Sodium dichloroacetate could inhibit the endothelial-to-mesenchymal transition:a novel treatment target for pulmonary arterial hypertension

Background and Purpose Recent studies found endothelialto-mesenchymal transition(EndoMT)played an important role in the pathogenesis of pulmonary arterial hypertension.Our pilot research demonstrated the existence of Warburg effect in the lung tissue of idiopathic pulmonary arterial hypertension patients.However the relationships and the underlying mechanisms between EndoMT and Warburg effect have not been elucidated.Therefore,the purpose of this study is to determine whether metabolic reprogramming happens in EndoMT cells.We also want to investigate whether sodium dichloroacetate(DCA),a metabolic modulator,could prevent EndoMT by inhibiting Warburg effect.

Single-Cell RNA Sequencing Reveals Potential for Endothelial-to-Mesenchymal Transition in Tetralogy of Fallot

Background:Tetralogy of Fallot(TOF)is a very common cyanotic congenital heart disease.Endothelial-to-mesenchymal transition(EndoMT)is recognized as a physiological mechanism involved in embryonic heart development and endothelial formation.However,there is still a gap in the reports related to the mechanism of EndoMT development in TOF.Methods:First,transcriptomic data of single cell nuclei of TOF and Donor were obtained based on the Gene Expression Omnibus(GEO)database,and the data were normalized and clus-tered by dimensionality reduction using the Seurat package.Subsequently,differentially expressed genes(DEGs)between TOF and Donor were screened using the“FindMarkers”function,and the gene sets of interest were enriched.Finally,to characterize the dynamics of EndoMT occurrence in TOF,we performed pseudotime cell tra-jectory inference as well as utilized SCENIC analysis to probe the gene regulatory networks(GRNs)dominated by transcription factors(TFs)in endothelial cells.Results:We identified a total of six cell clusters based on single-cell nuclear transcriptome data from TOF and Donor.We found that 611 genes with up-regulated expression within TOF showed conversion to mesenchyme.By subdividing endothelial cell subtypes,endothelial cells 2 were shown to be involved in cell adhesion,migration and extracellular matrix processes.Pseudo-time and SCENIC analyses showed that endothelial cell 2 has EndoMT potential.In addition,ERG and TEAD1 are TFs that play key reg-ulatory roles in this subtype,and both of their target genes are also highly expressed in TOF.This demonstrates that ERG and TEAD1 effectively promote the EndoMT process.Conclusion:Our study reveals the molecular mechanisms underlying the development of EndoMT in TOF,which demonstrates that manipulating the endothelial-to-mesenchymal transition may offer unprecedented therapeutic potential for the treatment of TOF.

Activation of Nrf2 attenuates pulmonary vascular remodeling via inhibiting endothelial-to-mesenchymal transition

OBJECTIVE To investigate the pharmacological effect and mechanism of Salvianolic acid A(SAA) on pulmonary vascular remodeling.METHODS In current study,we conducted a series of experiments to clarify the effect of SAA,a kind of polyphenol compound,in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline(MCT)-induced EndMT.EndMT was also induced by TGF-β1 in human pulmonary arterial endothelial cells(HPAECs) in vitro.RESULTS SAA significantly attenuated EndMT,simul.taneously inhibited cell migration and reactive oxygen species(ROS) formation.In MCT-induced pulmonary arterial hypertension(PAH) model,SAA improved vascular function,decreased TGF-β1 level and inhib.ited inflammation.Mechanistically,SAA stimulated Nrf2 translocation and subsequent heme oxygen.ase-1(HO-1) up-regulation.The effect of SAA on EndMT in vitro was abolished by ZnPP,a HO-1 inhibitor.CONCLUSION This study indicates a deleterious impact of oxidative stress on EndMT.Polyphenol antioxidant treatment may provide an adjunctive action to alleviate pulmonary vascular remodeling via inhibiting EndMT.

