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Penetrating neural electrodes provide a powerful approach to decipher brain circuitry by allowing for time-resolved electrical detections of individual action potentials. This unique capability has contributed tremendously to basic and translational neuroscience, enabling both fundamental understandings of brain functions and applications of human prosthetic devices that restore crucial sensations and movements. However, conventional approaches are limited by the scarce number of available sensing channels and compromised efficacy over long-term implantations. Recording longevity and scalability have become the most sought-after improvements in emerging technologies. In this review, we discuss the technological advances in the past 5-10 years that have enabled larger-scale, more detailed, and longer-lasting recordings of neural circuits at work than ever before. We present snapshots of the latest advances in penetration electrode technology, showcase their applications in animal models and humans, and outline the underlying design principles and considerations to fuel future technological development.
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Longevidad , Neurociencias , Animales , Humanos , Electrodos , Encéfalo/fisiología , Potenciales de Acción/fisiología , Electrodos ImplantadosRESUMEN
OBJECTIVE: The early differentiation of adrenal lipid-poor adenomas from non-adenomas is a crucial step in reducing excessive examinations and treatments. This study seeks to construct an eXtreme Gradient Boosting (XGBoost) predictive model utilizing the minimum attenuation values (minAVs) from non-contrast CT (NCCT) scans to identify lipid-poor adenomas. MATERIALS AND METHODS: Retrospective analysis encompassed clinical data, minAVs, CT histogram (CTh), mean attenuation values (meanAVs), and lesion diameter from patients with pathologically or clinically confirmed adrenal lipid-poor adenomas across two medical institutions, juxtaposed with non-adenomas. Variable selection transpired in Institution A (training set), with XGBoost models established based on minAVs and CTh separately. Institution B (validation set) corroborated the diagnostic efficacy of the two models. Receiver operator characteristic (ROC) curve analysis, calibration curves, and Brier scores assessed the diagnostic performance and calibration of the models, with the Delong test gauging differences in the area under the curve (AUC) between models. SHapley Additive exPlanations (SHAP) values elucidated and visualized the models. RESULTS: The training set comprised 136 adrenal lipid-poor adenomas and 126 non-adenomas, while the validation set included 46 and 40 instances, respectively. In the training set, there were substantial inter-group differences in minAVs, CTh, meanAVs, diameter, and body mass index (BMI) (p < 0.05 for all). The AUC for the minAV and CTh models were 0.912 (95% confidence interval [CI]: 0.866-0.957) and 0.916 (95% CI: 0.873-0.958), respectively. Both models exhibited good calibration, with Brier scores of 0.141 and 0.136. In the validation set, the AUCs were 0.871 (95% CI: 0.792-0.951) and 0.878 (95% CI: 0.794-0.962), with Brier scores of 0.156 and 0.165, respectively. The Delong test revealed no statistically significant differences in AUC between the models (p > 0.05 for both). SHAP value analysis for the minAV model suggested that minAVs had the highest absolute weight (AW) and negative contribution. CONCLUSION: The XGBoost predictive model based on minAVs demonstrates effective discrimination between adrenal lipid-poor adenomas and non-adenomas. The minAV variable is easily obtainable, and its diagnostic performance is comparable to that of the CTh model. This provides a basis for patient diagnosis and treatment plan selection.
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Neoplasias de las Glándulas Suprarrenales , Tomografía Computarizada por Rayos X , Humanos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Adenoma/diagnóstico por imagen , Adulto , Anciano , Lípidos , Curva ROCRESUMEN
Cooking oil is a critical component of human food and its main component, lipid, is influential to health, but assessing its authenticity and quality can be challenging due to its complex chemical composition. In this study, we introduce a novel application of time-resolved coherent anti-Stokes Raman scattering (T-CARS) spectroscopy for detecting adulteration and understanding the mechanisms of lipid oxidation in various cooking oils. Our research surpasses the limitations of conventional spontaneous Raman spectroscopy, demonstrating that intra-molecular interactions from unsaturated bonds in triglycerides significantly influence vibrational dephasing time. We observed that these dephasing times, although diverse initially, converge to a similar value after heating cycles. Notably, a longer vibrational dephasing of the CH2 symmetric stretching mode was found to correlate with a higher lipid oxidation rate. These findings underscore the potential of T-CARS in identifying and characterizing subtle molecular interactions, offering a transformative approach to understanding molecular dynamics. This research paves the way for broader applications of T-CARS across fields such as chemistry, biomedicine, and material science, marking a significant advancement in the development of innovative analytical techniques.
