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The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that Laminaria japonica - and Ascophyllum nodosum -derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in L. japonica -derived fucoidans than those of A. nodosum -derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both A. nodosum - and L. japonica -derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, L. japonica -derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.

Exserolides are isocoumarin derivatives containing lactone moiety. Recently, some isocoumarins have been demonstrated to ameliorate hyperlipidemia, a major factor for inducing cardiovascular diseases. However, the effects and mechanisms of action of exserolides on hyperlipidemia are not known. The aim of this study is to investigate whether the marine fungus Setosphaeria sp.-derived exserolides (compounds I, J, E, and F) exert lipid-lowering effects via improving reverse cholesterol transport (RCT) in vitro . RAW264.7 macrophages and HepG2 cells were used to establish lipid-laden models, and the levels of intracellular lipids and RCT-related proteins were determined by assay kits and Western blotting, respectively. We observed that exserolides (at a 5 μM concentration) significantly decreased intracellular cholesterol and triglyceride levels in oxidized low-density lipoprotein-laden RAW264.7 cells and markedly improved [ 3 H]-cholesterol efflux. Among the four tested compounds, exserolide J increased the protein levels of ATP-binding cassette transporter A1, peroxisome proliferator-activated receptor α (PPARα), and liver X receptor α (LXRα). Furthermore, treatment with exserolides significantly decreased oleic acid-laden lipid accumulation in HepG2 hepatocytes. Mechanistically, exserolides enhance PPARα protein levels; furthermore, compound J increases cholesterol 7 alpha-hydroxylase A1 and LXRα protein levels. Molecular docking revealed that exserolides, particularly compound J, can interact with PPARα and LXRα proteins. These data suggest that the terminal carboxyl group of compound J plays a key role in lowering lipid levels by stimulating LXRα and PPARα proteins. In conclusion, compound J exhibits powerful lipid-lowering effects in vitro . However, its hypolipidemic effects in vivo should be investigated in the future., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interestsWen-gang Song reports financial support was provided by 10.13039/501100001809National Natural Science Foundation of China. Shou-dong Guo reports financial support was provided by 10.13039/501100001809National Natural Science Foundation of China. Not applicable. reports a relationship with Not applicable. that includes:. Not applicable. has patent Not applicable. pending to Not applicable. Not applicable. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Inflammation and dyslipidemia are critical inducing factors of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and control the expression of multiple genes that are involved in lipid metabolism and inflammatory responses. However, synthesized PPAR agonists exhibit contrary therapeutic effects and various side effects in atherosclerosis therapy. Natural products are structural diversity and have a good safety. Recent studies find that natural herbs and compounds exhibit attractive therapeutic effects on atherosclerosis by alleviating hyperlipidemia and inflammation through modulation of PPARs. Importantly, the preparation of natural products generally causes significantly lower environmental pollution compared to that of synthesized chemical compounds. Therefore, it is interesting to discover novel PPAR modulator and develop alternative strategies for atherosclerosis therapy based on natural herbs and compounds. This article reviews recent findings, mainly from the year of 2020 to present, about the roles of natural herbs and compounds in regulation of PPARs and their therapeutic effects on atherosclerosis. This article provides alternative strategies and theoretical basis for atherosclerosis therapy using natural herbs and compounds by targeting PPARs, and offers valuable information for researchers that are interested in developing novel PPAR modulators., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Zhang, Shi, Ma, Lin, Song and Guo.)

Antiferromagnetic (AFM) materials have potential advantages for spintronics due to their robustness, ultrafast dynamics, and magnetotransport effects. However, the missing spontaneous polarization and magnetization hinders the efficient utilization of electronic spin in these AFM materials. Here, we propose a simple way to produce spin-splitting in AFM materials by making the magnetic atoms with opposite spin polarization locating in the different environment (surrounding atomic arrangement), which does not necessarily require the presence of spin-orbital coupling. We confirm our proposal by four different types of two-dimensional AFM materials within the first-principles calculations. Our works provide an intuitional design principle to find or produce spin-splitting in AFM materials., (© 2024 IOP Publishing Ltd.)

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and hyperlipidemia is one major inducing factor of CVD. It is worthy to note that fucoidans are reported to have hypolipidemic activity with species specificity; however, the underlying mechanisms of action are far from clarification. This study is aimed at investigating the plasma lipid-lowering mechanisms of the fucoidan from L. japonica Aresch by detecting the levels of hepatic genes that are involved in lipid metabolism. Our results demonstrated that the fucoidan F3 significantly lowered total cholesterol and triglyceride in C57BL/6J mice fed a high-fat diet. In the mouse liver, fucoidan F3 intervention significantly increased the gene expression of peroxisome proliferator-activated receptor (PPAR) α , liver X receptor (LXR) α and β , and ATP-binding cassette transporter (ABC) G1 and G8 and decreased the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor, cholesterol 7 alpha-hydroxylase A1, and sterol regulatory element-binding protein (SREBP) 1c and SREBP-2. These results demonstrated that the antihyperlipidemic effects of fucoidan F3 are related to its activation of PPAR α and LXR/ABC signaling pathways and inactivation of SREBPs. In conclusion, fucoidan F3 may be explored as a potential compound for prevention or treatment of lipid disorders., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Yan Zhang et al.)

A superior piezoelectric coefficient and diminutive lattice thermal conductivity are advantageous for the application of a two-dimensional semiconductor in piezoelectric and thermoelectric devices, whereas an imperfect piezoelectric coefficient and large lattice thermal conductivity limit the practical application of the material. In this study, we investigate how the equibiaxial strain regulates the electronic structure, and mechanical, piezoelectric, and thermal transport properties. Tensile strain can deduce the bandgap of the monolayer CrX 2 (X = S, Se, Te), whereas compressive strain has an opposite effect. Additionally, the transition from a semiconductor to a metal state and the transition between direct and indirect band gaps will occur at appropriate strain values, so the electronic structure can be effectively regulated. The reason is the different sensitivities of the energy corresponding to K and Γ on the valence band to the strain due to the changes in different orbital overlaps. The tensile strain can effectively improve the flexibility of monolayers CrX 2 , which provides a possibility for the application of flexible electronic devices. Furthermore, the tensile strain can improve the piezoelectric strain coefficient of monolayers CrX 2 . Using Slacks formulation, we calculate the lattice thermal conductivity, and the tensile biaxial strain can reduce the lattice thermal conductivity. Our research provides a strategy to enhance the piezoelectric and flexible electronic applications and decrease the lattice thermal conductivity, which can benefit the thermoelectric applications.

Accurately distinguishing between enantiomeric molecules is a fundamental challenge in the field of chemistry. However, there is still significant room for improvement in both the enantiomeric selectivity (K R(S) /K S(R) ) and binding strength of most reported macrocyclic chiral receptors to meet the demands of practical application scenarios. Herein, we synthesized a water-soluble conjugated tubular host-namely, corral[4]BINOL-using a chiral 1,1'-bi-2-naphthol (BINOL) derivative as the repeating unit. The conjugated chiral backbone endows corral[4]BINOL with good fluorescent emission (QY=34 % ) and circularly polarized luminescence (|g lum | up to 1.4×10 -3 ) in water. Notably, corral[4]BINOL exhibits high recognition affinity up to 8.6×10 10  M -1 towards achiral guests in water, and manifested excellent enantioselectivity up to 18.7 towards chiral substrates, both of which represent the highest values observed among chiral macrocycles in aqueous solution. The ultrastrong binding strength, outstanding enantioselectivity, and facile accessibility, together with the superior fluorescent and chiroptical properties, endow corral[4]BINOL with great potential for a wide range of applications., (© 2023 Wiley-VCH GmbH.)