Morin,a matrix metalloproteinase 9 inhibitor,attenuates endothelial-to-mesenchymal transition in atherosclerosis by downregulating Notch-1 signaling

Objective:Atherosclerotic cardiovascular disease poses a significant health challenge globally.Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition(End MT)in atherosclerosis.Morin is a bioflavonoid mainly extracted from white mulberry,a traditional Chinese herbal medicine with anti-inflammatory and antioxidant properties.This study examines whether morin can alleviate atherosclerosis by suppressing End MT and seeks to elucidate the underlying mechanism.Methods:We induced an in vitro End MT model in human umbilical vein endothelial cells(HUVECs)by stimulating the cells with transforming growth factor-β1(TGF-β1)(10 ng/m L)for 48 h.The in vivo experiments were performed in an atherosclerosis model using apolipoprotein E(Apo E)^(-/-)mice fed with a high-fat diet(HFD).Mice in the intervention group were given morin(50 mg/kg)orally for 4 weeks.Molecular docking and microscale thermophoresis were assayed to understand the interactions between morin and matrix metalloproteinase-9(MMP-9).Results:Morin inhibited the expression of End MT markers in a dose-dependent manner in TGF-β1-treated HUVECs.Administering 50μmol/L morin suppressed the upregulation of MMP-9 and Notch-1 signaling in TGF-β1-induced End MT.Moreover,the overexpression of MMP-9 activated Notch-1 signaling,thereby reversing morin's inhibitory effect on End MT.In the HFD-induced atherosclerotic Apo E^(-/-)mice,morin notably reduced aortic intimal hyperplasia and plaque formation by suppressing End MT.Furthermore,morin demonstrated a strong binding affinity for MMP-9.Conclusion:Morin acts as an MMP-9 inhibitor to disrupt End MT in atherosclerosis by limiting the activation of Notch-1 signaling.This study underscores morin's potential utility in the development of antiatherosclerotic medication.

Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

Bearing Fault Diagnosis Based on the Markov Transition Field and SE-IShufflenetV2 Model

A bearing fault diagnosis method based on the Markov transitionfield(MTF)and SEnet(SE)-IShufflenetV2 model is proposed in this paper due to the problems of complex working conditions,low fault diagnosis accuracy,and poor generalization of rolling bearing.Firstly,MTF is used to encode one-dimensional time series vibration sig-nals and convert them into time-dependent and unique two-dimensional feature images.Then,the generated two-dimensional dataset is fed into the SE-IShufflenetV2 model for training to achieve fault feature extraction and classification.This paper selects the bearing fault datasets from Case Western Reserve University and Paderborn University to experimentally verify the effectiveness and superiority of the proposed method.The generalization performance of the proposed method is tested under the variable load condition and different signal-to-noise ratios(SNRs).The experimental results show that the average accuracy of the proposed method under different working conditions is 99.2%without adding noise.The accuracy under different working conditions from 0 to 1 HP is 100%.When the SNR is 0 dB,the average accuracy of the proposed method can still reach 98.7%under varying working conditions.Therefore,the bearing fault diagnosis method proposed in this paper is characterized by high accuracy,strong anti-noise ability,and generalization.Moreover,the proposed method can also overcome the influence of variable working conditions on diagnosis accuracy,providing method support for the accurate diagnosis of bearing faults under strong noise and variable working conditions.

An Inspiring Transition

Xinjiang has undergone significant changes in recent years.Government efforts to create a peaceful environment are visibly yielding results.Once rife with conflict,the region now enjoys stability and growth.A sense of calm and safety is evident on its streets,which are now brimming with commerce and culture.

