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RationaleProprotein convertase subtilisin/kexin type 9 (PCSK9) circulates in a free and lipoprotein-bound form, yet the functional consequence of the association between PCSK9 and high-density lipoprotein (HDL) remains unexplored.ObjectiveThis study sought to interrogate the novel relationship between PCSK9 and HDL in humans.Methods and resultsComparing lipoprotein and apolipoprotein profiles by nuclear magnetic resonance and targeted mass spectrometry measurements with PCSK9 levels in the community-based Bruneck (n=656) study revealed a positive association of plasma PCSK9 with small HDL, alongside a highly significant positive correlation between plasma levels of PCSK9 and apolipoprotein-C3, an inhibitor of lipoprotein lipase. The latter association was replicated in an independent cohort, the SAPHIR study (n=270). Thus, PCSK9-HDL association was determined during the postprandial response in two dietary studies (n=20 participants each, 8 times points). Peak triglyceride levels coincided with an attenuation of the PCSK9-HDL association, a loss of apolipoprotein-C3 from HDL and lower levels of small HDL as measured by nuclear magnetic resonance. Crosslinking mass spectrometry (XLMS) upon isolated HDL identified PCSK9 as a potential HDL-binding partner. PCSK9 association with HDL was confirmed through size-exclusion chromatography and immuno-isolation. Quantitative proteomics upon HDL isolated from patients with coronary artery disease (n=172) returned PCSK9 as a core member of the HDL proteome. Combined interrogation of the HDL proteome and lipidome revealed a distinct cluster of PCSK9, phospholipid transfer protein, clusterin and apolipoprotein-E within the HDL proteome, that was altered by sex and positively correlated with sphingomyelin content. Mechanistically, HDL facilitated PCSK9-mediated low-density lipoprotein receptor degradation and reduced low-density lipoprotein uptake through the modulation of PCSK9 internalisation and multimerisation.ConclusionsThis study reports HDL as a binder of PCSK9 and regulator of its function. The combination of -omic technologies revealed postprandial lipaemia as a driver of PCSK9 and apolipoprotein-C3 release from HDL.

The reconstruction effect of peri-implantitis bone defects depends on their morphological characteristics. This paper reviews the morphological classification and treatment of peri-implantitis bone defects. A literature review shows that the morphological classification of bone defects in peri-implantitis includes morphology classification and clinical classification. At present, the Renvert classification is more commonly used in the clinic and is divided into four-wall bone pockets, three-wall bone pockets, two-wall bone pockets, one-wall bone pocket and dehiscence according to the number of bone walls. This has guiding significance in the treatment plan of peri-implantitis. The treatment of peri-implantitis depends on the severity of peri-implant bone defects. Peri-implantitis with mild bone defects is treated by nonsurgical treatment, peri-implantitis with severe bone defects is recommended to remove the implant, and peri-implantitis with moderate bone defects is further judged according to the shape of the bone defects. Four-wall bone pockets, three-wall bone pockets and dehiscence are mostly treated by bone regenerative surgery. For shallow two-wall bone pockets, one-wall bone pockets and horizontal bone resorption, bone resection is often used. However, most peri-implantitis has a variety of bone defect forms at the same time, which need to be treated with bone regenerative surgery and bone resection surgery.

The cost-effectiveness and abundance of sodium make sodium-ion batteries a compelling alternative to lithium-ion batteries. The hurdle is adapting the widely used graphite anodes in lithium-ion batteries for use in sodium-ion battery anodes, given the larger size of sodium. Macroporous carbon materials emerge as promising anode candidates for sodium-ion batteries due to their favorable electrolyte penetration and structural stability. In this research, an economical and readily available high-temperature coal pitch serves as the precursor for the anode material. Sodium chloride acts as the templating agent, while phosphorus atoms are intentionally introduced through disodium hydrogen phosphate to induce defects. The phosphorus-doped macroporous carbon demonstrates noteworthy specific capacity and cycling stability, even under high current density conditions, making it a viable choice for application in sodium-ion batteries: after 1000 cycles at a current density of 5 A g−1, the reversible specific capacity still reaches 135 mA h g−1 with a capacity retention rate of 94.4%; after increasing the current density to 10 A g−1, the reversible specific capacity still exceeds 100 mA h g−1 after 3500 cycles. [ABSTRACT FROM AUTHOR]

