Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application

Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usually result in treatment failure.In this study,an alginate-based hybrid hydrogel(SOG)is developed that can be injected into the resection surface of the lungs during surgery.Briefly,endoplasmic reticulum-modified liposomes(MSLs)pre-loaded with the signal transducer and activator of transcription 3(STAT3)small interfering RNA and lidocaine hydrochloride are encapsulated in SOG.Once applied,MSLs strongly downregulated STAT3 expression in the tumor microenvironment,resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype.Meanwhile,the release of lidocaine hydrochloride(LID)was beneficial for pain relief and natural killer cell activation.Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life,including reduced MPE volume and pain relief in orthotopic NSCLC mouse models,even with a single administration.MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC,and may alter the treatment paradigms for other cancers.

Process-microstructure-properties of CuAlNi shape memory alloys fabricated by laser powder bed fusion

Cu-based shape memory alloys(SMAs)show great potential in the application of high temperature,but their performance improvement combining with additive manufacturing is still challenging.In this paper,nearly defect-free(99.7%relative density)CuAlNi SMAs with two types of thermal-induced martensites,18R and 2H,were successfully fabricated by laser powder bed fusion(LPBF).The remelting printing strat-egy with systematic optimization framework including densification and printability analysis was used to get optimal process window.The twin-related self-accommodation structure with long period stacking order substructure was formed during additive manufacturing process.The as-build samples show excel-lent mechanical properties(ultimate compressive strength of 1593±10 MPa and large fracture strain of 23.0%±0.1%)with double-yielding,and outstanding shape memory effect,with maximum recoverable strain of 3.39% and nearly 100%recovery rate under compressive strain not exceeding 6%.Furthermore,the microstructural evolution in LPBF involving remelting,martensitic transformation,and 2H marten-site was discussed.This result not only builds the microstructure framework involving high reflectivity alloys and martensitic transformation but also provides insight into the applicability of LPBF process in producing Cu-based SMAs.

Clinical significance of Koebner's phenomenon in vitiligo:a hospital-based epidemiological investigation from China

To the Editor:Vitiligo is an asymptomatic but cosmetically disfiguring disorder that results in depigmented patches in the skin.The prevalence of vitiligo was 0.56%in China according to our study in 2008.[1]Based on clinical features,vitiligo can be classified into four subtypes:segmental(SV),non-segmental(NSV),mixed,and unclassified vitiligo.It also can be divided into active and stable phases according to the disease activity.[2]Koebner’s phenomenon(KP),also known as the isomorphic response,had been defined as the development of new lesions of a dermatosis over the sites of mechanical trauma.Unlike other disease(such as psoriasis),KP in vitiligo is related to daily activities,especially to chronic friction.The Vitiligo European Task Force(VETF)has recently updated the definition and classification of KP for vitiligo.[3]

Deformation mechanism of Cu-Al-Ni shape memory alloys fabricated via laser powder b e d fusion:Tension-compression asymmetry

Introducing the unique advantage of additive manufacturing technology into copper-based shape memory alloys(SMAs)to fabricate high-performance alloys has garnered great attention in recent years,but the intrinsic relationships between microstructure and mechanical properties need to be further clarified.In this paper,the microstructural evolution of ternary CuAlNi SMAs fabricated by laser powder bed fusion(LPBF)under the tensile-compressive loading was investigated to determine the underlying mechanism of tension-compression asymmetry,that is,excellent compressive but poor tensile properties.Multiscale characterization of the different deformation stages revealed the numerous activated deformation mech-anism on the 18R martensite matrix.A twin-related transformation dominated the main plastic defor-mation process due to lower stacking faults energy and high-density pre-existing planer defects in the CuAlNi SMAs.Deformation twinning nucleated at prior austenite boundaries and developed into parallel and network structures inside the parent grain of different sizes.In addition,the preferred orientation in different stages,the stress-inducedγphase transformation,and the interaction between dislocations and stacking faults are discussed.These results not only provide significant insights to understand the detwinning and deformation twinning process of SMAs but also establish the essential framework of mi-crostructure and mechanical properties of Cu-based SMAs fabricated by LPBF.

