Abstract
We report a strategy to boost Fenton reaction triggered by an exogenous circularly polarized magnetic field (MF) to enhance ferroptosis-like cell-death mediated immune response, as well as ...endow a responsive MRI capability by using a hybrid core-shell vesicles (HCSVs). HCSVs are prepared by loading ascorbic acid (AA) in the core and poly(lactic-co-glycolic acid) shell incorporating iron oxide nanocubes (IONCs). MF triggers the release of AA, resulting in the increase of ferrous ions through the redox reaction between AA and IONCs. A significant tumor suppression is achieved by Fenton reaction-mediated ferroptosis-like cell-death. The oxidative stress induced by the Fenton reaction leads to the exposure of calreticulin on tumor cells, which leads to dendritic cells maturation and the infiltration of cytotoxic T lymphocytes in tumor. Furthermore, the depletion of ferric ions during treatment enables monitoring of the Fe reaction in MRI-R2* signal change. This strategy provides a perspective on ferroptosis-based immunotherapy.
Orally administered ginsengs come in contact with the gut microbiota, and their hydrophilic constituents, such as ginsenosides, are metabolized to hydrophobic compounds by gastric juice and gut ...microbiota: protopanxadiol-type ginsenosides are mainly transformed into compound K and ginsenoside Rh2; protopanaxatriol-type ginsenosides to ginsenoside Rh1 and protopanaxatriol, and ocotillol-type ginsenosides to ocotillol. Although this metabolizing activity varies between individuals, the metabolism of ginsenosides to compound K by gut microbiota in individuals treated with ginseng is proportional to the area under the blood concentration curve for compound K in their blood samples. These metabolites such as compound K exhibit potent pharmacological effects, such as antitumor, anti-inflammatory, antidiabetic, antiallergic, and neuroprotective effects compared with the parent ginsenosides, such as Rb1, Rb2, and Re. Therefore, to monitor the potent pharmacological effects of ginseng, a novel probiotic fermentation technology has been developed to produce absorbable and bioactive metabolites. Based on these findings, it is concluded that gut microbiota play an important role in the pharmacological action of orally administered ginseng, and probiotics that can replace gut microbiota can be used in the development of beneficial and bioactive ginsengs.
ObjectiveCerebral amyloidosis and severe tauopathy in the brain are key pathological features of Alzheimer’s disease (AD). Despite a strong influence of the intestinal microbiota on AD, the causal ...relationship between the gut microbiota and AD pathophysiology is still elusive.DesignUsing a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLPAPT) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis.ResultsComposition of the gut microbiota in ADLPAPT mice differed from that of healthy wild-type (WT) mice. Besides, ADLPAPT mice showed a loss of epithelial barrier integrity and chronic intestinal and systemic inflammation. Both frequent transfer and transplantation of the faecal microbiota from WT mice into ADLPAPT mice ameliorated the formation of amyloid β plaques and neurofibrillary tangles, glial reactivity and cognitive impairment. Additionally, the faecal microbiota transfer reversed abnormalities in the colonic expression of genes related to intestinal macrophage activity and the circulating blood inflammatory monocytes in the ADLPAPT recipient mice.ConclusionThese results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLPAPT mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.
For wireless charging of electric vehicle (EV) batteries, high-frequency magnetic fields are generated from magnetically coupled coils. The large air-gap between two coils may cause high leakage of ...magnetic fields and it may also lower the power transfer efficiency (PTE). For the first time, in this paper, we propose a new set of coil design formulas for high-efficiency and low harmonic currents and a new design procedure for low leakage of magnetic fields for high-power wireless power transfer (WPT) system. Based on the proposed design procedure, a pair of magnetically coupled coils with magnetic field shielding for a 1-kW-class golf-cart WPT system is optimized via finite-element simulation and the proposed design formulas. We built a 1-kW-class wireless EV charging system for practical measurements of the PTE, the magnetic field strength around the golf cart, and voltage/current spectrums. The fabricated system has achieved a PTE of 96% at the operating frequency of 20.15 kHz with a 156-mm air gap between the coils. At the same time, the highest magnetic field strength measured around the golf cart is 19.8 mG, which is far below the relevant electromagnetic field safety guidelines (ICNIRP 1998/2010). In addition, the third harmonic component of the measured magnetic field is 39 dB lower than the fundamental component. These practical measurement results prove the effectiveness of the proposed coil design formulas and procedure of a WPT system for high-efficiency and low magnetic field leakage.
