tbuckley/cabot-search huggingface dataset:
Focus on mechano-immunology: new direction in cancer treatment
Authors: Lin Zhao, Yajun Gui, Xiangying Deng
Journal: International Journal of Surgery (2025)

The immune response is modulated by a diverse array of signals within the tissue microenvironment, encompassing biochemical factors, mechanical forces, and pressures from adjacent tissues. Furthermore, the extracellular matrix and its constituents significantly influence the function of immune cells. In the case of carcinogenesis, changes in the biophysical properties of tissues can impact the mechanical signals received by immune cells, and these signals c1an be translated into biochemical signals through mechano-transduction pathways. These mechano-transduction pathways have a profound impact on cellular functions, influencing processes such as cell activation, metabolism, proliferation, and migration, etc. Tissue mechanics may undergo temporal changes during the process of carcinogenesis, offering the potential for novel dynamic levels of immune regulation. Here, we review advances in mechanoimmunology in malignancy studies, focusing on how mechanosignals modulate the behaviors of immune cells at the tissue level, thereby triggering an immune response that ultimately influences the development and progression of malignant tumors. Additionally, we have also focused on the development of mechano-immunoengineering systems, with the help of which could help to further understand the response of tumor cells or immune cells to alterations in the microenvironment and may provide new research directions for overcoming immunotherapeutic resistance of malignant tumors.
Tumor-selective dye-based histological electrophoresis enables intraoperative tumor diagnosis via tumor-specific enhancement
Authors: Feiran Zhang, Jianing Cheng, Xu Peng, Chengbin Zhang, Limei Qu, Songling Zhang, Junhu Zhang, Shoujun Zhu
Journal: Theranostics (2025)

Solid tissue biopsy is fundamental in guiding surgeons during intraoperative and peri-operative management of cancer patients. However, conventional histopathologic methods depend heavily on the expertise of trained pathologists, facing challenges in accuracy and efficiency. Methods: Here, we show that unbiased labeling of proteins within tissue sections using tumor-selective dyes enhances tumor-specific signals, enabling robust and accurate differentiation of tumors from normal tissues in less than 45 min. This diagnostic approach combines a tumor-selective dye labeling strategy and a three-dimensional (3D) histological electrophoresis separation strategy to visualize protein differences between tissues and exclude off-target interference. Results: We successfully diagnose and delineate malignant tissue from frozen and fresh surgical specimens from 34 patients across six types of cancer (mean AUC = 0.93). Furthermore, we apply this method to distinguish different histological characteristics in liver cancer surgical specimens, as well as identify and quantify the degree of inflammation in tumor-surrounding tissues. Conclusion: This rapid, accurate, unbiased, and marker-free approach may enhance intraoperative detection of multiple types of tumor specimens.
Tumor microenvironment targeted nano-drug delivery systems for multidrug resistant tumor therapy
Authors: Xinyue Shao, Xiaoling Zhao, Binghao Wang, Jiahui Fan, Jinping Wang, Hailong An
Journal: Theranostics (2025)

In recent years, nano-drug delivery systems (Nano-DDS) that target the tumor microenvironment (TME) to overcome multidrug resistance (MDR) have become a research hotspot in the field of cancer therapy. By precisely targeting the TME and regulating its unique pathological features, such as hypoxia, weakly acidic pH, and abnormally expressed proteins, etc., these Nano-DDS enable effective delivery of therapeutic agents and reversal of MDR. This scientific research community is increasing its investment in the development of diversified systems and exploring their anti-drug resistance potential. Therefore, it is particularly important to conduct a comprehensive review of the research progress of TME-targeted Nano-DDS in recent years. After a brief introduction of TME and tumor MDR, the design principle and structure of liposomes, polymer micelles and inorganic nanocarriers are focused on, and their characteristics as TME-targeted nanocarriers are described. It also demonstrates how these systems break through the cancer MDR treatment through various targeting mechanisms, discusses their synthetic innovation, research results and resistance overcoming mechanisms. The review was concluded with deliberations on the key challenges and future outlooks of targeting TME Nano-DDS in cancer therapy.
Loss of DDX24 inhibits lung cancer progression by stimulating IKBKG splicing-mediated autophagy
Authors: Siwen Sun, Xiaomeng Jing, Guangquan Tong, Chaoqun Chen, Shuaijun Xie, Chong Wang, Dan Chen, Jinyao Zhao, Yangfan Qi, Wenjing Zhang, Congcong Liu, Ge Zhang, Jinrui Zhang, Bing Sun, Yang Wang, Yuesheng Lv
Journal: Theranostics (2025)

