Quantitative Parameters Analysis for Prenatally Echocardiographic Diagnosis of Atrioventricular Septal Defects

Background:Atrioventricular septal defects(AVSDs)are screened and diagnosed usually rely on the imaging characteristics of fetal echocardiography(FE).However,diagnosis on images is heavily depended on sonographers’experience and the quantitative data are rarely studied.Objective:This study aimed to realize the prenatal diagnosis of AVSDs by analyzing the quantitative data on FE.Methods:One hundred and thirteen cardiac quantitative data was analyzed in 370 normal and 49 AVSDs fetuses retrospectively.The top six with the highest diagnostic accuracy rate were acquired according to the area under the curve(AUC),and the diagnostic value of six variables was analyzed.Results:Six parameters obtained on the four-chamber view(4CHV),including the atrial to ventricular length ratio in end-diastole(AVLR-ED),AVLR-ED combined with the atrial to ventricular length ratio in end-systole(AVLR-ES),quantile score(Q score)of AVLR-ED,Q score of AVLR-ES,Q score of ventricle length in end-diastole(VL-ED),and AVLR-ES,were the top six with the highest diagnostic value,and the AUC was 0.99(95%CI 0.99–1.00),0.99(95%CI 0.99–1.00),0.99(95%CI 0.98–1.00),0.95(95%CI 0.91–0.99),0.93(95%CI 0.87–0.99),and 0.91(95%CI 0.83–1.00),respectively.And within the 20%false positive rate,the diagnostic sensitivity was greater than 100%,100%,100%,90%,90%,and 88%,respectively.Conclusions:Six variables could be used for prenatal diagnosis of AVSDs.Among them,AVLR-ED and Q score of AVLR-ED,obtained on the 4CHV,were more convenient to acquire and had higher diagnostic accuracy.

Role of pyroptosis in inflammation and cancer

Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures,resulting in the release of cellular contents that can activate strong inflammatory and immune responses.Pyroptosis,an innate immune response,can be triggered by the activation of inflammasomes by various influencing factors.Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11,both of which cleave gasdermin D to release its N-terminal domain,which can bind membrane lipids and perforate the cell membrane.Here,we review the latest advancements in research on the mechanisms of pyroptosis,newly discovered influencing factors,antitumoral properties,and applications in various diseases.Moreover,this review also provides updates on potential targeted therapies for inflammation and cancers,methods for clinical prevention,and finally challenges and future directions in the field.

Ferroptosis in cancer and cancer immunotherapy

The hallmark of tumorigenesis is the successful circumvention of cell death regulation for achieving unlimited replication and immortality.Ferroptosis is a newly identified type of cell death dependent on lipid peroxidation which differs from classical programmed cell death in terms of morphology,physiology and biochemistry.The broad spectrum of injury and tumor tolerance are the main reasons for radiotherapy and chemotherapy failure.The effective rate of tumor immunotherapy as a new treatment method is less than 30%.Ferroptosis can be seen in radiotherapy,chemotherapy,and tumor immunotherapy;therefore,fer-roptosis activation may be a potential strategy to overcome the drug resistance mechanism of traditional cancer treatments.In this review,the characteristics and causes of cell death by lipid peroxidation in ferroptosis are briefly described.In addition,the three metabolic regulations of ferroptosis and its crosstalk with classical signaling pathways are summarized.Collectively,these findings sug-gest the vital role of ferroptosis in immunotherapy based on the interaction of ferroptosis with tumor immunotherapy,chemotherapy and radiotherapy,thus,indicating the remarkable potential of ferroptosis in cancer treatment.

