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Nine-carbon aldehydes and their relative alcohols (C9 aromas) are the main aroma compounds of cucumber (Cucumis sativus L.) fruits and provide a unique cucumber-like note. However, the key regulators of C9 aroma accumulation in cucumber fruit are poorly characterized. Based on C9 aroma dynamic analysis and transcriptome analysis during fruit development of two different cucumber inbred lines, Q16 and Q24, Lipoxygenase09 (CsLOX09) was identified as a candidate gene for C9 aroma accumulation. Additionally, Q24 with higher CsLOX09 expression accumulated more C9 aromas than Q16. To verify the function of CsLOX09, Cslox09 homozygote knockout lines were created. C9 aroma content decreased by 80.79%-99.16% in these mutants compared to the wild type. To further explore the reasons for the difference in CsLOX09 expression between Q16 and Q24 fruits, a co-expression network was constructed by integrating the C9 aroma-associated metabolism and transcriptomic data. Eighteen candidate transcription factors were highly correlated with the expression of CsLOX09. DNA binding with One Finger 1.8 (CsDof1.8) was confirmed to bind directly to the A/TAAAG motif of the CsLOX09 promoter through dual-luciferase, yeast one-hybrid, chromatin immunoprecipitation-qPCR and electrophoretic mobility shift assays. Furthermore, C9 aroma content and CsLOX09 expression were significantly increased in the CsDof1.8 overexpression lines. Overall, these data elucidate the metabolic regulation of C9 aromas in cucumber and provide a foundation for facilitating the regulation of flavor in cucumber breeding.
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Optical sensors, with great potential to convert invisible bioanalytical response into readable information, have been envisioned as a powerful platform for biological analysis and early diagnosis of diseases. However, the current extraction of sensing data is basically processed via a series of complicated and time-consuming calibrations between samples and reference, which inevitably introduce extra measurement errors and potentially annihilate small intrinsic responses. Here, we have proposed and experimentally demonstrated a calibration-free sensor for achieving high-precision biosensing detection, based on an optically controlled terahertz (THz) ultrafast metasurface. Photoexcitation of the silicon bridge enables the resonant frequency shifting from 1.385 to 0.825 THz and reaches the maximal phase variation up to 50° at 1.11 THz. The typical environmental measurement errors are completely eliminated in theory by normalizing the Fourier-transformed transmission spectra between ultrashort time delays of 37 ps, resulting in an extremely robust sensing device for monitoring the cancerous process of gastric cells. We believe that our calibration-free sensors with high precision and robust advantages can extend their implementation to study ultrafast biological dynamics and may inspire considerable innovations in the field of medical devices with nondestructive detection.
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Neoplasias Gástricas , Humanos , Silício , Neoplasias Gástricas/diagnósticoRESUMO
Validation is the basis of synthetic aperture radar (SAR) image quantification applications. Based on the point target of the field site, the radiation characteristics of the backscattering coefficient image can be used to optimize the SAR imaging, and the product production system can be more closely targeted, to ensure the image product accuracy in the actual quantification application. In this study, the validation of the backscattering coefficient image was examined using calibrators, and the radiometric properties of the image were evaluated by extracting the radar cross-section of each point target. Bilinear interpolation and fast Fourier transform (FFT) interpolation methods were introduced for the local area interpolation of point targets, and the two methods were compared from the perspective of response function imaging and validation accuracy. The results show that the FFT interpolation method is more favorable for validating the backscattering coefficient.
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Diagnóstico por Imagem , Radar , Análise de Fourier , CalibragemRESUMO
To verify the performance of the high-resolution fully polarimetric synthetic aperture radar (SAR) sensor carried by the Xinzhou 60 remote-sensing aircraft, we used corner reflectors to calibrate the acquired data. The target mechanism in high-resolution SAR images is more complex than it is in low-resolution SAR images, the impact of the point target pointing error on the calibration results is more obvious, and the target echo signal of high-resolution images is more easily affected by speckle noise; thus, more accurate extraction of the point target position and the response energy is required. To solve this problem, this paper introduces image context information and proposes a method to precisely determine the integration region of the corner reflector using sliding windows based on the integral method. The validation indicates that the fully polarimetric SAR sensor on the Xinzhou 60 remote-sensing aircraft can accurately reflect the radiometric characteristics of the ground features and that the integral method can obtain more stable results than the peak method. The sliding window allows the position of the point target to be determined more accurately, and the response energy extracted from the image via the integral method is closer to the theoretical value, which means that the high-resolution SAR system can achieve a higher radiometric calibration accuracy. Additionally, cross-validation reveals that the airborne SAR images have similar quality levels to Sentinel-1A and Gaofen-3 images.
