Tendon injuries are common in orthopedics and sports medicine, often leading to pain, impaired mobility, and long-term disability. For severe tendon rupture or large tendon defects, surgical reconstruction usually relies on autografts, allografts, or artificial substitutes. However, current strategies remain limited by donor-site morbidity, immune rejection, insufficient tissue integration, and poor long-term durability. Meanwhile, conventional regenerated silk fibroin hydrogels, despite their excellent biocompatibility and processability, are typically too weak to meet the mechanical demands of load-bearing tendon repair.Recently, Prof. Wenwen Huang’s team, in collaboration with Prof. Weiliang Shen and Prof. Xiao Chen from Zhejiang University School of Medicine, published a research article entitled “Tough and hierarchically-structured silk hydrogel for artificial tendons” in Biomaterials. Inspired by the multiscale aligned architecture of native tendons, the study developed a water-based physical processing strategy combining directional freezing and hot-stretching to fabricate tough, hierarchically structured silk fibroin hydrogels, named DFHS hydrogels. At a high water content of approximately 70 wt%, the DFHS hydrogel achieved an ultimate tensile strength of 13.9 MPa and a fracture toughness of 45.5 kJ m⁻², with mechanical performance comparable to the human anterior cruciate ligament and excellent long-term structural stability.In this strategy, directional freezing first induces anisotropic ice crystal growth to generate micrometer-scale aligned honeycomb-like pore walls within the regenerated silk hydrogel. Subsequent hot-stretching above the water-associated glass transition temperature promotes the reorientation of silk fibroin molecular chains and β-sheet nanocrystals. Through this synergistic “microscale channel alignment + nanoscale β-sheet orientation” mechanism, the DFHS hydrogel recapitulates the hierarchical anisotropy of native tendon tissue.The optimized DF15H95S60 hydrogel, prepared with 15 wt% silk fibroin, hot-stretching at 95 °C, and a 60% stretching ratio, exhibited superior mechanical properties, including a tensile strength of 13.9 ± 2.1 MPa, a Young’s modulus of 16.3 ± 3.0 MPa, and a fracture toughness of 45.5 ± 7.5 kJ m⁻². Further analyses showed that the mechanical reinforcement was not simply caused by dehydration-induced densification, but arose from multiscale structural reorganization induced by directional freezing and hot-stretching.In biological evaluations, the DFHS hydrogel showed good cytocompatibility and pro-tenogenic potential. Its tendon-mimetic anisotropic microstructure guided cell alignment and activated signaling pathways related to extracellular matrix remodeling and tendon formation. In a rabbit Achilles tendon defect model, DFHS hydrogels maintained long-term structural and mechanical integrity, provided sustained mechanical support, and promoted the organized ingrowth and maturation of neo-tendon tissue. At 48 weeks after implantation, the regenerated tendon in the DFHS group displayed tissue morphology closer to that of native tendon.Overall, this study presents a facile and biocompatible physical processing strategy for transforming regenerated silk fibroin hydrogels from mechanically weak soft materials into tough, tendon-mimetic artificial scaffolds. The work provides a promising silk-based platform for tendon repair and offers a generalizable design principle for toughening other semicrystalline polymer hydrogels.Dr. Sicheng Zhou from Zhejiang University School of Medicine/Liangzhu Laboratory, Dr. Kexin Nie from the Zhejiang University–University of Edinburgh Institute, and Dr. Boxuan Wu are co-first authors of the paper. Congcong Qin, Jingyi Tian, Lele Li, Zhang Fan, Prof. Zi Yin, and Prof. Hongwei Ouyang made important contributions to this work. Prof. Xiao Chen, Prof. Weiliang Shen, and Prof. Wenwen Huang are the corresponding authors. This work was supported by the Key R&D Program of Zhejiang Province, the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China, the National Natural Science Foundation of China, and the Zhejiang Lingyan R&D Project.Original article: https://doi.org/10.1016/j.biomaterials.2026.124294

Silk fibroin (SF) is a naturally derived, biodegradable, and breathable material with excellent biocompatibility and processability, making it an ideal biomaterial for skin-friendly flexible electronic devices. However, natural silk fibroin is intrinsically nonconductive, which limits its direct use as a functional interface or charge-injection layer in electronic and optoelectronic devices. Endowing silk fibroin with efficient ion/electron transport capabilities while preserving its transparency, flexibility, and biocompatibility is therefore a key challenge for the development of next-generation wearable optoelectronic devices.Recently, the research team led by Researcher Wenwen Huang at the Zhejiang University-University of Edinburgh Institute (ZJE), in collaboration with the teams of Professor Dawei Di and Researcher Baodan Zhao from the College of Optical Science and Engineering and Haining International Joint Institute, Zhejiang University, published a research article in ACS Nano entitled “Silk Fibroin Ionotronics for High-Performance Wearable Perovskite LEDs.” The study proposes a strategy for converting naturally insulating silk fibroin into a high-performance silk fibroin ionotronic material (SFI). By introducing lithium salts into a silk fibroin system, the researchers constructed silk fibroin ionotronic films that combine high transparency, flexibility, biocompatibility, and ionic conductivity. These films were further integrated with PEDOT:PSS to form a mixed ion/electron-conducting interface, increasing the electrical conductivity to above 12.4 S cm⁻¹. Flexible perovskite light-emitting diodes (PeLEDs) based on this interface achieved a maximum luminance of 9,724 cd m⁻² and a current efficiency of 19.6 cd A⁻¹, and were successfully used for photoplethysmography (PPG) signal acquisition. This work provides a new materials and device platform for wearable displays, bioelectronics, and intelligent human-machine interaction.As shown in the figure below, the research team first used silk fibroin as a biofriendly flexible substrate and functional network, and