Cholesterol homeostasis is vital for proper cellular and systemic functions. Disturbed cholesterol balance underlies not only cardiovascular disease but also an increasing number of other diseases ...such as neurodegenerative diseases and cancers. The cellular cholesterol level reflects the dynamic balance between biosynthesis, uptake, export and esterification - a process in which cholesterol is converted to neutral cholesteryl esters either for storage in lipid droplets or for secretion as constituents of lipoproteins. In this Review, we discuss the latest advances regarding how each of the four parts of cholesterol metabolism is executed and regulated. The key factors governing these pathways and the major mechanisms by which they respond to varying sterol levels are described. Finally, we discuss how these pathways function in a concerted manner to maintain cholesterol homeostasis.
Cholesterol metabolism produces essential membrane components as well as metabolites with a variety of biological functions. In the tumour microenvironment, cell-intrinsic and cell-extrinsic cues ...reprogram cholesterol metabolism and consequently promote tumourigenesis. Cholesterol-derived metabolites play complex roles in supporting cancer progression and suppressing immune responses. Preclinical and clinical studies have shown that manipulating cholesterol metabolism inhibits tumour growth, reshapes the immunological landscape and reinvigorates anti-tumour immunity. Here, we review cholesterol metabolism in cancer cells, its role in cancer progression and the mechanisms through which cholesterol metabolites affect immune cells in the tumour microenvironment. We also discuss therapeutic strategies aimed at interfering with cholesterol metabolism, and how the combination of such approaches with existing anti-cancer therapies can have synergistic effects, thus offering new therapeutic opportunities.
Cholesterol metabolism has been linked to immune functions, but the mechanisms by which cholesterol biosynthetic signaling orchestrates inflammasome activation remain unclear. Here, we have shown ...that NLRP3 inflammasome activation is integrated with the maturation of cholesterol master transcription factor SREBP2. Importantly, SCAP-SREBP2 complex endoplasmic reticulum-to-Golgi translocation was required for optimal activation of the NLRP3 inflammasome both in vitro and in vivo. Enforced cholesterol biosynthetic signaling by sterol depletion or statins promoted NLPR3 inflammasome activation. However, this regulation did not predominantly depend on changes in cholesterol homeostasis controlled by the transcriptional activity of SREBP2, but relied on the escort activity of SCAP. Mechanistically, NLRP3 associated with SCAP-SREBP2 to form a ternary complex which translocated to the Golgi apparatus adjacent to a mitochondrial cluster for optimal inflammasome assembly. Our study reveals that, in addition to controlling cholesterol biosynthesis, SCAP-SREBP2 also serves as a signaling hub integrating cholesterol metabolism with inflammation in macrophages.
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•NLRP3 inflammasome activation couples SREBP2 maturation•SCAP-SREBP2 translocation and S1P are required for optimal NLRP3 inflammasome activity•SCAP escorts both NLRP3 and SREBP2 by forming a ternary complex•SCAP-SREBP2 inhibition protects mice from systemic inflammation
The metabolic-inflammatory crosstalk plays a key role in host defense against pathogens and inflammation. Guo and colleagues demonstrate that SCAP-SREBP2 complex integrates NLRP3 inflammasome activation and cholesterol biosynthetic signaling during inflammation.
Ultrathin, 2D organic layers of sub‐ten nanometer thicknesses and high aspect ratios have received a great deal of attention for their graphene‐like topological features and emerging properties. ...Rational synthetic strategies have led to the realization of periodic 2D layers with unprecedented structural precision. Herein, recent progress on the synthesis of 2D organic layers, including methods based on both non‐covalent and covalent interactions, is summarized, and potential applications are highlighted. Such 2D organic nanostructures have a brilliant future as prospective multifunctional materials, showing great promise as platforms for engineering novel optoelectronic, interfacial, and bioactive properties.
Two‐dimensional organic layers of molecular thickness and large surface area attract great interest from both synthetic chemists and materials scientists. Impressive synthetic progress has been made toward the fabrication of isolated layers with structural precision reaching the atomic level. The most recent synthetic advances are highlighted and linked to their functional perspectives.
The ability to confine light is important both scientifically and technologically. Many light confinement methods exist, but they all achieve confinement with materials or systems that forbid ...outgoing waves. These systems can be implemented by metallic mirrors, by photonic band-gap materials, by highly disordered media (Anderson localization) and, for a subset of outgoing waves, by translational symmetry (total internal reflection) or by rotational or reflection symmetry. Exceptions to these examples exist only in theoretical proposals. Here we predict and show experimentally that light can be perfectly confined in a patterned dielectric slab, even though outgoing waves are allowed in the surrounding medium. Technically, this is an observation of an 'embedded eigenvalue'--namely, a bound state in a continuum of radiation modes--that is not due to symmetry incompatibility. Such a bound state can exist stably in a general class of geometries in which all of its radiation amplitudes vanish simultaneously as a result of destructive interference. This method to trap electromagnetic waves is also applicable to electronic and mechanical waves.
Cholesterol is dynamically transported among organelles, which is essential for multiple cellular functions. However, the mechanism underlying intracellular cholesterol transport has remained largely ...unknown. We established an amphotericin B-based assay enabling a genome-wide shRNA screen for delayed LDL-cholesterol transport and identified 341 hits with particular enrichment of peroxisome genes, suggesting a previously unappreciated pathway for cholesterol transport. We show dynamic membrane contacts between peroxisome and lysosome, which are mediated by lysosomal Synaptotagmin VII binding to the lipid PI(4,5)P2 on peroxisomal membrane. LDL-cholesterol enhances such contacts, and cholesterol is transported from lysosome to peroxisome. Disruption of critical peroxisome genes leads to cholesterol accumulation in lysosome. Together, these findings reveal an unexpected role of peroxisome in intracellular cholesterol transport. We further demonstrate massive cholesterol accumulation in human patient cells and mouse model of peroxisomal disorders, suggesting a contribution of abnormal cholesterol accumulation to these diseases.
