Supplementary tables, figures and protocol.

Acute radiation-induced intestinal injury (ARIII) is a common side effect of abdominopelvic radiotherapy, with severe diarrhea and hematochezia occurring in approximately 60-80% of patients. Radiation inevitably damages the adjacent intestine, generating substantial reactive oxygen species (ROS) that impair intestinal function. Nanozymes, which combine enzyme-like catalytic activities with the advantages of nanomaterials, have broad applications in biomedicine. Applying nanozymes to mitigate radiation-induced intestinal damage represents a promising therapeutic strategy. Here, we developed PtCuS nanoclusters (NCs) with favorable biocompatibility and demonstrated their efficacy in mitigating ARIII after irradiation. PtCuS NCs scavenge ROS via enzyme-mimetic activity and activate glutathione metabolism to mitigate radiation-induced cell death and inflammation. PtCuS NCs also modulate macrophage polarization, suppressing M1-like pro-inflammatory activation and promoting an M2-like reparative phenotype through both direct macrophage regulation and epithelial-protective effects. Furthermore, PtCuS NCs help restore gut microbiota composition and metabolic profiles after irradiation, providing a microbiota-associated component of intestinal protection. Importantly, PtCuS NCs alleviate ARIII without compromising the therapeutic efficacy of radiotherapy. These findings demonstrate that oral administration of PtCuS NCs may safely and effectively mitigate ARIII, highlighting their potential to improve the quality of life of patients undergoing abdominopelvic radiotherapy.

Recent research has focused on gut bacteria in colorectal cancer, but the influence of other microbiota, including oral and nonbacterial gut microbiota, on treatment efficacy remains insufficiently explored. This study aimed to investigate their relationship with the efficacy of neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Saliva and fecal samples were collected from patients with LARC before treatment. Shotgun metagenomic sequencing was used to profile bacterial, archaeal, eukaryotic, and viral taxonomic groups and to examine oral and gut microbial functions. An artificial intelligence-based prediction model was developed by integrating oral and gut microbiome data with clinical information. Statistical analyses compared diversity and response-associated microbial features between responders and non-responders to nCRT. Response-associated differences were observed in bacterial and nonbacterial taxonomic profiles and in oral and gut microbial functional profiles. In the internal test subset, the integrated analysis yielded an observed AUC of 0.917. Given the small cohort and the exploratory comparison of candidate classifiers, this estimate requires confirmation in larger, independent cohorts. Baseline oral and gut microbiome profiles were associated with response to nCRT. Integrating microbiome and clinical features showed potential for response prediction, but the model remains exploratory and requires validation in larger, independent cohorts before clinical application. Retrospectively registered on 01/08/2026, NCT07346729.

3502 Background: Patients with mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) colorectal cancer (CRC) who achieve a clinical complete response (cCR) after PD-1 inhibitor therapy may undergo non-operative management (NOM) with active surveillance. We aimed to assess the necessity of maintenance immunotherapy after achieving cCR, with a focus on survival outcomes and the burden of immune-related toxicity. Methods: A multicentre observational cohort study was conducted at five tertiary hospitals in China between Jan 1, 2018, and March 21, 2025. Patients with dMMR/MSI-H CRC who achieved cCR after PD-1 inhibitor therapy and entered NOM were included. Patients were stratified into an observation group （discontinue PD-1 inhibitor after cCR) and a maintenance group (received ≥2 cycles of PD-1 inhibitors after cCR). Disease-free and overall survival were compared between groups using Kaplan–Meier methods with log-rank test, and local regrowth, distant metastasis, and immune-related adverse events were assessed. Results: Among 318 patients treated with PD-1 inhibitors, 195 (61·3%) achieved cCR. A total of 129 patients were analysed (observation n = 66; maintenance n = 63), including 58 with rectal cancer, 61 with colon cancer, and 10 with synchronous dual primary tumours; 14 had distant metastases at diagnosis. Clinical complete response was assessed with endoscopy and pelvic MRI/CT along with digital rectal examination for rectal cancer, and endoscopy with contrast-enhanced CT or PET/CT for colon cancer. Median PD-1 inhibitor exposure to achieve cCR was eight cycles in both groups; 69·8% achieved cCR within eight cycles. Median follow-up was 3·2 years (IQR 2·0–4·0). Local regrowth occurred in two patients in the observation group and none in the maintenance group, and no distant metastases were observed. The 3-year DFS was 96·4% (95% CI 91·6–100·0) in the observation group and 98·4% (95% CI 95·2–100·0) in the maintenance group (log-rank p = 0·55). The 3-year OS was 100·0% (95% CI 100·0–100·0) versus 98·4% (95% CI 95·2–100·0) (p = 0·34). Any-grade irAEs occurred in 42/66 (63·6%) versus 44/63 (69·8%); grade 3 irAEs were numerically higher with maintenance (7/63 [11·1%] vs 2/66 [3·0%]; p = 0·091). Conclusions: To our knowledge, this is the largest series of dMMR/MSI-H CRC patients achieving cCR after PD-1 inhibitor therapy and managed with NOM. Maintenance therapy after cCR did not provide a clear survival advantage but was associated with a higher burden of immune-related toxicity, supporting treatment discontinuation with close surveillance.

