The knee joint is the largest and most complex weight-bearing joint in the human body that enables us to stand and carry out our daily tasks. How much do you know your knee? Human body is the most perfect masterpiece of nature, the knee joint inside human body has a delicate ultrathin layer of osteochondral interface between SOFT cartilage and HARD subchondral bone. In this interface, the sophisticated structures and excellent force transfer properties allow the knee to resist fatigue damage over a lifetime of loading cycles. The interface’s secret to successfully preventing such damage should lie in its well-designed micro-nano structures and graded compositions in multiple levels. Thus, revealing this ultrathin interface is key to understanding its superb mechanics and for the future design of soft-hard composite interface materials. Against this backdrop, the team led by OUYANG Hongwei at the Zhejiang University School of Medicine conducted a high-resolution analysis of the osteochondral interface in human knee joints. It is the first time that researchers identified the osteochondral interface tissue from the perspectives of microstructure, component assembly and tissue mechanics. Moreover, they discovered the mechanism for the super-strong force transfer and fatigue-resistant adhesion of the ultrathin osteochondral interface. They identified an ultrathin ∼20−30 μm graded calcified region with two-layered micronano structures of osteochondral interface tissue in the human knee joint, which exhibited characteristic biomolecular compositions and complex nanocrystals assembly. Results from finite element simulations revealed that within this region, an exponential increase of modulus (3 orders of magnitude) was conducive to force transmission. Their research findings were published in an article entitled “Identification of an Ultrathin Osteochondral Interface Tissue with Specific Nanostructure at the Human Knee Joint” in the journal Nano Letters. In their study, the researchers collected normal cartilage tissues and identified the osteochondral interface tissue via histological staining. Using scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) line scan, they obtained an ultrathin graded calcified region, spanning over 20-30 μm. By analyzing the transition of the microstructure at the interface and the assembly pattern of HAp, they found the shift from the porous structure to the dense one. Meanwhile, HAp showed variations in morphology across the interface, denoting the maturity of the assembly. The spatially graded distribution of HAp was beneficial to reducing stress concentration and promoting force transmission.Microstructure transition of the osteochondral interfaceThe schematic view of the osteochondral interface indicated two-staged modulus increments, particularly the 3 orders of magnitude increment in the 30 μm spatial range. The FEA results further demonstrated that this modulus transition facilitated mechanical conduction.Biomechanics of the osteochondral interface tissues The tissue modulus map is intimately bound up with the two-layered micronano structure variation at the interface. In addition to the structure, the gradient shift of compositions at the interface can also modulate its mechanical function by redistributing stress. Therefore, the researchers further examined the compositional assembly of the interface at multiple scales. Using XRD and Raman spectroscopy, they found that inorganic nanocrystals at the osteochondral interface were dominated by carbonated substituted HAp. With the extension of the interface, the carbonated substitution rate decreased, mineral crystallinity increased, the HAp composition gradually increased, and the calcium-phosphorus ratio increased from 1.2 to 1.6. These implied that HAp became gradually mature at the interface. With the help of HRTEM, SAED and ELLS, the heterogeneity of HAp crystal assembly was confirmed at the nanoscale. HAp with nanoscale heterogeneity turned out to be insensitive to cracking and thus could promote force conduction through energy dissipation.Compositional analyses and nanoscale heterogeneity of HAp at the osteochondral interface Besides, the researchers examined the precise protein expression profiles at the interface using LC-MS / MS and found that the interface tissue had a high expression of elastic-responsive protein-titin, which could absorb energy through reversible deformation and transmit stress, thereby helping maintain elasticity and mechanical conduction at the interface.Quantitative proteome analysis of the difference in expression of osteochondral interface compared to AC and SB “A combination of characterization of microstructural, micromechanical, nanocompositional, and biomolecular features of the interface revealed the mechanism underlying toughening properties of the cartilage-to-bone interface tissue,” said Prof. Ouyang. “The identified mechanism of the soft-to-hard interface allows effective force transfer in a certain direction, thus laying a foundation for future approaches seeking to design biocomposite interface materials.” 

