Hierarchical learning of gastric cancer molecular subtypes by integrating multi-modal DNA-level omics data and clinical stratification

Molecular subtyping of gastric cancer(GC)aims to comprehend its genetic landscape.However,the efficacy of current subtyping methods is hampered by their mixed use of molecular features,a lack of strategy optimization,and the limited availability of public GC datasets.There is a pressing need for a precise and easily adoptable subtyping approach for early DNA-based screening and treatment.Based on TCGA subtypes,we developed a novel DNA-based hierarchical classifier for gastric cancer molecular subtyping(HCG),which employs gene mutations,copy number aberrations,and methylation patterns as predictors.By incorporating the closely related esophageal adenocarcinomas dataset,we expanded the TCGA GC dataset for the training and testing of HCG(n=453).The optimization of HCG was achieved through three hierarchical strategies using Lasso-Logistic regression,evaluated by their overall the area under receiver operating characteristic curve(auROC),accuracy,F1 score,the area under precision-recall curve(auPRC)and their capability for clinical stratification using multivariate survival analysis.Subtype-specific DNA alteration biomarkers were discerned through difference tests based on HCG defined subtypes.Our HCG classifier demonstrated superior performance in terms of overall auROC(0.95),accuracy(0.88),F1 score(0.87)and auPRC(0.86),significantly improving the clinical stratification of patients(overall p-value=0.032).Difference tests identified 25 subtype-specific DNA alterations,including a high mutation rate in the SYNE1,ITGB4,and COL22A1 genes for the MSI subtype,and hypermethylation of ALS2CL,KIAA0406,and RPRD1B genes for the EBV subtype.HCG is an accurate and robust classifier for DNA-based GC molecular subtyping with highly predictive clinical stratification performance.The training and test datasets,along with the analysis programs of HCG,are accessible on the GitHub website(github.com/LabxSCUT).

无托槽隐形矫治磨牙远中移动不同设计方式上颌牙列的三维受力分析

目的通过体外实验探究无托槽隐形矫治磨牙远中移动不同设计方式下上颌牙列的三维受力,以期为临床设计合理的磨牙远中移动方案提供依据。方法根据上颌磨牙远中移动方式,进行3种无托槽隐形矫治器设计:同时移动组设计上颌第一和第二磨牙同时远中移动;第二磨牙移动组设计上颌第二磨牙远中移动;第一磨牙移动组设计上颌第一磨牙远中移动;每组制作10个矫治器,移动量设计为0.2 mm。建立无托槽隐形矫治器上牙列三维力学传感测力装置,该装置包含14颗牙齿的上颌牙列模型,每颗牙齿与单独的传感器连接后将无托槽隐形矫治器戴入该上颌牙列模型,通过数据采集软件对14个传感器的数据进行采集。以移动牙为目标牙,除移动牙外的其余牙为支抗牙,测量3组无托槽隐形矫治器各牙位三维受力数据,并进行组间比较。结果同时移动组第一和第二磨牙矢状向受力分别为(5.61±0.94)和(5.81±1.08)N,均显著小于其他组相同牙位目标牙(P<0.05);第一磨牙移动组第二磨牙受到矢状向反作用力(-6.73±1.99)N;3组前牙均受到矢状向反作用力,力值从尖牙至中切牙逐渐减小。冠状向上,同时移动组第二前磨牙受到腭向反作用力,力值为(-2.17±1.06)N;第二磨牙移动组第一磨牙同样受到腭向反作用力,力值为(-1.99±0.70)N;第一磨牙移动组第二磨牙、第二前磨牙也受到腭向反作用力,分别为(-2.85±0.57)和(-1.85±0.74)N。相比矢状向与冠状向受力,3组目标牙和支抗牙的垂直向受力均较小。结论同时远中移动第一和第二磨牙时两者受到的矢状向矫治力较小;单独远中移动第一磨牙时第二磨牙受到较大的矢状向反作用力;磨牙远中移动时应设计相邻支抗牙的颊向位移以抵消支抗牙受到的腭向反作用力。

Atomically Precise Pd Species Accelerating CO_(2) Hydrodeoxygenation into CH_(4) with 100%Selectivity

High-rate CO_(2)-to-CH_(4)photoreduction with high selectivity is highly attractive,which is a win-win strategy for mitigating the greenhouse effect and the energy crisis.However,the poor photocatalytic activity and low product selectivity hinder the practical application.To precisely tailor the product selectivity and realize high-rate CO_(2)photoreduction,we design atomically precise Pd species supported on In_(2)O_(3)nanosheets.Taking the synthetic 1.30Pd/In_(2)O_(3)nanosheets as an example,the aberration-correction high-angle annular dark-field scanning transmission electron microscopy image displayed the Pd species atomically dispersed on the In_(2)O_(3)nanosheets.Raman spectra and X-ray photoelectron spectra established that the strong interaction between the Pd species and the In_(2)O_(3)substrate drove electron transfer from In to Pd species,resulting in electron-enriched Pd sites for CO_(2)activation.Synchrotronradiation photoemission spectroscopy demonstrated that the Pd species can tailor the conduction band edge of In_(2)O_(3)nanosheets to match the CO_(2)-to-CH_(4)pathway,instead of the CO_(2)-to-CO pathway,which theoretically accounts for the high CH_(4)selectivity.Moreover,in situ X-ray photoelectron spectroscopy unveiled that the catalytically active sites had a change from In species to Pd species over the 1.30Pd/In_(2)O_(3)nanosheets.In situ FTIR and EPR spectra reveal the atomically precise Pd species with rich electrons prefer to adsorb the electrophilic protons for accelerating the*COOH intermediates hydrogenation into CH_(4).Consequently,the 1.30Pd/In_(2)O_(3)nanosheets reached CO_(2)-to-CH_(4)photoconversion with 100%selectivity and 81.2μmol g^(−1)h^(−1)productivity.