Ecological comprehensive index can quantitatively and visually analyze the temporal and spatial variations of ecological environment quality in a region. Based on the five indices of fractional vegetation coverage, leaf area index, total primary productivity, land surface temperature and wetness obtained by MODIS satellite data in 2001, 2005, 2010, 2015 and 2020, and coupled the comprehensive quality of the eco-environment ( K ), we analyzed the temporal and spatial variations of ecological quality along the Yellow River of Shanxi Province from 2001 to 2020 by using the principal component analysis and spatial autocorrelation method. The results showed that the mean value of K in the study area increased from 0.3354 to 0.4389 during 2001-2020. The ecological quality along the Yellow River of Shanxi Province improved overall, but with obvious temporal and spatial variations. On the large scale, it presented a pattern of "better in the south and worse in the north". There was difference between hills and mountains on the small scale. It showed a trend of continuous improvement in time, but the rate of change was different. The trend of improvement in the south was stronger than that in the north. From 2001 to 2020, the global Moran I values of K were all greater than 0.93, indicating that the ecological quality along the Yellow River of Shanxi Province had a strong spatial correlation. The types of spatial agglomeration were mainly high-high and low-low. The high-high agglomeration areas were mainly distributed in blocks in the south, while the low-low agglomeration areas were mainly concentrated in the north. The ecological quality of areas alone the Yellow River of Shanxi Province had been greatly improved during the research period, but there was still obvious spatial heterogeneity, which need to strengthen ecological protection.

Two-dimensional (2D) half-metallic materials are highly desirable for nanoscale spintronic applications. Here, we propose a new mechanism that can achieve half-metallicity in 2D ferromagnetic (FM) materials with two-layer magnetic atoms by electric field tuning. We use a concrete example of an experimentally synthesized CrSBr monolayer to illustrate our proposal through first-principles calculations. It is found that half-metallic properties can be achieved in CrSBr within an appropriate electric field range, and the corresponding amplitude of electric field intensity can be realized experimentally. Janus monolayer Cr 2 S 2 BrI is constructed, which possesses a built-in electric field due to broken horizontal mirror symmetry. However, Cr 2 S 2 BrI without and with an applied external electric field is always a FM semiconductor. A possible memory device is also proposed based on the CrSBr monolayer. Our work will stimulate the application of 2D FM CrSBr in future spintronic nanodevices.

Electronic correlation combined with spin-orbit coupling (SOC) may have a significant impact on the physical properties of two-dimensional (2D) transition metal magnetic compounds. Moreover, magnetic anisotropy (MA) is very important in determining magnetic, ferrovalley (FV) and topological properties of these 2D systems. Based on a density-functional theory (DFT) + U approach, it is found that the electronic correlation can induce topological phase transition in some special 2D valleytronic materials (for example FeCl 2 and VSi 2 P 4 ) with out-of-plane MA, and a novel valley-polarized quantum anomalous Hall insulator (VQAHI) and half-valley-metal (HVM) can be produced. These topological phase transitions are connected with a sign-reversible Berry curvature and band inversion between d xy /d x 2 - y 2 and d z 2 orbitals. However, for in-plane MA, the FV and nontrivial topological properties will be suppressed. For a given material, the correlation strength is fixed, but these novel electronic states and topological phase transitions can still be exhibited by strain in practice. The mini-review sheds light on the possible role of correlation effects in some special 2D valleytronic materials.

Coexistence of ferromagnetism, piezoelectricity and valley in two-dimensional (2D) materials is crucial to advance multifunctional electronic technologies. Here, Janus ScXY (X≠Y = Cl, Br and I) monolayers are predicted to be piezoelectric ferromagnetic semiconductors with dynamical, mechanical and thermal stabilities. They all show an in-plane easy axis of magnetization by calculating magnetic anisotropy energy (MAE) including magnetocrystalline anisotropy energy and magnetic shape anisotropy energy. The MAE results show that they intrinsically have no spontaneous valley polarization. The predicted piezoelectric strain coefficients d 11 and d 31 (absolute values) are higher than ones of most 2D materials. Moreover, the d 31 (absolute value) of ScClI reaches up to 1.14 pm V -1 , which is highly desirable for ultrathin piezoelectric device application. To obtain spontaneous valley polarization, charge doping are explored to tune the direction of magnetization of ScXY. By appropriate hole doping, their easy magnetization axis can change from in-plane to out-of-plane, resulting in spontaneous valley polarization. Taking ScBrI with 0.20 holes per f.u. as an example, under the action of an in-plane electric field, the hole carriers of K valley turn towards one edge of the sample, which will produce anomalous valley Hall effect, and the hole carriers of Γ valley move in a straight line. These findings could pave the way for designing piezoelectric and valleytronic devices., (© 2023 IOP Publishing Ltd.)

Atherosclerosis, a chief pathogenic factor of cardiovascular disease, is associated with many factors including inflammation, dyslipidemia, and oxidative stress. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and are widely expressed with tissue- and cell-specificity. They control multiple genes that are involved in lipid metabolism, inflammatory response, and redox homeostasis. Given the diverse biological functions of PPARs, they have been extensively studied since their discovery in 1990s. Although controversies exist, accumulating evidence have demonstrated that PPAR activation attenuates atherosclerosis. Recent advances are valuable for understanding the mechanisms of action of PPAR activation. This article reviews the recent findings, mainly from the year of 2018 to present, including endogenous molecules in regulation of PPARs, roles of PPARs in atherosclerosis by focusing on lipid metabolism, inflammation, and oxidative stress, and synthesized PPAR modulators. This article provides information valuable for researchers in the field of basic cardiovascular research, for pharmacologists that are interested in developing novel PPAR agonists and antagonists with lower side effects as well as for clinicians., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Accumulating evidence has demonstrated that polysaccharides derived from edible fungi have lipid-lowering effects in mice. However, the lipid metabolism mechanisms in mice and humans are different. We have previously elucidated the structural characteristics of the alkali-extracted polysaccharide CM3-SII obtained from Cordyceps militaris. This study aimed to investigate whether CM3-SII could ameliorate hyperlipidemia in a heterozygous low-density lipoprotein receptor (LDLR)-deficient hamster model of hyperlipidemia. Our data demonstrated that CM3-SII significantly decreased total plasma cholesterol, non-high-density lipoprotein cholesterol, and triglyceride levels in heterozygous LDLR-deficient hamsters. Unlike ezetimibe, CM3-SII could enhance the concentration of plasma apolipoprotein A1 and the expression of liver X receptor α/ATP-binding cassette transporter G8 mRNA pathway and suppress the expression of Niemann-Pick C1-like 1, which help to reduce cholesterol levels further. Moreover, the results of molecular docking analysis demonstrated that CM3-SII could directly bind to Niemann-Pick C1-like 1 with high affinity. The triglyceride-lowering mechanisms of CM3-SII were related to its downregulation of sterol regulatory element-binding protein 1c and upregulation of peroxisome proliferator-activated receptor α. Importantly, CM3-SII increased the abundance of Actinobacteria and Faecalibaculum and the ratio of Bacteroidetes/Firmicutes. Thus, CM3-SII attenuated hyperlipidemia by modulating the expression of multiple molecules involved in lipid metabolism and the gut microbiota., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

In this paper, the electronic band structure, Rashba effect, hexagonal warping, and piezoelectricity of Janus group-VIA binary monolayers STe 2 , SeTe 2 , and Se 2 Te are investigated based on density functional theory (DFT). Due to the inversion asymmetry and spin-orbit coupling (SOC), the STe 2 , SeTe 2 and Se 2 Te monolayers exhibit large intrinsic Rashba spin splitting (RSS) at the Γ point with the Rashba parameters 0.19 eV Å, 0.39 eV Å, and 0.34 eV Å, respectively. Interestingly, based on the k · p model via symmetry analysis, the hexagonal warping effect and a nonzero spin projection component S z arise at a larger constant energy surface due to nonlinear k 3 terms. Then, the warping strength λ was obtained by fitting the calculated energy band data. Additionally, in-plane biaxial strain can significantly modulate the band structure and RSS. Furthermore, all these systems exhibit large in-plane and out-of-plane piezoelectricity due to inversion and mirror asymmetry. The calculated piezoelectric coefficients d 11 and d 31 are about 15-40 pm V -1 and 0.2-0.4 pm V -1 , respectively, which are superior to those of most reported Janus monolayers. Because of the large RSS and piezoelectricity, the studied materials have great potential for spintronic and piezoelectric applications.

