Recently, Dr. Jian Liu’s group from Zhejiang University-University of Edinburgh Institute (ZJE) published an article entitled “Overexpression of ELF3 in the PTEN-deficient Lung Epithelium Promotes Lung Cancer Development by Inhibiting Ferroptosis” in Cell Death & Disease.DOI：10.1038/s41419-024-07274-5Ferroptosis has been shown to play a crucial role in preventing cancer development, but the underlying mechanisms of dysregulated genes and genetic alternations driving cancer development by regulating ferroptosis remain unclear. Here, we showed that the synergistic role of ELF3 overexpression and PTEN deficiency in driving lung cancer development was highly dependent on the regulation of ferroptosis. Human ELF3 (hELF3) overexpression in murine lung epithelial cells only caused hyperplasia with increased proliferation and ferroptosis. hELF3 overexpression and Pten genetic disruption significantly induced lung tumor development with increased proliferation and inhibited ferroptosis. Mechanistically, we found it was due to the induction of SCL7A11, a typical ferroptosis inhibitor, and ELF3 directly and positively regulated SCL7A11 in the PTEN-deficient background. Erastin-mediated inhibition of SCL7A11 induced ferroptosis in cells with ELF3 overexpression and PTEN deficiency and thus inhibited cell colony formation and tumor development. Clinically, human lung tumors showed a negative correlation between ELF3 and PTEN expression and a positive correlation between ELF3 and SCL7A11 in a subset of human lung tumors with PTEN-low expression. ELF3 and SCL7A11 expression levels were negatively associated with lung cancer patients' survival rates. In summary, ferroptosis induction can effectively attenuate lung tumor development induced by ELF3 overexpression and PTEN downregulation or loss-of-function mutations.ELF3 has opposite effects on the regulation of the Ferroptosis pathway in the context of PTEN absence and present Pro. Jian Liu is the corresponding author. In addition, the Master student Zengzhuang Yuan (ZJE, 2021 entry) is the leading first author, while the Master students Xinyan Han (ZJE, 2022 entry) and Manyu Xiao (ZJE, 2022 entry) participated in this research as co-first authors. The ZJE undergraduate students, including Taoyu Zhu, Xinyu Yu, and Kehang Zhang, participated in this research as co-authors.About Jian Liu’s labJian Liu's group is now interested in investigating lung squamous cell carcinoma development and treatment using genetic mouse models and AI+ multi-omics, especially the research direction on cancer immunology and 3D genome. He has published over 50 papers, including publications in the past three years, as a co-corresponding author in Nature Communications (2), Advanced Science, Oncogene, Cell Death & Disease, and Molecular Oncology journals. Moreover, his lab developed a multi-omics web database Omics3D (http://omics3d.net/) to investigate the de novo functional genome during cancer development.Email:JianL@intl.zju.edu.cnJian Liu’s lab (https://person.zju.edu.cn/liujian) is recruiting postdoc and Ph.D. students, including the single-degree students from University of Edinburgh.

Soft robots offer numerous advantages, including integrated actuation, flexibility, compact size, lightweight structure, environmental adaptability, and low noise. These characteristics enable them to navigate unstructured environments and perform complex tasks, demonstrating immense potential in the field of medicine, human-machine interaction, and disaster rescue. However, the design, functionalization, and fabrication of soft materials remain complex. Integrating multiple responsive properties effectively to construct self-actuating, biocompatible soft robots for medical and pharmaceutical applications remains a significant challenge.Recently, Professor Wenwen Huang’s research team at Zhejiang University published a back cover article in Advanced Healthcare Materials. The study proposes a bioinspired strategy that integrates genetic engineering and chemical engineering to construct programmable, self-actuating protein hydrogel soft robots capable of complex spatial deformation. The paper has been featured on several science communication platforms, such as NetEase, MaterialsViews, and Hydrogel Science.Inspired by post-translational modifications in natural proteins, the research employs a multidisciplinary approach involving genetic engineering, materials chemistry, and multiscale simulations to design, fabricate, modify, and optimize recombinant protein hydrogels with specific stimulus-responsive properties from the molecular level in a bottom-up manner. As shown in the figure below, the authors used a genetic engineering strategy to design recombinant silk-elastin-like protein hydrogels with customizable stimulus responsiveness. Additionally, chemical engineering served as a secondary control point to specifically modulate the physicochemical properties of tyrosine side chains, enabling patterning and reprogramming of the stimulus-responsive hydrogel’s actuation behavior.The protein hydrogel soft robots developed in this study exhibit preprogrammed, controllable environmental-responsive actuation behaviors, such as bending/unfolding and coiling/uncoiling. These behaviors are driven by asymmetric swelling induced by temperature changes (via LCST properties) or by variations in ionic strength or pH (via zwitterionic properties).In summary, the authors proposed a strategy to modulate LCST-type and zwitterionic-type biomolecular stimulus responsiveness at the molecular level. Through the integration of genetic and chemical engineering, they controlled the topological structure of the active and passive layers within the soft robots. This approach effectively prevented layer separation and enabled the efficient fabrication of programmable, self-actuating soft robots. The strategy is highly customizable, adjustable, easy to process, and flexible, making it a promising solution to meet the demands of biomedical materials and medical robotics.This work was led by Ph.D. student Ting Ji from Wenwen Huang’s team at ZJE, who has since graduated and joined Northwest Normal University as faculty member. Professor Huang is the sole corresponding author of the paper. The research was supported by grants from the National Natural Science Foundation of China and the Zhejiang Provincial Natural Science Foundation.Article link: https://onlinelibrary.wiley.com/doi/10.1002/adhm.202470175

