摘要：Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown *** short,personalized medicine is a term that describes medical treatment that is tuned to the *** possible way to realize personalized medicine is 3D *** using materials that can be tuned upon stimulation,4D printing is *** recent years,many studies have been exploring a new field that combines 3D and 4D printing with *** has resulted in many concepts of pharmaceutical devices and formulations that can be printed and,possibly,tailored to an ***,the first 3D printed drug,Spritam®,has already found its way to the *** review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine.

摘要：A post-marketing study is an integral part of research that helps to ensure a favorable risk-benefit profile for approved drugs used in the market. Because most of post-marketing studies use observational designs, which are liable to confounding, estimation of the causal effect of a drug versus a comparative one is very challenging. This article focuses on methodological issues of importance in designing and analyzing studies to evaluate the safety of marketed drugs, especially marketed traditional Chinese medicine （TCM） products. Advantages and limitations of the current designs and analytic methods for postmarketing studies are discussed, and recommendations are given for improving the validity of postmarketing studies in TCM products.

摘要：理解铁电材料畴结构在低温条件下的翻转行为,对于铁电物理以及其在宽温域的应用都非常重要;然而,目前在低温条件下直接观测介观尺度下的畴翻转仍然面临着巨大的挑战.本论文利用铁酸铋(BiFeO_(3))作为模型来研究3.6–260 K温度范围内的铁电畴翻转行为.菱形相的BiFeO_(3)在温度为130 K时观测到了明显的铁电保持失效现象;这是因为BiFeO_(3)在130 K附近有较大的热释电系数,从而使其升温到该温度附近时释放了大量的热释电电荷,进而产生较强的退极化场,导致铁电极化翻转.另外,本论文还发现通过纳米尺度设计相界可以有效地抑制铁电保持失效.本研究为变温条件下,尤其是低温温域,研究铁电翻转提供了实验范式.

摘要：Metabolites play important roles in numerous cell biology processes,such as cell proliferation,differentiation,stress response,and cell death[1].Recently,lactate and lactate-derived lysine residue lactylation(Kla)have emerged as newly discovered epigenetic modifications that play critical roles in various physiological and pathological *** the history of lactate research,we can categorize the studies into three mile stones(Fig.S1 online).

摘要：Limitations of monolayer culture conditions have motivated scientists to explore new models that can recapitulate the architecture and function of human organs more *** advances in the improvement of protocols have resulted in establishing three-dimensional(3D)organ-like architectures called‘organoids’that can display the characteristics of their corresponding real organs,including morphological features,functional activities,and personalized responses to specific *** discuss different organoid-based 3D models herein,which are classified based on their original germinal *** of organoids simulating the complexity of real tissues could provide novel platforms and opportunities for generating practical knowledge along with preclinical studies,including drug screening,toxicology,and molecular pathophysiology of *** paper also outlines the key challenges,advantages,and prospects of current organoid systems.

摘要：Background Chronic obstructive pulmonary disease(COPD)is a severe public health *** smoke(CS)is a risk factor for COPD and lung *** underlying molecular mechanisms of CS-induced malignant transformation of bronchial epithelial cells remain *** this study,we describe a lung-on-a-chip to explore the possible mechanistic link between cigarette smoke extract(CSE)-associated COPD and lung *** An in vitro lung-on-a-chip model was used to simulate pulmonary epithelial cells and vascular endothelial cells with *** levels of IL-6 and TNF-αwere tested as indicators of inflammation using an enzyme-linked immune sorbent *** junction complex mRNA expression was detected with qRT-PCR as the index of epithelial-to-mesenchymal transition(EMT).The effects of CSE on the phosphorylation of signal transduction and transcriptional activator 3(STAT3)were detected by Western *** cytometry was performed to investigate the effects of this proto-oncogene on cell cycle *** Inflammation caused by CSE was achieved in a lung-on-a-chip model with a mimetic *** exposure induced the degradation of intercellular connections and triggered the EMT *** exposure also activated the phosphorylation of proto-oncogene STAT3,while these effects were inhibited with *** CSE exposure in the lung-on-a-chip model caused activation of STAT3 in epithelial cells and endothelial ***0152,an inhibitor of activated STAT3,could be a potential treatment for CS-associated COPD and lung cancer.

摘要：The three-dimensional (3D)bioprinting technology has progressed tremendously over the past *** controlling the size, shape,and architecture of the bioprinted constructs,3D bioprinting allows for the fabrication of tissue/organ-like constructs with strong structural-functional similarity with their in vivo counterparts at high *** bioink,a blend of biomaterials and living cells possessing both high biocompatibility and printability,is a critical component of *** particular, gelatin methacryloyl (GelMA)has shown its potential as a viable bioink material due to its suitable biocompatibility and readily tunable physicochemical *** GelMA-based bioinks and relevant bioprinting strategies for GelMA bioprinting are briefly reviewed.

摘要：Phage-inducible chromosomal islands(PICIs)are a widespread family of mobile genetic elements,which have an important role in bacterial *** elements mobilize among bacterial species at extremely high frequencies,representing an attractive tool for the delivery of synthetic ***,tools for their genetic manipulation are limited and timing ***,we have adapted a synthetic biology approach for rapidly editing of PICIs in Saccharomyces cerevisiae based on their ability to excise and integrate into the bacterial chromosome of their cognate host *** proof of concept,we engineered several PICIs from Staphylococcus aureus and Escherichia coli and validated this methodology for the study of the biology of these elements by generating multiple and simultaneous mutations in different PICI *** biotechnological purposes,we also synthetically constructed PICIs as Trojan horses to deliver different CRISPR-Cas9 systems designed to either cure plasmids or eliminate cells carrying the targeted *** results demonstrate that the strategy developed here can be employed universally to study PICIs and enable new approaches for diagnosis and treatment of bacterial diseases.

摘要：In silico modeling and analysis of small molecules substantially accelerates the process of drug development. Representing and understanding molecules is the fundamental step for various in silico molecular analysis tasks. Traditionally, these molecular analysis tasks have been investigated individually and separately.

摘要：Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory ***,the development of a model for effective drug screening is urgently *** the established therapeutic testing models for CCA are often ineffective,we fabricated an enabling three-dimensional(3D)-bioprinted CCA-on-a-chip model that to a good extent resembled the multicellular microenvironment and the anatomical microstructure of the hepato-vascular-biliary system to perform high-content antitumor drug ***,cholangiocytes,hepatocytes,and vascular endotheliocytes were employed for 3D bioprinting of the models,allowing for a high degree of spatial and tube-like microstructural ***,it was possible to observe CCA cells attached to the surfaces of the gelatin methacryloyl(GelMA)hydrogelembedded microchannels and overgrown in a thickening manner,generating bile duct stenosis,which was expected to be analogous to the in vivo *** 4000 differentially expressed genes were detected in the CCA cells in our 3D coculture model compared to the traditional two-dimensional(2D)*** screening revealed that the CCA cells grown in the 3D traditional model were more sensitive to the antitumoral prodrug than those in the 2D monoculture due to drug biotransformation by the neighboring functional *** study provides proof-of-concept validation of our bioprinted CCA-on-a-chip as a promising drug screening model for CCA treatment and paves the way for potential personalized medicine strategies for CCA patients in the future.