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A mucous permeable local delivery strategy based on manganese-enhanced bacterial cuproptosis-like death for the bacterial pneumonia treatment

A mucous permeable local delivery strategy based on manganese-enhanced bacterial cuproptosis-like death for the bacterial pneumonia treatment

Bacterial pneumonia is one of the challenging global infectious diseases with high morbidity and mortality. Considering the antibiotic abuse and resistance of bacterial biofilms, a variety of metal-based materials have been developed. However, due to the high oxygen environment of the lungs, some aerobic infection bacteria have high tolerance to oxygen and ROS, and most of the metal-based materials based on ROS may not achieve good therapeutic effects.Recently, Professor Min Zhou's team from the Second Affiliated Hospital of Zhejiang University School of Medicine/Zhejiang University-University of Edinburgh Institute published a research paper titled A mucous permeable local delivery strategy based on manganese-enhanced bacterial cuproptosis-like death for the bacterial pneumonia treatment in the ACS Nano, making new progress in the bacterial cuproptosis-like death for the bacterial pneumonia treatment.Copper, a long-established antimicrobial material, has recently been found to trigger copper-induced cell death after its accumulation within biofilms by interacting with components in the tricarboxylic acid (TCA) cycle. Cell death induced by copper is associated with cell respiration, in which cells dependent on aerobic respiration are more sensitive to copper-induced death, showing potential application in the treatment of pulmonary aerobic infections. However, the application of copper death to the treatment of bacterial infections has been limited, starting with the protective effect of glutathione, which can interact with copper and thus hinder the interaction of copper with proteins.Another key point is the concentration of copper ions, considering the toxicity of copper ions, direct intravenous injection of large doses of copper preparations can lead to serious toxic effects.Inspired by the sensitivity of cuproptosis to aerobic respiratory cells, we designed a copper composite antibacterial nanoparticle and found that it can effectively induce cuproptosis-like death in aerobic bacteria of the lung. To address the challenge of in vivo application of cuproptosis, manganese dioxide was first incorporated to deplete protective glutathione, and assists in antibacterial action through immune enhancement. Cuproptosis-like death also requires a large amount of copper ions. To meet this demand, we deliver positively hydrophilic modified composite nanoparticles that effectively penetrate the lung mucus layer directly to the lungs through local administration, and the copper ions were further released rapidly by the acidic environment at the infected site, which can further destroy bacterial biofilms in synergy with manganese. This drug delivery system can effectively treat pneumonia caused by aerobic bacteria and avoid the systemic toxicity that can be caused by large doses of copper.Dr. Shiyuan Hua from the Min Zhou team at the Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute) is the first author of the paper. Dr. Huiqun Hu from the Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine is the co-first author of the paper. Professor Min Zhou from the ZJU-UoE Institute and Professor Feng Xu from the Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine are the co corresponding authors of the paper.
2024-11-15
Steady development, cross exploration | ZJE graduate students participate in the 14th  Poster Day of  School of Basic Medical Sciences  Zhejiang University

Steady development, cross exploration | ZJE graduate students participate in the 14th Poster Day of School of Basic Medical Sciences Zhejiang University

On November 7th, ZJE organized more than 30 graduate students to participate in the 14th  Poster Day of School of Basic Medical Sciences (BMS). At the event, ZJE students actively communicated and discussed with students from the School of Basic Medical Sciences and the School of Brain Science and Brain Medicine, and detailed their research progress to the reviewing experts.Professor Ke Yuehai, Dean of ZJE and vice dean of the School of Medicine , Professor Xu Haoxin, Dean of School of Basic Medical Sciences and Mikael Bjorklund, Assistant Dean and Graduate Program Director of ZJE attended the opening ceremony. Professor Ke Yuehai  expressed his great honor to witness the 14 years history of the Poster Day in BMS, from the initial concept of "Happy Science and Happy Life " to "Better Science and Better Life". Currently, Professor Ke believed that "Better Self " should also be added because the ultimate demand of scientific research should be to find a better self. He hopes that researchers can find calmness, confidence, self-discipline, and happiness from scientific research.After a morning of exciting poster display, expert review, and on-site voting, the event finally selected the winners of awards such as the Original Academic Newcomer Award and Best Poster Award. Professor Mikael Bjorklund, Assistant Dean of ZJE and Vice Dean of BMS Hu Weiwei jointly presented awards to ZJE award-winning students.The list of ZJE graduate students who have won awards is as follows:ZJE Best Poster Award: Li Wenyue, Yang Yuzhi, Zhang Linkun, Zhao Xing, Zhang HaonanZJE Original Academic Newcomer Award: Chen Silin, Yuan Dailin, Li Shiqi, Yuan Pengkun, Huang HaoSecond prize in the competition for the most beautiful experimental image of protein detection technology: Li Wenjun
2024-11-13
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Jin Yinhua, Rush towards every passion