This paper details an innovative study on the development of human primordial germ cells (PGCs), the precursors to the germline, specified early in embryonic life. Despite the significance of PGCs in reproductive biology, their developmental pathways have remained largely unexplored due to the ethical and technical challenges associated with human embryonic research.To address these gaps, we established a comprehensive human PGC database (hPGCdb), which consists of 581 RNA-seq, 54 ATAC-seq, 45 ChIP-seq, and 69 single-cell RNA-seq samples from various stages of PGC development. This database serves as a pivotal resource for understanding the regulatory mechanisms governing human PGC specification and differentiation.Through integrated multi-omics analysis, we identified several key transcription factors and regulatory networks that control germ cell fate, highlighting the differences between human and model organisms like mice. We further validated the functional importance of specific transcription factors using Gene KnockDown and KnockOut, confirming their roles in germ cell development.Additionally, our research explored the soma-germline interaction network, revealing roles for SDC2 and LAMA4 in PGC development and the influence of soma-derived NOTCH2 signaling in germ cell differentiation. These findings enhance our understanding of the extrinsic factors influencing germ cell fate and open new avenues for research into reproductive health and disease.In summary, this study not only provides a detailed map of the regulatory landscape governing human PGC development but also introduces a valuable genomic resource that enhances our understanding of human reproductive biology and developmental genetics.

Bacterial pneumonia is one of the challenging global infectious diseases with high morbidity and mortality. Considering the antibiotic abuse and resistance of bacterial biofilms, a variety of metal-based materials have been developed. However, due to the high oxygen environment of the lungs, some aerobic infection bacteria have high tolerance to oxygen and ROS, and most of the metal-based materials based on ROS may not achieve good therapeutic effects.Recently, Professor Min Zhou's team from the Second Affiliated Hospital of Zhejiang University School of Medicine/Zhejiang University-University of Edinburgh Institute published a research paper titled A mucous permeable local delivery strategy based on manganese-enhanced bacterial cuproptosis-like death for the bacterial pneumonia treatment in the ACS Nano, making new progress in the bacterial cuproptosis-like death for the bacterial pneumonia treatment.Copper, a long-established antimicrobial material, has recently been found to trigger copper-induced cell death after its accumulation within biofilms by interacting with components in the tricarboxylic acid (TCA) cycle. Cell death induced by copper is associated with cell respiration, in which cells dependent on aerobic respiration are more sensitive to copper-induced death, showing potential application in the treatment of pulmonary aerobic infections. However, the application of copper death to the treatment of bacterial infections has been limited, starting with the protective effect of glutathione, which can interact with copper and thus hinder the interaction of copper with proteins.Another key point is the concentration of copper ions, considering the toxicity of copper ions, direct intravenous injection of large doses of copper preparations can lead to serious toxic effects.Inspired by the sensitivity of cuproptosis to aerobic respiratory cells, we designed a copper composite antibacterial nanoparticle and found that it can effectively induce cuproptosis-like death in aerobic bacteria of the lung. To address the challenge of in vivo application of cuproptosis, manganese dioxide was first incorporated to deplete protective glutathione, and assists in antibacterial action through immune enhancement. Cuproptosis-like death also requires a large amount of copper ions. To meet this demand, we deliver positively hydrophilic modified composite nanoparticles that effectively penetrate the lung mucus layer directly to the lungs through local administration, and the copper ions were further released rapidly by the acidic environment at the infected site, which can further destroy bacterial biofilms in synergy with manganese. This drug delivery system can effectively treat pneumonia caused by aerobic bacteria and avoid the systemic toxicity that can be caused by large doses of copper.Dr. Shiyuan Hua from the Min Zhou team at the Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute) is the first author of the paper. Dr. Huiqun Hu from the Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine is the co-first author of the paper. Professor Min Zhou from the ZJU-UoE Institute and Professor Feng Xu from the Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine are the co corresponding authors of the paper.

You might think that eating is just a daily routine, but it's actually a vital process that keeps our bodies running smoothly. Our small intestine is like a busy factory that absorbs nutrients from the food we eat, and it's also connected to other organs like the liver and fat cells that help with metabolism.But did you know that our small intestine has a special way of getting nutrients? It's like a two-way street, where nutrients come in from both the food we eat and the bloodstream. When this balance is disrupted, it can lead to problems like obesity, heart disease, and even damage to our immune system.A collaborative group of scientists from Wang Di (Zhejiang University School of Medicine), Liu Wanlu (Zhejiang University-University of Edinburgh Institute), and Liu Jia (Shanghai Institute of Materia Medica, CAS) has made a groundbreaking discovery about how our small intestine works. They found that the way we eat affects how our small intestine absorbs nutrients, and that different types of nutrients are absorbed in different ways. For example, fats are mainly absorbed in the top part of the small intestine, while a certain type of amino acid is absorbed in specific cells.They also found that when we don't eat regularly, our small intestine can become imbalanced, leading to problems like heart disease. If we don't eat breakfast, it can be especially harmful.So, what can we do? Eating a balanced diet and having regular meals is crucial for maintaining a healthy gut and preventing diseases. And who knows, maybe skipping breakfast isn't such a good idea after all!AcknowledgmentsProfessor Wang Di from Zhejiang University School of Medicine and Sir Run Run Shaw Hospital and Professor Liu Wanlu from the Zhejiang University-Edinburgh University Joint Institute are the corresponding authors of this paper. Dr. Zhang Jian, a postdoctoral fellow at Zhejiang University School of Medicine/Liangzhu Laboratory, PhD student Tian Ruonan from the Zhejiang University-Edinburgh University Joint Institute, and Dr. Liu Jia and Dr. Yuan Jie from the Shanghai Institute of Materia Medica are the co-first authors. The study was supported by the National Natural Science Foundation of China, the Zhejiang Provincial Natural Science Foundation, and other major projects.