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Molecular vibrational spectroscopy is widely used in various sensing and imaging applications, providing intrinsic information at the molecular level. Nonlinear optical interactions using ultrashort laser pulses facilitate the selective coherent excitation of molecular vibrational modes by focusing energy into specific molecular bonds, boosting the signal level for multiple orders of magnitude. The dephasing of such coherence, which is susceptible to the local molecular environment, however, is often neglected. The unique capability of vibrational dephasing dynamics to serve as a unique probe for complex molecular interactions and the effect of local nano- and microenvironments are beyond the reach of conventional, intensity-based spectroscopy. Here, we developed a novel multiorder coherent Raman spectroscopy platform with a special focus on the temporal evolution of molecular vibrational dephasing, termed as time-resolved coherent Raman scattering (T-CRS) spectroscopy. By utilizing a high dynamic range detection, molecular vibrational dynamics and the environmental effects are demonstrated with multidimensional spectroscopic sensing, which promises a new range of applications in biology, materials, and chemical sciences.
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Espectrometría Raman , Vibración , Diagnóstico por Imagen , Rayos Láser , Espectrometría Raman/métodosRESUMEN
Raman spectroscopy provides a non-invasive, chemically-specific optical imaging of biological objects without relying on endogenous labels. Nonlinear Raman spectroscopy allows non-invasive imaging at much faster speed with an improved spatial resolution and axial sectioning capability. In this report we propose a novel use of nonlinear Raman spectroscopy as a sensor of local nano-environment. Time-resolved coherent anti-Stokes Raman spectrograms are found to be sensitive to small variations of local structural changes, which are not normally observed using conventional Raman spectroscopy.
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Brain function can be best studied by simultaneous measurements and modulation of the multifaceted signaling at the cellular scale. Extensive efforts have been made to develop multifunctional neural probes, typically involving highly specialized fabrication processes. Here, we report a novel multifunctional neural probe platform realized by applying ultrathin nanoelectronic coating (NEC) on the surfaces of conventional microscale devices such as optical fibers and micropipettes. We fabricated the NECs by planar photolithography techniques using a substrate-less and multilayer design, which host arrays of individually addressed electrodes with an overall thickness below 1 µm. Guided by an analytic model and taking advantage of the surface tension, we precisely aligned and coated the NEC devices on the surfaces of these conventional microprobes and enabled electrical recording capabilities on par with the state-of-the-art neural electrodes. We further demonstrated optogenetic stimulation and controlled drug infusion with simultaneous, spatially resolved neural recording in a rodent model. This study provides a low-cost, versatile approach to construct multifunctional neural probes that can be applied to both fundamental and translational neuroscience.
