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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 is an important structural component of all animal cell membranes that functions in various processes, including membrane dynamics and cell signalling, and is also a precursor of other molecules. Deregulation of cholesterol metabolism — biosynthesis, dietary absorption and cellular uptake, storage and efflux — is linked to many diseases, including cardiovascular and genetic diseases, and cancer. A better understanding of cholesterol metabolism offers the possibility to control systemic cholesterol levels to improve human health.

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. Xu and colleagues provide a comprehensive overview of cholesterol metabolism in cancer cells and its effects on immune cells of the tumour microenvironment, highlighting its effects on cancer growth as well as opportunities for therapeutic intervention.

Exceptional points are singularities in non-Hermitian systems that can produce unusual effects, and it is shown that a Dirac cone in a photonic crystal can generate a continuous ring of exceptional points through flattening the tip of the cone. Lossless parity–time symmetry Exceptional points are singularities in the energy functions of a physical system that can produce unusual effects. Until recently, they existed mainly in theory, but received renewed attention with experimental demonstrations in optical systems such as in lasers with reversed pump dependence and photonic structures with unidirectional transmission or reflection. Most studies involve systems with 'parity–time symmetry', where gain as well as artificial loss is required, an undesirable combination for practical applications. Bo Zhen et al . demonstrate, with theory and experiments, a photonic structure — a thick photonic crystal slab — in which a continuous ring of exceptional points can be created through a carefully tuned energy band structure. The approach could open the way to accessing unusual physical properties that might be exploited, for example, in advanced light sources and control of light propagation. The Dirac cone underlies many unique electronic properties of graphene 1 and topological insulators, and its band structure—two conical bands touching at a single point—has also been realized for photons in waveguide arrays 2 , atoms in optical lattices 3 , and through accidental degeneracy 4 , 5 . Deformation of the Dirac cone often reveals intriguing properties; an example is the quantum Hall effect, where a constant magnetic field breaks the Dirac cone into isolated Landau levels. A seemingly unrelated phenomenon is the exceptional point 6 , 7 , also known as the parity–time symmetry breaking point 8 , 9 , 10 , 11 , where two resonances coincide in both their positions and widths. Exceptional points lead to counter-intuitive phenomena such as loss-induced transparency 12 , unidirectional transmission or reflection 11 , 13 , 14 , and lasers with reversed pump dependence 15 or single-mode operation 16 , 17 . Dirac cones and exceptional points are connected: it was theoretically suggested that certain non-Hermitian perturbations can deform a Dirac cone and spawn a ring of exceptional points 18 , 19 , 20 . Here we experimentally demonstrate such an ‘exceptional ring’ in a photonic crystal slab. Angle-resolved reflection measurements of the photonic crystal slab reveal that the peaks of reflectivity follow the conical band structure of a Dirac cone resulting from accidental degeneracy, whereas the complex eigenvalues of the system are deformed into a two-dimensional flat band enclosed by an exceptional ring. This deformation arises from the dissimilar radiation rates of dipole and quadrupole resonances, which play a role analogous to the loss and gain in parity–time symmetric systems. Our results indicate that the radiation existing in any open system can fundamentally alter its physical properties in ways previously expected only in the presence of material loss and gain.

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.

Theoretical and experimental studies reveal that light can be confined within a planar dielectric photonic crystal slab even though the frequency of this optical bound state is inside the continuous spectrum of extended states from the same symmetry group. Light confinement without mirrors The confinement of light has many practical applications — in optical fibres, waveguides and photonics for instance — but current methods of confinement all use materials or systems such as metallic mirrors that forbid outgoing waves. Here Chia Wei Hsu et al . demonstrate a new approach to confinement that does not rely on mirrors. The authors calculate and go on to show experimentally that for a patterned dielectric slab certain stable optical 'bound states' exist that trap light even though outgoing waves are allowed in the surrounding medium. This new method of trapping electromagnetic waves has wavevector and wavelength selectivity, so is suitable for optical filters, modulators and waveguides. In addition, it can be used with electronic and mechanical waves as well as light. 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 1 , by highly disordered media (Anderson localization 2 ) and, for a subset of outgoing waves, by translational symmetry (total internal reflection 1 ) or by rotational or reflection symmetry 3 , 4 . Exceptions to these examples exist only in theoretical proposals 5 , 6 , 7 , 8 . 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’ 9 —namely, a bound state in a continuum of radiation modes—that is not due to symmetry incompatibility 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 . 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 12 and mechanical waves 14 , 15 .

Statins are inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis, and have been clinically used to treat cardiovascular disease. However, a paradoxical increase of reductase protein following statin treatment may attenuate the effect and increase the side effects. Here we present a previously unexplored strategy to alleviate statin-induced reductase accumulation by inducing its degradation. Inspired by the observations that cholesterol intermediates trigger reductase degradation, we identify a potent degrader, namely Cmpd 81, through structure–activity relationship analysis of sterol analogs. Cmpd 81 stimulates ubiquitination and degradation of reductase in an Insig-dependent manner, thus dramatically reducing protein accumulation induced by various statins. Cmpd 81 can act alone or synergistically with statin to lower cholesterol and reduce atherosclerotic plaques in mice. Collectively, our work suggests that inducing reductase degradation by Cmpd 81 or similar chemicals alone or in combination with statin therapy can be a promising strategy for treating cardiovascular disease. Accumulated HMG-CoA reductase (HMGCR) limits the cholesterol-lowering effect of statins via a feedback loop. Here the authors developed a compound that degrades HMGCR, thus decreasing cholesterol levels and reducing atherosclerotic plaques.

A main determinant of the spatial resolution of live-cell super-resolution (SR) microscopes is the maximum photon flux that can be collected. To further increase the effective resolution for a given photon flux, we take advantage of a priori knowledge about the sparsity and continuity of biological structures to develop a deconvolution algorithm that increases the resolution of SR microscopes nearly twofold. Our method, sparse structured illumination microscopy (Sparse-SIM), achieves ~60-nm resolution at a frame rate of up to 564 Hz, allowing it to resolve intricate structures, including small vesicular fusion pores, ring-shaped nuclear pores formed by nucleoporins and relative movements of inner and outer mitochondrial membranes in live cells. Sparse deconvolution can also be used to increase the three-dimensional resolution of spinning-disc confocal-based SIM, even at low signal-to-noise ratios, which allows four-color, three-dimensional live-cell SR imaging at ~90-nm resolution. Overall, sparse deconvolution will be useful to increase the spatiotemporal resolution of live-cell fluorescence microscopy. The resolution of fluorescence microscopy is increased by incorporating prior information into deconvolution algorithms.

This paper proposes a human activity recognition (HAR) method for frequency-modulated continuous wave (FMCW) radar sensors. The method utilizes a multi-domain feature attention fusion network (MFAFN) model that addresses the limitation of relying on a single range or velocity feature to describe human activity. Specifically, the network fuses time-Doppler (TD) and time-range (TR) maps of human activities, resulting in a more comprehensive representation of the activities being performed. In the feature fusion phase, the multi-feature attention fusion module (MAFM) combines features of different depth levels by introducing a channel attention mechanism. Additionally, a multi-classification focus loss (MFL) function is applied to classify confusable samples. The experimental results demonstrate that the proposed method achieves 97.58% recognition accuracy on the dataset provided by the University of Glasgow, UK. Compared to existing HAR methods for the same dataset, the proposed method showed an improvement of about 0.9–5.5%, especially in the classification of confusable activities, showing an improvement of up to 18.33%.