The hydrolysis of an industrial titanyl sulfate (TiOSO4) solution to metatitanic acid (H2TiO3) is the crucial step in the production of titanium dioxide (TiO2) using the sulfuric acid process, and the extra-adding seeded route is generally adopted in industry, in which the quality of the crystal seeds plays a critical role. In this study, the optimal process conditions for preparing the crystal seeds via the NaOH neutralization method were first investigated. Then, the ultrasound-assisted preparation of crystal seeds was studied to explore the effect of the ultrasonic time and intensity on the particle size and particle size distribution of crystal seeds. The results demonstrated that ultrasonic assistance is helpful in obtaining crystal seeds with smaller particle sizes and more uniform particle size distribution, and the quality of the hydrolysis product of H2TiO3, i.e., the particle size and its distribution, is strictly correlated with those of the crystal seeds. Under the optimal process conditions for preparing the hydrolytic seeds, the average particle of the hydrolytic seeds prepared without ultrasonic assistance is 25.50 nm. In contrast, the introduction of ultrasonic assistance in the preservation stage could significantly decrease the particle size and narrow the particle size distribution of the hydrolytic seeds. When the ultrasonic time is 4 min and the ultrasonic intensity is 40 W, the average particle of the hydrolytic seeds is decreased to 23.48 nm. Therefore, the quality of the crystal seeds, as well as that of H2TiO3 products, could be significantly improved by introducing ultrasonic assistance with a suitable intensity at a suitable time in the preparation process of crystal seeds via the NaOH neutralization method. [ABSTRACT FROM AUTHOR]

Anatase TiO2 has been widely reported using as anodes of sodium-ion battery (SIB) due to its eco-friendly, electrochemical stability and favorable capacity of sodium ions storage. Herein, a facile and efficient method based on pyrolysis process converting polydopamine-coated industrial metatitanic acid to N-doped carbon-coated anatase TiO2 (TiO2@C) was introduced for sodium ion battery. The electrochemical measurements demonstrated that the TiO2@C sample delivered a reversible capacity of 270 mA h g−1 at a current of 0.1 A g−1 after 100 cycles in ether-based electrolyte. In particular, within ester-based electrolyte, an ultralong cycling life on the sample TiO2@C was obtained, 130 mA h g−1 at 1 A g−1 after 10,000 cycles. Furthermore, the Na-ion full-cell assembled TiO2@C with Na3V2(PO4)3 in ester-based electrolyte demonstrated an energy density as high as ca. 300 W h kg−1. [ABSTRACT FROM AUTHOR]

BACKGROUND. The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the 'vulnerable plaque,' necessitating an improved approach for predicting onset of symptoms. METHODS. We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques. Proteomics data were integrated with gene expression profiling of 121 carotid endarterectomies and an analysis of protein secretion by lipid-loaded human vascular smooth muscle cells. Finally, epidemiological validation of candidate biomarkers was performed in two community-based studies. RESULTS. Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study. CONCLUSION. The identified 4-biomarker signature may improve risk prediction and diagnostics for the management of cardiovascular disease. Further, our study highlights the strength of tissue-based proteomics for biomarker discovery. FUNDING. UK: British Heart Foundation (BHF); King's BHF Center; and the National Institute for Health Research Biomedical Research Center based at Guy's and St Thomas' NHS Foundation Trust and King's College London in partnership with King's College Hospital. Austria: Federal Ministry for Transport, Innovation and Technology (BMVIT); Federal Ministry of Science, Research and Economy (BMWFW); Wirtschaftsagentur Wien; and Standortagentur Tirol., Introduction Atherosclerosis is a chronic and progressive disease of the arterial wall and the main underlying cause of stroke, myocardial infarction (MI), and cardiac death (1, 2). The evolution of [...]