Meiosis is a special type of cell division used by sexually reproducing organisms to produce gametes. During meiosis, homologous chromosomes pair up and undergo mutual exchange through homologous recombination, which is crucial for the accurate separation of homologous chromosomes during the first meiotic division. Meiotic recombination is thus one of the driving forces behind genetic diversity and the adaptive evolution of sexually reproducing organisms. Meiotic recombination is initiated by DNA double-strand breaks (DSBs) created by the Spo11 core complex, and the subsequent repair of these DSBs can lead to the formation of chromosomal crossover structures, ensuring stable chromosome pairing and exchange. Although Spo11 evolved from the cleavage subunit Top6A of the archaeal topoisomerase VI (Topo VI), and almost all reproductive organisms use Spo11 to generate meiotic DSBs, the composition of the Spo11 core complex, its correspondence with Topo VI, and the molecular mechanisms of its binding to and cleaving DNA substrates are still not well understood.Recently, a research paper titled "Cryo-EM structures of the Spo11 core complex bound to DNA" was published in Nature Structural & Molecular Biology. The first author of the paper is researcher/assistant professor You Yu from ZJE (Zhejiang University- University of Edinburgh Institute), and the co-first authors are Dr. Juncheng Wang from the Institute of Advanced Medical Sciences at Shandong University, and postdoctoral researcher Kaixian Liu and PhD student Zhi Zheng from MSKCC (Memorial Sloan Kettering Cancer Center). The paper reported for the first time the Cryo-EM structures of the Spo11 core complex (Spo11-Rec102-Rec104-Ski8) bound to DNA (hairpin DNA/gapped DNA) at resolutions of 3.7Å and 3.3 Å. These structures revealed the detailed interactions between the subunits within the Spo11 core complex, as well as extensive interactions between the Spo11 core complex and the DNA backbone and with the recessed 3'-OH, and the first 5' overhanging nucleotide. The study determined the molecular mechanism by which the Spo11 core complex specifically binds to DNA ends and revealed the molecular mechanism by which the Spo11 core complex preferentially cleaves DNA in vivo. At the same time, yeast functional experiments also verified the interactions between subunits within the Spo11 core complex and between proteins and nucleic acids, and revealed the specificity of the Rec102 subunit structure, which is homologous to the archaeal Top6BL (Figure 1). Finally, the study provided an in-depth understanding of the dimerization of the Spo11 core complex and the role of divalent metal ions in catalyzing the enzymatic reaction of DNA double-strand breaks.图1. Gapped DNA结合Spo11核心复合物的冷冻电镜结构及蛋白-核酸相互作用This study was collaboratively completed by the teams of Scott Keeney and Dinshaw Patel from MSKCC. It also represents a new discovery by Dr. You Yu, who joined ZJE in 2024, in the field of chromosome structure maintenance and chromosome stability research.The You Yu Research Group at ZJE has long been engaged in structural and molecular biology research related to the maintenance of chromosome structure and chromosome stability. Innovative research achievements include studies on the molecular structure of the SMC5/6 complex and its molecular mechanisms of interaction with DNA, as well as research on the structure and molecular mechanisms of novel antiviral nucleic acid immune effectors, including the SMC5/6 complex (and the membrane protein Cam1). The laboratory is actively recruiting postdoctoral fellows in the fields of structural biology, molecular biology, genetics, and immunology, and encourages undergraduate students interested in these research directions to apply for M.S. or Ph.D. with our group.Link to the paper：https://www.nature.com/articles/s41594-024-01382-8 Introduction to Dr. You Yu's Research Group：https://person.zju.edu.cn/H124005

Organelles engage in signal transduction and material exchange through membrane contact sites, which play significant roles in lipid synthesis, calcium ion transfer, and autophagy. Mitochondria have been widely reported to form contact sites with the endoplasmic reticulum (ER), referred to as mitochondria-ER contact sites (MERCs). Early studies suggested that mitochondrial fusion proteins Mitofusin 1 and 2 (MFN1/2) function as physical linkers at these contact sites by forming dimers with MFN2 on the ER. However, super-resolution imaging of MFN2 fails to detect MFN2 signal on ER membranes. Thus, the model that ER-MFN2 dimerizes with mitochondrial-MFN2 requires re-examination.Recent findings propose that MFN2 specifically transports phosphatidylserine (PS) from the ER to mitochondria for the synthesis of phosphatidylethanolamine (PE), further indicating MFN2's potential involvement in multiple functions at MERCs. Whether all these functions are mediated by MFN2-MFN2 dimers and whether other unknown ER proteins participate with MFN2 remains unresolved. Therefore, identifying new ER protein partner for MFN2 and elucidating their biological functions will help in reevaluating the role of MFN2-MFN2 homodimers in mediating MERCs and functions related.On 12 August 2024, Dr. Zhi Hong's group at ZJE published an article titled "Dynamic interaction of REEP5-MFN1/2 enables mitochondrial hitchhiking on tubular ER" in the Journal of Cell Biology. This study is the first to reveal that the ER-shaping protein REEP5, as a novel interacting partner of MFN1/2, mediates the mitochondrial hitchhiking on the