Abstract
Dual-energy X-ray absorptiometry (DXA) is underutilized to measure bone mineral density (BMD) and evaluate fracture risk. We present an automated tool to identify fractures, predict BMD, and ...evaluate fracture risk using plain radiographs. The tool performance is evaluated on 5164 and 18175 patients with pelvis/lumbar spine radiographs and Hologic DXA. The model is well calibrated with minimal bias in the hip (slope = 0.982, calibration-in-the-large = −0.003) and the lumbar spine BMD (slope = 0.978, calibration-in-the-large = 0.003). The area under the precision-recall curve and accuracy are 0.89 and 91.7% for hip osteoporosis, 0.89 and 86.2% for spine osteoporosis, 0.83 and 95.0% for high 10-year major fracture risk, and 0.96 and 90.0% for high hip fracture risk. The tool classifies 5206 (84.8%) patients with 95% positive or negative predictive value for osteoporosis, compared to 3008 DXA conducted at the same study period. This automated tool may help identify high-risk patients for osteoporosis.
The oral absorption of a therapeutic peptide (such as exenatide; EXT) that can improve glycemic control in the treatment of type 2 diabetes is limited by multiple barriers of the intestinal ...epithelium. This work presents an oil‐structured nanoemulsion system that consists of a phase‐changeable fatty acid that allows EXT (EXT@PC/NEMs) to be delivered orally and absorbed efficiently in the small intestine. To construct an appropriate vehicle to encapsulate EXT, an oil‐in‐water single emulsion is generated at 37 °C, which is well above the melting point of the fatty acid but below the denaturation temperature of the peptide drug. The as‐prepared EXT@PC/NEMs are physically stable when stored at 4 °C, as they form a solid core, which prevents drug leakage. Upon their oral delivery at body temperature, the deformable liquid EXT@PC/NEMs may undergo effective cellular uptake, enhancing their permeability across the intestinal epithelium. The orally administered PC/NEMs significantly improve the bioavailability of EXT via intestinal lymphatic transport, ultimately accumulating in the pancreas, suggesting the possibility of orally delivering labile peptide drugs. The delivered EXT may act on pancreatic β‐ and α‐cells to stimulate insulin release and suppress glucagon secretion, respectively, reducing the blood glucose level, eventually having antidiabetic effects.
Phase‐changeable nanoemulsions are used to encapsulate a peptide drug during emulsification at 37 °C and are physically stable when stored at 4 °C. Upon oral ingestion at body temperature, the deformable liquid nanoemulsions undergo effective cellular uptake, enhancing their permeability across the intestinal epithelium, ultimately accumulating in the pancreas via lymphatic transport to exert their beneficial antidiabetic effects.
Abstract
The demand for sustainable energy has motivated the development of artificial photosynthesis. Yet the catalyst and reaction interface designs for directly fixing permanent gases (e.g. CO
2
, ...O
2
, N
2
) into liquid fuels are still challenged by slow mass transfer and sluggish catalytic kinetics at the gas-liquid-solid boundary. Here, we report that gas-permeable metal-organic framework (MOF) membranes can modify the electronic structures and catalytic properties of metal single-atoms (SAs) to promote the diffusion, activation, and reduction of gas molecules (e.g. CO
2,
O
2
) and produce liquid fuels under visible light and mild conditions. With Ir SAs as active centers, the defect-engineered MOF (e.g. activated NH
2
-UiO-66) particles can reduce CO
2
to HCOOH with an apparent quantum efficiency (AQE) of 2.51% at 420 nm on the gas-liquid-solid reaction interface. With promoted gas diffusion at the porous gas-solid interfaces, the gas-permeable SA/MOF membranes can directly convert humid CO
2
gas into HCOOH with a near-unity selectivity and a significantly increased AQE of 15.76% at 420 nm. A similar strategy can be applied to the photocatalytic O
2
-to-H
2
O
2
conversions, suggesting the wide applicability of our catalyst and reaction interface designs.
