YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway

Background:Myocardial infarction(MI)is associated with higher morbidity and mortality in the world,especially in cold weather.YBX1 is an RNA-binding protein that is required for pathological growth of cardiomyocyte by regulating cell growth and protein synthesis.But YBX1,as an individual RNA-binding protein,regulates cardiomyocytes through signaling cascades during myocardial infarction remain largely unexplored.Methods:In vivo,the mouse MI model was induced by ligating the left anterior descending coronary artery(LAD),and randomly divided into sham operation group,MI group,MI+YBX1 knockdown/overexpression group and MI+negative control(NC)group.The protective effect of YBX1 was verified by echocardiography and triphenyltetrazolium chloride staining.In vitro,mitochondrial-dependent apoptosis was investigated by using CCK8,TUNEL staining,reactive oxygen species(ROS)staining and JC-1 staining in hypoxic neonatal mouse cardiomyocytes(NMCMs).Results:YBX1 expression of cardiomyocytes was downregulated in a mouse model and a cellular model on the ischemic condition.Compared to mice induced by MI,YBX1 overexpression mediated by adeno-associated virus serotype 9(AAV9)vector reduced the infarcted size and improved cardiac function.Knockdown of endogenous YBX1 by shRNA partially aggravated ischemia-induced cardiac dysfunction.In hypoxic cardiomyocytes,YBX1 overexpression decreased lactic dehydrogenase(LDH)release,increased cell viability,and inhibited apoptosis by affecting the expression of apoptosis related proteins,while knockdown of endogenous YBX1 by siRNA had the opposite effect.Overexpression of YBX1 restored mitochondrial dysfunction in hypoxic NMCMs by increasing mitochondrial membrane potential and ATP content and decreasing ROS.In hypoxic NMCMs,YBX1 overexpression increased the expression of phosphorylated phosphatidylinositol 3 kinase(PI3K)/AKT,and the anti-apoptosis effect of YBX1 was eliminated t by LY294002,PI3K/AKT inhibitor.Conclusion:YBX1 protected the heart from ischemic damage by inhibiting the mitochondrial-dependent apoptosis through PI3K/AKT pathway.It is anticipated that YBX1 may serve as a novel therapeutic target for MI.

Magnetic Nonreciprocity in a Hybrid Device of Asymmetric Artificial Spin-Ice-Superconductors

Controlling the size and distribution of potential barriers within a medium of interacting particles can unveil unique collective behaviors and innovative functionalities.We introduce a unique superconducting hybrid device using a novel artificial spin ice structure composed of asymmetric nanomagnets.This structure forms a distinctive superconducting pinning potential that steers unconventional motion of superconducting vortices,thereby inducing a magnetic nonreciprocal effect,in contrast to the electric nonreciprocal effect commonly observed in superconducting diodes.Furthermore,the polarity of the magnetic nonreciprocity is in situ reversible through the tunable magnetic patterns of artificial spin ice.Our findings demonstrate that artificial spin ice not only precisely modulates superconducting characteristics but also opens the door to novel functionalities,offering a groundbreaking paradigm for superconducting electronics.

Notum protects against myocardial infarction-induced heart dysfunction by alleviating cardiac fibrosis

Background and Objective:Cardiac fibrosis is a pathological reparative process that follows myocardial infarctionand is associated with compromised cardiac systolic and reduced cardiac compliance.The Wnt signaling pathway is closely implicated in organ fibrosis,and Notum,a highly conserved secreted inhibitor,modulates Wnt signaling.The objective of this study was to explore the role and mechanism of Notum in cardiac fibrosis.Methods:A mouse model of cardiac remodeling was established through left coronary artery ligation surgery,with the addition of Notum injection following myocardial infarction surgery.The protective effect of Notum on myocardial infarction was assessed by evaluating cardiac function,including survival rate,echocardiographic assessment,and cardiac contraction analyses.Inflammatory cell necrosis and infiltration were confirmed through H&E and Masson staining.The expression of fibrosis-related genes andβ-catenin pathway markers was detected using Western blot quantificational RT-PCR(qRT-PCR).Additionally,EdU,wound healing,and immunofluorescence staining analyses were performed to detect the effect of Notum's in transforming growth factor beta-1(TGF-β1)induced myofibroblast transformation.Results:The administration of Notum treatment resulted in enhanced survival rates,improved cardiac function,and decreased necrosis and infiltration of inflammatory cells in mice subjected to left coronary artery ligation.Furthermore,Notum effectively impeded the senescence of cardiac fibroblasts and hindered their pathological transformation into cardiac fibroblasts.Additionally,it significantly reduced collagen production and attenuated the activation of the Wnt/β-catenin pathway.Our preliminary investigations successfully demonstrated the therapeutic potential of Notum in both fibroblasts in vitro and in a mouse model of myocardial infarction-induced cardiac fibrosis in vivo.Conclusion:Notum inhibition of the Wnt/β-catenin signaling pathway and cardiac fibroblast senescence ultimately hampers the onset of cardiac fibrosis.Our findings suggest that Notum could represent a new therapeutic strategy for the treatment of cardiac fibrosis.

