Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer＇s dis- ease patients, resulting in neuronal death. This study investigated whether components extracted ...from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer＇s disease patients. An APPs,~JPSI~E9 double transgenic mouse model of Alzheimer＇s disease was used. The intragas- tric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer＇s disease. These com- pounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer＇s disease.
In this work, a convenient, fast, low cost, small sample volume and in situ detection of glucose in human whole blood has been developed by using a disposable screen-printed carbon electrode (SPCE) ...coupled with a paper disk. To perform the assay, the SPCE was modified with graphene/polyaniline/Au nanoparticles/glucose oxidase (Gr/PANI/AuNPs/GOD) biocomposite and then covered by a paper disk impregnated with the sample. After introducing PBS on the paper disk, the electrochemical measurement was carried out. The assay was based on measuring the current decrease of flavin adenine dinucleotide (FAD) in GOD provoked by the enzyme–substrate reaction using differential pulse voltammetry (DPV). The analytical performance was comparable to conventional methods, and covered the full range of clinically relevant concentrations of glucose in whole blood. This new paper-based electrochemical glucose sensor shows promise in applying point-of-care (POC) device in whole blood tests, and particularly being appropriate for use in the developing world and in resource-limited settings.
•A novel fabrication method for the measurement of whole blood glucose was developed.•Small sample volume, and shorter assay time were required without any pretreatment steps.•It is easily expanded for detecting various selected analytes in the complex system.•It is suited for point-of-care test applications.
The RNA interference pathway mediated by microRNAs (miRNAs) is one of the methods to defend against viruses in insects. Recent studies showed that miRNAs participate in viral infection by binding to ...target genes to regulate their expression. Here, we found that the Bombyx mori miRNA, miR‐6498‐5p was down‐regulated, whereas its predicted target gene pyridoxal phosphate phosphatase PHOSPHO2 (BmPLPP2) was up‐regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Both in vivo and in vitro experiments showed that miR‐6498‐5p targets BmPLPP2 and suppresses its expression. Furthermore, we found miR‐6498‐5p inhibits BmNPV genomic DNA (gDNA) replication, whereas BmPLPP2 promotes BmNPV gDNA replication. As a pyridoxal phosphate (PLP) phosphatase (PLPP), the overexpression of BmPLPP2 results in a reduction of PLP content, whereas the knockdown of BmPLPP2 leads to an increase in PLP content. In addition, exogenous PLP suppresses the replication of BmNPV gDNA; in contrast, the PLP inhibitor 4‐deoxypyridoxine facilitates BmNPV gDNA replication. Taken together, we concluded that miR‐6498‐5p has a potential anti‐BmNPV role by down‐regulating BmPLPP2 to modulate PLP content, but BmNPV induces miR‐6498‐5p down‐regulation to promote its proliferation. Our findings provide valuable insights into the role of host miRNA in B. mori–BmNPV interaction. Furthermore, the identification of the antiviral molecule PLP offers a novel perspective on strategies for preventing and managing viral infection in sericulture.
Bmo‐miR‐6498‐5p inhibits BmNPV infection by negatively regulates BmPLPP2.
BmPLPP2 acts as a pyridoxal phosphate phosphatase to hydrolyze pyridoxal phosphate.
Pyridoxal phosphate inhibit BmNPV infection both in vitro and in vivo.
Boosting charge transfer in materials is critical for applications involving charge carriers. Engineering ionic channels in electrode materials can create a skeleton to manipulate their ion and ...electron behaviors with favorable parameters to promote their capacity and stability. Here, tailoring of the atomic structure in layered potassium niobate (K4Nb6O17) nanosheets and facilitating their application in lithium and potassium storage by dehydration‐triggered lattice rearrangement is reported. The spectroscopy results reveal that the interatomic distances of the NbO coordination in the engineered K4Nb6O17 are slightly elongated with increased degrees of disorder. Specifically, the engineered K4Nb6O17 shows enhanced electrical and ionic conductivity, which can be attributed to the enlarged interlamellar spacing and subtle distortions in the fine atomic arrangements. Moreover, subsequent experimental results and calculations demonstrate that the energy barrier for Li+/K+ diffusion is significantly lower than that in pristine K4Nb6O17. Interestingly, the diffusion coefficient of K+ is one order of magnitude higher than that of Li+ , and the engineered K4Nb6O17 presents superior electrochemical performance for K+ to Li+ . This work offers an ionic engineering strategy to enable fast and durable charge transfer in materials, holding great promise for providing guidance for the material design of related energy storage systems.
