人工智能在类器官研究中的应用进展与挑战

类器官是一种优异的肿瘤和干细胞研究模型,对其生长或药筛等过程的各种类型数据进行分析,有助于提升对类器官本身以及所代表疾病的了解。但人工观察和筛选类器官以及使用传统统计学方法在处理类器官数据时,存在分析准确度与效率低、难度系数大、人工成本高以及带有一定主观性等问题。而人工智能在很多生物学和医学研究领域已被证明会产生卓越效果。将人工智能引入类器官研究,有助于提升研究的客观性、准确性和速度,从而使类器官能更好地实现疾病建模、药物筛选、个性化医疗等。首先,类器官图像数据的人工智能分析取得了显著进展。结合深度学习的图像分析能够更精准地捕捉类器官的微观结构和变化,提高对类器官形态和生长的自动识别能力,达到较高的准确度,节约研究时间与成本。其次,对于类器官的组学数据,人工智能技术的引入同样取得了重要突破:可提高数据的处理效率以及发现潜在的基因表达模式,为细胞发育和疾病机制的解析提供新的工具。再次,类器官其他类型的数据如电信号和光谱等通过人工智能技术可实现对类器官类型和状态客观的分类,为类器官的全面表征进行了有益的尝试。而在类器官重要应用领域—药物筛选方面,人工智能可为过程监测和结果预测提供强有力的支持。通过高内涵显微镜图像和深度学习模型,研究者们能够实时监测类器官对药物的响应,实现了对药物作用的非侵入性检测,使药物筛选更加精准和高效。然而,尽管人工智能在类器官研究中取得了显著成果,仍然存在一系列挑战。数据获取的难度、样本质量和样本量的不足、模型解释性的问题等制约了其广泛应用。为了克服这些问题,未来的研究需要致力于提高数据的一致性,增强模型解释性,并探索多模态数据融合的方法,以更全面、可靠地应用人工智能于类器官研究中。因此本文认为人工智能技术的引入为类器官研究带来了前所未有的机遇,也取得了明显的研究进展。然而,我们仍然需要跨学科的研究与合作,共同应对挑战,推动人工智能在类器官研究中的更深层次应用。未来,人工智能有望在类器官研究中发挥更大的作用,加速其向临床转化和精准治疗的应用进程。

Advances in ATM,ATR,WEE1,and CHK1/2 inhibitors in the treatment of PARP inhibitor-resistant ovarian cancer

Ovarian cancer(OC)poses a significant challenge in modern gynecologic oncology,both diagnostically and therapeutically.According to the American Cancer Society,an estimated 21,000 new cases of OC were reported in the United States alone in 20211.The most prevalent subtype of OC87,highgrade serous(HGS),is characterized by heightened genomic instability and defects in DNA damage response(DDR)pathways,which contribute to disease development and progression2.Notably,approximately 50%of HGS ovarian cancer(HGSOC)patients exhibit homologous recombination repair(HRR)defects(HRDs)3.

Bone/cartilage organoid on-chip:Construction strategy and application

The necessity of disease models for bone/cartilage related disorders is well-recognized,but the barrier between ex-vivo cell culture,animal models and the real human body has been pending for decades.The organoid-on-a-chip technique showed opportunity to revolutionize basic research and drug screening for diseases like osteoporosis and arthritis.The bone/cartilage organoid on-chip(BCoC)system is a novel platform of multi-tissue which faithfully emulate the essential elements,biologic functions and pathophysiological response under real circumstances.In this review,we propose the concept of BCoC platform,summarize the basic modules and current efforts to orchestrate them on a single microfluidic system.Current disease models,unsolved problems and future challenging are also discussed,the aim should be a deeper understanding of diseases,and ultimate realization of generic ex-vivo tools for further therapeutic strategies of pathological conditions.

Organoid extracellular vesicle-based therapeutic strategies for bone therapy

With the rapid development of population ageing,bone-related diseases seriously affecting the life of the elderly.Over the past few years,organoids,cell clusters with specific functions and structures that are self-induced from stem cells after three-dimensional culture in vitro,have been widely used for bone therapy.Moreover,organoid extracellular vesicles(OEVs)have emerging as promising cell-free nanocarriers due to their vigoroso physiological effects,significant biological functions,stable loading capacity,and great biocompatibility.In this review,we first provide a comprehensive overview of biogenesis,internalisation,isolation,and characterisation of OEVs.We then comprehensively highlight the differences between OEVs and traditional EVs.Subsequently,we present the applications of natural OEVs in disease treatment.We also summarise the engineering modifications of OEVs,including engineering parental cells and engineering OEVs after isolation.Moreover,we provide an outlook on the potential of natural and engineered OEVs in bone-related diseases.Finally,we critically discuss the advantages and challenges of OEVs in the treatment of bone diseases.We believe that a comprehensive discussion of OEVs will provide more innovative and efficient solutions for complex bone diseases.