New insights into the formation of silicon-oxygen layer on lithium metal anode via in situ reaction with tetraethoxysilane

Lithium metal-based secondary batteries are very promising for next generation power battery due to their high energy density.However,lithium anodes suffer from poor electrochemical reversibility in organic electrolytes due to Li dendrites and instability of the solid electrolyte interphase.Recent research demonstrated that the problem can be alleviated via tetraethoxysilane(TEOS)treated lithium metal to form a silicon oxide layer on the lithium surface,however,its reaction mechanism is controversial.Herein,we deeply explore the reaction mechanism between TEOS and Li and propose:Fresh Li can directly react with TEOS even though no lithium hydroxide exists on the lithium surface,and the participation of water will accelerate the reaction process.Moreover,it was found that the silicon oxide layer can promote the uniform deposition of lithium ions by providing lithiophilic nucleation sites,thereby achieving a long cycle life of Li metal batteries.

Students’ Numeracy and Literacy Aptitude Analysis and Prediction Using Machine Learning

Education is one of the most pivotal services in societal development as it cultivates a wide variety of skills, especially numeracy and literacy skills. However, students may have varying masteries of these two aptitudes. Some attribute this to students’ intrinsic efforts while others attribute this to students’ capabilities and affiliated environments. In this work, I explore the numeracy and literacy aptitude patterns of students from various cultures based on a dataset that contains various demographic information, from which I deduced some preliminary trends. After the comparison of numerous machine learning algorithms, the optimal algorithm or combination of a few algorithms predicts students’ performances by classifying students of different backgrounds into various potential outcomes. The results suggest that proper resources and supports are necessary for enhanced learning.

不对称C―H/C―H交叉脱氢偶联反应研究进展

近年来交叉脱氢偶联(CDC)反应在有机合成化学领域受到广泛关注,该策略在构建碳-碳键的反应中避免了底物的预官能团化,具有很高的原子经济性,符合绿色化学的发展要求。通过不对称CDC反应可以实现立体选择性构建碳-碳键,是目前有机合成中的热点研究领域。本文综述了不对称CDC反应研究进展,并对该领域未来的发展方向进行了展望。

Optimization and standardization of transient expression assays for gene functional analyses in strawberry fruits

Strawberry is increasingly used as a model plant for research on fruit growth and development.The transient gene manipulation(TGM)technique is widely used to determine the function of plant genes,including those in strawberry fruits.However,its reliable application for the precise identification of gene function has been difficult owing to the lack of conditional optimization.In this study,we found that successful transient gene manipulation requires optimization,with the vector type,temperature,and fruit developmental stage being three major factors determining success.Notably,we found that transient gene manipulation was feasible only from the large green fruit stage onwards,making it especially suitable for identifying genes involved in strawberry fruit ripening.Furthermore,we established a method called percentage difference of phenotype(PDP),in which the functional effect of a gene could be precisely and efficiently identified in strawberry fruits.This method can be used to estimate the functional effect of a gene as a value from 0 to 100%,such that different genes can be quantitatively compared for their relative abilities to regulate fruit ripening.This study provides a useful tool for accelerating research on the molecular basis of strawberry fruit ripening.