Stretch, as a form of mechanical force, plays a crucial role in regulating cell behaviors, preventing injuries and repairing tissues such as lung, heart, brain and skeletal system. Among them, stretch in bone tissues has captured the most immense attention in clinical applications, for bone tissues are continuously exposed to stretch stimulation during physiological activities. The structure and function of bone tissues relies on a proper amount of stretch stimulation, while lack of exercises tends to result in the reduction of bone volume and osteoporosis. Under physiological conditions, bone tissues are subjected to micro-stretch with a variable frequency.  Although there has been a massive body of research into the effects of stretch stimulation with a constant frequency, the biological effects of micro-stretch with a variable frequency have not yet been identified. Moreover, commercial stretching devices are unable to generate stretch with a variable frequency similar to the in vivo condition of bone tissues. Against this backdrop, the research team led by Prof. OUYANG Hongwei proposed a novel cell stretcher, named as “musical dish”, which for the first time used the conversion of musical signals to mechanical signals to realize the regulation of stem cell fate by micro-stretch with a variable frequency (NUMS). Their research findings were published in Bioengineering & Translational Medicine, entitled “’Musical dish’ efficiently induces osteogenic differentiation of mesenchymal stem cells through music derived micro-stretch with variable frequency”. In this study, the researchers developed a musical dish with fast response, large deformation, optical transparency and robust controllability, based on dielectric elastomer actuators (DEAs) . This musical dish could convert musical signals into electrical ones, which could further converted into mechanical energy via a flexible dielectric elastomer membrane. It could trigger stretching stably. The actuating strain was featured by homogeneity and equiaxiality. When cells were seeded on the musical dish, they could proliferate normally. The cells showed displacement with the increase of the voltage. To evaluate the effect of NUMS, 1 kV constant voltage with musical signals was applied to cells. The stretch ranged from 0.833% to 0.867% which is close to the stretch condition in bone tissues. Quantitative analysis revealed that cells in the NUMS group exhibited more marked filamentous stress fibers than constant stretch and no stretch groups. Bone development and ossification were up-regulated according to the gene ontology (GO) enrichment analysis. Further, Experiments identified a significant increase in the expression of bone cell-related genes under NUMS, but the expression of stemness-related genes decreased tremendously. The NUMS also promoted osteogenic differentiation of cells in induction medium. These findings highlight a novel “musical dish,” which allows arbitrary strain waveforms to be applied to cells by converting music signals into the stretching force. In comparison with constant stretching, NUMS may have great potential for promoting bone differentiation of cells. For clinical applications, three strategies may contribute to the development of potential therapeutic ways for bone regeneration. First, NUMS could be used in the distraction osteogenesis surgery to replace or assist the current large-scale and slow stretching method for bone regeneration due to its superb performance in promoting osteogenic differentiation. Second, the musical dish could be further developed into a music-derived rehabilitation technology to promote bone healing. Finally, the musical dish could serve as a cell expansion bioreactor to produce cells with a high level of osteogenic differentiation to repair bones by transplantation. Thus, both the new stretching model and the newly-developed stretching device may have a brilliant clinical prospect.  

January银花烛夜，岁始正阳。The year begins in January, with bright lights illuminating the night sky.Feburary高府雾列，俊采星驰。Grand colleges are arranged like fog, while talents gallop like stars.March春意绽放，暖风微扬。The blooming of flowers and warm winds are the signals of spring.April掠水惊鸿，绿波漾漾。The startled bird skimmed the water, and the green waves are rippling.May日歇影斜，霞光覆宇。The sun breaks, the shadow slants and the glow cover the buildings.June碧荷摇曳，沐浴夏光。The lush lotus leaves stretch out in the summer sun.July影入清漪，木澄波底。The shadow is reflected in the ripples, and the wood makes the water waves clearer.August青青木林，悠悠前行。It is enjoyable to stroll under the green and flourishing trees.September金秋九月，谷莠流光。The dog tail grass in autumn looks like golden waves.October倒影秋黄，玉露生凉。The reflection of autumn is yellow and cool.November孟冬游廊，孑然独往。Someone who walks alone in the corridor is the early winter.December天门映雪，学府皇皇。Snow makes the campus more peaceful and beautiful.

Zhejiang University-University of Edinburgh Institute (ZJE)  is a collaboration in the field of Biomedical Sciences between Zhejiang University of China and The University of Edinburgh, United Kingdom. Relying on the institute advantages and cultural heritage of two universities, ZJE brings together world-class teachers and scientific research forces to attract outstanding students from all over the world and cultivate biomedical talents with excellent knowledge, innovative spirit, and international vision. ZJE now has four postgraduate programmes: dual degree PhD programme, UoE degree PhD programme, UoE degree MSc programme, ZJU degree MSc programme. We interviewed 7 PhD students, and they talked about their initial reasons for choosing ZJE and their feelings of learning and living now:  Jiayan WuUndergraduate school and major: Zhejiang University of Technology/ Green pharmaceuticalDoctoral supervisor and major: Prof. Linrong Lu / cell biologyWhy you choose ZJE?The biggest reason is that I came to my mentor in admiration. Also ZJE provides dual degree for students; The laboratory working environment is very comfortable (suitable for vlog shooting); The buildings in the campus are very beautiful; Don't worry about losing the badminton court; There are many vacancies in the library and the environment is comfortable; The supporting facilities of the single room in the academy are very good and the design is very reasonable; The gym in residential college is also very good (although I have only been there a few times). In short, the academic atmosphere is great, and the hardware facilities are also great! Jingyuan ChenUndergraduate school and major: University of Manchester/Finance (Bsc, Msc)Doctoral supervisor and major: Dr. Mikael Bjorklund/Cell BiologyWhy you choose ZJE?I have decided to pursue my PhD study in ZJE for several main reasons. First, ZJE is an international collaborative institute established