Kirsten rat sarcoma (KRAS)-mutant colorectal cancer (CRC) is characterized by aggressive metastatic progression and profound therapeutic resistance. While direct inhibitors have emerged recently, their clinical application is often limited by rapid adaptive resistance, highlighting the urgent need to explore new therapeutic targets. Here, we identify O6-methylguanine-DNA methyltransferase (MGMT), a classical DNA repair enzyme, as a novel epigenetic facilitator of metastasis in KRAS-mutant CRC. Through integrated analyses of clinical cohorts and orthotopic metastasis models, we found that MGMT is upregulated in KRAS-mutant tumors and correlates with liver metastasis. Functionally, MGMT promotes epithelial-mesenchymal transition (EMT) and enhances metastatic capacity in vivo and in vitro. Mechanistically, we unveil a non-canonical function of MGMT in CRC: it interacts with histone H3 and reduces repressive H3K9me3 marks at the promoter of the epithelial-mesenchymal transition master regulator TWIST1, thereby activating its transcription. Importantly, we demonstrate that targeting MGMT sensitizes KRAS-mutant colorectal cancer to anti-EGFR therapy in preclinical models, providing a novel combinatorial strategy for this recalcitrant cancer subtype. Our study redefines MGMT as a multifaceted chromatin-modifying protein and establishes it as a promising therapeutic vulnerability to bypass resistance in KRAS-mutant CRC.

Herein, we develop an orally administered cobalt single-atom nanozyme (Co-SAN) featuring pH-responsive, bifunctional catalytic activity to enable simultaneous intestinal radioprotection and tumor radiosensitization. In the alkaline intestinal microenvironment, Co-SAN effectively scavenges radiation-induced reactive oxygen species (ROS)-as validated by flow cytometry, thereby mitigating radiation-induced intestinal injury (RIII). Mechanistically, RNA-seq analysis reveals that beyond direct ROS elimination, Co-SAN downregulates the ROS-mediated PI3K/AKT signaling pathway, significantly suppressing the formation of detrimental neutrophil extracellular traps (NETs). Furthermore, this highly biocompatible nanozyme maintains gut microbiota homeostasis and preserves intestinal barrier integrity. In contrast, within the mildly acidic tumor microenvironment (TME), Co-SAN undergoes a catalytic switch to promote ROS generation and ameliorate hypoxia, potently augmenting radiotherapeutic efficacy. Collectively, this study presents a bifunctional single-atom nanozyme that resolves the spatial contradiction between normal tissue protection and targeted tumor sensitization, offering a promising paradigm to substantially widen the therapeutic window of radiotherapy.

