RESUMEN
Although existing reconstruction-based multivariate time series anomaly detection (MTSAD) methods have shown advanced performance, most assume the training data is clean. When faced with noise or contamination in training data, they can also reconstruct the anomaly well, weakening the distinction between normal and anomaly. Some probabilistic generation-based methods have been used to address this issue because of their implicit robust structure to noise, but the training process and suppression of anomalous generalization are not stable. The recently proposed explicit method based on the memory module would also sacrifice the reconstruction effect of normal patterns, resulting in limited performance improvement. Moreover, most existing MTSAD methods use a single fixed-length window for input, which weakens their ability to extract long-term dependency. This paper proposes a robust multi-scale feature extraction framework with the dual memory module to comprehensively extract features fusing different levels of semantic information and lengths of temporal dependency. First, this paper designs consecutive neighboring windows as inputs to allow the model to extract local and long-term dependency information. Secondly, a dual memory-augmented encoder is proposed to extract global typical patterns and local common features. It ensures the reconstruction ability of normal data while suppressing the generalization of the anomaly. Finally, this paper proposes a multi-scale fusion module to fuse latent variables representing different levels of semantic information and uses the reconstructed latent variables to reconstruct samples for anomaly detection. Experimental results on five datasets from diverse domains show that the proposed method outperforms 16 typical baseline methods.
Asunto(s)
Redes Neurales de la Computación , Algoritmos , Análisis Multivariante , Humanos , Factores de Tiempo , Memoria/fisiologíaRESUMEN
While existing reconstruction-based multivariate time series (MTS) anomaly detection methods demonstrate advanced performance on many challenging real-world datasets, they generally assume the data only consists of normal samples when training models. However, real-world MTS data may contain significant noise and even be contaminated by anomalies. As a result, most existing approaches easily capture the pattern of the contaminated data, making identifying anomalies more difficult. Although a few studies have aimed to mitigate the interference of the noise and anomalies by introducing various regularizations, they still employ the objective of fully reconstructing the input data, impeding the model from learning an accurate profile of the MTS's normal pattern. Moreover, it is difficult for existing methods to apply the most appropriate normalization schemes for each dataset in various complex scenarios, particularly for mixed-feature MTS. This paper proposes a filter-augmented auto-encoder with learnable normalization (NormFAAE) for robust MTS anomaly detection. Firstly, NormFAAE designs a deep hybrid normalization module. It is trained with the backbone end-to-end in the current training task to perform the optimal normalization scheme. Meanwhile, it integrates two learnable normalization sub-modules to deal with the mixed-feature MTS effectively. Secondly, NormFAAE proposes a filter-augmented auto-encoder with a dual-phase task. It separates the noise and anomalies from the input data by a deep filter module, which facilitates the model to only reconstruct the normal data, achieving a more robust latent representation of MTS. Experimental results demonstrate that NormFAAE outperforms 17 typical baselines on five real-world industrial datasets from diverse fields.
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Aprendizaje , Factores de TiempoRESUMEN
In traditional wastewater treatment methods, the removal of emerging contaminants including perfluorooctanoic acid (PFOA) can be challenging. To address this, biochar is commonly utilized as an activator for peroxymonosulphate (PMS) to effectively eliminate organic pollutants. Sewage sludge has shown potential as a biochar precursor, but its complex composition and variable iron content, as well as the low specific surface area of the product limit the practical use of iron-dominated sludge-derived catalysts. To overcome this limitation, N-doped citrate-sludge-derived carbon (NCSC) was synthesized, possessing a low iron content (0.29 at%) and a large specific surface area (315.31 m2 g-1). As a comparison, Fe-/N-doped citrate-sludge-derived carbon (Fe-NCSC) was prepared by introducing exogenous iron, resulting in a higher iron content (2.12 at%) but a significantly reduced specific surface area (73.87 m2 g-1). In performance evaluation, the NCSC/PMS system achieved impressive removal efficiency, effectively eliminating 99.8% of PFOA (at an initial concentration of 2 mg L-1) within 60 min, while Fe-NCSC/PMS only achieved 84.6%. The slightly lower reaction rate per specific surface area of NCSC/PMS proved that large specific surface area was NCSC's key advantage. The lower sensitivity of NCSC to pH and water substrates than FeNCSC suggested different activation mechanisms. Further analysis of reactive sites and species showed that the main oxidation mechanism of NCSC/PMS was forming the surface-bound PMS-NCSC complexes at the N sites, followed by PFOA donating electrons to the complexes to be oxidized, which was different from the Fe/N-dominated singlet oxygen mechanism of Fe-NSC/PMS. Furthermore, the reusability of the NCSC was demonstrated, with the removal rate decreasing to only 90.1% after four cycles and recovering to 94.8% after heated regeneration. In conclusion, this study provides a viable method for the elimination of emerging contaminants such as PFOA in water remediation.
