Emergent Edge Modes in Shifted Quasi-One-Dimensional Charge Density Waves.

We propose and study a two-dimensional phase of shifted charge density waves (CDW), which is constructed from an array of weakly coupled 1D CDW wires whose phases shift from one wire to the next. We show that the fully gapped bulk CDW has topological properties, characterized by a nonzero Chern number, that imply edge modes within the bulk gap. Remarkably, these edge modes exhibit spectral pseudoflow as a function of position along the edge, and are thus dual to the chiral edge modes of Chern insulators with their spectral flow in momentum space. Furthermore, we show that the CDW edge modes are stable against interwire coupling. Our predictions can be tested experimentally in quasi-1D CDW compounds such as Ta_{2}Se_{8}I.

Unconventional chiral charge order in kagome superconductor KV3Sb5.

Intertwining quantum order and non-trivial topology is at the frontier of condensed matter physics1-4. A charge-density-wave-like order with orbital currents has been proposed for achieving the quantum anomalous Hall effect5,6 in topological materials and for the hidden phase in cuprate high-temperature superconductors7,8. However, the experimental realization of such an order is challenging. Here we use high-resolution scanning tunnelling microscopy to discover an unconventional chiral charge order in a kagome material, KV3Sb5, with both a topological band structure and a superconducting ground state. Through both topography and spectroscopic imaging, we observe a robust 2 × 2 superlattice. Spectroscopically, an energy gap opens at the Fermi level, across which the 2 × 2 charge modulation exhibits an intensity reversal in real space, signalling charge ordering. At the impurity-pinning-free region, the strength of intrinsic charge modulations further exhibits chiral anisotropy with unusual magnetic field response. Theoretical analysis of our experiments suggests a tantalizing unconventional chiral charge density wave in the frustrated kagome lattice, which can not only lead to a large anomalous Hall effect with orbital magnetism, but also be a precursor of unconventional superconductivity.

Downregulation of P300/CBP-Associated Factor Protects from Vascular Aging via Nrf2 Signal Pathway Activation.

Increasing evidence has shown that vascular aging has a key role in the pathogenesis of vascular diseases. P300/CBP-associated factor (PCAF) is involved in many vascular pathological processes, but the role of PCAF in vascular aging is unknown. This study aims to explore the role and underlying mechanism of PCAF in vascular aging. The results demonstrated that the expression of PCAF was associated with age and aging, and remarkably increased expression of PCAF was present in human atherosclerotic coronary artery. Downregulation of PCAF could reduce angiotensin II (AngII)-induced senescence of rat aortic endothelial cells (ECs) in vitro. In addition, inhibition of PCAF with garcinol alleviated AngII-induced vascular senescence phenotype in mice. Downregulation of PCAF could alleviate AngII-induced oxidative stress injury in ECs and vascular tissue. Moreover, PCAF and nuclear factor erythroid-2-related factor 2 (Nrf2) could interact directly, and downregulation of PCAF alleviated vascular aging by promoting the activation of Nrf2 and enhancing the expression of its downstream anti-aging factors. The silencing of Nrf2 with small interfering RNA attenuated the protective effect of PCAF downregulation from vascular aging. These findings indicate that downregulation of PCAF alleviates oxidative stress by activating the Nrf2 signaling pathway and ultimately inhibits vascular aging. Thus, PCAF may be a promising target for aging-related cardiovascular disease.

Downregulation of p300/CBP-associated factor inhibits cardiomyocyte apoptosis via suppression of NF-κB pathway in ischaemia/reperfusion injury rats.

Cardiomyocyte apoptosis is the main reason of cardiac injury after myocardial ischaemia-reperfusion (I/R) injury (MIRI), but the role of p300/CBP-associated factor (PCAF) on myocardial apoptosis in MIRI is unknown. The aim of this study was to investigate the main mechanism of PCAF modulating cardiomyocyte apoptosis in MIRI. The MIRI model was constructed by ligation of the rat left anterior descending coronary vessel for 30 min and reperfusion for 24 h in vivo. H9c2 cells were harvested after induced by hypoxia for 6 h and then reoxygenation for 24 h (H/R) in vitro. The RNA interference PCAF expression adenovirus was transfected into rat myocardium and H9c2 cells. The area of myocardial infarction, cardiac function, myocardial injury marker levels, apoptosis, inflammation and oxidative stress were detected respectively. Both I/R and H/R remarkably upregulated the expression of PCAF, and downregulation of PCAF significantly attenuated myocardial apoptosis, inflammation and oxidative stress caused by I/R and H/R. In addition, downregulation of PCAF inhibited the activation of NF-κB signalling pathway in cardiomyocytes undergoing H/R. Pretreatment of lipopolysaccharide, a NF-κB pathway activator, could blunt these protective effects of PCAF downregulation on myocardial apoptosis in MIRI. These results highlight that downregulation of PCAF could reduce cardiomyocyte apoptosis by inhibiting the NF-κB pathway, thereby providing protection for MIRI. Therefore, PCAF might be a promising target for protecting against cardiac dysfunction induced by MIRI.

