Doxorubicin (DOX) is widely used as a first-line chemotherapeutic drug for various malignancies. However, DOX causes severe cardiotoxicity, which limits its clinical uses. Oxidative stress is one of ...major contributors to DOX-induced cardiotoxicity. While autophagic flux serves as an important defense mechanism against oxidative stress in cardiomyocytes, recent studies have demonstrated that DOX induces the blockage of autophagic flux, which contributes to DOX cardiotoxicity. The present study investigated whether nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD)
, prevents DOX cardiotoxicity by improving autophagic flux. We report that administration of NR elevated NAD
levels, and reduced cardiac injury and myocardial dysfunction in DOX-injected mice. These protective effects of NR were recapitulated in cultured cardiomyocytes upon DOX treatment. Mechanistically, NR prevented the blockage of autophagic flux, accumulation of autolysosomes, and oxidative stress in DOX-treated cardiomyocytes, the effects of which were associated with restoration of lysosomal acidification. Furthermore, inhibition of lysosomal acidification or SIRT1 abrogated these protective effects of NR during DOX-induced cardiotoxicity. Collectively, our study shows that NR enhances autolysosome clearance via the NAD
/SIRT1 signaling, thereby preventing DOX-triggered cardiotoxicity.
Colorectal cancer (CRC) is one of the most lethal tumor types worldwide. Circular RNAs (circRNAs), which are covalent closed loops of RNA, perform vital roles for the proliferation and metastasis of ...a variety of tumor types. In the present study, the expression, function and molecular mechanisms of action of a novel circRNA, circRNA_101951, were examined in CRC. The expression levels of circRNA_101951 in CRC tissue and cell lines were examined using reverse transcription-quantitative (RT-qPCR). Cell proliferation, the clone formation ability, cell apoptosis, the cell cycle and the cell migratory and invasive abilities were examined using MTT assays, colony formation assays, flow cytometric assays, and cell migration and invasion assays, respectively. The effects of circRNA_101951 on Kinesin II family member 3A (KIF3A) related gene expression were examined using RT-qPCR and western blot assays. The results indicated that circRNA_101951 was increased in CRC tissues and cell lines. The downregulation of circRNA_101951 inhibited cell proliferation and colony formation as well as cell migration and invasion of CRC cell lines. In addition, the downregulation of circRNA_101951 blocked the KIF3A-mediated epithelial-mesenchymal transition (EMT) pathway, which was detected by examining the expression levels of KIF3A and EMT related proteins. In conclusion, the current data revealed that circRNA_101951 may act as a potential biomarker for patients with CRC, and provided a novel insight demonstrating that the suppression of circRNA_101951 may be a potential therapeutic strategy for CRC.
Titanium dioxide (TiO
) nanorods (NRs) are widely used as photoanodes in photoelectrochemical (PEC) solar fuel production because of their remarkable photoactivity and stability. In addition, TiO
NR ...electrode materials can be decorated with active CdS quantum dots (QDs) to expand the sunlight photon capture. The overall photoelectric conversion efficiency for TiO
NR or QD-sensitized TiO
NR electrode materials in PEC is typically dominated by their interfacial electron transfer (ET) properties. To understand the key factors affecting the ET, the anatase TiO
seed layer was added into the interface between the rutile TiO
NRs and fluorine-doped tin oxide (FTO) substrate. This seed layer enhanced the photocatalytic performance of both the TiO
NR and CdS QD-sensitized TiO
NR photoanodes in PEC. Time-resolved photoluminescence spectroscopy and PEC analyses, including Mott-Schottky, electrochemical impedance spectroscopy, and photovoltage ( V
) measurements, were used to study the charge-carrier dynamics at the interfaces between the FTO, TiO
, and CdS QD. Analysis of the results showed that band alignment at the anatase/rutile junction between the TiO
and FTO promoted electron-collection efficiency ( e
) at the FTO/TiO
interface and ET rate constant ( k
) at the TiO
/CdS QD interface. Furthermore, 34% enhancement of the efficiency in hydrogen (H
) generation demonstrated the potential of the TiO
seed-layer-mediated TiO
/CdS QD NR photoanode in the application of PEC solar fuel production. The current work represents new insights into the mechanism of ET in TiO
and TiO
/CdS QD NR, which is very useful for the development of photoelectrode materials in solar energy conversions.