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In this paper, we aim to use odor fingerprint analysis to identify and detect various odors. We obtained the olfactory sensory evaluation of eight different brands of Chinese liquor by a lab-developed intelligent nose. From the respective combination of the time domain and frequency domain, we extract features to reflect the samples comprehensively. However, the extracted feature combined time domain and frequency domain will bring redundant information that affects performance. Therefore, we proposed data by Principal Component Analysis (PCA) and Variable Importance Projection (VIP) to delete redundant information to construct a more precise odor fingerprint. Then, Random Forest (RF) and Probabilistic Neural Network (PNN) were built based on the above. Results showed that the VIP-based models achieved better classification performance than PCA-based models. In addition, the peak performance (92.5%) of the VIP-RF model had a higher classification rate than the VIP-PNN model (90%). In conclusion, odor fingerprint analysis using a feature mining method based on the olfactory sensory evaluation can be applied to monitor product quality in the actual process of industrialization.
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Álcoois/química , Odorantes/análise , Animais , Humanos , Redes Neurais de Computação , Análise de Componente PrincipalRESUMO
Multi-sensor data fusion can provide more comprehensive and more accurate analysis results. However, it also brings some redundant information, which is an important issue with respect to finding a feature-mining method for intuitive and efficient analysis. This paper demonstrates a feature-mining method based on variable accumulation to find the best expression form and variables' behavior affecting beer flavor. First, e-tongue and e-nose were used to gather the taste and olfactory information of beer, respectively. Second, principal component analysis (PCA), genetic algorithm-partial least squares (GA-PLS), and variable importance of projection (VIP) scores were applied to select feature variables of the original fusion set. Finally, the classification models based on support vector machine (SVM), random forests (RF), and extreme learning machine (ELM) were established to evaluate the efficiency of the feature-mining method. The result shows that the feature-mining method based on variable accumulation obtains the main feature affecting beer flavor information, and the best classification performance for the SVM, RF, and ELM models with 96.67%, 94.44%, and 98.33% prediction accuracy, respectively.
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Basic oxygen furnace slag (BOFS) has the potential to remove hexavalent chromium (Cr(VI)) from wastewater by a redox process due to the presence of minerals containing Fe(2+). The effects of the solution pH, initial Cr(VI) concentration, BOFS dosage, BOFS particle size, and temperature on the removal of Cr(VI) was investigated in detail through batch tests. The chemical and mineral compositions of fresh and reacted BOFS were characterized using scanning electron microscope (SEM) equipped with an energy dispersive spectrometer (EDS) system and X-ray diffractometer (XRD). The results show that Cr(VI) in wastewater can be efficiently removed by Fe(2+) released from BOFS under appropriate acidic conditions. The removal of Cr(VI) by BOFS significantly depended on the parameters mentioned above. The reaction of Cr(VI) with BOFS followed the pseudo-second-order kinetic model. Fe(2+) responsible for Cr(VI) removal was primarily derived from the dissolution of FeO and Fe3O4 in BOFS. When H2SO4 was used to adjust the solution acidity, gypsum (CaSO4·2H2O) could be formed and become an armoring precipitate layer on the BOFS surface, hindering the release of Fe(2+) and the removal of Cr(VI). Finally, the main mechanism of Cr(VI) removal by BOFS was described using several consecutive reaction steps.
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Cromo/química , Resíduos Industriais , Metalurgia , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/química , Cromo/análise , Oxigênio , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Neuroendoscopy is an innovative technique for neurosurgery that can nonetheless result in traumatic brain injury. The accompanying neuroinflammation may lead to secondary tissue damage, which is the major cause of delayed neuronal death after surgery. The present study investigated the capacity of osthole to prevent secondary brain injury and the underlying mechanism of action in a mouse model of stab wound injury. METHODS: A mouse model of cortical stab wound injury was established by inserting a needle into the cerebral cortex for 20 min to mimic neuroendoscopy. Mice received an intraperitoneal injection of osthole 30 min after surgery and continued for 14 days. Neurological severity was evaluated 12 h and up to 21 days after the trauma. Brains were collected 3-21 days post-injury for histological analysis, immunocytochemistry, quantitative real-time PCR, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and enzyme-linked immunosorbent assays. RESULTS: Neurological function improved in mice treated with osthole and was accompanied by reduced brain water content and accelerated wound closure relative to untreated mice. Osthole treatment reduced the number of macrophages/microglia and peripheral infiltrating of neutrophils and lowered the level of the proinflammatory cytokines interleukin-6 and tumor necrosis factor α in the lesioned cortex. Osthole-treated mice had fewer TUNEL+ apoptotic neurons surrounding the lesion than controls, indicating increased neuronal survival. CONCLUSIONS: Osthole reduced secondary brain damage by suppressing inflammation and apoptosis in a mouse model of stab wound injury. These results suggest a new strategy for promoting neuronal survival and function after neurosurgery to improve long-term patient outcome.
