In Traditional Chinese Medicine (TCM), earthworm (Dilong) has been used for over two millennia in clinical practice. However, most existing studies focus on individual bioactive components or specific diseases, and the broader landscape of global research on their pharmacological effects has remained largely unexplored. This study conducted a bibliometric analysis of the pharmacological and therapeutic effects of earthworms (Dilong), aiming to identify current research hotspots, emerging trends, and collaborative networks (authors, institutions, countries) in this field. Data were retrieved from the Web of Science (WoS) Core Collection and analyzed using Bibliometrix and CiteSpace. A total of 313 publications were identified for the period 1989–2024. The results showed a steady increase in the number of publications on the pharmacological and therapeutic effects of earthworms. More than 60

Accurate dose estimation following radiation accidents remains challenging, particularly when personal dosimeter data are unavailable. This study presents a practical post-accident dose reconstruction approach based on minute-rate thermoluminescent dosimeter (TLD) measurements combined with exposure scenario reconstruction, demonstrated through a wavelength-dispersive X-ray fluorescence (WD‒XRF) spectrometer accident. The exposure scenario was reconstructed by placing LiF(Mg,Cu,P) TLDs at seven representative positions corresponding to head and hand locations, with the spectrometer operated under the recorded technical parameters (40 kV, 7 mA). Minute personal dose equivalent rates, H p ′(10), were measured and combined with reconstructed retention times to calculate cumulative doses, from which skin absorbed doses were derived. The measured dose rates ranged from 0.13 to 358.38 mSv/min for the head and from 0.07 to 620.24 mSv/min for the hands. The resulting cumulative skin absorbed doses were 7.58 Gy for the head and 12.52 Gy for the hands, consistent with reported dose ranges associated with localized radiation injury. This approach provides a feasible supplementary strategy for retrospective dose reconstruction under emergency or resource-limited conditions when conventional dosimetric information is unavailable.

Objective To investigate the molecular mechanisms of early mitochondrial stress in keratinocytes induced by ionizing radiation(IR),focusing on the key role of ROMO1 in radiation-induced skin injury(RISI).Methods HaCaT keratinocytes were used to assess cellular status,mitochondrial dysfunction and oxidative stress at various time points after different irradiation doses.Mitochondrial proteomics at 24 hours post-20 Gy irradiation identified ROMO1 as the protein with the greatest reduction in expression.ROMO1-overexpressing HaCaT cells and skin-specific Romo1 knockout(Romo1-sKO)mice were established to investigate its functional mechanisms.ROMO1 expression and localization were analyzed by Western blot and immunofluorescence;flow cytometry measured ROS,mtROS,and mitochondrial membrane potential in ROMO1-overexpressing cells,while CCK-8,LDH release,and colony formation assays evaluated viability and proliferation.The role of Romo1 in the progression and repair of radiation-induced skin injury was further examined in Romo1-sKO mice.Results At 24 hours post-20 Gy irradiation,HaCaT cells exhibited inhibited proliferation(P<0.05)and mitochondrial dysfunction(P<0.000 1).Mitochondrial proteomics identified 43 differentially expressed proteins(26 upregulated,17 downregulated),with enrichment analysis indicating their involvement in oxidative phosphorylation,mitochondrial assembly and stress response.Among these,reactive oxygen species modulator 1(ROMO1)was identified as the most significantly downregulated key protein in the early radiation response(P<0.01,FDR=0.03).In vitro,ROMO1 overexpression increased mtROS levels and mitochondrial membrane potential(P<0.000 1)but suppressed cell viability and promoted reproductive death(P<0.05)after radiation.In vivo,Romo1-sKO mice showed accelerated wound healing,with a reduction in skin injury score by approximately 1 point,along with enhanced tissue regeneration at 25 days post-irradiation compared to control mice.Conclusion The mitochondrial protein ROMO1 is a key regulator of the early keratinocyte stress response to radiation.It impedes the repair of radiation-induced skin injury by suppressing cell proliferation via modulation of mitochondrial function.Targeted inhibition of ROMO1 may represent a novel therapeutic strategy to promote healing and prevent chronic progression of radiation-induced skin injury.

