Perilipin 5 regulates hepatic stellate cell activation and high-fat diet-induced non-alcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases globally.Hepatic stellate cells(HSCs)are the major effector cells of liver fibrosis.HSCs contain abundant lipid droplets(LDs)in their cytoplasm during quiescence.Perilipin 5(PLIN 5)is a LD surface-associated protein that plays a crucial role in lipid homeostasis.However,little is known about the role of PLIN 5 in HSC activation.Methods:PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection.At the same time,PLIN 5 gene knockout mice were constructed and fed with a high-fat diet(HFD)for 20 weeks to study the role of PLIN 5 in NAFLD.The corresponding reagent kits were used to measure TG,GSH,Caspase 3 activity,ATP level,and mitochondrial DNA copy number.Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC-MS/MS.AMPK,mitochondrial function,cell proliferation,and apoptosis-related genes and proteins were detected by western blotting and qPCR.Results:Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria,inhibition of cell proliferation,and a significant increase in cell apoptosis through AMPK activation.In addition,compared with the HFD-fed C57BL/6J mice,PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition,decreased LD abundance and size,and reduced liver fibrosis.Conclusion:These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.

Unveiling the therapeutic potential:KBU2046 halts triple-negative breast cancer cell migration by constricting TGF-β1 activation in vitro

Background:Triple-negative breast cancer(TNBC)is a heterogeneous,recurring cancer characterized by a high rate of metastasis,poor prognosis,and lack of efficient therapies.KBU2046,a small molecule inhibitor,can inhibit cell motility in malignant tumors,including breast cancer.However,the specific targets and the corresponding mechanism of its function remain unclear.Methods:In this study,we employed(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium)(MTS)assay and transwell assay to investigate the impact of KBU2046 on the proliferation and migration of TNBC cells in vitro.RNA-Seq was used to explore the targets of KBU2046 that inhibit the motility of TNBC.Finally,confirmed the predicted important signaling pathways through RT-qPCR and western blotting.Results:In this study,we found that KBU2046 functioned as a novel transforming growth factor-β(TGF-β1)inhibitor,effectively suppressing tumor cell motility in vitro.Mechanistically,it directly down-regulated leucine-rich repeat-containing 8 family,member E(LRRC8E),latent TGFβ-binding protein 3(LTBP3),dynein light chain 1(DNAL1),and MAF family of bZIP transcription factors(MAFF)genes,along with reduced protein expression of the integrin family.Additionally,KBU2046 decreased phosphorylation levels of Raf and ERK.This deactivation of the ERK signaling pathway impeded cancer invasion and metastasis.Conclusions:In summary,these findings advocate for the utilization of TGF-β1 as a diagnostic and prognostic biomarker and as a therapeutic target in TNBC.Furthermore,our data underscore the potential of KBU2046 as a novel therapeutic strategy for combating cancer metastasis.

Study on Plant Landscaping Methods in Garden Landscape Construction

Garden landscape is a beautiful complex formed by space and time complementing each other and acting together.Garden plants are the core landscaping elements in garden landscape construction.It is necessary to flexibly use a variety of plant landscaping methods to create a richer and more vivid natural landscape,and promote the improvement of the quality of the living environment and the harmonious coexistence between man and nature.

Optimal Insurance with Background Risk under the Ambiguity and Belief Heterogeneity Structure

In this paper, we discuss the optimal insurance in the presence of background risk while the insured is ambiguity averse and there exists belief heterogeneity between the insured and the insurer. We give the optimal insurance contract when maxing the insured’s expected utility of his/her remaining wealth under the smooth ambiguity model and the heterogeneous belief form satisfying the MHR condition. We calculate the insurance premium by using generalized Wang’s premium and also introduce a series of stochastic orders proposed by [1] to describe the relationships among the insurable risk, background risk and ambiguity parameter. We obtain the deductible insurance is the optimal insurance while they meet specific dependence structures.