Background: Colorectal cancer (CRC) ranks among the leading causes of cancer-related mortality, with a sharp rise in incidence among patients diagnosed before age 40, a group classified as having very-earlyonset CRC (VEO-CRC). Because synchronous distant organ metastasis (DOM) at diagnosis is common and worsens survival, this study aimed to identify predictors of DOM, develop and internally validate a nomogram to estimate individual DOM risk, and evaluate its potential clinical utility. Methods: Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2020, we identified patients diagnosed with malignant colorectal adenocarcinoma under 40 years. Patients who met the inclusion criteria were randomly assigned to the training set and the validation set. Logistic regression analyses were performed to identify risk factors for DOM, which were subsequently used to construct a nomogram. The model's performance was assessed through receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results: A total of 8,097 VEO-CRC patients were assigned to training (n=5,667) and validation (n=2,430) cohorts. DOM among patients with malignant colorectal adenocarcinoma under 40 years was 23.04%. Multivariate analysis revealed seven independent risk factors for DOM: race, tumor size, primary tumor location, histopathological grade, tumor (T) stage, node (N) stage, and carcinoembryonic antigen (CEA) level. The nomogram demonstrated an area under the curve (AUC) of 0.846 [95% confidence interval (CI): 0.834-0.858] for the training cohort and 0.833 (95% CI: 0.813-0.852) for the validation cohort, indicating strong predictive accuracy. The clinical utility of the nomogram was verified in the DCA. Conclusions: The predictive nomogram, derived from demographic, clinical, and pathological data from the SEER database, provides an estimation of the DOM risk in VEO-CRC patients. This is a promising tool to improve outcomes for young patients by assisting physicians in early risk stratification and bespoke treatment planning. At prespecified risk thresholds, the predicted probabilities may assist early risk stratification and inform imaging and follow-up decisions, though their clinical application will require confirmation through rigorous external validation.

Abscopal effect refers to the shrinkage or regression of metastatic tumours that are distant from the irradiated field. Radiotherapy combined with immunotherapy can increase the occurrence of the abscopal effect. This case report describes a female patient with lung metastases from hepatocellular carcinoma who exhibited shrinkage and regression of non-irradiated lung lesions following combined radiotherapy and immunotherapy. The patient is currently stable and remains on treatment and follow-up. We discuss the potential mechanisms of the abscopal effect to provide clinical evidence supporting the combined use of radiotherapy and immunotherapy.

Background/Objectives: Frailty and postoperative symptom burden are prevalent in older adults undergoing colorectal cancer (CRC) surgery, but their temporal, within-person interplay remains unclear. We aimed to investigate this bidirectional relationship using a Random Intercept Cross-Lagged Panel Model (RI-CLPM) to overcome the limitations of conventional models that conflate between-person and within-person variances. Methods: This prospective longitudinal study enrolled 242 older patients (≥60 years) undergoing CRC surgery. Frailty and symptom burden were evaluated preoperatively and at 1 week, 1, 3, 6, and 12 months postoperatively. An RI-CLPM was applied to decompose variance and estimate bidirectional cross-lagged effects across these six time points. Results: Both frailty and symptom burden peaked at 1 week postoperatively. The RI-CLPM demonstrated good fit (CFI = 0.984; RMSEA = 0.063). At the between-person level, frailty and symptom burden were strongly correlated (r = 0.90, p < 0.001). At the within-person level, greater symptom burden significantly predicted subsequent frailty worsening from 1 to 3 months (β = 0.268, p = 0.033) and 3 to 6 months (β = 0.378, p = 0.004) postoperatively. Conversely, frailty did not significantly predict subsequent symptom changes at any time point. Additionally, conventional CLPM yielded biased cross-lagged estimates compared to the RI-CLPM. Conclusions: The within-person longitudinal relationship between frailty and symptom burden is unidirectional. Elevated symptom burden prospectively predicts frailty worsening between 1 and 6 months postoperatively, whereas frailty does not drive subsequent symptom changes. This 1-to-6-month window represents a critical period for targeted symptom management to attenuate frailty progression in older CRC survivors.

AbstractPurpose: Evidence for radiotherapy (RT) in oligoprogressive hepatocellular carcinoma (OP-HCC) is limited. We evaluated the efficacy and safety of progression-directed RT (PDRT) alongside ongoing first-line systemic therapy (FLST) in patients with OP-HCC. Patients and Methods: Patients who developed OP-HCC during FLST were enrolled and received PDRT with a biologically effective dose of at least 60 Gy while continuing FLST. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), toxicities, and quality of life (QoL). Results: From March 2024 through May 2025, 36 patients were enrolled from 10 cancer centers. At a median follow-up time of 10.9 months, median PFS time was 7.0 months (95% confidence interval 4.9–9.7), with 3-, 6-, and 9-month PFS rates of 73.7%, 64%, and 38.8%, respectively. Type of FLST and albumin–bilirubin (ALBI) grade at oligoprogression were independently associated with PFS. Median OS and DOR times were not reached; 1-year OS rates were 86.4%, and 3-, 6-, and 9-month DOR rates were 84.6%, 79.6%, and 70.8%, respectively. ORR and DCR were 64.7% and 98.0%, respectively. QoL measures generally remained stable, except for transient increases in fatigue and pain scores 1 month after PDRT. RT-related toxicities (mostly grades 1–2) occurred in 16 patients (44.4%), including grade ≥3 events in four patients (11.1%). Conclusions: Maintaining FLST with PDRT was effective, safe, and preserved QoL, supporting its feasibility for OP-HCC. FLST type and baseline ALBI grade may provide risk stratification and prognosis for PFS.