constructed silk fibroin ionotronic materials by incorporating lithium chloride (LiCl). The introduction of lithium salts not only significantly increased the concentration of mobile ions in the system, but also enhanced the structural stability and mechanical properties of the material. Meanwhile, the SFI films retained excellent optical transparency: SF and SFI films with a thickness of 150 micrometers both exhibited transmittance above 90% in the visible-light range, higher than that of commonly used ITO transparent electrode substrates. This laid the foundation for their application in flexible transparent optoelectronic devices.In terms of interface design, the team combined SFI with PEDOT:PSS to construct a PEDOT:PSS/SFI hybrid conducting interface. The SFI substrate showed better wettability toward the PEDOT:PSS precursor solution, facilitating the formation of a uniform, low-defect conducting film. When the LiCl/SF mass ratio was 50%, the conductivity of the PEDOT:PSS/SFI film reached 12.49 S cm⁻¹, significantly higher than that of PEDOT:PSS/SF and PEDOT:PSS films directly deposited on PET substrates. Ultraviolet photoelectron spectroscopy and Kelvin probe force microscopy measurements showed that this interface had a higher work function and a more favorable surface-potential distribution, which helped improve hole injection and charge-transport efficiency.Based on this bio-ionotronic interface, the team fabricated ITO-free flexible perovskite LED devices with the structure PET/SFI/PEDOT:PSS/TFB/LiF/perovskite/PO-T2T/LiF/Al. Compared with PEDOT:PSS/SF control devices, PEDOT:PSS/SFI devices exhibited higher current density and luminance at the same voltage, ultimately achieving a maximum luminance of 9,724 cd m⁻² and a peak current efficiency of 19.56 cd A⁻¹, demonstrating excellent performance among ITO-free flexible LED systems.Further studies showed that the PEDOT:PSS/SFI interface could enhance the photoluminescence quantum efficiency of perovskite films and prolong the transient photoluminescence lifetime, indicating effective suppression of interfacial defect recombination. Space-charge-limited current measurements showed that devices based on PEDOT:PSS/SFI had a lower trap-filled limit voltage, lower trap-state density, and higher hole mobility. In addition, after 100 bending cycles at a bending radius of 10 mm, the devices retained approximately 80% of their initial luminance, indicating good flexibility and stability.The research team also demonstrated the potential of SFI-based flexible PeLEDs in wearable bioelectronics. By integrating the flexible PeLED with a silicon photodiode and a semiconductor analysis system, the team constructed a wearable optoelectronic sensing system for PPG signal acquisition. The green light emitted by the device can be effectively absorbed by blood, and the backscattered signal fluctuates periodically with changes in blood volume, enabling pulse-wave monitoring. The experimental results showed that the system could clearly capture PPG signals and further obtain acceleration plethysmogram (APG) features for the analysis of heart rate and parameters related to arterial elasticity.In terms of biocompatibility, the team evaluated SFI materials using human umbilical vein endothelial cells (HUVECs). Live/dead cell staining and CCK-8 assays showed that SFI had good cytocompatibility and supported cell proliferation. In addition, infrared thermal imaging showed that, during operation at a luminance of 1,000 cd m⁻², conventional ITO-based PeLEDs exhibited a temperature rise of up to 20.5 °C, whereas SFI-based devices showed a temperature rise of only about 1.7 °C. This suggests that SFI helps reduce local heat accumulation and improves safety and comfort in wearable applications.In summary, through ion doping and interface engineering, this study converted naturally insulating silk fibroin into a silk fibroin ionotronic material that combines high transparency, flexibility, biocompatibility, and high electrical conductivity. The hybrid conducting interface formed by this material and PEDOT:PSS effectively improved charge injection and transport in perovskite LEDs, enabling high-luminance, high-efficiency ITO-free flexible PeLED devices. The work further demonstrated a wearable bioelectronic system for PPG signal monitoring. This study not only offers a new approach for applying natural biomaterials such as silk fibroin in high-performance optoelectronic devices, but also opens new directions for the development of biofriendly ionotronic materials for wearable displays, health monitoring, and intelligent human-machine interaction.Jiawei Hong, a master’s student in Wenwen Huang’s team at the Zhejiang University-University of Edinburgh Institute; Zhongkai Yu, a specially appointed professor at the College of Physics and Optoelectronic Engineering, Yangtze University; and Weidong Tang, a postdoctoral researcher at the College of Optical Science and Engineering, Zhejiang University, are the co-first authors of the paper. The co-authors include Ke Zhou, Zhe Liu, and Gan Zhang, postdoctoral researchers at the College of Optical Science and Engineering, Zhejiang University; Hang Zhao and Junhan Ou, doctoral students in Wenwen Huang’s team at the Zhejiang University-University of Edinburgh Institute; Xinyi Yang, a master’s student; Bo Yu, an undergraduate student; Yichen Yang and Shengnan Liu, doctoral students at the College of Optical Science and Engineering, Zhejiang University; Wentao Xiong, a postdoctoral researcher; Zhixiang Ren, a doctoral student; Minhui Yu, a research assistant; Professor Nicola Gasparini of Imperial College London; and Chen Zou, a specially appointed researcher at the College of Optical Science and Engineering, Zhejiang University. Researcher Baodan Zhao of the College of Optical Science and Engineering, Zhejiang University; Researcher Wenwen Huang of the Zhejiang University-University of Edinburgh Institute; and tenured Professor Dawei Di of the College of Optical Science and Engineering, Zhejiang University, are the co-corresponding authors. This work was supported by the National Natural Science Foundation of China, the Zhejiang Provincial Natural Science Foundation of China, and other funding sources.Original article: https://doi.org/10.1021/acsnano.6c048431.Research Group ProfileResearcher