Macrophages are involved in the whole process of atherosclerosis, which is characterized by accumulation of lipid and inflammation. Presently, clinically used lipid-lowering drugs cannot completely retard the progress of atherosclerosis. Liver X receptor (LXR) plays a key role in regulation of lipid metabolism and inflammation. Accumulating evidence have demonstrated that synthetic LXR agonists can significantly retard the development of atherosclerosis. However, these agonists induce sever hypertriglyceridemia and liver steatosis. These side effects have greatly limited their potential application for therapy of atherosclerosis. The rapid development of drug delivery system makes it possible to delivery interested drugs to special organs or cells using nanocarriers. Macrophages express various receptors which can recognize and ingest specially modified nanocarriers loaded with LXR agonists. In the past decades, a great progress has been made in this field. These macrophage-targeted nanocarriers loaded with LXR agonists are found to decrease atherosclerosis by reducing cholesterol accumulation and inflammatory reactions. Of important, these nanocarriers can alleviate side effects of LXR agonists. In this article, we briefly review the roles of macrophages in atherosclerosis, mechanisms of action of LXR agonists, and focus on the advances of macrophage-targeted nanocarriers loaded with LXR agonists. This work may promote the potential clinical application of these nanocarriers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Miao, Yu, Wang, Xia, Li and Guo.)

Strong structural asymmetry is actively explored in two-dimensional (2D) materials, because it can give rise to many interesting physical properties. Motivated by the recent synthesis of monolayer Si 2 Te 2 , we explored a family of 2D materials, named Janus Si dichalcogenides (JSD), which parallel the Janus transition metal dichalcogenides and exhibit even stronger inversion asymmetry. Using first-principles calculations, we show that their strong structural asymmetry leads to a pronounced intrinsic polar field, sizable spin splitting, and large piezoelectric response. The spin splitting involves an out-of-plane spin component, which is beyond the linear Rashba model. The piezoelectric tensor has a large value in both in-plane d 11 coefficient and out-of-plane d 31 coefficient, making monolayer JSDs distinct among existing 2D piezoelectric materials. In addition, we find interesting strain-induced phase transitions in these materials. Particularly, there are multiple valleys that compete for the conduction band minimum, which will lead to notable changes in the optical and transport properties under strain. Our work reveals a new family of Si based 2D materials, which could find promising applications in spintronic and piezoelectric devices.

Coexistence of intrinsic ferromagnetism and piezoelectricity, namely piezoelectric ferromagnetism (PFM), is crucial to advance multifunctional spintronic technologies. In this work, we demonstrate that Janus monolayer YBrI is a PFM, which is dynamically, mechanically and thermally stable. The electronic correlation effects on the physical properties of YBrI are investigated by using generalized gradient approximation plus U (GGA+ U ) approach. For out-of-plane magnetic anisotropy, YBrI is a ferrovalley (FV) material, and its valley splitting is larger than 82 meV within the considered U range. The anomalous valley Hall effect (AVHE) can be achieved under an in-plane electric field. However, for in-plane magnetic anisotropy, YBrI is a common ferromagnetic (FM) semiconductor. When considering intrinsic magnetic anisotropy, the easy axis of YBrI is always in-plane, and its magnetic anisotropy energy (MAE) varies from 0.309 meV to 0.237 meV ( U = 0.0 eV to 3.0 eV). However, the magnetization can be adjusted from the in-plane to out-of-plane direction by an external magnetic field, and then lead to the occurrence of valley polarization. Moreover, the missing centrosymmetry along with broken mirror symmetry results in both in-plane and out-of-plane piezoelectricity in the YBrI monolayer. At a typical U = 2.0 eV, the piezoelectric strain coefficient d 11 is predicted to be -5.61 pm V -1 , which is higher than or comparable with the ones of other known two-dimensional (2D) materials. The electronic and piezoelectric properties of YBrI can be effectively tuned by applying biaxial strain. For example, tensile strain can enhance valley splitting and d 11 (absolute value). The predicted magnetic transition temperature of YBrI is higher than those of experimentally synthesized 2D FM materials CrI 3 and Cr 2 Ge 2 Te 6 . Our findings of these distinctive properties could pave the way for designing multifunctional spintronic devices, and bring forward a new perspective for constructing 2D materials.

Two-dimensional (2D) ferromagnets have been a fascinating subject of research, and magnetic anisotropy (MA) is indispensable for stabilizing the 2D magnetic order. Here, we investigate magnetic anisotropy energy (MAE), magnetic and electronic properties ofVSi2P4by using the generalized gradient approximation plus U approach. For large U , the magnetic shape anisotropy (MSA) energy has a more pronounced contribution to the MAE, which can overcome the magnetocrystalline anisotropy (MCA) energy to evince an easy-plane. For fixed out-of-plane MA, monolayerVSi2P4undergoes ferrovalley (FV), half-valley-metal (HVM), valley-polarized quantum anomalous Hall insulator (VQAHI), HVM and FV states with increasing U . However, for assumptive in-plane MA, there is no special quantum anomalous Hall (QAH) state and spontaneous valley polarization within considered U range. According to the MAE and electronic structure with fixed out-of-plane or in-plane MA, the intrinsic phase diagram shows common magnetic semiconductor, FV and VQAHI in monolayerVSi2P4. At representative U  = 3 eV widely used in references,VSi2P4can be regarded as a 2D- XY magnet, not Ising-like 2D long-range order magnets predicted in previous works with only considering MCA energy. Our findings shed light on importance of MSA in determining magnetic and electronic properties of monolayerVSi2P4., (© 2022 IOP Publishing Ltd.)

Direct Z-scheme water-splitting is a promising route to enhancing the photocatalytic performance due to the effective separation of photogenerated carriers while simultaneously preserving the strong oxidation activity of holes and reduction activity of electrons. In this work, the MoSSe/XY 2 (X = Hf, Zr; S, Se) heterostructures (HSs) with different contacts are proposed for Z-scheme photocatalytic water-spitting by first principles calculation. The separation of photogenerated carriers for HfSe 2 /SMoSe and ZrSe 2 /SMoSe HSs is limited by the type-I band alignment, while the hydrogen production ability of HfSe 2 /SeMoS and ZrSe 2 /SeMoS HSs is limited by the lower conduction band edge positions relative to the water reduction potential. The HfS 2 /SMoSe, HfS 2 /SeMoS, ZrS 2 /SMoSe, and ZrS 2 /SeMoS HSs are direct Z-scheme water-splitting photocatalysts with the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) occurring at the Hf(Zr)S 2 layer and MoSSe layer, respectively. More excitingly, the S (or Se) vacancies effectively lower the HER overpotentials. Besides, the solar-to-hydrogen efficiencies are 6.1%, 5.9%, 6.4%, and 6.3% for HfS 2 /SMoSe, HfS 2 /SeMoS, ZrS 2 /SMoSe, and ZrS 2 /SeMoS HSs, respectively. This work paves the way for designing highly efficient overall water-splitting photocatalysts using 2D materials.