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Lesões Encefálicas , Córtex Cerebral/efeitos dos fármacos , Cumarínicos/uso terapêutico , Encefalite/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Análise de Variância , Animais , Edema Encefálico/etiologia , Edema Encefálico/prevenção & controle , Lesões Encefálicas/complicações , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/patologia , Caspase 3/metabolismo , Córtex Cerebral/patologia , Citocinas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Encefalite/etiologia , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Exame Neurológico , Peroxidase/metabolismo , RNA Mensageiro/metabolismo , Fatores de TempoRESUMO
Neurogenesis is the process by which neural stem cells (NSCs) proliferate and differentiate into neurons. This is diminished in several neurodegenerative disorders such as Alzheimer's disease (AD), which is characterized by the deposition of amyloid (A)ß peptides and neuronal loss. Stimulating NSCs to replace lost neurons is therefore a promising approach for AD treatment. Our previous study demonstrated that osthole modulates NSC proliferation and differentiation, and may reduce Aß protein expression in nerve cells. Here we investigated the mechanism underlying the effects of osthole on NSCs. We found that osthole enhances NSC proliferation and neuronal differentiation while suppressing apoptosis, effects that were exerted via activation of Wnt/ß-catenin signaling. These results provide evidence that osthole can potentially be used as a therapeutic agent in the treatment of AD and other neurodegenerative disorders.
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Doença de Alzheimer/tratamento farmacológico , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Cumarínicos/farmacologia , Neurogênese/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismoRESUMO
It is believed that neuronal death caused by abnormal deposition of amyloid-beta peptide is the major cause of the cognitive decline in Alzheimer's disease. Adult neurogenesis plays a key role in the rescue of impaired neurons and amelioration of cognitive impairment. In the present study, we demonstrated that osthole, a natural coumarin derivative, was capable of promoting neuronal stem cell (NSC) survival and inducing NSC proliferation in vitro. In osthole-treated APP/PS1 transgenic mice, a significant improvement in learning and memory function was seen, which was associated with a significant increase in the number of new neurons (Ki67(+)/NF-M(+)) and a decrease in apoptotic cells in the hippocampal region of the brain. These observations suggested that osthole promoted NSC proliferation, supported neurogenesis, and thus efficiently rescued impaired neurons in the hippocampus and ameliorated cognitive impairment. We also found that osthole treatment activated the Notch pathway and upregulated the expression of self-renewal genes Notch 1 and Hes 1 mRNA in NSCs. However, when Notch activity was blocked by the γ-secretase inhibitor DAPT, the augmentation of Notch 1 and Hes 1 protein was ameliorated, and the proliferation-inducing effect of osthole was abolished, suggesting that the effects of osthole are at least in part mediated by activation of the Notch pathway.
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Transtornos Cognitivos/tratamento farmacológico , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Células-Tronco Neurais/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transtornos Cognitivos/metabolismo , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células-Tronco Neurais/citologia , Neurogênese/efeitos dos fármacos , Presenilina-1/genéticaRESUMO
In abandoned open-pit coal mines, surface water and groundwater form acidic waters with high concentrations of metal ions due to chemical interactions with ores such as pyrite, and the formation of acid mine drainage (AMD) is one of the major sources of pollution of world concern. For this reason, this paper reviews the formation mechanisms and influencing factors of AMD. It also describes the prediction, prevention, and remediation techniques for AMD, identifying key research gaps. It also discusses the current challenges and shortcomings faced globally in the management of AMD. The formation of AMD is mainly caused by the oxidation of pyrite in mines, but it is mainly influenced by history, climate, topography, and hydrogeology, making the formation mechanism of AMD extremely complex. Currently, the remediation technologies for AMD mainly include active treatment and passive treatment, which can effectively neutralize acidic wastewater. However, the prediction technology for AMD is blank, and the source treatment technology such as passivation and microencapsulation only stays in the experimental stage. This leads to the high cost of treatment technologies at this stage and the inability to identify potential risks in mines. Overall, this review provides remediation tools for AMD from predicting root causes to treatment. Geophysical technology is an effective method for predicting the motion path and pollution surface of AMD in the future, and resource recovery for AMD is a key point that must be paid attention to in the future. Finally, integrated treatment technologies that deserve further exploration need to be emphasized.