Dysbiosis of gut microbiota plays a crucial role in acute radiation-induced intestinal injury. However, studies on the influence of gut microbiota on acute radiation-induced intestinal injury are inconsistent. In this study, we established an acute radiation-induced intestinal injury mouse model and performed fecal microbiota transplantation to explore the role of the gut microbiota in acute radiation-induced intestinal injury. We observed a significant increase in Akkermansia muciniphila following irradiation, whereas fecal microbiota transplantation effectively reduced A. muciniphila levels. Contrary to expectations, A. muciniphila supplementation increased acute radiation-induced intestinal injury and mortality. Mechanistically, postradiation A. muciniphila upregulates mucin metabolism genes and consumes mucin, thinning the mucosal barrier and promoting the adhesion and translocation of potential pathogens to epithelial cells, thus exacerbating acute radiation-induced intestinal injury. This enables A. muciniphila to use mucin as an energy source. Additionally, A. muciniphila increases the inflammatory macrophage changes and secretion of inflammatory cytokines, leading to a decrease in epithelial stem cell density and inhibition of goblet cell differentiation, further exacerbating acute radiation-induced intestinal injury. Our findings suggest that in certain intestinal environments, the addition of A. muciniphila may worsen radiation-induced intestinal damage; thus, alternative approaches to reverse the dysbiosis associated with radiotherapy should be explored.

Acute chemoradiotherapy-induced intestinal injury (ACRIII) is a common and debilitating complication in patients with colorectal cancer, significantly impairing both quality of life and treatment outcomes. This study aimed to investigate the role of the gut microbiome in mitigating ACRIII. Through bioinformatics analysis of clinical fecal samples and fecal microbiota transplantation (FMT) experiments in mice, we identified a strong association between a high abundance of Lactobacillus species and the absence of ACRIII. From the fecal samples of rectal cancer patients who achieved complete remission without experiencing ACRIII during chemoradiotherapy, 10 novel Lactobacillus strains were isolated and characterized. Among these, Lacticaseibacillus rhamnosus DY801 exhibited a robust capacity to synthesize methionine through metB. This microbial methionine production modulated methionine metabolism in host gut lymphoid tissue inducer (Lti) cells, without diminishing the therapeutic efficacy of chemoradiotherapy. Supplementation with methionine increased intracellular levels of S-adenosylmethionine and enhanced histone H3 lysine 4 trimethylation (H3K4me3) in Lti cells. These epigenetic modifications led to the suppression of pro-inflammatory cytokines interleukin-17A (IL-17A) and interleukin-22 (IL-22), ultimately reducing ACRIII severity. Our findings suggest that specific Lactobacillus strains derived from patients with exceptional treatment responses may offer a novel therapeutic avenue for preventing or alleviating ACRIII. This microbiome-based approach holds significant potential for improving patient outcomes and enhancing the tolerability of chemoradiotherapy in colorectal cancer.

TMEM147, an ER membrane protein, is linked to lung adenocarcinoma (LUAD) but its role remains unclear. This study combines bioinformatics and experiments to explore TMEM147’s function in LUAD progression. TMEM147 expression was analyzed using TCGA/GEO data and validated in LUAD cells. Survival analysis assessed its prognostic value. GO/KEGG and ssGSEA revealed functional pathways and immune microenvironment interactions. Transcription factor binding predictions and in vitro assays (migration, invasion, proliferation) evaluated TMEM147’s role. TMEM147 was upregulated in LUAD and correlated with poor outcomes. FLI1 was predicted as a transcriptional regulator. TMEM147 influenced immune cell infiltration and was associated with ribonucleoprotein biogenesis and oxidative phosphorylation (OXPHOS) . Silencing TMEM147 reduced cancer cell migration, invasion, and proliferation, suggesting its potential as a biomarker and therapeutic target.

