Ageing is the main risk factor for human diseases and death. Due to the global ageing, it has been urgent and challenging to understand the molecular basis of this complex biology process. Dietary restriction (DR), reduced food in-take without malnutrition, is one of the most robust environmental interventions that delays ageing. Using model organisms such as C. elegans, previous studies have identified key regulators that mediate the anti-ageing effect of DR. However, it has not been clear whether and how lipid metabolism, a process that is closely related to human health, plays any roles in the response to DR, and whether lipid metabolic enzymes serve as key mediators of DR.  To address these scientific questions, Dr. Di Chen's group carried out a series of research. The results have been recently published in Nature Communications as an article entitled “ACS-20/FATP4 mediates the anti-ageing effect of dietary restriction in C. elegans”.Dr. Chen's group focused on the acyl-CoA synthetase (ACS) family of enzymes, which play a critical role in the initial stage of fatty acid metabolism. Through an RNAi-based genetic screen, Dr. Chen's group identified ACS-20, the C. elegans ortholog of the fatty acid transporter 4 (FATP4), as a key mediator of DR's protective effect on lifespan and healthspan. Using genomic, genetic, genome editing, molecular and biochemical approaches, Dr. Chen's group demonstrates that the acs-20 mutant functions through the NHR-23 nuclear hormone receptor to regulate transcription of ptr-8, which encodes the Patched receptor ortholog from the Hedgehog pathway. Overexpression of ptr-8 leads to disruption of proteostasis, ER stress, and reduced lifespan and healthspan under DR. This study identifies highly conserved genes as key modulators of ageing in response to nutrients and reveals the underlying transcriptional regulation mechanisms.   ACS-20 mediates the beneficial effect of DR on ageing. Under DR conditions, ACS-20 activates the NHR-23 nuclear receptor to restrict the expression of ptr-8 with an unknown factor. When the acs-20 mutant is subject to DR, NHR-23 fails to bind to the ptr-8 promoter, which leads to ptr-8 overexpression, disruption of proteostasis, ER stress, and reduced lifespan and healthspan.Zi Wang, a Ph.D. student from Dr. Chen's group, is the first author, and Dr. Di Chen from ZJE is the corresponding author of this paper. Dr. Huanhu Zhu's group from the ShanghaiTech University provided support in lipid analysis. This work was supported by grants from the National Key Research and Development Program of China and National Natural Science Foundation of China (General Projects).

Biomedical research is essential for human health, but many biomedical research activities use lab animals and the use can entail animal suffering. This suffering obviously harms the animal but can also personally affect the researcher or weaken the scientific validity of research. Taking a compassionate approach in these research activities could address these issues, but compassion is rarely discussed in biomedical sciences teaching and research. Dr. John Menzies and Dr. Nicola Romano have published a paper in Animals exploring the validation and use of a new survey to measure compassion towards laboratory animals. The survey was done in groups of biomedical sciences UG students. Different levels of compassion were observed in different groups, and using a harm-benefit task, they showed that students with lower levels of compassion are more likely to accept higher levels of animal suffering in a research setting. When exploring whether certain beliefs about animals were linked with compassion, they found that a belief that animals are conscious is associated with higher levels of compassion. This work will help us understand differences and similarities in values and beliefs about lab animals in different groups of students, and contribute to the development of teaching and learning activities on the ethics and practice of lab animal use.Access to the publication: https://doi.org/10.3390/ani13223584

Recently, Prof. Min Zhou’s group from Zhejiang University-University of Edinburgh Institute (ZJE) and the collaborators published an article entitled “A biodegradable, flexible photonic patch for in vivo phototherapy” in Nature Communications.Diagnostic and therapeutic illumination on internal organs and tissues with high controllability and adaptability in terms of spectrum, area, depth, and intensity remains a major challenge. Here, this group developed a flexible, biodegradable photonic device called iCarP with a micrometer scale air gap between a refractive polyester patch and the embedded removable tapered optical fiber. The iCarP combines the advantages of light diffraction by the tapered optical fiber, dual refractions in the air gap, and reflection inside the patch to obtain a bulb-like illumination, guiding light towards target tissue. ICarP supports long-term, wide spectrum, continuous/pulsatile, deep penetrating (1.5 cm) illumination on beating animal hearts, without physically damaging the target tissue. In vivo photosynthesis as a potential application and the compatibility with minimally invasive implantation in large animal models were demonstrated. This study showed that iCarP could be a safe and powerful device suitable for internal organs/tissues illumination and associated therapy and diagnosis.Link：https://www.nature.com/articles/s41467-023-38554-x

