{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:25:29Z","timestamp":1771241129714,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172140"],"award-info":[{"award-number":["82172140"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study introduces a minimally invasive, in\u00a0situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers. The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus. Postsurgical monitoring of physiological parameters, systemic inflammatory markers, liver function, and intestinal integrity was conducted over 72\u2009h. Histopathological analysis was performed. The delivery of the functional protein TAT\u2010EGFP (Tat protein fused to enhanced green fluorescent protein) to intestinal epithelial cells was evaluated and compared with oral gavage. As a proof of concept, single\u2010cell RNA sequencing of the intestinal epithelium was performed after high\u2010mobility group box\u00a01 administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Postsurgical monitoring indicated only transient, anesthesia\u2010related hypothermia and minor behavioral alterations. No significant changes were observed over 72\u2009h in body weight, core temperature, clinical severity scores, systemic inflammatory markers (C\u2010reactive protein and leukocytes), liver function (alanine aminotransferase), or intestinal integrity. Histopathological analysis confirmed preserved tissue architecture and normal digestive, absorptive, and barrier functions. The model successfully delivered TAT\u2010EGFP to intestinal epithelial cells, an outcome not achievable via oral gavage due to gastric degradation. Single\u2010cell RNA sequencing of the intestinal epithelium after high\u2010mobility group box\u00a01 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Compared to traditional methods such as oral gavage or organoid culture, this technique offers precise, degradation\u2010resistant delivery of macromolecules in a physiological context. The model's versatility makes it a powerful platform for intestinal research, with applications in drug delivery assessment, gene therapy evaluation, and host\u2013microbiota interaction studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70123","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T04:01:17Z","timestamp":1769227277000},"page":"128-141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of an in\u00a0situ small intestinal injection technique for targeted macromolecule delivery and in\u00a0vivo functional studies in mice"],"prefix":"10.1002","volume":"9","author":[{"given":"Yawen","family":"Lai","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Proteomics, Department of Pathophysiology, School of Basic Medical Science Southern Medical University  Guangzhou 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