. The experiments showed that as the volume fraction of formic acid in the binary mixture decreased, the cyclic dimer gradually converted to the open dimer, and at a volume fraction of 0.1, fully depolymerized into monomer form (free monomer, solvated monomer, and hydrogen bonding monomer clusters with solvent). The contribution percentage of the total CîO stretching intensity of each structure at different concentrations was quantitatively calculated using high resolution infrared spectroscopy, and the results were consistent with the conclusions predicted by polarization Raman spectroscopy. Concentration-triggered 2D-COS synchronous and asynchronous spectra also confirmed the kinetics of formic acid diluted in acetonitrile. This work provides a spectroscopic method for studying the structure of organic compounds in solution and concentration-triggering kinetics in mixtures.
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Ferromagnets are known to support spin-polarized currents that control various spin-dependent transport phenomena useful for spintronics. On the contrary, fully compensated antiferromagnets are expected to support only globally spin-neutral currents. Here, we demonstrate that these globally spin-neutral currents can represent the Néel spin currents, i.e., staggered spin currents flowing through different magnetic sublattices. The Néel spin currents emerge in antiferromagnets with strong intrasublattice coupling (hopping) and drive the spin-dependent transport phenomena such as tunneling magnetoresistance (TMR) and spin-transfer torque (STT) in antiferromagnetic tunnel junctions (AFMTJs). Using RuO_{2} and Fe_{4}GeTe_{2} as representative antiferromagnets, we predict that the Néel spin currents with a strong staggered spin polarization produce a sizable fieldlike STT capable of the deterministic switching of the Néel vector in the associated AFMTJs. Our work uncovers the previously unexplored potential of fully compensated antiferromagnets and paves a new route to realize the efficient writing and reading of information for antiferromagnetic spintronics.
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Background: Early diagnosis and treatment can improve the survival rates of patients with laryngeal squamous cell carcinoma (LSCC). Therefore, it is necessary to discover new biomarkers for laryngeal cancer screening and early diagnosis. Methods: We collected fasting plasma from LSCC patients and healthy volunteers, as well as cancer and para-carcinoma tissues from LSCC patients, and performed quantitative detection of amino acid levels using liquid chromatography-mass spectrometry. We used overall analysis and multivariate statistical analysis to screen out the statistically significant differential amino acids in the plasma and tissue samples, conducted receiver operating characteristic (ROC) analysis of the differential amino acids to evaluate the sensitivity and specificity of the differential amino acids, and finally determined the diagnostic value of amino acids for laryngeal cancer. Additionally, we identified amino acids in the plasma and tissue samples that are valuable for the early diagnosis of laryngeal cancer classified according to the tumor-node-metastasis (TNM) classification. Results: Asparagine (Asp) and homocysteine (Hcy) were two amino acids of common significance in plasma and tissue samples, and their specificity and sensitivity analysis showed that they may be new biomarkers for the diagnosis and treatment of LSCC. According to the TNM staging system, phenylalanine (Phe) and isoleucine (Ile) were screened out in the plasma of LSCC patients at early (I and II) and advanced (III and IV) stages; ornithine hydrochloride (Orn), glutamic acid (Glu), and Glycine (Gly) were selected in the tissue. These dysregulated amino acids found in LSCC patients may be useful as clinical biomarkers for the early diagnosis and screening of LSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Laríngeas , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Neoplasias Laríngeas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Aminoácidos , Biomarcadores de Tumor , Detección Precoz del CáncerRESUMEN
An effective method has been developed to facilitate the synthesis of amides and esters at ambient temperature within 5 min, in which a stable and easily accessible triflylpyridinium reagent is used. Remarkably, this method not only has a wide range of substrate compatibility but also could realize the scalable synthesis of peptide and ester via a continuous flow process. Moreover, excellent chirality retentions are presented during activation of carboxylic acid.
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Amidas , Ésteres , Péptidos , Ácidos CarboxílicosRESUMEN
Candida albicans (C. albicans), a major fungal pathogen, causes life-threatening infections in immunocompromised individuals. Fluconazole (FLC) is recommended as first-line therapy for treatment of invasive fungal infections. However, the widespread use of FLC has resulted in increased antifungal resistance among different strains of Candida, especially C. albicans, which is a leading source of hospital-acquired infections. Here, by hyperspectral stimulated Raman scattering imaging of single fungal cells in the fingerprint window and pixel-wise spectral unmixing, we report aberrant ergosteryl ester accumulation in azole-resistant C. albicans compared to azole-susceptible species. This accumulation was a consequence of de novo lipogenesis. Lipid profiling by mass spectroscopy identified ergosterol oleate to be the major species stored in azole-resistant C. albicans. Blocking ergosterol esterification by oleate and suppressing sterol synthesis by FLC synergistically suppressed the viability of C. albicans in vitro and limited the growth of biofilm on mouse skin in vivo. Our findings highlight a metabolic marker and a new therapeutic strategy for targeting azole-resistant C. albicans by interrupting the esterified ergosterol biosynthetic pathway.
