Ginsenoside Rk3 is a novel PI3K/AKT-targeting therapeutics agent that regulates autophagy and apoptosis in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.

A Study on the Pedagogical Application of Chinese New Year Culture in International Chinese Language Education

Culture teaching is an inseparable part of International Chinese Language Education,and it has great significance in international Chinese language teaching.Students can enhance their interest in Chinese language learning and improve their learning effect through understanding the excellent traditional Chinese culture,at the same time,culture teaching can help to disseminate the Chinese culture and promote the development of a multicultural world.Taking the teaching of Chinese New Year culture as an example,we analyze the current teaching materials involving Chinese New Year culture with high popularity and acceptance,put forward effective teaching methods matching the feasibility of teaching Chinese New Year culture,and then present the specific teaching design of Chinese New Year culture,in order to provide references for the teaching of culture in International Chinese Language Education.

Magnetic phase transition and continuous spin switching in a high-entropy orthoferrite single crystal

Rare-earth orthoferrite REFeO_(3)(where RE is a rare-earth ion)is gaining interest.We created a high-entropy orthoferrite(Tm_(0.2)Nd_(0.2)Dy_(0.2)Y_(0.2)Yb_(0.2))FeO_(3)(HEOR)by doping five RE ions in equimolar ratios and grew the single crystal by optical floating zone method.It strongly tends to form a single-phase structure stabilized by high configurational entropy.In the low-temperature region(11.6‒14.4 K),the spin reorientation transition(SRT)ofΓ_(2)(F_(x),C_(y),G_(z))‒Γ_(24)‒Γ_(4)(G_(x),A_(y),F_(z))occurs.The weak ferromagnetic(FM)moment,which comes from the Fe sublattices distortion,rotates from the a-to c-axis.The two-step dynamic processes(Γ_(2)‒Γ_(24)‒Γ_(4))are identified by AC susceptibility measurements.SRT in HEOR can be tuned in the range of 50‒60000 Oe,which is an order of magnitude larger than that of orthoferrites in the peer system,making it a candidate for high-field spin sensing.Typical spin-switching(SSW)and continuous spin-switching(CSSW)effects occur under low magnetic fields due to the strong interactions between RE‒Fe sublattices.The CSSW effect is tunable between 20‒50 Oe,and hence,HEOR potentially can be applied to spin modulation devices.Furthermore,because of the strong anisotropy of magnetic entropy change()and refrigeration capacity(RC)based on its high configurational entropy,HEOR is expected to provide a novel approach for refrigeration by altering the orientations of the crystallographic axes(anisotropic configurational entropy).

Recent advances in systemic and local delivery of ginsenosides using nanoparticles and nanofibers

Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure,metabolism and immune function.Following the technological advances in isolation,purification and mass production,their mechanisms of action are gradually elucidated,providing solid basis for clinical applications.Ginseng extracts(total ginsenosides)and ginsenoside Rg3,CK,Rd have been marketed or entered clinical trials as drugs or dietary supplements.Despite the proven safety and efficacy of some ginsenosides,their applications are hindered by inferior pharmacokinetics such as low solubility,poor membrane permeability and metabolic instability.Nanoparticle formulation of drugs and implantable drug depots are effective strategies to improve the pharmacokinetics of therapeutic agents by enhancing solubility,providing protection,facilitating intracellular transport,and enabling sustained and controlled release.This mini-review summarizes the recent advances in systemic delivery of ginsenosides using liposomes,micelles,albumin-based nanoparticles,and inorganic nanoparticles,as well as local delivery of ginsenosides by electronspun fibrous membranes and hydrogels.

Electrical programmable multilevel nonvolatile photonic random-access memory

Photonic Random-Access Memories(P-RAM)are an essential component for the on-chip non-von Neumann photonic computing by eliminating optoelectronic conversion losses in data links.Emerging Phase-Change Materials(PCMs)have been showed multilevel memory capability,but demonstrations still yield relatively high optical loss and require cumbersome WRITE-ERASE approaches increasing power consumption and system package challenges.Here we demonstrate a multistate electrically programmed low-loss nonvolatile photonic memory based on a broadband transparent phase-change material(Ge2Sb2Se5,GSSe)with ultralow absorption in the amorphous state.A zero-staticpower and electrically programmed multi-bit P-RAM is demonstrated on a silicon-on-insulator platform,featuring efficient amplitude modulation up to 0.2 dB/μm and an ultralow insertion loss of total 0.12 dB for a 4-bit memory showing a 100×improved signal to loss ratio compared to other phase-change-materials based photonic memories.We further optimize the positioning of dual microheaters validating performance tradeoffs.Experimentally we demonstrate a half-a-million cyclability test showcasing the robust approach of this material and device.Low-loss photonic retention-of-state adds a key feature for photonic functional and programmable circuits impacting many applications including neural networks,LiDAR,and sensors for example.

Design and Realization of Communication Platform "CDream Creating a Dream" for College Students

With the increase of employment pressure,college students have aroused strong interest in innovation,entrepreneurship and competition,and they hope to get enough exercise to lay the foundation for future work. But since college students lack relevant experience and project model for reference,the descriptions on project title,format,plan and innovation angle are vague,and its declaration is often unsuccessful,which has frustrated the enthusiasm of college students. We hope to help college students declare " double creation" project via content design of " CDream creating a dream",to realize their dreams.

Thermal control magnetic switching dominated by spin reorientation transition in Mn-doped PrFeO_(3) single crystals

Spin reorientation transition (SRT) has attracted substantial attention due to its important role in the ultrafast control of spins. However, the transition temperature is usually too low for its practical applications. Here, we demonstrate the ability to modulate the SRT temperature in PrFe_(1−x)Mn_(x)O_(3) single crystals from 196 K to 317 K across the room temperature by varying the Mn concentration. Interestingly, the Γ_(4) to Γ_(1) spin reorientation of the Mn-doped PrFeO_(3) is distinct from the Γ_(4) to Γ_(2) spin reorientation transition as in the parent material. Because of the coupling between rare-earth ions and transition-metal ions in determining the SRT temperature, the demonstrated control scheme of spin reorientation transition temperature by Mn-doping is expected to be used in temperature control magnetic switching devices and applicable to many other rare-earth orthoferrites.

A secreted catalase contributes to Puccinia striiformis resistance to host-derived oxidative stress

Plants can produce reactive oxygen species(ROS)to counteract pathogen invasion,and pathogens have also evolved corresponding ROS scavenging strategies to promote infection and pathogenicity.Catalases(CATs)have been found to play pivotal roles in detoxifying H_(2)O_(2)formed by superoxide anion catalyzed by superoxide dismutases(SODs).However,few studies have addressed H_(2)O_(2)removing during rust fungi infection of wheat.In this study,we cloned a CAT gene PsCAT1 from Puccinia striiformis f.sp.tritici(Pst),which encodes a monofunctional heme-containing catalase.PsCAT1 exhibited a high degree of tolerance to pH and temperature,and forms high homopolymers.Heterologous complementation assays in Saccharomyces cerevisiae reveal that the signal peptide of PsCAT1 is functional.Overexpression of PsCAT1 enhanced S.cerevisiae resistance to H_(2)O_(2).Transient expression of PsCAT1 in Nicotiana benthamiana suppressed Bax-induced cell death.Knockdown of PsCAT1 using a host-induced gene silencing(HIGS)system led to the reduced virulence of Pst,which was correlated to H_(2)O_(2)accumulation in HIGS plants.These results indicate that PsCAT1 acts as an important pathogenicity factor that facilitates Pst infection by scavenging host-derived H_(2)O_(2).