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Técnicas Electroquímicas/instrumentación , Nanoestructuras/química , Animales , Encéfalo/diagnóstico por imagen , Electrodos , Humanos , Bombas de Infusión , Masculino , Ratones Endogámicos C57BL , Neuronas/metabolismo , Fibras Ópticas , Imagen Óptica , Optogenética , Tamaño de la PartículaRESUMEN
Hydrogen bond (HB) networks are essential for stabilizing molecular structures in solution and govern the solubility and functionality of molecules in an aqueous environment. HBs are important in biological processes such as enzyme-substrate interactions, protein folding, and DNA replication. However, the exact role of weakly polarized C-H bonds as HB proton donors in solution, such as CH/n HBs, remains mostly unknown. Here, we employ a novel approach focusing on vibrational dephasing to investigate the coherence relaxation of induced dipoles in C-H bonds within CH/n HB networks, utilizing time-resolved coherent anti-Stokes Raman scattering (T-CARS) spectroscopy. Using a representative binary system of dimethyl sulfoxide (DMSO)-water, known for its C-H backboned HB system (i.e., C-Hâ¯S), we observed an increase in the dephasing time of the C-H bending mode with increasing water content until a percolation threshold at a 6 : 1 water : DMSO molar ratio, where the trend is reversed. These results provide compelling evidence for the existence of C-Hâ¯S structures and underscore the presence of a percolation effect, suggesting a critical threshold where long-range connectivity is disputed.
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OBJECTIVE: This study aims to evaluate the application value of multi-parametric magnetic resonance imaging (MRI) radiomics in predicting the response of patients with locally advanced rectal cancer (LARC) to neoadjuvant chemoradiotherapy(nCRT), aiming to provide non-invasive biomarkers for clinical decision-making in personalized treatment. METHODS: A retrospective analysis was conducted on the clinical data and imaging records of patients with LARC who received nCRT and total mesorectal excision (TME) in two medical centers from 2017 to 2023. The patients were divided into a training group and a test group in a 7:3 ratio. Through radiomics analysis, radiomics features of tumor volume and mesorectal fat at baseline, before and after neoadjuvant therapy were extracted. Radiomics models based on single sequences (T2WI, DWI) and multi-sequence fusion were constructed, and the logistic regression classifier model was used to evaluate the prediction performance. RESULTS: A total of 82 patients were included, with 30 in the good response group and 52 in the poor response group. Through the selection of radiomics features, radiomics models based on baseline MRI of tumor volume, mesorectal fat, and differences before and after treatment (Delta) were constructed. The area under the receiver operating characteristic curve (AUC) of the multi-parametric radiomics fusion model in the training and test groups was 0.852 and 0.848, respectively, showing high prediction performance and good calibration. CONCLUSION: This study demonstrates that the multi-parametric MRI radiomics model can effectively predict the response of patients with locally advanced rectal cancer to neoadjuvant chemoradiotherapy. Especially, the fusion model provides high accuracy and good calibration. This result is conducive to the formulation of personalized treatment plans and optimization of treatment strategies.
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The central lymph node metastasis (CLNM) status in the cervical region serves as a pivotal determinant for the extent of surgical intervention and prognosis in papillary thyroid carcinoma (PTC). This paper seeks to devise and validate a predictive model based on clinical parameters for the early anticipation of high-volume CLNM (hv-CLNM, > 5 nodes) in high-risk patients. A retrospective analysis of the pathological and clinical data of patients with PTC who underwent surgical treatment at Medical Centers A and B was conducted. The data from Center A was randomly divided into training and validation sets in an 8:2 ratio, with those from Center B serving as the test set. Multifactor logistic regression was harnessed in the training set to select variables and construct a predictive model. The generalization ability of the model was assessed in the validation and test sets. The model was evaluated through the receiver operating characteristic area under the curve (AUC) to predict the efficiency of hv-CLNM. The goodness of fit of the model was examined via the Brier verification technique. The incidence of hv-CLNM in 5897 PTC patients attained 4.8%. The occurrence rates in males and females were 9.4% (128/1365) and 3.4% (156/4532), respectively. Multifactor logistic regression unraveled male gender (OR = 2.17, p < .001), multifocality (OR = 4.06, p < .001), and lesion size (OR = 1.08 per increase of 1 mm, p < .001) as risk factors, while age emerged as a protective factor (OR = 0.95 per an increase of 1 year, p < .001). The model constructed with four predictive variables within the training set exhibited an AUC of 0.847 ([95%CI] 0.815-0.878). In the validation and test sets, the AUCs were 0.831 (0.783-0.879) and 0.845 (0.789-0.901), respectively, with Brier scores of 0.037, 0.041, and 0.056. Subgroup analysis unveiled AUCs for the prediction model in PTC lesion size groups (≤ 10 mm and > 10 mm) as 0.803 (0.757-0.85) and 0.747 (0.709-0.785), age groups (≤ 31 years and > 31 years) as 0.778 (0.720-0.881) and 0.837 (0.806-0.867), multifocal and solitary cases as 0.803 (0.767-0.838) and 0.809 (0.769-0.849), and Hashimoto's thyroiditis (HT) and non-HT cases as 0.845 (0.793-0.897) and 0.845 (0.819-0.871). Male gender, multifocality, and larger lesion size are risk factors for hv-CLNM in PTC patients, whereas age serves as a protective factor. The clinical predictive model developed in this research facilitates the early identification of high-risk patients for hv-CLNM, thereby assisting physicians in more efficacious risk stratification management for PTC patients.
