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Alzheimer's disease (AD) presents a significant challenge to global healthcare systems, with current treatments offering only modest relief and often bringing unwanted side effects, necessitating the exploration of more effective and safer drugs. In this study, we employed the Caenorhabditis elegans (C. elegans) model, specifically the AD-like CL4176 strain expressing the human Aß(1-42) protein, to investigate the potential of Reineckia carnea extract and its fractions. Our results showed that the Reineckia carnea ether fraction (REF) notably diminished the paralysis rates of CL4176 worms. Additionally, REF also attenuated the neurotoxicity effects prompted by Tau proteins in the BR5270 worms. Moreover, REF was observed to counteract the accumulation of Aß and pTau proteins and their induced oxidative stress in C. elegans AD-like models. Mechanistic studies revealed that REF's benefits were associated with the induction of autophagy in worms; however, these protective effects were nullified when autophagy-related genes were suppressed using RNAi bacteria. Together, these findings highlight Reineckia carnea ether fraction as a promising candidate for AD treatment, warranting further investigation into its autophagy-inducing components and their molecular mechanisms.
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Enfermedad de Alzheimer , Proteínas de Caenorhabditis elegans , Animales , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Caenorhabditis elegans/metabolismo , Animales Modificados Genéticamente , Péptidos beta-Amiloides/metabolismo , Éter/farmacología , Proteínas de Caenorhabditis elegans/metabolismo , Éteres de Etila/metabolismo , Éteres de Etila/farmacología , Éteres de Etila/uso terapéutico , Éteres/farmacología , Modelos Animales de EnfermedadRESUMEN
As is well-known, ship-radiated noise (SN) signals, which contain a large number of ship operating characteristics and condition information, are widely used in ship recognition and classification. However, it is still a great challenge to extract weak operating characteristics from SN signals because of heavy noise and non-stationarity. Therefore, a new mono-component extraction method is proposed in this paper for taxonomic purposes. First, the non-local means algorithm (NLmeans) is proposed to denoise SN signals without destroying its time-frequency structure. Second, adaptive chirp mode decomposition (ACMD) is modified and applied on denoised signals to adaptively extract mono-component modes. Finally, sub-signals are selected based on spectral kurtosis (SK) and then analyzed for ship recognition and classification. A simulation experiment and two application cases are used to verify the effectiveness of the proposed method and the results show its outstanding performance.
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To suppress the noise interference in underwater acoustic signals for recognition, a practical denoising representation and recognition method is proposed. This algorithm first generates the multi-images between marine noise and target signal by correlation and "dropout" processing, adaptively. Second, a convolutional denoising autoencoder is designed to train the segmented multi-images in parallel to acquire denoising features. Finally, to improve the classification accuracy of random forest (RF), the weight fusion is exploited to initialize parallel RF classifier. Numerical experiments are shown that demonstrate superiority to three other methods in feature denoising and classification under underwater acoustic scenes.
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A rapid strategy for the ß-glycosidase (ß-Gal) and Escherichia coli (E. coli) sensing is presented, which is based on selective recognition reactions of QDs using visualization/fluorescence (FL)/atomic fluorescence spectrometry (AFS)/inductively coupled plasma mass spectrometry (ICP-MS) multimode assay. CdTe QDs can selectively recognize Ag+ and Ag NPs with a cation exchange reaction (CER) where Ag+ triggers the release of Cd2+ and quenches the fluorescence signal of QDs. Taking advantage of the fact that ß-Gal can hydrolyze 4-Aminophenyl ß-D-galactopyranoside (PAPG) to produce p-aminophenol (PAP), which has the ability to reduce Ag+ to form Ag NPs. The ß-Gal can be easily detected by visualization or FL in a turn-on manner. Furthermore, combining with the selective separation of Cd2+ by filter membrane, AFS and ICP-MS with higher sensitivity were used for the determination of the enzyme. Under optimized conditions, the system limits of detections (LODs) were 0.01 U/L, 0.03 mU/L, and 0.02 mU/L using FL, AFS, and ICP-MS as the detector, respectively. The relative standard deviations (RSDs, n = 7) for 0.1 U/L ß-Gal were 2.2, 2.0, and 1.3% using FL/AFS/ICP-MS as the detector, respectively. And 0.1 U/L of ß-Gal can be discriminated from the blank solution with the naked eye. In addition, given that the ß-Gal can serve as an indicator of E. coli, we have successfully applied this strategy for the detection of E. coli with a LOD of 25 CFU/mL. Application of the method was demonstrated by analyzing human urine samples and milk samples for ultra-trace detection of E. coli. Graphical abstract The CVG-AFS/ICP-MS/visual/FL multimode ß-Gal and E.coli detection via CER.