Signatures of Weyl Fermion Annihilation in a Correlated Kagome Magnet.

The manipulation of topological states in quantum matter is an essential pursuit of fundamental physics and next-generation quantum technology. Here we report the magnetic manipulation of Weyl fermions in the kagome spin-orbit semimetal Co_{3}Sn_{2}S_{2}, observed by high-resolution photoemission spectroscopy. We demonstrate the exchange collapse of spin-orbit-gapped ferromagnetic Weyl loops into paramagnetic Dirac loops under suppression of the magnetic order. We further observe that topological Fermi arcs disappear in the paramagnetic phase, suggesting the annihilation of exchange-split Weyl points. Our findings indicate that magnetic exchange collapse naturally drives Weyl fermion annihilation, opening new opportunities for engineering topology under correlated order parameters.

A Nonlinear Double Model for Multisensor-Integrated Navigation Using the Federated EKF Algorithm for Small UAVs.

Aimed at improving upon the disadvantages of the single centralized Kalman filter for integrated navigation, including its fragile robustness and low solution accuracy, a nonlinear double model based on the improved decentralized federated extended Kalman filter (EKF) for integrated navigation is proposed. The multisensor error model is established and simplified in this paper according to the near-ground short distance navigation applications of small unmanned aerial vehicles (UAVs). In order to overcome the centralized Kalman filter that is used in the linear Gaussian system, the improved federated EKF is designed for multisensor-integrated navigation. Subsequently, because of the navigation requirements of UAVs, especially for the attitude solution accuracy, this paper presents a nonlinear double model that consists of the nonlinear attitude heading reference system (AHRS) model and nonlinear strapdown inertial navigation system (SINS)/GPS-integrated navigation model. Moreover, the common state parameters of the nonlinear double model are optimized by the federated filter to obtain a better attitude. The proposed algorithm is compared with multisensor complementary filtering (MSCF) and multisensor EKF (MSEKF) using collected flight sensors data. The simulation and experimental tests demonstrate that the proposed algorithm has a good robustness and state estimation solution accuracy.

Loss of Junctional Adhesion Molecule A Promotes Severe Steatohepatitis in Mice on a Diet High in Saturated Fat, Fructose, and Cholesterol.

BACKGROUND & AIMS: There is evidence from clinical studies that compromised intestinal epithelial permeability contributes to the development of nonalcoholic steatohepatitis (NASH), but the exact mechanisms are not clear. Mice with disruption of the gene (F11r) encoding junctional adhesion molecule A (JAM-A) have defects in intestinal epithelial permeability. We used these mice to study how disruption of the intestinal epithelial barrier contributes to NASH. METHODS: Male C57BL/6 (control) or F11r(-/-) mice were fed a normal diet or a diet high in saturated fat, fructose, and cholesterol (HFCD) for 8 weeks. Liver and intestinal tissues were collected and analyzed by histology, quantitative reverse-transcription polymerase chain reaction, and flow cytometry. Intestinal epithelial permeability was assessed in mice by measuring permeability to fluorescently labeled dextran. The intestinal microbiota were analyzed using 16S ribosomal RNA sequencing. We also analyzed biopsy specimens from proximal colons of 30 patients with nonalcoholic fatty liver disease (NAFLD) and 19 subjects without NAFLD (controls) undergoing surveillance colonoscopy. RESULTS: F11r(-/-) mice fed a HFCD, but not a normal diet, developed histologic and pathologic features of severe NASH including steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis, whereas control mice fed a HFCD developed only modest steatosis. Interestingly, there were no differences in body weight, ratio of liver weight:body weight, or glucose homeostasis between control and F11r(-/-) mice fed a HFCD. In these mice, liver injury was associated with significant increases in mucosal inflammation, tight junction disruption, and intestinal epithelial permeability to bacterial endotoxins, compared with control mice or F11r(-/-) mice fed a normal diet. The HFCD led to a significant increase in inflammatory microbial taxa in F11r(-/-) mice, compared with control mice. Administration of oral antibiotics or sequestration of bacterial endotoxins with sevelamer hydrochloride reduced mucosal inflammation and restored normal liver histology in F11r(-/-) mice fed a HFCD. Protein and transcript levels of JAM-A were significantly lower in the intestinal mucosa of patients with NAFLD than without NAFLD; decreased expression of JAM-A correlated with increased mucosal inflammation. CONCLUSIONS: Mice with defects in intestinal epithelial permeability develop more severe steatohepatitis after a HFCD than control mice, and colon tissues from patients with NAFLD have lower levels of JAM-A and higher levels of inflammation than subjects without NAFLD. These findings indicate that intestinal epithelial barrier function and microbial dysbiosis contribute to the development of NASH. Restoration of intestinal barrier integrity and manipulation of gut microbiota might be developed as therapeutic strategies for patients with NASH.