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Antifúngicos , Candida albicans , Animales , Ratones , Antifúngicos/química , Azoles/farmacología , Azoles/metabolismo , Espectrometría Raman , Ésteres/metabolismo , Ácido Oléico/metabolismo , Pruebas de Sensibilidad Microbiana , Fluconazol/metabolismo , Ergosterol/farmacología , Ergosterol/metabolismoRESUMEN
The efficacies and toxicities of chiral drug enantiomers are often dissimilar, necessitating chiral recognition methods. Herein, a polylysine-phenylalanine complex framework was used to prepare molecularly imprinted polymers (MIPs) as sensors with enhanced specific recognition capabilities for levo-lansoprazole. The properties of the MIP sensor were investigated using Fourier-transform infrared spectroscopy and electrochemical methods. The optimal sensor performance was achieved by applying self-assembly times of 30.0 and 25.0 min for the complex framework and levo-lansoprazole, respectively, eight electropolymerization cycles with o-phenylenediamine as the functional monomer, an elution time of 5.0 min using an ethanol/acetic acid/H2O mixture (2/3/8, V/V/V) as the eluent, and a rebound time of 10.0 min. A linear relationship was observed between the sensor response intensity (ΔI) and logarithm of the levo-lansoprazole concentration (l-g C) in the range of 1.0 × 10-13-3.0 × 10-11 mol/L. Compared with a conventional MIP sensor, the proposed sensor showed more efficient enantiomeric recognition, with high selectivity and specificity for levo-lansoprazole. The sensor was successfully applied to levo-lansoprazole detection in enteric-coated lansoprazole tablets, thus demonstrating its suitability for practical applications.
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Impresión Molecular , Polímeros Impresos Molecularmente , Fenilalanina , Polilisina , Polímeros/química , Impresión Molecular/métodos , Técnicas Electroquímicas/métodos , Límite de DetecciónRESUMEN
To explain the polarization Raman noncoincidence effect of specific polar bonds and the noncoincidence phenomenon between FT-Raman and FT-IR spectra, aggregation-induced spectral splitting theory was proposed. In this paper, the vibration splitting theory was demonstrated using two strategies: improving the spectral resolution with cryogenic matrix isolation techniques and identifying cases where the coupling splitting is large enough to be distinguishable. The monomer and dimer splitting bands of acetone were detected when cryogenically isolated by the Ar matrix. Additionally, the polarization Raman and two-dimensional infrared spectra of a ß-propiolactone (PIL)/CCl4 binary mixture were collected at room temperature, and the spectral splitting phenomenon was clearly observed. The dynamic transformation between the monomer and dimer could be achieved and detected by adjusting the PIL concentration. The observed splitting phenomenon was further confirmed by theoretical DFT calculations based on the monomer and dimer of PIL, as well as the FT-IR and FT-Raman spectra of PIL. Concentration-triggered 2D-COS synchronous and asynchronous spectra also confirmed the splitting phenomenon and the dilution kinetics of PIL/CCl4.
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High-speed three-dimensional (3D) intravital imaging in animals is useful for studying transient subcellular interactions and functions in health and disease. Light-field microscopy (LFM) provides a computational solution for snapshot 3D imaging with low phototoxicity but is restricted by low resolution and reconstruction artifacts induced by optical aberrations, motion and noise. Here, we propose virtual-scanning LFM (VsLFM), a physics-based deep learning framework to increase the resolution of LFM up to the diffraction limit within a snapshot. By constructing a 40 GB high-resolution scanning LFM dataset across different species, we exploit physical priors between phase-correlated angular views to address the frequency aliasing problem. This enables us to bypass hardware scanning and associated motion artifacts. Here, we show that VsLFM achieves ultrafast 3D imaging of diverse processes such as the beating heart in embryonic zebrafish, voltage activity in Drosophila brains and neutrophil migration in the mouse liver at up to 500 volumes per second.
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Microscopía , Pez Cebra , Animales , Ratones , Imagenología Tridimensional/métodosRESUMEN
Introduction: To our knowledge, this is the first study to use MRI (Magnetic Resonance Imaging) before and after an intensive flight training. This study aimed to investigate the effectiveness of flight training in civil flying cadets. Methods: The civil flying cadets and controls completed two study visits. Visit 1 was performed in 2019, and high spatial resolution structural image and resting-state functional MRI data were collected. The second visit was completed in 2022. In addition to the MRI data mentioned above, participants completed the cognitive function assessment at the second visit. Results: Mixed-effect regression model analysis found that flight training enhanced the degree centrality (DC) values of the left middle frontal gyrus and left lingual gyrus. The subsequent correlation calculation analysis suggested a possible relationship between these alterations and cognitive function. Discussion: These results suggest that flight training might promote the DC value of the prefrontal and occipital cortices and, in turn, enhance their executive function.