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Proteínas Bacterianas/análisis , Técnicas Bacteriológicas/métodos , Pruebas de Enzimas/métodos , Escherichia coli/aislamiento & purificación , beta-Galactosidasa/análisis , Animales , Proteínas Bacterianas/química , Proteínas Bacterianas/orina , Compuestos de Cadmio/química , Escherichia coli/enzimología , Galactósidos/química , Humanos , Límite de Detección , Espectrometría de Masas , Nanopartículas del Metal/química , Leche/microbiología , Oxidación-Reducción , Puntos Cuánticos/química , Plata/química , Espectrometría de Fluorescencia , Telurio/química , Orina/microbiología , beta-Galactosidasa/química , beta-Galactosidasa/orinaRESUMEN
This paper aims to present an improved bicoherence spectrum (IBS) combined with cyclic modulation spectrum (CMS) and cross-correlation that is suitable for classification of hydrophone signals involving deep learning (DL). First, the proposed feature utilizes the all-phase fast Fourier transform to modify the spectrum leakage caused by CMS; this can be used to detect line spectra with low signal-to-noise ratios (SNRs). Second, the cross-correlation and bispectrum are both exploited to suppress non-periodic line spectra interference from CMS. Based on numerous numerical simulations and experimental verification, compared with CMS and conventional bispectrum, the prominent characteristics of IBS include: detecting higher-precision periodic harmonics without single-line interference, superior robustness under low SNR, and greatly reducing the data redundancy. In addition, to test the performance of IBS for DL application, three deep belief network (DBN)-based classifiers-DBN-softmax, DBN-support vector machine, and DBN-random forest-are introduced and employed for five experimental scenarios (including ships and underwater source). The results indicate that benefiting from DBN pre-training, the IBS classification accuracy of DBN-based models is generally higher than 80%.
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Aprendizaje Profundo , Procesamiento de Señales Asistido por Computador , Espectrografía del Sonido/métodos , Análisis de Fourier , Ruido , Océanos y Mares , Relación Señal-RuidoRESUMEN
Pharmacological strategies to delay aging and combat age-related diseases are increasingly promising. This study explores the anti-aging and therapeutic effects of two novel 18-norspirostane steroidal saponins from Trillium tschonoskii Maxim, namely deoxytrillenoside CA (DTCA) and epitrillenoside CA (ETCA), using Caenorhabditis elegans (C. elegans). Both DTCA and ETCA significantly extended the lifespan of wild-type N2 worms and improved various age-related phenotypes, including muscle health, motility, pumping rate, and lipofuscin accumulation. Furthermore, these compounds exhibited notable alleviation of pathology associated with Parkinson's disease (PD) and Huntington's disease (HD), such as the reduction of α-synuclein and poly40 aggregates, improvement in motor deficits, and mitigation of neuronal damage. Meanwhile, DTCA and ETCA improved the lifespan and healthspan of PD- and HD-like C. elegans models. Additionally, DTCA and ETCA enhanced the resilience of C. elegans against heat and oxidative stress challenges. Mechanistic studies elucidated that DTCA and ETCA induced mitophagy and promoted mitochondrial biogenesis in C. elegans, while genetic mutations or RNAi knockdown affecting mitophagy and mitochondrial biogenesis effectively eliminated their capacity to extend lifespan and reduce pathological protein aggregates. Together, these compelling findings highlight the potential of DTCA and ETCA as promising therapeutic interventions for delaying aging and preventing age-related diseases.