非晶相电催化剂在电解水领域的研究进展

化石燃料短缺和环境污染引发了人们对可持续、清洁和高效新能源的关注.氢具有能量密度高、燃烧产物清洁等优点,是一种重要的能源载体,具有替代化石燃料的潜力.在各种制氢方法中,电解水制氢是获取高纯氢气的有效技术,其包含阴极析氢反应(HER)和阳极析氧反应(OER).为了实现高效的电化学水分解,需要使用高效的电催化剂以克服HER和OER的热力学势垒并降低制氢电耗.目前,广泛使用的HER和OER催化剂分别是Pt和RuO_(2)/IrO_(2)基金属或金属氧化物,该类贵金属催化剂的高成本和稀缺性严重限制了其在水分解制氢中的广泛应用.此外,金红石型RuO_(2)和IrO_(2)在阳极高电位下可溶于酸性和碱性电解质溶液中,致使催化活性下降,因此,亟需发展新型高效且稳定的电解水催化剂.相较于目前报道的晶相电解水催化剂材料,非晶相催化剂材料没有严格限定的晶体结构,并具有硬度低、比表面积大和化学稳定性好等优点,特别是其含有大量随机取向的化学键和表面暴露的缺陷,可以显著提高活性位点数量,优化反应物的吸脱附,因此在电催化领域具有良好的应用前景.自20世纪80年代末以来,一系列非晶相材料被成功制备出来且用于HER,OER和全解水中.考虑到当前非晶相电催化剂在电解水领域取得的进展,本综述对其合成方法、稳定策略、性能评估、机制探索和理论研究等进行了系统的总结.阐述了酸性和碱性条件下HER和OER的反应过程和机理,介绍了非晶电催化剂材料的制备方法,以及提升其稳定性的策略.重点介绍了含贵金属(Pt,Pd和Ir等)和非贵金属(Fe,Co,Ni和Mo等)基非晶态电催化剂在HER,OER和全解水中的性能评价,以及采用能带理论和第一性原理相结合阐述相应的电催化机理.深入讨论了当前非晶态电催化剂在电解水实际应用中遇到的关键问题,如非晶催化剂所面临的导电率低、稳定性差(尤其是高电流下)、制备困难、缺乏深入的催化机制研究和工业化前景不明朗等问题,简要地指出了该领域未来的研究方向:(1)高导电材料的引入.为了解决非晶材料导电性差的问题,可考虑引入高导电介质或引入特殊导电结构(如核壳结构等).(2)新颖的合成策略(非晶/结晶结构集成、非晶表面涂覆和创造离子缺陷等).(3)非晶材料结构高度可调的合理使用.非晶催化剂的结构具有高度可调性,在催化过程中易发生相转变,可考虑合理诱导其可控转变.(4)先进的表征手段(原位电镜、原位拉曼、原位XPS和同步辐射等)的开发.(5)理论计算工具(进一步引入机器学习、材料基因组等理论)的使用.(6)更多应用层面的探索.通过研究催化机制加深对非晶催化剂结构的认知,提高稳定性,一方面探究其在实际环境条件(高/低温、高/低pH)下的电解水性能,另一方面将其扩展到甲醇、甘油等小分子氧化应用中的探究.综上,本综述旨在更好地理解非晶相电催化剂在电解水领域的研究现状、机理研究以及存在的挑战等,从而推动非晶相电催化剂在未来电解水领域中的实际应用.

The combination of DNA methylation and positive regulation of anthocyanin biosynthesis by MYB and bHLH transcription factors contributes to the petal blotch formation in Xibei tree peony

Xibei tree peony is a distinctive cultivar group that features red–purple blotches in petals.Interestingly,the pigmentations of blotches and non-blotches are largely independent of one another.The underlying molecular mechanism had attracted lots of attention from investigators,but was still uncertain.Our present work demonstrates the factors that are closely related to blotch formation in Paeonia rockii‘Shu Sheng Peng Mo’.Non-blotch pigmentation is prevented by the silencing of anthocyanin structural genes,among which PrF3H,PrDFR,and PrANS are the three major genes.We characterized two R2R3-MYBs as the key transcription factors that control the early and late anthocyanin biosynthetic pathways.PrMYBa1,which belongs to MYB subgroup 7(SG7)was found to activate the early biosynthetic gene(EBG)PrF3H by interacting with SG5 member PrMYBa2 to form an‘MM’complex.The SG6 member PrMYBa3 interacts with two SG5(IIIf)bHLHs to synergistically activate the late biosynthetic genes(LBGs)PrDFR and PrANS,which is essential for anthocyanin accumulation in petal blotches.The comparison of methylation levels of the PrANS and PrF3H promoters between blotch and non-blotch indicated a correlation between hypermethylation and gene silencing.The methylation dynamics of PrANS promoter during flower development revealed a potential early demethylating reaction,which may have contributed to the particular expression of PrANS solely in the blotch area.We suggest that the formation of petal blotch may be highly associated with the cooperation of transcriptional activation and DNA methylation of structural gene promoters.

