Demonstration of a manufacturable SOT-MRAM multiplexer array towards industrial applications

We have successfully demonstrated a 1 Kb spin-orbit torque(SOT)magnetic random-access memory(MRAM)multiplexer(MUX)array with remarkable performance.The 1 Kb MUX array exhibits an in-die function yield of over 99.6%.Additionally,it provides a sufficient readout window,with a TMR/RP_sigma%value of 21.4.Moreover,the SOT magnetic tunnel junctions(MTJs)in the array show write error rates as low as 10^(-6)without any ballooning effects or back-hopping behaviors,ensuring the write stability and reliability.This array achieves write operations in 20 ns and 1.2 V for an industrial-level temperature range from-40 to 125℃.Overall,the demonstrated array shows competitive specifications compared to the state-of-the-art works.Our work paves the way for the industrial-scale production of SOT-MRAM,moving this technology beyond R&D and towards widespread adoption.

Integration of high-performance spin-orbit torque MRAM devices by 200-mm-wafer manufacturing platform

We demonstrate in-plane field-free-switching spin-orbit torque(SOT)magnetic tunnel junction(MTJ)devices that are capable of low switching current density,fast speed,high reliability,and,most importantly,manufactured uniformly by the 200-mm-wafer platform.The performance of the devices is systematically studied,including their magnetic properties,switch-ing behaviors,endurance and data retention.The successful integration of SOT devices within the 200-mm-wafer manufactur-ing platform provides a feasible way to industrialize SOT MRAMs.It is expected to obtain excellent performance of the devices by further optimizing the MTJ film stacks and the corresponding fabrication processes in the future.

Smac在非小细胞肺癌表达的临床意义(英文)

Objective:The aim of our study was to investigate the clinical significance of Smac(second mitochondria-derived activator of caspase) expression on non-small cell lung cancer(NSCLC).Methods:The expression of Smac was evaluated on RNA and protein level in tumor tissues.The expression of Smac mRNA was examined by RT-PCR in 59 samples of tumor tissues and matched normal lung tissues.The expression of Smac protein was examined by IHC in 213 cancer tissues.Results:The positive rate of Smac mRNA was found in 59.3% of cancer tissues,but only in 30.5% of matched normal tissues(P<0.05).The positive rate of Smac protein was 76.5%.The expression of Smac in stage II disease was significantly higher than that in stage I disease(P=0.001).The survival of patients with Smac overexpression was significantly shorter than those who were negative.Conclusion:Smac might be involved in the progression of NSCLC,the biologic significance of Smac in primary lung cancer needs further study.

Bispecific antibodies in cancer therapy:Target selection and regulatory requirements

In recent years,the development of bispecific antibodies(bsAbs)has been rapid,with many new structures and target combinations being created.The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China.However,there is a high degree of similarity in target selection,which could affect the development of diversity in bsAbs.This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies(mAbs).Through database research,we have identified the preferences of available bsAbs combinations,suggesting rational target selection options and warning of potential wastage of medical resources.We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.

Apoptosis and Proinflammatory Cytokine Responses of Primary Mouse Microglia and Astrocytes Induced by Human H1N1 and Avian H5N1 Influenza Viruses

Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication, mouse microglia and astrocytes were isolated, infected with human H1N1 and avian H5N1 influenza viruses, and examined for their immune responses. We observed homogeneously distributed viral receptors, sialic acid （SA）-a2,3-Galactose （Gal） and SA-a2,6-Gal, on microglia and astrocytes. Both viruses were replicative and productive in microglia and astrocytes. Virus-induced apoptosis and cytopathy in infected cells were observed at 24 h post-infection （p.i.）. Expression of IL-1β, IL-6 and TNF-a mRNA examined at 6 h and 24 h p.i. was up-regulated, and their expression levels were considerably higher in H5N1 infection. The amounts of secreted proinflammatory IL-1β, IL-6 and TNF-a at 6 h and 24 h p.i. were also induced, with greater induction by H5N1 infection. This study is the first demonstration that both human H1N1 and avian H5N1 influenza viruses can infect mouse microglia and astrocytes and induce apoptosis, cytopathy, and proinflammatory cytokine production in them in vitro. Our results suggest that the direct cellular damage and the consequences of immunopathological injury in the CNS contribute to the influenza viral pathogenesis. Cellular ＆ Molecular Immunology.