Dyslipidemias are disorders of plasma levels of lipids, such as elevated levels of total cholesterol and triglyceride, that are associated with various human diseases including cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Statins are the first-line drugs for treatment of dyslipidemia. However, a substantial proportion of patients cannot reach the recommended LDL-c level even with the highest tolerated doses of statins, and there is no available drug specifically for NAFLD therapy. Sea cucumbers are one of the widely distributed invertebrates, and are an important resource of food and medicine. Sea cucumbers have many valuable nutrients including saponins, fatty acids, phospholipids, cerebrosides, sulfated polysaccharides, as well as proteins and peptides. In recent years, these natural products derived from sea cucumbers have attracted attentions for treatment of CVD and NAFLD because of their lipid-lowering effect and low toxicity. However, the hypolipidemic mechanisms of action and the structure-activity relationship of these bioactive components have not been well-documented in literature. This review article summarizes the signaling pathways and the potential structure-activity relationship of sea cucumber-derived bioactive compounds including saponins, lipids, carbohydrates as well as peptides and proteins. This article will provide information useful for the development of sea cucumber-derived lipid-lowering compounds as well as for investigation of hypolipidemic compounds that are derived from other natural resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Shen, Yin and Guo.)

Obesity is characterized by lipid accumulation in distinct organs. Presently, fenofibrate is a commonly used triglyceride-lowering drug. This study is designed to investigate whether long-term fenofibrate intervention can attenuate lipid accumulation in ob/ob mouse, a typical model of obesity. Our data demonstrated that fenofibrate intervention significantly decreased plasma triglyceride level by 21.0%, increased liver index and hepatic triglyceride content by 31.7 and 52.1%, respectively, and elevated adipose index by 44.6% compared to the vehicle group. As a PPARα agonist, fenofibrate intervention significantly increased the expression of PPARα protein in the liver by 46.3% and enhanced the expression of LDLR protein by 3.7-fold. However, fenofibrate dramatically increased the expression of PPARγ and SREBP-1c proteins by ~2.1- and 0.9-fold in the liver, respectively. Fenofibrate showed no effects on the expression of genes-related to fatty acid β-oxidation. Of note, it significantly increased the gene expression of FAS and SCD-1 . Furthermore, fenofibrate modulated the gut microbiota. Collectively, long-term fenofibrate induces lipid accumulation in liver and adipose tissues in ob/ob mice by enhancing the expression of adipogenesis-related proteins and gut microbiota. These data suggest that fenofibrate may have limited effects on attenuating lipid deposition in obese patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Jia, Liu, Yu, Si and Guo.)

Among the diseases causing human death, cardiovascular disease (CVD) remains number one according to the World Health Organization report in 2021. It is known that atherosclerosis is the pathological basis of CVD. Low-density lipoprotein (LDL) plays a pivotal role in the initiation and progression of atherosclerotic CVD (ASCVD). LDL cholesterol (LDL-C) is the traditional biological marker of LDL. However, large numbers of patients who have achieved the recommended LDL-C goals still have ASCVD risk. In multiple prospective studies, LDL particle (LDL-P) is reported to be more accurate in predicting CVD risk than LDL-C. LDL-Ps differ in size, density and chemical composition. Numerous clinical studies have proved that the atherogenic mechanisms of LDL-Ps are determined not only by LDL number and size but also by LDL modifications. Of note, small dense LDL (sdLDL) particles possess stronger atherogenic ability compared with large and intermediate LDL subfractions. Besides, oxidized LDL (ox-LDL) is another risk factor in atherosclerosis. Among the traditional lipid-lowering drugs, statins induce dramatic reductions in LDL-C and LDL-P to a lesser extend. Recently, proprotein convertase subtilsin/kexin type 9 inhibitors (PCSK9i) have been demonstrated to be effective in lowering the levels of LDL-C, LDL-P, as well as CVD events. In this article, we will make a short review of LDL metabolism, discuss the discordance between LDL-C and LDL-P, outline the atherogenic mechanisms of action of LDL by focusing on sdLDL and ox-LDL, summarize the methods used for measurement of LDL subclasses, and conclude the advances in LDL-lowering therapies using statins and PCSK9i., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qiao, Zou and Guo.)

The combination of piezoelectricity with a nontrivial topological insulating phase in two-dimensional (2D) systems, namely piezoelectric quantum spin Hall insulators (PQSHI), is intriguing for exploring novel topological states toward the development of high-speed and dissipationless electronic devices. In this work, we predict a PQSHI Janus monolayer VCClBr constructed from VCCl 2 , which is dynamically, mechanically and thermally stable. In the absence of spin orbital coupling (SOC), VCClBr is a narrow gap semiconductor with a gap value of 57 meV, which is different from Dirac semimetal VCCl 2 . The gap of VCClBr is due to a built-in electric field caused by asymmetrical upper and lower atomic layers, which is further confirmed by the external-electric-field induced gap in VCCl 2 . When including SOC, the gap of VCClBr is increased to 76 meV, which is larger than the thermal energy of room temperature (25 meV). The VCClBr is a 2D topological insulator (TI), which is confirmed by Z 2 topological invariant and nontrivial one-dimensional edge states. It is proved that the nontrivial topological properties of VCClBr are robust against strain (biaxial and uniaxial cases) and external electric fields. Due to broken horizontal mirror symmetry, only an out-of-plane piezoelectric response can be observed, when a biaxial or uniaxial in-plane strain is applied. The predicted piezoelectric strain coefficients d 31 and d 32 are -0.425 pm V -1 and -0.219 pm V -1 , respectively, and they are higher than or compared with those of many 2D materials. Finally, Janus monolayer VCFBr and VCFCl (dynamically unstable) are also constructed, and they are still PQSHIs. Moreover, the d 31 and d 32 of VCFBr and VCFCl are higher than those of VCClBr, and the d 31 (absolute value) of VCFBr is larger than one. According to out-of-plane piezoelectric coefficients of VCXY (X ≠ Y = F, Cl and Br), CrX 1.5 Y 1.5 (X = F, Cl and Br; Y = I) and NiXY (X ≠ Y = Cl, Br and I), it is concluded that the size of the out-of-plane piezoelectric coefficient has a positive relation with the electronegativity difference of X and Y atoms. Our studies enrich the diversity of Janus 2D materials, and open a new avenue in the search for PQSHI with a large out-of-plane piezoelectric response, which provides a potential platform in nanoelectronics.

This study was designed to explore the prevalence of recommended anticoagulation by guidelines before admission and its impact on the incidence of acute myocardial infarction (AMI) and the AMI associated in-hospital outcomes in patients with atrial fibrillation (AF). 10,725 patients with AF at their first hospitalizations in our hospitals were retrospectively reviewed, with a prevalence of recommended anticoagulation preadmission 24.41% (Number = 2618). They had lower risk of AMI incidence (Adjusted OR 0.66, 95%CI 0.54-0.81, p < 0.001) compared to those without recommended anticoagulation after multivariate logistic regression. Furthermore, recommended anticoagulation preadmission reduced in-hospital all-cause death associated with AMI in univariate logistic analysis, but had no impact on the risk of in-hospital bleeding and stroke after AMI both in univariate and multivariate logistic analysis. The prevalence of recommended anticoagulation before admission was 24.41% in China. Recommended anticoagulation reduced incidence of hospitalized AMI, but had no impact on the associated in-hospital bleeding and stroke risk after AMI., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cordyceps militaris is a parasitic edible fungus and has been used as tonics for centuries. Polysaccharides are a major water-soluble component of C. militaris . Recently, C. militaris -derived polysaccharides have been given much attention due to their various actions including antioxidant, anti-inflammatory, anti-tumor, anti-hyperlipidemic, anti-diabetic, anti-atherosclerotic, and immunomodulatory effects. These bioactivities are determined by the various structural characteristics of polysaccharides including monosaccharide composition, molecular weight, and glycosidic linkage. The widespread use of advanced analytical analysis tools has greatly improved the elucidation of the structural characteristics of C. militaris -derived polysaccharides. However, the methods for polysaccharide structural characterization and the latest findings related to C. militaris -derived polysaccharides, especially the potential structure-activity relationship, have not been well-summarized in recent reviews of the literature. This review will discuss the methods used in the elucidation of the structure of polysaccharides and structural characteristics as well as the signaling pathways modulated by C. militaris -derived polysaccharides. This article provides information useful for the development of C. militaris -derived polysaccharides as well as for investigating other medicinal polysaccharides., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miao, Yu, Li, Sun and Guo.)