Background:Total neoadjuvant therapy (TNT) is recommended for locally advanced rectal cancer (LARC) with high-risk factors. The objective of this multi-center phase 2 study is to evaluate the impact of a newly designed TNT consist of TAS-102 concurrent with long-course radiotherapy followed by consolidative TAS-102 and oxaliplatin on the pathological complete response (pCR) rate in patients with LARC. Methods:Patients with LARC were to receive a newly designed TNT consisting of radiotherapy (50 Gy/25 fractions) concurrently with oral TAS-102 (35 mg/m2 given twice a day on days 1-5 during the 1st, 3rd and 5th week of radiotherapy) followed by 2 cycles of consolidation chemotherapy (oxaliplatin 85 mg/m2 on day 1 and TAS-102 35 mg/m2 twice a day on days 1-5, repeated on a 14-day cycle), with total mesorectal excision to follow within 7-11 weeks after radiotherapy completion. The primary endpoint was the pCR (ypT0 ypN0) rate. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063142. Findings:From September 1, 2022 through January 11, 2024, 50 patients were enrolled and treated; 44 (88%) received surgery. Among all 50 patients, the overall complete response rate (pCR and clinical complete response [cCR]) was 32% (95% confidence interval [CI] 20-47). Among the 44 patients who underwent surgery, the pCR rate was 32% (95% CI 19-48), exceeding the hypothesized standard pCR rate of 13%. The major pathological regression rate was 52% (95% CI 37-68), and the pathological complete lymph node regression rate was 61% (95% CI 45-76). Of the 6 patients who did not receive surgery, 2 achieved cCR followed by observation, 1 was confirmed to have high microsatellite instability and refused surgery, and 3 refused surgery for personal reasons. Grade 3 hematologic toxicity was recorded in 10 patients (20%) and grade 4 in 3 (6%), consisting largely of myelosuppression. Most patients had mild gastrointestinal toxicity; the most common grade 3 and 4 toxicity was diarrhea (14%). No patients had hand-foot skin reactions. Interpretation:We found that TAS-102 concurrent with preoperative radiotherapy led to a high pCR rate (32%) with acceptable toxicity among patients with stage Ⅱ/Ⅲ rectal cancer. Prospective randomized controlled trials comparing fluoropyrimidine-based and TAS-102-based TNT are warranted. Funding:National Natural Science Foundation of China and Shandong Provincial Natural Science Foundation.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. While immunotherapy is effective in microsatellite instability-high (MSI-H) CRC, its benefits in microsatellite-stable (MSS) CRC are limited. Radiotherapy may modify the immune microenvironment in MSS-CRC, enhancing immunotherapy efficacy, but individual responses vary. We employed MSS-CRC mouse models to examine the effects of combined radiotherapy and immunotherapy, with and without antibiotics (ABX). Various analyses, including metagenomic, nontargeted metabolomic, and gas chromatography-mass spectrometry (GC-MS), were performed to identify factors influencing treatment outcomes. Flow cytometry, immunohistochemistry and in vivo antibody blockade experiments assessed the role of metabolites and bacteria on CD8+ T cell infiltration and treatment responses, complemented by transcriptomic sequencing and molecular biology experiments. Our analyses identified propionic acid and Bacteroides fragilis (B. fragilis) as crucial factors enhancing the efficacy of combined therapies in MSS-CRC. Both propionic acid and B. fragilis improved CD8+ T cell infiltration and treatment outcomes, with molecular assays indicating that propionic acid facilitates H3K14 acetylation, activating the Meox1-Cxcr6/Ccl5 axis. This study highlights the pivotal role of the gut microbiome, specifically propionic acid and B. fragilis, in modulating the efficacy of combined radiotherapy and immunotherapy in MSS-CRC.