Boosting charge transfer in materials is critical for applications involving charge carriers. Engineering ionic channels in electrode materials can create a skeleton to manipulate their ion/electron behaviors with favorable parameters to promote their performance. Tailoring of the atomic structure in layered potassium niobate and facilitating its application in Li/K storage by dehydration‐triggered lattice rearrangement is reported.
Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long ...noncoding RNA taurine upregulated gene 1 (TUG1). In this study, we explored the functional significance and molecular mechanisms of TUG1/miR-132-3p axis in ischemia-challenged cardiomyocytes. In primary cardiomyocytes challenged with H
O
, expressions of miR-132-3p, TUG1, and other target proteins were measured by RT quantitative PCR or Western blot analysis; cell viability by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay; apoptosis by annexin V and propidium iodide staining; the abundance of acetylated H3K9 or histone deacetylase 3 (HDAC3) within the promoter of target genes by chromatin immunoprecipitation; the direct interaction between miR-132-3p and HDAC3 or TUG1 by luciferase reporter assay. The biological significance of miR-132-3p, TUG1, and HDAC3 was assessed using miR-132-3p mimic, siRNA-targeting TUG1 and HDAC3 inhibitor RGF966, respectively, in H
O
-challenged cells in vitro or ischemia-reperfusion (I/R)-induced AMI in vivo. miR-132-3p was downregulated, whereas TUG1 upregulated in H
O
-challenged cardiomyocytes. Overexpressing miR-132-3p or knocking down TUG1 significantly improved viability, inhibited apoptosis, and reduced ROS production in H
O
-stressed cardiomyocytes in vitro and alleviated I/R-induced AMI in vivo. Mechanistically, TUG1 sponged miR-132-3p and upregulated HDAC3, which reduced the acetylation of H3K9 and epigenetically inhibited expressions of antioxidative genes, including Bcl-xL, Prdx2, and Hsp70. The TUG1/miR-132-3p/HDAC3 axis critically regulates ROS production and the pathogenic development of AMI. Targeting TUG1, upregulating miR-132-3p, or inhibiting HDAC3 may benefit AMI treatment.
Increased production of reactive oxygen species (ROS) significantly contributed to the pathogenesis of acute myocardial infarction (AMI). Recent studies suggest that hypoxia upregulated the long noncoding RNA taurine upregulated gene 1 (TUG1). However, the underlying mechanisms remain elusive. In the present study, we reported for the first time that H
O
or ischemia-reperfusion-induced TUG1, by sponging microRNA 132-3p, activated histone deacetylase 3, which in turn targeted multiple protective genes, stimulated intracellular ROS accumulation, and aggravated the injury of AMI. Our findings might provide some insight to seek new targets for AMI treatment.
Central presbycusis is caused by degradation of the auditory centre during ageing. Its main characteristics are difficulties in understanding language and localizing sound. Presbycusis is an ...increasingly critical public health problem, but the underlying molecular mechanism has not been fully elucidated. Ferroptosis is a form of regulated cell death caused by iron‐ and reactive oxygen species‐induced lipid peroxidation. Ferroptosis is related to many pathological processes, but whether it participates in the degeneration of the auditory system remains unclear. To investigate this, we measured iron levels in a simulated ageing model established by the addition of d‐galactose (d‐gal). We found, for the first time, that iron accumulated within cells and that the ultrastructural features of ferroptosis appeared in the auditory cortex with ageing. These changes were accompanied by upregulation of iron regulatory protein 2 (IRP‐2), which led to an increase in transferrin receptor 1 (TfR‐1), thus increasing iron entry into cells and potentially leading to ferroptosis. In addition, the malondialdehyde (MDA) content and the occurrence of mitochondrial DNA common deletions (CDs) increased, neuron degeneration appeared, and glutathione (GSH) and superoxide dismutase (SOD) activity decreased. Furthermore, we found that treatment with the iron chelator deferoxamine (DFO) and knockdown of IRP‐2 both relieved ferroptosis during the simulated ageing process, thus achieving a partial protective effect to delay ageing. In summary, we describe here the first discovery that age‐related iron deposition and ferroptosis may be associated with auditory cortex neurodegeneration. Relieving ferroptosis might thus be a new intervention strategy for age‐related hearing loss.