Cardiovascular disease (CVD) is still the leading cause of death globally, and atherosclerosis is the main pathological basis of CVDs. Low-density lipoprotein cholesterol (LDL-C) is a strong causal factor of atherosclerosis. However, the first-line lipid-lowering drugs, statins, only reduce approximately 30% of the CVD risk. Of note, atherosclerotic CVD (ASCVD) cannot be eliminated in a great number of patients even their LDL-C levels meet the recommended clinical goals. Previously, whether the elevated plasma level of triglyceride is causally associated with ASCVD has been controversial. Recent genetic and epidemiological studies have demonstrated that triglyceride and triglyceride-rich lipoprotein (TGRL) are the main causal risk factors of the residual ASCVD. TGRLs and their metabolites can promote atherosclerosis via modulating inflammation, oxidative stress, and formation of foam cells. In this article, we will make a short review of TG and TGRL metabolism, display evidence of association between TG and ASCVD, summarize the atherogenic factors of TGRLs and their metabolites, and discuss the current findings and advances in TG-lowering therapies. This review provides information useful for the researchers in the field of CVD as well as for pharmacologists and clinicians., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Yin, Qiao and Guo.)

Achieving combination of spin and valley polarized states with topological insulating phase is pregnant to promote the fantastic integration of topological physics, spintronics and valleytronics. In this work, a spin-valley-coupled quantum spin Hall insulator (svc-QSHI) is predicted in Janus monolayer CSb 1.5 Bi 1.5 with dynamic, mechanical and thermal stabilities. Calculated results show that the CSb 1.5 Bi 1.5 is a direct band gap semiconductor with and without spin-orbit coupling, and the conduction-band minimum and valence-band maximum are at valley point. The inequivalent valleys have opposite Berry curvature and spin moment, which can produce a spin-valley Hall effect. In the center of Brillouin zone, a Rashba-type spin splitting can be observed due to missing horizontal mirror symmetry. The topological characteristic of CSb 1.5 Bi 1.5 is confirmed by the Z 2 invariant and topological protected conducting helical edge states. Moreover, the CSb 1.5 Bi 1.5 shows unique Rashba-splitting edge states. Both energy band gap and spin-splitting at the valley point are larger than the thermal energy of room temperature (25 meV) with generalized gradient approximation level, which is very important at room temperature for device applications. It is proved that the spin-valley-coupling and nontrivial quantum spin Hall state are robust again biaxial strain. Our work may provide a new platform to achieve integration of topological physics, spintronics and valleytronics., (© 2022 IOP Publishing Ltd.)

Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) are expressed in a variety of tumors. Activation of the PDGF/PDGFR signaling pathway is associated with cancer proliferation, metastasis, invasion, and angiogenesis through modulating multiple downstream pathways, including phosphatidylinositol 3 kinase/protein kinase B pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Therefore, targeting PDGF/PDGFR signaling pathway has been demonstrated to be an effective strategy for cancer therapy, and accordingly, some great progress has been made in this field in the past few decades. This review will focus on the PDGF isoforms and their binding with the related PDGFRs, the PDGF/PDGFR signaling and regulation, and especially present strategies and inhibitors developed for cancer therapy, and the related clinical benefits and side effects., (Copyright © 2022. Published by Elsevier B.V.)

An N -glycosidic polysaccharide-peptide complex CMPS-80 was obtained from the fruiting body of C. militaris . Of importance, CMPS-80 significantly ameliorated formation of atherosclerotic lesions and plasma lipid profiles in apolipoprotein E-deficient mice. Integrated informatics analysis suggested that CMPS-80 can modulate multiple lncRNA-microRNA-mRNA axes. CMPS-80 has a potential application for prevention of hyperlipidemia and atherosclerosis.

The valley degree of freedom of carriers in crystals is useful to process information and perform logic operations, and it is a key factor for valley application to realize valley polarization. Here, we propose a model that the valley polarization transition at different valley points (- K and K points) is produced by biaxial strain. Using first-principles calculations, we illustrate our idea with a concrete example of a Janus GdClF monolayer. The predicted GdClF monolayer is dynamically, mechanically and thermally stable, and is a ferromagnetic (FM) semiconductor with perpendicular magnetic anisotropy (PMA), valence band maximum (VBM) at valley points and a high Curie temperature ( T C ). Due to its intrinsic ferromagnetism and spin-orbit coupling (SOC), a spontaneous valley polarization will be induced, but the valley splitting is only -3.1 meV, which provides an opportunity to achieve valley polarization transition at different valley points by strain. In the considered strain range ( a / a 0 : 0.94-1.06), the strained GdClF monolayer always has an energy bandgap, strong FM coupling and PMA. The compressive strain is in favour of - K valley polarization, while the tensile strain is favorable for K valley polarization. The corresponding valley splittings at 0.96 and 1.04 strains are -44.5 meV and 29.4 meV, respectively, which are higher than the thermal energy at room temperature (25 meV). Due to its special Janus structure, both in-plane and out-of-plane piezoelectric polarizations can be observed. It is found that the direction of in-plane piezoelectric polarization can be overturned by strain, and the d 11 values at 0.96 and 1.04 strains are -1.37 pm V -1 and 2.05 pm V -1 , respectively. Our work paves the way to design ferrovalley materials for application in multifunctional valleytronic and piezoelectric devices by strain.

Background: Cordyceps militaris is cultured widely as an edible mushroom and accumulating evidence in mice have demonstrated that the polysaccharides of Cordyceps species have lipid-lowering effects. However, lipid metabolism in mice is significantly different from that in humans, making a full understanding of the mechanisms at play critical., Methods: After 5 months, the hamsters were weighed and sampled under anesthesia after overnight fasting. The lipid-lowering effect and mechanisms of the polysaccharide CM1 was investigated by cellular and molecular technologies. Furthermore, the effect of the polysaccharide CM1 (100 μg/mL) on inhibiting adipocyte differentiation was investigated in vitro., Results: CM1, a polysaccharide from C. militaris, significantly decreased plasma total cholesterol, triglyceride and epididymal fat index in LDLR (+/-) hamsters, which have a human-like lipid profile. After 5 months' administration, CM1 decreased the plasma level of apolipoprotein B48, modulated the expression of key genes and proteins in liver, small intestine, and epididymal fat. CM1 also inhibited preadipocyte differentiation in 3T3-L1 cells by downregulating the key genes involved in lipid droplet formation., Conclusions: The polysaccharide CM1 lowers lipid and adipocyte differentiation by several pathways, and it has potential applications for hyperlipidemia prevention., (© 2021. The Author(s).)