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Carbono , Aguas del Alcantarillado , Carbono/química , Ácido Cítrico , Electrones , Peróxidos/química , Hierro/química , Citratos , AguaRESUMEN
Intimately coupled photocatalysis and biodegradation (ICPB) combining photocatalysis with microbial degradation is an attractive wastewater treatment technology. However, when prepared in conventional ways, the supported-photocatalysts aggregate frequently, detach easily from carriers, and prohibit the colonization of microorganisms inside the carriers. To overcome these challenges, silane coupling agent (SCA)-enhanced TiO2 coating method is developed in this study. The coupling agent γ-glycidoxypropyltrimethoxysilane (KH560) greatly enhanced the adhesion between photocatalysts and the carrier through ether and Ti-O-Si linkages. The dense TiO2 layer was firmly adhered to the carrier outer surface, and the loading amount reached 351.8±8.2 mg/g, over ten times higher than using the powder sintering method (31.5±2.4 mg/g). In the ICPB system constructed with the KH560-enhanced TiO2-supported polyurethane sponge (KH560-TiO2-PU) carriers, removal efficiencies of two model odor substances, 2-methylisoborneol (2-MIB) and geosmin (GSM), reached 88.9±0.3% and 85.0±1.0% in 12 h at an initial concentration of 500 ng/L respectively, which were 17.7±0.6% and 19.4±0.4% greater than those of the ICPB system prepared with the powder sintering method. After 5 operating cycles, the novel ICPB system remained stable with high 2-MIB and GSM removal efficiencies, reaching 89.9±0.8% and 86.1±0.2% respectively after 12h, while TiO2 peeling ratio was as low as 5.0±2.8%. Biofilms attached onto the carrier inner surface were resilient over the operating cycles with the increase of both richness and diversity of microbial communities. Analysis of biofilm microbial community and pollutant degradation pathways revealed the enhanced removal of 2-MIB and GSM in the novel ICPB system might be attributed to multiple factors. First, the alleviated aggregation and increased adhesion of photocatalysts onto carriers improved the overall photocatalysis efficiency. Second, biofilm inside of the carrier was protected and the microbial activity was well remained. Third, photocatalytic intermediate products were efficiently biodegraded by the enriched functional microbial populations, such as Thauera and Flavobacterium, with little concern of excessive oxidation. Collectively, this research provides a new technological solution that synergizes photocatalysis and biodegradation for effective removal of odorous substances in polluted natural water.
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Odorantes , Silanos , Biodegradación Ambiental , TitanioRESUMEN
Disulfiram (DSF) in combination with copper (Cu) has been reported to override drug resistance in cancer cells, and DSF combined with chemotherapy based on the microtubule inhibitor vinorelbine appears to prolong survival in non-small cell lung cancer patients. Here, we investigated the mechanisms underlying these findings. DSF/Cu reversed the microtubule inhibitor resistance in A549/Taxol and KB/VCR cells in vitro, and had anti-tumor effects in A549/Taxol and KB/VCR xenograft mice. DSF/Cu and DSF reduced the cancer stem cell (CSC) characteristics of drug-resistant A549/Taxol and KB/VCR cells, including sphere formation, colony generation and migration, and DSF/Cu was more effective than DSF alone. DSF/Cu also decreased the aldehyde dehydrogenase (ALDH) activity and the expression of P-gp and stem cell transcription factors in A549/Taxol and KB/VCR cells. Knockdown of ALDH2 attenuated the CSC characteristics of resistant cancer cells and enhanced their sensitivity to Taxol or VCR. Importantly, DSF/Cu treatment inhibited the expression of ALDH2 in vitro and in vivo. Our findings suggest that DSF/Cu reverses microtubule inhibitor resistance in cancer cells by suppressing ALDH2 expression, and Cu improves the activity of DSF.
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Aldehído Deshidrogenasa Mitocondrial/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cobre/administración & dosificación , Disulfiram/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Moduladores de Tubulina/uso terapéutico , Células A549 , Animales , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Sinergismo Farmacológico , Humanos , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Terapia Molecular Dirigida/métodos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Disulfiram (DSF) possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. DSF also potently inhibits angiogenesis, but the effect of Cu on this anti-angiogenic activity is unknown. Here we show that DSF inhibits the proliferation, migration, invasion, adhesion and complex tube formation of human umbilical vascular endothelial cells (HUVECs). Aortic ring assays and Matrigel plug assays revealed that DSF significantly inhibited the formation of microvessels. Importantly, Cu improved the anti-angiogenic activity of DSF in all these assays, while copper alone had no effect. DSF/Cu treatment of U87 human glioblastoma cells resulted in suppression of VEGF secretion through the EGFR/c-Src/VEGF pathway. Reduction of EGFR phosphorylation disables recruitment of multiple Src homology 2 (SH2) domains, resulting in transcriptional down-regulation of VEGF. The role of EGFR/c-Src/VEGF pathway was further confirmed by using specific inhibitor, which significantly improved the anti-angiogenic activity of DSF/Cu. DSF/Cu also exerted increased anti-tumor effects on subcutaneous and intracerebral U87 xenograft models by reducing microvessel density (MVD) and VEGF expression. These results indicate that Cu improves the anti-angiogenic activity of DSF by targeting the EGFR/Src/VEGF signaling pathway, thus providing a rationale for the use of DSF/Cu rather than DSF alone as an angiogenesis inhibitor in clinical applications.