Rationale: Lung cancer remains a major global health burden with limited therapeutic options. Alternative splicing, a critical post-transcriptional process, contributes to lung cancer progression through autophagy, although the underlying mechanisms remain largely unexplored. This study aims to elucidate the role of DDX24 as a splicing factor that contributes to lung cancer progression via autophagy. Methods: To establish the link between DDX24 and lung cancer progression, we performed colony formation assays, growth curve analyses, and xenograft tumor models in nude mice. Mass spectrometry and RNA sequencing were employed to investigate the involvement of DDX24 in alternative splicing, with a specific focus on the splicing of IKBKG. The mechanisms by which DDX24 regulates autophagy were further explored using co-immunoprecipitation and luciferase reporter assays. Results: The splicing factor DDX24 is significantly elevated in lung cancer tissues. Loss of DDX24 suppresses lung cancer growth by promoting autophagy. We identified DDX24 as a splicing factor that plays critical roles in the regulation of alternative splicing. Mechanistically, DDX24 regulates the alternative splicing of autophagy-related genes, including IKBKG. We demonstrate that DDX24 directly binds to IKBKG pre-mRNA, whereas DDX24 ablation stimulates the generation of the long splicing isoform of IKBKG, thereby promoting autophagy through activating of the NF-kB signaling pathway and the transcription of the BECN1 gene. Functional rescue experiments confirm that the long IKBKG isoform-mediated autophagy confers the anti-tumor effects of DDX24 depletion. In addition, IKBKG-L is positively associated with improved survival in lung cancer patients. Conclusions: This study uncovers a novel regulatory axis involving DDX24, IKBKG splicing, and autophagy in lung cancer. Our findings suggest that targeting DDX24 may represent a promising therapeutic strategy for lung cancer treatment, offering new insights into the molecular underpinnings of this disease.
LETM-domain containing 1 (LETMD1) protects against obesity via enhancing UCP1-independent energy expenditure in human beige adipocytes
Authors: Jiaxing Liu, Ying Cheng, Qing Liu, Qiaoyun Long, Shiqing Liang, Wei Sun, Kerry M. Loomes, Xuefei Gao, Bin Lin, Xingguo Liu, Donghai Wu, Hannah Xiaoyan Hui
Journal: Theranostics (2025)

Rationale: Brown and beige adipocytes are specialized fat cells that dissipate energy in the form of heat, and hold therapeutic potential for obesity and metabolic diseases. Although in the classical viewpoint brown and beige adipocytes dissipate energy solely via uncoupling protein 1 (UCP1), emerging evidence suggests the importance of non-canonical UCP1-independent energy expenditure in regulating energy expenditure, especially in human beige adipocytes. Leucine zipper-, EF-hand-containing transmembrane protein 1 domain containing 1 (LETMD1) was recently identified as a key protein in maintaining UCP1 expression and the thermogenic activity of brown adipocytes in animal models. But the exact function of LETMD1 and its mechanism of action in human beige adipocytes are unclear. Methods: We tested the function of LETMD1 in human induced pluripotent stem cell (hiPSC)-derived beige adipocytes in vitro in both wildtype (WT) and UCP1 knockout (KO) background. Furthermore, human beige adipocytes harboring a doxycycline-inducible LETMD1 expression cassette were transplanted to NOD/SCID mice and the function of LETMD1 in human beige adipocytes was evaluated in the in vivo setting. RNA-Seq was conducted in normal and LETMD1-overexpressing human beige adipocytes to examine the genes and pathways regulated by LETMD1. Using a knock-in human iPSC line, a preclinical small molecule compound library was screened for compounds increasing LETMD1 expression in human beige adipocytes. The effects of the compound in inducing LETMD1 and UCP1-independent energy expenditure in beige adipocytes were examined in vitro and in animal models. Results: LETMD1 plays an essential role in engaging energy dissipation, in a manner independent of UCP1, in human beige adipocytes. Transplantation of LETMD1-overexpressing human beige adipocytes improved whole-body metabolism of the recipient mice independent of UCP1. Mechanistically LETMD1 enhances the transcription of PPARGC1A, a key regulator of mitochondrial biogenesis. The expression of genes related to UCP1-independent energy expenditure, including creatine futile cycle, was also stimulated upon LETMD1 overexpression. Using LETMD1 reporter human beige adipocytes, SP-8356 was identified as a compound significantly increasing LETMD1 expression. Oral administration of SP-8356 induced genes related to UCP1-independent energy expenditure in beige adipocytes, and counteracted body weight gain and metabolic disorders in mice. Conclusion: Increased LETMD1 action, either genetically or pharmacologically, enhances the non-canonical UCP1-independent energy expenditure in beige adipocytes.
Stimulus-responsive smart bioactive glass composites for repair of complex tissue defects
Authors: Yulian Yang, Yonghao Qiu, Cai Lin, Xiaofeng Chen, Fujian Zhao
Journal: Theranostics (2025)

