Modeling of microstructure evolution of AZ80 magnesium alloy during hot working process using a unified internal state variable method

In this paper, a unified internal state variable(ISV) model for predicting microstructure evolution during hot working process of AZ80 magnesium alloy was developed. A novel aspect of the proposed model is that the interactive effects of material hardening, recovery and dynamic recrystallization(DRX) on the characteristic deformation behavior were considered by incorporating the evolution laws of viscoplastic flow, dislocation activities, DRX nucleation and boundary migration in a coupled manner. The model parameters were calibrated based on the experimental data analysis and genetic algorithm(GA) based objective optimization. The predicted flow stress, DRX fraction and average grain size match well with experimental results. The proposed model was embedded in the finite element(FE) software DEFORM-3 D via user defined subroutine to simulate the hot compression and equal channel angular extrusion(ECAE) processes. The heterogeneous microstructure distributions at different deformation zones and the dislocation density evolution with competitive deformation mechanisms were captured.This study can provide a theoretical solution for the hot working problems of magnesium alloy.

Reversal of the immunosuppressive tumor microenvironment via platinum-based neoadjuvant chemotherapy in cervical cancer

Background Immunotherapy favors patients with tumors;however,only 3-26.3%of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors.Combined immunotherapy and chemotherapy has been explored against tumor;however,the combination remains controversial.This study aimed to investigate the tumor immune microenvironment(TIME)and the effects of platinum-based neoadjuvant chemotherapy(NACT)in cervical cancer to identify the clinical value of combining chemotherapy with immunotherapy.Methods Multiplex immunohistochemistry(IHC)with 11 markers(cluster of differentiation[CD]3,CD8,CD4,CD11c,CD68,forkhead box P3[Foxp3],programmed cell death 1[PD-1],programmed cell death 1 ligand 1[PD-L1],indoleamine 2,3-dioxygenase[IDO],cyclin-dependent kinase inhibitor 2A[p16],and cytokeratin[CK])was performed to evaluate TIME from 108 matched pre-and post-NACT cervical cancer samples.The mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing(RNA-seq)from four paired samples and subsequently verified in 41 samples using IHC.Results The infiltration rate of the CD8^(+)T cells in treatment-naive cervical cancer was 0.73%,and those of Foxp3^(+)regulatory T cells(Tregs)and IDO^(+)cells were 0.87%and 17.15%,respectively.Moreover,immunoreactive T cells,dendritic cells,and macrophages were more in the stromal than the intratumor region.NACT increased dendritic,CD3^(+)T,CD8^(+)T,and CD4^(+)T cells and decreased Tregs.The aforementioned alterations occurred predominantly in the stromal region and were primarily in responders.Non-responders primarily showed decreased Tregs and no increase in CD8^(+)T or dendritic cell infiltration.Furthermore,dendritic cells interacted more closely with CD3^(+)T cells after NACT,an effect primarily observed in responders.RNA-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex(MHC)I and MHC II after chemotherapy,validated using IHC.Conclusions NACT can reduce Tregs,and when tumor cells are effectively killed,antigen presentation is enhanced,subsequently activating antitumor immunity finitely.Our study provides the molecular characteristics and theoretical basis for the simultaneous or sequential combination of platinum-based NACT and immunotherapy for cervical cancer.

MoS2-intercalated carbon hetero-layers bonded on graphene as electrode materials for enhanced sodium/potassium ion storage

MoS2 is considered as an ideal electrode material in the field of energy storage due to high theoretical specific capacity and unique layered structure.However,limited interlayer distance and poor intrinsic electrical conductivity restrict its potential realworld application.Herein,an alternately intercalated structure of MoS2 monolayer and N-doped porous carbon(NC)layer is grown on reduced graphene oxide(rGO)via a chemical intercalated strategy.The expanded interlayer distance of MoS2(0.96 nm),enlarged by the intercalation of N-doped porous carbon layers,can enhance ion diffusion mobility,provide additional reactive sites for ion storage and maintain the stability of electrode structure.In addition,the hierarchical structures between rGO substrate and intercalated N-doped carbon layers construct a three-dimensional(3D)conductive network,which can significantly improve the electrical conductivity and the structural stability.As a result,the rGO-supported MoS2/NC electrode exhibits an ultrahigh reversible capacity and remarkable long cycling stability for sodium-ion batteries(SIBs)and potassium-ion(PIBs).Meanwhile,the as-obtained MoS2/NC@rGO electrode also delivers a superior cycle performance of 250 mAh·g−1 after 160 cycles at 0.5 A·g−1 when employed as an anode for sodium-ion full cells.