Clinical characteristics of 19 neonates born to mothers with COVID-19

The aim of this study was to investigate the clinical characteristics of neonates born to SARS-CoV-2 infected mothers and increase the current knowledge on the perinatal consequences of COVID-19.Nineteen neonates were admitted to Tongji Hospital from January 31 to February 29,2020.Their mothers were clinically diagnosed or laboratory-confirmed with COVID-19.We prospectively collected and analyzed data of mothers and infants.There are 19 neonates included in the research.Among them,10 mothers were confirmed COVID-19 by positive SARS-CoV-2 RT-PCR in throat swab,and 9 mothers were clinically diagnosed with COVID-19.Delivery occurred in an isolation room and neonates were immediately separated from the mothers and isolated for at least 14 days.No fetal distress was found.Gestational age of the neonates was 38.61.5 weeks,and average birth weight was 3293425 g.SARS-CoV-2 RT-PCR in throat swab,urine,and feces of all neonates were negative.SARS-CoV-2 RT-PCR in breast milk and amniotic fluid was negative too.None of the neonates developed clinical,radiologic,hematologic,or biochemical evidence of COVID-19.No vertical transmission of SARS-CoV-2 and no perinatal complications in the third trimester were found in our study.The delivery should occur in isolation and neonates should be separated from the infected mothers and care givers.

T cell-depleting nanoparticles ameliorate bone loss by reducing activated T cells and regulating the Treg/Th17 balance

Estrogen deficiency is one of the most frequent causes of osteoporosis in postmenopausal women.Under chronic inflammatory conditions caused by estrogen deficiency,activated T cells contribute to elevated levels of proinflammatory cytokines,impaired osteogenic differentiation capabilities of bone marrow mesenchymal stem cells(BMMSCs),and disturbed regulatory T cell(Treg)/Th17 cell balance.However,therapeutic strategies that re-establish immune homeostasis in this disorder have not been well developed.Here,we produced T cell-depleting nanoparticles(TDNs)that ameliorated the osteopenia phenotype and rescued the osteogenic deficiency of BMMSCs in ovariectomized(OVX)mice.TDNs consist of monocyte chemotactic protein-1(MCP-1)-encapsulated mesoporous silica nanoparticles as the core and Fas-ligand(FasL)as the corona.We showed that the delicate design of the TDNs enables rapid release of MCP-1 to recruit activated T cells and then induces their apoptosis through the conjugated FasL both in vitro and in vivo.Apoptotic signals recognized by macrophages help skew the Treg/Th17 cell balance and create an immune tolerant state,further attenuating the osteogenic deficiency of BMMSCs and the osteopenia phenotype.Mechanistically,we found that the therapeutic effects of TDNs were partially mediated by apoptotic T cell-derived extracellular vesicles(ApoEVs),which promoted macrophage transformation towards the M2 phenotype.These findings demonstrate that TDNs may represent a promising strategy for treating osteoporosis and other immune disorders.

Engineered neutrophil apoptotic bodies ameliorate myocardial infarction by promoting macrophage efferocytosis and inflammation resolution

Inflammatory response plays a critical role in myocardial infarction(MI)repair.The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration,while the therapeutic strategy that simulates and enhances this natural process has not been established.Here,we constructed engineered neutrophil apoptotic bodies(eNABs)to simulate natural neutrophil apoptosis,which regulated inflammation response and enhanced MI repair.The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties,and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride(HAL).The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release,thereby further enhancing the anti-inflammation effects.In in vivo studies,the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function.This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.

Immobilization of heparin on decellularized kidney scaffold to construct microenvironment for antithrombosis and inducing reendothelialization

In recent years, rapid development of tissue engineering technology provides possibilities for the construction of artificial tissues or organs. In construction of engineered kidneys, researchers used native decellularized extracellular matrix(ECM) as the scaffolds to recellularization. However, thrombosis has been a great issue that hinders the progress of transplantation in vivo. In this study, heparin was immobilized to the collagen part of decellularized scaffold with collagen-binding peptide(CBP). Through the anticoagulant and endothelial cell reperfusion experiments, it can be demonstrated that the heparinized scaffolds absorbed less platelets and red blood cells which can effectively reduce the formation of thrombosis. Moreover, it is conducive to longterm adhesion of endothelial cells which is important for the formation of subsequent vascularization. Taken together, our results reveal that the whole kidney can be modified by CBP-heparin composite to reduce the thrombosis and provide the better conditions for neovascularization.