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Inhibidores de la Angiogénesis/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Glioma/tratamiento farmacológico , Células Endoteliales de la Vena Umbilical Humana/fisiología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Movimiento Celular , Disulfiram/administración & dosificación , Sinergismo Farmacológico , Receptores ErbB/metabolismo , Gefitinib , Glioma/irrigación sanguínea , Glioma/patología , Gluconatos/administración & dosificación , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Quinazolinas/farmacología , Transducción de Señal , Carga Tumoral/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Familia-src Quinasas/metabolismoRESUMEN
Retinoid X receptor (RXR) and Histone deacetylase (HDAC) are considered important targets for cancer therapy due to their crucial roles in genetic or epigenetic regulations of cancer development and progression. Here, we evaluated the potential of dual targeting of RXR and HDAC using DW22 as a novel therapeutic approach to cancer treatment. We found that the co-expression of RXR-α and HDAC1 was frequently appeared in lung cancer and breast cancer tissues and cell lines. RXR was activated by DW22 in RXRα and HDAC1 overexpressed A549 and MDA-MB-435 cell lines. Meanwhile, DW22 inhibited the activity of HDAC by decreasing its expression in A549 and MDA-MB-435 cell lines, but not in RXRα and HDAC1 deficient cell lines. Moreover, DW22 suppressed cell growth, induced cell differentiation, prompted cell apoptosis and arrested cell cycle in A549, MDA-MB-435 or HL60 cell lines. Treatment human umbilical vascular endothelial cells (HUVECs) with DW22 suppressed migration, invasion and tube formation through decreasing VEGF expression. The up-regulation of Ac-H3 and p21, and down-regulation of VEGF caused by DW22 was markedly attenuated by silencing of HDAC1. Furthermore, knockdown of RXRα by siRNA completely blocked DW22-induced cell differentiation, but partially attenuated DW22-caused inhibition of cell proliferation, induction of cell apoptosis, and suppression of cell migration, invasion and tube formation. Moreover, intravenous administration of DW22 significantly retarded tumor growth of A549 and MDA-MB-435 xenograft mice models, and induced no substantial weight loss and gross toxicity. In addition, DW22 also reduced cell proliferation, angiogenesis, and induced cell apoptosis in vivo. Collectively, our data demonstrates that dual targeting of RXR and HDAC using DW22 possesses pleiotropic antitumor activities both in vitro and in vivo, providing a novel therapeutic approach for cancer treatment.
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Antineoplásicos/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Histona Desacetilasa 1/metabolismo , Ácidos Hidroxámicos/uso terapéutico , Receptor alfa X Retinoide/metabolismo , Tetrahidronaftalenos/uso terapéutico , Anciano , Animales , Bexaroteno , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Diferenciación Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Silenciador del Gen , Células HL-60 , Histonas/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones SCID , Persona de Mediana Edad , Invasividad Neoplásica , Trasplante de Neoplasias , Neovascularización Patológica , ARN Interferente Pequeño/metabolismo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Our previous study revealed that intracerebroventricular oxytocin (OT) markedly inhibited the restraint stress-priming conditioned place preference (CPP) reinstatement induced by methamphetamine (MAP) via the glutamatergic system. In this study, the effect of microinjection with OT into mesocorticolimbic regions, the medial prefrontal cortex (mPFC) and the dorsal hippocampus (DHC), on the restraint stress-priming CPP reinstatement were further studied. The results showed that a 15-min restraint stress significantly reinstated MAP-induced CPP, which was inhibited by the microinjection of OT (0.5 and 2.5µg/µl/mouse) into the mPFC. Atosiban (Ato), a selective inhibitor of OT receptor, could absolutely block the effect of OT (2.5µg/µl/mouse). The reinstatement was inhibited by microinjecting with OT (2.5 but not 0.5µg/µl/mouse) into the DHC, which could not be reversed by Ato. Western blotting results showed that the levels of GLT1, VGLUT2, NR2B, p-ERK1/2 and p-CREB expressions in the mPFC were increased and CaMKII was decreased markedly after the stress-priming MAP-induced CPP reinstatement test. OT blocked the changing levels of GLT1, VGLUT2, NR2B, p-CREB and CaMK II, which were reversed by Ato, but failed to affect the elevated expression of p-ERK1/2. In DHC, the levels of VGLUT2, p-ERK1/2 and CREB expressions were reduced during the stress-induced reinstatement, which could be reversed by OT and further abolished by Ato. The present results suggest that mPFC and DHC play differential roles in restraint stress-priming CPP reinstatement induced by MAP and OT via OT receptor affects the reinstatement in which the glutamatergic system is involved.