Recently, Dr. Qianting Zhang’s group from Zhejiang University-University of Edinburgh Institute (ZJE) and the collaborators published an article entitled “BBOF1 is required for sperm motility and male fertility by stabilizing the flagellar axoneme in mice” in Cellular and Molecular Life Sciences. Defects of sperm flagella is a direct cause of male infertility, manifested by varying degrees of oligoasthenoteratozoospermia (OAT). A group of these OAT patients are affected by genetic mutations. Although they can still produce biological offsprings relying on intracytoplasmic sperm injection (ICSI), the diseases cannot be improved by conventional clinical treatment and needs to be screened before clinical treatment. Therefore, to clarify and screen the pathogenic mutants involving OAT has scientific and clinical significance for improving the diagnosis and treatment of male infertility and cutting off the transmission of pathogenic genes.  The axonemal outer dynein arm protein MNS1 is closely related to cilia movement. Genetic mutations of Bbof1 in mice and humans cause OAT and primary ciliary dyskinesia (PCD). In this research, we identified BBOF1 as a new MNS1-interacting protein, and it is robustly expressed in mouse testes. Knockout of Bbof1 in mice caused OAT and male sterility. Sperm derived from knockout males exhibited disrupted sperm axonemal ultrastructure and reduced mobility, which phenocopied MNS1 mutant. In this project, we will use gene-modified mouse models to clarify the molecular mechanisms of BBOF1 and its interaction with MNS1 in mammalian sperm flagella assembly and sperm motility. Besides, BBOF1 is found to interact with an outer dense fiber protein, ODF2, and is required for the stabilization of MNS1 and ODF2. BBOF1 is dispensable for the assembly and function of motile cilia in brain and trachea, mainly essential for the structural integrity of the sperm flagellum. In the future, BBOF1 could be identified as a new OAT-related pathogenic gene in clinics, aiming to improve the standard of genetic diagnosis and precision medicine in male infertility. BBOF1 deletion causes severe defects in axonemal organization, indicated by the absence of certain peripheral MTDs on cross sections of sperm flagella shown in a representative TEM image. Access to the publication: https://link.springer.com/article/10.1007/s00018-023-04800-0 

