Biomarker-activatable theranostic formulations offer the potential for removing specific tumors with a high diagnostic accuracy and a significant pharmacological effect. Herein, we developed a novel ...activatable theranostic nanoformulation UAS-PD upconversion nanophosphor (UCNP)-aptamer/ssDNA-pyropheophorbide-a (PPA)-doxyrubicin (DOX), which can recognize specific cancer cells with sensitivity and trigger the localized photodynamic destruction and enhanced chemotherapy. UAS-PD was constructed by the conjugation of UCNPs and aptamer probes containing the photosensitizer PPA and the chemotherapeutic drug DOX. When cancer cells are present, the UAS-PD specifically binds to PTK7, an overexpressed protein present on the surface of cancer cells, through conformational recombination of the aptamer structure and switches its upconversion luminescence from 655 to 540 nm. This long-lived ratiometric optical signal provides an ultrasensitive detection limit as low as 3.9 nM for PTK7. Changes in the conformation of UAS-PD can also induce PPA to approach UCNPs, which can produce cytotoxic singlet oxygens under near-infrared excitation to destroy the cell membrane and enhance its permeability for the simultaneously released DOX that targets cellular DNA degradation, which results in a highly effective tumor-killing effect by synergistic extra-intracellular sequential damage.
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IJS, KILJ, NUK, PNG, UL, UM
Water pollution has become a serious problem owing to the development of society. Photocatalysis is a promising approach to remove various pollutants in water, such as organic pollutants and ...antibiotic resistance bacteria. Meanwhile, the design of heterojunction between two semiconductors is an effective path to improve photocatalytic properties due to its potential in improving separation and transfer of photoinduced carriers. In this study, Nb2O5/g-C3N4 (NO/CN) composite materials were prepared through a one-step heating method. Characterizations confirmed successful preparation of NO/CN heterojunction structure and better optical properties than pure g-C3N4 and Nb2O5. NO/CN composite materials showed excellent photocatalytic efficiency for Escherichia coli (E. coli) inactivation (95%) compared with the pure Nb2O5 (10%) and g-C3N4 (77%). Meanwhile, NO/CN exhibited better organic pollutants removal (RhB for 94%, methyl orange (MO) for 15% and methylene blue (MB) for 87%) under visible light, which is likely owing to the heterojunction structure between g-C3N4 and Nb2O5 that leads to the good separation of photogenerated electron-hole pair. Free radical scavenging and electron spin resonance (ESR) experiments demonstrated that superoxide radicals (•O2−) and holes (h+) were the dominant radicals. Therefore, the NO/CN was proposed to be a promising material for effective disinfection and removal of organic contaminants in water treatment.
Nb2O5/g-C3N4 (NO/CN) composite was synthesized and exhibited strong photocatalytic performance for decomposition of organic pollutants, and bacteria. Better removal efficiency was achieved by the generation of type-II heterojunction between g-C3N4 and Nb2O5
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The ...molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show that, in mouse OPCs, nuclear entry of SIRT2 is impaired and NAD
levels are reduced during ageing. When we supplement β-nicotinamide mononucleotide (β-NMN), an NAD
precursor, nuclear entry of SIRT2 in OPCs, OPC differentiation, and remyelination were rescued in aged animals. We show that the effects on myelination are mediated via the NAD
-SIRT2-H3K18Ac-ID4 axis, and SIRT2 is required for rejuvenating OPCs. Our results show that SIRT2 and NAD
levels rescue the aged OPC differentiation potential to levels comparable to young age, providing potential targets to enhance remyelination during ageing.
In the absence of externally applied mechanical loading, it would seem counterintuitive that a solid particle sitting on the surface of another solid could not only sink into the latter, but also ...continue its rigid-body motion towards the interior, reaching a depth as distant as thousands of times the particle diameter. Here, we demonstrate such a case using in situ microscopic as well as bulk experiments, in which diamond nanoparticles ~100 nm in size move into iron up to millimeter depth, at a temperature about half of the melting point of iron. Each diamond nanoparticle is nudged as a whole, in a displacive motion towards the iron interior, due to a local stress induced by the accumulation of iron atoms diffusing around the particle via a short and easy interfacial channel. Our discovery underscores an unusual mass transport mode in solids, in addition to the familiar diffusion of individual atoms.
Due to the inherent parasitic inductance and high switching speed, the SiC MOSFET generally experience significant overvoltage and oscillation, reducing the voltage margin and causing substantial ...electromagnetic interference. To mitigate these challenges, a novel auxiliary circuit using the gate charge injection (GCI) concept is proposed in this paper. The GCI circuit, assembled across the drain-gate of the SiC MOSFET, injects charges into the gate during the overvoltage stage of the turn-off process, effectively reducing overvoltage and oscillation without affecting the turn-off speed. The mechanism of the proposed GCI circuit is meticulously analyzed interval by interval based on the cell structure of the SiC MOSFET, and its parameters are designed and validated through the circuit simulation. Additionally, the proposed GCI circuit, comprising Si-RC and PiN diode die, is integrated into the SiC power module and assessed by the double pulse test and power cycling test. Experimental results show a 70% reduction in the transient overvoltage at 600 V/30 A and complete the oscillation elimination, with only a 3.4% increase in the switching loss. The GCI circuit does not affect the turn-on process, making it an effective and cost-competitive solution for suppressing the overvoltage and oscillation in the SiC power module.