Metabolomic approaches have been used to identify new diagnostic biomarkers for various types of cancers, including breast cancer. In this study, we aimed to identify potential biomarkers of breast ...cancer using plasma metabolic profiling. Furthermore, we analyzed whether these biomarkers had relationships with clinicopathological characteristics of breast cancer. Our study used two liquid chromatography-mass spectrometry sets: a discovery set (40 breast cancer patients and 30 healthy controls) and a validation set (30 breast cancer patients and 16 healthy controls). All breast cancer patients were randomly selected from among stage I-III patients who underwent surgery between 2011 and 2016. First, metabolites distinguishing cancer patients from healthy controls were identified in the discovery set. Then, consistent and reproducible metabolites were evaluated in terms of their utility as possible biomarkers of breast cancer. Receiver operating characteristic (ROC) analysis was applied to the discovery set, and ROC cut-off values for the identified metabolites derived therein were applied to the validation set to determine their diagnostic performance. Ultimately, four candidate biomarkers (L-octanoylcarnitine, 5-oxoproline, hypoxanthine, and docosahexaenoic acid) were identified. L-octanoylcarnitine showed the best diagnostic performance, with a 100.0% positive predictive value. Also, L-octanoylcarnitine levels differed according to tumor size and hormone receptor expression. The plasma metabolites identified in this study show potential as biomarkers allowing early diagnosis of breast cancer. However, the diagnostic performance of the metabolites needs to be confirmed in further studies with larger sample sizes.
While it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of ...endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a high-fat diet.
C57BL/6J and TLR4-deficient C57BL/10ScNJ mice were maintained on a low-fat (10 kcal % fat) diet (LFD) or a high-fat (60 kcal % fat) diet (HFD) for 8 weeks.
HFD induced macrophage infiltration and inflammation in the adipose tissue, as well as an increase in the circulating proinflammatory cytokines. HFD increased both plasma and fecal endotoxin levels and resulted in dysregulation of the gut microbiota by increasing the Firmicutes to Bacteriodetes ratio. HFD induced the growth of Enterobecteriaceae and the production of endotoxin in vitro. Furthermore, HFD induced colonic inflammation, including the increased expression of proinflammatory cytokines, the induction of Toll-like receptor 4 (TLR4), iNOS, COX-2, and the activation of NF-κB in the colon. HFD reduced the expression of tight junction-associated proteins claudin-1 and occludin in the colon. HFD mice demonstrated higher levels of Akt and FOXO3 phosphorylation in the colon compared to the LFD mice. While the body weight of HFD-fed mice was significantly increased in both TLR4-deficient and wild type mice, the epididymal fat weight and plasma endotoxin level of HFD-fed TLR4-deficient mice were 69% and 18% of HFD-fed wild type mice, respectively. Furthermore, HFD did not increase the proinflammatory cytokine levels in TLR4-deficient mice.
HFD induces inflammation by increasing endotoxin levels in the intestinal lumen as well as in the plasma by altering the gut microbiota composition and increasing its intestinal permeability through the induction of TLR4, thereby accelerating obesity.
The learning and inference efficiencies of an artificial neural network represented by a cross‐point synaptic memristor array can be achieved using a selector, with high selectivity (Ion/Ioff) and ...sufficient death region, stacked vertically on a synaptic memristor. This can prevent a sneak current in the memristor array. A selector with multiple jar‐shaped conductive Cu filaments in the resistive switching layer is precisely fabricated by designing the Cu ion concentration depth profile of the CuGeSe layer as a filament source, TiN diffusion barrier layer, and Ge3Se7 switching layer. The selector performs super‐linear‐threshold‐switching with a selectivity of > 107, death region of −0.70–0.65 V, holding time of 300 ns, switching speed of 25 ns, and endurance cycle of > 106. In addition, the mechanism of switching is proven by the formation of conductive Cu filaments between the CuGeSe and Ge3Se7 layers under a positive bias on the top Pt electrode and an automatic rupture of the filaments after the holding time. Particularly, a spiking deep neural network using the designed one‐selector‐one‐memory cross‐point array improves the Modified National Institute of Standards and Technology classification accuracy by ≈3.8% by eliminating the sneak current in the cross‐point array during the inference process.