Recently, a review article entitled "Cytoplasmic DNAs: sources, sensing, and roles in the development of lung inflammatory diseases and cancer" was published in Frontiers in Immunology (Official Journal of International Union of Immunological Societies (IUIS), JCR Q1 Journal) by a group of undergraduate students supervised by Jian Liu lab from Zhejiang University - University of Edinburgh Institute (ZJE). This review focuses on recent discoveries and advances in cytoplasmic DNA and its signaling pathways in inflammatory lung disease and lung cancer (Figure 1). The authors find that sustained activation of cytoplasmic DNA sensing pathways contributes to the development of common lung diseases, which can be caused by external factors or mutations in key genes in the body. The interaction of cytoplasmic DNA with anti-inflammatory or antitumor effects and its potential in immunotherapy are further discussed.Mislocated cytoplasmic DNA will be induced by cytoplasmic sensors such as cGAS and inflammatory bodies to induce innate immune responses such as IFN response and inflammatory cell death. A growing number of studies have reported the role of such signaling pathways in the progression of common diseases, including pulmonary inflammatory disease and lung cancer. This article summarizes the latest research results of cytoplasmic DNA sensing in the progression of these lung diseases and proposes the corresponding immunotherapy methods. In addition, the role of pathogens and self-derived cytoplasmic DNA in the development of several types of pulmonary inflammatory diseases, such as COVID-19, has been described. More importantly, the authors note the important contribution of cytoplasmic DNA sensing in some specific genotypes of lung cancer, such as TP53 mutants. This provides a theoretical basis for the accurate treatment of lung cancer. In conclusion, the authors suggest that cytoplasmic DNA plays a crucial role in the progression of common lung diseases, and that its understanding could help explore more therapeutic strategies.Professor Jian Liu is the corresponding author of this paper. He Xintong, Sun Ye and Lu Jianzhang are the co-first authors of this paper. Shenglin Ma is the co-corresponding author of this paper. Co-authors include Faiza Naz, a foreign doctoral student in Jian Liu's lab. Although undergraduate students of ZJE are always busy with their studies, it only took three months from drafting to finishing the article, and only six months from publication. This fully reflects the subjective initiative in research and self-learning ability of ZJE undergraduates. Moreover, these ZJE undergraduate students, the first authors of this publication, conducted some related research in Pro. Jian Liu’s lab, supported by the Zhejiang Province College Students Science and Technology Innovation Activity Plan (New Seedling Talent Program) in 2022.Link of the article：https://www.frontiersin.org/articles/10.3389/fimmu.2023.1117760/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Immunology&id=1117760 About labLiu Jian's research group was founded in November 2020. Currently, its main research interests are tumor biology, AI multi-omics, and gene editing. At present, it focuses on studying the molecular mechanism of lung cancer (lung squamous cell carcinoma) by combining clinical database, transgenic mouse model, and various sequencing methods, aiming at promoting targeted therapy of lung cancer (lung squamous cell carcinoma). Established "groups of databases of lung cancer and other cancers (http://www.canceromics3d.net/ or http://www.lungcancer3d.net/)" and WeChat public account “肺鳞癌”. The leader of the research group can be contacted at JianL@intl.zju.edu.cnLab website: https://person.zju.edu.cn/liujian; Recruit highly motivated postgraduates. Photo of the authorsJian's Lab

Quantitative single-cell analysis has revolutionised our approach to study the molecular events that lead to cell fate decisions. However, a common challenge when performing single-cell analysis is the limited computational tools available to track single-cells over multiple cell generations robustly. This is because when cells undergo cell division, they form daughter cells that can confound the algorithms used to track the cells, leading to high false mother-daughter assignments. This means extensive manual corrections are often required, making it a time-consuming practice.In the recent publication in Bioinformatics, Kuan Yoow Chan's lab developed an application that uses deep learning to classify cells based on the pattern of the well-established fluorescently tagged PCNA protein. By using the PCNA pattern to identify the cell cycle state of cells, we were able to assign mother-daughter relationships rapidly and accurately. This novel approach has high accuracy rates and relatively low computational costs, allowing us to generate high-quality single-cell lineages from large long-term imaging datasets.LINK：https://academic.oup.com/bioinformatics/advance-article/doi/10.1093/bioinformatics/btac602/6680181About labUsing genetic, cell biology and biochemical assays, Kuan Yoow Chan' Lab aim to study how the changes in centrosomal signalling lead to the deregulation of the cell cycle in cancer.

Recently, Dr. Qianting Zhang’s lab from Zhejiang University-University of Edinburgh Institute (ZJE) published a review entitled “Ubiquitin-Proteasome System–Regulated Protein Degradation in Spermatogenesis” on Cells. The review systematically discusses the physiological functions and molecular mechanisms of the components of the ubiquitin-proteasome system (UPS) in regulating spermatogenesis, suggesting that exploring the functions of UPS machineries is critical for the improvement of human Assisted Reproductive Technology (ART) and the popularization of Preimplantation Genetic Diagnosis (PGD). ZJE student Yi Xiong also participated in writing this review. Dr. Qianting Zhang is the corresponding author and Yi Xiong, an undergraduate student (2018 Cohort) from ZJE, is the first author of this article. Spermatogenesis, which maintains sustainable production of male gametes, the spermatozoa, includes more than 40 steps. Spermatogonia, differentiated from the primordial germ cells, undergo meiotic division to form round spermatids, which further mature to become motile, fertile spermatozoa. During this process, male germ cells experience dramatic changes in morphology as well as cellular contents and these changes are tightly regulated through the UPS (Figure 1). According to reports, there are extensive protein degradation events and unique molecular machineries controlling protein homeostasis during spermatogenesis. The UPS plays a broad and precise role in regulating both protein degradation and activity for the step-by-step progression in spermatogenesis. This review includes three main parts: 1. Proteasomes in male germ cells; 2. E3 ubiquitin ligase in spermatogenesis; 3. Protein deubiquitination in spermatogenesis. Exploring the functions of UPS machineries in spermatogenesis provides a global picture of the proteome dynamics during male germ cell production and shed light on the etiology and pathogenesis of human male infertility Figure 1: The processes of mammalian spermatogenesis. (The degradation timing of regulatory proteins involved in meiotic prophase I and histones as substrates of UPS, as well as the expression pattern of 20S proteasome subunits PSMA7 and PSMA8 are labeled with Gradient bar.) Access to the publication: https://www.mdpi.com/2073-4409/11/6/1058 