Low-cost all-iron flow battery with high performance towards long-duration energy storage

Long duration energy storage(LDES)technologies are vital for wide utilization of renewable energy sources and increasing the penetration of these technologies within energy infrastructures.Herein,we propose a low-cost alkaline all-iron flow battery by coupling ferri/ferro-cyanide redox couple with ferric/ferrous-gluconate complexes redox couple.The designed all-iron flow battery demonstrates a coulombic efficiency of above 99%and an energy efficiency of~83%at a current density of80 m A cm^(-2),which can continuously run for more than 950 cycles.Most importantly,the battery demonstrates a coulombic efficiency of more than 99.0%and an energy efficiency of~83%for a long duration(~12,16 and 20 h per cycle)charge/discharge process.Benefiting from the low cost of iron electrolytes,the overall cost of the all-iron flow battery system can be reached as low as$76.11 per k Wh based on a10 h system with a power of 9.9 k W.This work provides a new option for next-generation cost-effective flow batteries for long duration large scale energy storage.

A highly stable membrane with hierarchical structure for wide pH range flow batteries

A membrane with high stability and ion conductivity in wide pH range is essential for energy storage devices.Here,we report a novel membrane with hierarchical core-shell structure,which demonstrates high stability and ion conductivity,simultaneously under a wide pH range applications.Spectral characterizations and theoretical calculation indicate that the non-solvent induces the chain segment configuration and eventually leads to polymer-polymer phase separation,thus forming hierarchical porous core-shell structure.Benefiting from this structure,an acidic vanadium flow battery(VFB)with such a membrane shows excellent performance over 400 cycles with an energy efficiency(EE)of above 81%at current density of 120 mA cm^(-2) and an alkaline zinc-iron flow battery(AZIFB)delivers a cycling stability for more than 200 cycles at 160 mA cm^(-2),along with an EE of above 82%.This paper provides a cost-effective and simple way to fabricate membranes with high performance for variety of energyrelated devices.

A low-cost bromine-fixed additive enables a high capacity retention zinc-bromine batteries

In recent years,more and more efforts are devoting to clean energy,renewable energies in particular to achieving net zero carbon dioxide emissions[1].However,renewable energies,like solar power and wind power,are generally intermittent and random,hindering their wide application[2,3].To address this problem,there is an urgent need in effective and reliable energy storage device.

Two-Dimensional Quantum Walk with Non-Hermitian Skin Effects

We construct a two-dimensional, discrete-time quantum walk, exhibiting non-Hermitian skin effects under openboundary conditions. As a confirmation of the non-Hermitian bulk-boundary correspondence, we show that the emergence of topological edge states is consistent with the Floquet winding number, calculated using a non-Bloch band theory, invoking time-dependent generalized Brillouin zones. Further, the non-Bloch topological invariants associated with quasienergy bands are captured by a non-Hermitian local Chern marker in real space, defined via the local biorthogonal eigenwave functions of a non-unitary Floquet operator. Our work aims to stimulate further studies of non-Hermitian Floquet topological phases where skin effects play a key role.

Ambiguous clear cell carcinoma in medullary sponge kidney:A case report

Medullary sponge kidney(MSK)is a characteristic renal malformation,with a relatively low incidence.Radiologically,identification of MSK is sometimes ambiguous when compared to a renal mass.Here,we report a novel renal clear cell carcinoma in MSK,and discuss our approach to treatment.We recommended that a preoperative biopsy should be performed,followed by a comprehensive discussion regarding the appropriate perioperative preparations and careful surgical techniques that should be performed for this complex disease.

An effector-reporter system to study cellular signal transduction in strawberry fruit (Fragaria ananassa)

An effector-reporter system is a powerful tool used to study cellular signal transduction,but this technique has been traditionally used in protoplasts.A similar system to study cellular signal transduction in fruits has not yet been established.In this study,we aimed to establish an effector–reporter system for strawberry fruit,a model nonclimacteric fruit.We first investigated the characteristics of transient gene expression in strawberry fruits and found marked variation in gene expression levels among individual fruits,and this variation has complicated the establishment of a technical system.To overcome this difficulty,we investigated a sampling strategy based on a statistical analysis of the activity pattern of four different reporters(GUS,GFP,FLuc,and RLuc)among individual fruits and combinations of pairs of reporters(GUS/GFP and RLuc/FLuc).Based on an optimized sampling strategy,we finally established a step-by step protocol for the effector/reporter assay.Using FaMYB10 and FaWRKY71 as the effectors and GUS driven by the FaCHS promoter as the reporter,we demonstrated that this effector/reporter system was practical and reliable.This effector/reporter technique will contribute to an in-depth exploration of the signaling mechanism for the regulation of strawberry fruit ripening.