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Proteínas de Caenorhabditis elegans , Enfermedad de Parkinson , Saponinas , Animales , Caenorhabditis elegans/metabolismo , Longevidad , Mitofagia , Biogénesis de Organelos , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Saponinas/farmacologíaRESUMEN
Natural killer (NK) cells are cytotoxic innate lymphocytes that eradicate tumor cells. Inducing durable antitumor immune responses by NK cells represents a major priority of cancer immunotherapy. While cytosolic DNA sensing plays an essential role in initiating antitumor immunity, the role of NK cell-intrinsic STING signaling remains unclear. Here, we find that NK cell-intrinsic STING promotes antitumor responses and maintains a reservoir of TCF-1+ NK cells. In contrast, tumor cell-intrinsic cGAS and mtDNA are required for NK cell antitumor activity, indicating that tumor mtDNA recognition by cGAS partially triggers NK cell-intrinsic STING activation. Moreover, addition of cGAMP enables STING activation and type I interferon production in NK cells, thereby supporting the activation of NK cells in vitro. In humans, STING agonism promotes the expansion of TCF-1+ NK cells. This study provides insight into understanding how STING signaling drives NK cell antitumor immunity and the development of NK cell-based cancer immunotherapy.
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Antineoplásicos , Neoplasias , Humanos , Neoplasias/patología , Antineoplásicos/farmacología , Nucleotidiltransferasas/metabolismo , ADN Mitocondrial , Células Asesinas Naturales/metabolismo , Inmunidad InnataRESUMEN
Microplastics (MPs) and cadmium (Cd) exist extensively in ambient environments and probably influence negatively on human health. However, the potential reproductive toxicity of MPs or MPs + Cd remains unknown. This study was aimed to observe the reproductive changes of male mice treated orally for 35 days with PS-MPs (100 mg/kg), CdCl2 (5 mg/kg) and PS-MPs plus CdCl2 mixture. We found that subchronic exposure to PS-MPs damaged mouse testicular tissue structure, reduced sperm quality and testosterone levels. Moreover, the reproductive toxicity in 0.1 µm group was stronger than 1 µm group, and mixture group was more severe than single particle size ones. Meanwhile, co-exposure of PS-MPs and Cd exacerbated reproductive injury in male mice, with an ascending toxicity of Cd, 1 µm + Cd, 0.1 µm + Cd, and 0.1+1 µm + Cd. In addition, we discovered that the testicular damage induced by PS-MPs or PS-MPs + Cd was associated with interfering the miR-199a-5p/HIF-1α/ferroptosis pathway. Promisingly, these findings will shed new light on how PS-MPs and PS-MPs + Cd damage male reproductive function.
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Ferroptosis , MicroARNs , Humanos , Masculino , Ratones , Animales , Microplásticos/toxicidad , Cadmio/toxicidad , Plásticos/toxicidad , Semen , Poliestirenos/toxicidadRESUMEN
Introduction: In recent years, a growing number of near-death experience (NDE) testimonies have been collected worldwide due to an increasing interest in research on this phenomenon. China has many patients who survive life-threatening situations, leaving over much data on NDEs to be collected for research. In the historical context of Eastern civilization, many mentally controlled practices in China can also lead to "NDEs-like" (e.g., meditation). This study aimed (1) to translate and validate the recently developed Near-Death Experience Content (NDE-C) scale into Chinese and (2) to quantify and identify NDEs and NDEs-like in China with this new Chinese version of the NDE-C scale. Methods: Here, we presented the work that had been performed to translate the NDE-C scale into Chinese and validated this version on 79 NDE testimonies. Results: Brislin's back-translation model was performed to translate a Chinese version of the NDE-C scale and internal consistency (the Cronbach's α value for the total group = 0.846) as well as the confirmatory factor analysis was conducted. Discussion: Currently, the Chinese version of the NDE-C scale is ready for use in research practice in the context of Eastern culture, to screen people who have experienced an NDEs(-like) and to quantify their subjective experience, promoting further NDEs-related research in China.