Highly expressed long non-coding RNA CRNDE promotes cell proliferation through PI3K/AKT signalling in non-small cell lung carcinoma.

Recently, numerous studies have revealed that long non-coding RNAs (lncRNAs) play complex roles in various lung diseases, while the colorectal neoplasia differentially expressed (CRNDE) functions in non-small cell lung carcinomas (NSCLC) remain largely unknown. In the present study, we investigate the role and mechanism of CRNDE in the progression of NSCLC. The mRNA level of CRNDE in NSCLC patients and cells was detected by qRT-PCR. The influence of CRNDE silencing or over-expression on NSCLC cell proliferation and growth were assessed by MTT and flow cytometry, respectively. We also investigated the effect of abnormal CRNDE expression on cyclins and PI3K/AKT pathway. Furthermore, si-CRNDE NSCLC cell lines were injected subcutaneously into nude mice to explore tumour formation in vivo. The expression of CRNDE was significantly upregulated in NSCLC patients and cells. In addition, both loss and gain function assays revealed that CRNDE promoted NSCLC cell proliferation and growth both in vitro and in vivo. Moreover, CRNDE regulated the cell cycle transition from G0 /G1 stage to S stage and modulated the expression of CDK4, CDK6 and CCNE1. We further illustrated that CRNDE activated PI3K/AKT signalling in NSCLC cell lines. In conclusion, CRNDE was highly expressed in NSCLC malignant tissues and the heightened CRNDE strongly promoted NSCLC cell proliferation and growth through activating PI3K/AKT signalling; our results shed a light on utilizing CRNDE as a potential novel therapeutic target for the treatment of NSCLC.

Cardioprotective role of growth/differentiation factor 1 in post-infarction left ventricular remodelling and dysfunction.

Growth/differentiation factor 1 (GDF1) is a secreted glycoprotein of the transforming growth factor-ß (TGF-ß) superfamily that mediates cell differentiation events during embryonic development. GDF1 is expressed in several tissues, including the heart. However, the functional role of GDF1 in myocardial infarction (MI)-induced cardiac remodelling and dysfunction is not known. Here, we performed gain-of-function and loss-of-function studies using cardiac-specific GDF1 transgenic (TG) and knockout (KO) mice to determine the role of GDF1 in the pathogenesis of functional and architectural cardiac remodelling after MI, which was induced by surgical left anterior descending coronary artery ligation. Our results demonstrate that overexpression of GDF1 in the heart causes a significant decrease in MI-derived mortality post-MI and leads to attenuated infarct size expansion, left ventricular (LV) dilatation, and cardiac dysfunction at 1 week and 4 weeks after MI injury. Compared with control animals, cardiomyocyte apoptosis, inflammation, hypertrophy, and interstitial fibrosis were all remarkably reduced in the GDF1-TG mice following MI. In contrast, GDF1 deficiency greatly exacerbated the pathological cardiac remodelling response after infarction. Further analysis of the in vitro and in vivo signalling events indicated that the beneficial role of GDF1 in MI-induced cardiac dysfunction and LV remodelling was associated with the inhibition of non-canonical (MEK-ERK1/2) and canonical (Smad) signalling cascades. Overall, our data reveal that GDF1 in the heart is a novel mediator that protects against the development of post-infarction cardiac remodelling via negative regulation of the MEK-ERK1/2 and Smad signalling pathways. Thus, GDF1 may serve as a valuable therapeutic target for the treatment of MI.