A Truncated SVD-Based ARIMA Model for Multiple QoS Prediction in Mobile Edge Computing

In the mobile edge computing environments,Quality of Service(QoS)prediction plays a crucial role in web service recommendation.Because of distinct features of mobile edge computing,i.e.,the mobility of users and incomplete historical QoS data,traditional QoS prediction approaches may obtain less accurate results in the mobile edge computing environments.In this paper,we treat the historical QoS values at different time slots as a temporal sequence of QoS matrices.By incorporating the compressed matrices extracted from QoS matrices through truncated Singular Value Decomposition(SVD)with the classical ARIMA model,we extend the ARIMA model to predict multiple QoS values simultaneously and efficiently.Experimental results show that our proposed approach outperforms the other state-of-the-art approaches in accuracy and efficiency.

Hepatitis B virus evades immune recognition via RNA adenosine deaminase ADAR1-mediated viral RNA editing in hepatocytes

HBV is considered as a“stealth”virus that does not invoke interferon(IFN)responses;however,the mechanisms by which HBV bypasses innate immune recognition are poorly understood.In this study,we identified adenosine deaminases acting on RNA 1(ADAR1),which is a key factor in HBV evasion from IFN responses in hepatocytes.Mechanically,ADAR1 interacted with HBV RNAs and deaminated adenosine(A)to generate inosine(I),which disrupted host immune recognition and thus promoted HBV replication.Loss of ADAR1 or its deficient deaminase activity promoted IFN responses and inhibited HBV replication in hepatocytes,and blocking the IFN signaling pathways released the inhibition of HBV replication caused by ADAR1 deficiency.Notably,the HBV X protein(HBx)transcriptionally promoted ADAR1 expression to increase the threshold required to trigger intrinsic immune activation,which in turn enhanced HBV escape from immune recognition,leading to persistent infection.Supplementation with 8-azaadenosine,an ADAR1 inhibitor,efficiently enhanced liver immune activation to promote HBV clearance in vivo and in vitro.Taken together,our results delineate a molecular mechanism by which HBx promotes ADAR1-derived HBV immune escape and suggest a targeted therapeutic intervention for HBV infection.

Nanobubbles loaded with carbon quantum dots for ultrasonic fluorescence dual detection

To increase the efficiency and accuracy of clinical tumor detection,we explored multiple imaging by preparing carbon quantum dot(CQD)-loaded nanobubbles for ultrasonic fluorescence dual detection.In this experiment,we prepared 1,2-dioleoyl-3-trimethylammonium-propane chloride(DOTAP)cationic liposomes using the film dispersion method and chose perfluoropentane as the core gas material of the nanobubbles.The nanobubbles were coupled with the negatively charged CQDs through the charge effect to prepare the testing agent for two-way diagnosis with ultrasound contrast and fluorescence detection.The formulation and preparation of the loaded CQD liposome nanobubbles were screened.In vivo experiments showed that nanobubbles can be enriched to the tumor site within 5 min,which enables clearer ultrasound imaging and is conducive to tumor detection.We expect CQD-loaded liposome(Lip-CQD)nanobubbles to become a new ultrasonic contrast agent for clinical applications that can provide a basis for early tumor diagnosis and thus earlier treatment.

Electron configurations at 3d orbital of metal ion determining charge transition process in memory devices

Functional polymeric materials with electrical bi-stable states possess significant potential for high-density data storage due to their nanoscale memory site,threedimensional-stacking ability and intrinsic flexibility.Aromatic polyimides bearing donor-acceptor(D-A)skeleton could form the charge transfer complex(CTC)under an electrical field,leading to their feasibility as memory materials.Three novel porphyrinated polyimides DATPP-DSDA,Zn-DATPP-DSDA and Mn-DATPP-DSDA were designed and synthesized for information memory applications.Metal ions with different electron configurations at 3 d orbital have a determining influence on memory behaviors of polyimides:nonvolatile write-once-read-many-times memory(WORM)for DATPP-DSDA,volatile static random access memory(SRAM)for Zn-DATPP-DSDA,but no memory performance for Mn-DATPP-DSDA.By comparing the contribution of orbital transition and hole-electron distribution of chargetransfer excited states,roles of metal ions in regulating memory types were discussed.Molecular simulation results indicate that the Zn ion could play a bridge role in paving the route for excited electrons from a D to an A,while a trap role for the Mn ion in hindering this process.This study proves the feasibility of the strategy for modulating the memory behaviors of porphyrinated polyimides by varying the central metal ion and provides the exact effects of various metal ions on regulating charge transfer processes.