Excessive iron leads to an increase in ROS production and abnormalities in the antioxidant system. Excessive reactive oxygen species attack mitochondria, leading to mitochondrial DNA damage and mitochondrial dysfunction; meanwhile, reactive oxygen species cause lipid peroxidation, which leads to ferroptosis. These mechanisms interact, eventually leading to ageing. Preventing excessive iron from entering cells or removing excessive iron from cells may reverse the onset of ageing.
In this study, we present a broadband nano-photodetector based on single-layer graphene (SLG)-carbon nanotube thin film (CNTF) Schottky junction. It was found that the as-fabricated device exhibited ...obvious sensitivity to a wide range of illumination, with peak sensitivity at 600 and 920 nm. In addition, the SLG-CNTF device had a fast response speed (τ
= 68 μs, τ
= 78 μs) and good reproducibility in a wide range of switching frequencies (50-5400 Hz). The on-off ratio, responsivity, and detectivity of the device were estimated to be 1 × 10
, 209 mAW
and 4.87 × 10
cm Hz
W
, respectively. What is more, other device parameters including linear performance θ and linear dynamic range (LDR) were calculated to be 0.99 and 58.8 dB, respectively, which were relatively better than other carbon nanotube based devices. The totality of the above study signifies that the present SLG-CNTF Schottky junction broadband nano-photodetector may have promising application in future nano-optoelectronic devices and systems.
WirelessHART is a networking technology that is widely used in industrial wireless sensor networks. Its reliability and real-time performance are essential to industrial production. Many works have ...studied these two aspects, primarily focusing on a single WirelessHART network. However, multiple WirelessHART networks usually coexist in a real industrial environment. Applying existing approaches to such coexisting networks would cause performance degradation due to communication interference among these networks. In this paper, we propose a holistic framework that optimizes both reliability and temporality for multiple coexisting networks. The framework consists of two levels. The upper level targets communication channel management, and the lower level addresses data flow scheduling. For the upper level, we propose a network isolation algorithm that improves the data transmission reliability through dynamically adjusting channel assignments to different WirelessHART networks. For the lower level, we propose data flow scheduling algorithms that guarantee the temporality of data flows within each isolated network. These algorithms minimize the number of channels reserved by each isolated network and further enhance the transmission reliability through alleviating channel resource contention. We conduct trace-driven simulations of the channel management algorithm, and the results demonstrate that our algorithm exhibits stable performance and reduces packet loss by 36%. For the scheduling algorithms, the simulations demonstrate that in contrast with existing algorithms, the greater the number of coexisting networks, the fewer resources our algorithms use. When eight networks coexist, our algorithms outperform existing ones by consuming up to 63% fewer channel resources.
Central-western Hunan in South China hosts the largest antimony belt in the world with two types of Sb deposits identified: Sb-Au Woxi-type and Sb only Xikuangshan-type. Banxi is the most ...representative deposit in the region with vein-type Sb mineralization hosted in Neoproterozoic clastic rocks, stibnite developing in ores, and arsenopyrite mainly occurring in altered country rocks.