Dickkopf-3 protects against cardiac dysfunction and ventricular remodelling following myocardial infarction.

Dickkopf-3 (DKK3) is a secreted glycoprotein of the Dickkopf family (DKK1-4) that modulates Wnt signalling. DKK3 has been reported to regulate cell development, proliferation, apoptosis, and immune response. However, the functional role of DKK3 in cardiac remodelling after myocardial infarction (MI) has not yet been elucidated. This study aimed to explore the functional significance of DKK3 in the regulation of post-MI remodelling and its underlying mechanisms. MI was induced by surgical left anterior descending coronary artery ligation in transgenic mice expressing cardiac-specific DKK3 and DKK3 knockout (KO) mice as well as their non-transgenic and DKK3(+/+) littermates. Our results demonstrated that after MI, mice with DKK3 deficiency had increased mortality, greater infarct size, and exacerbated left ventricular (LV) dysfunction. Significantly, at 1 week post-MI, the hearts of DKK3-KO mice exhibited increased apoptosis, inflammation, and LV remodelling compared with the hearts of their DKK3(+/+) littermates. Conversely, DKK3 overexpression led to the opposite phenotype after infarction. Similar results were observed in cultured neonatal rat cardiomyocytes exposed to hypoxia in vitro. Mechanistically, DKK3 promotes cardioprotection by interrupting the ASK1-JNK/p38 signalling cascades. In conclusion, our results indicate that DKK3 protects against the development of MI-induced cardiac remodelling via negative regulation of the ASK1-JNK/p38 signalling pathway. Thus, our study suggests that DKK3 may represent a potential therapeutic target for the treatment of heart failure after MI.

Vinexin-ß exacerbates cardiac dysfunction post-myocardial infarction via mediating apoptotic and inflammatory responses.

Vinexin-ß is one of the adaptor proteins that are primarily involved in signal transduction and cytoskeletal organization under various pathological conditions, including cardiac hypertrophy. However, the role of Vinexin-ß in myocardial infarction (MI) remains unknown. In this study, dramatically up-regulated Vinexin-ß expression was observed in both ischaemic human hearts and infarcted animal hearts. To explore the potential involvement of Vinexin-ß in MI further, we induced MI injury in global Vinexin-ß-knockout mice and wild-type (WT) controls as well as in mice with cardiac-specific over-expression of the human Vinexin-ß gene-transgenic (TG) and -non-transgenic (NTG) littermates. Compared with that observed in WT controls, Vinexin-ß deficiency significantly decreased MI-induced infarct size, concomitant with an improved cardiac function, leading to an increase in the survival rate. The myocardial apoptosis in the border zone was dramatically reduced by Vinexin-ß deficiency, resulting from the altered expression of apoptotic factors. Furthermore, Vinexin-ß depletion mitigated the inflammatory response, as evidenced by reduced inflammatory cell infiltration, decreased expression of cytokines and the inactivation of NF-κB (nuclear factor κB) signalling. In contrast, Vinexin-ß-TG mice were much more susceptible to MI injury compared with NTG controls. Further mechanism analyses suggested that Vinexin-ß exerted detrimental effects largely dependent on blocking AKT signalling. The effects and mechanisms of Vinexin-ß on MI observed in vivo were further confirmed by our in vitro assays. When collected, these data demonstrate for the first time that Vinexin-ß increases MI-induced mortality and worsens cardiac dysfunction through aggravation of myocardial apoptosis and inflammatory response.

Interferon regulatory factor 9 is an essential mediator of heart dysfunction and cell death following myocardial ischemia/reperfusion injury.