Organocatalytic enantioselective construction of bicyclic γ-butrolactones

An enantioselective organo-catalyzed reaction of furanones with α,β-unsaturated ketones has been established herein, which provides an efficient access to chiral bicyclic γ-butyrolactones in good yields, enantioselectivities and diastereoselectivities. Further transformations of product are demonstrated. A diamine mediated catalytic cycle is proposed.

Instant formation of nanopores on flexible polymer membranes using intense pulsed light and nanoparticle templates

The development of simple and high-throughput approaches to yield solid-state nanopores on large surface membranes may facilitate the prevalence of nanopore analysis technology and in-vitro diagnosis using portable devices.However,solidstate nanopores are typically realized by complex and highend nanofabrication equipments.Here,we present a method to achieve nanopores on polymer membranes using,silver nanoparticles(AgNPs)as templates and intense pulsed light(IPL)as a heating source.The density and size of nanopores are controllable by adjusting the spin coating rate,the concentration of nanoparticle suspension,and the size of nanoparticles(NPs).The temperature of the AgNPs can rapidly reach 1132 K under instant heating of photothermal effect through light irradiation in 2 ms,resulting in localized melting and decomposition of an underneath polycarbonate(PC)membrane to yield nanopores with sizes ranging from 10 to 270 nm.After removing the nanoparticle residues,the flexible membrane with nanopores can be integrated into a flow cell to achieve a nanopore sensor that has been used to measure the translocation behaviors of bovine serum albumin(BSA).The results have demonstrated the capability of the sensor in protein denaturation identification.This low-cost and highthroughput technique to fabricate solid-state nanopores on flexible polymeric membranes may facilitate the development of more nanopore-based flexible sensors that can be integrated with other flexible components for wearable diagnosis.

香港大学教师教学发展中心的实践及启示

依托于明确的权责分工、国际化的运行模式、多样的实现路径以及完备的服务框架,近年来香港大学教与学促进中心(CETL)在提升教师教与学品质方面成果显著。因而,系统介绍其功能与结构,归纳分析其体系特征,以期为大陆教师发展的建设提供经验和借鉴。

Precise nanomedicine for intelligent therapy of cancer

Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.

NaNbO_(3) modulated phase transition behavior and antiferroelectric stability evolution in 0.88(Bi_(0.5)Na_(0.5))TiO_(3)-0.12BaTiO_(3) lead-free ceramics

Giant strains in(Bi_(0.5)Na_(0.5))TiO_(3) based ceramics are usually attributed to electric field induced nonpolar to polar phase transition.Whether it is an ergodic relaxor R3c/P4mm ferroelectric(FE)to long-range ordered FE phase transformation or a reversible P4bm antiferroelectric(AFE)to FE phase transition is still unclear.Herein,lead-free(0.88-x)(Bi_(0.5)Na_(0.5))TiO_(3)-0.12BaTiO_(3-x)NaNbO_(3) ceramics exhibit a compositionmodulated FE tetragonal P4mm to relaxor AFE tetragonal P4bm phase transition,in which double hysteresis loop,sprout-shaped S-E curves,near-zero quasi-static d33 together with a large volume change suggest the AFE characteristics of P4bm phase.An interesting finding is that the reversibility of fieldinduced AFE P4bm phase to FE P4mm phase transition strongly depends on the NN content,from being completely irreversible at x=0.01e0.02,to partially reversible at x=0.03e0.05,and finally to completely reversible at x=0.06e0.08.It is indicated that the variation of reversibility should be attributed to the change of relative free energy caused by decreasing the FE to AFE phase transition temperature with increasing the NN content.

Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy

Autologous tumor cells and cell-derived secretions(CDS)can induce antitumor immune responses.The conditions in which cells are cultured and treated impact CDS,and cellular insults alter their composition and function.In this study,we generated CDS from tumor cells exposed to normal culture conditions,hypoxia,cisplatin,radiotherapy,photodynamic therapy,or hypochlorous acid(HOCl).In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia,cisplatin,radiotherapy or photodynamic therapy.To improve HOCl-CDS activity at the tumor site,we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold.When injected intratumorally,the HOCl-CDS hydrogel promoted tumor cell death,cytotoxic T lymphocyte infiltration,and tumor-associated macrophage reprogramming towards an M1 phenotype.The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16-F10 melanoma.Furthermore,hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade.These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.