Objective:Ultraviolet B radiation (UVB) in sunlight is classified by the WHO as a Group 1 carcinogen. UVB is readily absorbed by the epidermis, and excessive exposure causes skin injury and photoaging. Peroxisome proliferator-activated receptor α (PPARα), a key member of the nuclear receptor family, plays a central role in lipid metabolism. This study aims to observe and investigate the effects of PPARα deletion on the progression of UVB-induced damage and changes in the skin lipid profile using PPARα-knockout (PPARα －/－) and wild-type mice. Methods:A mouse model of ultraviolet-induced skin damage was established using excessive UVB exposure (2 J/cm²) administered for a single time. C57BL/6J mice were divided into PPARα －/－ and wild-type groups. Qualitative and quantitative analyses were performed using skin photodamage scoring, hematoxylin-eosin (HE) staining, and Western blotting. A photoaging model was established using repeated low-dose UVB exposure, and the C57BL/6 mice were again divided into PPARα －/－ and wild-type groups for qualitative and quantitative analyses through HE staining and Western blotting. Skin samples collected from PPARα －/－ and wild-type mice either sham-irradiated or exposed to a single dose 2 J/cm2 UVB irradiation were subjected to lipidomic analysis. Results:In the photodamage model, PPARα －/－ mice exhibited significantly higher skin photodamage scores and delayed wound healing than wild-type controls on days 0-32 after a single excessive UVB exposure. In the photoaging model, the expression levels of senescence-associated proteins were markedly up-regulated in the skin of PPARα －/－ mice compared with wide-type mice (wild-type vs. PPARα －/－) (p16: 0.11 ± 0.02 vs. 0.82 ± 0.18, P < 0.05; p21: 0.54 ± 0.03 vs. 1.29 ± 0.07, P < 0.01; p53: 0.54 ± 0.04 vs. 1.33 ± 0.06, P < 0.01; β-galactosidase: 0.80 ± 0.06 vs. 1.20 ± 0.15, P < 0.05). In addition, PPARα －/－ mice exhibited reduced numbers of hair follicles and follicular atrophy. Lipidomic analysis revealed that PPARα deletion aggravated UVB-induced skin lipid metabolic disturbances, involving aberrant expression of multiple lipids, including Cer(d18:1/30:2), OAHFA(44:4), PE(50:1), LPC(19:1), LPS(44:11), and PC(19:1/20:1). Conclusion:PPARα plays a protective role in UVB-induced skin damage and photoaging. Its deficiency aggravates skin damage and lipid metabolic disturbances.

The widespread use of nuclear technology has increased concerns over occupational radiation exposure, while conventional physical shielding remains insufficient for protecting the skin and deeper tissues in clinical workflows. In this study, we developed a series of sunscreen-inspired radiation shielding creams by incorporating high atomic numbers (high-Z) fillers (BaSO4, Bi2O3 and Yb2O3) into an oil-in-water emulsion, forming a continuous radiation-attenuating layer on the skin that reduced radiation penetration into the skin and deeper tissues to alleviate radiation injury. By optimizing the vehicle cream's viscosity through precise aqueous phase adjustment without phase separation, we achieved higher particle loading while maintaining comfort and spreadability. The resulting radiation shielding creams demonstrated excellent adhesion, moiture retention, temperature stability, application flexibility and biocompatibility. Monte Carlo (MC) simulations predicted strong attenuation of electron radiation and low-energy X-rays by the radiation-shielding creams, while experimental results further demonstrated maximum shielding efficiencies of 90% against 90Sr radiation and 76% against X-rays. In vitro studies demonstrated significant reduction in X-ray induced cellular injury. Furthermore, in mouse models, the radiation shielding creams effectively mitigated radiation-induced mortality and skin injury in a concentration-dependent manner. Comparative analysis identified the optimal formulation, with shielding efficacy following the trend: Bi2O3 > Yb2O3 > BaSO4. This study provided a comfortable, safe and highly efficient daily radiation protection strategy, paving the way for next-generation shielding solutions tailored for occupational populations.

Radiotherapy remains a mainstream approach for cancer treatment, utilizing ionizing radiation to kill tumor cells or inhibit their proliferation. Despite its clinical success, radiotherapy inevitably causes damage to normal tissues. Therefore, protecting normal tissues and reducing radiotherapy toxicity remain pressing challenges in the field. Current radioprotective agents exhibit notable limitations, such as significant side effects, lack of targeting specificity, short biological half-lives, and low therapeutic ratios (i.e., the ratio between tumor control probability and the probability of complications in normal tissues). Biomaterials based on nano-microscale and hydrogels structures offer new solutions for developing more efficient and safer strategies for radioprotection and treatment. By providing barrier protection, targeted delivery, and precise release mechanisms, as well as intrinsic radioprotective properties, these biomaterials can significantly enhance radioprotection, reduce toxic side effects on healthy tissues. Meanwhile, these biomaterials also maintain the tumor-killing effects. These materials also show potential in addressing nuclear accidents and emergencies, thereby boosting their strategic role in public safety. This review delves into the multifaceted roles of biomaterials based on nanoparticles, micromaterials and hydrogels structures in reducing radiotherapy toxicity, analyzing their latest advances as drug delivery systems, direct application materials, and drug-cooperative carriers. Specifically, how these materials intervene in radiotherapy toxicity and radiation-induced diseases through various mechanisms is discussed, including targeted smart release, antioxidant activity, immune regulation, DNA repair, cell protection, and tissue repair. Looking forward, innovative biomaterial-based strategies for radiotoxicity reduction will continue to develop towards more efficient and personalized directions to improve the overall therapeutic outcome of radiotherapy.