Transmembrane channel-like 5 drives hepatocellular carcinoma progression by regulating epithelial-mesenchymal transition

BACKGROUND Hepatocellular carcinoma(HCC)is a difficult cancer to manage due to its highly invasive and metastatic nature.AIM To investigate the molecular function of transmembrane channel-like 5(TMC5)in vitro and in vivo,with the objective of identifying novel diagnosis and treatment targets for HCC.METHODS The expression of TMC in cancer and normal tissues,along with its correlation with HCC prognosis,was analyzed using the GENT2,GEPIA database,and Human Protein Atlas.COX analysis was conducted to assess the relationship between TMC5 expression and overall survival in TCGA-LIHC patients.Further experiments were conducted to investigate the effect of TMC5 in cancer progression through loss-and gain-of-function assays in vitro and in vivo.RESULTS Bioinformatics revealed that TMC5 expression was generally higher in tumors than in normal tissues,and its expression was associated with poorer patient survival outcomes.TMC5 expression in HCC tissues and cells was consistent with the results of the bioinformatics analysis.Suppression of TMC5 expression reduced migration,invasion,and proliferation,while also decreasing the expression of epithelial-mesenchymal transition(EMT)-associated molecules in MHCC97-LM3 cells.Conversely,higher TMC5 expression significantly increased cell migration,invasion,proliferation,and EMT in MHCC97 L cells.TMC5 knockdown significantly decreased both the formation and spread of nodules in liver tissue,whereas TMC5 overexpression promoted them.CONCLUSION Our study provides compelling evidence that TMC5 is highly expressed in HCC and drives cancer progression through the activation of EMT-mediated invasion.TMC5 could represent a valuable molecular target for the diagnosis and treatment of HCC.

Suppression of PFKFB3-driven glycolysis restrains endothelial-to-mesenchymal transition and fibrotic response

Endothelial-to-mesenchymal transition(EndoMT),the process wherein endothelial cells lose endothelial identity and adopt mesenchymal-like phenotypes,constitutes a critical contributor to cardiac fibrosis.The phenotypic plasticity of endothelial cells can be intricately shaped by alteration of metabolic pathways,but how endothelial cells adjust cellular metabolism to drive EndoMT is incompletely understood.Here,we identified 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)as a critical driver of EndoMT via triggering abnormal glycolysis and compromising mitochondrial respiration.Pharmacological suppression of PFKFB3 with salvianolic acid C(SAC),a phenolic compound derived from Salvia miltiorrhiza,attenuates EndoMT and fibrotic response.PFKFB3-haplodeficiency recapitulates the anti-EndoMT effect of SAC while PFKFB3-overexpression augments the magnitude of EndoMT and exacerbates cardiac fibrosis.Mechanistically,PFKFB3-driven glycolysis compromises cytoplasmic nicotinamide adenine dinucleotide phosphate(reduced form,NADPH)production via hijacking glucose flux from pentose phosphate pathway.Efflux of mitochondrial NADPH through isocitrate/α-ketoglutarate shuttle replenishes cytoplasmic NADPH pool but meanwhile impairs mitochondrial respiration by hampering mitochondrial iron-sulfur cluster biosynthesis.SAC disrupts PFKFB3 stability by accelerating its degradation and thus maintains metabolic homeostasis in endothelial cells,underlying its anti-EndoMT effects.These findings for the first time identify the critical role of PFKFB3 in triggering EndoMT by driving abnormal glycolysis in endothelial cells,and also highlight the therapeutic potential for pharmacological intervention of PFKFB3(with SAC or other PFKFB3 inhibitors)to combat EndoMT-associated fibrotic responses via metabolic regulation.

Templated synthesis of transition metal phosphide electrocatalysts for oxygen and hydrogen evolution reactions