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Metástasis Linfática , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Masculino , Femenino , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/cirugía , Persona de Mediana Edad , Metástasis Linfática/patología , Adulto , Neoplasias de la Tiroides/patología , Estudios Retrospectivos , Curva ROC , Ganglios Linfáticos/patología , Pronóstico , Factores de Riesgo , Anciano , Modelos Logísticos , Adulto JovenRESUMEN
OBJECTIVE: To develop and validate a radiomics-clinical combined model combining preoperative CT and clinical data from patients with papillary thyroid carcinoma (PTC) to predict the efficacy of initial postoperative 131I treatment. METHODS: A total of 181 patients with PTC who received total thyroidectomy and initial 131I treatment were divided into training and testing sets (7:3 ratio). Univariate analysis and multivariate logistic regression were used to screen clinical factors affecting the therapeutic response to 131I treatment and construct a clinical model. Radiomics features extracted from preoperative CT images of PTCs were dimensionally reduced through recursive feature elimination and least absolute shrinkage and selection operator. Logistic regression was used to establish a radiomics model, and a radiomics-clinical combined model was developed by integrating the clinical model. The area under the curve (AUC), sensitivity, and specificity were used to evaluate the prediction performance of each model. RESULTS: Multivariate analysis revealed that pre-131I treatment sTg was an independent clinical risk factor affecting the efficacy of initial 131I treatment (P = 0.002), and the AUC, sensitivity, and specificity for predicting the efficacy of initial 131I treatment were 0.895, 0.899, and 0.816, respectively. After dimensionality reduction, 14 key CT radiomics features of PTCs were included. The established radiomics model predicted the efficacy of 131I treatment in the training and testing sets with AUCs of 0.825 and 0.809, sensitivities of 0.828 and 0.636, and specificities of 0.745 and 0.944, respectively. The combined model improved the AUC, sensitivity, and specificity in both sets. CONCLUSION: The preoperative CT-based radiomics model can effectively predict the efficacy of initial postoperative 131I treatment in patients with intermediate- or high-risk PTC, and the radiomics-clinical combined model exhibits better predictive performance.
