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Mitochondria-targeting photothermal therapy could significantly enhance the tumor cell killing effect. However, since therapeutic reagents need to overcome a series of physiological obstacles to arrive at mitochondria accurately, precise mitochondria-targeting photothermal therapy still faces great challenges. In this study, we developed a self-delivery nanoplatform that specifically targeted the mitochondria of tumor cells for precise photothermal therapy. Photothermal agent IR780 was encapsulated by amphiphilic apoptotic peptide KLA with mitochondria-targeting ability to form nanomicelle KI by self-assembly through hydrophilic and hydrophobic interactions. Subsequently, negatively charged tumor-targeting polymer HA was coated on the surface of KI through electrostatic interactions, to obtain tumor mitochondria-targeting self-delivery nanoplatform HKI. Through CD44 receptor-mediated recognition, HKI was internalizated by tumor cells and then disassembled in an acidic environment with hyaluronidase in endosomes, resulting in the release of apoptotic peptide KLA and photothermal agent IR780 with mitochondria anchoring capacity, which achieved precise mitochondria guidance and destruction. This tumor mitochondria-targeting self-delivery nanoplatform was able to effectively deliver photothermal agents and apoptotic peptides to tumor cell mitochondria, resulting in precise destruction to mitochondria and enhancing tumor cell inhibition at the subcellular organelle level.

ABSTRACTBackgroundMagnesium is an essential nutrient required to maintain brain health throughout life, and adequate magnesium intake is positively associated with cognitive performance in older adults. However, sex differences in magnesium metabolism have not been adequately assessed in humans.ObjectivesWe investigated sex differences in the effect of dietary magnesium intake and the risk of different types of cognitive impairment in older Chinese adults.MethodsWe collected and assessed dietary data and cognitive function status in people aged 55 years and older in northern China who participated in the Community Cohort Study of Nervous System Diseases from 2018 to 2019 to explore the relationship between dietary magnesium intake and the risk of each type of mild cognitive impairment (MCI) in sex-specific cohorts of older adults.ResultsThe study included 612 people: 260 (42.5%) men and 352 (57.5%) women. Logistic regression results showed that for the total sample and women's sample, high dietary magnesium intake reduced the risk of amnestic MCI (ORtotal= 0.300; ORwomen= 0.190) and multidomain amnestic MCI (ORtotal= 0.225; ORwomen= 0.145). The results of restricted cubic spline analysis showed that the risk of amnestic MCI (ptotal= 0.0193; pwomen= 0.0351) and multidomain amnestic MCI (ptotal= 0.0089; pwomen= 0.0096) in the total sample and women's sample gradually decreased with increasing dietary magnesium intake.ConclusionsThe results suggest that adequate magnesium intake may have a preventive effect against the risk of MCI in older women.

The low-molecular-weight proteins (LMWP) in serum and plasma are related to various human diseases and can be valuable biomarkers. A small open reading frame-encoded peptide (SEP) is one kind of LMWP, which has been found to function in many bioprocesses and has also been found in human blood, making it a potential biomarker. The detection of LMWP by a mass spectrometry (MS)-based proteomic assay is often inhibited by the wide dynamic range of serum/plasma protein abundance. Nanoparticle protein coronas are a newly emerging protein enrichment method. To analyze SEPs in human serum, we have developed a protocol integrated with nanoparticle protein coronas and liquid chromatography (LC)/MS/MS. With three nanoparticles, TiO2, Fe3O4@SiO2, and Fe3O4@SiO2@TiO2, we identified 164 new SEPs in the human serum sample. Fe3O4@SiO2and a nanoparticle mixture obtained the maximum number and the largest proportion of identified SEPs, respectively. Compared with acetonitrile-based extraction, nanoparticle protein coronas can cover more small proteins and SEPs. The magnetic nanoparticle is also fit for high-throughput parallel protein separation before LC/MS. This method is fast, efficient, reproducible, and easy to operate in 96-well plates and centrifuge tubes, which will benefit the research on SEPs and biomarkers.

Severe weather events, such as extreme temperatures and water scarcity, can have significant impacts on the operation of critical electrical power infrastructure and, consequently, pose major threats to its resilience. Differently from existing studies that focus on the impact of extreme weather on individual power plants, this article quantifies the resilience of thermal power generation to extreme temperatures and the different levels of water availability from a system-level perspective. This article starts by introducing the fundamental engineering models of thermal power plants' cooling systems. A system-level quantification methodology is then proposed, which also introduces a multicoordinate resilience-oriented metric that assesses system vulnerability through the concepts of conditional value-at-risk and its rate of change in response to changes in the considered weather conditions. The numerical results obtained using a simplified version of the British transmission system not only demonstrate that the proposed framework is well suited to quantify the system-level resilience of the test system to extreme temperatures and different levels of water availability and scarcity but also highlight the benefits of using the newly defined resilience metric in such studies.