Transition metal phosphides(TMPs)have been regarded as alternative hydrogen evolution reaction(HER)and oxygen evolution reaction(OER)catalysts owing to their comparable activity to those of noble metal-based catalysts.TMPs have been produced in various morphologies,including hollow and porous nanostructures,which are features deemed desirable for electrocatalytic materials.Templated synthesis routes are often responsible for such morphologies.This paper reviews the latest advances and existing challenges in the synthesis of TMP-based OER and HER catalysts through templated methods.A comprehensive review of the structure-property-performance of TMP-based HER and OER catalysts prepared using different templates is presented.The discussion proceeds according to application,first by HER and further divided among the types of templates used-from hard templates,sacrificial templates,and soft templates to the emerging dynamic hydrogen bubble template.OER catalysts are then reviewed and grouped according to their morphology.Finally,prospective research directions for the synthesis of hollow and porous TMP-based catalysts,such as improvements on both activity and stability of TMPs,design of environmentally benign templates and processes,and analysis of the reaction mechanism through advanced material characterization techniques and theoretical calculations,are suggested.

Correction:Impact of Transition Metal Layer Vacancy on the Structure and Performance of P2 Type Layered Sodium Cathode Material

Following publication of the original article[1],the authors reported that the author Hun-Gi Jung should be affiliated as 3,4 and 5 instead of 4 and 5.The author’s name“A.-Yeon Kim”needed to be updated to“A-Yeon Kim”,removing the period.The correct author’s name and affiliation have been provided in this Correction.The original article[1]has been corrected.

Evolution of Superconducting-Transition Temperature with Superfluid Density and Conductivity in Pressurized Cuprate Superconductors

What factors fundamentally determine the value of superconducting transition temperature Tc in high temperature superconductors has been the subject of intense debate.Following the establishment of an empirical law known as Homes'law,there is a growing consensus in the community that the Tc value of the cuprate superconductors is closely linked to the superfluid density(ρ_(s))of its ground state and the conductivity(σ)of its normal state.However,all the data supporting this empirical law(ρ_(s)=AσT_(c))have been obtained from the ambientpressure superconductors.In this study,we present the first high-pressure results about the connection of the quantities of ρ_(s) and σ with T_(c),through the studies on the Bi_(1.74)Pb_(0.38)Sr_(1.88)CuO_(6+δ)and Bi_(2)Sr_(2)CaCu_(2)O_(8+δ),in which the value of their high-pressure resistivity(ρ=1/σ)is achieved by adopting our newly established method,while the quantity ofρs is extracted using Homes'law.We highlight that the Tc values are strongly linked to the joint response factors of magnetic field and electric field,i.e.,ρ_(s) and σ,respectively,implying that the physics determining T_(c) is governed by the intrinsic electromagnetic fields of the system.

From VIB‑to VB‑Group Transition Metal Disulfides:Structure Engineering Modulation for Superior Electromagnetic Wave Absorption

The laminated transition metal disulfides(TMDs),which are well known as typical two-dimensional(2D)semiconductive materials,possess a unique layered structure,leading to their wide-spread applications in various fields,such as catalysis,energy storage,sensing,etc.In recent years,a lot of research work on TMDs based functional materials in the fields of electromagnetic wave absorption(EMA)has been carried out.Therefore,it is of great significance to elaborate the influence of TMDs on EMA in time to speed up the application.In this review,recent advances in the development of electromagnetic wave(EMW)absorbers based on TMDs,ranging from the VIB group to the VB group are summarized.Their compositions,microstructures,electronic properties,and synthesis methods are presented in detail.Particularly,the modulation of structure engineering from the aspects of heterostructures,defects,morphologies and phases are systematically summarized,focusing on optimizing impedance matching and increasing dielectric and magnetic losses in the EMA materials with tunable EMW absorption performance.Milestones as well as the challenges are also identified to guide the design of new TMDs based dielectric EMA materials with high performance.