The function and clinical application of extracellular vesicles in innate immune regulation

The innate immune system plays a crucial role in the host defense against viral and microbial infection.Exosomes constitute a subset of extracellular vesicles(EVs)that can be released by almost all cell types.Owing to their capacity to shield the payload from degradation and to evade recognition and subsequent removal by the immune system,exosomes efficiently transport functional components to recipient cells.Accumulating evidence has recently shown that exosomes derived from tumor cells,host cells and even bacteria and parasites mediate the communication between the invader and innate immune cells and thus play an irreplaceable function in the dissemination of pathogens and donor cell-derived molecules,modulating the innate immune responses of the host.In this review,we describe the current understanding of EVs(mainly focusing on exosomes)and summarize and discuss their crucial roles in determining innate immune responses.Additionally,we discuss the potential of using exosomes as biomarkers and cancer vaccines in diagnostic and therapeutic applications.

珊瑚来源真菌Parengyodontium album SCSIO SX7W11中聚酮化合物的发现及其生物合成途径分析

海洋来源真菌的天然产物因其独特的结构与生物学活性而备受关注,而利用基因组信息对其代谢产物进行深入挖掘也成为研究策略之一。【目的】本文以一株南海珊瑚来源的真菌Parengyodontium album SCSIO SX7W11为目标菌株,挖掘其生产聚酮类化合物的潜能。【方法】本研究利用Illumina Miseq技术对SX7W11菌株进行全基因组扫描测序,运用生物信息学手段对其基因组的生物合成基因簇进行预测和基因功能注释,挖掘可能产生新颖聚酮化合物的基因簇。对SX7W11进行放大发酵后,利用正相色谱、中压反相色谱、Sephadex LH-20凝胶色谱、HPLC半制备等分离手段分离纯化出单体化合物。再利用高分辨质谱(HR-ESI-MS)、^(1)H NMR、^(13)C NMR、X-ray单晶衍射等波谱手段确定化合物的结构,并根据生物合成基因簇对化合物的生物合成途径进行推导。【结果】全基因组扫描测序结果显示,P.album SCSIO SX7W11基因组大小为34.0 Mb,含有24个生物合成基因簇,包括6个聚酮合酶基因簇以及3个萜烯合酶基因簇。从发酵产物中分离鉴定到3个聚酮类化合物:emodin(1)、alternaphenol B(2)和sydowinin A(3),其中化合物3获得了单晶结构数据。通过生物信息学方法从菌株基因组中定位到了sydowinin A的生物合成基因簇。结合文献对emodin(1)、alternaphenol B(2)和sydowinin A(3)的生物合成途径进行了分析。【结论】本研究通过基因组挖掘及培养基优化,发现1株珊瑚来源的真菌P.album SCSIO SX7W11具有生产sydowinins类聚酮类化合物的能力,为该类化合物生物合成机制深入研究奠定了基础。

Aqueous lubrication and surface microstructures of engineering polymer materials (PEEK and PI) when sliding against Si3N4

Polyether-ether-ketone (PEEK) and polyimide (PI) are two kinds of engineering polymer materials widely used as roller bearing cages and rings under extreme environment because of their noise reduction and corrosion resistance properties.The Si3N4 ceramic is the most common ball bearing material.Many current engineering applications of ball bearings require aqueous lubrication.Therefore,this study presents the aqueous lubrication of tribopairs formed by PEEK and PI material sliding against Si3N4 ceramic.Experimental results show that two tribopairs exhibited the similar tribological properties under the dry condition.Water as a lubricant for the PI-Si3N4 tribopair pairs effectively reduces both friction coefficients by 35.5％ and wear rates by 32％.The water absorption of PI induces better tribological properties by changing the tribopair surface properties.In addition,the dimples appearing on the PI tribopair surface under water generate additional hydrodynamic lubrication and further improve the friction properties of surface.The PEEK-Si3N4 tribopair shows similar friction coefficients under two kinds of environments.The wear rates under water are approximately more than two times of that under dry sliding.However,water inhibits the appearance of the crush phenomenon and enhances the carrying capacity of the tribopair.Energy dispersive spectroscopy and X-ray diffraction spectra demonstrate no chemical corrosion.The 3D profiler and SEM morphologies illustrate that the transfer film would be formed from the surface of PEEK under water but hindered under dry friction.Overall,the PI-Si3N4 tribopair exhibits better properties than PEEK under water and is promising for future applications in the bearing industry.