Microfluidic Electrospray Niacin Metal-Organic Frameworks Encapsulated Microcapsules for Wound Healing

Niacin metal-organic frameworks(MOFs)encapsulated microcapsules with alginate shells and copper-/zinc-niacin framework cores were in situ synthesized by using a microfuidic electrospray approach for wound healing.As the alginate shells were bacteriaresponsively degradable,the niacin MOFs encapsulated microcapsules could intelligently,controllably,and programmably release calcium,copper,and zinc ions,depending on the degree of infections.Te released ions could not only kill microbes by destroying their membrane and inducing the outfow of nutrient substance,but also activate copper/zinc superoxide dismutase(Cu/ZnSOD)to eliminate oxygen free radicals and rescue the cells from oxidative stress injury.Furthermore,the simultaneously released niacin could promote hemangiectasis and absorption of functional metal ions.Tus,the niacin MOFs encapsulated microcapsules were imparted with outstanding antibacterial,antioxidant,and angiogenesis properties.Based on an in vivo study,we have also demonstrated that the chronic wound healing process of an infected full-thickness skin defect model could be signifcantly enhanced by using the niacin MOFs encapsulated microcapsules as therapeutic agent.Terefore,the microfuidic electrospray niacin MOFs encapsulated microcapsules are potential for clinical applications.

Effects of NS1 variants of H5N1 influenza virus on interferon induction, TNFa response and p53 activity

Non-structural protein 1(NS1)is an important virulence factor of the highly pathogenic H5N1 avian influenza virus.A five-amino-acid(5 aa)deletion at position 80–84 and an aspartic acid to glutamic acid substitution at position 92(D92E)are two major NS1 mutations that are highly correlated with enhanced virulence.To investigate the effect of these mutations in H5N1 virulence,three H5N1-NS1 variants were constructed:NS51(lacking 5 aa at position 80–84),NS51(I)(carrying a 5-aa insertion at position 80–84)and NS51(IM)(carrying both the 5-aa insertion and the D92E mutation).We examined the effects of these mutations on interferon(IFN)induction,tumor-necrosis factor(TNF)a response,p53 activity and apoptosis.We found that the D92E mutation eliminated NS1’s repressive effect on IFN induction,while the 5-aa deletion resulted in enhanced resistance to TNFa responses.We also observed that all three variants exhibited a similar suppressive effect on p53 transcriptional activity,although none of them significantly influenced apoptosis of host cells.Our findings shed new light on the role of NS1 in the pathogenicity of H5N1 virus.

Novel phthalimides regulating PD-1/PD-L1 interaction as potential immunotherapy agents

Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy.Despite the inherent advantages of small-molecule inhibitors over antibodies,the discovery of small-molecule inhibitors has fallen behind that of antibody drugs.Based on docking studies between small molecule inhibitor and PD-L1 protein,changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein,which was not reported before.A series of novel phthalimide derivatives from structure-based rational design was synthesized.P39 was identified as the best inhibitor with promising activity,which not only inhibited PD-1/PD-L1 interaction(IC_(50)=8.9 nmol/L),but also enhanced killing efficacy of immune cells on cancer cells.Co-crystal data demonstrated that P39 induced the dimerization of PD-L1 proteins,thereby blocking the binding of PD-1/PD-L1.Moreover,P39 exhibited a favorable safety profile with a LD_(50)>5000 mg/kg and showed significant in vivo antitumor activity through promoting CD8^(+)T cell activation.All these data suggest that P39 acts as a promising small chemical inhibitor against the PD-1/PD-L1 axis and has the potential to improve the immunotherapy efficacy of T-cells.

Damps’role in inflammatory bowel disease:a paradoxical player of mtDNA-STING signaling pathway in gut homeostasis

The inflammatory bowel disease(IBD),including Crohn’s disease(CD)and ulcerative colitis,are chronic,relapsing immune mediated disorders of the gastrointestinal homeostasis and intestinal inflammation[1].Failure to resolve mucosal inflammation and maintain gut barrier are notable shared clinical challenges in IBD,in particular when they activate immune cells within the gut lamia propria.Clinical trials and animal model studies aiming towards DAMPs have demonstrated that they can be effective therapeutic targets in mucosal inflammation of IBD.