Overexpressed miR-9 promotes tumor metastasis via targeting E-cadherin in serous ovarian cancer

MicroRNAs （miRNAs） play critical roles in the development and progression in various cancers. Dysfunctional miR-9 expression remains ambiguous, and no consensus on the metastatic progression of ovarian cancer has been reached. In this study, results from the bioinformatics analysis show that the 3＇-UTR of the E- cadherin mRNA was directly regulated by miR-9. Luciferase reporter assay results confirmed that miR-9 could directly target this 3＇-UTR. miR-9 and E-cadherin expression in ovarian cancer tissue was quantified by qRT- PCR. Migration and invasion were detected by wound healing and Transwell system assay in SKOV3 and A2780. qRT-PCR and Western blot were performed to detect the epithelial-mesenchymal transition-associated mRNA and proteins. Immunofluorescence technique was used to analyze the expression and subcellular localization of E- cadherin, N-cadherin, and vimentin. The results showed that miR-9 was frequently upregulated in metastatic serous ovarian cancer tissue compared with paired primary ones. Upregulation of miR-9 could downregulate the expression of E-cadherin but upregulate the expression of mesenchymal markers （N-cadherin and vimentin）. Overexpression of miR-9 could promote the cell migration and invasion in ovarian cancer, and these processes could be effectively inhibited via miR-9 inhibitor. Thus, our study demonstrates that miR-9 may promote ovarian cancer metastasis via targeting E-cadherin and a novel potential therapeutic approach to control metastasis of ovarian cancer.

Gd_(2)O_(3) nanoparticles modified g-C_(3)N_(4) with enhanced photocatalysis activity for degradation of organic pollutants

Gd_(2) O_(3) nanoparticles modified g-C_(3) N_(4) photocatalytic composites were synthesized by a simple one-step hydrothermal method.The structure,morphology,optical properties of the prepared photocatalyst were characterized by X-ray diffraction(XRD),field emission scanning electron microscopy(FESEM),field emission transmission electron microscopy(FETEM) and X-ray photoelectron spectroscopy(XPS).The result demonstrates that gadolinium is mainly dispersed on the surface of g-C_(3) N_(4) in the form of Gd_(2) O_(3),and does not destroy the lattice structure of g-C_(3) N_(4).Besides,the gadolinium can cause the red shift of the absorption edge of light,narrow the band gap,and increase the separation efficiency of the photogenerated electron and hole of g-C_(3) N_(4).Especially,the specific surface area of g-C_(3) N_(4) can be significantly increased.Furthermore,g-C_(3) N_(4)/Gd-0.05 displays the highest photodegradation performance when it is used for degradation of methyl orange(MO),methylene blue(MB) and Rhodamine B(RhB).The photodegradation rate of g-C_(3) N_(4)/Gd-0.05 composites is 72.4% for MO,95.5% for RhB,100% for MB after120 min under visible light(λ> 420 nm) irradiation.Narrow band gap promotes the separation of photogenerated electron and hole,which enhances the photocatalytic activity of g-C_(3) N_(4).It is noted that g-C_(3) N_(4)/Gd-0.05 exhibits excellent photocatalytic stability by the photocurrent and the cyclic photodegradation of MO.

Profiling of immune features to predict immunotherapy efficacy

Immune checkpoint blockade(ICB)therapies exhibit substantial clinical benefit in different cancers,but relatively low response rates in the majority of patients highlight the need to understand mutual relationships among immune features.Here,we reveal overall positive correlations among immune checkpoints and immune cell populations.Clinically,patients benefiting from ICB exhibited increases for both immune stimulatory and inhibitory features after initiation of therapy,suggesting that the activation of the immune microenvironment might serve as the biomarker to predict immune response.As proof-of-concept,we demonstrated that the immune activation score(ISD)based on dynamic alteration of interleukins in patient plasma as early as two cycles(4-6 weeks)after starting immunotherapy can accurately predict immunotherapy efficacy.Our results reveal a systematic landscape of associations among immune features and provide a noninvasive,cost-effective,and time-efficient approach based on dynamic profiling of pre-and on-treatment plasma to predict immunotherapy efficacy.

Differential immune responses in pregnant patients recovered from COYID-19

Pregnant women are generally more susceptible to viral infection.Although the impact of SARS-CoV-2 in pregnancy remains to be determined,evidence indicates that the risk factors for severe COVID-19 are similar in pregnancy to the general population.Here we systemically analyzed the clinical characteristics of pregnant and non-pregnant female COVID-19 patients who were hospitalized during the same period and found that pregnant patients developed marked lymphopenia and higher inflammation evident by higher C-reactive protein and IL-6.To elucidate the pathways that might contribute to immunopathology or protective immunity against COVID-19 during pregnancy,we applied single-cell mRNA sequencing to profile peripheral blood mononuclear cells from four pregnant and six non-pregnant female patients after recovery along with four pregnant and three non-pregnant healthy donors.We found normal clonal expansion of T cells in the pregnant patients,heightened activation and chemotaxis in NK,NKT,and MAIT cells,and differential interferon responses in the monocyte compartment.Our data present a unique feature in both innate and adaptive immune responses in pregnant patients recovered from COVID-19.