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BACKGROUND: Insulin resistance (IR) is the central pathophysiological feature in the pathogenesis of metabolic syndrome, obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia. As the main active ingredient in Lithocarpus litseifolius [Hance] Chun, previous studies have shown that phlorizin (PHZ) can reduce insulin resistance in the liver. However, the effect of phlorizin on attenuating hepatic insulin resistance has not been fully investigated, and whether this effect is related to AMPK remains unclear. PURPOSE: The present study aimed to further investigate the effect of phlorizin on attenuating insulin resistance and the potential action mechanism. METHODS: Free fatty acids (FFA) were used to induce insulin resistance in HepG2 cells. The effects of phlorizin and FFA on cell viability were detected by MTT analysis. Glucose consumption, glycogen synthesis, intracellular malondialdehyde (MDA), superoxide dismutase (SOD), total cholesterol (TC), and triglyceride (TG) contents were quantified after phlorizin treatment. Glucose uptake and reactive oxygen species (ROS) levels in HepG2 cells were assayed by flow cytometry. Potential targets and signaling pathways for attenuating insulin resistance by phlorizin were predicted by network pharmacological analysis. Moreover, the expression levels of proteins related to the AMPK/PI3K/AKT signaling pathway were detected by western blot. RESULTS: Insulin resistance was successfully induced in HepG2 cells by co-treatment of 1 mM sodium oleate (OA) and 0.5 mM sodium palmitate (PA) for 24 h. Treatment with phlorizin promoted glucose consumption, glucose uptake, and glycogen synthesis and inhibited gluconeogenesis in IR-HepG2 cells. In addition, phlorizin inhibited oxidative stress and lipid accumulation in IR-HepG2 cells. Network pharmacological analysis showed that AKT1 was the active target of phlorizin, and the PI3K/AKT signaling pathway may be the potential action mechanism of phlorizin. Furthermore, western blot results showed that phlorizin ameliorated FFA-induced insulin resistance by activating the AMPK/PI3K/AKT signaling pathway. CONCLUSION: Phlorizin inhibited oxidative stress and lipid accumulation in IR-HepG2 cells and ameliorated hepatic insulin resistance by activating the AMPK/PI3K/AKT signaling pathway. Our study proved that phlorizin played a role in alleviating hepatic insulin resistance by activating AMPK, which provided experimental evidence for the use of phlorizin as a potential drug to improve insulin resistance.
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Ácidos Grasos no Esterificados , Resistencia a la Insulina , Florizina , Transducción de Señal , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Supervivencia Celular/efectos de los fármacos , Glucosa/metabolismo , Células Hep G2 , Florizina/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Implantable electrode arrays are powerful tools for directly interrogating neural circuitry in the brain, but implementing this technology in the spinal cord in behaving animals has been challenging due to the spinal cord's significant motion with respect to the vertebral column during behavior. Consequently, the individual and ensemble activity of spinal neurons processing motor commands remains poorly understood. Here, we demonstrate that custom ultraflexible 1-µm-thick polyimide nanoelectronic threads can conduct laminar recordings of many neuronal units within the lumbar spinal cord of unrestrained, freely moving mice. The extracellular action potentials have high signal-to-noise ratio, exhibit well-isolated feature clusters, and reveal diverse patterns of activity during locomotion. Furthermore, chronic recordings demonstrate the stable tracking of single units and their functional tuning over multiple days. This technology provides a path for elucidating how spinal circuits compute motor actions.
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Electrodos Implantados , Médula Espinal , Animales , Médula Espinal/fisiología , Ratones , Potenciales de Acción/fisiología , Actividad Motora/fisiología , Neuronas/fisiología , Locomoción/fisiología , Ratones Endogámicos C57BL , MasculinoRESUMEN
"Dao Ban Xiang" is a famous traditional Chinese dry-cured meat product. This study aimed to comparatively analyze the difference in the volatile flavor information of "Dao Ban Xiang" produced in winter and summer. In this study, we determine the physical and chemical properties, free amino acids (FAAs), free fatty acids (FFAs), and volatile compounds in the four processing stages of samples in winter and summer. The content of FAAs decreased significantly during the curing period in winter while increasing steadily in summer. The content of total FFAs increased in both winter and summer, and polyunsaturated fatty acids (PUFAs) decreased significantly in summer. The characteristic compound in winter samples is hexanal, nonanal, and (E)-2-octenal, which may mainly come from the degradation of FAAs, while the characteristic compound in winter samples is hexanal, nonanal, and (E)-2-nonenal, which may mainly be derived from the oxidation of FFAs. This study extends our knowledge on flavor from traditional cured meat products at different processing stages in different seasons and could be useful for the standardization of the traditional and regional meat products.