Trace element contents (including rare earth elements; REE) and isotopic ratios (S, Pb, Sr, Nd, He and Ar) in stibnite and/or arsenopyrite were analyzed to determine the timing of ore formation and to elucidate fluid origin and evolution processes. Most sulfides have high ΣREE contents (45–103ppm), moderate fractionation between LREE and HREE (LREE/HREE=6.38–11.56) and slightly negative Eu anomalies (Eu/Eu*=0.53–0.72). The δ34S values are 3.88–5.81‰ for stibnite and 9.25–11.82‰ for arsenopyrite. The 206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb ratios range from 18.617 to 18.635, 15.695 to 15.739, and 38.965 to 38.981 for stibnite, and from 18.594 to 18.609, from 15.587 to 15.698, and from 38.893 to 38.926 for arsenopyrite. The 87Rb/86Sr and 87Sr/86Sr ratios are 0.3016–3.538 and 0.711463–0.717591, respectively for stibnite, and 0.2251–2.214 and 0.711244–0.711565, respectively for arsenopyrite. The 147Sm/144Nd and 143Nd/144Nd ratios are 0.1174–0.9816 and 0.511942–0.512768 for stibnite, with εNd(t) values (t=130Ma) ranging from −12.4 to −6.6, and two-stage model ages (T2DM) ranging from 1457 to 1932Ma. The 40Ar/36Ar and R/Ra ratios (where Ra is the atmospheric 3He/4He ratio of 1.4×10−6) are 409–545 and 0.0088–0.0348, respectively for stibnite. The Rb–Sr and Sm–Nd isotopic analyses of the sulfides yield isochron ages of 129.4±2.4Ma (2σ, MSWD=1.3) and 130.4±1.9Ma (2σ, MSWD=1.6), respectively.
The combined trace element and isotopic data-set indicates that the ore-forming fluids were a mixture of dominantly deep basement-derived, solute-rich parent water and a small amount of dilute, heated meteoric water. The decreases in ΣREE, δ34S, 206Pb/204Pb, 207Pb/204Pb, 208Pb/204Pb, 87Rb/86Sr, 87Sr/86Sr, 147Sm/144Nd and 143Nd/144Nd and increases in 40Ar/36Ar and 4He contents in the stibnite from the earlier quartz-stibnite mineralization stage (Stage II) through to the later stibnite mineralization stage (Stage III) indicate that the influx of meteoric water increased during Sb mineralization. The deep-sourced, relatively high temperature, rock-reacted fluid mixed with increasing amounts of more oxidized, low temperature meteoric fluids, causing the precipitation of arsenopyrite and stibnite sequentially at the Banxi deposit.
A two-period genetic model has been proposed for the world-class Sb mineralization in the central-western Hunan region. The Woxi-type Sb–Au deposits were derived from orogenic fluids generated from folding and shearing during the Caledonian and Indosinian Orogeny, whereas the Xikuangshan-type Sb deposits were formed by mixing heated basement-derived hydrothermal fluid circulating during the flare-up of magmatism in South China, with lower temperature meteoric water.
Display omitted
•Rb–Sr and Sm–Nd isotopic analyses at the Banxi Sb deposit yield isochron ages of ~130Ma.•The genesis of Banxi is resolved using S, Pb, Sr, Nd, Ar and He isotopic analysis of stibnite and arsenopyrite.•The deposit was formed from a basement-derived fluid mixed with meteoric water.•An orogenic-magmatic two-period model is proposed for regional Sb mineralization.
In this study, we aim to investigate the regulation of specific long non-coding RNAs (lncRNAs) on the progression of ischemia/reperfusion (I/R) injury. We identified and characterized the exosomes ...derived from mouse primary aortic endothelial cells. Subsequently, we found that these exosomes expressed typical exosomal markers and high levels of LINC00174, which significantly ameliorated I/R-induced myocardial damage and suppressed the apoptosis, vacuolation, and autophagy of myocardial cells. Mechanistic approaches revealed that LINC00174 directly interacted with SRSF1 to suppress the expression of p53, thus restraining the transcription of myocardin and repressing the activation of the Akt/AMPK pathway that was crucial for autophagy initiation in I/R-induced myocardial damage. Moreover, this molecular mechanism was verified by in vivo study. In summary, exosomal LINC00174 generated from vascular endothelial cells repressed p53-mediated autophagy and apoptosis to mitigate I/R-induced myocardial damage, suggesting that targeting LINC00174 may be a novel strategy to treat I/R-induced myocardial infarction.
Display omitted
In the present study, Su and colleagues show that exosomal LINC00174 derived from vascular endothelial cells attenuates myocardial ischemia-reperfusion (I/R) injury by suppressing p53-mediated autophagy and apoptosis. This discovery reveals a new regulation mechanism for I/R-induced injury and provides a potential therapeutic strategy to treat I/R-induced myocardial infarction.
PDF
