Retinal fundus diseases can lead to irreversible visual impairment without timely diagnoses and appropriate treatments. Single disease-based deep learning algorithms had been developed for the ...detection of diabetic retinopathy, age-related macular degeneration, and glaucoma. Here, we developed a deep learning platform (DLP) capable of detecting multiple common referable fundus diseases and conditions (39 classes) by using 249,620 fundus images marked with 275,543 labels from heterogenous sources. Our DLP achieved a frequency-weighted average F1 score of 0.923, sensitivity of 0.978, specificity of 0.996 and area under the receiver operating characteristic curve (AUC) of 0.9984 for multi-label classification in the primary test dataset and reached the average level of retina specialists. External multihospital test, public data test and tele-reading application also showed high efficiency for multiple retinal diseases and conditions detection. These results indicate that our DLP can be applied for retinal fundus disease triage, especially in remote areas around the world.
Innate immunity is an indispensable arm of tumor immune surveillance, and the liver is an organ with a predominance of innate immunity, where mucosal-associated invariant T (MAIT) cells are enriched. ...However, little is known about the phenotype, functions, and immunomodulatory role of MAIT cells in hepatocellular carcinoma (HCC).
The distribution, phenotype, and function of MAIT cells in patients with HCC were evaluated by both flow cytometry (FCM) and
bioassays. Transcriptomic analysis of MAIT cells was also performed. Prognostic significance of tumor-infiltrating MAIT cells was validated in four independent cohorts of patients with HCC.
Despite their fewer densities in HCC tumor than normal liver, MAIT cells were significantly enriched in the HCC microenvironment compared with other mucosa-associated organs. Tumor-derived MAIT cells displayed a typical CCR7
CD45RA
CD45RO
CD95
effector memory phenotype with lower costimulatory and effector capabilities. Tumor-educated MAIT cells significantly upregulated inhibitory molecules like PD-1, CTLA-4, TIM-3, secreted significantly less IFNγ and IL17, and produced minimal granzyme B and perforin while shifting to produce tumor-promoting cytokines like IL8. Transcriptome sequencing confirmed that tumor-derived MAIT cells were reprogrammed toward a tumor-promoting direction by downregulating genes enriched in pathways of cytokine secretion and cytolysis effector function like
and
and by upregulating genes like
, and
(
). High infiltration of MAIT cells in HCC significantly correlated with an unfavorable clinical outcome, revealed by FCM, qRT-PCR, and multiplex IHC analyses, respectively.
HCC-infiltrating MAIT cells were functionally impaired and even reprogrammed to shift away from antitumor immunity and toward a tumor-promoting direction.
.
Substrate–molecule vibronic coupling enhancement, especially the efficient photoinduced charge transfer (PICT), is pivotal to the performance of nonmetal surface-enhanced Raman scattering (SERS) ...technology. Here, through developing novel two-dimensional (2D) amorphous TiO2 nanosheets (a-TiO2 NSs), we successfully obtained an ultrahigh enhancement factor of 1.86 × 106. Utilizing the Kelvin probe force microscopy (KPFM) technology, we found that these 2D a-TiO2 NSs possessed more positive surface potential than their 2D crystalline counterpart (c-TiO2 NSs). First-principles density functional theory (DFT) was used to further reveal that the low coordination number of surface Ti atoms and the large amount of surface oxygen defects endowed the 2D a-TiO2 with high electrostatic potential, which allowed significant charge transfer from the adsorbed molecule to the 2D a-TiO2 and facilitated the formation of a stable surface charge-transfer (CT) complex. Significantly, comparing with the 2D c-TiO2, the smaller band gap and higher electronic density of states (DOS) of the 2D a-TiO2 effectively enhanced the vibronic coupling of resonances in the substrate–molecule system. The strong vibronic coupling within the CT complex obviously enhanced the PICT resonance and lead to the remarkable SERS activity of a-TiO2 NSs. To the best of our knowledge, this is the first report on the remarkable SERS activity of 2D amorphous semiconductor nanomaterials, which may bring the cutting edge of development of stable and highly sensitive nonmetal SERS technology.
