Umea Universitet

Nil Medical has developed a medical vest to help seriously ill children and adolescents with intravenous drip stands to regain their mobility. The company developed the ergonomic medical vest to conceal fluids, pumps and tubing within the garments, allowing children to play and move without restrictions. Nil Medical is currently conducting a national quality-of-life study in collaboration with Swedish healthcare to introduce it to the international market. “I learned about the challenge faced by children who are willing and able to play but are restricted in their movement due to being attached to an IV stand. After visiting the pediatric cancer ward, I felt inspired to address this issue using a user-centered design methodology,” said Martin Hanberger, an industrial design student at Norrlands Universitetssjukhus. ”It feels incredible to finally have a finished product after so many years of development – especially when we see how much the children appreciate it. Making things easier for them has always been our driving force”. The company developed an early prototype and tested it without being connected to any treatment or IV bags. After, a group of specialists in design, product development and CE marking of medical devices collaborated with experienced staff in the pediatric oncology department to develop the Nil Medical Vestpack. Researchers on the project established requirements and conducted risk analyses to ensure the vest was safe and user-friendly. Interviews with patients, families and healthcare providers were also integral to the development process. “One of the young users said, ‘I want it to be nothing,'” Hanberger said. “The name Nil (English for ‘zero’) was thus born from the freedom of movement that our medical vest provides. Those who use it no longer have to be confined to drip stands; instead, they can move freely, safely, and securely.” Quality of life study Nil Medical is conducting a quality of life study in Sweden for the Vestpack in collaboration with Region Jönköping, Sahlgrenska University Hospital, and Norrlands Universitetssjukhus. The goal is to introduce a CE-marked infusion vest to the international market, giving children new possibilities and greater freedom of movement. The company is developing the system and testing it in collaboration with the Umeå Biotech Incubator. “Umeå Biotech Incubator has extensive business development expertise, a solid reputation and track record, and a broad network of contacts,” Hanberger said. “We are really looking forward to start collaborating with UBI.”

引言 结直肠癌对于很多人来说并不陌生，它就像一个沉默的杀手，威胁着越来越多人的健康。全球每年新增病例约190万，发病率居所有癌症第三位，更可怕的是，约20%的患者在确诊时已发生转移，死亡率高居各类癌症第二位！ 面对如此严峻的形势，科学家们从未停止探索。近日，瑞典乌普萨拉大学联合华大生命科学研究院、华大基因智惠医学研究院对1063例结直肠癌样本进行了全基因组及转录组测序分析，发现了一系列与癌症不同阶段相关的基因，并识别了结直肠癌关键预后因子，为结直肠癌的预防、治疗及预后都提供了数据基础，相关研究于8月7日发表于全球顶级学术期刊《自然》（Nature）“Prognostic genome and transcriptome signatures in colorectal cancers”。值得一提的是，这也是目前全球最大的结直肠癌多组学研究。 基因信息+临床数据，双剑合璧破解“癌症密码” 本研究基于华大智造DNBSEQ测序平台，对瑞典知名癌症样本与数据库U-CAN队列中的1063例结直肠癌样本（包括782例结肠癌和281例直肠癌，其中，21%（223例）为微卫星不稳定肿瘤（结直肠癌中的一种特定类型））进行全基因组和转录组测序分析，鉴定得到了96个显著突变基因，其中，有24个为新发现的潜在驱动基因，而与WNT, EGFR和TGF-β通路相关的驱动基因与结直肠癌生存显著相关。 不止如此，研究人员还利用突变时序分析，推导出了9个与癌症发生早期事件相关的驱动突变基因（APC, TP53, KRAS, BRAF, ZFP36L2, TCF7L2, FBXW7, BCL9L和SOX9），和更倾向于在癌症发生的后期阶段出现的突变基因TRPS1, GNAS和CEP170。这些发现为结直肠癌的早期检测和靶向治疗的开发提供了临床研究策略，并揭示了与肿瘤后期侵袭和转移相关的重要分子变化。 本次分析的结直肠癌样本中，94%的病人有完整的5年临床随访记录，这也为研究人员更好地将基因数据与临床数据进行结合，破解“癌症密码”提供了可能。 突破“盲区”，非编码区也暗藏玄机 既往对结直肠癌基因相关的研究主要集中在编码区突变，但其实非编码区也可能会对癌症发生发展造成影响。 本研究中，研究人员通过全基因组和转录组测序分析发现在线粒体基因组和非编码区域中也存在与疾病相关的突变，并对与疾病进展显著相关的突变进行了系统性的总结，这些突破性的发现填补了非编码区在结直肠癌相关研究中的空白，将进一步推动对结直肠癌发病机制的理解。 重构预后分型，推动个性化诊疗 随后，分析团队利用同一肿瘤样本的基因组和转录组数据进行了整合分析，验证了无论是否为微卫星不稳定肿瘤，其抑癌基因APC，PTEN和TP53上的突变均导致基因表达降低，从而更容易患癌。 进一步地，研究团队基于肿瘤基因表达差异，将结直肠癌预后分为了5个预后亚型CRPS，相较于结直肠癌经典的共识分子分型CMS，本研究构建的CRPS能更加准确地预测预后。 例如，在经典的CMS分型中，CMS4（其中一种分型）被普遍认为是预后较差的肿瘤，但在本研究新构建的CRPS分型系统中，部分CMS4型肿瘤实际上被判定为预后较好的CRPS2型，这些结果提示整合基因组和转录组数据的分子分型，能得到更精细准确的患者预后分层，对优化临床肿瘤分型，指导结直肠癌精准治疗具有重要意义。 （Credit: Nature） 文章通讯作者、乌普萨拉大学的Tobias Sjöblom教授表示：“这项研究实现了迄今为止最大规模的结直肠癌基因组和转录组的综合分析，并将分子层面的发现与高质量的临床数据相结合，从而识别关键预后因子，这使这项研究有别于其他绝大多数癌症基因组学的研究。U-CAN大规模的临床患者队列与华大杰出的测序及数据分析能力相结合，对于本项目的成功至关重要，我们期待未来能在这一科学领域与华大持续合作。” 文章共同通讯作者、华大基因智惠医学研究院林从博士表示：“此次通过将华大先进的基因组学技术和数据分析资源应用于大规模结直肠癌人群，不仅发现多种突变事件对预后的显著预测效应，新构建的表达谱精细分型也将在未来指导结直肠癌个体化诊疗中发挥重要作用。期望未来能更加系统深入地解析不同肿瘤的发生发展机制，利用华大前沿技术探索开发更具临床应用价值的标志物，真正实现肿瘤的早诊早治。” 文章共同第一作者、华大基因智惠医学研究院李甫强表示：“大队列的深入研究离不开技术的辅助。得益于国产测序仪高质量的数据生产能力和成本优势，才可能支撑针对疾病队列如此大规模的多组学数据产出。未来，集合规化、标准化、自动化、信息化、智能化、规模化为一体的多组学技术平台，将赋能大规模基因组科研合作项目，助力大人群大数据的研究与应用。” 作为全球领先的生命科学前沿机构，华大一直致力于推动基因科技普惠民生，已在中国多个城市开展消化道肿瘤民生筛查项目，其中哈尔滨市消化系统肿瘤和“四高”检测项目由哈尔滨市政府联合华大共同开展，是哈尔滨市十大民生项目之一，项目第一期通过华大基因的粪便DNA甲基化检测技术，为80万适检人群（45-64周岁哈尔滨市常住居民）评估患结直肠癌和进展期腺瘤的风险，是全球率先开展的“从民生切入的大规模精准公共卫生项目”，依托华大智惠未来实验室13311i的工程化范式，助力“健康中国”目标的更早实现。（https://mp.weixin.qq.com/s/NM84ypGCXDcijf_N71xB3g） 乌普萨拉大学Tobias Sjöblom、Bengt Glimelius教授、华大基因林从博士和吴逵研究员为文章共同通讯作者；乌普萨拉大学Luís Nunes、华大基因李甫强、吴美珍和罗甜为文章共同第一作者。 关于U-CAN队列：Uppsala University联合Umeå University、Stockholm university、Kungliga Tekniska Högskolan (KTH) 等研究团队于2010年启动U-CAN队列建设，截至2023年底，已经采集了27,476名癌症患者的样本、影像及临床数据，该队列对患者进行每年定期随访，近20%的患者随访超过10年，75%以上的患者随访超过5年。（https://www.uu.se/en/research/u-can/about-u-can/u-can-statistics） 参考文献 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41586-024-07769-3 责编|探索君 排版|探索君 转载请注明来源于【生物探索】 End 往期精选 围观 一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版） 热文 Cell | 是什么决定了细胞的大小？ 热文 Nature | 2024年值得关注的七项技术 热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望 热文 CRISPR技术进化史 | 24年Cell 综述

