摘要：癌症作为全球主要的致死原因之一,对公共卫生构成了巨大的挑战。癌症的防控策略不仅需要治疗技术的进步,也同样需要诊断技术的发展。肿瘤的发生和发展伴随着细胞结构和功能的多种变化,以及肿瘤微环境的显著改变。在这些变化过程中,特定分子的表达水平会出现异常,这些异常表达的分子可以作为肿瘤诊断的生物标志物。近年来,正电子发射断层扫描(Positron Emission Tomography,简称PET)作为一种重要的分子成像技术,已被广泛应用于检测肿瘤的结构和功能变化。PET技术的核心在于放射性示踪剂的开发与应用,这些示踪剂的设计和合成一般基于化学原理的深入理解和创新应用。本文旨在综述PET中几种典型的放射性示踪剂,并探讨核素标记过程中涉及的化学原理,增进对PET在肿瘤诊断中应用的理解,并提升对化学在生物医学领域中作用的认识。此外,PET放射性示踪剂的设计和合成过程是化学教育的宝贵资源,对化学在生命科学相关学科的教学具有重要意义。

摘要：The immune response after implantation of a biomaterial may shorten the functional life of the implant,depending on the degree of the *** this study,we used a polyacrylamide-alginate(PAAm-Alg)hydrogel,which has been previously characterized as a biocompatible material and shown to enhance regeneration of cartilage in vivo,along with a graphiteenhanced hydrogel(PAAm-Alg-G)as a non-biocompatible counterpart,to evaluate macrophage attachment and polarization to pro-or anti-inflammatory *** performance of each biomaterial in the presence of fibroblasts and chondrocytes was validated by an in vitro model which demonstrated modulation of the foreign-body response.A blend of 5%gelatin methacryloyl and 0.1%methacrylated hyaluronic acid was optimized to mimic the extracellular matrix(ECM)and support cell viability,proliferation,migration,and functionality at an initial concentration of 3.25×10^(5) cells/*** PAAm-Alg-G hydrogel localized in the simulated ECM showed cytotoxic and genotoxic effects for both fibroblasts and chondrocytes,while exhibiting a proliferative effect on macrophages with elevated immune *** M1/M2 ratio was 0.73 for PAAm-Alg hydrogel but 2.64 for PAAm-Alg-G,leading to significant M1 dominance(p0.05).The interleukin-6(IL-6)concentration secreted in the presence of PAAm-Alg hydrogel(4.58 pg/mL)significantly decreased(p<0.0001)on day 13,while the increase(p<0.0001)in interleukin-10(IL-10)concentration(120.73 pg/mL)confirmed the switch from a pro-inflammatory to an anti-inflammatory *** immune responses by developing a simplistic yet powerful three-dimensional in vitro model provides advantages in preparing for clinical use of biomaterials.

摘要：In the era of burgeoning breakthroughs around medical and biomedical technologies,personalizing our medicine still sounds like a dream yet to be *** cancer as an example,while the pool of anti-cancer therapeutic agents is tremendously large,pinpointing a drug or a combination of drugs that would always work out well for a given patient,remains quite impossible—in fact,we are not even close to this ideal *** an incapability,of course,originates primarily from the overly complex,volumetrically structured and dynamic microenvironments in a patient’s tumor,meaning that the same tumor as seen on Day 1 might be entirely different than when seen again a month later.

摘要：We report the development of a metastasis-on-a-chip platform to model and track hepatocellular carcinoma(HCC)-bone metastasis and to analyze the inhibitory effect of an herb-based compound,thymoquinone(TQ),in hindering the migration of liver cancer cells into the bone *** bioreactor consisted of two chambers,one accommodating encapsulated HepG2 cells and one bone-mimetic niche containing hydroxyapatite(HAp).Above these chambers,amicroporous membrane was placed to resemble the vascular barrier,where medium was circulated over the *** was observed that the liver cancer cells proliferated inside the tumor microtissue and disseminated from the HCC chamber to the circulatory flow and eventually entered the bone *** number of metastatic HepG2 cells to the bone compartment was remarkably higher in the presence of HAp in the *** was then used as ametastasis-controlling agent in both free form and encapsulated nanoparticles,to analyze its suppressing effect on HCC *** indicated that the nanoparticle-encapsulated TQ provided a longer period of inhibitory *** summary,HCC-bone metastasis-on-a-chip platform was demonstrated to model certain key aspects of the cancer metastasis process,hence corroborating the potential of enabling investigations on metastasis-associated biology as well as improved anti-metastatic drug screening.

摘要：The human gut microbiota is widely considered to be a metabolic organ hidden within our bodies,playing a crucial role in the host’s *** factors affect its composition,so a wide variety of microbes residing in the gut are present in the world *** excessive imbalances in microbial composition are often associated with human disorders and pathologies,and new investigative strategies to gain insight into these pathologies and define pharmaceutical therapies for their treatment are *** vitro models of the human gut microbiota are commonly used to study microbial fermentation patterns,community composition,and host-microbe *** and microfluidic devices have been designed to culture microorganisms from the human gut microbiota in a dynamic environment in the presence or absence of eukaryotic cells to interact *** this review,we will describe the overall elements required to create a functioning,reproducible,and accurate in vitro culture of the human gut *** addition,we will analyze some of the devices currently used to study fermentation processes and relationships between the human gut microbiota and host eukaryotic cells.