Smart biomaterials with active environmental responsiveness have attracted widespread attention in recent years. Previous studies on bioactive glass (BG) have mainly focused on the property of bioactivity, while little attention has been paid to the property of smart response of BG. Herein, we propose the concept of Smart Bioactive Glass Composites (SBGC) which are capable of actively responding to the endogenous disease microenvironment or exogenous physical stimuli, thereby enabling active treatment of tissue defect sites and ultimately promoting tissue regeneration. In this review, the response characteristics of SBGC to different internal and external environments are described. Subsequently, the applications of SBGC in complex tissue defect repair of tumors, infections, and diabetes are reviewed. By deeply analyzing the recent progress of SBGC in different fields, this review will point out the direction for the research of next-generation BG.
Autoimmune diseases and risk of gastrointestinal cancer: an umbrella review of meta-analyses of observational studies
Authors: Xiao Bai, Yunran Guo, Xinmao Zhu, Dongqiu Dai
Journal: International Journal of Surgery (2025)

Several autoimmune diseases (ADs) are considered risk factors for gastrointestinal (GI) cancers. This study pooled and appraised the evidence associating ADs with GI cancer risks. Three databases were examined from initiation through 26 January 2024. Evidence was determined by the criteria including the P -value of random-effects, small-study effects, excess significance bias, heterogeneity, and 95% prediction interval. Fourteen meta-analyses including 211 primary studies describing 31 associations were selected. Inflammatory bowel disease (IBD) and Crohn's disease (CD) are strong risk factors (with effect sizes of 10.33 and 12.12, respectively) for small bowel cancer (SBC), as indicated by highly suggestive evidence. Another highly suggestive evidence is that gastric cancer (GC) risk was elevated in individuals suffering from pernicious anemia (PA, effect size: 2.80). Suggestive evidence emerged that the risks of colorectal cancer (CRC) were decreased in patients with rheumatoid arthritis (RA, effect size: 0.79) but increased in patients with IBD (effect size: 1.82). This study finds three highly suggestive pieces of evidence of IBD and CD patients with higher SBC risk and PA patients with higher GC risk. Future studies should identify these associations to provide more personalized cancer screenings for patients with ADs.
Safety and clinical efficacy of neoadjuvant chemoradiation therapy with immunotherapy for organ preservation in ultra-low rectal cancer: preliminary results of the CHOICE-I trial: a prospective cohort study
Authors: Leqi Zhou, Guanyu Yu, Yuxin Shen, Rongbo Wen, Haibo Ding, Jidian Zhou, Xiaoming Zhu, Yonggang Hong, Haifeng Gong, Lianjie Liu, Hao Wang, Huojun Zhang, Chenguang Bai, Liqiang Hao, Wei Zhang
Journal: International Journal of Surgery (2025)