tubular ER, ultimately achieving uniform mitochondrial distribution throughout cytoplasm and regulating cellular reactive oxygen species (ROS) homeostasis.Previous results indicated that knockdown or knockout of REEP family members in the ER leads to mitochondrial dysfunction. Thus the study initially performed a small-scale screening of the REEP protein family, discovering that REEP5 specifically binds MFN1/2. Live-cell imaging further confirmed the enrichment of REEP5 and MFN1/2 at MERCs. The Using GI-SIM super-resolution live imaging, ER and mitochondria displayed a dynamic “association-dissociation” pattern, with REEP5-MFN2 tethers driving mitochondrial hitchhiking on the tubular ER. The study found that weakening REEP5-MFNs interactions leads to mitochondrial collapse to the perinuclear region. Interestingly, when REEP5-MFNs interactions are locked, mitochondrial can no longer be randomly released from tubular ER, they remained attached to the ER instead and resulting in mitochondrial hyperfusion. The findings suggest that the dynamic binding between REEP5 and MFN1/2 underlies the molecular mechanism of dynamic ER-mitochondria contact.Previous studies have shown that the subcellular localization of mitochondria is closely related to mitochondrial ROS homeostasis. Using the mitochondrial-localized ROS sensors roGFP2 and HyPer7, the researchers found that mitochondrial ROS level is tightly regulated by REEP5-MFN1/2 tethering strengths, e.g. mitochondrial ROS is upregulated once REEP5-MFN1/2 tethering is disrupted.In summary, this study elucidates a novel mechanism by which the REEP5-MFN1/2 protein complex facilitates mitochondrial "hitchhiking" along the tubular ER, thereby promoting uniform mitochondrial distribution within the cell and regulating cellular ROS homeostasis. The findings offer theoretical evidence suggesting that organelle interactions are intrinsically dynamic processes featured by cycles of association and dissociation.Dr. Zhi Hong from ZJE serves as the corresponding author, with Dr. Shue Chen and Ph.D. candidate Yang Sun as co-first authors. Additionally, Ph.D. candidates Lan Yang and Yuling Qin from ZJE contributed significantly to this study. This research received support from the National Natural Science Foundation of China.Link to the paper: https://doi.org/10.1083/jcb.202304031About Dr. Zhi Hong’ labDr. Zhi Hong’s research group focuses on organelle interactions and cellular homeostasis, as well as investigating the molecular mechanisms and biological functions related to lipid metabolism. Their findings have been published in esteemed journals such as the Journal of Cell Biology, Cell Research, Autophagy, and Antiviral Research.

Chronic lung infections caused by opportunistic pathogens such as Pseudomonas aeruginosa affect the lives and health of people around the world, especially the majority of people who are sick or immunocompromised. Antibiotics are the main treatment option for infections caused by bacteria. However, the treatment of chronic lung infections is more challenging due to the unique biofilm-dominated lifestyle. Compared with planktonic cells, biofilms formed by microbial communities and complex polymer matrices are inherently more resistant to antimicrobial drugs, which is a major factor in clinical relapse. Among the various mechanisms of biofilm resistance, the heterogeneity of microbial biofilms, including chemical gradients and oxygen gradients, has an important impact on drug resistance. For example, cell subpopulations located on the surface of biofilms are metabolically active and grow rapidly. In contrast, cell subpopulations deep in the biofilm are metabolically inactive, grow slowly, or do not grow, corresponding to the spatial heterogeneity of nutrient and oxygen distribution. This means that although antimicrobial agents represented by antibiotics can successfully eliminate bacteria on the surface, they may not be able to fight against metabolically dormant bacteria embedded in biofilms. Therefore, it may be a practical and promising approach to treat difficult biofilm-related chronic infections by combining biofilm metabolic characteristics with biofilm heterogeneity.To this end, Professor Zhou Min's team from the Second Affiliated Hospital of Zhejiang University School of Medicine/Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Professor Xu Feng from the Department of Infectious Diseases of the Second Affiliated Hospital of Zhejiang University School of Medicine, and Professor Chen Xiaoyuan from the National University of Singapore published an online research paper titled "Wake Biofilm Up to Enhance Suicidal Uptake of Gallium for Chronic Lung Infection Treatment" in the internationally renowned journal "Biomaterials".In this study, we developed a maltohexaose (Glucose polysaccharide, GP)-modified catalase and gallium ion co-loaded delivery polydopamine-coated mesoporous silica (MCPGaGP) nanosystem that can activate the metabolism of dormant bacteria inside the biofilm by converting endogenous hydrogen peroxide in the infection site and biofilm into oxygen, thereby awakening the Pseudomonas aeruginosa (PAO1) biofilm. Activated PAO1 secretes more iron ion acquisition tools, such as siderophores, to enhance the suicidal uptake of gallium ions that mimic iron nutrition. In addition, the internalized gallium ions act as a "Trojan horse" to destroy the biofilm by interfering with the bacterial physiological processes of iron ion acquisition and utilization, biofilm formation, and quorum sensing. Subsequently, the