She is a lovely girl from Northeast China, gentle towards all things in the world. She approaches science with reverence, delving into the mysteries of life. Using her soul to ignite the fireworks in her aspirations, she decorates the joys of life with her actions. In this edition, we introduce Dr. Jin Yinhua, a researcher and doctoral supervisor at ZJE."Dr. Jin YinhuaResearcher, PhD Supervisor, Tenure-Track Assistant ProfessorDr. Jin Yinhua graduated from the University of Heidelberg in Germany under the guidance of Prof. Dr. Bruce A. Edgar. She subsequently pursued postdoctoral training at Stanford University School of Medicine in the United States, mentored by Prof. Dr. Roel Nusse, a fellow of the National Academy of Sciences and an HHMI investigator. During this period, her research focused on elucidating the mechanisms by which signals from the stem cell microenvironment regulate tissue homeostasis and regeneration.By establishing a unique set of genetic, cellular, and molecular biology tools, she first revealed the mechanisms through which microenvironmental signals such as EGF and Wnt control the potential of stem cells, as well as the roles of these mechanisms in tissue regeneration and repair. In May 2023, Dr. Jin Yinhua joined Zhejiang University-University of Edinburgh Institute as a researcher and PhD supervisor. She formed the Stem Cell Microenvironment and Tissue Regeneration research group, where she primarily investigates how microenvironmental signals control cell behavior and cell interactions during tissue development and regeneration.ACADEMIC CAREERThe journey of learning began in 2003 when the Human Genome Project was nearing completion, planting the seeds of ideals in the young and tender heart. The seeds, imbued with vibrant vitality, quickly took root and sprouted, breaking through the soil, fueled by curiosity, exploration, and the quest for knowledge. Starting with the study of biotechnology at China Agricultural University, focusing on the application of technology in production, to researching plant stem cells at Seoul National University, and further delving into adult stem cells and understanding the regulation of intestinal stem cells by growth factors at the University of Heidelberg. Then, journeying to Stanford University to continue in this field, Dr. Jin, like a helmsman, held the oar, steered the course, adjusted the direction, cut through waves, and sailed towards the ideal shore.In the pursuit of biology, Dr. Jin Yinhua's journey began with interest, and she consistently nurtured that interest with the purest passion, focusing single-mindedly on watering and cultivating it. Over the years, that initial interest quietly shed its youthfulness and transformed into a deep-seated aspiration.During her academic journey, Dr. Jin Yinhua was influenced by the diligent efforts of Korean students, admired the rigorous, meticulous, and high-standard work attitude of German researchers, and was amazed by the active thinking, daring spirit, and courage to tackle cutting-edge work displayed by American researchers. Under the influence of a multicultural environment, Dr. Jin Yinhua embraced the strengths of various cultures, developed her style, and explored infinite truths in the endless river of the universe.Behind Dr. Jin Yinhua's calm and easygoing narrative, there ripples the unknown hardships and challenges. Cultural clashes, language barriers, and unfamiliar environments are tests that every international student must face. The comforting language rules, habits, and ways of thinking in one's native tongue can become barriers and misunderstandings in cross-cultural communication. In other words, what was once familiar and understood has turned into confusion.Courage is the belief that life holds onto in difficult times, a belief that time endows with enduring resilience. On this note, Dr. Jin Yinhua also provides advice: bravely step out of the comfort zone of the Chinese community, communicate more with locals, and embrace each other's cultural habits. This is indeed something that takes time and effort, but it is worth doing.SCIENTIFIC RESEARCH JOURNEY"Passionate, enjoyable, challenging" is Dr. Jin Yinhua's summary of her journey in scientific research. Maintaining a childlike curiosity is the driving force for researchers. The pursuit originates from love, and love achieves the pursuit. The scientific research career begins with curiosity and passion, and what is most precious is retaining the initial expectation after experiencing numerous challenges. In our conversation with Dr. Jin Yinhua, we can feel her passion for research and enjoyment of the process. She attributes this to the influence of two mentors.Her American mentor, despite being elderly, left a deep impression on Dr. Jin with his pure passion. His relentless pursuit of truth, continuous progress, and unwavering commitment inspired her. "Life gains value when you can find joy in your profession," he once said. Scientific research is challenging, but we can still find enjoyment in it.Her German mentor, on the other hand, is someone who truly enjoys scientific research. He finds pleasure in the seriousness of research, immersing himself in the process with a philosophical mindset and a comfortable and relaxed state. Despite the difficulties of scientific research, he manages to derive enjoyment from it, showcasing a unique approach to the scientific journey.THE JOURNEY OF LIFE Andrew Carnegie once said, "Everyone should have a strong interest or hobby to enrich the soul and add flavor to life." Wise individuals can make ordinary lives vibrant and colorful. Volleyball, comics, books, movies, travel, and everyday meals and seasons are all cherished as the most beautiful scenery in Dr. Jin Yinhua's heart, enriching her life beyond scientific research. Dr. Jin enjoys playing volleyball, having been a member of the university team at China Agricultural University, and participating in intercollegiate volleyball competitions with friends, a joyful and satisfying experience.What stands out most in Dr. Jin Yinhua's memories? Undoubtedly, it's travel. Leafing through the pages of her life, she realizes that many unforgettable memories are closely tied to her travels. Whether it's reaching for the stars in accessible Alaska, the romantic encounter with the aurora and snow near the Arctic Circle, or personally visiting the small village mentioned in the textbook's "The Last Lesson" and experiencing the wonderful overlap of reality and memory. Dr. Jin particularly emphasizes that compared to short-term tourist visits, the long-term immersive travel experienced during her overseas studies made it easier to discover vibrant corners and encounter unexpected beauty.For undergraduate students, Dr. Jin Yinhua's message is: "The guidance of good mentors is like a lighthouse at sea, guiding lost ships. Dr. Jin Yinhua wants to say to our undergraduate classmates, 'It should be a fun journey, enjoy it.' She plainly states that looking back on her academic journey, the undergraduate phase was undoubtedly the most interesting. Therefore, undergraduate students should wholeheartedly enjoy this period, striking a balance between diligent learning and embracing the pleasures of life. Fear not the length of youth, and let's explore new horizons while the fire is still burning, sipping poetry and wine in the bloom of our time!"