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Objectives: To evaluate the value of computed tomography (CT) enhancement degree in diagnosing lymph node (LN) metastasis in papillary thyroid carcinoma (PTC) by determining the ratio and difference between the Hounsfield units (HU) of CT enhancement and plain scan of the LNs, as well as between the HU of CT-enhanced LNs and the sternocleidomastoid muscle. Methods: The plain and enhanced CT findings of 114 metastasis-positive LNs in 89 cases and 143 metastasis-negative LNs in 114 cases of PTC were analyzed retrospectively. Plain HU of LNs (PNHU), enhanced HU of LNs (ENHU), and enhanced HU of the sternocleidomastoid muscle (EMHU) were measured. The ENHU, difference between ENHU and PNHU (EN-PNHU), ratio of ENHU to PNHU (EN/PNHU), difference between ENHU and EMHU (EN-EMHU), and ratio of ENHU to EMHU (EN/EMHU) in metastasis-positive and metastasis-negative LN groups were calculated, the corresponding diagnostic efficacy for differentiating metastasis-positive from metastasis-negative LNs in PTC were sought using the receiver-operating curve. The interobserver agreement between readers was assessed using the interobserver correlation coefficient (ICC). Results: The ENHU of 114 metastasis-positive LNs and 143 metastasis-negative LNs was 113.39 ± 24.13 and 77.65 ± 15.93, EN-PNHU was 65.84 ± 21.72 HU and 34.07 ± 13.63 HU, EN/PNHU was 2.36 (1.98, 2.75) and 1.76 (1.54, 2.02), EN-EMHU was 49.42 ± 24.59 HU and 13.27 ± 15.41 HU, and EN/EMHU was 1.79 ± 0.40 and 1.21 ± 0.24, respectively (all P < 0.001). The area under the curve, cutoff value, sensitivity, specificity, and accuracy of ENHU for identifying metastasis-positive and metastasis-negative LNs were 0.895, 97.3 HU, 0.746, 0.895, and 0.829, EN-PNHU was 0.894, 47.8 HU, 0.807, 0.874, and 0.844, EN/PNHU was 0.831, 1.9, 0.877, 0.650, and 0.751, EN-EMHU was 0.890, 26.4 HU, 0.807, 0.839, and 0.825, and EN/EMHU was 0.888, 1.5, 0.728, 0.902, and 0.825, respectively. The readers had an excellent interobserver agreement on these five parameters (ICC = 0.874-0.994). Conclusion: In the preoperative evaluation of LN metastasis in PTC, ENHU, EN-PNHU, EN-EMHU, and EN/EMHU had similarly high diagnostic efficacy, with ENHU, EN-PNHU, and EN/EMHU having higher specificity and EN-PNHU and EN-EMHU having higher sensitivity.