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IJS, KILJ, NUK, PNG, UL, UM
Enhancement of the semiconductor–molecule interaction, in particular, promoting the interfacial charge transfer process (ICTP), is key to improving the sensitivity of semiconductor‐based surface ...enhanced Raman scattering (SERS). Herein, by developing amorphous ZnO nanocages (a‐ZnO NCs), we successfully obtained an ultrahigh enhancement factor of up to 6.62×105. This remarkable SERS sensitivity can be attributed to high‐efficiency ICTP within a‐ZnO NC molecule system, which is caused by metastable electronic states of a‐ZnO NCs. First‐principles density functional theory (DFT) simulations further confirmed a stronger ICTP in a‐ZnO NCs than in their crystalline counterparts. The efficient ICTP can even generate π bonding in Zn−S bonds peculiar to the mercapto molecule adsorbed a‐ZnO NCs, which has been verified through the X‐ray absorption near‐edge structure (XANES) characterization. To the best of our knowledge, this is the first time such remarkable SERS activity has been observed within amorphous semiconductor nanomaterials, which could open a new frontier for developing highly sensitive and stable SERS technology.
Amorphous ZnO nanocages (a‐ZnO NCs) were developed and used to obtain an ultrahigh SERS enhancement factor of up to 6.62×105. This remarkable SERS sensitivity can be attributed to the high‐efficiency interfacial charge transfer process (ICTP) within the a‐ZnO NC–molecule system, which is caused by metastable electronic states of a‐ZnO NCs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Millilensing of gamma-ray bursts (GRBs) is expected to manifest as multiple emission episodes in a single triggered GRB with similar light-curve patterns and similar spectrum properties. ...Identifying such lensed GRBs could help improve constraints on the abundance of compact dark matter. Here we present a systemic search for millilensing among 3000 GRBs observed by the Fermi GBM up to 2021 April. Eventually we find four interesting candidates by performing an autocorrelation test, hardness test, and time-integrated/resolved spectrum test. GRB 081126A and GRB 090717A are ranked as the first-class candidates based on their excellent performance in both temporal and spectrum analysis. GRB 081122A and GRB 110517B are ranked as the second-class candidates (suspected candidates), mainly because their two emission episodes show clear deviations in part of the time-resolved spectrum or in the time-integrated spectrum. Considering a point-mass model for the gravitational lens, our results suggest that the density parameter of lens objects with mass
M
L
∼ 10
6
M
⊙
is larger than 1.5 × 10
−3
.
F− substituted Bi2WO6 (Bi2WO6−X F2X ) photocatalysts with high activity have been successfully synthesized by a two-step process. The effects of F− substitution on the crystal structure and ...photocatalytic activity of Bi2WO6 were investigated. F− substitution could change the original coordination around the W and Bi atoms. Comparing with Bi2WO6, the photocatalytic activity of Bi2WO6−X F2X increased about 2 times for degradation of MB under visible-light (λ > 420 nm) irradiation. Density functional calculations revealed that Bi2WO6−X F2X has a wider valence bandwidth and lower valence band position. The high activities of Bi2WO6−X F2X photocatalysts come from its valence band which increase the mobility of photoexcited charge carriers and possess a stronger oxidation power.
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The development of effective nitrogen-doped (N-doped) metal-free carbon nanotube electrocatalysts with high activity and stability to replace the scarce Pt-based catalysts for the oxygen reduction ...reaction (ORR) is of great importance in energy conversion devices. The hierarchical porosity and content of nitrogen atoms in carbon nanotubes play an important role in the determination of active sites. The use of metal–organic frameworks (MOFs) as templates and/or precursors to fabricate porous carbon could endow the resulting products with their merits including highly doped heteroatoms, large surface areas and controllable structures. Herein, core–shell ZnO@ZIF-8 nanorods were employed as templates and precursors to fabricate hierarchically porous N-doped carbon nanotubes (NCNTs) using a self-sacrifice template approach. The high level of graphitization and nitrogen content of the NCNTs could be tuned by adjusting the core–shell ZnO@ZIF-8 nanorod precursors and pyrolysis temperature. The obtained hierarchically porous NCNTs exhibit superior performances for the ORR in alkaline media. Impressively, NCNT-24-800, which was pyrolyzed at 800 °C, exhibits an excellent performance with a positive onset potential of 0.06 V (
vs.
Ag/AgCl), a more positive half-wave potential at −0.103 V (
vs.
Ag/AgCl, a positive shift of 27 mV compared with Pt/C) and a high diffusion-limited current density of 5.68 mA cm
−2
at −0.8 V, which are comparable to the benchmark commercial 20 wt% Pt/C catalyst. Furthermore, compared with the traditional Pt/C, the NCNTs show excellent long term stability and methanol tolerance. The self-sacrifice template approach could open up a new avenue towards the fabrication of materials with unique porous structures from MOFs as highly efficient metal-free electrocatalysts for the ORR.