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Aaron Irving, Befriending Biology, Keeping up with Interests

Aaron IrvingAaron Irving, Assistant Professor at the Zhejiang University-University of Edinburgh Institute (ZJE). His journey into the world of life sciences began with a movie and a deep connection to China.Dr. Aaron Irving, an Assistant Professor at ZJE, brings a wealth of academic and research experience from his training at institutions like the University of Queensland (Australia), Diamantina Institute (UQ Australia), Monash Biomedicine Discovery Institute (Melbourne), and the Duke-NUS Medical School (Singapore).Dr. Irving's focus lies in newly emerging zoonotic viral infections and the host-pathogen interactions they trigger. He uses bats as a model organism, exploring key factors in bat immune responses that could be harnessed to enhance human immunity against pathogens. His lab also works on new diagnostic techniques to identify wildlife infections with zoonotic viruses like SARS-CoV-2 and factors contributing to the potential for zoonotic diseases.But what led Aaron to this fascinating field of virology? It all started with a childhood fascination with viruses, but it was a movie that changed the course of his life. The film "Outbreak," which tells the story of the Ebola virus jumping from monkeys to humans and spreading among the population, convinced him to become a research scientist. With curiosity about viruses and a concern for human health, he embarked on the path of scientific research.During his undergraduate years, Aaron pursued a Bachelor of Science degree, allowing him to freely explore his interests and build a solid foundation in biology. He worked diligently, fueled by passion and guided by his interests, eventually earning dual degrees in molecular biology and cell biology.After his undergraduate studies, he continued for an additional year of research (known as an Honours degree in Australia) and achieved the highest honors (Class I). During this time, he delved into the study of the herpes simplex virus (HSV1), which causes cold sores, and how it evades the human immune system. This research laid the groundwork for his future career in host-pathogen interactions.When it comes to bats, Aaron's eyes light up with excitement. "Bats are truly fascinating creatures," he says. What makes Aaron so enamored with these flying mammals?Initially, Aaron was not well-acquainted with the mysteries of bats. However, he stumbled upon a new world that captured his interest. Bats have undergone many evolutionary adaptations, making them exceptionally healthy, robust, and resilient animals with strong immune systems, immunity to aging, cancer resistance, inflammation prevention, and autoimmune disease avoidance. Aaron's research on bats aims to uncover the secrets of their exceptional health and apply that knowledge to benefit human health.Today, Aaron is involved in various projects, including those related to coronaviruses. His primary focus is on understanding the different genes that bats activate in their immune responses and comparing them to humans.One of his most intriguing projects examines the differences between bat and human aging. According to Aaron, wild-caught bats show no signs of aging, with 20-year-old bats appearing as youthful as 1-year-olds. He hopes to compare this phenomenon with research on human aging and humorously suggests that the findings could potentially be applied to skincare products to prevent human skin aging.Before joining ZJE, Aaron had already established a connection with China. He had previously visited Yunnan, known as the "Kingdom of Flora and Fauna," and collaborated with a local organization. He describes Yunnan as an incredible place with diverse biological species, making bat capture relatively easy due to the vast bat populations in a small area.When asked why he chose ZJE, Aaron believes that science in China is rapidly growing, offering abundant opportunities and possibilities. ZJE warmly welcomes fresh talent and provides excellent research facilities and an environment conducive to teaching. Additionally, the international platform at ZJE allows him to adapt and integrate into a foreign culture. Despite being a newcomer, he appreciates the students' critical thinking abilities and their knack for posing thought-provoking questions, which continually surprise him. He encourages students to express their opinions boldly and actively participate in the classroom.

