SCOPE: Exosomes, small vesicles participating in intercellular communication, have been extensively studied recently; however, the role of edible plant derived exosomes in interspecies communication ...has not been investigated. Here, we investigate the biological effects of edible plant derived exosome‐like nanoparticles (EPDENs) on mammalian cells. METHODS AND RESULTS: In this study, exosome‐like nanoparticles from four edible plants were isolated and characterized. We show that these EPDENs contain proteins, lipids, and microRNA. EPDENs are taken up by intestinal macrophages and stem cells. The results generated from EPDEN‐transfected macrophages indicate that ginger EPDENs preferentially induce the expression of the antioxidation gene, heme oxygenase‐1 and the anti‐inflammatory cytokine, IL‐10; whereas grapefruit, ginger, and carrot EPDENs promote activation of nuclear factor like (erythroid‐derived 2). Furthermore, analysis of the intestines of canonical Wnt‐reporter mice, i.e. B6.Cg‐Tg(BAT‐lacZ)3Picc/J mice, revealed that the numbers of β‐galactosidase⁺ (β‐Gal) intestinal crypts are increased, suggesting that EPDEN treatment of mice leads to Wnt‐mediated activation of the TCF4 transcription machinery in the crypts. CONCLUSION: The data suggest a role for EPDEN‐mediated interspecies communication by inducing expression of genes for anti‐inflammation cytokines, antioxidation, and activation of Wnt signaling, which are crucial for maintaining intestinal homeostasis.
Introduction:
Power load forecasting and market price analysis have become crucial in the context of complex power energy systems and volatile market prices. Deep learning technology has gained ...significant attention in time series forecasting, and this article aims to enhance the accuracy and reliability of power load and market price predictions by integrating and optimizing deep learning models.
Methods:
We propose a deep learning framework that combines artificial neural networks (ANNs), long short-term memory (LSTM), and transformer models to address key challenges in electricity load forecasting and market price prediction. We leverage ANNs for their versatility and use LSTM networks for sequence modeling to generate initial predictions. Additionally, we introduce transformer technology and utilize its self-attention mechanism to capture long-distance dependencies within the data, further enhancing the model’s performance.
Results:
In our experiments, we validate the proposed framework using multiple public datasets. We compare our method with traditional forecasting approaches and a single-model approach. The results demonstrate that our approach outperforms other methods in predicting power load and market prices. This increased accuracy and reliability in forecasting can be of significant value to decision-makers in the energy sector.
Discussion:
The integration of deep learning models, including ANN, LSTM, and transformer, offers a powerful solution for addressing the challenges in power load and market price prediction. The ability to capture long-distance dependencies using the transformer's self-attention mechanism improves forecasting accuracy. This research contributes to the field of energy and finance by providing a more reliable framework for decision-makers to make informed choices in a complex and dynamic environment.
The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven ...translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.
The quality control of plastic products is an essential aspect of the plastic injection molding (PIM) process. However, the warpage and shrinkage deformations continue to exist because the PIM ...process is easily interfered with by several related or independent process parameters. Thus, great efforts have been devoted to optimizing process parameters to minimize the warpage and shrinkage deformations of products during the last decades. In this review, we begin by introducing the manufacturing process in PIM and the cause of warpage and shrinkage deformations, followed by the mechanism about how process parameters, like mold temperature, melt temperature, injection rate, injection pressure, holding pressure, holding and cooling duration, affect those defects. Then, we summarize the recent progress of the design of experiments and four advanced methods (artificial neural networks, genetic algorithm, response surface methodology, and Kriging model) on optimizing process parameters to minimize the warpage and shrinkage deformations. In the end, future perspectives of quality control in injection molding machines are discussed.