Objective: To explore the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) combined with a PD-1 antibody in improving complete clinical response (cCR) and organ preservation in patients with ultra-low rectal cancer. Methods: This was a prospective phase II, single-arm, open-label trial. Patients with confirmed pMMR status T 1-3a N 0-1 M 0 retcal adenocarcinoma were included. Long-course chemoradiotherapy was delivered to a dose of 50 Gy. A PD-1 antibody was added 2 weeks after the first radiotherapy session, and two courses were administered. After chemoradiotherapy, CapeOX plus PD-1 antibody was administered to patients for two cycles. After evaluation, patients with cCR were managed with a watch-and-wait (W&amp;W) approach. Local excision or a W&amp;W approach was performed for patients with near complete clinical response (ncCR) as per multidisciplinary team decision. Radical surgery was recommended for poorly regressed or progressed tumors. Results: Twenty-five patients were enrolled, but two patients withdrew from the study. A total of 23 patients completed the entire neoadjuvant therapy. Ten and five patients achieved cCR and ncCR, respectively, and the rest had a partial clinical response. Patients with cCR were managed with W&amp;W. Four patients with ncCR underwent local excision and were managed using W&amp;W. Eight patients with partial clinical response underwent anus-preserving surgery. At the last follow-up, the rectum and anus preservation rates were 63.4% (14/22) and 95.5% (21/22), respectively. Conclusion: nCRT combined with immunotherapy tended to achieve better cCR and rectum preservation rates with good tolerance in patients.
Single-cell nanocapsules of gut microbiota facilitate fecal microbiota transplantation
Authors: Weiliang Hou, Yuan Cao, Jifeng Wang, Fang Yin, Jiahui Wang, Ning Guo, Ziyi Wang, Xiaoqiong Lv, Chunlian Ma, Qiyi Chen, Rong Yang, Hong Wei, Juanjuan Li, Ruibing Wang, Huanlong Qin
Journal: Theranostics (2025)

Rationale: Fecal microbiota transplantation (FMT) is advantageous for treating intractable diseases via the microbiota-gut-organ axis. However, invasive administration of gut microbiota via nasal feeding tubes limits the widespread application of FMT. Here, we attempted to develop a novel strategy to deliver gut microbiota using nanocapsules. Methods: Single-cell nanocapsules were fabricated within 1 h by layer-by-layer assembly of silk fibroin and phosphatidylcholine to generate a protective nanoshell on the cell surface of complicated microbiota. The physical properties of the microbiota nanocapsules were analyzed. The protective effects of nanocapsules on the gastrointestinal tract were analyzed both in vitro and in vivo. The efficacy of FMT assisted by single-cell nanocapsules (NanoFMT) was evaluated using the inflammatory response, gut microbiota balance, and histopathological analysis in animal model. Results: The nanocapsules achieved a good coating ratio for a single type of microbe and complex microbiota, resulting in a remarkable increase in the survival rate of microbes in the gastrointestinal tract. NanoFMT improved the diversity and abundance of the gut microbiota better than common FMT in germ-free mice. Moreover, NanoFMT alleviated intestinal inflammation and positively reversed the microbiota balance in a mouse model of colitis compared with common FMT, assisted by the inherent anti-inflammatory effects of silk fibroin and phosphatidylcholine. Conclusions: Considering its rapid preparation, convenient delivery, and perfect therapeutic effect, we anticipate that NanoFMT may be a promising clinical candidate for next-generation FMT treatment.
Silybin A from <i>Silybum marianum</i> reprograms lipid metabolism to induce a cell fate-dependent class switch from triglycerides to phospholipids
Authors: Solveigh C. Koeberle, Maria Thürmer, Fengting Su, Markus Werner, Julia Grander, Laura Hofer, André Gollowitzer, Loc Le Xuan, Felix J. Benscheid, Ehsan Bonyadi Rad, Armando Zarrelli, Giovanni Di Fabio, Oliver Werz, Valeria Romanucci, Amelie Lupp, Andreas Koeberle
Journal: Theranostics (2025)