In Greek mythology, Achilles was the son of the mortal Peleus and Thetis, the goddess of the sea. In order to make his son invulnerable, Thetis carried it upside down and immersed it in the Styx River when he was just born. However, Achilles' heel pinched by his mother was accidentally exposed outside the Styx River, leaving the only fatal weakness in his body. In the Trojan War, Achilles was shot in the ankle by Paris and died.In the human body, there is also such a soft spot- Achilles tendon. As its name suggests, the Achilles tendon is one of the most powerful and fragile tendons in the body. The Achilles tendon could endure a load close to 8 times the body weight during exercise, making it extremely sensitive to injury. Furthermore, due to the unique nature of tendons, failing to consult a doctor soon after an injury can lead to chronic tendon disease, which is characterized by pain, swelling, and movement problems. Heterotopic ossification of tendon is a special type of chronic tendon disease, that is, the bone grows in the place (tendon) where the it shouldn’t, further destroying the morphological structure and function of the tendon tissue. Famous athletes such as Xiang Liu and Kobe Bryant had to retire early from sports due to a lack of a radical solution for Achilles tendon injuries.Figure 1 Achilles tendon - the powerful and fragile Achilles heel of the human body (picture from the Internet)Using single-cell sequencing technology, the Ouyang Hongwei team of Zhejiang University revealed tissue microenvironment changes during tendon heterotopic ossification alters gene expression and cell fate determination of tendon stem progenitor cells, and demonstrated that this process can be blocked by small molecule inhibitor BIBF1120, providing a novel treatment for heterotopic tendon ossification.The authors firstly found that the tendon specific transcription factor MKX decreased significantly in heterotopic ossified human tendon, and knockout of Mkx lead to spontaneous ossification of mouse tendon, suggesting that MKX plays a critical role in heterotopic ossification of tendon.Fig. 2 Heterotopic ossification of tendon caused by decreased MKX expression or Mkx knockoutFurther studies revealed that Mkx knockout mouse tendon cells expressed high levels of angiogenesis related genes, resulting in vascular invasion and tendon extracellular matrix microenvironment remodeling, and abnormal activation of osteogenic and chondrogenic differentiation related genes in tendon stem progenitor cells. These data indicated that inhibition of angiogenesis may improve the tendon tissue microenvironment and prevent HO progression.Figure 3 Single cell sequencing reveals tendon cell subpopulations and altered gene expression patternTherefore, the author focused on finding drugs that can inhibit angiogenesis process. Finally, they found that local injection of BIBF1120 significantly inhibited the neovascularization of tendon after injury, and significantly alleviated the tendon heterotopic ossification.Figure 4 Small molecule inhibitor BIFB1120 significantly improved the microenvironment of tendon injury and inhibited heterotopic ossificationThis work was published in Bone research entitled "Single cell analysis reveals investment of angiogenesis concerns progress of heterotopic ossification in Mkx-/- mice". The first author of the paper is Junxin Lin, a postdoctoral researcher of the Zhejiang University-University of Edinburgh Institute. The corresponding authors are professor Hongwei Ouyang and Wanlu Liu. The research was supported by the National Key R&D Program of China (2017YFA0104900), the National Natural Science Foundation of China (31830029, 81501937, 81522029) and the Fundamental Research Funds for the Central Universities (K20200099).Link：https://www.nature.com/articles/s41413-021-00175-9