by two of the world-class universities. Beyond the reputation, it has combined the resources from both universities such as sharing on teaching staff. More importantly, all the courses are taught in English, this is more suitable for me. Secondly, the dual degree programme is really great as it is verified by both ZJU and UoE which means we receive two valid certificates with much less cost. Finally, the well-kept environment makes the campus stand out as one of the most comfortable campuses in China. Teng WangUndergraduate school and major: Zhejiang University of Technology/ Pharmaceutical EngineeringDoctoral supervisor and major: Dr. Chaochen Wang/Cell BiologyWhy you choose ZJE?The most important thing is I found my favorite supervisor and ideal research direction in ZJE. Also I can be awarded the dual doctoral degrees of Zhejiang University and University of Edinburgh at the same time after I finish my study here, which is very attractive to me. It is equivalent to that I can spend the same time to obtain the doctoral degrees of two world-class universities and enjoy the educational resources of the two universities, which is conducive to my personal growth and future development; Secondly, my undergraduate major adopted bilingual teaching and small class management. 80% of the core courses were taught in English, so I'm used to such training mode, and I don't want to waste the advantages brought by undergraduate training; The third is that I once had an experience of visiting the University of California, San Diego in my sophomore summer. I have a certain longing for the foreign educational environment, and ZJE can provide me with a similar educational environment, which makes me more determined to choose to study in ZJE. Although my undergraduate course is pharmacy, I prefer biomedical experiments. ZJE's good biomedical experimental environment and strong biomedical background also attract me. Finally, it is also a coincidence to choose to study in ZJE. Thanks to my senior for her guidance and recommendation, so I also hope more people can know more about ZJE and join the big family of ZJE. Qizhe ShaoUndergraduate school and major: Zhejiang University / Biomedical ScienceDoctoral supervisor and major: Dr. Di Chen / Stem Cells and Regenerative MedicineWhy you choose ZJE?1. First, I met a great supervisor. Dr. Chen is not only an excellent researcher, but also a very charming life mentor. He has been very helpful to me in scientific research and life. Stem cells and regenerative medicine are my favorite research directions, and I also like the atmosphere of the laboratory very much. 2. ZJE is a very good platform. ZJE has a strong scientific research atmosphere. Through the weekly ZJE symposium, we can understand the topics being done by the students around us, and can exchange progress with teachers and students, promote each other. At the biweekly ZJE Biomed-X research seminar, we can face-to-face contact with great experts in various fields of biomedicine, broaden our scientific vision and appreciate the charm of scientific research.3. ZJE's scientific research platform has been gradually improved and managed in an orderly manner. We can arrange our own experiments well. Platform technology and management personnel are also very nice.4. The campus environment is very beautiful. The accommodation and diet are very good, and various facilities are also very complete, which makes people feel happy. Caitlin ButalaUndergraduate school and major：Illinois State University, BS in AnthropologyDoctoral supervisor and major ：Prof. Susan Welburn/Biomedical SciencesWhy you choose ZJE?Joining ZJE provided an opportunity to work with leaders in the field of Neglected Tropical Diseases while having the benefit of the Dual Award PhD. At the end of my time here I will have two PhDs from two top universities, valuable experience in research, connections with professors from around the globe, and memories of my life in China.  Studying at ZJE has also been a great opportunity to interact with faculty from all disciplines and find cross institute collaborations. Long MaPostgraduate school and major：Zunyi Medical University/immunologyDoctoral supervisor and major ：Dr. Sebastian Leptihn/ Biochemistry and molecular biologyWhy you choose ZJE?When I first came to International Campus, I was attracted by the beautiful campus when I got off the school bus.When I first entered the research group laboratory, my supervisor took me around the whole ZJE building, introduced every teacher and student I met, and introduced the design and planning of Leptihn lab and experimental platform. I had a deep sense of belonging in one morning.When I checked in at the residential college for the first time, the housekeeper gave warm help and guidance, spacious and bright public rest area, and warm single room, gave me the warmth of going home; The reading room, gym, discussion room, recording room, study room and multi-function room on the first floor of the residential college exceeded my expectations for accommodation.From the first time I came to ZJE, I decided to finish my doctoral study here. In the past two years, the discussion with my supervisor, the academic seminar series, the group exchanges every Friday, the poster exhibition every academic year, the annual academic conference, etc., I have felt a strong academic atmosphere and expanded my horizons. IAN TIMOTHY SEMBIRING MELIALAUndergraduate school and major：Corban University, USA-Biology Education(B.Sc.) & Chongqing University, China-Biomedical Engineering (M.Eng.)Doctoral supervisor and major ：Dr. Mikael Bjorklund /Cell BiologyWhy you choose ZJE?Located in the developing Haining International Campus, ZJE provides an excellent research platform and the academic environment from two world-class universities: the University of Edinburgh (UoE) and Zhejiang University (ZJU). Before attending ZJE, the Dual Ph.D. program piqued my interest since this program allows us to obtain 2 degrees from both universities. Once enrolled in the program, I enjoyed my research life here. The classes provided broadened my perspective as an aspiring scientist. My supervisor is supportive and constructive in providing feedback for the progression of my project. The core facilities have top-notch research instruments and very supportive staff who are always ready to help us when we encounter problems in using the instruments. ZJE also holds timely seminars delivered by renowned scientists from all over China. Joining this program also qualifies me to utilize academic and non-academic resources from UoE and ZJU. Although I am staying in ZJU, I can apply to join various workshops and professional development programs offered by UoE as well. ZJE is an excellent and conducive incubator for me to be a better scientist.  