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Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Mineração , Ferro , SulfetosRESUMO
In the light of circular economy aspects, processing of large-scale municipal wastewater treatment plants (WWTPs) needs reconsideration to limit the overuse of energy, implement of non-green technologies and emit abundant greenhouse gas. Along with the huge increase in the worldwide population and agro-industrial activities, global environmental organizations have issued several recent roles to boost scientific and industrial communities towards sustainable development. Over recent years, China has imposed national and regional standards to control and manage the discharged liquid and solid waste, as well as to achieve carbon peaking and carbon neutrality. The aim of this report is to analyze the current state of Chinese WWTPs routing and related issues such as climate change and air pollution. The used strategies in Chinese WWTPs and upgrading trends were critically discussed. Several points were addressed including the performance, environmental impact, and energy demand of bio-enhanced technologies, including hydrolytic acidification pretreatment, efficient (toxic) strain treatment, and anaerobic ammonia oxidation denitrification technology, as well as advanced treatment technologies composed of physical and chemical treatment technologies, biological treatment technology and combined treatment technology. Discussion and critical analysis based on the current data and national policies were provided and employed to develop the future development trend of municipal WWTPs in China from the construction of sustainable and "Zero carbon" WWTPs.
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Bacterial infection can cause a series of diseases and play a vital role in medical care. Therefore, early diagnosis of pathogenic bacteria is crucial for effective treatment and the prevention of further infection. However, restricted by the current technology, bacterial detection is usually time-consuming and laborious and the samples need tedious processing even to be tested. Herein, we present a terahertz metasensor based on the coupling of electrical and toroidal dipoles to achieve rapid, non-destructive, label-free identification and highly sensitive quantitative detection of the two most common pathogenic bacteria. The reinforcement of the toroidal dipole significantly boosts the light-matter interactions around the surface of the microstructure, and thus the sensitivity and Q factor of the designed metasensor reach as high as 378 GHz per refractive index unit (RIU) and 21.28, respectively. Combined with the aforementioned advantages, the proposed metasensor successfully identified Escherichia coli and Staphylococcus aureus and quantitatively detected four concentrations with the lowest detectable concentration being â¼104 cfu mL-1 in the experiment. This work naturally enriches the research on THz metasensors based on the interference mechanism and inspires more innovations to facilitate the development of biosensing applications.
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Técnicas Biossensoriais , Infecções Estafilocócicas , Humanos , Limite de Detecção , Escherichia coli , BactériasRESUMO
Early gastric cancer (EGC) has a desirable prognosis compared with advanced gastric cancer (AGC). The surgical concept of EGC has altered from simply emphasizing radical resection to both radical resection and functional preservation. As the mainstream surgical methods for EGC, both endoscopic resection and laparoscopic resection have certain inherent limitations, while the advent of laparoscopic and endoscopic cooperative surgery (LECS) has overcome these limitations to a considerable extent. LECS not only expands the surgical indications for endoscopic resection, but greatly improves the quality of life (QOL) in EGC patients. This minireview elaborates on the research status of LECS for EGC, from the conception and development of LECS, to the tentative application of LECS in animal experiments, then to case reports and retrospective clinical studies. Finally, the challenges and prospects of LECS in the field of EGC are prospected and expounded, hoping to provide some references for relevant researchers. With the in-depth understanding of minimally invasive technology, LECS remains a promising option in the management of EGC. Carrying out more related multicenter prospective clinical researches is the top priority of promoting the development of this field in the future.
