Non-Hermitian topological whispering gallery.

In 1878, Lord Rayleigh observed the highly celebrated phenomenon of sound waves that creep around the curved gallery of St Paul's Cathedral in London1,2. These whispering-gallery waves scatter efficiently with little diffraction around an enclosure and have since found applications in ultrasonic fatigue and crack testing, and in the optical sensing of nanoparticles or molecules using silica microscale toroids. Recently, intense research efforts have focused on exploring non-Hermitian systems with cleverly matched gain and loss, facilitating unidirectional invisibility and exotic characteristics of exceptional points3,4. Likewise, the surge in physics using topological insulators comprising non-trivial symmetry-protected phases has laid the groundwork in reshaping highly unconventional avenues for robust and reflection-free guiding and steering of both sound and light5,6. Here we construct a topological gallery insulator using sonic crystals made of thermoplastic rods that are decorated with carbon nanotube films, which act as a sonic gain medium by virtue of electro-thermoacoustic coupling. By engineering specific non-Hermiticity textures to the activated rods, we are able to break the chiral symmetry of the whispering-gallery modes, which enables the out-coupling of topological 'audio lasing' modes with the desired handedness. We foresee that these findings will stimulate progress in non-destructive testing and acoustic sensing.

Pseudospin-dependent acoustic topological edge and corner states in silica aerogel metamaterialsa).

Fueled by the concepts of topological insulators, analogous topological acoustics offer an alternative approach to manipulate sound. Theoretical proposals for subwavelength acoustic topological insulators are considered to be ideal effective parameters or utilizeing artificial coiling-space metamaterials. However, the corresponding realization using realistic soft metamaterials remains challenging. In this study, we present the design of an acoustic subwavelength second-order topological insulator using nanoscale porous solid material, silica aerogel, which supports pseudospin-dependent topological edge and corner states simultaneously. Through simulations and experiments, we demonstrate that silica aerogel can function as a soft acoustic metamaterial at the subwavelength scale. By embedding silica aerogel in an air matrix to construct a honeycomb lattice, a double Dirac cone is obtained. A topological phase transition is induced by expanding or contracting the supercell, resulting in band inversion. Additionally, we propose topologically robust acoustic transmission along the one-dimensional edge. Furthermore, we discover that the proposed sonic crystal sustains zero-dimensional corner states, which can efficiently confine energy at subwavelength corners. These findings offer potential for the realization of subwavelength topological acoustic devices using realistic soft metamaterials.

Anti-Parity-Time Symmetry in a Su-Schrieffer-Heeger Sonic Lattice.

The Su-Schrieffer-Heeger (SSH) model is an important cornerstone in modern condensed-matter topology, yet it is the simplest one-dimensional (1D) tight binding approach to dwell into the characteristics of spinless electrons in chains of staggered bonds. Moreover, the chiral symmetry assures that its surface-confining states pin to zero energy, i.e., they reside midgap in the energy dispersion. Symmetry is also an attribute related to artificial media that are subject to parity P and time-reversal T operations. This non-Hermitian family has been thoroughly nourished in a wave-based context, where anti-PT (APT) symmetric systems are the youngest belonging members, permitting refractionless optics, inverse PT-symmetry breaking transition, and asymmetric mode switching. Here, we report the first extension of APT symmetry in an acoustic setting by endowing a SSH lattice with gain and loss components. We show that the in-gap topological defect state hinges on the non-Hermitian phase, in that the broken symmetry suppresses it, yet when PT or APT symmetry is intact, it is observed with either damped or evanescent decay, respectively. Our experiments showcase how the non-Hermitian SSH lattice serves as a utile platform to investigate topological properties across various PT symmetric phases using sound.

Echinocystic acid prevents obesity and fatty liver via interacting with FABP1.