Rationale:Silybum marianum is used to protect against degenerative liver damage. The molecular mechanisms of its bioactive component, silybin, remained enigmatic, although membrane-stabilizing properties, modulation of membrane protein function, and metabolic regulation have been discussed for decades. Methods: Experiments were performed with hepatocyte cell lines and primary monocytes in vitro under both basal and stressed conditions, and in mice in vivo. Quantitative lipidomics was used to detect changes in phospholipids and triglycerides. Key findings were confirmed by Western blotting, quantitative PCR, microscopy, enzyme activity assays, metabolic flux studies, and functional relationships were investigated using selective inhibitors. Results: We show that specifically the stereoisomer silybin A decreases triglyceride levels and lipid droplet content, while enriching major phospholipid classes and maintaining a homeostatic phospholipid composition in human hepatocytes in vitro and in mouse liver in vivo under normal and pre-disease conditions. Conversely, in cell-based disease models of lipid overload and lipotoxic stress, silybin treatment primarily depletes triglycerides. Mechanistically, silymarin/silybin suppresses phospholipid-degrading enzymes, induces phospholipid biosynthesis to varying degrees depending on the conditions, and down-regulates triglyceride remodeling/biosynthesis, while inducing complex changes in sterol and fatty acid metabolism. Structure-activity relationship studies highlight the importance of the 1,4-benzodioxane ring configuration of silybin A in triglyceride reduction and the saturated 2,3-bond of the flavanonol moiety in phospholipid accumulation. Enrichment of hepatic phospholipids and intracellular membrane expansion are associated with a heightened biotransformation capacity. Conclusion: Our study deciphers the structural features of silybin contributing to hepatic lipid remodeling and suggests that silymarin/silybin protects the liver in individuals with mild metabolic dysregulation, involving a lipid class switch from triglycerides to phospholipids, whereas it may be less effective in disease states associated with severe metabolic dysregulation.
Surgical treatment of congenital pseudarthrosis of the Tibia in children: CPAM-LRC consensus and guidelines
Authors: Wenqi Song, Runhua Zhou, Pei Liu, Yanjie Guo, Lei Shao, Delin Liu, Jia Xu, Tianyi Wu, Zhong Bai, Chi Su, Fuyun Liu, Jun Liu, Qinglin Kang, Shengdi Lu
Journal: International Journal of Surgery (2025)

Congenital pseudarthrosis of the tibia (CPT) is a rare condition typically manifesting within the first decade of life. The primary objectives of surgical intervention for CPT include achieving long-term bony union of the tibia, preventing or minimizing limb length discrepancies (LLD), avoiding mechanical axis deviations of the tibia and adjacent joints, and preventing refracture. This study aims to conduct a systematic review of current treatment methods for CPT to determine the most effective non-surgical and surgical management strategies for pediatric patients with this condition. A review of the literature was performed according to the PRISMA guidelines. A comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase, and Google Scholar databases was performed over the years 1989 to 2024. Randomized controlled trials, cohort studies and case-control studies on the surgical treatments of CPT in children were included. Random-effects models were used to estimate the pooled primary union rate, primary union time and refracture rate. Then a consensus statement of surgical treatment of CPT in children was achieved based on Delphi methodology which included 2 rounds of electronic questionnaires and 1 round of virtual consensus meeting. Seventy-four studies were included, 23 of which on intramedullary rods (IMR) involving 364 patients, 15 on Ilizarov methods with 230 patients, and 23 studies combining IMR with Ilizarov involving 458 patients. The pooled primary union rate for IMR, Ilizarov method, and Ilizarov combined with IMR was 69% (95% CI: 0.55-0.82), 89% (95% CI: 0.77-0.98) and 85% (95% CI: 0.74-0.94), respectively. The pooled primary union time for IMR, Ilizarov method, and Ilizarov combined with IMR was 8.95 months (95% CI: 6.53-11.37), 7.14 months (95% CI: 5.53-8.74), and 5.62 months (95% CI: 4.89-6.35), respectively. The pooled refracture rate among primary unions for IMR, Ilizarov method, and Ilizarov combined with IMR was 85% (95% CI: 0.60-1.00), 81% (95% CI: 0.56-0.98), and 60% (95% CI: 0.26-0.90), respectively. After 2 rounds of electronic questionnaires and 1 round of virtual consensus meeting, a consensus statement and guidelines of surgical treatment of CPT in children was provided. The CPAM-LRC consensus panel provided recommendations to improve management of pediatric patients with CPT in clinical practice. Combined techniques for pediatric patients after fracture or the formation of pseudarthrosis commonly include excision of the pseudarthrosis site, external fixation, intramedullary fixation, and autogenous bone grafting. Vascularized fibular graft and cross-union can be considered a viable alternative to corticocancellous autograft. Use of recombinant bone morphogenic protein (rhBMP) is not currently conclusive.