Zhejiang University – University of Edinburgh InstituteUndergraduate Programmes for International StudentsAre open to Apply for 2022  I.           About ZJU-UoE InstituteZhejiang University-University of Edinburgh Institute (ZJE) is a collaboration in the field of Biomedical Sciences between Zhejiang University of China and The University of Edinburgh, United Kingdom. The two universities established an international research institute at the International Campus of Zhejiang University in Haining, Zhejiang, which builds on the existing strengths of both, and aims to foster collaborations in teaching and research. The Institute provides undergraduate education programmes that produce students with academic excellence, leadership skills, innovative capacity and global vision. Top-tier Universities in the world-Founded in 1897, Zhejiang University (ZJU) is one of China's oldest and most prestigious higher education institutions. It is ranked 45th in the 2021/22 QS world University Rankings. ZJU owns 7 affiliated hospitals and 7 campuses. -Founded in 1583, The University of Edinburgh (UoE) has been providing students with world-class teaching for more than 400 years. It is one of the world's top universities, consistently ranked in the world top 20, and placed 16th in the 2021/22 QS World University Rankings. II.           Academic ProgrammesZJE offers all English-taught undergraduate academic programmes in Integrative Biomedical Sciences and Biomedical Informatics. BSc Integrative Biomedical Sciences OverviewIntegrative Biomedical Sciences is a multidisciplinary degree programme that provides opportunities to investigate the biomedical sciences in the 21st century. The core structure of the programme provides the knowledge, skills and personal and professional development appropriate to meet the needs of a future career as a leader in biomedical sciences. The programme provides opportunities to develop skills and knowledge in the biomedical, chemical, and clinical sciences. In addition, in later years focused optional courses provide opportunities to explore the biomedical disciplines of physiology, pharmacology, neuroscience, immunology, reproductive biology, medical microbiology and developmental biology. Integrative Biomedical Sciences is founded on developing skills in academic research and scientific enquiry thereby encouraging awareness and understanding of the research that is needed to continue to advance clinical practice. Alongside a depth of knowledge in Integrative Biomedical Sciences, graduates will have developed a breadth of skills and experience, including interpersonal skills, critical judgement and computer literacy.BSc Biomedical Informatics OverviewBiomedical informatics encompasses the study of information and computation in biology and health. Researchers in this area create computational tools to manage, share and study information and generate knowledge from biomedical data.The first year of the programme is an exciting exploration of the application of biomedical informatics, facilitating student development in the key areas of biomedical sciences. The programme will build extensively on the existing BSc Biomedical Sciences courses which students will study together with peers from this programme while introducing new courses in all four years. The goal of the programme is to train undergraduate students in the overarching principles of Biomedical Informatics and apply these skills in fundamental biomedical research.III.           Dual DegreeStudents admitted to this dual-degree programme are enrolled in both Zhejiang University and the University of Edinburgh. Students who successfully complete the programme and meet the requirements of both universities will receive two bachelor’s degrees in their respective major fields and a graduation certificate of ZJU:·       Bachelor of Science (Honours) from the University of Edinburgh·       Bachelor of Science from Zhejiang University·       Graduation Certificate from Zhejiang UniversityIV.           Enrollment, fees and ScholarshipsWe plan to enroll 20 international students. Scholarships are awarded on an individual basis to outstanding students. Fees·          Application Fee: CNY 800 yuan (non-refundable).·          Tuition fee: CNY 200,000 per year·          Accommodation on campus: CNY 8,000 per year·          International student medical insurance: CNY 800 per year. (Relevant medical insurance items can be found at www.lxbx.net).·          Living costs: CNY 20,000-30,000 per year (estimated) ScholarshipsThe Institute offers three types of scholarship support: Undergraduate Scholarship, Academic Scholarship and Oversea-exchange Scholarship.Duration: 4 years (The scholarship will be reviewed and given on the condition that the student meets the requirements for satisfactory progress toward a degree and follows the rules of the ZJU-UoE Institute.)V.           EligibilityRequired by ZJU registration regulation and Ministry of Education of the PRC, applicants shall be aged at 18-25, non-Chinese passport holders, high school graduates, mentally and physically healthy and must obey by Chinese law and University’s regulations, and respect Chinese culture and habits. For more detail, please review on ZJU International College: http://iczu.zju.edu.cn/english/redir.php?catalog_id=22210 VIII Minimum academic requirements:SQA/HighersIBGCE A-levelABBB by end of S5 or ABBBB/AABB from S4-S6, with a minimum of BBB   achieved in one year of S4-S6, to include Biology and Chemistry. Mathematics   and/or Physics are recommended. Qualified applicants are advised to take   Biology and Chemistry at Advanced Higher level where possible. National 5:   Mathematics at Grade B. English at Grade C. Overall score of 32 points, including HL Biology and Chemistry, one at   Grade 5 and one at Grade 6. Mathematics and/or Physics are recommended. SL:   English at Grade 4 and Mathematics at Grade 4. If you are using English /   English Language at SL as part of the English language requirements, you must   obtain Grade 5.ABB, in one sitting, to include Biology and Chemistry. Mathematics   and/or Physics are recommended. GCSEs: Mathematics at Grade B or 6 and   English at Grade C or 4.. If your qualifications are not in the list above, please check UoE Undergraduate Requirements by Region website https://www.ed.ac.uk/studying/international/country which contains the national examinations for many countries worldwide. VI.           