形貌可控的共价有机骨架材料的合成与应用

共价有机骨架(COFs)作为一种新型晶体多孔材料,在分离富集、催化、药物释放、光电等领域引起了广泛关注。COFs材料的结晶度和形貌决定了其应用。本文综述了不同形貌COFs材料,如:球形、薄膜状、棒状、管状、纤维状、带状、棒状、辊状、笼状等的合成方法和应用,提出存在的问题及解决办法,并展望其应用前景。

Quercetin-derivatives painting the yellow petals of American lotus(Nelumbo lutea)and enzymatic basis for their accumulation

American lotus(Nelumbo lutea)is one of the two species in Nelumbo and has only yellow flower.Identification of total flavonoids showed wild American lotus contained almost only flavonols with quercetin 3-O-glucuronide to be the dominant pigment.The variation tendency of the total flavonol content was coincident with yellow color variation of petals during flower development.To understand the mechanism of accumulation and constituent of pigments in petals,three pivotal genes,NlFLS1,NlFLS2 and NlFLS3,which were predicted to encode flavonol synthases were isolated and characterized by analyses of basic bioinformatics,temporal and spatial expression patterns and enzymatic activity.Their temporal expression levels showed the same variation tendency,which was also consistent with the development-dependent variation of total flavonol content.Spatial expression patterns indicated the three genes should function in petals.All the three proteins were demonstrated to be bifunctional dioxygenase,possessing both flavonol synthase activity and flavanone 3-hydroxylase activity.Besides,other flavonol biosynthesis related genes were also investigated on their expression levels to give more clues on the mechanism.Substrate preferences of the three FLSs,substrate competitions between the FLSs and other flavonol biosynthesis related enzymes,and the greatly differential expression levels between F3’H(flavonoid 3-hydroxylase)and F3’5’H(flavonoid 3,5-hydroxylase)contributed to the flavonol constituent in the petals of America lotus,namely abundant quercetin-derivatives while very few kaempferol-derivatives and myricetin-derivatives.

35例睾丸良性肿瘤的临床病例分析

目的:探讨睾丸良性肿瘤行保留睾丸手术的治疗效果、预后及其影响因素。方法:回顾性分析2004年5月至2017年5月中山大学肿瘤防治中心35例睾丸良性肿瘤患者的临床病例资料,分为保留睾丸手术组和根治性睾丸切除术组。结果:35例患者平均年龄为18.8(0.4~44.0)岁,其中14例(40.0%)行保留睾丸手术、21例(60.0%)行根治性睾丸切除术。两组患者的肿瘤大小分别为1.8(0.4~4.0)cm和2.7(1.0~8.0)cm,围手术期均未见明显并发症,且均治愈出院。术后病理为表皮囊肿18例、成熟型畸胎瘤10例、间质细胞瘤4例和腺瘤样瘤3例。10例患者行术中冰冻快速病理检查,均与石蜡病理结果相符。行保留睾丸手术的患者,随访期间均未发现复发及转移,且性功能和生育能力保存良好。结论:保留睾丸手术是可靠的,肿瘤的大小影响其实施。对于术前诊断考虑良性或性质不定的睾丸肿瘤,应行术中冰冻快速病理检查,确定为良性者行保留睾丸手术,否则行根治性睾丸切除术。

具有频率选择性的TPU/FeCo@CNT/MXene复合泡沫材料的制备与电磁屏蔽性能

鉴于目前电磁辐射日益严重,电磁屏蔽材料的研究与开发得到高度重视。文中通过填料铁钴合金改性碳纳米管(FeCo@CNT)和MXene联用,以热塑性聚氨酯(TPU)为基体材料,利用二氧化碳(CO_(2))间歇发泡法成功制备了TPU/FeCo@CNT/MXene三明治复合泡沫材料。通过矢量网络仪分析其电磁屏蔽性能,结果表明,三明治复合泡沫材料展现出频率选择性电磁屏蔽,且屏蔽峰频率随发泡条件的变化,从9.2 GHz提高至13.0 GHz。同时,实现了电磁屏蔽材料的轻量化,在密度为0.76 g/cm^(3)时,平均电磁屏蔽性能可达53.7 dB。

Turbulent combustion modeling using a flamelet generated manifold approach——a validation study in Open FOAM