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Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Metástasis Linfática/diagnóstico por imagen , Estudios Retrospectivos , Carcinoma Papilar/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Rosa roxburghii Tratt (RRT) is a famous healthy and medicinal edible fruit in southwest China and has been shown to have some hepatoprotective properties. However, whether the active components, such as the triterpene acids from Rosa roxburghii Tratt fruits (TAR), have anti-hepatocellular carcinoma (HCC) effects and the potential molecular mechanisms are still unclear. PURPOSE: This study aimed to investigate the anti-HCC effects and potential action mechanisms of triterpene components in RRT fruits. METHODS: The triterpene acids in TAR were analyzed by using UPLC-Q-Exactive Orbitrap/MS, and the main components were virtual screening for targets based on pharmacophore and then performed enrichment analysis. HepG2 cells were used for in vitro experiments, including MTT assay, wound healing assay, and flow cytometry to detect cell cycle, reactive oxygen species (ROS) level, caspase-3 activity, and mitochondrial membrane potential (MMP) changes. Moreover, the western blot was used to detect mitochondrial apoptosis and ROS/ c-Jun N-terminal kinase (JNK) signaling pathway-related proteins. RESULTS: The main components in TAR are pentacyclic triterpene acids (mainly euscaphic acid and roxburic acid). TAR could inhibit cell viability, cell migration ability and suppress the proliferation of HepG2 cells through G2/M cell cycle arrest. On the other hand, TAR could induce HepG2 cells apoptosis, which was achieved by causing the accumulation of ROS and activation of the JNK signaling pathway, and our research showed that this apoptosis was mediated through the mitochondrial pathway. In addition, the free radical scavenger N-acetyl cysteine (NAC) could attenuate TAR-induced ROS accumulation and JNK signaling pathway activation, which ultimately reversed mitochondrial apoptosis. CONCLUSION: TAR could activate the ROS/JNK signaling pathway, which could inhibit the proliferation through G2/M cell cycle arrest and promote apoptosis through the mitochondrial pathway in HCC cells. This supports the anti-tumor potential in RRT fruits.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Rosa , Triterpenos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Sistema de Señalización de MAP Quinasas , Frutas , Carcinoma Hepatocelular/patología , Puntos de Control del Ciclo Celular , Apoptosis , Células Hep G2 , Triterpenos/farmacología , Neoplasias Hepáticas/patología , Línea Celular TumoralRESUMEN
Spatiotemporal dynamics of small-molecule metabolites have gained increasing attention for their essential roles in deciphering the fundamental machinery of life. However, subcellular-level regulatory mechanisms remain less studied, particularly due to a lack of tools to track small-molecule metabolites. To address this challenge, we developed high-resolution stimulated Raman scattering (SRS) imaging of a genetically engineered model (GEM) to map metabolites in subcellular resolution. As a result, an unexpected regulatory mechanism of a critical metabolite, sterol, was discovered in yeast by amplifying the strength of vibrational imaging by genetic modulation. Specifically, isozymes of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) were evident to promote ergosterol distribution to distinct subcellular locations, where ergosterol was enriched by a local HMGR-directed synthesis. The heterogeneity of this expression pattern thus provides new insights into sterol metabolism and related disease treatment strategies. These findings demonstrate SRS-GEM as a promising platform for new possibilities in investigating metabolic regulation, disease mechanisms, and biopharmaceutical research.
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Objective: This study aimed to investigate the application of modified region-of-interest (ROI) segmentation method in unenhanced computed tomography in the radiomics model of adrenal lipid-poor adenoma, and to evaluate the diagnostic performance using an external medical institution data set and select the best ROI segmentation method. Methods: The imaging data of 135 lipid-poor adenomas and 102 non-adenomas in medical institution A and 30 lipid-poor adenomas and 43 non-adenomas in medical institution B were retrospectively analyzed, and all cases were pathologically or clinically confirmed. The data of Institution A builds the model, and the data of Institution B verifies the diagnostic performance of the model. Semi-automated ROI segmentation of tumors was performed using uAI software, using maximum area single-slice method (MAX) and full-volume method (ALL), as well as modified single-slice method (MAX_E) and full-volume method (ALL_E) to segment tumors, respectively. The inter-rater correlation coefficients (ICC) was performed to assess the stability of the radiomics features of the four ROI segmentation methods. The area under the curve (AUC) and at least 95% specificity pAUC (Partial AUC) were used as measures of the diagnostic performance of the model. Results: A total of 104 unfiltered radiomics features were extracted using each of the four segmentation methods. In the ROC analysis of the radiomics model, the AUC value of the model constructed by MAX was 0.925, 0.919, and 0.898 on the training set, the internal validation set, and the external validation set, respectively, and the AUC value of MAX_E was 0.937, 0.931, and 0.906, respectively. The AUC value of ALL was 0.929, 0.929, and 0.918, and the AUC value of ALL_E was 0.942, 0.926, and 0.927, respectively. In all samples, the pAUCs of MAX, MAX_E, ALL, and ALL_E were 0.021, 0.025, 0.018, and 0.028, respectively. Conclusion: The diagnostic performance of the radiomics model constructed based on the full-volume method was better than that of the model based on the single-slice method. The model constructed using the ALL_E method had a stronger generalization ability and the highest AUC and pAUC value.