Atherosclerotic cardiovascular disease has a high mortality worldwide. Our lab previously purified a polysaccharide designated as CM1 with (1→4)-β-D-Glc p and (1→2)-α-D-Man p glycosyls as the backbone. In this study, we investigated the anti-atherosclerosis effect of CM1 and the underlying mechanisms of action in a low-density lipoprotein receptor knockout (LDLR (-/-) mouse model. It was found that CM1 significantly decreased the formation of atherosclerotic plaques. Mechanistically, CM1 enhanced plasma level of apolipoprotein A-I and decreased the plasma levels of triglyceride, apolipoprotein B, and total cholesterol. In the absence of LDLR, CM1 elevated the expression of very low-density lipoprotein receptor for liver uptake of plasma apolipoprotein B-containing particles and reduced hepatic triglyceride synthesis by inhibiting sterol regulatory element binding protein 1c. CM1 improved lipids excretion by increasing the liver X receptor α/ATP-binding cassette G5 pathway in small intestine. CM1 reduced lipogenesis and lipolysis by inhibiting peroxisome proliferator-activated receptor γ and adipose triglyceride lipase in epididymal fat. Furthermore, CM1 improved lipid profile in C57BL/6J mice. Collectively, CM1 can modulate lipid metabolism by multiple pathways, contributing to reduced plasma lipid level and formation of atherosclerotic plaques in LDLR (-/-) mice. This molecule could be explored as a potential compound for prevention and treatment of hyperlipidemia and atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yin, Lin, Yu, Shen, Li and Guo.)

To easily synthesize a piezoelectric quantum anomalous Hall insulator (PQAHI), the Janus monolayer Fe 2 IBr (FeI 0.5 Br 0.5 ) as a representative PQAHI, is generalized to monolayer FeI 1- x Br x ( x = 0.25 and 0.75) with α and β phases. By first-principles calculations, it is proved that monolayer FeI 1- x Br x ( x = 0.25 and 0.75) are dynamically, mechanically and thermally stable. They are excellent room-temperature PQAHIs with high Curie temperatures, sizable gaps and high Chern number ( C = 2). Because the considered crystal structures of α and β phases possess M x and M y mirror symmetries, the topological properties of monolayer FeI 1- x Br x ( x = 0.25 and 0.75) are maintained. Namely, if the constructed structures have M x and M y mirror symmetries, the mixing ratio of Br and I atoms can be generalized for other proportions. It is also found that different crystal phases have important effects on the out-of-plane piezoelectric response, and the piezoelectric strain coefficient, d 32 , of the β phase is higher than or comparable with those of other known two-dimensional (2D) materials. To further confirm this idea, the physical and chemical properties of monolayer LiFeSe 0.75 S 0.25 with α and β phases, as a generalization of PQAHI LiFeSe 0.5 S 0.5 , is investigated, as it has a similar electronic structure, magnetic and topological properties as LiFeSe 0.5 S 0.5 . Our work provides a practical guide to achieve PQAHIs experimentally, and the combination of piezoelectricity, topological and ferromagnetic (FM) orders makes Fe 2 I 2 -based monolayers a potential platform for multi-functional spintronics and piezoelectric electronics.

Ferulic acid, a kind of phenolic substance widely existing in plants, is an important active component of many traditional Chinese medicines. So far, it has been proved that ferulic acid has a variety of biological activities, especially in oxidative stress, inflammation, vascular endothelial injury, fibrosis, apoptosis and platelet aggregation. Many studies have shown that ferulic acid can inhibit PI3K/AKT pathway, the production of ROS and the activity of aldose reductase. The anti-inflammatory effect of ferulic acid is mainly related to the levels of PPAR γ, CAM and NF-κ B and p38 MAPK signaling pathways. Ferulic acid not only protects vascular endothelium by ERK1/2 and NO/ET-1 signal, but also plays an anti-fibrosis role by TGF-β/Smad and MMPs/TIMPs system. Moreover, ferulic acid has ant-apoptotic and anti-platelet effects. In addition to the pharmacological effects of ferulic acid, its pharmacokinetics and derivatives were also discussed in this paper. This review provides the latest summary of the latest research on ferulic acid., (Copyright © 2021. Published by Elsevier Inc.)

Two-dimensional (2D) piezoelectric ferromagnetism (PFM) is essential for the development of the next-generation multifunctional spintronic technologies. Recently, the layered van der Waals (vdW) compound MnBi 2 Te 4 as a platform to realize the quantum anomalous Hall effect (QAHE) has attracted great interest. In this work, the Janus monolayer MnSbBiTe 4 with dynamic, mechanical and thermal stabilities is constructed from a synthesized non-piezoelectric MnBi 2 Te 4 monolayer by replacing the top Bi atomic layer with Sb atoms. The calculated results show that monolayer MnSbBiTe 4 is an intrinsic ferromagnetic (FM) semiconductor with a gap value of 0.25 eV, whose easy magnetization axis is out-of-plane direction with magnetic anisotropy energy (MAE) of 158 μeV per Mn. The predicted Curie temperature T C is about 20.3 K, which is close to that of monolayer MnBi 2 Te 4 . The calculated results show that the in-plane d 11 is about 5.56 pm V -1 , which is higher than or comparable to those of other 2D known materials. Moreover, it is found that strain engineering can effectively tune the piezoelectric properties of Janus monolayer MnSbBiTe 4 . The calculated results show that tensile strain can improve the d 11 , which is improved to be 21.16 pm V -1 at only 1.04 strain. It is proved that the ferromagnetic order, semiconducting properties, out-of-plane easy axis and a large d 11 are robust against electronic correlations. Our work provides a possible way to achieve PFM with a large d 11 in well-explored vdW compound MnBi 2 Te 4 , which makes it possible to use the piezoelectric effect to tune the quantum transport process.

A two-dimensional (2D) material with piezoelectricity, topological and ferromagnetic (FM) properties, namely a 2D piezoelectric quantum anomalous hall insulator (PQAHI), may open new opportunities to realize novel physics and applications. Here, by first-principles calculations, a family of 2D Janus monolayer Fe 2 IX (X = Cl and Br) with dynamic, mechanical, and thermal stabilities is predicted to be a room-temperature PQAHI. In the absence of spin-orbit coupling (SOC), the monolayer Fe 2 IX (X = Cl and Br) is in a half Dirac semimetal state. When the SOC is included, these monolayers become quantum anomalous Hall (QAH) states with sizable gaps (more than 200 meV) and two chiral edge modes (Chern number C = 2). It is also found that the monolayer Fe 2 IX (X = Cl and Br) possesses robust QAH states against the biaxial strain. By symmetry analysis, it is found that only an out-of-plane piezoelectric response can be induced by a uniaxial strain in the basal plane. The calculated out-of-plane d 31 of Fe 2 ICl (Fe 2 IBr) is 0.467 pm V -1 (0.384 pm V -1 ), which is higher than or comparable with those of other 2D known materials. Meanwhile, using Monte Carlo (MC) simulations, the Curie temperature T C is estimated to be 429/403 K for the monolayer Fe 2 ICl/Fe 2 IBr at the FM ground state, which is above room temperature. Finally, the interplay of electronic correlations with nontrivial band topology is studied to confirm the robustness of the QAH state. The combination of piezoelectricity, topological and FM orders makes the monolayer Fe 2 IX (X = Cl and Br) become a potential platform for multi-functional spintronic applications with a large gap and high T C . Our work provides the possibility to use the piezotronic effect to control QAH effects, and can stimulate further experimental works.