aerosol administration method and the modification of the bacterial-specific transporter maltohexaose enable the delivery of MCPGaGP to the biofilm-induced chronic lung infection area and the targeted release of gallium into the bacteria, providing excellent therapeutic effects. Therefore, we propose an important strategy to awaken biofilms by coordinating biofilm heterogeneity across bacterial nutrition, metabolism, and oxygen gradients and improving the antimicrobial efficacy of gallium-based “Trojan Horse” strategies in biofilm-associated lung diseases.Figure 1: Enhance suicidal uptake of gallium Trojan horses for the treatment of chronic lung infectionsProfessor Zhou Min of ZJU-UoE Institute and Professor Ouyang Hongwei of Liangzhu Laboratory jointly trained postdoctoral fellow He Jian and Lin Xiuhui, an infectious physician at the Second Affiliated Hospital of Zhejiang University School of Medicine, are the co-first authors of the paper, and Professor Zhou Min of Zhejiang University-Edinburgh Joint College, Professor Xu Feng of the Second Affiliated Hospital of Zhejiang University School of Medicine and Professor Chen Xiaoyuan of Yong Loo Lin School of Medicine/School of Engineering, National University of Singapore are the co-corresponding authors of the paper. The above research was strongly supported by the National Key R&D Program, the National Natural Science Foundation, the Zhejiang Provincial Key R&D Program Project Fund, and the Innovation Institute Medical Transformation Project.In terms of developing new anti-infection treatment strategies, Professor Zhou Min has conducted in-depth research in recent years on bacterial keratitis, endophthalmitis, and other ophthalmic resistant bacterial infections, refractory fungal keratitis, pneumonia caused by resistant bacteria and difficult-to-heal wounds. In particular, the copper-source ophthalmic nanogel antibacterial method he designed has been clinically tested and has achieved satisfactory clinical antibacterial effects. (Biomaterials 2024； Nano Today 2023; ACS Nano 2023; Adv. Mater. 2022； ACS Nano 2022; Nano Today 2022； ACS Appl. Mater. Interfaces 2022; ACS Nano 2021; Bioact. Mater. 2021; Biomaterials 2021； ACS Nano 2020; Theranostics 2020; Appl. Mater. Interfaces 2019; Appl. Mater. Interfaces 2018；）。

Alternative splicing is a widespread post-transcriptional regulation mechanism that produces various mRNA transcript isoforms. Accurate identification of transcript types and their abundance is essential for studying the biological functions of alternative splicing. Emerging long-read sequencing technologies (LRS), capable of producing reads ranging from thousands to tens of thousands of bases, offer the potential to overcome the bottlenecks of precise transcript identification faced by short-read sequencing.In recent years, numerous new bioinformatics tools have been developed to reconstruct transcript structures using LRS data. These algorithms can be categorized into two main types: guided and unguided. Guided algorithms require known reference gene annotations to assist in the transcript identification process, whereas unguided algorithms perform de novo reconstruction based solely on the sequence data, without needing reference annotations. Various strategies are employed by these tools to enhance detection accuracy, such as constructing splicing graphs, utilizing support read abundances, and applying machine learning models. Among them, TALON and FLAMES utilize a guided approach, whereas Freddie, TAMA, and UNAGI operate in an unguided mode. Meanwhile, StringTie2, FLAIR, IsoQuant, and Bambu include algorithms of both types. However, due to a lack of systematic evaluation, the performance of these tools under different data types and parameter settings remains unknown.On May 10, 2024, Nature Communications published the latest research advancements from the team of researcher Dr. Wanlu Liu at the Zhejiang University-University of Edinburgh Institute (ZJE), titled "Comprehensive assessment of mRNA isoform detection methods for long-read sequencing data."The study integrates various simulated and experimental data covering a wide range of biological scenarios, to conduct a comprehensive and in-depth evaluation of nine long-read mRNA isoform detection tools. The results demonstrate that IsoQuant is currently the most outstanding transcript identification tool, with Bambu and StringTie2 also showing impressive performances. Additionally, FLAMES and FLAIR are functionally comprehensive, supporting both upstream and downstream analyses. The authors analyzed the advantages and limitations of each algorithm and provided suggestions for improvement, directing future method development. This research establishes a foundation for fully exploiting long-read technologies to decipher transcriptome complexity. Concurrently, the authors developed the YASIM (Yet Another SIMulator) for long-read RNA sequencing, capable of simulating new alternative splicing events and real gene expression profiles and allowing precise control over various parameters such as sequencing depth, transcript complexity, read completeness, and sequencing accuracy to facilitate a comprehensive evaluation of the robustness of different tools.Initially, the authors used YASIM to generate simulated data under various conditions to assess the precision and sensitivity of different algorithms concerning sequencing depth, transcript complexity, read completeness, sequencing accuracy, and reference annotation completeness. The results