An artificial neural network consisting of a hardware‐based cross‐point synaptic memristor array should employ selectors with two‐terminal electrodes to prevent an undesired sneak current and to improve learning and inference efficiencies. Here, a highly reliable super‐linear‐threshold‐switching selector with multiple jar‐shaped Cu‐filaments in the amorphous Ge3Se7 resistive switching layer by controlling the Cu ion concentration depth profile is developed.
Black melanin inks are prepared to selectively exhibit colors under strong light, inspired by human hair. High absorbance of melanin suppresses multiple scattering, causing resonant Mie scattering ...predominant. Various colors can be developed as the resonant wavelength dictated by nanosphere diameter. Therefore, the melanin inks can be used to encrypt and selectively disclose multicolor patterns for anticounterfeiting applications.
Black melanin inks are prepared to selectively exhibit colors under strong light, inspired by human hair. The high absorbance of melanin suppresses multiple scattering, causing resonant Mie scattering to be predominant. Various colors can be developed as the resonant wavelength dictated by nanosphere diameter. Therefore, the melanin inks can be used to encrypt and selectively disclose multicolor patterns for anticounterfeiting applications.
In this study, the possibility of inactivating viral, bacterial, and fungal aerosols in a chamber-type air disinfection system by using a UVC light-emitting-diode (LED) array was investigated and ...inactivation rate constants of each microorganism were calculated in fitting curves of surviving populations. UVC LED array treatment effectively inactivated viral infectivity, achieving 5-log reductions within 45 mJ/cm
for MS2, Qβ, and ϕX174 viruses. UVC LED array effectiveness in inactivating
O157:H7,
serovar Typhimurium,
, and
aerosols achieved 2.5- to 4-log reductions within 1.5 to 4.6 mJ/cm
Also, 4-log reductions of
and
were achieved at a dosage of 23 mJ/cm
using UVC LED array irradiation. The highest UV susceptibility, represented by the inactivation rate constant, was calculated for bacteria, followed by fungi and viruses. UVC LED, an innovative technology, can effectively inactivate microorganisms regardless of taxonomic classification and can sufficiently substitute for conventional mercury UV lamps.
The United Nations Environment Programme (UNEP) convened the Minamata Convention on Mercury in 2013 to ban mercury-containing products in order to ensure human and environmental health. It will be effectuated in 2020 to discontinue use of low-pressure mercury lamps and new UV-emitting sources have to replace this conventional technology. However, the UV germicidal irradiation (UVGI) system still uses conventional UV lamps, and no research has been conducted for air disinfection using UVC LEDs. The research reported here investigated the inactivation effect of aerosolized microorganisms, including viruses, bacteria, and fungi, with an UVC LED module. The results can be utilized as a primary database to replace conventional UV lamps with UVC LEDs, a novel type of UV emitter. Implementation of UVC LED technology is truly expected to significantly reduce the extent of global mercury contamination, and this study provides important baseline data to help ensure a healthier environment and increased health for humanity.
Xenobiotic metabolism involves the biochemical modification of drugs and phytochemicals in living organisms, including humans and other animals. In the intestine, the gut microbiota catalyzes the ...conversion of hydrophilic drugs into absorbable, hydrophobic compounds through hydroxyzation and reduction. Drugs and phytochemicals are transformed into bioactive (sulfasalazine, lovastatin, and ginsenoside Rb1), bioinactive (chloramphenicol, ranitidine, and metronidazole), and toxic metabolites (nitrazepam), thus affecting the pharmacokinetics of the original compounds. Antibiotics suppress the activities of drug-metabolizing enzymes by inhibiting the proliferation of gut microbiota. Antibiotic treatment might influence xenobiotic metabolisms more extensively and potently than previously recognized and reduce gut microbiota-mediated transformation of orally administered drugs, thereby altering the systemic concentrations of intact drugs, their metabolites, or both. This review describes the effects of antibiotics on the metabolism of drugs and phytochemicals by the gut microbiota.
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