Long-term high-fat diet (HFD) will lead to obesity and their complications. Echinocystic acid (EA), a triterpene, shows anti-inflammatory and antioxidant effects. We predict that EA supplementation can prevent obesity, diabetes, and nonalcoholic steatohepatitis. To test our hypothesis, we investigated the effects of EA supplementation on mice with HFD-induced obesity in vivo and in vitro by adding EA to the diet of mice and the medium of HepG2 cells, the protein target of EA was analyzed by molecular docking. The results showed that EA ameliorated obesity and inhibited blood triglyceride and liver triglyceride concentrations than those in the HFD groups. The data on molecular docking indicated that FABP1 was a potential target of EA. Further experimental results confirmed that EA affected the triglyceride level by regulating the function of FABP1. This study may provide a new potential inhibitor for FABP1 and a new strategy for the treatment of obesity.

Comprehensive analysis of the translatome reveals the relationship between the translational and transcriptional control in high fat diet-induced liver steatosis.

Translational regulation plays a critical role in gene expression. However, there are few genome-wide studies on translational regulation in non-alcoholic fatty liver disease (NAFLD), which is a severe non-communicable epidemic worldwide. In this study, we performed RNC-mRNA (mRNAs bound to ribosome-nascent chain complex) sequencing and mRNA sequencing to probe the translation status of high-fat-diet (HFD) induced mouse fatty liver. Generally, in the HFD group compared to the control group, changes of translation ratios and changes in mRNA abundance had a negative correlation. The relative abundance of RNC-mRNAs and mRNAs were positively correlated, yet the former changed more slowly than the latter. However, the rate of change became more balanced when it came to the livers of mice that were fed the HFD plus lycopene, an antioxidant. This indicated relatively independent roles of translational modulation and transcriptional regulation. Furthermore, many genes were differentially regulated at the transcriptional or translational levels, suggesting a new screening strategy for functional genes. In conclusion, our analysis revealed the different and correlated role of translational control with transcriptional regulation in the HFD-induced mouse fatty liver relative to the control, which indicates critical roles of translational control for liver steatosis; thus, adding a new dimension towards a better understanding and improvement of treatment for NAFLD.

Non-Hermitian Sonic Second-Order Topological Insulator.

Topological phases of matter that have been recently extended to topological phases of sound can confine acoustic energy at the corners of higher-order topological insulators. We broaden this concept by incorporating parity-time symmetry and show new topologically protected confinement rules that are dictated by the geometrical arrangement of gain and loss units. Particularly, our findings reveal how sound trapping occurs at all corners when parity-time symmetry is intact, beyond the exceptional point within the broken phase; however, opposite corners sustain either sink- or sourcelike states that could lead to novel non-Hermitian guides for sound.

Comparison of plantar loads among runners with different strike patterns.

This study aimed to explore the plantar loading variables between habitual rearfoot strike (RFS) and non-rearfoot strike (NRFS) during running. 78 healthy males participated in this study (41 RFS, 37 NRFS). In-shoe pressure sensors were used to measure plantar loading while the participants were running on a 15 m indoor runway with their preferred foot strike pattern (FSP) at 12.0 ± 5% km/h. Results indicate that force and pressure parameters were much higher in the rearfoot and midfoot regions during RFS running and relatively greater in forefoot region during NRFS running. However, compared with NRFS running, the contact area, maximum force and force-time-integrals during RFS running on total foot were 21.44% (P < 0.001, ES = 2.29), 13.99% (P = 0.006, ES = 0.64) and 21.27% (P < 0.001, ES = 0.85) higher, respectively. Total foot peak pressure and pressure-time-integral between two FSPs were similar. Higher loads in the rearfoot region may transmit to the knee joint and result in patellofemoral joint injuries. NRFS runners' higher loads in forefoot seem to be ralated to metatarsal stress fractures and compensatory damage to the Achilles tendon. Therefore, runners should choose proper FSPs according to their unique physical conditions.

Proteomic Analyses of Cysteine Redox in High-Fat-Fed and Fasted Mouse Livers: Implications for Liver Metabolic Homeostasis.