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•Genome-wide RNAi screen reveals 341 genes important for cholesterol transport•Lysosomal Syt7 binds peroxisomal PI(4,5)P2 to bridge the organelle contact•Organelle contacts mediate cholesterol transport from lysosome to peroxisome•Cholesterol is accumulated in cells and animal models of peroxisomal disorders
Lysosome forms dynamic membrane contacts with peroxisome, and cholesterol is transported from lysosome to peroxisome. Massive cholesterol accumulates in the cells from patients with peroxisomal disorders.
Extreme fast charging (XFC) of high‐energy Li‐ion batteries is a key enabler of electrified transportation. While previous studies mainly focused on improving Li ion mass transport in electrodes and ...electrolytes, the limitations of charge transfer across electrode–electrolyte interfaces remain underexplored. Herein we unravel how charge transfer kinetics dictates the fast rechargeability of Li‐ion cells. Li ion transfer across the cathode–electrolyte interface is found to be rate‐limiting during XFC, but the charge transfer energy barrier at both the cathode and anode have to be reduced simultaneously to prevent Li plating, which is achieved through electrolyte engineering. By unlocking charge transfer limitations, 184 Wh kg−1 pouch cells demonstrate stable XFC (10‐min charge to 80 %) which is otherwise unachievable, and the lifetime of 245 Wh kg−1 21700 cells is quintupled during fast charging (25‐min charge to 80 %).
Extreme fast charging of high‐energy Li‐ion batteries is achieved by simultaneously reducing the anode and cathode charge transfer energy barriers through electrolyte engineering. Ah‐level commercial cells demonstrate rapid charging from 0 to 80 % state of charge (SOC) within 10 to 25 minutes.
Wastewater-based epidemiology (WBE) has become a valuable tool for monitoring SARS-CoV-2 infection trends throughout the COVID-19 pandemic. Population biomarkers that measure the relative human fecal ...contribution to normalize SARS-CoV-2 wastewater concentrations are needed for improved analysis and interpretation of community infection trends. The Centers for Disease Control and Prevention National Wastewater Surveillance System (CDC NWSS) recommends using the wastewater flow rate or human fecal indicators as population normalization factors. However, there is no consensus on which normalization factor performs best. In this study, we provided the first multistate assessment of the effects of flow rate and human fecal indicators (crAssphage, F+ Coliphage, and PMMoV) on the correlation of SARS-CoV-2 wastewater concentrations and COVID-19 cases using the CDC NWSS dataset of 182 communities across six U.S. states. Flow normalized SARS-CoV-2 wastewater concentrations produced the strongest correlation with COVID-19 cases. The correlation from the three human fecal indicators were significantly lower than flow rate. Additionally, using reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) significantly improved correlation values over samples that were analyzed with real-time reverse transcription quantitative polymerase chain reaction (rRT-qPCR). Our assessment shows that utilizing flow normalization with RT-ddPCR generate the strongest correlation between SARS-CoV-2 wastewater concentrations and COVID-19 cases.
Glucose and fatty acids are the major sources of energy for human body. Cholesterol, the most abundant sterol in mammals, is a key component of cell membranes although it does not generate ATP. The ...metabolisms of glucose, fatty acids and cholesterol are often intertwined and regulated. For example, glucose can be converted to fatty acids and cholesterol through de novo lipid biosynthesis pathways. Excessive lipids are secreted in lipoproteins or stored in lipid droplets. The metabolites of glucose and lipids are dynamically transported intercellularly and intracellularly, and then converted to other molecules in specific compartments. The disorders of glucose and lipid metabolism result in severe diseases including cardiovascular disease, diabetes and fatty liver. This review summarizes the major metabolic aspects of glucose and lipid, and their regulations in the context of physiology and diseases.
Microbial fuel cells (MFCs) have got tremendous attention for their capability to enhance the degradation of some recalcitrant pollutants and simultaneous electricity production. A microbial fuel ...cell coupled constructed wetland (CW-MFC) is a new device to treat the wastewater and produce energy which has more wastewater treatment volume and more easily to maintenance than others MFCs. The studies on the performance of CW-MFCs are necessary. In this work, the effects of hydraulic residence time (HRT), reactive brilliant red X-3B (ABRX3) proportion and COD concentration on the electricity production of CW-MFC and the degradation characteristics of ABRX3 were investigated. The decolorization rate and the electricity production increased to a peak before slowing down with the elongation of HRT. The highest decolorization rate and electricity production were obtained when HRT was 3 days. The ABRX3 proportion (calculated as COD) in the wastewater played an important role in decolorization and electricity production, which may influence the distribution of electrons in the system. The power density of CW-MFC and the decolorization rate decreased concomitantly with an increasing ABRX3 proportion. The COD concentration influenced the CW-MFC performance slightly. The highest decolorization rate and power density reached 95.6% and 0.852 W/m(3), respectively, when the COD concentration was 300 mg/L while the ABRX3 proportion was 30%. The coulombic efficiency of the CW-MFC depended on glucose and ABRX3 proportions in the wastewater. ABRX3 acquired more electrons than the anode. Further investigations are needed to optimize CW-MFC performance and explain the mechanism of biorefractory compounds degradation and electron motion in CW-MFCs.
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