摘要：Advances in biomimetic three-dimensional(3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is more accurate than traditional two-dimensional(2D) cell culture. Gelatin methacryloyl(GelMA) is widely used as a tissue-engineered scaffold hydrogel for 3D cell culture. In the present study, an in vitro 3D malignant melanoma model based on Gel MA was fabricated to evaluate the efficiency of hypericin(Hy)-loaded microemulsion(ME) in photodynamic therapy against melanoma. The ME was produced by the spontaneous emulsification method to enhance the bioavailability of Hy at tumor sites. Hy-loaded MEs were applied to a 3D malignant melanoma model made using 6% Gel MA and the co-culture of B16F10 and Balb/c 3T3 cells,followed by crosslinking using violet light(403 nm). The observation revealed excellent cell viability and the presence of F-actin cytoskeleton network. Hy-loaded MEs exhibited higher phototoxicity and cell accumulation(about threefold) than free Hy, and the cells cultured in the 3D system displayed lower susceptibility(about 2.5-fold) than those in 2D *** findings indicate that the developed MEs are potential delivery carriers for Hy;furthermore, Gel MA hydrogel-based modeling in polydimethylsiloxane(PDMs) molds is a user-friendly and cost-effective in vitro platform to investigate drug penetration and provide a basis for evaluating nanocarrier efficiency for skin cancer and other skin-related diseases.

摘要：Paper devices have recently attracted considerable attention as a class of cost-effective cell culture substrates for various biomedical *** paper biomaterial can be used to partially mimic the in vivo cell microenvironments mainly due to its natural three-dimensional *** paper-based devices provide precise control over their structures as well as cell distributions,allowing recapitulation of certain interactions between the cells and the extracellular *** features have shown great potential for the development of normal and diseased human tissue *** this review,we discuss the fabrication of paper-based devices for in vitro tissue modeling,as well as the applications of these devices toward drug screening and personalized *** is believed that paper as a biomaterial will play an essential role in the field of tissue model engineering due to its unique performances,such as good biocompatibility,eco-friendliness,cost-effectiveness,and amenability to various biodesign and manufacturing needs.

摘要：Background RNA interference （RNAi） is a potential cure for amyotrophic lateral sclerosis （ALs） caused by dominant, gain-of-function superoxide dismutase 1 （sOD1） mutations. The success of such therapy relies on the functional small interfering RNAs （siRNAs） that can effectively deliver RNAi. This study aimed to design the functional siRNAs targeting ALs-associated mutant alleles. Methods A modified dual luciferase system containing human sOD1 mRNA target was established to quantify siRNA efficacy. Coupled with validated siRNAs identified in the literature, we analyzed the rationale of siRNA design and subsequently developed an asymmetry rule-based strategy for designing siRNA. We then further tested the effectiveness of this design strategy in converting a naturally symmetric siRNA into functional siRNAs with favorable asymmetry for gene silencing of sOD1 alleles. Results The efficacies of siRNAs could vary tremendously by one base-pair position change. Functional siRNAs could target the whole span of sOD1 mRNA coding sequence as well as non-coding region. While there is no distinguishable pattern of the distribution of nucleobases in these validated siRNAs, the high percent of GC count at the last two positions of siRNAs （P18 and P19） indicated a strong effect of asymmetry rule. Introducing a mismatch at position 1 of the 5＇ of antisense strand of siRNA successfully converted the inactive siRNA into functional siRNAs that silence sOD1 with desired efficacy. Conclusions Asymmetry rule-based strategy that incorporates a mismatch into siRNA most consistently enhances RNAi efficacy and guarantees producing functional siRNAs that successfully silence ALs-associated sOD1 mutant alleles regardless target positions. This strategy could also be useful to design siRNAs for silencing other disease-associated dominant, gain-of-function mutant genes.

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：This study presents a simple and robust three-dimensional human hepatic tissue model to emulate steatotic and fibrotic conditions and provide an in vitro model for drug testing and mechanistic *** a photolithographic biofabrication method with a photomask featuring hexagonal units,liver cells,including a human hepatic cell line(HepG2-C3A)and a human hepatic stellate cell line(LX-2)were embedded in gelatin methacryloyl *** steatosis was induced by supraphysiological concentration of free fatty acids;hepatic fibrosis was induced by transforming growth factor-β*** of steatosis was confirmed by Oil Red O and BODIPY staining and was inhibited with toyocamycin and obeticholic *** of fibrosis was confirmed by immunostaining for collagen type I and alpha smooth muscle actin and inhibited by rapamycin and curcumin *** model was further preliminarily validated using primary human hepatocytes in a similar *** constructs provide a viable,biologically relevant,and higher throughput model of hepatic steatosis and fibrosis and may facilitate the study of the mechanisms of disease and testing of liver-directed drugs.