Perovskite quantum dots (PQDs) have attracted much attention in the field of photoelectrochemical (PEC) sensors owing to their superb optical properties and efficient charge transport, but the ...inherent poor stability severely hinders their PEC applications. Herein, hydrolysis‐resistant CsPbBr3/reduced graphene oxide nanoscrolls (CsPbBr3/rGO NSs) are obtained by solvent‐assisted self‐rolling process toward water‐stable PEC sensors. CsPbBr3 QDs embedded in rGO nanosheets can be prevented from water since the multilayer rGO shell layers, which maintains excellent optical properties. On account of strong interfacial interactions, rGO nanosheets are crimped spontaneously with CsPbBr3 QDs, which offer access to superb structural and long‐term storage stability. Moreover, appropriate band alignment and ultrafast interfacial carrier transfer enable CsPbBr3/rGO NSs to exhibit greatly enhanced anode photocurrent response for subsequent PEC sensing. As a demonstration, the molecular imprinted PEC sensors for two kinds of mycotoxins (aflatoxin B1 or ochratoxin A) presents an ultra‐high sensitivity and good anti‐interference ability. Significantly, this work provides an inspirable and convenient route for hydrolysis‐resistant PQDs‐based optoelectronic and photoelectrocatalytic applications in aqueous ambience.
Water‐stable CsPbBr3/reduced graphene oxide nanoscrolls (CsPbBr3/rGO NSs) are successfully achieved via rGO self‐rolling and CsPbBr3 encapsulation, appropriate band alignment and ultrafast interfacial carrier transfer enable CsPbBr3/rGO NSs to exhibit greatly enhanced anode photocurrent response for subsequent photoelectrochemical sensing. This work provides an inspirable and convenient strategy for hydrolysis‐resistant perovskite‐based further applications in aqueous ambience.
The phosphor‐converted light‐emitting diode (PC‐LED) has become an indispensable solid‐state lighting and display technologies in the modern society. Nevertheless, the use of scarce rare‐earth ...elements and the thermal quenching (TQ) behavior are still two most crucial issues yet to be solved. Here, this work successfully demonstrates a highly efficient and thermally stable green emissive MnI2(XanPO) crystals showing a notable photoluminescence quantum yield (PLQY) of 94% and a super TQ resistance from 4 to 623 K. This unprecedented superior thermal stability is attributed to the low electron–phonon coupling and the unique rigid crystal structure of MnI2(XanPO) over the whole temperature range based on the temperature‐dependent photoluminescence (PL) and single crystal X‐ray diffraction (SCXRD) analyses. Considering these appealing properties, green PC‐LEDs with a power efficacy of 102.5 lm W−1, an external quantum efficiency (EQE) of 22.7% and a peak luminance up to 7750 000 cd m−2 are fabricated by integrating MnI2(XanPO) with commercial blue LEDs. Moreover, the applicability of MnI2(XanPO) in both micro‐LEDs and organic light‐emitting diodes (OLEDs) is also demonstrated. In a nutshell, this study uncovers a candidate of highly luminescent and TQ resistant manganese halide suitable for a variety of emission applications.
A highly efficient and thermally stable manganese halide crystal, MnI2(XanPO) is demonstrated. The low electron–phono coupling along with rigid crystal structure contributes to excellent photoluminescent quantum yield of 94% with unprecedented near zero thermal quenching from 4 to 623 K. The crystals find their applications in light emitting diodes and micro light emitting diodes with excellent external quantum efficiency (EQE) up to 22.7% and power efficacy as high as 102.5 lm W−1.
Coptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main ...active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet β-cell-specific Kcnh6 knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels.
Afterglow imaging with long-lasting luminescence after cessation of light excitation provides opportunities for ultrasensitive molecular imaging; however, the lack of biologically compatible ...afterglow agents has impeded exploitation in clinical settings. This study presents a generic approach to transforming ordinary optical agents (including fluorescent polymers, dyes, and inorganic semiconductors) into afterglow luminescent nanoparticles (ALNPs). This approach integrates a cascade photoreaction into a single-particle entity, enabling ALNPs to chemically store photoenergy and spontaneously decay it in an energy-relay process. Not only can the afterglow profiles of ALNPs be finetuned to afford emission from visible to near-infrared (NIR) region, but also their intensities can be predicted by a mathematical model. The representative NIR ALNPs permit rapid detection of tumors in living mice with a signal-to-background ratio that is more than three orders of magnitude higher than that of NIR fluorescence. The biodegradability of the ALNPs further heightens their potential for ultrasensitive in vivo imaging.