at Zhejiang University; doctoral supervisor; Zhejiang Province high-level talent; adjunct professor at the Second Affiliated Hospital of Zhejiang University School of Medicine; Honorary PI at the University of Edinburgh. Professor Huang has led multiple projects funded by the National Natural Science Foundation of China and provincial/ministerial programs. Her research has long focused on protein-based materials, including the rational design of recombinant proteins, protein-material processing, regenerative medicine, and combined tumor therapies. She has published more than 50 related international papers, with an H-index of 31. She has been invited to serve as regional chair and publication chair for the International Conference on Biomedical Engineering and Applications, and as a reviewer for more than 30 academic journals. She is also a fixed member of the State Key Laboratory of Automotive Biofuels Technology and the Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine.The group applies engineering technologies to address the emerging shift from a disease-treatment-centered model to a health-centered model. It has established a recombinant-protein innovation platform guided by protein function, based on biosynthesis and simulation prediction, and validated and optimized through high-throughput preparation, analysis, and functional testing. The group conducts systematic research on the design and clinical translation of new biomaterials.Group website: https://wenwenhuang.com/Contact email: wenwenhuang@intl.zju.edu.cnThe group is recruiting highly self-motivated postdoctoral fellows, doctoral students, and master’s students, including applicants for the University of Edinburgh’s single PhD and single master’s programs through the application-based route. Further information: https://biomedical-sciences.ed.ac.uk/connections-outreach/international-activities/zje-institute 

Yang et al. develop a light-based approach to precisely shape astrocytic Ca²⁺ signals via endogenous IP₃ receptors and reveal how local calcium spikes and global waves differentially control organelle transport and astrocyte process morphogenesis. This work links “calcium patterns–organelle positioning–synaptic stability” and offers a powerful tool to dissect astrocyte functions in health and disease.Paper: https://doi.org/10.1083/jcb.202506032Video summary: https://www.youtube.com/watch?v=4KtKZlyvBoIDr Zhi Hong, Associate Professor at ZJE, Honorary Lecturer at University of Edinburgh, is the corresponding author of this paper; Dr Shue Chen (Hainan Medical University) and Dr Cong Yi (School of Basic Medical Sciences, Zhejiang University) are co-corresponding authors; Lan Yang, a PhD student at ZJE, is the first author, and Prof Mikael Björklund (University of Edinburgh) is a co-author.The Hong lab focuses on organelle interactions and homeostasis, lipid metabolism, and calcium signaling, with a particular interest in how astrocyte–organelle crosstalk contributes to neurodegenerative diseases. Undergraduate and graduate students interested in astrocytes, organelle dynamics, and advanced imaging are welcome to learn more about the group: https://person.zju.edu.cn/hongzhi

Recently, Prof. Donal O’Carroll’s group at the University of Edinburgh (UoE), together with Prof. Wanlu Liu (刘琬璐)’s group at ZJU-UoE Institute (ZJE) and Prof. Elly M. Tanaka’s group at the Research Institute of Molecular Pathology (IMP) in Vienna, published a collaborative study in The EMBO Journal titled “A mammalian-like piRNA pathway in Axolotl reveals the origins of piRNA-directed DNA methylation.” Using the axolotl as a model organism, the study uncovers for the first time the evolutionary origins of the mammalian nuclear piRNA pathway.Xinyu Xiang (相欣雨), a dual-degree ZJU-UoE PhD at ZJE, is the first author of this study. Her ZJU supervisor is Prof. Wanlu Liu, and her UoE supervisor is Prof. Donal O’Carroll FRS FRSE (corresponding author). Anni Gao (高安妮), an undergraduate student in the bioinformatics dual-degree program at ZJE, is the second author; she conducted research training in Prof. Liu’s lab during her undergraduate studies. This work highlights the strong strengths of the ZJU-UoE Institute in fostering high-level research collaboration and talent development, and exemplifies the impactful synergy and innovation arising from the international partnership between the two universities in the field of biomedical research.(1) piRNA-mediated transposon silencing is essential for germline integrityDuring the development of animal germ cells (such as sperm and oocytes), active transposonsbehave like “genomic time bombs.” As highly abundant mobile DNA elements, transposons can “jump” to new genomic locations, disrupt genes, induce DNA double-strand breaks, and consequently impair germ cell development and lead to infertility. The piRNA (PIWI-interacting RNA) pathwayfunctions as an efficient “demining system,” precisely recognizing and silencing active transposons 【1, 2】. It serves as a critical defense mechanism that safeguards genome integrity in the germline.(2) The nuclear piRNA pathway is believed to be bespoke to mammalspiRNAs are small non-coding RNAs that associate with PIWI proteins to silence transposons in germ cells, effectively defusing these “genomic time bombs.” The piRNA pathway consists of two parts: the cytoplasmic pathwayand the nuclear pathway. The cytoplasmic piRNA pathway is common to most animals 【3】 and functions by cleaving transposon transcripts, providing rapid and timely silencing. In contrast, the nuclear piRNA pathway acts as a “permanent seal,” guiding DNA methylation to stably silence transposons over the long term. For many years, this nuclear piRNA pathway was thought to be a mammal-specific mechanism 【1,2】.(3) Axolotl is an ideal model for studying transposons and the piRNA pathwayThe axolotl is a classic model organism in regenerative biology, well known for its remarkable tissue repair capacity, such as limb regeneration. Beyond its remarkable regenerative abilities, the axolotl also possesses an exceptionally large genome, as one of the largest among known animals (approximately 32 Gb, about ten times the size of the human genome) 【4】. This huge genome is largely result from extensive transposon expansion. Around 70% of the axolotl genome consists of transposons, compared with about 50% in humans. Its high transposon content and huge genome make the axolotl an ideal model for investigating transposon activity and their silencing mechanisms.