An OpenFOAM based turbulence combustion solver with flamelet generated manifolds (FGMs) is presented in this paper. A series of flamelets, representative for turbulent flames, are calculated first by a one-dimensional (1D) detailed chemistry solver with the consideration of both transport and stretch/curvature contributions. The flame structure is then parameterized as a function of multiple reaction control variables. A manifold, which collects the 1D flame properties, is built from the 1D flame solutions. The control variables of the mixture fraction and the progress variable are solved from the corresponding transport equations. During the calculation, the scalar variables, e.g., temperature and species concentration, are retrieved from the manifolds by interpolation. A transport equation for NO is solved to improve its prediction accuracy. To verify the ability to deal with the enthalpy loss effect, the temperature retrieved directly from the manifolds is compared with the temperature solved from a transport equation of absolute enthalpy. The resulting FGM-computational fluid dynamics (CFD) coupled code has three significant features, i.e., accurate NO prediction, the ability to treat the heat loss effect and the adoption at the turbulence level, and high quality prediction within practical industrial configurations. The proposed method is validated against the Sandia flame D, and good agreement with the experimental data is obtained.

Optical phonon behavior and magnetism of columbite Zn0.8Co0.2Nb2O6

Columbite Zn0.8Co0.2Nb2O6 crystals were grown by optical floating zone methods. The x-ray diffraction(XRD) was used to check the structure information of the grown Zn0.8Co0.2Nb2O6 crystal. The room temperature and temperature-dependent Raman spectra were tested to investigate the optical phonon behaviors of columbite Zn0.8Co0.2Nb2O6, which exhibited a temperature stable property. The magnetics properties of Zn0.8Co0.2Nb2O6, measured by a physical property measurement system(PPMS), were also presented in this work.

Measuring Quantum Geometric Tensor of Non-Abelian System in Superconducting Circuits

Topology played an important role in physics research during the last few decades.In particular,the quantum geometric tensor that provides local information about topological properties has attracted much attention.It will reveal interesting topological properties but have not been measured in non-Abelian systems.Here,we use a four-qubit quantum system in superconducting circuits to construct a degenerate Hamiltonian with parametric modulation.By manipulating the Hamiltonian with periodic drivings,we simulate the Bernevig-Hughes-Zhang model and obtain the quantum geometric tensor from interference oscillation.In addition,we reveal its topological feature by extracting the topological invariant,demonstrating an effective protocol for quantum simulation of a non-Abelian system.

Broadband Sheet Parametric Oscillator for x^((2)) Optical Frequency Comb Generation via Cavity Phase Matching

We demonstrate a broadband optical parametric oscillation,using a sheet cavity,via cavity phase-matching.A21.2 THz broad comb-like spectrum is achieved,with a uniform line spacing of 133.0 GHz,despite a relatively large dispersion of 275.4 fs^(2)/mm around 1064 nm.With 22.6% high slope efficiency,and 14.9 kW peak power handling,this sheet optical parametric oscillator can be further developed for x^((2)) comb.

Advancements in S-scheme heterojunction materials for photocatalytic environmental remediation

Recently,S-scheme heterojunctions have gained considerable attention in the field of photocatalytic environmental remediation as their potential to achieve efficient spatial charge separation coupled with strong redox capacities.Herein,this review provides an overview of the current state-of-the-art in the development of S-scheme-based photocatalysts for the purification of environmental contaminants.The review first covers the fundamentals of heterogeneous photocatalysis for environmental purification.Subsequently,an introduction to the background,mechanism,design principles,and characterization techniques of S-scheme heterojunctions is presented.Then,the review presents a comparison and summary of using various S-scheme photocatalysts for the removal of several target pollutants,such as bacteria,heavy metals,nitrogen oxides,antibiotics,and phenols.Additionally,the modification strategies of S-scheme heterojunction photocatalysts are also provided.Finally,a brief discussion of the challenges and prospects associated with S-scheme photocatalytic systems is demonstrated.

Reversibly Cross-Linking Polyimide and Cyclophosphazene Toward Closed-Loop Recyclable Plastics with High Mechanical Strength,Excellent Flame Retardancy,and Chemical Resistance

Traditional flame-retardant plastics are technically difficult to chemically recycle.The development of newtypes of flame-retardant plastics that are intrinsically capable of being closed-loop recycled and are sufficiently robust and stable to satisfy their practical application is urgently needed.In this study,closed-loop recyclable flame-retardant plastics with high mechanical strength and excellent chemical resistance are fabricated by cross-linking amino-terminated polyimide(PI-NH_(2))and aldehyde-terminated cyclophosphazene(CP-CHO)with imine bonds.The resultant flame-retardant plastic,which is denoted as PI-CP,exhibits a tensile strength of∼115.6 MPa,Young’s modulus of∼2.5 GPa,and glass transition temperature of 316°C.In the PI-CP plastic,the imine bonds are isolated within hydrophobic microenvironments generated by the rigid and hydrophobic polyimide chains and the benzene ring of cyclophosphazenes.As a result,the PI-CP plastics are highly stable in highly acidic and basic aqueous solutions and other commonly used organic solvents.The PI-CP plastic shows outstanding flame retardancy with a limiting oxygen index value of 48.8%.More importantly,the PI-CP plastic can be depolymerized to generate the original PI-NH_(2)and CPCHO monomers in high yields(∼97%)and purity.The recovered monomers can be used to refabricate the original plastics,establishing highly efficient polymer-monomer-polymer circulation and a sustainable plastics economy.