To improve the accuracy and generalization ability of hyperspectral image classification, a feature extraction method integrating principal component analysis (PCA) and local binary pattern (LBP) is ...developed for hyperspectral images in this article. The PCA is employed to reduce the dimension of the spectral features of hyperspectral images. The LBP with low computational complexity is used to extract the local spatial texture features of hyperspectral images to construct multifeature vectors. Then, the gray wolf optimization algorithm with global search capability is employed to optimize the parameters of kernel extreme learning machine (KELM) to construct an optimized KELM model, which is used to effectively realize a hyperspectral image classification (PLG-KELM) method. Finally, the Indian pines dataset, Houston dataset, and Pavia University dataset and an application of WHU-Hi-LongKou dataset are selected to verify the effectiveness of the PLG-KELM. The comparison experiment results show that the PLG-KELM can obtain higher classification accuracy, and takes on better generalization ability for small samples. It provides a new idea for processing hyperspectral images.
Most orally administered drugs fail to reach the intracerebral regions because of the intestinal epithelial barrier (IEB) and the blood–brain barrier (BBB), which are located between the gut and the ...brain. Herein, an oral prodrug delivery system that can overcome both the IEB and the BBB noninvasively is developed for treating gliomas. The prodrug is prepared by conjugating an anticancer drug on β‐glucans using a disulfide‐containing linker. Following oral administration in glioma‐bearing mice, the as‐prepared prodrug can specifically target intestinal M cells, transpass the IEB, and be phagocytosed/hitchhiked by local macrophages (Mϕ). The Mϕ‐hitchhiked prodrug is transported to the circulatory system via the lymphatic system, crossing the BBB. The tumor‐overexpressed glutathione then cleaves the disulfide bond within the prodrug, releasing the active drug, improving its therapeutic efficacy. These findings reveal that the developed prodrug may serve as a gut‐to‐brain oral drug delivery platform for the well‐targeted treatment of gliomas.
Following oral administration, a prodrug transpasses the intestinal epithelial barrier via M cells, and then undergoes endocytosis by resident macrophages. The macrophage‐hitchhiked prodrug is transported to the circulatory system via the lymphatic system, crossing the blood–brain barrier, ultimately penetrating a brain tumor. The tumor‐overexpressed glutathione cleaves the disulfide bond within the prodrug, releasing the active drug, facilitating antitumor efficacy.
In Taiwan, coronavirus disease 2019 (COVID‐19) involving the delta variant occurred after that involving the alpha variant in 2021. In this study, we aimed to analyze the Delta variant. A total of ...318 patients in Taiwan infected with delta variants were identified. The case fatality rate (CFR) of patients infected with delta variants was 0.94% in Taiwan compared with that of those infected with alpha variants (5.95%). The possible reasons for the low CFR might be hybrid immunity due to infection and rapid promotion of the COVID‐19 vaccination program during the alpha variant outbreak. We identified three 21J delta variants. Two long gene deletions were detected in these severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) isolates: ORF7aΔ91 in KMUH‐8 and SpikeΔ30 in KMUH‐9. Protein structure prediction indicates that ORF7aΔ91 results in malfunction of NS7a as an interferon antagonist and that SpikeΔ30 results in a truncated spike protein (N679–A688del), resulting in a lower infection rate compared with the delta variant without these deletions. The impact of these two deletions on SARS‐CoV‐2‐associated pathogenesis deserves further investigation. Delta variants still exist in many regions in the omicron era, and the backbone of the delta variant genome possibly spread worldwide in the form of delta‐omicron hybrids (deltacron; e.g., XBC.1 and XAY.2), which casts a potential threat to public health. Our study further highlighted the importance of more understanding of the delta variants.
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