An emerging concept is that the hypothalamic nutrient sensor can regulate peripheral energy metabolism via a brain-liver circuit. Valine is an essential branched-chain amino acid (BCAA) that drives ...intracellular signaling cascades by the activation of target of rapamycin complex 1 (TORC1) which is critical to protein metabolism in mammals. However, in teleost fish, it remains scarce in this area especially about how the intraventricular (ICV) injection of valine can mediate the protein metabolism in peripheral organs. This study would tentatively explore the effects of ICV injection of valine on protein metabolism in peripheral organs through evaluating the postprandial ammonia-N excretion rate in Chinese perch. The control group was injected with 5-μL PBS, and the Val group was injected with 20-μg L valine dissolved into 5-μL PBS. The ammonia-N excretion rate of Val group was lower than control group at 4-, 12-, and 24-h postinjection, while the concertation of plasma glucose was increased sharply at 0.5-, 4-, 12-, and 24-h postinjection. We further checked both mRNA level and the enzyme activity of glutamate dehydrogenase (GDH) in the liver and adenosine monophosphate deaminase (AMPD) in muscle, and we found that they were obviously decreased in Val group at 4-, 12-, and 24-h postinjection. The phosphorylation level of ribosomal protein S6, a downstream target protein of TORC1, was markedly enhanced in the liver of Val group at 4-, 12-, and 24-h postinjection. Collectively, these results illustrated that ICV injection of valine can attenuate protein degradation in peripheral organs by depressing the GDH and AMPD enzyme activity; on the other hand, the injected valine can trigger the activation of TORC1 in the liver via a brain-liver circuit and then interdict proteolysis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease that typically leads to respiratory failure and death within 3–5 years of diagnosis. Sub-pleural pulmonary fibrosis is a ...pathological hallmark of IPF. Bleomycin treatment of mice is a an established pulmonary fibrosis model. We recently showed that bleomycin-induced epithelial-mesenchymal transition (EMT) contributes to pleural mesothelial cell (PMC) migration and sub-pleural pulmonary fibrosis. MicroRNA (miRNA) expression has recently been implicated in the pathogenesis of IPF. However, changes in miRNA expression in PMCs and sub-pleural fibrosis have not been reported. Using cultured PMCs and a pulmonary fibrosis animal model, we found that miR-18a-5p was reduced in PMCs treated with bleomycin and that downregulation of miR-18a-5p contributed to EMT of PMCs. Furthermore, we determined that miR-18a-5p binds to the 3′ UTR region of transforming growth factor β receptor II (TGF-βRII) mRNA, and this is associated with reduced TGF-βRII expression and suppression of TGF-β-Smad2/3 signaling. Overexpression of miR-18a-5p prevented bleomycin-induced EMT of PMC and inhibited bleomycin-induced sub-pleural fibrosis in mice. Taken together, our data indicate that downregulated miR-18a-5p mediates sub-pleural pulmonary fibrosis through upregulation of its target, TGF-βRII, and that overexpression of miR-18a-5p might therefore provide a novel approach to the treatment of IPF.
Sub-pleural pulmonary fibrosis is a pathological hallmark of idiopathic pulmonary fibrosis (IPF). Zhang et al. found that downregulated miR-18a-5p mediates sub-pleural pulmonary fibrosis through upregulation of its target, TGF-βRII, suggesting that overexpression of miR-18a-5p might be an approach to the treatment of IPF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The design of multicomponent materials has captured considerable attention due to its extraordinary ability to tailor functional properties. However, how a single element affects the behavior of the ...overall material has yet to be explored in depth. In this study, the heteroepitaxy of high entropy (Fe, Co, Ni, Cr, Mn)3O4 films with varying strain states are investigated in magnetic performance. It is discovered that the high entropy oxide thin film with compressive strain exhibits an effect of crystalline magnetic anisotropy. Diverse analyses provide a detailed understanding of high entropy magnetic oxide systems, including X‐ray diffraction, reciprocal space mapping, macroscopic magnetic characterization, X‐ray absorption spectroscopy (XAS), etc. Notably, the element‐specific XAS technique proves effective in uncovering the origin of the crystalline magnetic anisotropy. Due to the substrate‐induced epitaxial strain, the eg orbitals of Mn3+ form different energy levels, leading to different preferred electron occupancy. The exploration of magnetic properties in epitaxial high entropy oxide film is then raveled. By navigating the complexities introduced by the random atom distribution and intricate magnetic interactions, this study pioneers novel methodologies for probing the core physics of high entropy oxides.
In a strain‐driven local environment, the magnetic properties of high entropy oxide (Fe, Co, Ni, Cr, Mn)3O4 induced by individual elements are discovered. By utilizing atomic‐spatial‐resolution scanning transmission electron microscopy and element‐specific X‐ray absorption techniques, a thorough understanding of the high entropy oxide can be achieved, establishing a novel methodology for investigating the magnetic origin of high entropy oxides.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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