•Heat treatment effectively inactivated the lipoxygenase and peroxidase enzymes.•Protein dispersibility index was decreased sharply under excessive roasting.•Methionine, arginine, and cysteine showed ...higher heat sensitivity.•Pyrazines were the richest compounds in headspace volatiles of roasted soybean.•Roasted flavor were positive associated with pyrazines, heterocycles, and furanoids.
We applied oven-roasting on soybean in order to investigate their physicochemical, sensory, and volatile profiles using electronic nose and HS-SPME-GC–MS. Results revealed a temperature dependent kinetic on the physicochemical index except fat content. Roasting at 200 °C for 20 min decreased the protein dispersibility index about 38%; while, lipoxygenase and peroxidase were entirely inactivated. The primary heat sensitive amino acids were methionine, arginine, and cysteine. Electronic nose showed certain capacity to discriminate varying roasted soybeans. Out of 41 volatile compounds identified in soybean headspace, 2,5-dimethylpyrazine showed the highest abundance of 411.18 μg/Kg. Regression model suggested the association of hexanal and aliphatic alcohols with beany flavor, while pyrazines, heterocycles, and furanoids showed a positive correlation with roasted flavor. The selected flavor markers can be used to predict the development of flavor in roasted soybeans. Our study emphasized the effect of roasting level on nutritive value and flavor profiles of soybeans.
•PBS polymer showed well performance for real RAS wastewater denitrification.•High nitrate loading was favor to inhibit sulfate reduction and DNRA activity.•Variation in microbial population was ...responsible for changed reactor performance.•Precise carbon release was crucial for RAS denitrification process in practice.
Nitrate removal is essential for the sustainable operation of recirculating aquaculture system (RAS). This study evaluated the heterotrophic denitrification using poly(butylene succinate) as carbon source and biofilm carrier for RAS wastewater treatment. The effect of varied operational conditions (influent type, salinity and nitrate loading) on reactor performance and microbial community was investigated. The high denitrification rates of 0.53±0.19kgNO3−-Nm−3d−1 (salinity, 0‰) and 0.66±0.12kgNO3−-Nm−3d−1 (salinity, 25‰) were achieved, and nitrite concentration was maintained below 1mg/L. In addition, the existence of salinity exhibited more stable nitrate removal efficiency, but caused adverse effects such as excessive effluent dissolved organic carbon (DOC) and dissimilation nitrate reduce to ammonia (DNRA) activity. The degradation of PBS was further confirmed by SEM and FTIR analysis. Illumina sequencing revealed the abundance and species changes of functional denitrification and degradation microflora which might be the primary cause of varied reactor performance.
A hermetic Micro-Electro-Mechanical Systems (MEMS) package with a metal lid is investigated to prevent lid-off failure and improve its reliability during the precondition test. While the MEMS package ...benefits from miniaturization and low cost, a hermetic version is highly sensitive to internal pressure caused by moisture penetration and the reflow process, thus affecting its reliability. In this research, the finite element method is applied to analyze the contact stress between the metal lid and the silver epoxy by applying the cohesive zone model (CZM). Moreover, the red dye penetration test is applied, revealing a microcrack at the metal lid/silver epoxy interface. Further analyses indicate that the crack is caused by internal pressure. According to the experimental testing and simulation results, the silver epoxy material, the curing process, the metal lid geometry, and the bonding layer contact area can enhance the bonding strength between the metal lid and the substrate.
Aims
Noninvasive music adjuvant therapy shows great potential in improving seizure control when combined with routine antiepileptic drugs. However, the diversity of previous music protocols has ...resulted in disparate outcomes. The optimized protocol and features for music adjuvant therapy are still not fully understood which limits its feasibility.
Methods
By applying different regimens of music therapy in various temporal lobe epilepsy models, we evaluated the effect of music in combination with sub‐dose drugs on epileptic seizures to determine the optimized protocol.
Results
A subgroup of kindled mice that were responsive to music adjuvant therapy was screened. In those mice, sub‐dose drugs which were noneffective on kindled seizures, alleviated seizure severity after 12 h/day Mozart K.448 for 14 days. Shorter durations of music therapy (2 and 6 h/day) were ineffective. Furthermore, only full‐length Mozart K.448, not its episodes or other music varieties, was capable of enhancing the efficacy of sub‐dose drugs. This music therapeutic effect was not due to increasing cerebral drug concentration, but instead was related with the modulation of seizure electroencephalogram (EEG) spectral powers in the hippocampus.
Conclusion
These results indicate that long‐term full‐length Mozart K.448 could enhance the anti‐seizure efficacy of sub‐dose drugs and may be a promising noninvasive adjuvant therapy for temporal lobe epilepsy.