Acute and chronic myelosuppression occurs in up to 80% of abdomen pelvic tumor patients undergoing chemoradiotherapy, severely impacting survival outcomes and quality of life. Currently, treatments for chemotherapy-induced acute myelosuppression are limited and inadequate for prevention, highlighting the urgent need for novel preventative and therapeutic strategies. We investigated the role of gut microbiota in a 5-fluorouracil (5-FU)-induced acute myelosuppression mouse model using a four-antibiotic cocktail to disrupt the gut microbiota. Metagenomics of intestinal contents and single-strain gavage mouse models identified key gut bacteria that mitigate myelosuppression. Untargeted metabolomics of intestinal contents and a metabolite gavage mouse model revealed key bacterial metabolites that alleviate myelosuppression. Bioinformatics analysis, in vitro whole gut microbial culturing, and LC-MS confirmed that Lachnospiraceae produce the critical metabolite vanillylamine. Molecular mechanisms were explored using HE staining, flow cytometry, colony assays, RNA sequencing, Western blot, qPCR, and siRNA gene knockdown to understand how Lachnospiraceae and vanillylamine alleviate myelosuppression and accelerate ST-HSC proliferation. Our findings show that antibiotic-induced dysbiosis exacerbates 5-FU-induced myelosuppression and increases mortality in mice. Conversely, Lachnospiraceae and Akkermansiaceae significantly alleviate myelosuppression and accelerate ST-HSC proliferation. Metabolites such as vanillylamine and several indole-derived metabolites from gut bacteria also alleviate myelosuppression and promote ST-HSC proliferation. Lachnospiraceae positively correlates with vanillylamine production, and Lachnospiraceae-derived vanillylamine significantly activates the JNK pathway, accelerating ST-HSC proliferation. In conclusion, gut bacteria such as Lachnospiraceae and their metabolites like vanillylamine accelerate ST-HSC proliferation through activating the JNK pathway and alleviate chemotherapy-induced acute myelosuppression, enriching our understanding of the gut-bone marrow axis.

Immune checkpoint blockade (ICB) faces limitations owing to high cost and restricted efficacy. This study identifies SNX17 as a key mediator of ICB resistance. Elevated SNX17 correlates with poor anti-PD-1 response in humans and mice. SNX17 deletion in tumor cells inhibits tumor growth via CD8+ T cell-dependent mechanisms. SNX17 reduces uridine in the tumor microenvironment (TME), suppressing IFN-γ and upregulating PD1 in CD8+ T cells. Exogenous uridine shows antitumor efficacy comparable to anti-PD-1/PD-L1 in low-SNX17 tumors and overcomes resistance in high-SNX17 models. Uridine enhances CD8+ T cell function by promoting CD45 N-glycosylation and LCK phosphorylation. Mechanistically, SNX17 stabilizes RUNX2, promoting UPP1 transcription and uridine degradation in the TME. These findings position SNX17 as an ICB response biomarker and nominate uridine as a cost-effective immunotherapeutic strategy.

Acute radiation-induced bowel injury is a serious and inevitable adverse effect of pelvic radiotherapy, with few standardized therapies available in clinical practice. Interestingly, fecal microbiota transplantation (FMT) has been shown to be an effective therapeutic method. Among the probiotics, Lactobacillus rhamnosus GG (LGG) has the most prominent effect. However, due to its poor tolerance and viability in vitro and its potential to cause bacteremia in vivo, this study chose a natural and biosafe polymer called chitosan (CS) to act as a carrier, avoiding the aforementioned limitations of FMT. In this study, we successfully synthesized a curative probiotic biomaterial, named CS@LGG, to protect the intestinal epithelium from radiation-induced damage. It repaired the intestinal barrier with increased expression of occludin, claudin-3, and Ki-67, while decreasing γH2A.X. In addition, it enabled clearance of local and systemic pro-inflammatory factors, such as interleukin (IL)-6, IL1-β, and tumor necrosis factor alpha. Surprisingly, this biomaterial demonstrated good biosafety in vitro and in vivo, with a certain extent of tumor suppression. Furthermore, this study shed light on the possible mechanism underlying its therapeutic effect. RNA sequencing analysis indicated that overproduction of immunoglobulin A on local mucosa might be the core factor of damaged intestinal microenvironment leading to acute radiation-induced bowel injury. In conclusion, CS@LGG created in this work is a biosafe and effective new probiotic biomaterial that holds promise in the treatment and relief of acute radiation-induced bowel injury.

Supplementary Figure S2. The high-performance liquid chromatography (HPLC) of NK224.