Medial arterial calcification (MAC), a systemic vascular disease different from atherosclerosis, is associated with an increased incidence of cardiovascular events. Several studies have demonstrated ...that ambient temperature is one of the most important factors affecting cardiovascular events. However, there has been limited research on the effect of different ambient temperatures on MAC. In the present study, we showed that cold temperature exposure (CT) in mice slowed down the formation of vitamin D (VD)-induced vascular calcification compared with room temperature exposure (RT). To investigate the mechanism involved, we isolated plasma-derived exosomes from mice subjected to CT or RT for 30 days (CT-Exo or RT-Exo, respectively). Compared with RT-Exo, CT-Exo remarkably alleviated the calcification/senescence formation of vascular smooth muscle cells (VSMCs) and promoted autophagy by activating the phosphorylation of AMP-activated protein kinase (p-AMPK) and inhibiting phosphorylation of mammalian target of rapamycin (p-mTOR). At the same time, CT-Exo promoted autophagy in β-glycerophosphate (β-GP)-induced VSMCs. The number of autophagosomes and the expression of autophagy-related proteins ATG5 and LC3B increased, while the expression of p62 decreased. Based on a microRNA chip microarray assay and real-time polymerase chain reaction, miR-320a-3p was highly enriched in CT-Exo as well as thoracic aortic vessels in CT mice. miR-320a-3p downregulation in CT-Exo using AntagomiR-320a-3p inhibited autophagy and blunted its anti-calcification protective effect on VSMCs. Moreover, we identified that programmed cell death 4 (PDCD4) is a target of miR-320a-3p, and silencing PDCD4 increased autophagy and decreased calcification in VSMCs. Treatment with CT-Exo alleviated the formation of MAC in VD-treated mice, while these effects were partially reversed by GW4869. Furthermore, the anti-arterial calcification protective effects of CT-Exo were largely abolished by AntagomiR-320a-3p in VD-induced mice. In summary, we have highlighted that prolonged cold may be a good way to reduce the incidence of MAC. Specifically, miR-320a-3p from CT-Exo could protect against the initiation and progression of MAC via the AMPK/mTOR autophagy pathway.
Metasurfaces are artificially engineered two‐dimensional materials composed of sub‐wavelength meta‐atoms, which have shown unprecedented capabilities in manipulating the amplitude, phase, frequency, ...and polarization states of electromagnetic waves. Specifically, polarization control can be attained via suitable anisotropic, linear, and time‐invariant designs, while frequency conversion is realized via nonlinear or time‐varying platforms. Simultaneous manipulations of polarization and frequency would be of considerable practical interest in many application scenarios, but remain unattainable with current approaches. Here, a time‐division‐multiplexing metasurface is proposed to realize the simultaneous conversion of polarization and frequency. The platform relies on time‐modulated polarization switches and, by varying the duty cycle and time delays of the polarization channels, can arbitrarily rotate the polarization at the central frequency of operation, and synthesize various polarization states at selected harmonic frequencies. Theoretical predictions are validated via measurements on a prototype operating at microwave frequencies, providing the first experimental evidence of simultaneous polarization and frequency conversions via time‐division‐multiplexing metasurfaces. The outcomes open a new pathway in manipulating the electromagnetic waves via time‐varying metasurfaces, and may be of interest for a broad variety of applications in scenarios ranging from polarization imaging to quantum optics.
A time‐division‐multiplexing metasurface, based on time‐modulated polarization switches, is proposed for the simultaneous conversion of polarization and frequency. Theory and experiments demonstrate the possibility to realize arbitrary rotations of the polarization at the central frequency of operation, and to synthesize various polarization states at selected harmonic frequencies. Possible applications range from polarization imaging to quantum optics.
Mitochondrial transfer is a new cell-to-cell communication manner. Whether the mitochondrial transfer is also involved in the macrophage infiltration-induced cardiac injury is unclear.
This study ...aimed to determine whether macrophage mitochondria can be transferred to cardiomyocytes, and to investigate its possible role and mechanism.
Mitochondrial transfer between macrophages and cardiomyocytes was detected using immunofluorescence staining and flow cytometry. Cellular metabolites were analyzed using LC-MS technique. Differentially expressed mRNAs were identified using RNA-seq technique.
(1) After cardiomyocytes were cultured with macrophage-conditioned medium (COND + group), macrophage-derived mitochondria have been found in cardiomyocytes, which could be blocked by dynasore (an inhibitor of clathrin-mediated endocytosis). (2) Compared with control (CM) group, there were 545 altered metabolites found in COND + group, most of which were lipids and lipid-like molecules. The altered metabolites were mainly enriched in the β-oxidation of fatty acids and glutathione metabolism. And there were 4824 differentially expressed mRNAs, which were highly enriched in processes like lipid metabolism-associated pathway. (3) Both RNA-seq and qRT-PCR results found that ferroptosis-related mRNAs such as Ptgs2 and Acsl4 increased, and Gpx4 mRNA decreased in COND + group (P < 0.05 vs CM group). (4) The levels of cellular free Fe2+ and mitochondrial lipid peroxidation were increased; while GSH/GSSG ratio, mitochondrial aspect ratio, mitochondrial membrane potential, and ATP production were decreased in cardiomyocytes of COND + group (P < 0.05 vs CM group). All the above phenomena could be blocked by a ferroptosis inhibitor ferrostatin-1 (P < 0.05).