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Terahertz (THz) meta-devices are considered to be a promising framework for constructing integrated photonic circuitry, which is significant for processing the upsurge of data brought about by next-generation telecommunications. However, present active metasurfaces are typically restricted by a single external driving field, a single modulated frequency, fixed switching speed, and deficiency in logical operation functions which prevents devices from further practical applications. Here, to overcome these limitations, we propose a hybrid THz metasurface consisting of vanadium dioxide (VO2) and germanium (Ge) that enables electrical and optical tuning methods individually or simultaneously and theoretically investigate its performance. Each of the two materials is arranged in the meta-atom to dominate the resonance strength of toroidal or magnetic dipoles. Controlled by either or both of the external excitations, the device can switch on or off at four different frequencies, possessing two temporal degrees of freedom in terms of manipulation when considering the nonvolatility of VO2 and ultrafast photogenerated carriers of Ge. Furthermore, the "AND" and "OR" logic operations are respectively achieved at two adjacent frequency bands by weighing normalized transmission amplitude. This work may provide an auspicious paradigm of THz components, such as dynamic filters, multiband switches, and logical modulators, potentially promoting the design and implementation of multifunctional electro-optical devices in future THz computing and communication.
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Background: Chemotherapy, radiotherapy, targeted therapy and immunotherapy have demonstrated expected clinical efficacy, while drug resistance remains the predominant limiting factor to therapeutic failure in patients with colorectal cancer (CRC). Although there have been numerous basic and clinical studies on CRC resistance in recent years, few publications utilized the bibliometric method to evaluate this field. The objective of current study was to provide a comprehensive analysis of the current state and changing trends of drug resistance in CRC over the past 20 years. Methods: The Web of Science Core Collection (WOSCC) was utilized to extracted all studies regarding drug resistance in CRC during 2002-2021. CiteSpace and online platform of bibliometrics were used to evaluate the contributions of various countries/regions, institutions, authors and journals in this field. Moreover, the recent research hotspots and promising future trends were identified through keywords analysis by CiteSpace and VOSviewer. Results: 1451 related publications from 2002 to 2021 in total were identified and collected. The number of global publications in this field has increased annually. China and the USA occupied the top two places with respect to the number of publications, contributing more than 60% of global publications. Sun Yat-sen University and Oncotarget were the institution and journal which published the most papers, respectively. Bardelli A from Italy was the most prolific writer and had the highest H-index. Keywords burst analysis identified that "Growth factor receptor", "induced apoptosis" and "panitumumab" were the ones with higher burst strength in the early stage of this field. Analysis of keyword emergence time showed that "oxaliplatin resistance", "MicroRNA" and "epithelial mesenchymal transition (EMT)" were the keywords with later average appearing year (AAY). Conclusions: The number of publications and research interest on drug resistance in CRC have been increasing annually. The USA and China were the main driver and professor Bardelli A was the most outstanding researcher in this field. Previous studies have mainly concentrated on growth factor receptor and induced apoptosis. Oxaliplatin resistance, microRNA and EMT as recently appeared frontiers of research that should be closely tracked in the future.
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Terahertz (THz) plasmonic resonance based on an arbitrarily designed resonance metasurface is the key technique of choice for enhancing fingerprint absorption spectroscopy identification of biomolecules. Here, we report a broadband THz micro-photonics sensor based on a pixelated frequency-agile metasurface and illustrate its application ability to enhance and differentiate the detection of broadband absorption fingerprint spectra. The design uses symmetrical metal C-shape resonators with the functional graphene micro-ribbons selectively patterned into the gaps. A strong electric resonance with a high quality factor was formed, consisting of an electric dipole mode associated with the excitation of a dark toroidal dipole (TD) mode through the coupling from the electric dipole moment of the individual frequency-agile meta-unit. The resonance positions are nearly linearly modulated with the varying Fermi level of graphene. The configuration arranges a certain metapixel of the metasurface to multiple response spectra assembling a one-to-many mapping between spatial and spectral information which is instrumental in greatly shrinking the actual size of the sensor. By the synchronous regulation of graphene and C-shape rings, we have obtained highly surface-sensitive resonances over a wide spectral range (â¼1.5 THz) with a spectral resolution less than 20 GHz. The target multiple enhanced absorption spectrum of glucose molecules is read out in a broadband region with high sensitivity. More importantly, the design can be extended to cover a larger spectral region by altering the range of geometrical parameters. Our microphotonic technique can resolve absorption fingerprints without the need for spectrometry and frequency scanning, thereby providing an approach for highly sensitive and versatile miniaturized THz spectroscopy devices.