Intensive oxidative stress occurs during high-fat-diet-induced hepatic fat deposition, suggesting a critical role for redox signaling in liver metabolism. Intriguingly, evidence shows that fasting could also result in redox-profile changes largely through reduced oxidant or increased antioxidant levels. However, a comprehensive landscape of redox-modified hepatic substrates is lacking, thereby hindering our understanding of liver metabolic homeostasis. We employed a proteomic approach combining iodoacetyl tandem mass tag and nanoliquid chromatography tandem mass spectrometry to quantitatively probe the effects of high-fat feeding and fasting on in vivo redox-based cysteine modifications. Compared with control groups, ∼60% of cysteine residues exhibited downregulated oxidation ratios by fasting, whereas ∼94% of these ratios were upregulated by high-fat feeding. Importantly, in fasted livers, proteins exhibiting diminished cysteine oxidation were annotated in pathways associated with fatty acid metabolism, carbohydrate metabolism, insulin, peroxisome proliferator-activated receptors, and oxidative respiratory chain signaling, suggesting that fasting-induced redox changes targeted major metabolic pathways and consequently resulted in hepatic lipid accumulation.

FTO reduces mitochondria and promotes hepatic fat accumulation through RNA demethylation.

Fat mass and obesity-associated protein (FTO) is a RNA demethylase, whether FTO regulates fat metabolism through its demethylation is unclear. The results of this study confirmed that N6-methyladenosine (m6 A) is associated with fat accumulation both in vivo and in vitro. The data showed that FTO down-regulated m6 A levels, decreased mitochondrial content, and increased triglyceride (TG) deposition. However, an FTO (R316A) mutant lacking demethylation activity could not regulate mitochondria and TG content, indicating that FTO affects mitochondrial content and fat metabolism by modulating m6 A levels in hepatocytes. In addition, the regulatory roles of cycloleucine (methylation inhibitor) and betaine (methyl donor) could regulate m6 A levels and fat deposition. This work clarified that the demethylation function of FTO plays an essential role in the fat metabolism of hepatocytes and links the epigenetic modification of RNA with fat deposition, thereby providing a new target (m6 A) for regulation of hepatic fat metabolism.

Topological Creation of Acoustic Pseudospin Multipoles in a Flow-Free Symmetry-Broken Metamaterial Lattice.

The discovery of topological acoustics has revolutionized fundamental concepts of sound propagation, giving rise to strikingly unconventional acoustic edge modes immune to scattering. Because of the spinless nature of sound, the "spinlike" degree of freedom crucial to topological states in acoustic systems is commonly realized with circulating background flow or preset coupled resonator ring waveguides, which drastically increases the engineering complexity. Here we realize the acoustic pseudospin multipolar states in a simple flow-free symmetry-broken metamaterial lattice, where the clockwise (anticlockwise) sound propagation within each metamolecule emulates pseudospin down (pseudospin up). We demonstrate that tuning the strength of intermolecular coupling by simply contracting or expanding the metamolecule can induce the band inversion effect between the pseudospin dipole and quadrupole, which leads to a topological phase transition. Topologically protected edge states and reconfigurable topological one-way transmission for sound are further demonstrated. These results provide diverse routes to construct novel acoustic topological insulators with versatile applications.

Characteristics of Plantar Loads During Walking in Patients with Knee Osteoarthritis.

BACKGROUND Knee osteoarthritis (KOA) is a common disease that can change the load on lower limbs during walking. Plantar loads in patients with KOA may provide a basis for clinical decisions regarding footwear and foot orthoses. This study aimed to compare plantar loads in females with and without KOA during gait. MATERIAL AND METHODS Plantar pressure during walking was recorded in 23 females with KOA and 23 females without KOA. Maximum force (MF), contact area (CA), and peak pressure (PP) were measured at 7 different regions underneath the foot, named heel (M1), midfoot (M2), first metatarsophalangeal joint (MPJ) (M3), second MPJ (M4), third to fifth MPJ (M5), hallux (M6), and lesser toes (M7). RESULTS PPs for M2 and (M3) in females with KOA were higher than those in females without KOA. High PPs were also found in females with KOA for M2, M3, and M4. CONCLUSIONS Increased plantar loading in females with KOA may lead to foot pronation and gait changes during walking. Plantar loading may be offered to patients with KOA when considering footwear and foot orthoses.

Deletion of the mitochondrial calcium uniporter in adipose tissue promotes energy expenditure and alleviates diet-induced obesity.