Music adjuvant therapy promotes the efficacy of sub‐dose antiepileptic drugs in both hippocampal and amygdaloid kindled temporal lobe epileptic mice. Listening to full‐length Mozart K.448 for 12 h/day is the optimal protocol for music adjuvant therapy.
Na+/K+-ATPase targeted cancer therapy has attracted increasing interests of oncologists in lung cancer field. Although multiple anti-cancer mechanisms of cardiac glycosides as Na+/K+-ATPase ...inhibitors are revealed, the role of autophagy and related molecular signaling pathway for the class of compounds in human non-small cell lung cancer (NSCLC) cells has not been systematically examined. We herein investigated the anti-cancer effects of two representative cardiac glycosides, digoxin and ouabain, in A549 and H460 cell lines. Both agents caused significant growth inhibition at nanomolar level. The cardiac glycosides were found to induce moderate G2/M arrest but not apoptosis at IC50 level in the NSCLC cell lines. Moreover, autophagy was markedly induced by both agents, as evidenced by the time- and dose-dependent increase of LC3-II, up-regulation of Atg5 and Beclin1, as well as by the observations through acridine orange staining, transmission electron microscopy and quantification of GFP-LC3 fluorescence. Importantly, AMP-activated protein kinase (AMPK) pathway was activated, resulting in mammalian target of rapamycin (mTOR) deactivation during autophagy induction. Moreover, extracellular-signal-regulated kinase 1/2 (ERK1/2) activation was simultaneously found to be involved in the autophagy regulation. Co-treatment with respective inhibitors or siRNAs could either block the autophagic phenotypes and signals, or significantly increase the cellular viability, indicating the drugs-induced autophagy plays tumor-suppressing role. This work provides first evidence showing that the cardiac glycosides induce autophagy in human NSCLC cells through regulation of both mTOR and ERK1/2 signaling pathways. The autophagy may at least partially account for the growth inhibitory effects of the compounds in human NSCLC cells.
Interleukin‐35 (IL‐35) is implicated in tumorigenesis, but its exact impact on intrahepatic cholangiocarcinoma (ICC) is not clear. The aim of the present study was to explore the specific effect of ...IL‐35 on patient prognosis. Additionally, we formulated an effective prognostic nomogram for ICC patients after curative resection. Immunohistochemistry was applied to explore IL‐35 expression as well as IL‐35 receptor (IL‐35R) in 102 ICC patients. Results showed that IL‐35 was highly expressed in ICC tumor tissues and was positively associated with lymph node metastasis (LNM), TNM stage and vascular invasion and was an independent prognostic factor for patients' overall survival (OS) and recurrence‐free survival (RFS). High expression of IL‐35R (gp130 and IL‐12Rβ2) was also observed in ICC cancer tissues, but only gp130 was an independent prognostic factor for OS and RFS and was indispensable in IL‐35‐mediated ICC clinical prognosis. The nomogram comprising carcinoembryonic antigen, LNM, IL‐35 and gp130 expression achieved better predictive accuracy compared with TNM stage for OS. Our data support that high IL‐35 expression correlates with ICC aggressiveness and emerges as a valuable biomarker for evaluating ICC progression and prognosis in clinical work.
Raised IL‐35 expression is positively associated with lymph node metastasis, TNM stage and vascular invasion and is an independent prognostic factor for patients' OS and RFS. High expression of IL‐35R (gp130 and IL‐12Rβ2) is also observed in ICC tissues, but only gp130 is an independent prognostic factor for OS and RFS and is indispensable in IL‐35‐mediated ICC clinical prognosis. Our nomogram comprising CEA, lymph node metastasis, IL‐35 and gp130 expression achieves better predictive accuracy compared with TNM stage for OS. IL‐35 could be viewed as a convenient novel prognostic factor for the prediction of survival and recurrence in ICC patients.
Chikungunya fever is an acute infectious disease caused by the chikungunya virus (CHIKV) that is characterized by fever, rash, and joint pain. CHIKV has infected millions of people in Africa, Asia, ...America, and Europe since it re‐emerged in the Indian Ocean region in 2004. Here, we report an outbreak of Chikungunya fever that occurred in Ruili of Yunnan Province, a city located on the border between China and Myanmar, in September 2019. The outbreak lasted for three months from September to December. Overall, 112 cases were confirmed by a real‐time reverse‐transcription polymerase chain reaction in the Ruili People's Hospital, and they showed apparent temporal, spatial, and population aggregation. Among them, 91 were local cases distributed in 19 communities of Ruili City, and 21 were imported cases. The number of female patients was higher than that of male patients, and most patients were between 20 and 60 years old. The main clinical manifestations included joint pain (91.96%), fever (86.61%), fatigue (58.04%), chills (57.14%), rash (48.21%), headache (39.29%), and so forth. Biochemical indexes revealed increased C‐reactive protein (63.39%), lymphopenia (57.17%), increased hemoglobin (33.04%), neutrophilia (28.57%), and thrombocytopenia (16.07%). Phylogenetic analysis of the complete sequences indicated that the CHIKV strains in this outbreak belonged to the Indian Ocean clade of the East/Central/South African genotype. We speculated that this chikungunya outbreak might be caused by CHIKV‐infected persons returning from Myanmar, and provided a reference for the formulation of effective treatment and prevention measures.
