水通道蛋白在眼科疾病中的研究进展

水通道蛋白(aquaporins,AQPs)是一类活化能低、选择性高、能迅速转运水分子的跨膜通道蛋白家族,在眼组织中表达广泛。研究发现,AQPs在眼组织中具有维持晶状体内部循环稳态、参与房水循环、介导视网膜信号转导和促进损伤修复等生理功能。AQPs突变或功能异常会导致各种眼科疾病的发生。如果能使用一定的药物或技术手段改变AQPs的表达量和功能,有望在未来成为眼科疾病治疗的新靶点。

Skyrmion transport driven by pure voltage generated strain gradient

The magnetic skyrmion transport driven by pure voltage-induced strain gradient is proposed and studied via micromagnetic simulation.Through combining the skyrmion with multiferroic heterojunction,a voltage-induced uniaxial strain gradient is adjusted to move skyrmions.In the system,a pair of short-circuited trapezoidal top electrodes can generate the symmetric strain.Due to the symmetry of strain,the magnetic skyrmion can be driven with a linear motion in the middle of the nanostrip without deviation.We calculate the strain distribution generated by the trapezoidal top electrodes pair,and further investigate the influence of the strain intensity as well as the strain gradient on the skyrmion velocity.Our findings provide a stable and low-energy regulation method for skyrmion transport.

Shape Anisotropy and Resonance Mode Guided Reliable Interconnect Design for In-plane Magnetic Logic

Dipole coupled nanomagnets controlled by the static Zeeman field can form various magnetic logic interconnects.However, the corner wire interconnect is often unreliable and error-prone at room temperature. In this study, we address this problem by making it into a reliable type with trapezoid-shaped nanomagnets, the shape anisotropy of which helps to offer the robustness. The building method of the proposed corner wire interconnect is discussed,and both its static and dynamic magnetization properties are investigated. Static micromagnetic simulation demonstrates that it can work correctly and reliably. Dynamic response results are reached by imposing an ac microwave field on the proposed corner wire. It is found that strong ferromagnetic resonance absorption appears at a low frequency. With the help of a very small ac field with the peak resonance frequency, the required static Zeeman field to switch the corner wire is significantly decreased by ~21 m T. This novel interconnect would pave the way for the realization of reliable and low power nanomagnetic logic circuits.

Voltage-Driven Adaptive Spintronic Neuron for Energy-Efficient Neuromorphic Computing

A spintronics neuron device based on voltage-induced strain is proposed.The stochastic switching behavior,which can mimic the firing behavior of neurons,is obtained by using two voltage signals to control the in-plane magnetization of a free layer of magneto-tunneling junction.One voltage signal is used as the input,and the other voltage signal can be used to tune the activation function(Sigmoid-like) of spin neurons.Therefore,this voltage-driven tunable spin neuron does not necessarily use energy-inefficient Oersted fields and spin-polarized current.Moreover,a voltage-control reading operation is presented,which can achieve the transition of activation function from Sigmoid-like to Re LU-like.A three-layer artificial neural network based on the voltage-driven spin neurons is constructed to recognize the handwritten digits from the MNIST dataset.For the MNIST handwritten dataset,the design achieves 97.75% recognition accuracy.The present results indicate that the voltage-driven adaptive spintronic neuron has the potential to realize energy-efficient well-adapted neuromorphic computing.

Rare earth-based MOF@mesoporous silica nanoplatform for long-term and luminescence trackable chemotherapy

Developing the multifunctional nanocarriers for long-term drug release and luminescence traceability is a challenging assignment.In this task,we designed a novel nanoplatform for long-term and luminescence trackable chemotherapy,which is prepared via a hollow ZIF-8(where ZIF is zeolitic imidazolate frameworks)coated by the Eu^(3+)-doped mesoporous silica(ZIF-8@mesoporous silica).The hollow ZIF-8 is used as a drug library for loading the anticancer drug,and the pH-sensitive properties of ZIF-8 can targeted-release drugs in the tumor and cut down the poisonousness of drugs to normal cells.The shell layer of mesoporous silica can achieve the long-term drug release,which solves the problem of short drug circulation time in the body,reduces the drug administration frequency,and improves the therapeutic effect.Notably,the ZIF-8@mesoporous+doxorubicin(DOX)is injected only once during the 14-day chemotherapy.In addition,Eu^(3+)doped in mesoporous silica ensures luminescence tracking and detection of drug pathways in living cells.Hence,this nanoplatform provides a whole new strategy for the longterm treatment of tumors.

Elaiophylin triggers paraptosis and preferentially kills ovarian cancer drug-resistant cells by inducing MAPK hyperactivation

Finely tuned mitogen-activated protein kinase(MAPK)signaling is important for cancer cell survival.Perturbations that push cells out of the MAPK fitness zone result in cell death.Previously,in a screen of the North China Pharmaceutical Group Corporation’s pure compound library of microbial origin,we identified elaiophylin as an autophagy inhibitor.Here,we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum(ER)stress,ER-derived cytoplasmic vacuolization,and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells.Genome-wide CRISPR/Cas9 knockout library screening identified SHP2,an upstream intermediary of the MAPK pathway,as a critical target in elaiophylin-induced paraptosis.The cellular thermal shift assay(CETSA)and surface plasmon resonance(SPR)assay further confirmed the direct binding between the SHP2 and elaiophylin.Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition.Interestingly,elaiophylin markedly increased the alreadyelevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels.Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum,taxane,or PARPi,suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.

Platelet RNA enables accurate detection of ovarian cancer:an intercontinental,biomarker identification study

Platelets are reprogrammed by cancer via a process called education,which favors cancer development.The transcriptional profile of tumor-educated platelets(TEPs)is skewed and therefore practicable for cancer detection.This intercontinental,hospital-based,diagnostic study included 761 treatment-naive inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers(China,n=3;Netherlands,n=5;Poland,n=1)between September 2016 and May 2019.The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese(VC1 and VC2)and the European(VC3)validation cohorts collectively and independently.Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets.The AUCs for TEPs in the combined validation cohort,VC1,VC2,and VC3 were 0.918(95%CI 0.889-0.948),0.923(0.855-0.990),0.918(0.872-0.963),and 0.887(0.813-0.960),respectively.Combination of TEPs and CA125 demonstrated an AUC of 0.922(0.889-0.955)in the combined validation cohort;0.955(0.912-0.997)in VC1;0.939(0.901-0.977)in VC2;0.917(0.824-1.000)in VC3.For subgroup analysis,TEPs exhibited an AUC of o.858,0.859,and 0.920 to detect early-stage,borderline,non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis.TEPs had robustness,compatibility,and universality for preop.erative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities,heterogeneous histoiogical subtypes,and early-stage ovarian cancer.However,these observations warrant prospective validations in a larger population beforeclinicalutilities.

Platelet RNA signature independently predicts ovarian cancer prognosis by deep learning neural network model

Dear Editor,Platelets are circulating anucleate cytoplasmic fragments of megakaryocytes and characterized by their functions in wound healing and vascular integrity maintenance.Increasing evidence highlights the extensive reciprocal signaling interactions between platelets and tumor cells(Haemmerle et al.,2018).Tumor cells activate and aggregate platelets to sustain proliferation(Cho et al.,2012),resist apoptosis,and promote metastasis(Haemmerle et al.,2017).