This study aimed to investigate whether interferon regulatory factor 9 (IRF9) is involved in the pathogenesis of myocardial ischemia-reperfusion (I/R) injury and to explore the underlying molecular mechanisms of this process. Cell death plays a major role in myocardial I/R injury. We recently determined the importance of IRF9 in coordinating molecular events in response to hypertrophic stress in cardiomyocytes. However, the roles of IRF9 in lethal myocardial injury remain to be elucidated. The involvement of IRF9 was assessed via functional assays in a mouse myocardial I/R injury model by genetic knockout and cardiomyocyte-specific transgenic overexpression of IRF9, and its effects on cardiomyocyte apoptosis and inflammation were further studied in vivo and in vitro. IRF9 was upregulated in human ischemic heart tissue and mouse hearts after I/R injury. Ablation of IRF9 protected the heart against I/R-induced cardiomyocyte death, development of inflammation, and loss of heart function. In contrast, cardiomyocyte-specific transgenic overexpression of IRF9 aggravated myocardial reperfusion injury and inflammation. IRF9 negatively regulated the Sirt1-p53 axis under I/R conditions in vivo and in vitro. Downregulation of Sirt1 expression and its downstream apoptosis-related signaling cascade, which results from I/R, was ameliorated by loss of IRF9 and exacerbated by overexpression of IRF9. Cardiomyocyte-specific deletion of Sirt1 abolished the protective effect of IRF9 knockout against I/R injury, which further indicated that IRF9 mediated myocardial reperfusion injury by modulating the Sirt1-p53 axis. Thus, IRF9 may be a novel therapeutic target for the prevention of I/R injury resulting from revascularization therapy after acute myocardial infarction (MI).

Inhibition of Sema4D attenuates pressure overload-induced pathological myocardial hypertrophy via the MAPK/NF-κB/NLRP3 pathways.

Sema4D (CD100) is closely related to pathological and physiological processes, including tumor growth, angiogenesis and cardiac development. Nevertheless, the role and mechanism of Sema4D in cardiac hypertrophy are still unclear to date. To assess the impact of Sema4D on pathological cardiac hypertrophy, TAC surgery was performed on C57BL/6 mice which were transfected with AAV9-mSema4D-shRNA or AAV9-mSema4D adeno-associated virus by tail vein injection. Our results indicated that Sema4D knockdown mitigated cardiac hypertrophy, fibrosis and dysfunction when exposed to pressure overload, and Sema4D downregulation markedly inhibited cardiomyocyte hypertrophy induced by angiotensin II. Meanwhile, Sema4D overexpression had the opposite effect in vitro and in vivo. Furthermore, analysis of signaling pathways showed that Sema4D activated the MAPK pathway during cardiac hypertrophy induced by pressure overload, and the pharmacological mitogen-activated protein kinase kinase 1/2 inhibitor U0126 almost completely reversed Sema4D overexpression-induced deteriorated phenotype, resulting in improved cardiac function. Further research indicated that myocardial hypertrophy induced by Sema4D was closely related to the expression of the pyroptosis-related proteins PP65, NLRP3, caspase-1, ASC, GSDMD, IL-18 and IL-1ß. In conclusion, our study demonstrated that Sema4D regulated the process of pathological myocardial hypertrophy through modulating MAPK/NF-κB/NLRP3 pathway, and Sema4D may be the promising interventional target of cardiac hypertrophy and heart failure.

A cascaded nonlinear fault-tolerant control for fixed-wing aircraft with wing asymmetric damage.

This paper investigates the flight dynamics of the aircraft with wing asymmetric damage and the fault-tolerant control problem to improve the stability and flight quality of damaged aircraft. A high-fidelity wing asymmetric damaged aircraft nonlinear model is developed, as well as the impact of wing asymmetric damage on the physical and aerodynamic properties of the aircraft is also analyzed. The trim strategies for damaged aircraft are investigated to achieve a rapid estimation of trim states after damage occurs. This paper presents a robust cascaded nonlinear fault-tolerant control framework that integrates the incremental nonlinear dynamic inversion control with improved piecewise-constant-based nonlinear L1 adaptive control for the stability control to enhance the stability and tracking performance of the damaged aircraft. Theoretical analysis proves that the presented fault-control structure is robust to disturbances and can decouple rapidity and robustness while guaranteeing steady-state and transient performance. Finally, the hardware-in-the-loop flight control experiment platform is developed to validate the cascaded nonlinear fault-tolerant controller. In the experiment, the proposed controller is verified under wing asymmetric damage and compared with existing methods. Experimental results show that the proposed fault-tolerant control is able to overcome wing asymmetric damage and significantly improve the tracking performance of the damaged aircraft even with 27.2% of the severe damage to the left-wing.