Highlights
One of the longest CHIKV epidemics in China was described, lasting for three months.
All cases showed apparent temporal, spatial and population aggregation.
The CHIKV strains belonged to the Indian Ocean clade of the ECSA genotype.
The first vertical transmission of CHIKV in China was recorded.
Abstract Targeting cancer cells is crucial for improving the efficiency of laryngeal cancer treatment. However, the signaling pathway and therapeutic strategy, related to the tumor, still need ...further research. Dietary flavonoid fisetin (3,3′,4′,7-tetrahydroxyflavone) found in many fruits and vegetables has been shown in preclinical studies to inhibit cancer growth through regulating cell cycle, apoptosis, angiogenesis, invasion and metastasis without causing any toxicity to normal cells. PI3K/AKT and ERK1/2 have been known as essential signaling pathways to modulate cell proliferation, apoptosis as well as autophagy via mTOR, Caspase-3 and NF-κB signals. In our study, flow cytometry and western blot assays suggested that apoptosis was induced by fisetin administration, promoting Caspase-3 expressions by regulating PI3K/AKT/NF-κB. Additionally, fisetin suppressed TU212 cells proliferation, which was linked with ERK1/2 inactivation. Further, the activation of PI3K/AKT-regulated mTOR was inhibited by fisetin, leading to transcription suppression and proliferation inhibition of TU212 cells. In vivo studies also showed that the tumor volume and weight of nude mice were reduced for fisetin use with KI-67 decrease and LC3II increase in tumor tissue samples. Together, our data indicated that fisetin had a potential role in controlling human laryngeal cancer through inhibiting tumor cell proliferation, inducing apoptosis and autophagy regulated by ERK1/2 and AKT/NF-κB/mTOR signaling pathways, which might provide a therapeutic strategy for laryngeal cancer inhibition in future.
Colorimetric sensors with instant visual readout are significant and highly required for convenient detection of various analytes, especially in the post-COVID-19 era. Noble metal-based bimetallic ...nanoparticles (NMBNPs), considered as promising nanoprobes for colorimetric sensing, are significantly superior to monometallic nanoparticles due to their improved optical property, catalytic activity, stability and selectivity. In this review, we focus on the recent progress in the colorimetric sensors based on NMBNPs with alloy, core-shell, core-satellite and Janus nanostructures. Firstly, we comprehensively introduce the synthesis approaches of NMBNPs which can be classified into three classes, including the top-down physical methods, bottom-up chemical methods and other emerging methods. Depending on these NMBNPs, the main sensing strategies exploiting their unique localized surface plasmon resonance (LSPR) property and nanozyme activity for various applications in colorimetric detection are critically summarized and discussed in detail. Finally, challenges and opportunities for the future development of NMBNPs-based colorimetric sensors are proposed and summarized. We hope that this review will help readers to better understand the current research status of NMBNPs for colorimetric sensing.
•Noble metal-based bimetallic nanoparticles (NMBNPs) are promising nanoprobes for colorimetric sensing.•The common synthesis approaches of NMBNPs are summarized.•Main detection mechanisms of NMBNPs for colorimetric sensing are reviewed.•Challenges and perspectives of NMBNPs for the colorimetric sensing application are discussed.
Abstract Hybrid drug delivery system containing both organic and inorganic nanocarriers is expected to achieve its complementary advantages for the aim of improving the performance of antineoplastic ...drugs in tumor therapy. Here we report the use of liposomes and gold nanoparticles to construct a liposome with a hybrid Cluster Bomb structure and discuss its unique multi-order drug release property for liver tumor treatment. A very simple method is used for the hybrid liposome preparation and involves mixing two solutions containing liposomes loaded with either non-covalent or covalent Paclitaxel (PTX, namely free PTX or PTX-conjugated GNPs, respectively) by different ratio of volume (25:75, 50:50, 25:75, v/v). Various mixed liposomes were tested to determine the optimal conditions for maximum drug delivery. The optimized liposome was then tested using xenograft Heps tumor-bearing mice and showed the best efficacy for chemotherapeutic inhibition of tumor at PTX liposome: PTX-conjugated GNP liposome of 25:75 ratio (v/v). This system allows for simple and easy preparation while providing a more accurate site- and time-release mode for tumor treatment using antitumor drugs.