Synthesis and molecular recognition characteristics of a tetrapodal benzene cage

In this contribution,we describe the preparation and recognition characteristics of a novel tetrapodal benzene cage(1).The cage can express a wide recognition range without losing selectivity for the object of appropriate size and functional groups.The key to obtaining the desired structural isomer of 1 is the synthesis and isolation of the o-bis(bromomethyl)benzene precursor(5).Three distinct guests,F^(−)(ex-tremely small size),d-lactate(appropriate size)and l-Asp(branched shape),were selected as examples to demonstrate the recognition characteristics of 1.By NMR titration studies,they all expressed good binding affinity(K>10^(5) L/mol)in competitive medium(10%DMSO/THF),indicating that 1 has a wide recognition scope.The highest binding constant was observed for d-lactate,revealing that 1 has good selectivity for d-lactate versus F^(−)and L-Asp.Moreover,the NMR titration study of F^(−)in DMSO indicates 1 can achieve different binding modes(1:1 and 2:1 guest-host)for small-sized guests,which allows for the further development of binary binding properties and thereafter applications in the field of catalysis.

Starting materials, processes and characteristics of bio-based foams: A review

Biofoam products have attracted considerable attention lately because there is a growing demand for green/sustainable products.To this end,various biobased foams have either been developed or are currently in development,e.g.,bio-based polyurethanes(PUs),polylactic acid(PLA),starch,and polyhydroxyalkanotates(PHAs).Indeed,significant progress has been made;however,chal-lenges still persist,for example,biobased foam products have poor processability,inferior com-patibility,thermal and strength properties.In this review,we focus on five biofoam products:namely bio-based PUs,PLA,starch,PHAs,and cellulose biofoam products,along with their prop-erties and performance,as well as their manufacturing processes.Further efforts are still needed to unlock the full potential of these bio-based products and meet the goal of complementing and gradually replacing some of their fossil-based counterparts.Finally,the challenges,as well as arising opportunities of future research directions are discussed.

Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear

Hearing loss has become increasingly prevalent and causes considerable disability,thus gravely burdening the global economy.Irreversible loss of hair cells is a main cause of sensorineural hearing loss,and currently,the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids,but these are of limited benefit in patients.It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies.At present,how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research.Multi-ple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells,and in this article,we first review the principal mechanisms underlying hair cell reproduction.We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration,and we summarize current achievements in hair cell regeneration.Lastly,we discuss potential future approaches,such as small molecule drugs and gene therapy,which might be applied for regenerating functional hair cells in the clinic.

LncRNA CFAR promotes cardiac fibrosis via the miR-449a-5p/LOXL3/mTOR axis

Cardiac fibrosis is one of the crucial pathological factors in the heart,and various cardiac conditions associated with excessive fibrosis can eventually lead to heart failure.However,the exact molecular mechanism of cardiac fibrosis remains unclear.In the present study,we show that a novel lnc RNA that we named cardiac fibrosis-associated regulator(CFAR)is a profibrotic factor in the heart.CFAR was upregulated in cardiac fibrosis and its knockdown attenuated the expression of fibrotic marker genes and the proliferation of cardiac fibroblasts,thereby ameliorating cardiac fibrosis.Moreover,CFAR acted as a ce RNA sponge for mi R-449a-5p and derepressed the expression of LOXL3,which we experimentally established as a target gene of mi R-449a-5p.In contrast to CFAR,mi R-449a-5p was found to be significantly downregulated in cardiac fibrosis,and artificial knockdown of mi R-449a-5p exacerbated fibrogenesis,whereas overexpression of mi R-449a-5p impeded fibrogenesis.Furthermore,we found that LOXL3 mimicked the fibrotic factor TGF-β1 to promote cardiac fibrosis by activating m TOR.Collectively,our study established CFAR as a new profibrotic factor acting through a novel mi R-449a-5p/LOXL3/m TOR axis in the heart and therefore might be considered as a potential molecular target for the treatment of cardiac fibrosis and associated heart diseases.