Application and DeadlineApplicants must log in to the Online Application System for International Students of Zhejiang University (http://isinfosys.zju.edu.cn/recruit/login.shtml), fill in clearly and upload completely the original or notarized scanned copies of the following materials as required.1. A photocopy of the passport.2. Senior high school diploma. Graduating high school students can provide pre-graduation certificate. The original or notarized copy of the high school graduation certificate must be submitted upon registration.3. Transcript for all the courses in senior high school.4. Language (English) proficiency certificates.Applicants must provide grade report of TOEFL or IELTS test, or other proof which can reflect the applicants’ English proficiency. (Not required for English native speakers)5. Two recommendation letters from high school teachers. Teachers’ signature, contact phone number and email address must put on the letter.6. Personal statement, should include study experience, reasons for application, personal strengths. Less than 800 words.7. Award-winning Certificates related to academic courses during your senior high school period. (If applicable) 8. Applicants who have given up their original Chinese citizenship and become foreign citizens should submit (1) Cancellation certificate of Chinese citizenship (2) Current citizenship certificate (3) Exit and Entry Record on passport, from April 30, 2018 to April 30, 2022. 9. Applicant who has acquired foreign citizenship automatically at the time of birth in a foreign country, whose parents are both Chinese citizens, or one of the parents is a Chinese citizen should submit:(1) Birth certificate of foreign country.(2) Chinese parents’ permanent resident certificate of foreign country should be obtained prior to the birth of the applicant.(3) Exit and Entry Record on passport, from April 30, 2018 to April 30, 2022. 10. Applicants under the age of 18 (by September 1st, 2022) should submit:(1) Letter of Guardian Guarantee（Download）and the guardian must be an adult living in Hangzhou.(2) A notarized copy of the Guardianship Authorization from the applicant’s parents.Deadline Undergraduate students should plan to apply by 23:59 April 15th, 2022 (GMT+8) for full consideration.  VII.           Admission 1.       Students are enrolled on the basis of competitive selection according to their academic performance in senior high school, language proficiency and etc. We will contact the successful applicant via email and applicants can also log on the Online Application System to track the admission process. For more detail, please refer to the offer letter.2.       Applicants who receive the Pre-Admission Notice should prepay the first year tuition fee on the Online Application System within the specific time period stated on the Offer. If the applicant is not able to make the online payment due to certain reason, then one MUST pay the tuition fee to the University’s Bank Account (Link), and upload the remittance letter to the System. The pre-admission will be canceled if applicants fail to prepay the first year tuition fee within the stated time period.3.       The official Admission Notice, Visa Application Form (JW202 Form) and other relevant admission documents will be mailed to enrolled applicants once the prepaid tuition fee is confirmed to be received and the University Calendar is released.  VIII.           AccommodationStudents at International Campus of Zhejiang University enjoy single room dormitory.IX.           RegistrationThe usual on-campus registration period is late August or early September. The exact time will be specified in the matriculation notice. Students should apply for an X1 visa at a Chinese embassy or consulate. Usually a valid passport, matriculation notice, and JW202 Form are needed for the visa application.  For registration, students should report to International Campus of Zhejiang University at the time specified in the offer letter with the following documents: a valid passport, matriculation notice, JW202 Form and an X1 visa.  High school diplomas are required for students who have submitted pre-graduation certificate. Failure to do so will result into cancellation of admission. X.           LocationInternational Campus of Zhejiang University718 East Haizhou Rd., Haining, Zhejiang 314400, P.R. ChinaXI.           Contact PersonZJU-UoE InstituteMs. Hannah HuangPhone: +86 571 87572813; Email: xiaohanhuang@intl.zju.edu.cnFor more information, please refer to ZJU International College Homepage http://iczu.zju.edu.cn and ZJU-UoE Institute Homepage http://zje.zju.edu.cn/  

Richard Fitzpatrick, who just completed his PhD in the Stefan lab, won a Commendation for Innovation at this year's Alison Douglas Dissertation Prize. You may have met Richard when he came to Haining to do some teaching as part of his career development PhD programme. His dissertation was about using computational modelling to understand biological systems. As part of this, he created the ambitious and highly acclaimed neuroscience outreach project NeuronSafari (https://www.neuronsafari.com/), a tour of the human brain in the computer game Minecraft. The Alison Douglas Prize is awarded every year to the best dissertation at the Centre for Discovery Brain Sciences, University of Edinburgh. Congratulations to Richard Fitzpatrick!

This time, ZJEers are using our strengths to illustrate excellence!Recently, major universities in China announced the proposed admission list of examination exemption students，and the students of the Class of 2022 who were granted guaranteed admission to Zhejiang University and University of Edinburgh Institute have achieved great results. All 20 students recommended by our institute were accepted by top universities in China without examination. Admissions include Tsinghua University, Peking University, Zhejiang University, Chinese Academy of Sciences and Shanghai Jiao Tong university.19 of them were directly admitted to PhD and one was a”2+2” Master in Civic Studies from Zhejiang University, the admission rate for PhD programme is 95%.What’s more, ZJE opened a Bioinformatics(BMI) program in 2018, and the acceptance rate of this first Bioinformatics program for doctoral candidates was as high as 100%. “A broad view of the world and a thick accumulation of ideas”, getting the opportunity to become exam-exempted students is a long way to go, and it takes a lot of hard work to build up. During their time at ZJE, these 20 students have faced challenges head-on and have worked hard to become professionally outstanding, fluent in English, independent thinkers with an international perspective and a multidisciplinary background. This makes them stand out in the highly competitive professional interviews and highly sought after by top schools. Examination Exemption Students’ Message for all ZJEers Yuwei HePlanning is very important. Clear and firm goals can greatly improve the motivation. Moming GuoIt's normal to meet confusion in life. Don't worry too much. If you have something you want to do, think clearly and do it. Zeen XuOn the road of life, there are always many choices. The most important thing is to prepare early, seize as many opportunities as possible and give yourself more options to find the most suitable way for yourself.Hope you can broaden your horizons, clarify goals and seize opportunities. All roads lead to Rome! Jiayi ShenWe must combine work and rest. Learn to relax, communicate with family and friends, and adjust your state. Health is the most important! Behind every glory, there is day and night work and tireless perseverance. We hope that every ZJEer will follow the example of these outstanding seniors and always look forward to working hard. Seize the day and live it to the fullest. Carve out a wonderful life of your own!