Macrophages could transfer mitochondria to cardiomyocytes. Macrophage-derived mitochondria were internalized into cardiomyocytes through clathrin- and/or lipid raft-mediated endocytosis. Uptake of exogenous macrophage mitochondria induced cardiomyocyte injury via triggering ferroptosis.
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•Macrophages could transfer mitochondria to cardiomyocytes.•Macrophage-derived mitochondria are internalized through clathrin- and/or lipid raft-mediated endocytosis.•Macrophage-derived mitochondria trigger ferroptosis in cardiomyocytes.
Subclinical hypothyroidism (SCH) is reportedly associated with an increased risk of adverse events in patients undergoing percutaneous coronary intervention (PCI). The prognostic significance of SCH ...in the elderly was poorly defined. The purpose of this study was to evaluate the association between SCH and long-term outcomes in older patients undergoing PCI.
Three thousand one hundred sixty-eight patients aged 65 years or older who underwent PCI from January 2012 to October 2014 were included. Patients were divided into SCH group (n = 320) and euthyroidism (ET) group (n = 2848) based on thyroid function test. Cox proportional hazard regression analyses were used to estimate the relative risks (RRs) of all-cause death and cardiac death for patients with SCH during a 4-year follow-up period.
There were 227 deaths during the follow-up period including 124 deaths caused by cardiac events. There was no significant difference in mortality rate between the SCH group and the ET group (p > 0.05). After adjustment for covariates, compared with patients with ET, the RRs of death from all-cause and cardiac in patients with SCH were 1.261 (95%CI: 0.802-1.982, p = 0.315) and 1.231 (95%CI: 0.650-2.334, p = 0.524), respectively. When SCH was stratified by age, gender, and degree of thyroid-stimulating hormone elevation, no significant associations were also found in any stratum.
Our investigation revealed that SCH was negatively associated with the outcome of PCI in older patients.
Abstract
To understand the distribution and diversity of archaea in Chinese soils, the archaeal communities in a series of topsoils and soil profiles were investigated using quantitative PCR, T-RFLP ...combining sequencing methods. Archaeal 16S rRNA gene copy numbers, ranging from 4.96 × 106 to 1.30 × 108 copies g−1 dry soil, were positively correlated with soil pH, organic carbon and total nitrogen in the topsoils. In the soil profiles, archaeal abundance was positively correlated with soil pH but negatively with depth profile. The relative abundance of archaea in the prokaryotes (sum of bacteria and archaea) ranged from 0.20% to 9.26% and tended to increase along the depth profile. T-RFLP and phylogenetic analyses revealed that the structure of archaeal communities in cinnamon soils, brown soils, and fluvo-aquic soils was similar and dominated by Crenarchaeota group 1.1b and 1.1a. These were different from those in red soils, which were dominated by Crenarchaeota group 1.3 and 1.1c. Canonical correspondence analysis indicated that the archaeal community was primarily influenced by soil pH.
Mesoporous Co3O4 nanoparticles with different textural parameters were prepared by using mesoporous silicas, KIT-6 and SBA-15, as templates and Co(NO3)2·6H2O as precursor via an improved solid−liquid ...route. The results of N2 adsorption−desorption analysis indicated that the calcination temperature did not obviously affect the textural parameters of Co3O4 samples and the BET surface areas of Co3O4 samples could be regulated by different KIT-6 templates. The effects of calcination temperature and textural parameters on the electrochemical capacitive behaviors of Co3O4 samples were discussed. The results of electrochemical tests show the following: the capacitance value of the sample decreases slightly with the increase of the calcination temperature; the BET surface area is the crucial factor for the specific capacitance value; for mesoporous materials, large pore size and high ordering degree of mesopore facilitate ion transfer; and the meso-structure (2D hexagonal structure or 3D Ia3d cubic structure) of mesoporous Co3O4 nanoparticles does not obviously affect the specific capacitance value of the samples, but 2D hexagonal mesoporous structure is more advantageous to ion transfer than 3D Ia3d cubic mesoporous structure.
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