indicated that IsoQuant and Bambu, under guided mode, showed the highest precision; IsoQuant and StringTie2 in guided mode demonstrated the best sensitivity. Most algorithms suffered degraded performance with shorter reads or lower sequencing accuracy.Subsequently, the authors analyzed 16 published spike-in control datasets, and the results suggested that algorithms in guided mode outperformed those in unguided mode, with IsoQuant, Bambu, and StringTie2 in guided mode performing optimally overall. The authors also collected 25 real experimental datasets from four species for further detection analysis, which reconfirmed the high accuracy of IsoQuant and Bambu in guided mode for known transcript identification. Additionally, the authors conducted downstream analyses of differential isoform usage detected by various software, finding that the results from guided-mode tools were the most consistent, with IsoQuant and Bambu performing best. Based on mRNA isoform detection results from long-read sequencing data on a human embryonic stem cell line using StringTie2 and Bambu, the authors successfully validated a new isoform of the RPL39L gene through RT-qPCR experiments.Finally, a computational efficiency analysis revealed that StringTie2 had the fastest run time and the lowest memory usage, with FLAMES, FLAIR, Bambu, and IsoQuant also performing well.In summary, this study conducted a systematic evaluation of the main existing tools for mRNA isoform identification using LRS data by integrating simulation data, sequins control data, and experimental data. This evaluation work provides a reference for tool selection and highlights the strengths and weaknesses of various algorithms, facilitating the further optimization of long-read data mRNA isoform detection algorithms and promoting the application of long-read technologies in unraveling transcriptome complexity.Yaqi Su, a 2019 undergraduate in Bioinformatics at ZJE (currently a PhD student at UC Berkeley), is the first author of this article, and Zhejian Yu, a 2019 undergraduate in Bioinformatics at ZJE (now a master’s student at the University of Edinburgh), is the second author. Dr. Wanlu Liu is the corresponding author. Other contributing authors include Siqian Jin, Ziwei Xue, Yixin Guo (doctoral students in bioinformatics at ZJE), Xinyi Chen (master's student in bioinformatics at ZJE), Zhipeng Ai (doctoral student in Zhejiang University School of Medicine), Ruihong Yuan (2019 undergraduate in Bioinformatics at ZJE), Dr. Di Chen (researcher at ZJE), Dr. Hongqing Liang (researcher at Zhejiang University School of Medicine), and Dr. Zuozhu Liu (researcher at the ZJUI institute).

Contemporarily, the fast-paced society made people live under huge stress. Irregular eating habits and excessive drinking are common, causing frequent complaints of stomachache, bloating, and acid reflux. These symptoms often indicate the presence of underlying stomach diseases. China is a nation plagued by stomach disease. According to statistics, the incidence of gastric diseases in China is as high as 85%. A healthy stomach acts like a food grinder, secreting strong acidic gastric juices. However, an overproduction of hydrochloric acid or excessive activity of gastric enzymes can damage the stomach lining, leading to gastritis and gastric ulcers. Oral drug delivery is considered the preferred route of drug administration due to its safety, non-invasiveness, low cost, high patient compliance, and benefits regarding targeted or localized therapy, such as the treatment of diabetes and gastric diseases. However, gastric emptying limits the retention and absorption of drugs in the stomach, and the acidic environment and proteases may also affect the activity of drugs, especially for biological products. To retain drugs in the stomach, strategies such as increasing adhesion, changing shape, using microneedles, and generating buoyancy have been used, as exemplified by the “floating systems” for diltiazem, verapamil, and others. These floating systems can decrease their density by swelling or producing gas, which promotes their flotation in gastric juice. Compared to other strategies, flotation systems have been well developed and widely used in the clinic, but they are mainly designed as tablets to carry drugs and maintain buoyancy, which are not friendly to patients with dysphagia, and the swelling or gas produced by tablets in the stomach may cause indigestion and even aggravate gastric diseases. Spirulina has been widely used in the field of food and health food, and its safety has been unanimously recognized in domestic and overseas. In addition, spirulina is rich in alkaline ions such as potassium and sodium, which can directly neutralize gastric acid and inhibit pepsin to reduce the occurrence of gastric ulcers, and is also rich in chlorophyll a, γ-linolenic acid, antioxidants β-carotene, dismutase SOD and phycocyanin and other good anti-ulcer factors. The comprehensive effect of these factors has obvious auxiliary effects on gastritis and gastric ulcers. A large number of clinical trials in domestic and overseas have shown that spirulina consumption has a certain protective effect on gastric diseases, and has good application potential in the design of gastric delivery system. Recently, Professor Min Zhou's team from the Second Affiliated Hospital of Zhejiang University School of Medicine/Zhejiang University-University of Edinburgh Institute published a research paper titled Natural floating biosystem for oral induced diseases in the Matter (the Cell sister journal), making new progress in the design of oral gastric delivery systems. This research has developed a novel oral drug delivery strategy based on spirulina, which utilizes a spirulina biological floating system to load drugs and improve their gastric retention time. While ensuring safety, it significantly improves the therapeutic effect of drugs on gastric diseases. Good results have been achieved in mouse acute and chronic models and pig animal models, and it is expected to be applied to the treatment of various gastric diseases and the delivery of special drugs that require absorption through the stomach. Before this, various microbial drug carriers (such as bacteria, blood cells, and microalgae) have gained considerable interest because of their special biological functions. However, the current studies on microbial carriers mostly focus on intravenous or intestinal delivery, and few have been reported for large-scale production. The possible reasons are as follows: (1) gastric emptying makes it difficult for these microbial systems to remain in the stomach, and the acidic environment and proteases may rapidly disrupt their bioactivity;(2) the traditional drug-loading process needs to incubate the microorganism with a high concentration of the drug for a long time, which may affect the activity of microalgae, especially for water-insoluble drugs, which require organic solvents that are mostly toxic;(3) special modification or multi-step processing of microorganisms will increase the cost, make production more difficult, and reduce the advantages of the microorganisms as natural drug carriers. Under appropriate conditions, algae in the water will grow rapidly and then accumulate, float, cover the surface of the water, and eventually cause algal blooms. As a natural micron-sized floating system, floatable microalgae are low-cost and dysphagia-friendly, and most of them have beneficial biological components (such as phycocyanin and spirulina polysaccharides), which show great application potential to overcome the above problems of gastric floating tablets. To challenge the above dilemmas, we mimic the formation of algal blooms, use the spatial structure between microalgae for rapid drug loading, and add gastric-acid-sensitive bismuth pectin instead of EPS to promote the accumulation of microalgae. Based on RSV and Spirulina platensis (S. platensis [SP], a kind of floatable microalgae with a special structure), here we design a grid-like drug-loading system. With the help of the long strip structure of RSV after recrystallization and the natural long helical structure of spirulina, the SP-based RSV loading system (SP-RSV) can be quickly obtained by simple mixing, which does not affect the bioactivity of microalgae and is suitable for large-scale production. Through the spatial grid structure formed between RSV and SP, almost all the RSV can be evenly dispersed throughout the SP and further float in gastric juice by the buoyancy of SP. In addition, bismuth pectin has been reported to interact with mucin and aggregate rapidly in the stomach acidic environment, which may enhance the adhesion of drugs and provide some protection for the stomach from alcohol. The combination of bismuth pectin (which gelatinizes rapidly upon contact with gastric juice) with SP-RSV (SP-RSV-Bi) can effectively prolong the floating time of SP-RSV in gastric juice while increasing its adhesion, both of which help SP-RSV to reside in the stomach for a long time, and finally release RSV rapidly after exposure to alcohol. In mice with acute or chronic alcohol injury models, the SP based floating system can stay in the stomach for a long time, better alleviating alcohol-induced gastrointestinal injury and alcoholic liver symptoms. In addition to the mouse models, we evaluate the therapeutic effects of this floating system in piglet models where the gastrointestinal tract is more similar to that of humans. Through gastroscopy, it is observed that the system can accumulate and float effectively in the stomach of piglet, and the retention time of stomach is greatly prolonged. In both mouse and piglet models, this biosystem can float in the stomach effectively, and its therapeutic efficacy and safety are also demonstrated, indicating its promising clinical application. Dr. Shiyuan Hua from the Min Zhou team at the Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute) and Dr. Shiqi Liu from the College of Animal Science at Zhejiang University are the co first authors of the paper. Professor Min Zhou from the ZJU-UoE Institute, Professor Tizhong Shan from the College of Animal Science at Zhejiang University, and Professor Xiaoyuan Chen from Yong Loo Lin School of Medicine and Faculty of Engineering at the National University of Singapore are the co corresponding authors of the paper. In recent years, Min Zhou's research group has conducted a series of innovative studies in the field of medical applications based on microalgae active biomaterials. In the early stage, the Min Zhou team carried out a series of research based on engineering microalgae for tumor treatment (Science Advances 2020; Advanced Functional Materials 2020; Small 2020; ACS Applied Materials&Interface 2020; Theranotics 2021; View 2021), infection disease treatment (Nano Today 2022; Adv. Therapeutics 2020), gastrointestinal inflammation treatment (ACS Nano 2023; Nature Communications 2022; Science Advances 2021), and brain disease treatment (Advanced Materials 2024), and made a series of pioneering progress.