OBJECTIVE: Studies have shown a correlation between obesity and mitochondrial calcium homeostasis, yet it is unclear whether and how Mcu regulates adipocyte lipid deposition. This study aims to provide new potential target for the treatment of obesity and related metabolic diseases, and to explore the function of Mcu in adipose tissue. METHODS: We firstly investigated the role of mitoxantrone, an Mcu inhibitor, in the regulation of glucose and lipid metabolism in mouse adipocytes (3T3-L1 cells). Secondly, C57BL/6J mice were used as a research model to investigate the effects of Mcu inhibitors on fat accumulation and glucose metabolism in mice on a high-fat diet (HFD), and by using CRISPR/Cas9 technology, adipose tissue-specific Mcu knockdown mice (Mcufl/+ AKO) and Mcu knockout of mice (Mcufl/fl AKO) were obtained, to further investigate the direct effects of Mcu on fat deposition, glucose tolerance and insulin sensitivity in mice on a high-fat diet. RESULTS: We found the Mcu inhibitor reduced adipocytes lipid accumulation and adipose tissues mass in mice fed an HFD. Both Mcufl/+ AKO mice and Mcufl/fl AKO mice were resistant to HFD-induced obesity, compared to control mice. Mice with Mcufl/fl AKO showed improved glucose tolerance and insulin sensitivity as well as reduced hepatic lipid accumulation. Mechanistically, inhibition of Mcu promoted mitochondrial biogenesis and adipocyte browning, increase energy expenditure and alleviates diet-induced obesity. CONCLUSIONS: Our study demonstrates a link between adipocyte lipid accumulation and mCa2+ levels, suggesting that adipose-specific Mcu deficiency alleviates HFD-induced obesity and ameliorates metabolic disorders such as insulin resistance and hepatic steatosis. These effects may be achieved by increasing mitochondrial biosynthesis, promoting white fat browning and enhancing energy metabolism.

Maximum Decentral Projection Margin Classifier for High Dimension and Low Sample Size problems.

Compared with relatively easy feature creation or generation in data analysis, manual data labeling needs a lot of time and effort in most cases. Even if automated data labeling​ seems to make it better in some cases, the labeling results still need to be checked and verified by manual. The High Dimension and Low Sample Size (HDLSS) data are therefore very common in data mining and machine learning. For classification problems with the HDLSS data, due to data piling and approximate equidistance between any two input points in high-dimension space, some traditional classifiers often give poor predictive performance. In this paper, we propose a Maximum Decentral Projection Margin Classifier (MDPMC) in the framework of a Support Vector Classifier (SVC). In the MDPMC model, the constraints of maximizing the projection distance between decentralized input points and their supporting hyperplane are integrated into the SVC model in addition to maximizing the margin of two supporting hyperplanes. On ten real HDLSS datasets, the experiment results show that the proposed MDPMC approach can deal well with data piling and approximate equidistance problems. Compared with SVC with Linear Kernel (SVC-LK) and Radial Basis Function Kernel (SVC-RBFK), Distance Weighted Discrimination (DWD), weighted DWD (wDWD), Distance-Weighted Support Vector Machine (DWSVM), Population-Guided Large Margin Classifier (PGLMC), and Data Maximum Dispersion Classifier (DMDC), MDPMC obtains better predictive accuracy and lower classification errors than the other seven classifiers on the HDLSS data.

BATF relieves hepatic steatosis by inhibiting PD1 and promoting energy metabolism.

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) has become a global health threat that needs to be addressed urgently. Basic leucine zipper ATF-like transcription factor (BATF) is commonly thought to be involved in immunity, but its effect on lipid metabolism is not clear. Here, we investigated the function of BATF in hepatic lipid metabolism. BATF alleviated high-fat diet (HFD)-induced hepatic steatosis and inhibited elevated programmed cell death protein (PD)1 expression induced by HFD. A mechanistic study confirmed that BATF regulated fat accumulation by inhibiting PD1 expression and promoting energy metabolism. PD1 antibodies alleviated hepatic lipid deposition. In conclusion, we identified the regulatory role of BATF in hepatic lipid metabolism and that PD1 is a target for alleviation of NAFLD. This study provides new insights into the relationship between BATF, PD1, and NAFLD.