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Penetrating flexible electrode arrays can simultaneously record thousands of individual neurons in the brains of live animals. However, it has been challenging to spatially map and longitudinally monitor the dynamics of large three-dimensional neural networks. Here we show that optimized ultraflexible electrode arrays distributed across multiple cortical regions in head-fixed mice and in freely moving rats allow for months-long stable electrophysiological recording of several thousand neurons at densities of about 1,000 neural units per cubic millimetre. The chronic recordings enhanced decoding accuracy during optogenetic stimulation and enabled the detection of strongly coupled neuron pairs at the million-pair and millisecond scales, and thus the inference of patterns of directional information flow. Longitudinal and volumetric measurements of neural couplings may facilitate the study of large-scale neural circuits.
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Fenómenos Electrofisiológicos , Roedores , Ratas , Ratones , Animales , Electrodos Implantados , Fenómenos Electrofisiológicos/fisiología , Encéfalo/fisiología , Neuronas/fisiologíaRESUMEN
Untethered soft magnetoresponsive actuators (SMRAs), which can realize rapid shape transformation, have attracted widespread attention for their strategic applications in exploration, transportation, and minimally invasive medicine. It remains a challenge to fabricate SMRAs with complicated morphing modes (more than bending and folding), limiting their applications to simple shape-morphing and locomotion. Herein, a method integrating the ancient kirigami art and an advanced mechanical assembly method is proposed, which realizes 2D-to-3D and 3D-to-3D complicated shape-morphing and precise magnetization programming through cut-guided deformation. The kirigami-inspired SMRAs exhibit good robustness after actuating more than 10000 times. An integrated finite element analysis method is developed to quantitatively predict the shape transformation of SMRAs under magnetic actuation. By leveraging this method, a set of 3D curved responsive morphologies with programmed Gaussian curvature are fabricated (e.g., ellipsoid and saddle structures), specifically 3D multilayer structures and face-like shapes with different expressions, which are difficult to realize using previous approaches. Furthermore, a bionic-scaled soft crawling robot with significant obstacle surmounting ability is fabricated using the kirigami-inspired method. The ability of the method to achieve programmable SMRAs with versatile morphing modes may broaden its applications in soft robotics, color-switchable devices, and clinical treatments.
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Robótica , Robótica/métodos , Análisis de Elementos Finitos , Distribución NormalRESUMEN
Flexible neural electrodes improve the recording longevity and quality of individual neurons by promoting tissue-electrode integration. However, the intracortical implantation of flexible electrodes inevitably induces tissue damage. Understanding the longitudinal neural and vascular recovery following the intracortical implantation is critical for the ever-growing applications of flexible electrodes in both healthy and disordered brains. Aged animals are of particular interest because they play a key role in modeling neurological disorders, but their tissue-electrode interface remains mostly unstudied. Here we integrate in-vivo two-photon imaging and electrophysiological recording to determine the time-dependent neural and vascular dynamics after the implantation of ultraflexible neural electrodes in aged mice. We find heightened angiogenesis and vascular remodeling in the first two weeks after implantation, which coincides with the rapid increase in local field potentials and unit activities detected by electrophysiological recordings. Vascular remodeling in shallow cortical layers preceded that in deeper layers, which often lasted longer than the recovery of neural signals. By six weeks post-implantation vascular abnormalities had subsided, resulting in normal vasculature and microcirculation. Putative cell classification based on firing pattern and waveform shows similar recovery time courses in fast-spiking interneurons and pyramidal neurons. These results elucidate how structural damages and remodeling near implants affecting recording efficacy, and support the application of ultraflexible electrodes in aged animals at minimal perturbations to endogenous neurophysiology.