Recently, the research group of Dr. Liu Jian from Zhejiang University-University of Edinburgh Institute (ZJE) published a review article titled “Neutrophils in Cancer: Dual Roles through Intercellular Interactions” in Oncogene, a classic oncology journal of the Nature Publishing Group (SCI Q1). Dr. Jian Liu is the corresponding author of this article. Undergraduate student Xinyu Yu from ZJE is the first author. The article elucidates the dual roles of neutrophils in the tumor microenvironment (TME) from the perspective of cell-cell interactions and summarizes two therapeutic strategies targeting the anti-tumor and pro-tumor abilities of neutrophils. Access to the publication: https://www.nature.com/articles/s41388-024-03004-5。As the first author of the article, Xinyin Yu entered Jian Liu's lab for research training early in her undergraduate studies. At the first meeting in the lab, she listened to her senior sister's systematic report on the topic of neutrophils, from which she learned that in the context of tumours, neutrophils have two sides: they can both suppress and promote cancer development. This started her path of learning and researching about neutrophils. Through long-term knowledge accumulation, nearly half a year of writing and repeated revisions, the article was finally published. Looking back on her journey, Yu feels that the training of students' scientific writing ability in the ZJE and the help of professors and siblings to her are all indispensable factors for the publication of the article.This was my first encounter with knowledge beyond textbooks, and the discovery did not align with my understanding of neutrophils. I was shocked and intrigued, "Could the body's own immune cells actually promote tumor development?" After the meeting, I researched related materials and followed many relevant WeChat accounts, gradually learning about many cutting-edge discoveries through their posts. Given my interest, I chose literature on cancer-related neutrophils for the lab's monthly article recommendations, accumulating considerable knowledge over time. Later, a casual conversation with a senior inspired me to write a review article. Considering my familiarity with the field and the ample time in my freshman year, and ZJE's emphasis on training students' research writing skills (having written several small essays before), I started writing the article with Professor Liu's support after receiving his encouragement.I began writing in June during my freshman summer vacation and completed the text in August. The article was submitted in November and accepted in March of the following year. This period was incredibly meaningful for me. In June, on a green train from Chongqing to Beijing, I couldn't get a sleeper ticket and had to sit for 18 hours. Unable to sleep, I spent the night writing the article's framework and organizing the hundreds of references I had collected. Given the considerable workload, I complained more than once to my labmates, "I never want to write a review again in my life," but I persevered with their encouragement and help. During the National Day holiday, I chose to stay at the North Campus to meticulously create the figures for the paper, spending an entire day on each figure. Before submission, Professor Liu and my seniors patiently helped me review and revise the article. Fortunately, the article was eventually published in Oncogene, an outcome I had never imagined before the review process.I sincerely thank Professor Liu for his consistent support, my labmates for their patience and help, and the research group for educating and training me. I am fortunate to be at ZJE, where the liberal environment and rich educational resources have given me the opportunity to engage closely with scientific research.As a member of the ZJEers, Yu has realised ZJE's talent cultivation model of "whole-person training, global immersion and whole-chain practice". ZJE will continue to provide a fertile ground for future leaders in the medical field and cultivate the international talents needed for the development of the world's medical and healthcare industry.About Jian Liu’s labJian Liu's group is now interested in investigating lung squamous cell carcinoma development and treatment using genetic mouse models and AI+ multi-omics, especially the research direction on cancer immunology and the 3D genome. He has published over 50 papers, including publications in the past three years, as a co-corresponding author in Nature Communications, Advanced Science, Oncogene, Molecular Oncology, and Frontiers in Immunology journals. Moreover, his lab developed a multi-omics web database Omics3D (http://omics3d.net/) to investigate the de novo functional genome during cancer development.Email:JianL@intl.zju.edu.cnJian Liu’s lab (https://person.zju.edu.cn/liujian) is recruiting postdoc and Ph.D. students, including the single degree from the University of Edinburgh

Recently, Dr. Jian Liu’s group from Zhejiang University-University of Edinburgh Institute (ZJE) and the collaborators, Pro. Aifu Lin from College of Life Sciences of Zhejiang University, published an article entitled “LncRNA LINK-A Remodels Tissue Inflammatory Microenvironments to Promote Obesity” in Advanced Science. http://doi.org/10.1002/advs.202303341High-fat diet (HFD)-induced obesity is a crucial risk factor for metabolic syndrome, mainly due to adipose tissue dysfunctions associated with it. However, the underlying mechanism remains unclear. This study used genetic screening to identify an obesity-associated human lncRNA LINK-A as a critical molecule bridging the metabolic microenvironment and energy expenditure in vivo by establishing the HFD-induced obesity knock-in (KI) mouse model. Mechanistically, HFD LINK-A KI mice induced the infiltration of inflammatory factors, including IL-1β and CXCL16, through the LINK-A/HB-EGF/HIF1α feedback loop axis in a self-amplified manner, thereby promoting the adipose tissue microenvironment remodeling and adaptive thermogenesis disorder, ultimately leading to obesity and insulin resistance. Notably, LINK-A expression was positively correlated with inflammatory factor expression in individuals who are overweight. Of note, targeting LINK-A via nucleic acid drug antisense oligonucleotides (ASO) attenuated HFD-induced obesity and metabolic syndrome, pointing out LINK-A as a valuable and effective therapeutic target for treating HFD-induced obesity. Briefly, our results revealed the roles of lncRNAs (such as LINK-A) in remodeling tissue inflammatory microenvironments to promote HFD-induced obesity. Pro. Aifu Lin and Pro. Jian Liu are the corresponding authors. In addition, the master student Zengzhuang Yuan (ZJE, 2021 entry) participates in this research. Lin’s group is mainly responsible for the generation of mouse models, mechanism investigations and manuscript writing; Liu’s group is mainly responsible for bioinformatics analyses, project designing, and manuscript revision. About Jian Liu’s labJian Liu's group is now interested in investigating lung squamous cell carcinoma development and treatment using genetic mouse models and AI+ multi-omics, especially the research direction on cancer immunology and 3D genome. He has published over 50 papers, including publications in the past three years, as a co-corresponding author in Nature Communications, Advanced Science, Molecular Oncology, Frontiers in Immunology journals. Moreover, his lab developed a multi-omics web database Omics3D (http://omics3d.net/) to investigate the de novo functional genome during cancer development.Email:JianL@intl.zju.edu.cnJian Liu’s lab (https://person.zju.edu.cn/liujian) is recruiting postdoc and Ph.D. students, including the single degree from University of Edinburgh

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

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).