Atherosclerosis is a chronic disease starting with the entry of monocytes into the subendothelium and the subsequent differentiation into macrophages. Macrophages are the major immune cells in atherosclerotic plaques and are involved in the dynamic progression of atherosclerotic plaques. The biological properties of atherosclerotic plaque macrophages determine lesion size, composition, and stability. The heterogenicity and plasticity of atherosclerotic macrophages have been a hotspot in recent years. Studies demonstrated that lipids, cytokines, chemokines, and other molecules in the atherosclerotic plaque microenvironment regulate macrophage phenotype, contributing to the switch of macrophages toward a pro- or anti-atherosclerosis state. Of note, M1/M2 classification is oversimplified and only represent two extreme states of macrophages. Moreover, M2 macrophages in atherosclerosis are not always protective. Understanding the phenotypic diversity and functions of macrophages can disclose their roles in atherosclerotic plaques. Given that lipid-lowering therapy cannot completely retard the progression of atherosclerosis, macrophages with high heterogeneity and plasticity raise the hope for atherosclerosis regression. This review will focus on the macrophage phenotypic diversity, its role in the progression of the dynamic atherosclerotic plaque, and finally discuss the possibility of treating atherosclerosis by targeting macrophage microenvironment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lin, Ji, Li and Guo.)

Background: Several scores were available for predicting atrial fibrillation (AF) recurrence post radiofrequency ablation. However, the role of different scores predicting AF recurrence after ablation in patients with concurrent AF and pulmonary diseases (PDs) remained obscure. Herein, we aimed to investigate their predicting values and differences in patients with concurrent AF and PDs., Methods: From January 2008 to April 2015, 304 patients with concurrent AF and PDs treated with catheter ablation were divided into 2 groups according to whether they experienced AF recurrence in our centers. Factors related with AF recurrence were explored using Cox regression and scores predicting recurrent AF were compared in these patients using ROC curves., Results: During a median of 6-month of follow-up, factors correlating with late AF recurrence included heart failure (HF) history [hazard ratio (HR): 2.79; 95% confidence interval (CI): 1.49-5.22, P=0.001], current smoking (1.73; 1.13-2.68, P=0.01) and early AF recurrence (3.85; 95% CI: 2.62-5.66, P<0.001) according to univariate Cox regression analysis. When analyzed using multivariate Cox model, HF history (2.21; 1.12-4.37, P=0.02), hypertension history (1.54; 1.02-2.33, P=0.04) and early AF recurrence (3.90; 2.60-5.85, P<0.001) were related to late AF recurrence. The BASE-AF2 score had higher c-index than the MB-LATER, APPLE, CHADS2, CHA2DS2-VASc, CAAP-AF and HATCH scores when compared using ROC curves analysis (all P<0.05). The optimal point for predicting AF recurrence of the BASE-AF2 score in the ROC analysis was 1 point with sensitivity of 69.03% and specificity of 60.21%., Conclusions: The predicting AF recurrence value of BASE-AF2 score was superior to MB-LATER, APPLE, CHADS2, CHA2DS2-VASc, CAAP-AF and HATCH scores in patients with concurrent AF and PDs, which can be an effective and helpful score for making AF treatment decisions.

Purposes: To explore the association of anaemia with risk of outcomes of in-hospital patients with acute myocardial infarction (AMI) and atrial fibrillation (AF)., Methods: Patients with AF and AMI at their first hospitalizations in three hospitals (Beijing Tongren Hospital, Beijing Friendship Hospital, Capital Medical University and China-Japan Friendship Hospital) were retrospectively reviewed and divided into two groups (with vs. without anaemia) according to haemoglobin within one day before or after admission., Results: 864 patients with AF and AMI (mean age:74.22 years; 39.9% female) were included in the current study. Patients with anaemia had increased risk of any bleeding (adjusted OR: 2.29, 95% CI: 1.43-3.68, p  = 0.001), minor bleeding (adjusted OR: 2.37, 95% CI:1.40-4.01, p  = 0.001), gastrointestinal bleeding (adjusted OR: 2.53, 95% CI:1.51-4.25, p  < 0.001) and other death causes (adjusted OR: 1.71, 95% CI: 1.07-2.72, p  = 0.02) compared to those without anaemia according to logistic regression. However, there was no difference in the risk of stroke or/and systematic embolism (SE) between patients with and without anaemia., Conclusions: In the Chinese in-hospital AMI and AF cohort, anaemia was shown to be associated with increased risk of any bleeding, minor bleeding, gastrointestinal bleeding and other death causes, but not the risk of stroke or/and SE.

The septuple-atomic-layer VSi2P4 with the same structure of experimentally synthesized MoSi2N4 is predicted to be a spin-gapless semiconductor (SGS) with the generalized gradient approximation (GGA). In this work, the biaxial strain is applied to tune the electronic properties of VSi2P4, and it spans a wide range of properties upon increasing the strain from a ferromagnetic metal (FMM) to SGS to a ferromagnetic semiconductor (FMS) to SGS to a ferromagnetic half-metal (FMHM). Due to broken inversion symmetry, the coexistence of ferromagnetism and piezoelectricity can be achieved in FMS VSi2P4 with the strain range of 0% to 4%. The calculated piezoelectric strain coefficients d11 for 1%, 2% and 3% strains are 4.61 pm V-1, 4.94 pm V-1 and 5.27 pm V-1, respectively, which are greater than or close to a typical value of 5 pm V-1 for bulk piezoelectric materials. Finally, similar to VSi2P4, the coexistence of piezoelectricity and ferromagnetism can be realized by strain in the VSi2N4 monolayer. Our works show that VSi2P4 in the FMS phase with intrinsic piezoelectric properties can have potential applications in spin electronic devices.

Background: This study was designed to explore the prevalence of pulmonary embolism (PE) and sex and age-related risk of incident PE in in-hospital patients with atrial fibrillation (AF) in China., Methods: A retrospective cohort of 15,688 AF patients (mean age: 72.56 years; 55.7% male) was identified from 2008 to 2018 in our hospitals. The prevalence and incidence of PE over a 2.28-year follow-up were studied. Unadjusted, age or sex-adjusted, and multivariate Cox regression were used to explore the risk of PE in the studied patients., Results: One hundred eighty-two AF patients (1.2%) had PE at their first hospitalizations. Over a mean follow-up of 2.28 years, 85 patients developed PE, with an incidence of 0.24% per person-year. PE was more likely to occur in female and older patients with AF according to the unadjusted, age or sex-adjusted, and multivariate Cox regression analysis (all P<0.05). Moreover, a significant higher risk of PE was seen in female and older patients in AF using Kaplan-Meier analysis, respectively (log-rank: both P<0.001)., Conclusions: In the current AF cohort, the prevalence of PE was 1.2% and the incidence of PE was 0.24% per person-year during a mean follow-up of 2.28 years. Female and older patients were more likely to experience PE compared to male and younger patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-2718). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Cardiac hypertrophy causes heart failure and is associated with hyperglycemia in patients with diabetes mellitus. Mibefradil, which acts as a T-type calcium channel blocker, exerts beneficial effects in patients with heart failure. In this study, we explored the effects and mechanism of mibefradil on high-glucose-induced cardiac hypertrophy in H9c2 cells. H9c2 cells were incubated in a high-glucose medium and then treated with different concentrations of mibefradil in the presence or absence of the Akt inhibitor MK2206 or mTOR inhibitor rapamycin. Cell size was evaluated through immunofluorescence, and mRNA expression of cardiac hypertrophy markers (atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain) was assessed by using quantitative real-time polymerase chain reaction. Changes in the expression of p-PI3K, p-Akt, and p-mTOR were evaluated using Western blotting, and autophagosome formation was detected using transmission electron microscopy. Our results indicate that mibefradil reduced the size of H9c2 cells, decreased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain, and decreased the level of autophagic flux. However, MK2206 and rapamycin induced autophagy and reversed the effects of mibefradil on high-glucose-induced H9c2 cells. In conclusion, mibefradil ameliorated high-glucose-induced cardiac hypertrophy by activating the PI3K/Akt/mTOR pathway and inhibiting excessive autophagy. Our study shows that mibefradil can be used therapeutically to ameliorate cardiac hypertrophy in patients with diabetes mellitus.