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Dmytro Shytikov, A dreamer with a heart of gold

Dmytro ShytikovDr. Dmytro Shytikov is from Ukraine and is currently a lecturer at ZJE. He graduated with his PhD from Kiev National University in 2015, focusing on the mechanisms of immune response, the interaction of the adaptive immune system with the natural immune system, and the mechanisms of aging of the immune system.Dmytro started his research at university by joining Prof. Gennadii Butenko's lab, a team that studied the effects of blood exchange between animals of different ages, focusing on the immune system, which got Dmytro interested in the field of immunity, and guided him on an exploratory journey to study the immune system from then on.In 2016, Dmytro came to China and joined the School of Basic Medical Sciences at Zhejiang University for a postdoctoral position. In a country where most people tend to go to Western countries to pursue research, coming to China to do research seemed like a "surprising choice." "But why not go? I'm enjoying everything here," Dmytro says with a smile. Dmytro joined ZJE in April 2021. Dmytro believes that ZJE's model of talent development is markedly different from where he went to school, with significant crossover and a cutting-edge curriculum of integrated courses for students.During his time at ZJE, Dmytro has learned a lot of new things, especially about statistics (which he thinks is very important), and he has met many friendly colleagues, which has made him enjoy his research and life at ZJE even more. Dmytro is mainly responsible for the Biomedical Horizon course at ZJE, an interdisciplinary course that brings together the expertise of both ZJU and the University of Edinburgh to explore the potential of the Biomedical Horizon. Edinburgh University to explore how biomedicine can be used to address the challenges facing the world. The students enjoy his classes very much, and all see Dmytro as a friendly and fun teacher who loves in front of life. He had a lively approach to his classes, encouraging people to express themselves and guiding his classmates to solve problems independently. But when it comes to students' work, Dmytro is very serious, students can not only learn professional knowledge from him but also be infected by his rigorous attitude!Although busy is Dmytro's daily routine, work is not all he does. In his leisure time, Dmytro reads, plays sports, takes walks with his wife, and does origami and postcrossing (postcard exchange). To understand Chinese culture and integrate into his new environment, Dmytro has tried to learn Chinese and happily accepted the Chinese name "Shi Mingcheng" which a friend suggested for him. "It sounds and looks good! My original name was a bit long," he jokes. This year, Dmytro and his wife experienced an authentic Chinese New Year, spending New Year's Eve with their twinned Haining family over a hot pot, and Dmytro thoughtfully prepared the ingredients to teach everyone how to make Ukrainian dumplings. That night, everyone sat around and had a great time talking about Eastern and Western cultures and Chinese New Year customs.When it comes to the future, Dmytro hopes to become a researcher in the field of immunology and explore more deeply in immunotherapy. This is his second year as a lecturer, and there are many memorable experiences and much-needed updates that he hopes to pass on to his students in a way that is recognized by ZJE. At the same time, he looks forward to learning more Chinese and experiencing Chinese culture more deeply in the future.