(4) Axolotl has a mammalian-like piRNA pathwayTo trace the evolutionary origin of the mammalian piRNA pathway, we constructed a phylogenetic tree of key piRNA pathway genes across vertebrates. The analysis revealed that the core nuclear piRNA factors in mammals, such as PIWIL4, SPOCD1, C19ORF84, and TEX15, are found all together for the first time in the axolotl. Whereas these factors are partially missing in both lobe-finned and ray-finned fish. This suggests that the nuclear piRNA pathway may not have emerged in earlier vertebrate lineages. Furthermore, transcriptomic analyses show that these piRNA pathway genes exhibit germline-specific expressionin the axolotl, same as the mammalian expression pattern, thereby indicating their potential functional roles.(5) Axolotl possesses a functional cytoplasmic piRNA pathwayTo better understand transposon activity and silencing in the axolotl, we first predicted and annotated active transposons in axolotl genome, identifying a set of potentially active transposons. We then performed small RNA sequencing to profile piRNAs in axolotl germlines. The results revealed an abundantrepertoire of piRNAs in both male and female germlines (~88 million), with a substantial fraction derived from transposon sequences.The cytoplasmic piRNA pathway involves piRNA biogenesis and the classic ping-pong cycle, which mediates post-transcriptional silencing by cleaving transposon transcripts. These piRNAs are primarily generated from genomic piRNA clusters, which display clear sex-specific patterns in the axolotl. Moreover, transposon-targeting piRNAs exhibit hallmark features of the ping-pong cycle, providing strong evidences that a functional cytoplasmic piRNA pathway in the axolotl germline.(6) Evidence for an active nuclear piRNA pathway in axolotl is presentedThe nuclear piRNA pathway, or piRNA-directed DNA methylation, has been reported exclusively in mammals. This pathway is mediated by the piRNA-PIWIL4 complex together with associated nuclear factors, which recruit de novo DNA methyltransferases to specifically methylate the promoters of young and active transposons, ensuring their long-term silencing. During epigenetic reprogramming of the germline, the genome undergoes extensive DNA demethylation and is therefore particularly vulnerable to transposon activation, making piRNA-directed methylation silencing especially critical at this stage. The terminal outcome of this process is the high methylation levels of young transposons in sperm.Whole-genome bisulfite sequencing of axolotl sperm revealed an overall CpG methylation level of approximately 90%, higher than mammals (~75%-85%). Importantly, the entire transposon region, including promoter regions, exhibited tight methylation control. Moreover, young and potentially active transposons also showed significantly higherDNA methylation levels. Together, these findings provide the first evidence outside mammals that DNA methylation mediated transposon silencing, characteristic of the nuclear piRNA pathway, also exists in the axolotl. Overall, this study identifies a mammalian-like cytoplasmic and nuclear piRNA pathway in the axolotl. Small RNA sequencing and whole-genome methylation profiling together demonstrate that the axolotl possesses a functional cytoplasmic piRNA pathway for transposon transcript cleavage, as well as a nuclear piRNA pathway for long-term transposon silencing through DNA methylation. This work provides the first evidence that the mammalian piRNA pathway, particularly the piRNA-directed DNA methylation mechanism, can be traced back to the common ancestor of the axolotl and mammals, which are the early tetrapods. These findings not only fill a critical gap in the evolution of the piRNA pathway but also offer new insights into germline development, epigenetic reprogramming, and genome defense mechanisms.Original Publication:https://www.embopress.org/doi/full/10.1038/s44318-025-00631-w【1】 Wang X, Ramat A, Simonelig M, and Liu M-F Emerging roles and functional mechanisms of PIWI-interacting RNAs Nat Rev Mol Cell Biol 2023 24 123-141【2】 Ozata DM, Gainetdinov I, Zoch A, O’Carroll D, and Zamore PD PIWI-interacting RNAs: small RNAs with big functions Nat Rev Genet 2019 20 89-108【3】 Grimson A, Srivastava M, Fahey B, Woodcroft BJ, Chiang HR, King N, Degnan BM, Rokhsar DS, and Bartel DP Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals Nature 2008 455 1193-1197【4】 Nowoshilow S, Schloissnig S, Fei J-F, Dahl A, Pang AWC, Pippel M, Winkler S, Hastie AR, Young G, Roscito JG, et al. The axolotl genome and the evolution of key tissue formation regulators Nature 2018 554 50-55

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that accounts for 15–20% of all cases and is characterized by early onset, rapid progression, and high metastatic potential. Due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), TNBC offers limited therapeutic options. The primary treatment of TNBC patients is chemotherapy due to the high chemosensitivity of TNBC tumors. However, rapid recurrence and drug resistance often result in poor outcomes. Although immune checkpoint blockade (ICB) therapy has shown promise, its clinical efficacy in advanced and metastatic TNBC remains unsatisfactory. Therefore, developing a strategy that integrates precise drug delivery, tumor microenvironment (TME) modulation, and multimodal therapy is urgently needed.Recently, the research team led by Dr. Wenwen Huang from the Zhejiang University–University of Edinburgh Institute published a research article in Advanced Science, reporting a genetically engineered light-responsive in situ hydrogel system for immunomodulation and multimodal therapy of metastatic TNBC. The team designed a family of cysteine-tagged silk-elastin-like proteins (cSELPs) through synthetic biology and rational protein design strategies. These tri-block chimeric proteins integrate silk-inspired crosslinking motifs, elastin-based thermo-responsive motifs, and a photothermal agent-binding motif to form a biocompatible and stimuli-responsive protein hydrogel platform.As shown below, the cSELP hydrogel precursor solution undergoes in situ gelation