Galangin delivered by retinoic acid-modified nanoparticles targeted hepatic stellate cells for the treatment of hepatic fibrosis.

Hepatic fibrosis (HF) is a chronic hepatic pathological process induced by various liver injuries, with few available therapies. Previous research studies revealed that HF is characterized by the accumulation of excess extracellular matrix in the liver, mainly overexpressed by activated hepatic stellate cells (HSC). Therefore, HSC have been targeted in clinical trials for the management of HF. The aim of the present study was to develop an anti-HF drug delivery system with acrylic resin (Eudragit® RS100, Eud RS100) nanoparticles (NPs) through modification by retinoic acid (RA), modified for binding the retinol-binding protein reporter (RBPR) in HSC. Galangin (GA), is a multiple effects flavonoid which has demonstrated an anti-HF effect in our previous studies. In this study, GA was utilized for the treatment of HF. The results revealed that the NPs were well formed (diameter: 70 nm), spherical in shape, and exhibited uniform distribution and a high encapsulation efficiency. Moreover, a prominent controlled release effect and a significant increase in bioavailability was observed following the encapsulation of GA in NPs. These findings indicated that the limitation of low bioavailability due to the hydrophobic feature of GA was overcome. Furthermore, the pharmacodynamics studies demonstrated that NPs could drastically influence the anti-HF effects of GA after modification with retinoic acid. The results of the present study suggested that retinoic acid-modified GA NPs represent a promising candidate in the development of an anti-HF drug delivery system for the treatment of HF.

Panaxynol ameliorates cardiac ischemia/reperfusion injury by suppressing NLRP3-induced pyroptosis and apoptosis via HMGB1/TLR4/NF-κB axis.

BACKGROUND AND PURPOSE: Panaxynol (PNN) is a common natural minor component in Umbelliferae plants. Many clinical studies have shown that PNN exhibits nutritional value and anti-inflammatory and other pharmacological activities. However, whether PNN can mediate cardiac ischemia/reperfusion injury (IRI) remains unclear. Here, we aimed to determine the potential effects of PNN on myocardial IRI. METHODS: Myocardial IRI was stimulated in a mouse IRI model, and neonatal rat ventricle myocytes (NRVMs) were exposed to hypoxia/reoxygenation to construct in an vitro model. Myocardial infarction size, myocardial tissue injury, myocardial apoptotic index, hemodynamic monitoring, pyroptosis-related proteins, cardiac enzyme activities and inflammatory responses were examined to assess myocardial injury. RESULTS: It was found that PNN administration markedly reduced myocardial infarct size and apoptosis, suppressed myocardial damage and cell pyroptosis, attenuated pro-inflammatory cytokines and neutrophil infiltration via NLRP3 inhibitor. More importantly, PNN treatment remarkably decreased the expression of TLR4/NF-κB pathway-associated proteins and NLRP3-related pyroptosis proteins by HMGB1 inhibitor. PNN also enhanced cell viability, reduced cardiac enzyme activities, suppressed apoptosis and attenuated inflammation in the isolated NRVMs. Furthermore, vitro studies indicated that MCC950 (a NLRP3 inhibitor) increased the anti-inflammatory and anti-apoptotic effects of PNN on NRVMs via HMGB1/TLR4 pathway. CONCLUSION: To sum up, our results demonstrate that PNN exhibits a cardioprotective effect by modulating heart IRI-induced apoptosis and pyroptosis via HMGB1/TLR4/NF-κB pathway, thereby inhibiting NLRP3 inflammasome stimulation.

Galangin inhibits neointima formation induced by vascular injury via regulating the PI3K/AKT/mTOR pathway.