Recently, Jian Liu’s group from Zhejiang University-University of Edinburgh Institute (ZJE) in Zhejiang University published their lung cancer metastasis research entitled “Loss of Smad4 promotes aggressive lung cancer metastasis by de-repression of PAK3 via miRNA regulation” at Nature Communications by collaborating with multiple groups, including the Pro. Xiao Yang from State Key Laboratory of Proteomics in National Center for Protein Sciences (Beijing) and Pro. Xiaotao Li from Shanghai Key Laboratory of Regulatory Biology in East China Normal University, and Pro. Dianwen Song from The First People’s Hospital of Shanghai Jiao Tong University. By developing different genetic mouse models mimicking lung cancer metastasis and the comprehensive mechanism studies, they revealed that the de novo role of SMAD4 in repressing lung cancer metastasis, independent of TGFβ, and the therapeutic targets (SMAD4/miRNA-495/PAK3) for treating lung cancer metastasis. Access to the publication：https://www.nature.com/articles/s41467-021-24898-9Lung cancer is the leading cause of cancer death worldwide and in China1. Over 85% of lung cancer patients harbor overt or subclinical metastases at diagnosis, and therefore most patients die of progressive metastatic disease despite aggressive local and systemic therapies1. SMAD4 is the crucial downstream transcription factor of the TGFβ pathway and has been found to have some somatic mutations and the decreased expression in human lung tumors2,3. Although Jian Liu et al. reported that Smad4 ablation promoted lung cancer development and metastasis, the mechanism of SMAD4 in regulating lung cancer metastasis remains unclear.    Jian Liu et al. have reported that ablation of Smad4 in mouse lungs could not cause cell hyperplasia and tumor formation2,6. This research found that some lung cancer patients harbored the mutations of KRAS, TP53, and SMAD4 in the same tumors by analyzing the TCGA lung cancer datasets. Therefore, this research generated KrasG12DTrp53flox/flox (PK) and KrasG12DTrp53flox/floxSmad4flox/flox (SPK) mouse models to mimic the lung cancer metastasis to investigate the role of SMAD4 in regulating lung cancer under the background of Kras mutation and Trp53 ablation. Moreover, this research found that the ratio of lung tumor metastasis in SPK mice was much higher than that of PK mice. By conducting the transcriptome analysis of the isolated lung tumor cells from PK and SPK mice, followed by the functional analyses (e.g., cell invasion), this research found that Smad4 ablation increased the mRNA and protein expression of PAK3 (Figure 1, Step 3), and consequently activated the JNK-JUN pathway of the downstream of PAK3 (Figure 1, Steps 4 and 5), and eventually promoted lung cancer metastasis. Unexpectedly, the negative regulation of SMAD4 on PAK3 is independent of TGFβ. Analysis of SMAD4 ChIP-Seq data showed that there was no SMAD4 binding on the PAK3 promoter. Furthermore, the exogenous expression of SMAD4 did not alter the luciferase activity driven by the PAK3 promoter. Thus, it indicated that the negative regulation of SMAD4 on PAK3 is independent of TGFβ, belonging to the non-classic role of SMAD4. Some published studies showed that the transcriptional regulation of gene expression could be regulated either by the promoter or the 3’ UTR7. This research further showed that Smad4 loss altered the luciferase activity driven by the PAK3 3’ UTR. Given that miRNA can negatively regulate gene expression by binding on the targeting gene’s 3’ UTR, this research raised a hypothesis that SMAD4 negatively regulates the PAK3 mRNA expression through miRNAs. Through the bioinformatical analysis, as well as the functional validations, this research found that miR-495 and miR-543, directly and positively regulated by SMAD4, mediated the negative regulation of SMAD4 on PAK3 (Figure 1, Steps 1 and 2). Clinically, the negative correlation between SMAD4 and PAK3-JNK-JUN was observed in a group of human lung cancer samples, including the control lungs, early-stage lung tumors, late-stage lung tumors, and metastatic lung tumors. In sum, this research identified SMAD4/miRNA-495/PAK3 to be the de novo targets in treating lung tumor metastases. Figure 1. The TGFβ-independent role of SMAD4 in regulating lung cancer metastasis Of note, the SMAD4 repression on PAK3 is independent of TGFβ since SMAD4 is a typical functional player of the TGFβ pathway. Moreover, they showed that miRNA-495 was able to prevent the lung cancer metastasis induced by Smad4 loss. The biggest challenge of the application of RNA drugs is the in vivo stability of RNA8,9. Given that the mRNA vaccine (Moderna) was successful against COVID-19, it suggested that the concerns of the low stability of RNA drug in vivo have been partially resolved during the clinical applications. Therefore, miRNA-495 against lung cancer metastasis may benefit developing clinical treatment. Dr. Jian Liu is the co-corresponding author of the article. In addition, the master student Feiran Gao (ZJE, 2020 entry) participates in this research. To overcome the difficulties of this research, such as a large number of genetic mouse experiments, the non-classic role of SMAD4, and the different stages of human lung cancer samples, all collaborators effectively communicated with each other and worked together. For example, Dr. Xiao Yang’s group was mainly responsible for generating the mouse models; Drs. Xiaotao Li and Lei Li’s group was mainly in charge of the mechanism investigation and the initial version of the manuscript; Dr. Jian Liu’s group took the responsibility to conduct all bioinformatic analyses, parts of experimental designs, and the whole revision process; Drs. Dianwen Song’s and Junjiang Fu’s groups collected the clinical samples. Meanwhile, the international collaborators also contributed to this research, including Dr. Nabeel Bardeesy from Massachusetts General Hospital of Harvard University, Dr. Kwok-kin Wong from Laura and Isaac Perlmutter Cancer Center of New York University, and Dr. Robb E. Moses from Dan L. Duncan Cancer Center of Baylor College of Medicine.About Jian Liu’s lab (https://person.zju.edu.cn/en/jian_liu) References1.    