at the tumor site, forming a stable therapeutic reservoir. Genetically introduced cysteine tags bind to gold nanorods (AuNRs) through strong Au–S bonds, eliminating the need for toxic surfactants and achieving stable photothermal conversion under near-infrared (NIR) irradiation. This enables precise and on-demand drug release while maintaining excellent biocompatibility. Upon NIR light exposure, the system induces mild photothermal therapy (PTT) and facilitates the coordinated release of the chemotherapeutic drug doxorubicin (DOX) and the immune checkpoint inhibitor anti-PD-L1 (aPD-L1). Through synergistic “photothermal–chemo–immuno” therapy, the hydrogel promotes immunogenic cell death (ICD), enhances T-cell infiltration, and activates systemic immune responses, effectively converting immunologically “cold” tumors into “hot” ones.In vivo, the c2Y@Au/DOX/aPD-L1 hydrogel achieved simultaneous suppression of both primary and distal tumors while exhibiting excellent biocompatibility and long-term safety. Compared to monotherapies, the system achieved strong antitumor efficacy with low drug doses and short irradiation time, and minimal systemic toxicity. In addition, the hydrogel demonstrated remarkable antibacterial performance, broadening its potential applications to post-surgical infection control and wound healing.In summary, Dr. Huang’s team developed a versatile, controllable, and expandable light-responsive hydrogel platform by integrating genetic engineering and materials design. This work offers a new strategy for treating metastatic TNBC through precise locoregional delivery and synergistic immunomodulation, showcasing broad potential for clinical translation.Authorship and AcknowledgmentsXinchen Shen (dual-degree Ph.D.) is the first author. Jiajia Zhang (M.Sc.), Ziheng Bai (currently a Ph.D. student under Dr. Angelica Foggetti at ZJE), Junhan Ou (Ph.D. candidate), and Kaiyue Zhang (Ph.D. candidate) from Dr. Huang’s group, and Tongyan Liu (M.Sc.) from Dr. Qianting Zhang’s group at ZJE are co-authors. Dr. Kaixiang Zhu from the Second Affiliated Hospital of Zhejiang University School of Medicine, as well as Dr. James Q. Wang, Dr. Chaochen Wang, Dr. Qianting Zhang, and Dr. Linrong Lu from ZJE, made important contributions to the study. Dr. Wenwen Huang (Zhejiang University–University of Edinburgh Institute) is the sole corresponding author. This research was supported by the National Natural Science Foundation of China and the Zhejiang Provincial Natural Science Foundation.Article Link: https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202512355

Decoding the tissue microenvironment and identifying potential therapeutic targets in cancer immunotherapy remain pressing frontiers of biomedical research. In recent years, spatial omics technologies have advanced rapidly. Spatial transcriptomics (ST) enables gene expression profiling within the spatial context of tissues, while spatial metabolomics (SM) uses mass spectrometry imaging to capture metabolite distributions. The integration of ST and SM offers multidimensional insights into the tissue microenvironment, particularly useful for uncovering metabolic heterogeneity and immune microenvironmental features in tumors. However, effective cross-modal and cross-sample integration has been hindered by fundamental differences in data type, spatial resolution, and tissue processing between ST and SM.Recently, Dr. Wanlu Liu’s research group at the Zhejiang University-University of Edinburgh Institute (ZJE) published a study in Nature Communications titled: “Integrating cross-sample and cross-modal data for spatial transcriptomics and metabolomics with SpatialMETA.” The team developed a next-generation spatial multi-omics integration algorithm, SpatialMETA, which simultaneously achieves cross-modal and cross-sample integration of ST and SM data. The method is built upon a conditional variational autoencoder (CVAE) framework, featuring tailored decoders and loss functions for ST and SM to accurately capture modality-specific feature distributions. SpatialMETA not only enables fusion across ST and SM modalities but also corrects batch effects between samples, facilitating consistent clustering across multiple datasets. Moreover, the model quantifies the contributions of different modalities to the integrated representation, thereby enhancing the biological interpretability of integration results.The research team applied SpatialMETA to publicly available multi-omics datasets, including clear cell renal cell carcinoma (ccRCC), glioblastoma (GBM), and mouse brain. Results demonstrated that SpatialMETA accurately reconstructed the feature distributions of ST and SM and successfully identified immune-associated spatial clusters with unique metabolic features. These findings provide novel perspectives for understanding metabolic heterogeneity within tumor microenvironments. Compared with existing single-cell or spatial multi-omics integration tools, SpatialMETA outperforms in reconstruction accuracy, cross-modal fusion, and cross-sample consistency. In addition, SpatialMETA offers a wide range of practical analysis modules, including automatic metabolite annotation based on m/z values, characterization of cluster-specific marker genes and metabolites, and correlation analysis between user-defined genes and metabolites. Notably, even with SM-only datasets, SpatialMETA supports cross-sample integration and analysis, expanding its applicability to diverse research scenarios.Authors and Funding Information:Dr. Wanlu Liu from the Zhejiang University-University of Edinburgh Institute (ZJE) is the corresponding author of this work. PhD candidates Ruonan Tian and ZJU-UoE dual-degree PhD candidates Ziwei Xue from ZJE are co-first authors. This research was conducted in collaboration with Professor Di Wang from Zhejiang University School of Medicine, Professor Jia Liu from the Shanghai Institute of Materia Medica, and Professor Youqiong Ye from Shanghai Jiaotong University. ZJE undergraduates Yiru Chen and Yicheng Qi also actively contributed to this study. This work has been supported by the National Key R&D Program of China, National Natural Science Foundation of China, the ZJU-YST joint research center for fundamental science, and the State Key Laboratory (SKL) of Biobased Transportation Fuel Technology.