Phase instability poses a serious challenge to the commercialization of formamidinium lead iodide (FAPbI
)-based solar cells and optoelectronic devices. Here, we combine density functional theory and ...machine learning molecular dynamics simulations, to investigate the mechanism driving the undesired α-δ phase transition of FAPbI
. Prevalent iodine vacancies and interstitials can significantly expedite the structural transition kinetics by inducing robust covalency during transition states. Extrinsically, the detrimental roles of atmospheric moisture and oxygen in degrading the FAPbI
perovskite phase are also rationalized. Significantly, we discover the compositional design principles by categorizing that A-site engineering primarily governs thermodynamics, whereas B-site doping can effectively manipulate the kinetics of the phase transition in FAPbI
, highlighting lanthanide ions as promising B-site substitutes. A-B mixed doping emerges as an efficient strategy to synergistically stabilize α-FAPbI
, as experimentally demonstrated by substantially higher initial optoelectronic characteristics and significantly enhanced phase stability in Cs-Eu doped FAPbI
as compared to its Cs-doped counterpart. This study provides scientific guidance for the design and optimization of long-term stable FAPbI
-based solar cells and other optoelectronic devices through defect control and synergetic composition engineering.
Whistler mode hiss acts as an important loss mechanism contributing to the radiation belt electron dynamics inside the plasmasphere and plasmaspheric plumes. Based on Van Allen Probes observations ...from September 2012 to December 2015, we conduct a detailed analysis of hiss properties in plasmaspheric plumes and illustrate that corresponding to the highest occurrence probability of plumes at L = 5.0–6.0 and MLT = 18–21, hiss emissions occur concurrently with a rate of >~80%. Plume hiss can efficiently scatter ~10‐ to 100‐keV electrons at rates up to ~10−4 s−1 near the loss cone, and the resultant electron loss timescales vary largely with energy, that is, from less than an hour for tens of kiloelectron volt electrons to several days for hundreds of kiloelectron volt electrons and to >100 days for >5‐MeV electrons. These newly obtained statistical properties of plume hiss and associated electron scattering effects are useful to future modeling efforts of radiation belt electron dynamics.
Key Points
Plume hiss occurs concurrently with a rate of >~80%, corresponding to the highest occurrence rate of plumes at L = 5.0‐6.0 and MLT = 18‐21
Plume hiss is efficient for pitch angle scattering ~10‐ to 100‐keV electrons near the loss cone
Plume hiss can drive more efficient scattering of >500‐keV electrons at higher L‐shells than normal frequency hiss at lower L‐shells
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Obesity is a crucial risk factor for obstructive sleep apnea (OSA), but the association between adiposity deposition and OSA risk has not reached a consistent conclusion. This ...study sought to reveal the association of multiple adiposity indicators with OSA risk.
Methods
This cross-sectional study included 9,733 participants aged 35–74 years, recruited from an ongoing population-based cohort. OSA was assessed by the Berlin Questionnaire. Six adiposity indicators, including neck circumference (NC), body fat percentage (BF%), waist-to-hip ratio (WHR), visceral adiposity index (VAI), lipid accumulation product (LAP), and resting metabolic rate (RMR), were selected. Multivariate logistic regression models were used to examine the association of adiposity indicators with OSA risk.
Results
One thousand six hundred twenty-six participants (16.71%) were classified into the OSA group. NC, BF%, WHR, VAI, LAP, and RMR were all positively associated with the risk of OSA after adjusting for confounders, regardless of age, sex, and history of dyslipidemia. Every 1-unit increment of NC, BF%, and VAI was associated with a 13%, 9%, and 14% increased risk of OSA, respectively; every 0.01-unit increment of WHR was associated with a 3% increased risk of OSA; every 10-unit increment of LAP and RMR was associated with 2% and 4% increased risk of OSA, respectively.
Conclusions
NC, BF%, WHR, VAI, LAP, and RMR were all independently and positively associated with OSA risk, regardless of age, sex, history of dyslipidemia, and menopausal status. Application of these new indicators could help to more comprehensively reflect and predict the risk of OSA in the general population.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although PIWI-interacting RNAs (piRNAs) have recently been linked to human diseases, their roles and functions in malignancies remain unclear. This study aimed to investigate the significance of some ...piRNAs in colorectal cancer (CRC).
We first analyzed the expression profile of piRNAs in CRC using the TCGA and GEO databases. The top 20 highly expressed piRNAs were selected and tested in our CRC tumor and non-tumor tissue samples. We then examined the relevance of the significantly differentially expressed piRNA to the CRC outcomes in 218 patients receiving postoperative chemotherapy and 317 patients receiving neoadjuvant chemotherapy. A series of biochemical and molecular biological assays were conducted to elucidate the functional mechanism of a piRNA of interest in CRC. Furthermore, experiments with mice xenografts were performed to evaluate the therapeutic effect of an inhibitor specific to the piRNA.
We found that among the examined 20 piRNAs, only piRNA-54265 was overexpressed in CRC compared with non-tumor tissues and higher levels in tumor or in serum were significantly associated with poor survival in patients. Functional assays demonstrated that piRNA-54265 binds PIWIL2 protein and this is necessary for the formation of PIWIL2/STAT3/phosphorylated-SRC (p-SRC) complex, which activates STAT3 signaling and promotes proliferation, metastasis and chemoresistance of CRC cells. Treatment with a piRNA-54265 inhibitor significantly suppressed the growth and metastasis of implanted tumors in mice.
These results indicate that piRNA-54265 is an oncogenic RNA in CRC and thus might be a therapeutic target.