Bark protects the tree against environmental insults. Here, we analyzed whether this defensive strategy could be utilized to broadly enhance protection against colitis. As a proof of concept, we show ...that exosome‐like nanoparticles (MBELNs) derived from edible mulberry bark confer protection against colitis in a mouse model by promoting heat shock protein family A (Hsp70) member 8 (HSPA8)‐mediated activation of the AhR signaling pathway. Activation of this pathway in intestinal epithelial cells leads to the induction of COP9 Constitutive Photomorphogenic Homolog Subunit 8 (COPS8). Utilizing a gut epithelium‐specific knockout of COPS8, we demonstrate that COPS8 acts downstream of the AhR pathway and is required for the protective effect of MBELNs by inducing an array of anti‐microbial peptides. Our results indicate that MBELNs represent an undescribed mode of inter‐kingdom communication in the mammalian intestine through an AhR‐COPS8‐mediated anti‐inflammatory pathway. These data suggest that inflammatory pathways in a microbiota‐enriched intestinal environment are regulated by COPS8 and that edible plant‐derived ELNs may hold the potential as new agents for the prevention and treatment of gut‐related inflammatory disease.
Synopsis
Mulberry bark derived exosome‐like nanoparticles (MBELNs) prevent gut inflammation via plant heat shock protein HSPA8‐mediated activation of AhR/COPS8 pathways. Treatment with MBELNs promotes the restoration of gut microbiome homeostasis, ameliorating intestinal inflammatory pathologies.
Mulberry bark derived exosome‐like nanoparticles (MBELNs) prevent mouse colitis via the AhR/COPS8 pathway.
Binding of MBELN‐derived heat shock protein HSPA8 to AhR leads to the activation of AhR signaling.
Activation of AhR leads to the induction of an array of anti‐microbial peptides (AMPs) via COP9/COPS8.
AhR/COPS8‐dependent induction of AMPs inhibits intestinal inflammation and alters fecal gut microbiota composition.
Mulberry bark derived exosome‐like nanoparticles (MBELNs) prevent gut inflammation via plant heat shock protein HSPA8‐mediated activation of AhR/COPS8 pathways. Treatment with MBELNs promotes the restoration of gut microbiome homeostasis, ameliorating intestinal inflammatory pathologies.
Daily exposure of humans to nanoparticles from edible plants is inevitable, but significant advances are required to determine whether edible plant nanoparticles are beneficial to our health. ...Additionally, strategies are needed to elucidate the molecular mechanisms underlying any beneficial effects. Here, as a proof of concept, we used a mouse model to show that orally given nanoparticles isolated from ginger extracts using a sucrose gradient centrifugation procedure resulted in protecting mice against alcohol-induced liver damage. The ginger-derived nanoparticle (GDN)-mediated activation of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the expression of a group of liver detoxifying/antioxidant genes and inhibited the production of reactive oxygen species, which partially contributes to the liver protection. Using lipid knock-out and knock-in strategies, we further identified that shogaol in the GDN plays a role in the induction of Nrf2 in a TLR4/TRIF-dependent manner. Given the critical role of Nrf2 in modulating numerous cellular processes, including hepatocyte homeostasis, drug metabolism, antioxidant defenses, and cell-cycle progression of liver, this finding not only opens up a new avenue for investigating GDN as a means to protect against the development of liver-related diseases such as alcohol-induced liver damage but sheds light on studying the cellular and molecular mechanisms underlying interspecies communication in the liver via edible plant-derived nanoparticles.
We have demonstrated a one-step approach for the fabrication of flexible, robust, reproducible and free-standing SERS substrates (AuNPs/polyvinyl chloride (PVC) film) through a polymer induced ...interfacial self-assembly method. In this method, the polymer (PVC) plays dual roles, that is, inducing the interfacial self-assembly of nanoparticles and fixing the assembled nanostructure in the PVC matrix. As the assembled nanoparticles are orderly half-embedded in the PVC film, the AuNPs/PVC film exhibits outstanding reproducibility and stability. In addition, the film could be easily regenerated by rinsing with NaBH
4
solution. As a proof of concept, the film was directly wrapped on an apple surface for
in situ
detection of pesticide residues, and a detection limit of 10 ng cm
−2
thiram was achieved. Furthermore, rapid on-site and
in situ
detection of multi-pesticide residues has been proved to be feasible with the aid of a portable Raman spectrometer. Due to its simple preparation, good reliability, outstanding stability and reusability, the AuNPs/PVC film has great potential in practical applications.
A polymer induced one-step interfacial self-assembly method was developed to fabricate flexible, robust and free-standing SERS substrates for rapid pesticide residue detection.