Objective: This study was aimed at investigating the regulation of mitochondrial function by histone deacetylase 6 (HDAC6) and the role of HDAC6 in the development and progression of sepsis., Results: HDAC6 downregulated PHB1 and subsequently promoted the development of CLP-induced sepsis. Inhibition of HDAC6 significantly attenuated CLP-induced sepsis through inhibition of mitochondrial dysfunction and reduced oxidant production, thus protecting the rats from oxidative injury., Conclusions: In this sepsis model, HDAC6 inhibits the expression and function of PHB1 and alters the function of the mitochondrial respiratory chain mediated by PHB1, thus enhancing the production of oxidants and increasing oxidative stress and thereby leading to severe oxidative injury in multiple organs., Methods: The expression of HDAC6 and prohibitin 1 (PHB1) in humans and in a rat model of sepsis was measured by quantitative reverse-transcription PCR and western blotting. Sepsis induction by cecal ligation and puncture (CLP) was confirmed by histological analysis. Concentrations of different sepsis markers were measured by an enzyme-linked immunosorbent assay, and mitochondrial function was assessed via the mitochondrial respiratory control rate.

Recent studies have demonstrated that commercially available lipid-lowering drugs cause various side effects; therefore, searching for anti-hyperlipidaemic compounds with lower toxicity is a research hotspot. This study was designed to investigate whether the marine-derived compound, 5-hydroxy-3-methoxy-5-methyl-4-butylfuran-2(5H)-one, has an anti-hyperlipidaemic activity, and the potential underlying mechanism in vitro. Results showed that the furanone had weaker cytotoxicity compared to positive control drugs. In RAW 264.7 cells, the furanone significantly lowered ox-LDL-induced lipid accumulation (~50%), and its triglyceride (TG)-lowering effect was greater than that of liver X receptor (LXR) agonist T0901317. In addition, it significantly elevated the protein levels of peroxisome proliferator-activated receptors (PPARα) and ATP-binding cassette (ABC) transporters, which could be partially inhibited by LXR antagonists, GSK2033 and SR9243. In HepG2 cells, it significantly decreased oleic acid-induced lipid accumulation, enhanced the protein levels of low-density lipoprotein receptor (LDLR), ABCG5, ABCG8 and PPARα, and reduced the expression of sterol regulatory element-binding protein 2 (~32%). PPARα antagonists, GW6471 and MK886, could significantly inhibit the furanone-induced lipid-lowering effect. Furthermore, the furanone showed a significantly lower activity on the activation of the expression of lipogenic genes compared to T0901317. Taken together, the furanone exhibited a weak cytotoxicity but had powerful TC- and TG-lowering effects most likely through targeting LXRα and PPARα, respectively. These findings indicate that the furanone has a potential application for the treatment of dyslipidaemia., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The Janus structure, by combining properties of different transition metal dichalcogenide (TMD) monolayers in a single polar material, has attracted increasing research interest because of its particular structure and potential application in electronics, optoelectronics and piezoelectronics. In this work, Janus SnSSe monolayer is predicted by means of first-principles calculations, and it exhibits dynamic and mechanical stability. By using the generalized gradient approximation (GGA) and spin-orbit coupling (SOC), the Janus SnSSe monolayer is found to be an indirect band-gap semiconductor, whose gap can easily be tuned by strain. High carrier mobilities are obtained for SnSSe monolayer, and the hole mobility is higher than the electron mobility. For SnSSe monolayer, a uniaxial strain in the basal plane can induce both strong in-plane and much weaker out-of-plane piezoelectric polarizations, which reveals the potential as a piezoelectric two-dimensional (2D) material. High absorption coefficients in the visible light region are observed, suggesting a potential photocatalytic application. Calculated results show that SnSSe monolayer has a very high power factor, making it a promising candidate for thermoelectric applications. Our works reveal that the Janus SnSSe structure can be fabricated with unique electronic, optical, piezoelectric and transport properties, and can motivate related experimental works.

Background: Cardiovascular diseases (CVD) are the leading cause of death globally. Electrocardiogram (ECG) analysis can provide thoroughly assessment for different CVDs efficiently. We propose a multi-task group bidirectional long short-term memory (MTGBi-LSTM) framework to intelligent recognize multiple CVDs based on multi-lead ECG signals., Methods: This model employs a Group Bi-LSTM (GBi-LSTM) and Residual Group Convolutional Neural Network (Res-GCNN) to learn the dual feature representation of ECG space and time series. GBi-LSTM is divided into Global Bi-LSTM and Intra-Group Bi-LSTM, which can learn the features of each ECG lead and the relationship between leads. Then, through attention mechanism, the different lead information of ECG is integrated to make the model to possess the powerful feature discriminability. Through multi-task learning, the model can fully mine the association information between diseases and obtain more accurate diagnostic results. In addition, we propose a dynamic weighted loss function to better quantify the loss to overcome the imbalance between classes., Results: Based on more than 170,000 clinical 12-lead ECG analysis, the MTGBi-LSTM method achieved accuracy, precision, recall and F1 of 88.86%, 90.67%, 94.19% and 92.39%, respectively. The experimental results show that the proposed MTGBi-LSTM method can reliably realize ECG analysis and provide an effective tool for computer-aided diagnosis of CVD.

This study employed a data envelopment analysis (DEA) by using slacks-based measure (SBM) with undesirable outputs to assess the industrial environmental efficiency of western China during the period of 2001-2015. The Malmquist index was further used to examine the changes in the industrial environmental efficiency of the analyzed region. The result showed that western China presented a low industrial environmental efficiency throughout the period of 2001-2015. Chongqing City was the only province that exhibited strong economic and environmental coordination. The level of technical development was identified as a key determinant of industrial environmental efficiency. This study provided policy implications on emissions reduction and the improvement of industrial efficiency. Limitations of the approach were provided to lay foundation for future studies.

Aim: Multiple sclerosis (MS) is a relapsing-remitting inflammatory demyelinating disease that requires long-term treatment. Although Rho kinase inhibitor Fasudil shows good therapeutic effect in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, certain side effects may limit its clinical use. This study aimed at observing the therapeutic potential of Fasudil-modified encephalitogenic mononuclear cells (MNCs) via nasal delivery in EAE and exploring possible mechanisms of action., Methods: Experimental autoimmune encephalomyelitis was induced with myelin oligodendrocyte glycoprotein 35-55 in C57BL/6 mice, and encephalitogenic MNCs were treated with Fasudil in vitro. Mice received 3 × 10 6  cells/10 μL per nasal cavity on day 3 and 11 postimmunization, respectively., Results: Fasudil-modified MNCs reduced clinical severity of EAE, improved demyelination, and decreased inflammatory cells in spinal cords. Immunohistochemical results indicated that CD4 + T cells and CD68 + macrophages were barely detected in Fasudil-MNCs group. Fasudil-modified MNCs decreased CD4 + IFN-γ + and CD4 + IL-17 + T cells, increased CD4 + IL-10 + T cells, restrained M1 markers CD16/32, CCR7, IL-12, CD8a, enhanced M2 markers CD206, CD200, CD14 in spleen. Fasudil-modified MNCs inhibited the activation of inflammatory signaling p-NF-kB/P38, accompanied by the decrease of COX-2 and the increase of Arg-1 in spinal cord, as well as the reduction of IL-17, TNF-α, IL-6 and the elevation of IL-10 in cultured supernatant of splenocytes. Fasudil-modified MNCs enhanced the levels of neurotrophic factors BDNF and NT-3 in spinal cord., Conclusion: Our results indicate that intranasal delivery of Fasudil-modified MNCs have therapeutic potential in EAE, providing a safe and effective cell therapeutic strategy to MS and/or other related disorders., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)