The advancement of clinical and therapeutic innovations is fundamentally dependent on a deepened understanding of the human immune system. In the Voices article recently published in Immunity, leading experts in the field deliberated on emerging approaches in human immunology research. The discourse underscored the essential role of stringent experimental design and standardized specimen acquisition in driving the frontiers of immunological science.Researcher Wanlu Liu from the Zhejiang University-University of Edinburgh Institute (ZJE) was invited to contribute a Voices article to Immunity, entitled "Building the TCR Repertoire". The article provides a systematic exposition of recent advances and emerging challenges in T cell receptor (TCR) research within human immunology, offering innovative perspectives and insights that further the development of the field.Researcher Wanlu Liu emphasized: "The T cell receptor (TCR) serves as the cornerstone of adaptive immunity, with its diversity directly dictating the organism's capacity to combat disease." She highlighted that due to inherent limitations in MHC diversity and antigen-specific environments in mouse models, direct and systematic investigation of human TCRs holds irreplaceable scientific value. From early bulk sequencing techniques to single-cell immune profiling—capable of simultaneously resolving T cell transcriptional states and paired TCR chain information and further to the newly emerging spatial transcriptomics technologies, the methodological landscape has evolved substantially. Liu pointed out that, alongside the rapid development of diverse TCR databases and AI-based predictive models, the field has now entered a new era of data-driven research.In light of the three major challenges currently facing the field—data scatter, multimodality, and insufficient data scale—Wanlu Liu has proposed a set of transformative solutions. She advocates for the establishment of a unified TCR database, the development of foundational models capable of integrating multimodal information, and the expansion of data generation through ultra-high-throughput single-cell sequencing technologies. These insights provide a clear and actionable technological roadmap for the advancement of the field.Article link：Approaches toward understanding human immunity - ScienceDirectZJE Ph.D. student Ziwei Xue from Wanlu Liu Lab Invited to Contribute a Tools of the trade Article to Nature Reviews Cancer: scAtlasVAE: a deep learning framework for generating a human CD8+ T cell atlas Wanlu Liu’s research group believes that the growing volume of immunomics (omics for immunology) data would benefit our understanding of the human immune system. The most important part of the immunomics data is the single-cell RNA-sequencing data (scRNA-seq) which has profiled human T cells across various organs and disease conditions, yet significant challenges remain in integrating these datasets to obtain a comprehensive view of T cell heterogeneity and functional states. Current efforts are often limited by batch effects, inconsistent cell annotations, and differences in experimental protocols and sequencing platforms, making cross-study comparisons difficult. To address these issues, Wanlu Liu’s research group is working on deep learning based computational method that unify diverse scRNA-seq datasets into a standardized reference atlas. Such approaches not only enhance our capacity to identify conserved and context-specific T cell subsets, but also provide deeper insights into their roles in disease pathogenesis and therapeutic outcomes. Using scAtlasVAE, Ziwei Xue and his collegues have integrated datasets from the human antigen receptor database (huARdb) and generated a CD8+ T cell reference atlas. Leveraging the reference datasets, the research group have discovered signatures of CD8+ T cells in cancers and immune-related adverse effects (irAEs). In the future, the research groups is aiming to extend the huARdb database and develop more scalable computational framework for the T cell computational immunology. They envision that such integrative frameworks will serve as a valuable community resource, guiding T cell biomarker discovery, and informing the rational design of next-generation immunotherapies.Article linkTools of the Trade – Nature Reviews CancerResearch Laboratory IntroductionAbout labDr. Wanlu Liu’s research team specializes in the development of single-cell spatial multi-omics technologies and deep learning algorithms, with a dedicated focus on bioinformatics and computational immunology of T cells. The team has published 50 articles as corresponding author (including co-corresponding authorships) in leading international journals including Cell, Nature Methods, Nature Communications, and Nucleic Acids Research. They have filed four national invention patents, one of which has been granted. The group leads research projects supported by the National Natural Science Foundation of China General Program and the Tencent AI Lab Rhino-Bird Special Research Program.Dr. Liu has been recognized as a National-level Young Talent and a Zhejiang Provincial Young Talent. She also holds several academic appointments, including Member of the Immunocyte Biology Branch of the Chinese Society for Cell Biology, Member of the Molecular Immunology Committee of the Chinese Society of Biochemistry and Molecular Biology, Council Member of the Zhejiang Society of Bioinformatics, Member of its Youth Committee, and Honorary Lecturer at the University of Edinburgh, UK.Email：wanluliu@intl.zju.edu.cn；Laboratory Website：https://labw.org

Over 30% of candidate drugs fail clinical trials due to uncontrollable toxicity caused by systemic off-target effects. Addressing this challenge through precise drug delivery strategies could revive these discarded therapies by mitigating systemic toxicity, thereby transforming promising drug candidates into viable treatments. Magnetic soft robots, capable of operating in hard-to-access anatomical regions, represent a transformative advancement in targeted drug delivery. However, achieving robust in vivo functionality for active drug delivery remains challenging. This requires innovative base materials that simultaneously satisfy mechanical robustness, biocompatibility, and responsiveness to external stimuli, as well as optimized interactions between materials and magnetic functional units to prevent failure caused by magnetic component leakage.Recently, the research team led by Dr. Huang Wenwen from Zhejiang University published an Inside Front Cover article in Advanced Science, introducing a synergistic strategy that integrates genetic engineering and electrochemical engineering to construct a protein-based magnetic soft robot. Leveraging in-situ magnetization of electrochemically generated coordination sites, the team employed classical crystal nucleation-growth theory and interdisciplinary methodologies—including genetic engineering, electrochemistry, and microfabrication—to design, fabricate, and functionalize stimuli-responsive recombinant protein hydrogels from the molecular level via a "bottom-up" approach. This breakthrough offers a novel fabrication strategy for precision drug delivery systems.Building on their prior development of a temperature-responsive recombinant silk-elastin-like protein (SELP) hydrogel, the authors utilized electrochemical techniques to establish ion-protein coordination sites within the hydrogel network. By tailoring electrode pattern and optimizing electric field parameters (voltage, duration), these sites were functionalized as nucleation centers for superparamagnetic nanocrystals under controlled ion supply and growth conditions. Combined with microfabrication, this approach enabled the creation of a protein-based magnetic soft robot.The flexibility and compatibility of electrochemical methods allowed magnetic material patterning and reprogrammable actuation behaviors (e.g., controlled bending/unfolding) through electrode geometry optimization. Furthermore, the "in-situ magnetization via electrochemically created coordination sites" strategy endowed the robot with enhanced mechanical properties and multi-physical field responsiveness. The improved mechanical integrity facilitates encapsulation into minimally invasive delivery systems (e.g., capsules or catheters), while the superparamagnetic nanocrystals act as a magnetic field-responsive medium for precise locomotion control. Additionally, the nanocrystals’ photothermal conversion capability serves as an on-demand drug release trigger, utilizing a photothermal effect to release payloads stored within the hydrogel matrix.In summary, this work synergizes genetic and electrochemical engineering to establish a protein-based magnetic soft robot for active drug delivery. The strategy’s design flexibility, tunability, and processing simplicity position it as a promising platform for advancing medical robotics and precision therapeutics.Authorship and AcknowledgmentsHang Zhao (Ph.D. candidate) is the first author. Co-authors Bo Yu (Class of 2022 undergraduate), Dingyi Yu (Ph.D. candidate), and Dongfang Xiao (Class of 2023 undergraduate) from the Zhejiang University-University of Edinburgh Institute contributed critically to this work. Dr. Qi Zhou (University of Edinburgh) provided essential support during manuscript preparation and revision. Dr. Huang Wenwen (Zhejiang University-University of Edinburgh Institute) is the sole corresponding author. This research was funded by the National Natural Science Foundation of China and the Zhejiang Provincial Natural Science Foundation.Article Link: https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202503404