In the framework of the chiral quark model (ChQM), we systematically investigate the strange hidden-charm tetraquark systems
c
s
c
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u
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with two structures:
q
q
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-
q
q
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and
q
q
-
q
¯
q
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. The ...bound-state calculation shows that there is no any bound state in present work, which excludes the molecular state explanation (
D
0
D
s
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/
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∗
0
D
s
-
/
D
∗
0
D
s
∗
-
) of the reported
Z
cs
(
3985
)
-
or
Z
cs
(
4000
)
+
. However, the effective potentials for the
c
s
-
c
¯
u
¯
systems show the possibility of some resonance states. By applying a stabilization calculation and coupling all channels of both two structures, two new resonance states are obtained, which are the
I
J
P
=
1
2
0
+
state with the energy around 4111–4116 MeV and the
I
J
P
=
1
2
1
+
state with energy around 4113–4119 MeV, respectively. Both of them are worthy of search in future experiments. Our results show that the coupling calculation between the bound channels and open channels is indispensable to provide the necessary information for experiments to search for exotic hadron states.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acute myocardial infarction is a major cause of death worldwide. The most important therapy for limiting ischemic injury and infarct size is timely and efficient myocardial reperfusion treatment, ...which may instead induce cardiomyocyte necrosis due to myocardial ischemia–reperfusion (I/R) injury. Heat shock protein 70 (HSP70), a stress‐inducible protein, is overexpressed during myocardial I/R. The induced HSP70 is shown to regulate several intracellular proteins (e.g., transcription factors, enzymes, and apoptosis‐related proteins) and signaling pathways (e.g., c‐Jun N‐terminal kinase pathway and extracellular‐signal‐regulated kinase 1/2 pathway), forming a complicated network that contributes to reducing reactive oxygen species accumulation, improving calcium homeostasis, inhibiting cellular apoptosis, thereby enhancing the stress adaption of myocardium to I/R injury. In addition, the extracellular HSP70, which is released from injured cardiomyocytes during I/R, acts as a proinflammatory mediator that results in cell death, while the intracellular HSP70 exerts antiinflammatory effects by suppressing proinflammatory signaling pathways. Notably, HSP70 is induced and contributes to the cardioprotection in several types of preconditioning and postconditioning. Meanwhile, it is shown that the cardioprotective effectiveness of preconditioning‐induced HSP70 (e.g., hyperthermia preconditioning‐induced HSP70) can be impaired by certain pathological conditions, such as hyperlipidemia and hyperglycemia. Thus, we highlight the widespread cardioprotective involvement of HSP70 in preconditioning and postconditioning and elucidate how HSP70‐mediated cardioprotection is impaired in these pathological conditions. Furthermore, several therapeutic potentials of HSP70 against myocardial I/R injury and potential directions for future studies are also provided in this review.
During myocardial ischemia–reperfusion (I/R), HSP70 is overexpressed and exerts numerous cardioprotective effects against I/R injury. In this review, we highlight these protective effects of HSP70, elucidate the mechanisms involved, and provide several HSP70‐driven therapeutic potentials against myocardial I/R injury. In summary, it is considered that HSP70 is a promising therapeutic target against myocardial I/R injury.
The gut mucosal immune system is considered to play an important role in counteracting potential adverse effects of food-derived antigens including nanovesicles. Whether nanovesicles naturally ...released from edible fruit work in a coordinated manner with gut immune cells to maintain the gut in a noninflammatory status is not known. Here, as proof of concept, we demonstrate that grapefruit-derived nanovesicles (GDNs) are selectively taken up by intestinal macrophages and ameliorate dextran sulfate sodium (DSS)-induced mouse colitis. These effects were mediated by upregulating the expression of heme oxygenase-1 (HO-1) and inhibiting the production of IL-1β and TNF-α in intestinal macrophages. The inherent biocompatibility and biodegradability, stability at wide ranges of pH values, and targeting of intestinal macrophages led us to further develop a novel GDN-based oral delivery system. Incorporating methotrexate (MTX), an anti-inflammatory drug, into GDNs and delivering the MTX-GDNs to mice significantly lowered the MTX toxicity when compared with free MTX, and remarkably increased its therapeutic effects in DSS-induced mouse colitis. These findings demonstrate that GDNs can serve as immune modulators in the intestine, maintain intestinal macrophage homeostasis, and can be developed for oral delivery of small molecule drugs to attenuate inflammatory responses in human disease.
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