Converging technologies in biomaterial translational research

In the realm of scientific innovation,the study of biomaterials emerges as a field of profound significance,bridging the gap between theoretical exploration and translational application.1 The essence of biomaterial research lies not only in understanding the intricate relationships between biological systems and materials but more importantly,in the translational potential these materials hold.2 The true value of this research unfolds in its application-from regenerative medicine to bioengineered solutions,where these materials become pivotal in addressing some of the most pressing clinical challenges.Meanwhile,the necessity for translating laboratory research into real-world applications has become increasingly urgent,as global ageing intensifies and public attention to health concerns grows.

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery,as demonstrated by the approval of patisiran for amyloidosis therapy in 2018.To illuminate the unique superiority of lipid nanovehicles in RNA delivery,in this review,we first introduce various RNA therapeutics,describe systemic delivery barriers,and explain the lipid components and methods used for lipid nanovehicle preparation.Then,we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery.Finally,the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed.Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery,inspiring the development of more high-performance RNA lipid nanovesicles in the future.

Engineered plant extracellular vesicles for autoimmune diseases therapy

Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy tissues.Plant extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive molecules.Due to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of AID.This review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in AID.Additionally,we propose engineering approaches and administration methods for PEVs.Finally,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of AID.By gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for AID.Natural and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.

Bone/cartilage targeted hydrogel: Strategies and applications

The skeletal system is responsible for weight-bearing,organ protection,and movement.Bone diseases caused by trauma,infection,and aging can seriously affect a patient’s quality of life.Bone targeted biomaterials are suitable for the treatment of bone diseases.Biomaterials with bone-targeted properties can improve drug utilization and reduce side effects.A large number of bone-targeted micro-nano materials have been developed.However,only a few studies addressed bone-targeted hydrogel.The large size of hydrogel makes it difficult to achieve systematic targeting.However,local targeted hydrogel still has significant prospects.Molecules in bone/cartilage extracellular matrix and bone cells provide binding sites for bone-targeted hydrogel.Drug delivery systems featuring microgels with targeting properties is a key construction strategy for bone-targeted hydrogel.Besides,injectable hydrogel drug depot carrying bone-targeted drugs is another strategy.In this review,we summarize the bone-targeted hydrogel through application environment,construction strategies and disease applications.We hope this article will provide a reference for the development of bone-targeted hydrogels.We also hope this article could increase awareness of bone-targeted materials.

M2 macrophage-derived exosomes promote diabetic fracture healing by acting as an immunomodulator

Diabetes mellitus is a chronically inflamed disease that predisposes to delayed fracture healing.Macrophages play a key role in the process of fracture healing by undergoing polarization into either M1 or M2 subtypes,which respectively exhibit pro-inflammatory or anti-inflammatory functions.Therefore,modulation of macrophage polarization to the M2 subtype is beneficial for fracture healing.Exosomes perform an important role in improving the osteoimmune microenvironment due to their extremely low immunogenicity and high bioactivity.In this study,we extracted the M2-exosomes and used them to intervene the bone repair in diabetic fractures.The results showed that M2-exosomes significantly modulate the osteoimmune microenvironment by decreasing the proportion of M1 macrophages,thereby accelerating diabetic fracture healing.We further confirmed that M2-exosomes induced the conversion of M1 macrophages into M2 macrophages by stimulating the PI3K/AKT pathway.Our study offers a fresh perspective and a potential therapeutic approach for M2-exosomes to improve diabetic fracture healing.

Smart Hydrogels for Bone Reconstruction via Modulating the Microenvironment

Rapid and effective repair of injured or diseased bone defects remains a major challenge due to shortages of implants.Smart hydrogels that respond to internal and external stimuli to achieve therapeutic actions in a spatially and temporally controlled manner have recently attracted much attention for bone therapy and regeneration.These hydrogels can be modified by introducing responsive moieties or embedding nanoparticles to increase their capacity for bone repair.Under specific stimuli,smart hydrogels can achieve variable,programmable,and controllable changes on demand to modulate the microenvironment for promoting bone healing.In this review,we highlight the advantages of smart hydrogels and summarize their materials,gelation methods,and properties.Then,we overview the recent advances in developing hydrogels that respond to biochemical signals,electromagnetic energy,and physical stimuli,including single,dual,and multiple types of stimuli,to enable physiological and pathological bone repair by modulating the microenvironment.Then,we discuss the current challenges and future perspectives regarding the clinical translation of smart hydrogels.

Bioactive elements manipulate bone regeneration

While bone tissue is known for its inherent regenerative abilities,various pathological conditions and trauma can disrupt its meticulously regulated processes of bone formation and resorption.Bone tissue engineering aims to replicate the extracellular matrix of bone tissue as well as the sophisticated biochemical mechanisms crucial for effective regeneration.Traditionally,the field has relied on external agents like growth factors and pharmaceuticals to modulate these processes.Although efficacious in certain scenarios,this strategy is compromised by limitations such as safety issues and the transient nature of the compound release and half-life.Conversely,bioactive elements such as zinc(Zn),magnesium(Mg)and silicon(Si),have garnered increasing interest for their therapeutic benefits,superior stability,and reduced biotic risks.Moreover,these elements are often incorporated into biomaterials that function as multifaceted bioactive components,facilitating bone regeneration via release on-demand.By elucidating the mechanistic roles and therapeutic efficacy of the bioactive elements,this review aims to establish bioactive elements as a robust and clinically viable strategy for advanced bone regeneration.