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Background: Colorectal cancer (CRC) is the third most prevalent cancer worldwide and the second leading cause of cancer mortality. Signal transducer and activator of transcription (STAT) proteins are a group of transcription factors implicated in cell signal transduction and gene transcription in several cancer types. However, the level of expression, genetic alterations, and biological function of different STATs, as well as their prognostic and immunotherapeutic value in CRC remain unclear. Methods: The mRNA and protein expression levels, genetic alterations, prognostic value, gene-gene and protein-protein interaction networks, and biological function of STATs in CRC were studied using the GEPIA, HPA, cBioPortal, PrognoScan, Kaplan-Meier plotter, GeneMANIA, STRING, and Metascape databases. The expression of STATs in CRC was confirmed using immunohistochemistry (IHC). Finally, the relationship between STAT expression and immune infiltration as well as immunotherapy-associated indicators was also investigated. Results: The expression levels of STAT2/5A/5B are downregulated in CRC, and the STAT1/3/4/5B expressions were significantly associated with the tumor stage of patients with CRC. The abnormal expression of STAT2/4/5B in patients with CRC is related to the prognosis of patients with CRC. The STATs and their neighboring proteins are primarily associated with lymphocyte activation, cytokine-mediated signaling pathways, positive regulation of immune response, regulation of cytokine production, and growth hormone receptor signaling pathways in cancer. The expression of STATs was significantly associated with immune infiltration and immunotherapy response-associated indicators. Conclusion: This study may help further understand the molecular mechanism of CRC and provide new prognostic biomarkers and immunotherapy targets in patients with CRC.
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Alzheimer's disease (AD) is an age-related neurological disorder. Currently, there is no effective cure for AD due to its complexity in pathogenesis. In light of the complex pathogenesis of AD, the traditional Chinese medicine (TCM) formula Kai-Xin-San (KXS), which was used for amnesia treatment, has been proved to improve cognitive function in AD animal models. However, the active ingredients and the mechanism of KXS have not yet been clearly elucidated. In this study, network pharmacology analysis predicts that KXS yields 168 candidate compounds acting on 863 potential targets, 30 of which are associated with AD. Enrichment analysis revealed that the therapeutic mechanisms of KXS for AD are associated with the inhibition of Tau protein hyperphosphorylation, inflammation, and apoptosis. Therefore, we chose 7-month-old senescence-accelerated mouse prone 8 (SAMP8) mice as AD mouse model, which harbors the behavioral and pathological hallmarks of AD. Subsequently, the potential underlying action mechanisms of KXS on AD predicted by the network pharmacology analyses were experimentally validated in SAMP8 mice after intragastric administration of KXS for 3 months. We observed that KXS upregulated AKT phosphorylation, suppressed GSK3ß and CDK5 activation, and inhibited the TLR4/MyD88/NF-κB signaling pathway to attenuate Tau hyperphosphorylation and neuroinflammation, thus suppressing neuronal apoptosis and improving the cognitive impairment of aged SAMP8 mice. Taken together, our findings reveal a multi-component and multi-target therapeutic mechanism of KXS for attenuating the progression of AD, contributing to the future development of TCM modernization, including KXS, and broader clinical application.
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Doença de Alzheimer , Medicamentos de Ervas Chinesas , Doença de Alzheimer/tratamento farmacológico , Animais , Apoptose , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Camundongos , Proteínas tauRESUMO
Metasurfaces with a strongly enhanced local field are envisioned as a powerful platform for ultrasensitive optical sensors to significantly amplify imperceptible differences between compatible bioanalytes. Through the use of phototunable silicon-based terahertz (THz) metasurfaces, we experimentally demonstrate ultrafast switchable sensing functions. It is found that the THz responses of the coupled-resonances in the metasurfaces shift from Lorentz-lattice mode to electromagnetism-induced transparency (EIT) mode under optical pumping within an ultrashort time of 32 ps, enabling an ultrafast sensitive sensor. For the Lorentz-lattice mode, the THz time-domain signal directly shows a highly sensitive response to detect tiny analytes without extra Fourier transformation as the mismatch between the two modes increases. Once the metasurfaces are switched to the EIT mode, the silicon-metal hybrid structure supports frequency-domain sensing ability due to strong field confinement with a sensitivity of 118.4 GHz/RIU. Both of the sensing configurations contribute to more subtle information and guarantee the accuracy of the sensor performance. Combined with the aforementioned advantages, the proposed metasurfaces have successfully identified colorectal cells between normal, adenoma, and cancer states in experiments. This work furnishes a new paradigm of constructing reliable and flexible metasurface sensors and can be extended to other optics applications.