Cancer, a disease that strikes fear into the hearts of countless people, is essentially a "genetic war" that occurs within the human body. The gradual accumulation of genetic mutations within cells leads to a loss of normal growth and division control, thereby influencing the onset, progression, maintenance, spread, and metastasis of cancer.Studying genomic mutations not only helps us better understand the biological mechanisms of cancer but also provides crucial clues for developing new treatment methods. Scientists have been researching these mutations in the hope of finding breakthroughs to combat cancer.This study discovered a direct link between synonymous mutations and the epitranscriptome, revealing a novel regulatory mechanism in tumorigenesis and progression, offering new insights for precision medicine and targeted drug therapy in oncology. Additionally, this discovery expands our understanding of the "central dogma" of molecular biology—genomic DNA sequences can achieve fine regulation by directly influencing mRNA modifications.The concept of gene mutations is familiar to many, with those that promote cancer development being termed "driver mutations." If genes are likened to a complex "book of life," then gene mutations are akin to "errors" in the book: some are "typos," others are "misordered paragraphs," and perhaps some are "omissions." Sometimes, these errors do not affect "reading," but other times, they can drastically alter the story of the "book of life."Among these, point mutations (changes in a single base pair) are a very common and crucial type of driver mutation in cancer. Existing research shows that a single tumor typically acquires 2 to 8 driver mutations, most of which are point mutations.Among these point mutations, there is a type called "synonymous mutations," which account for a significant proportion, about 25-30%. These do not alter the amino acid sequence of proteins and seem to have no impact on protein function, appearing unrelated to tumorigenesis.At this point, a chemical modification occurring on RNA molecules caught the team's attention — epitranscriptomic modifications. These modifications do not change the nucleotide sequence of RNA but can affect RNA's structure, stability, and function. Recent extensive research has shown that epitranscriptomic modifications, especially RNA N6-methyladenosine (m6A) modifications, play a key role in the onset and progression of cancer. For example, abnormal m6A modifications have been found in acute myeloid leukemia and glioblastoma.Based on these clues, the research team hypothesized that the seemingly "harmless" synonymous mutations accumulated in cancer cells might be linked to "epitranscriptomic modifications".In October 2022, the laboratory officially launched the project.First, they systematically quality-controlled and organized the human pan-cancer genomic mutations using the latest COSMIC database and TCGA data, while also collecting and organizing the latest human m6A data (m6A-Atlas v2.0 and REPIC database, etc.). Through three stringent screening criteria (Figure 1, including mutation reproducibility screening, m6A data coverage, and further reliability screening), they ultimately identified 12,849 potential m6A Disruption Mutations (m6A-DMs). These mutations can be further divided into synonymous mutations (sm6A-DM) and missense mutations (mm6A-DM).They found that synonymous mutations (sm6A-DM) are more likely to occur in tumor suppressor genes. Tumor suppressor genes inhibit abnormal cell proliferation; once these genes mutate or lose function, cells may lose control over proliferation, leading to tumor formation.Figure 1. The identification process of m6A-DM and the distribution characteristics of genes.Subsequently, based on the analysis of cancer genomic mutation frequencies, the researchers identified two top-ranked sm6A-DM sites (CDKN2A-c.A294B and BRCA2-c.A1365G) among the more than ten thousand potential disruptive mutations and conducted functional validation and mechanistic exploration.They employed previously developed regulatory tools (dCasRx site-specific methylation editing system) combined with knock-in based site-specific mutation technology to regulate highly associated tumor type cells at both the epitranscriptomic modification level and the genomic in situ level. Experimental results showed that the m6A modification levels at these two sites were positively correlated with the abundance of corresponding gene transcripts, meaning that higher m6A modification levels at these sites corresponded to higher mRNA quantities, and vice versa. When mutations occurred at these sites, they disrupted the m6A modifications and affected mRNA stability, leading to a decrease in the corresponding gene's mRNA quantity and affecting gene expression levels (Figure 2).Figure 2.The significant impact of sm6A-DM on mRNA stability.Returning to our initial topic, how do these findings relate to the onset and progression of cancer? As mentioned earlier, epitranscriptomic modifications play a key role in tumorigenesis and progression. Since synonymous mutations can affect epitranscriptomic modifications, they might similarly influence tumorigenesis and progression.Through experimental analysis, the research team found that a mutation at the CDKN2A-c.A294B site led to a significant downregulation of CDKN2A transcript and protein levels, accelerating the tumor cell division cycle, thereby enhancing tumor cell proliferation and tumor formation speed in mice, greatly increasing the malignancy of the tumor.At this point, a novel regulatory mechanism for tumorigenesis and progression became clear—sm6A-DMs genomic synonymous mutations can disrupt normal m6A modifications of mRNA, weaken mRNA stability, cause changes in mRNA and protein abundance levels, and alter the tumorigenesis and progression process.It turns out that synonymous mutations are not entirely "harmless"!Based on the rigor of scientific research, the team further advanced these results—clinically, an inhibitor called Olaparib has been approved by the FDA for treating tumors with BRCA1 and BRCA2 defects. The research team designed a set of experiments to validate the implications of their findings for tumor diagnosis and treatment. As expected, tumor cells with the BRCA2-c.A1365G mutation were more sensitive to PARPi drug Olaparib treatment, and tumor growth was well suppressed in tumor-bearing mice with this sm6A-DM mutation after Olaparib treatment. This discovery provides new insights for precision medicine and targeted drug therapy in oncology. In the future, more detection and targeted therapies for sm6A-DMs may emerge, allowing for more precise identification and treatment of specific types of cancer.Figure 3. The role of sm6A-DM in the process of tumorigenesis and development.Moreover, this study holds a more significant meaning, revealing a previously overlooked dimension of the central dogma of molecular biology: DNA mutations can directly determine mRNA modification patterns. The familiar "central dogma" posits that DNA information is transcribed into mRNA, which is then translated into proteins. This study further expands this dogma, indicating that DNA mutations can directly influence mRNA modifications, thereby finely regulating gene expression, enriching our understanding of the essence of life.Dr. Di Chen from the Zhejiang University-University of Edinburgh Institute, Dr. Qi Xie and Dr. Yanmei Dou from Westlake Laboratory are the co-corresponding authors of this study. Qizhe Shao, a Ph.D. student at the Zhejiang University-University of Edinburgh Institute, and Yiheng Lan, an assistant researcher in Qi Xie's team, and Zhen Xia, a Ph.D. student, are the co-first authors of this paper. This research received funding support from the National Natural Science Foundation of China, the Major Projects of Technological Innovation 2030, the Zhejiang "Pioneer" and "Leading Goose" R&D Program, and the Westlake Education Foundation.