Rebecca L Siegel, et al. Cancer statistics, 2019. CA Cancer J Clin (2019).2.    Xiaohong Tan, et al. Loss of Smad4 promotes aggressive lung cancer metastasis by de-repression of PAK3 via miRNA regulation. Nature Communications (2021)3.    Jian Liu. et al. ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis. Cell Reports (2015).4.    Jian Liu, et al. ERBB2 Regulates MED24 during Cancer Progression in Mice with Pten and Smad4 Deletion in the Pulmonary Epithelium. Cells (2019).5.    Ran You, et al. IL17A regulates tumor latency and metastasis in lung adeno and squamous SQ. 2b and AD. 1 cancer. Cancer immunology research (2018)6.    Jian Liu. et al. JNK1/2 represses Lkb1-deficiency-induced lung squamous cell carcinoma progression. Nature Communications (2019)7.    Yuval Malka. et al. Post-transcriptional 3´-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments. Nature Communications (2017)8.     Ugur Sahin. et al. mRNA-based therapeutics — developing a new class of drugs. Nature Reviews Drug Discovery (2014)9.     Meirav Segal. Et al. Challenges identifying efficacious miRNA therapeutics for cancer. Expert Opinion on Drug Discovery (2020) 

Recently, ZJE post-doc Prasanth Manohar participated in the International Conference on Bacteriophage Research, delivering a talk on his research: Characterization of a novel bacteriophage PA01_φmotto infecting Pseudomonas aeruginosa, and won the Young Scientist Award.The 2nd International Conference on Bacteriophage Research was held virtually and there are more than 500 participants and 15 guest speakers from various countries./Profile/Prasanth Manohar’s work on bacteriophages focuses mainly on the application of phages in medicine to cure antibiotic-resistant bacterial infections. Mainly working on Klebsiella pneumonia and Pseudomonas aeruginosa phages which are top priority pathogens needing alternative treatments.Contact Email: PrasanthM@intl.zju.edu.cn

Recently, two undergraduate students from Zhejiang University-University of Edinburgh Institute (ZJE) in Dr. Jian Liu’s research group published a review entitled “Comparison of COVID-19 and Lung Cancer Via Reactive Oxygen Species Signaling” at Frontiers in Oncology. This article reviews the role of reactive oxygen species (ROS) and their associated signaling pathways, NRF2, HIF-1, and Nf-κB, in the pathogenesis of COVID-19 and lung cancer (Figure 1) and suggests the interplay between the two diseases. The HIF-1 and Nf-κB pathways are upregulated in both diseases, leading to inflammation, oxidation, tumor cell proliferation, and metastasis. Thus, the authors suggest that targeted therapies to these pathways, such as miRNA and plant-derived chemicals, are attractive and deserve further study in treating both diseases. Given that COVID-19 and lung cancer are two severe pulmonary diseases that cause millions of deaths globally, understanding the dysregulated signaling pathways between them can benefit treating the related patients. Our work emphasizes the significance of ROS in the two mutually impacted pulmonary diseases and would provide a clue in developing more novel preventive and therapeutic strategies for them.Dr. Jian Liu is the corresponding author of the article. Undergraduate students Zilan Zhu and Ziyi Zheng (2018 entry) from ZJE are co-first authors. Of note, although the ZJE undergraduates are almost fulfilled with multiple education tasks, this review was finished by them within six months. Access to the publication:  https://www.frontiersin.org/articles/10.3389/fonc.2021.708263/abstract In June 18th 2021, Dr. Jian Liu published an article entitled “Dependency of human and murine LKB1-inactivated lung cancer on aberrant CRTC-CREB activation” at Elife as a co-author. this study provides direct proof for an essential role of the CRTC-CREB activation in promoting the malignant phenotypes of LKB1-null lung cancer and proposes the CRTC-CREB interaction interface as a novel therapeutic target. Access to the publication: https://elifesciences.org/articles/66095 At the end of March 2021, Jian Liu’s lab and Aifu Lin’s lab in College of Life Science, Zhejiang University, published an article entitled “LncRNAs: Architectural Scaffolds or More Potential Roles in Phase Separation” at Frontiers in Genetics together. This article reviews the functions of phase separation and associated studies of lncRNAs. This review will facilitate our understanding of the formation and function of phase separation and the role of lncRNAs in these processes and related biological activities. A deeper understanding of the formation and maintaining of phase separation will benefit disease diagnosis and treatment. Dr. Jian Liu is the co-corresponding author of the article. Postgraduate student Feiran Gao (2020 entry) from ZJE is a co-author. Access to the publication: https://www.frontiersin.org/articles/10.3389/fgene.2021.626234/full In early March 2021, Dr. Jian Liu published an article entitled “Progesterone receptor isoform B regulates the Oxtr-Plcl2-Trpc3 pathway to suppress uterine contractility” at PNAS as a co-author. In this study, a novel transgenic mouse model was established to reveal the mechanism of uterine contraction. Access to the publication: https://www.pnas.org/content/118/11/e2011643118/tab-article-info In January 2021, Dr. Jian Liu published an article entitled “Mitochondrial long non-coding RNA GAS5 tunes TCA metabolism in response to nutrient stress” at Nature Metabolism as a co-author. In this study, the authors investigated the molecular mechanism of mitochondrial lncRNAs regulating TCA metabolism in response to nutrient stimulation. Access to the publication: https://www.nature.com/articles/s42255-020-00325-z About Jian Liu’s lab (https://person.zju.edu.cn/liujian;）Dr. Jian Liu’s lab studies cancer biology, epigenetics, and gene editing and aims to promote the targeted therapy of squamous cell lung carcinoma. Currently, the lab explores the molecular mechanism of lung cancer (especially squamous cell lung carcinoma) through the combination of clinical database, transgenic mouse models, and sequencing. Dr. Jian Liu’s E-mail address: JianL@intl.zju.edu.cn; Look for the self-motivated Postdocs.