Aims: The proliferation and migration of vascular smooth muscle cells (VSMCs) play vital roles in the pathological process of neointima formation after vascular injury. Galangin, an extract of the ginger plant galangal, is involved in numerous biological activities, including inhibiting the proliferation and migration of tumor cells, but its effect on VSMCs is unknown. This study focused on the role and mechanism of galangin in the neointima formation induced by vascular injury. Methods and results: In this study, we found that galangin restrained the PDGF-BB-induced proliferation, migration and phenotypic switching of VSMCs in a concentration-dependent manner. In vivo, we established a model of carotid artery balloon injury in rats, followed by intragastric administration of galangin (40 mg kg-1 day-1 or 80 mg kg-1 day-1) for 14 or 28 consecutive days. Then, the degree of neointima hyperplasia was evaluated by H&E staining, and the level of relevant protein expression was assessed by immunofluorescence and western blotting. In vitro, we isolated and grew primary rat aortic smooth muscle cells, which were treated with PDGF-BB and different doses of galangin, and then CCK-8 assay, wound healing assay, transwell assay, western blotting and immunofluorescence assays were performed. We found that galangin significantly inhibited PDGF-BB-induced proliferation, migration, and phenotypic switching of VSMCs and promoted autophagy in VSMCs in vitro, and galangin significantly inhibited neointimal hyperplasia after the common carotid artery balloon injury in rats. In terms of mechanisms, galangin inhibited the PI3K/AKT/mTOR pathway, thereby suppressing VSMC's switch from a contractile to a synthetic phenotype, inhibiting VSMC proliferation, migration and phenotypic switching and upregulating the Beclin1 protein expression levels and the ratio of LC3BII/I, promoting VSMC autophagy, and thereby inhibiting neointimal hyperplasia after vascular injury. Conclusion: Our study suggests that galangin inhibits neointimal hyperplasia after vascular injury by inhibiting smooth muscle cell proliferation, migration and phenotypic switching and by promoting autophagy, and that galangin may be a promising drug for the prevention and treatment of vascular restenosis after PCI.

Serum metabolomic abnormalities in survivors of non-severe COVID-19.

Metabolic reprogramming is a distinctive characteristic of SARS-CoV-2 infection, which refers to metabolic changes in hosts triggered by viruses for their survival and spread. It is current urgent to understand the metabolic health status of COVID-19 survivors and its association with long-term health consequences of infection, especially for the predominant non-severe patients. Herein, we show systemic metabolic signatures of survivors of non-severe COVID-19 from Wuhan, China at six months after discharge using metabolomics approaches. The serum amino acids, organic acids, purine, fatty acids and lipid metabolism were still abnormal in the survivors, but the kynurenine pathway and the level of itaconic acid have returned to normal. These metabolic abnormalities are associated with liver injury, mental health, energy production, and inflammatory responses. Our findings identify and highlight the metabolic abnormalities in survivors of non-severe COVID-19, which provide information on biomarkers and therapeutic targets of infection and cues for post-hospital care and intervention strategies centered on metabolism reprogramming.

[Teeth segmentation from CBCT images using deformable triangle mesh model].

Considering the dental CBCT images' characteristics, the method of deformable surface of 3D triangle mesh model is proposed. The method uses a deformable model which is initialized from an icosahedron and evolves to fit the teeth's surface by the application of the locally adaptive external forces computed from the image data and internal forces coming from the model itself. The experimental results indicate that the proposed method is robust and accurate.

Physalin B inhibits PDGF-BB-induced VSMC proliferation, migration and phenotypic transformation by activating the Nrf2 pathway.

Vascular intimal hyperplasia is a hallmark event in vascular restenosis. The excessive proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) play important roles in the pathological mechanism of vascular intimal hyperplasia. Physalin B is an alcoholate isolated from Physalis (Solanaceae) that has a wide range of biological activities. However, the effect of physalin B on VSMCs is currently unclear. In this study, we demonstrated that physalin B significantly inhibited the proliferation, migration and phenotypic transformation of VSMCs induced by PDGF-BB. Physalin B also reduced inflammation and oxidative stress in VSMCs induced by PDGF-BB. Mechanistic studies showed that physalin B plays a role mainly by activating Nrf2. After Nrf2 activation, physalin B mitigates oxidative stress by enhancing the expression of the antioxidant gene HO-1; on the other hand, physalin B inhibits the NF-κB pathway to alleviate the inflammatory response. These two effects ultimately reduce the proliferation, migration and phenotypic transformation of VSMCs induced by PDGF-BB. In addition, in the mouse carotid artery ligation model, physalin B prevented intimal hyperplasia and inhibited the proliferation, migration and phenotypic transformation of cells in the hyperplastic intima. In conclusion, we provided significant evidence that physalin B abrogates PDGF-BB-induced VSMC proliferation, migration, phenotypic transformation and intimal hyperplasia by activating Nrf2-mediated signal transduction. Therefore, physalin B may be a potential therapeutic agent for preventing or treating restenosis.