Role of inclination angle on columnar-to-equiaxed transition in the eutectic Al-5Mg-2Si alloy fabricated by laser powder bed fusion

In this study,the effect of inclination angles relative to the building direction in the additively manufactured eutectic Al-5Mg-2Si alloy was investigated through the laser powder bed fusion(LPBF).The microstructures and mechanical properties of the Al-5Mg-2Si alloy manufactured with different inclination angles(0°,30°,45°,60°and 90°)were reported and discussed.It is found that the“semicircular”melt pool(MP)in the load bearing face of 0°sample was eventually transformed into“stripe-like”MP in the 90°sample,accompanied by an increased fraction of melt pool boundaries(MPBs).Moreover,the microstructural analysis revealed that the columnar-to-equiaxed transition(CET)of theα-Al grains and eutectic Mg2Si was completed in the 90°sample,which were significantly refined with the average size of 10.6μm and 0.44μm,respectively.It is also found that the 90°sample exhibited good combination of strength and elongation(i.e.yield strength of 393 MPa,ultimate tensile strength of 483 MPa and elongation of 8.1%).The anisotropic mechanical properties were highly associated with the refined microstructures,thermal stress,and density of MPBs.Additionally,the CET driven by inclination angles was attributed to the variation of thermal conditions inside the local MPs.

Farm buildings and agri-food transitions in Southern France:Mapping dynamics using a stakeholder-based diagnosis

This study's goal is to present a dynamic portrait of the farm-buildings environment in Occitania,in Southern France,in order to better identify the transitions underway in agri-food chains.To this end,we undertook a ter-ritorial diagnosis based on actor statements,using 28 semi-structured interviews across Occitania.This diagnosis was enriched by graphic modelling,which enabled the spatialization of the dynamics described.We show that the process of standardisation of farm buildings prevails in the majority of the territories studied.This phenomenon has intensified in recent years with the development of vast photovoltaic-roofed sheds,accentuating the farm-land conversion and soil sealing.At the same time,in areas with strong environmental,landscape and heritage contexts,a'new adventure in farm buildings'(2022 survey)is taking shape.It is primarily driven by local short food chains,which rely on self-construction,repurposing and refurbishment,the sharing of tools and equipment,and which favour the use and reuse of local resources.This study shows that farm-buildings dynamics crystallise many challenges confronting the reterritorialisation of agriculture and food production.

Recent advances in transition metal phosphide materials:Synthesis and applications in supercapacitors

Supercapacitors(SCs)are considered promising energy storge systems because of their outstanding power density,fast charge and discharge rate and long-term cycling stability.The exploitation of cheap and efficient electrode materials is the key to improve the performance of supercapacitors.As the battery-type materials,transition metal phosphides(TMPs)possess high theoretical specific capacity,good electrical conductivity and superior structural stability,which have been extensively studied to be electrode materials for supercapacitors.In this review,we summarize the up-to-date progress on TMPs materials from diversified synthetic methods,diverse nanostructures and several prominent TMPs and their composites in application of supercapacitors.In the end,we also propose the remaining challenges toward the rational discovery and synthesis of high-performance TMP electrodes materials for energy storage.

Synthesis and Modulation of Low-Dimensional Transition Metal Chalcogenide Materials via Atomic Substitution

In recent years,low-dimensional transition metal chalcogenide(TMC)materials have garnered growing research attention due to their superior electronic,optical,and catalytic properties compared to their bulk counterparts.The controllable synthesis and manipulation of these materials are crucial for tailoring their properties and unlocking their full potential in various applications.In this context,the atomic substitution method has emerged as a favorable approach.It involves the replacement of specific atoms within TMC structures with other elements and possesses the capability to regulate the compositions finely,crystal structures,and inherent properties of the resulting materials.In this review,we present a comprehensive overview on various strategies of atomic substitution employed in the synthesis of zero-dimensional,one-dimensional and two-dimensional TMC materials.The effects of substituting elements,substitution ratios,and substitution positions on the structures and morphologies of resulting material are discussed.The enhanced electrocatalytic performance and photovoltaic properties of the obtained materials are also provided,emphasizing the role of atomic substitution in achieving these advancements.Finally,challenges and future prospects in the field of atomic substitution for fabricating low-dimensional TMC materials are summarized.