A study provides new clues in the understanding of how antibiotic resistance spreads. The study shows how an enzyme breaks down the bacteria's protective outer layer, the cell wall, and thus facilitates the transfer of genes for resistance to antibiotics. A study at Umeå University, Sweden, provides new clues in the understanding of how antibiotic resistance spreads. The study shows how an enzyme breaks down the bacteria's protective outer layer, the cell wall, and thus facilitates the transfer of genes for resistance to antibiotics. "You could say that we are adding a piece of the puzzle to the understanding of how antibiotic resistance spreads between bacteria," says Ronnie Berntsson, Associate Professor at Umeå University and one of the authors behind the study. The Umeå researchers have studied Enterococcus faecalis, which is a bacterium that often causes hospital infections, where in many cases treatment with antibiotics no longer bites because the bacteria have developed resistance. These bacteria can also spread the resistance further via the type 4 secretion systems, T4SS. It is a kind of protein complex that acts as a copying device, allowing properties in the form of genetic material to be spread to other bacteria. Resistance to antibiotics is one such trait that can be moved between bacteria with the help of T4SS. An important part of T4SS is the enzyme PrgK, which breaks down the bacterial cell wall and thus facilitates the transfer of properties between bacteria. This enzyme has three parts or domains, LytM, SLT, and CHAP. PrgK works like scissors that cut into the bacterial cell wall. Contrary to what the researchers previously thought, it turned out that only the SLT domain was active, but in a different way than expected. The other two domains instead turned out to have an important role in the regulation of the enzyme. The researchers also identified that another T4SS protein, PrgL, binds to PrgK and ensures that it ends up in the right place in the protein machinery. "The findings are important for continued research into how to prevent T4SS from transferring properties such as resistance to antibiotics to other bacteria," says Josy ter Beek, Staff scientist at Umeå University. The study has been conducted through a combination of biochemical analyses of the protein linked to functional studies in vivo, and supplemented with structural studies of PrgK using both X-ray crystallography and AlphaFold modelling.