The Roles of Natural Alkaloids and Polyphenols in Lipid Metabolism: Therapeutic Implications and Potential Targets in Metabolic Diseases.

The prevalence of obesity and its associated diseases has increased dramatically, and they are major threats to human health worldwide. A variety of approaches, such as physical training and drug therapy, can be used to reduce weight and reverse associated diseases; however, the efficacy and the prognosis are often unsatisfactory. It has been reported that natural food-based small molecules can prevent obesity and its associated diseases. Among them, alkaloids and polyphenols have been demonstrated to regulate lipid metabolism by enhancing energy metabolism, promoting lipid phagocytosis, inhibiting adipocyte proliferation and differentiation, and enhancing the intestinal microbial community to alleviate obesity. This review summarizes the regulatory mechanisms and metabolic pathways of these natural small molecules and reveals that the binding targets of most of these molecules are still undefined, which limits the study of their regulatory mechanisms and prevents their further application. In this review, we describe the use of Discovery Studio for the reverse docking of related small molecules and provide new insights for target protein prediction, scaffold hopping, and mechanistic studies in the future. These studies will provide a theoretical basis for the modernization of anti-obesity drugs and promote the discovery of novel drugs.

Structured sonic tube with carbon nanotube-like topological edge states.

A single-wall carbon nanotube can be viewed as a one-dimensional material created by rolling up a sheet of graphene. Its electronic band structure depends on the chirality, i.e., how the sheet has been rolled up, yet synthesizing the symmetry at will is rather challenging. We structure an artificial honeycomb lattice in both a zigzag and an armchair tube and explore their topological features for sound. Our findings reveal how armchair tubes remain gapless, whereas the zigzag counterparts host nontrivial edge states of non-zero quantized Zak phase, which are dictated by the circumferential number of units. Unlike man-made planar lattices whose underling symmetry must be broken to harvest quantum Hall and pseudospin phases, interestingly, the structured tubular lattice symmetry remains intact, while its nontrivial phase alone is governed by the chirality and the tube diameter. We foresee that our results, not only for sound, but also in photonics, mechanics and electronics will broaden future avenues for fundamental and applied sciences.

A New lncRNA, lnc-LLMA, Regulates Lipid Metabolism in Pig Hepatocytes.

A large variety of long noncoding RNAs (lncRNAs) have been discovered through high-throughput sequencing technology and some have been demonstrated to play important roles in lipid metabolism regulation. In our study, we found a highly expressed lncRNA (lnc-LLMA, liver lipid metabolism-associated lncRNA) in the liver of Duroc pigs, which was enriched in the nucleus. It displays potent tissue specificity among different pig breeds. Overexpression of lnc-LLMA can cause a decline in intracellular triglyceride (TG) levels and increases in ATP and mitochondrial DNA levels in pig primary hepatocytes and HepG2 cells. In addition, the expression levels of MTTP, APOB, CPT1α, and other genes were increased by overexpression of lnc-LLMA. It downregulated expression of G6Pase and SREBP1 genes. Chromatin isolation by RNA purification (ChRIP) experiments demonstrated that microsomal triglyceride transfer protein (MTTP) and glycogen synthase 2 (GYS2) were the potential interacting proteins of lnc-LLMA. The overexpression of the GYS2 gene rescued the decreasing intracellular TG levels caused by the increase of lnc-LLMA. Similarly, overexpression of MTTP was also able to save the lnc-LLMA-induced decrease in intracellular TG. Our study demonstrated that this novel lncRNA was closely related to lipid metabolism and affected lipid transport and mitochondrial function through MTTP and GYS2. Our results provided a new direction for further studying the effect of lncRNA on lipid metabolism regulation.

Ruthenium 360 and mitoxantrone inhibit mitochondrial calcium uniporter channel to prevent liver steatosis induced by high-fat diet.

BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD) affects over 25% of the general population and lacks an effective treatment. Recent evidence implicates disrupted mitochondrial calcium homeostasis in the pathogenesis of hepatic steatosis. EXPERIMENTAL APPROACH: In this study, mitochondrial calcium uniporter (MCU) was inhibited through classical genetic approaches, viral vectors or small molecule inhibitors in vivo to study its role in hepatic steatosis induced by high-fat diet (HFD). In vitro, MCU was overexpressed or inhibited to change mitochondrial calcium homeostasis, endoplasmic reticulum-mitochondrial linker was adopted to increase mitochondria-associated membranes (MAMs) and MICU1-EF hand mutant was used to decrease the sensitivity of mitochondrial calcium uptake 1 (MICU1) to calcium and block MCU channel. KEY RESULTS: Here, we found that inhibition of liver MCU by AAV virus and classical genetic approaches can prevent HFD-induced liver steatosis. MCU regulates mitochondrial calcium homeostasis and affects lipid accumulation in liver cells. In addition, a HFD in mice enlarged the MAM. The high-calcium environment produced by MAM invalidated the function of MICU1 and led to persistent open of MCU channels. Therefore, it caused mitochondrial calcium overload and liver fat deposition. Inhibition of MAM and MCU alleviated HFD-induced hepatic steatosis. MCU inhibitors (Ru360 and mitoxantrone) can block MCU channels and reduce mitochondrial calcium levels. Intraperitoneal injection of MCU inhibitors (0.01-µM·kg-1 bodyweight) can alleviate HFD-induced hepatic steatosis. CONCLUSION AND IMPLICATIONS: These findings provide molecular insights into the way HFD disrupts mitochondrial calcium homeostasis and identify MCU as a promising drug target for the treatment of hepatic steatosis.

Prediction of protein interaction hot spots using rough set-based multiple criteria linear programming.

Protein-protein interactions are fundamentally important in many biological processes and it is in pressing need to understand the principles of protein-protein interactions. Mutagenesis studies have found that only a small fraction of surface residues, known as hot spots, are responsible for the physical binding in protein complexes. However, revealing hot spots by mutagenesis experiments are usually time consuming and expensive. In order to complement the experimental efforts, we propose a new computational approach in this paper to predict hot spots. Our method, Rough Set-based Multiple Criteria Linear Programming (RS-MCLP), integrates rough sets theory and multiple criteria linear programming to choose dominant features and computationally predict hot spots. Our approach is benchmarked by a dataset of 904 alanine-mutated residues and the results show that our RS-MCLP method performs better than other methods, e.g., MCLP, Decision Tree, Bayes Net, and the existing HotSprint database. In addition, we reveal several biological insights based on our analysis. We find that four features (the change of accessible surface area, percentage of the change of accessible surface area, size of a residue, and atomic contacts) are critical in predicting hot spots. Furthermore, we find that three residues (Tyr, Trp, and Phe) are abundant in hot spots through analyzing the distribution of amino acids.

Calcium supplementation relieves high-fat diet-induced liver steatosis by reducing energy metabolism and promoting lipolysis.

Nonalcoholic fatty liver disease (NAFLD) is a chronic disease affecting the health of many people worldwide. Previous studies have shown that dietary calcium supplementation may alleviate NAFLD, but the underlying mechanism is not clear. In this study investigating the effect of calcium on hepatic lipid metabolism, 8-week-old male C57BL/6J mice were divided into four groups (n = 6): (1) mice given a normal chow containing 0.5% calcium (CN0.5), (2) mice given a normal chow containing 1.2% calcium (CN1.2), (3) mice given a high-fat diet (HFD) containing 0.5% calcium (HFD0.5), and (4) mice fed a HFD containing 1.2% calcium (HFD1.2). To understand the underlying mechanism, cells were treated with oleic acid and palmitic acid to mimic the HFD conditions in vitro. The results showed that calcium alleviated the increase in triglyceride accumulation induced by oleic acid and/or palmitic acid in HepG2, AML12, and primary hepatocyte cells. Our data demonstrated that calcium supplementation alleviated HFD-induced hepatic steatosis through increased liver lipase activity, proving calcium is involved in the regulation of hepatic lipid metabolism. Moreover, calcium also increased the level of glycogen in the liver, and at the same time had the effect of reducing glycolysis and promoting glucose absorption. Calcium addition increased calcium levels in the mitochondria and cytoplasm. Taken together, we concluded that calcium supplementation could relieve HFD-induced hepatic steatosis by changing energy metabolism and lipase activity.