Progress on Transition Metal Ions Dissolution Suppression Strategies in Prussian Blue Analogs for Aqueous Sodium-/Potassium-Ion Batteries

Aqueous sodium-ion batteries(ASIBs)and aqueous potassium-ion batteries(APIBs)present significant potential for large-scale energy storage due to their cost-effectiveness,safety,and environmental compatibility.Nonetheless,the intricate energy storage mechanisms in aqueous electrolytes place stringent require-ments on the host materials.Prussian blue analogs(PBAs),with their open three-dimensional framework and facile synthesis,stand out as leading candidates for aqueous energy storage.However,PBAs possess a swift capacity fade and limited cycle longevity,for their structural integrity is compromised by the pronounced dis-solution of transition metal(TM)ions in the aqueous milieu.This manuscript provides an exhaustive review of the recent advancements concerning PBAs in ASIBs and APIBs.The dissolution mechanisms of TM ions in PBAs,informed by their structural attributes and redox processes,are thoroughly examined.Moreover,this study delves into innovative design tactics to alleviate the dissolution issue of TM ions.In conclusion,the paper consolidates various strategies for suppressing the dissolution of TM ions in PBAs and posits avenues for prospective exploration of high-safety aqueous sodium-/potassium-ion batteries.

Advancements in transition bimetal catalysts for electrochemical 5-hydroxymethylfurfural(HMF) oxidation

The electrochemical oxidation of 5-hydroxymethylfurfural(HMF) represents a significant avenue for sustainable chemical synthesis, owing to its potential to generate high-value derivatives from biomass feedstocks. Transition metal catalysts offer a cost-effective alternative to precious metals for catalyzing HMF oxidation, with transition bimetallic catalysts emerging as particularly promising candidates. In this review, we delve into the intricate reaction pathways and electrochemical mechanisms underlying HMF oxidation, emphasizing the pivotal role of transition bimetallic catalysts in enhancing catalytic efficiency. Subsequently, various types of transition bimetallic catalysts are explored, detailing their synthesis methods and structural modulation strategies. By elucidating the mechanisms behind catalyst modification and performance enhancement, this review sets the stage for upcoming advancements in the field, ultimately advancing the electrochemical HMF conversion and facilitating the transition towards sustainable chemical production.

Assessment of challenges and strategies for driving energy transitions in emerging markets:A socio-technological systems perspective

The pursuit of improved quality of life standards has significantly influenced the contemporary mining model in the 21st century.This era is witnessing an unprecedented transformation driven by pressing concerns related to sustainability,climate change,the just energy transition,dynamic operating environments,and complex social challenges.Such transitions present both opportunities and obstacles.The aim of this study is to provide an extensive literature review on energy transition to identify the challenges and strategies associated with navigating transformations in energy systems.Understanding these transformations is particularly critical in the face of the severe consequences of global warming,where an accelerated energy transition is viewed as a universal remedy.Adopting a socio-technological systems perspective,specifically through the application of Actor Network Theory(ANT),this research provides a theoretical foundation while categorising challenges into five distinct domains and outlining strategies across these different dimensions.These insights are specifically tailored for emerging market countries to effectively navigate energy transition while fostering the development of resilient societies.Furthermore,our findings highlight that energy transition encompasses more than a mere technological shift;it entails fundamental changes in various systemic socio-economic imperatives.Through focusing on the role of social structures in transitions,this study makes a significant and innovative contribution to ANT,which has historically been criticised for its limited acknowledgement of social structures.Consequently,we propose an emerging market energy transition framework,which not only addresses technological aspects,but also integrates social considerations.This framework paves the way for future research and exploration of energy transition dynamics.The outcomes of this study offer valuable insights to policymakers,researchers,and practitioners engaged in the mining industry,enabling them to comprehend the multifaceted challenges involved and providing practical strategies for effective resolution.Through incorporating the social dimension into the analysis,we enhance the understanding of the complex nature of energy system transformations,facilitating a more holistic approach towards achieving sustainable and resilient energy transitions in emerging markets and beyond.