The second cohort of students to graduate with a Dual Award from The University of Edinburgh and Zhejiang University celebrated their achievements at an event on 22 June. The graduates were joined at the celebration by their friends and staff at the Institute, as well as receiving messages of congratulations from Prof Peter Mathieson, the Vice President of ZJU Prof He Lianzhen, the Dean of International Campus Prof Ouyang Hongwei, the ZJE Executive Dean Prof Sue Welburn, and the Dean of Biomedical Sciences at the University of Edinburgh Prof Mike Shipston, the ZJE Vice Dean Prof Linrong Lu as well as many staff who have been with them on this journey.     In the vastness of space and the boundlessness of timeIt is our good fortune to share the same starry sky and the same period of timeZJE will always be your strong backing, accompanying you to further distances and brighter lights.

Recently, Dr.Wanlu Liu from Zhejiang University-University of Edinburgh Institute and Prof. Steven E. Jacobsen from UCLA published an article, entitled Ectopic targeting of CG DNA methylation in Arabidopsis with the bacterial SssI methyltransferase, on Nature Communications. The study shows that targeting the CG-specific methyltransferase M.SssI with an artificial zinc finger protein to the promoter of the Arabidopsis FLOWERING WAGENINGEN (FWA) gene can establish heritable CG methylation and silencing of FWA in Arabidopsis (Figure 1). In addition, the author observes highly heritable widespread ectopic CG methylation mainly over euchromatic regions (Figure 2 A, B). By using the techniques including WGBS, ChIP-seq, ATAC-seq, etc., the author identified the Differentially methylated region (DMR), analyze the epigenetic marks on these DMRs, and study the relationship between the CG methylation and other epigenetic modifications. In addition, by analyzing the DMRs across multiple generations of Arabidopsis, the author studies the inheritance pattern of ectopic CG methylation.  Dr.Wanlu Liu is the first author and co-corresponding author of the article. The undergraduate student from Zhejiang University-University of Edinburgh Institute Yuxing Zhou participates in the research. AbstractDNA methylation is an evolutionarily conserved epigenetic modification that plays critical roles in regulating gene expression, silencing transposable elements, genomic imprinting, X-chromosome silencing, etc. In Arabidopsis, DNA methylation occurs within three sequence contexts: CG, CHG, and CHH (where H represents A, T, or C). The maintenance of CG methylation requires the DNA methyltransferase METHYLTRANSFERASE 1 (MET1, the homolog of mammalian DNMT1), while maintenance of CHG and CHH methylation redundantly requires CHROMOMETHYLASE 3 (CMT3), CMT2, and DRM2. Using techniques including zinc fingers (ZF), TAL, or CRISPR/Cas9 to target epigenetic marks like DNA methylation to specific loci is important in both basic research and in crop plant engineering. However, the heritability of targeted DNA methylation, how it impacts gene expression, and which epigenetic features are required for proper establishment is mostly unknown.Figure 1By comparing ectopic CG methylation and other epigenetic modification, the author finds that ectopic methylation occurs preferentially at less open chromatin that lacks positive histone marks. Although the ectopic CG methylation is enriched in the gene body region, this hypermethylation shows little effect on transcription (Figure 2 C-E). The author also observes that the ectopic methylation triggers a mild but significant reduction in the accumulation of H2A.Z and H3K27me3. By analyzing through four generations of Arabidopsis, the author observes the significant heritability of the CG methylation region. These results outline general principles of the heritability and interaction of CG methylation with other epigenomic features that should help guide future efforts to engineer epigenomes.Figure 2

The Edinburgh University Students Association (EUSA) is run for and by students. EUSA represents and supports >40,000 Edinburgh students, with the aim of promoting their interests, health and welfare within the University community.Each year, EUSA organises the Teaching Awards. These Awards give students an opportunity acknowledge staff and celebrate the best of teaching and support at the University.This year, nine members of ZJE staff were nominated for awards in four categories:For ‘Outstanding Course’: Joanne Murray, Richard Sloan and Kuan Yoow Chan.For ‘Supervisor of the Year’: Rob Young, Sebastian Leptihn and John Menzies.For ‘Personal Tutor of the Year’: Sander van den Driesche.For ‘Teacher of the Year’: Nico Romano, Sebastian Leptihn and Melanie Stefan.Congratulations to all nominees and thank you to all the ZJE students who took the time to nominate their teachers.https://eusa.ed.ac.uk/whatson/awards/teachingawards/rollofhonour

Several ZJE faculty members have been nominated for Teaching Award from  the Edinburgh University Students' Association (EUSA). EUSA TeachingAwards are a student-run initiative to recognise and celebrate the best in teaching and student support from across the University of Edinburgh.This year, ZJE staff members have been nominated across several categories, including Outstanding Course (Joanne Murray, Richard Sloan),  Supervisor of the Year (Sebastian Leptihn, John Menzies, Melanie Stefan, Robert Young), Teacher of the Year (Sebastian Leptihn, Nicola Romanò, Melanie Stefan), and Personal Tutor of the Year (Sebastian Leptihn, Sander Van den Driesche). A full list of nominations can be found here:https://www.eusa.ed.ac.uk/yourvoice/ourwork/teachingawards/rollofhonour/