A. Professor Irving's laboratory at ZJU-UoE Institute, in collaboration with the Sloan Lab, University of Edinburgh, and the Compton laboratory, National Cancer Institute USA, have published an article on the chinese horseshoe bat IFITM3 antiviral protein in PLOS Pathogens. https://doi.org/10.1371/journal.ppat.1012763Zoonotic transmission occurs when viruses ‘jump’ from animals into human，potentially leading to viral outbreaks such as the COVID-19 pandemic, which poses a significant threat to public health. Bats serve as the origin of many zoonotic viruses; their unique immune system may allow them to harbor these pathogens without developing diseases.The human interferon-induced transmembrane protein (IFITM) family are critical antiviral components that have been shown to influence the pathogenesis of viral infections. They restrict virus entry and are key players in antiviral interferon responses. In addition, the unique IFITM repertoires in different species influence their resistance to viral infections, but the role of IFITMs in shaping the enhanced antiviral immunity of reservoir bat species is unclear. Thus characterization of bat IFITMs is needed to identify factors that predispose species to act as viral reservoirs. Here, we identified an IFITM gene in Chinese rufous horseshoe bat, a natural host of severe acute respiratory syndrome (SARS)-related coronaviruses, that is alternatively spliced to produce two IFITM isoforms in native cells as shown by transcriptomics. These bat IFITMs have conserved structures in vitro as demonstrated by circular dichroism spectroscopy, yet they exhibit distinct antiviral specificities against influenza A virus, Nipah virus and coronaviruses including SARS-CoV, SARS-CoV-2 and MERS-CoV. In parallel with human IFITM1-3, bat IFITM isoforms localize to distinct sites of virus entry which influences their antiviral potency.Further bioinformatic analysis of IFITM repertoires in 206 mammals reveals that alternative splicing is a recurring strategy for IFITM diversification, albeit less widely adopted than gene duplication. 13% of sampled mammals have only one predicted IFITM transcript. These findings demonstrate that alternative splicing is a key strategy for evolutionary diversification in the IFITM family. Altogether, our studyhighlights an example of convergent evolution where species-specific selection pressures led to expansion of the IFITM family through multiple means, underscoring the importance of IFITM diversity as a component of innate immunity.

Research Question:T-cell receptors (TCRs) play a crucial role in the adaptive immune system by recognizing and responding to pathogens and abnormal cells. In recent years, various methods have been developed to reconstruct TCRs from single-cell RNA sequencing (scRNA-seq) datasets, each with distinct characteristics and functionalities. However, comprehensive evaluations of these methods under different conditions remain lacking. This study conducted benchmark analyses using both single-cell immune sequencing and simulated datasets, providing a benchmark study aimed at helping researchers select the appropriate method to reconstruct TCRs from scRNA-seq data.Research Methods:This research conducted a comprehensive performance evaluation of seven TCR reconstruction methods using multiple types of datasets, including scRNA-seq, scTCR-seq, pseudo-bulk RNA-seq, and bulk TCR-seq data. Additionally, the research team developed the YASIM-scTCR simulation tool, which generates scTCR-seq data containing TCR and non-TCR sequences based on user-defined parameters (such as sequencing depth and read length), allowing for precise comparative analysis of different methods in terms of accuracy and sensitivity. The study also provided a systematic evaluation of these seven methods in terms of sensitivity, accuracy, and computational efficiency, offering a reference for related fields. Key Results: In real scRNA-seq data, TRUST4 and MiXCR showed the highest sensitivity, while DeRR and MiXCR performed exceptionally well in terms of accuracy. The YASIM-scTCR tool was developed to generate scTCR-seq simulated data containing TCR and non-TCR reads, supporting user customization of parameters such as sequencing depth and read length. The study found that sequencing depth significantly affects TCR assembly performance in simulated data. For pseudo-bulk RNA-seq data, TRUST4, MiXCR, and CATT outperformed other methods. In most cases, higher TCR abundance was closely associated with improved performance. A comprehensive evaluation across six aspects—accuracy, sensitivity, adaptability, usability, runtime, and memory consumption—showed that TRUST4 ranked highest, followed by MiXCR and DeRR.Authors and Funding Information:Professor Liu Wanlu from ZJE is the corresponding author of this paper. PhD student Tian Ruonan and Master's student Yu Zhejian from the University of Edinburgh are co-first authors of this paper. The study involved collaboration with Tencent AI Lab’s Chief Scientist Yao Jianhua, Senior Researchers He Bing and Zhao Yu, and Professor Lu Linrong from Zhejiang University School of Medicine. Additionally, 2019 bioinformatics undergraduate student Cai Shuo from Zhejiang University actively contributed to the research. The project was supported by funding from the National Natural Science Foundation and the Tencent AI Lab Rhino-Bird Special Research Program.

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.