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Qianting Zhang, 90s Newcomer PhD Supervisor

Qianting Zhang2007-2017 Undergraduate degree, College of Life Sciences, Zhejiang University2017-2018 Postdoctoral Fellow, University of Gothenburg2020.4 Assistant Professor, Zhejiang University-University of Edinburgh (ZJE)She focuses on signal regulation and molecular mechanisms during mammalian gametogenesis or tumourigenesis using mammalian cells, gene-edited mouse models and human samples.Zhejiang University personal homepage: https://person.zju.edu.cn/qiantingzhangPersonal Email: qiantingzhang@intl.zju.edu.cnIn her long academic journey,  Qianting  Zhang never imagined she would have an unbreakable bond with Zhejiang University - obtaining her bachelor's and doctoral degrees, building a family, and returning as an independent researcher at the Zhejiang University-University of Edinburgh (ZJE). At every turning point in life, she coincidentally encountered Zhejiang University's proactive establishment of new academic institutions, providing favorable conditions and flexible space for individuals like Teacher Zhang to pursue their life ambitions.In response to the needs of the new era, where world-class university construction and the globalization of education and research are essential, Zhejiang University established an international campus in Haining, offering Teacher Zhang another opportunity and the confidence to return to her alma mater. She says, "I have always chosen Zhejiang University because opportunities kept coming my way. Additionally, many mentors, friends, and advisors at Zhejiang University have been instrumental in propelling my career forward."Research has always been Qianting  Zhang's pursuit, and her path in early-stage tumor development and the molecular mechanisms of mammalian gametogenesis, especially during 2018 and 2019, led to the publication of numerous articles in renowned journals like Nature Cell Biology. To outsiders, it may seem like an extraordinary amount of energy and time to achieve so much in just two years. Yet, Qianting  Zhang modestly attributes it to "coincidence." She says, "Each research project has a long cycle, such as my work with gene knockout mice, where good samples appeared in the past two years, and that's when the articles were published." She further emphasizes that research is not a solo effort; it requires continuous dedication, hard work, and contributions from numerous collaborators at every stage.For many, research may appear tedious and unexciting, a sentiment shared by Qianting  Zhang when she first entered university. She initially chose biology due to her passion for the subject, but she initially had doubts and uncertainties about research. Nevertheless, she firmly believed in "loving what you do" and persevered in improving her expertise. When faced with challenges in research projects, she approached problems with a rational mindset, conquered her negative emotions, and sought solutions. She stresses the importance of being open to changing directions when necessary, emphasizing the value of timely communication with mentors and considering problems from different angles.Qianting  Zhang believes that research and education complement and are inseparable from each other. Having top-notch scientists and significant advancements in research is important, but it is equally crucial to prioritize the cultivation of excellent students and research professionals. Disseminating advanced scientific concepts systematically and enhancing the creativity of the entire research team is essential for maintaining international competitiveness and becoming pioneers in the forefront of life sciences.As an Assistant Professor, Qianting  Zhang's role includes helping the institute design cutting-edge, technology-driven professional courses and exploring diversified higher education models. Beyond the classroom, she mentions that thanks to the rich educational model, many students have a strong foundational knowledge and different perspectives on classroom discussions. They actively participate and often provide unique insights, which is why she loves teaching.

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