Radiation-induced skin injury is a severe complication frequently encountered in nuclear accident emergencies or radiation-related occupations, necessitating the establishment of standardized, specificity-focused injury models for mechanistic research. Conventional gamma or high-energy X-rays, with strong penetrating ability, induce skin damage but inevitably trigger complex deep-tissue reactions, interfering with investigations of superficial skin effects. Given the risk of pronounced superficial tissue damage from β-radiation in scenarios such as nuclear fallout, we developed a strontium-90 (90Sr) β-rays source-based animal model of radiation-induced skin injury to address this challenge. This model leverages the physical property of β-rays, which deposit energy predominantly in superficial tissues, enabling precise simulation of localized biological effects caused by radiation material contact with the skin while avoiding the potential systemic responses triggered by deep-penetrating radiation. This study systematically outlines the entire workflow, including 90Sr radiation source parameterization, animal irradiation protocols, and pathological specimen collection and evaluation methods. This model provides a reliable animal tool for elucidating the pathophysiological mechanisms of radiation-induced skin injury and stimulating the development of mechanistic investigations or therapeutic strategies.

Radiation recall dermatitis (RRD) is a rare but severe inflammatory reaction induced by certain drugs in previously irradiated skin, which can markedly impair quality of life and disrupt cancer treatment. However, the molecular mechanisms underlying RRD remain poorly understood. In this study, a radiation recall–like dermatitis model (RRLD) was established in Sprague–Dawley rats by localized skin irradiation followed by subcutaneous administration of non-toxic concentrations of chemotherapeutic agents, including 5-fluorouracil (5-Fu, 10 µg/µL) or Epirubicin (EPI, 0.05 µg/µL), into the irradiated area. Transcriptomic and miRNA sequencing of rat skin tissues from RRLD rats identified a panel of dysregulated miRNAs, among which miR-338-3p was the most prominently upregulated and was further corroborated by elevated miR-338-3p levels in serum samples from patients with RRD. Dual-luciferase reporter assays demonstrated that pleiotrophin (PTN) is a direct target of miR-338-3p. Functional studies showed that miR-338-3p overexpression in HaCaT and WS1 cells significantly enhanced apoptotic cell death and exacerbated radiation recall–associated cellular injury, whereas miR-338-3p inhibition attenuated apoptosis and promoted cellular recovery. In vivo, pharmacological or genetic inhibition of miR-338-3p, as well as activation of PTN, significantly alleviated the severity of RRLD. Enrichment analyses indicated that miR-338-3p–mediated suppression of PTN resulted in downregulation of the PI3K/Akt/Bcl2 signaling pathway, thereby compromising pro-survival signaling cascades. Consistently, rescue experiments using an Akt activator (SC79) partially restored p-Akt and Bcl2 expression and markedly reduced apoptotic responses, supporting the functional relevance of this pathway in RRLD. Collectively, these findings indicate that miR-338-3p acts as a critical epigenetic regulator of RRLD through modulation of the PTN/PI3K/Akt/Bcl2 axis and suggest that this molecular circuit represents a promising therapeutic target for mitigating clinical radiation recall–associated skin injury.

BACKGROUND:Melanoma is an aggressive malignancy with one of the highest mortality rates among skin cancers. Radiotherapy is a common treatment modality, but radioresistance remains a significant challenge. The stimulator of interferon genes (STING) pathway has been implicated in antitumor immunity and cancer treatment, yet its role in melanoma radiosensitivity is poorly understood. OBJECTIVE:This study aimed to investigate the role of STING in enhancing the radiosensitivity of cutaneous melanoma cells and to explore the underlying mechanisms involving reactive oxygen species (ROS) and the NLRP3 inflammasome. METHODS:Using TCGA database analysis, we examined the correlation between cGAS-STING pathway expression and melanoma patient survival. In vitro experiments were conducted on A375 and B16F10 melanoma cell lines, where STING was overexpressed or activated using the STING agonist cGAMP. Cell viability, apoptosis, ROS levels, and NLRP3/ASC complex activity were assessed following radiation treatment. In vivo studies involved tumor-bearing mice treated with cGAMP and radiation to evaluate tumor growth and survival. RESULTS:High expression of cGAS and STING was associated with improved survival in melanoma patients. STING overexpression or cGAMP treatment significantly reduced cell viability, increased ROS levels, and enhanced apoptosis in irradiated melanoma cells. Mechanistically, the activation of STING elevated NLRP3/ASC complex activity, and the NLRP3 inhibitor CY-09 reversed the radiosensitization effects. In vivo, cGAMP combined with radiation suppressed tumor growth and improved survival in melanoma-bearing mice. CONCLUSION:STING enhances radiosensitivity of melanoma through ROS-NLRP3 axis, and combining STING agonists with radiotherapy may be a new strategy to overcome radioresistance.

Prophylactic cerebral irradiation (PCI) reduces the rate of brain metastasis and improves the prognosis of patients with small cell lung cancer (SCLC), but little is known about the effect of PCI on second-line chemotherapy in patients with relapsed sensitive SCLC. This retrospective cohort study included a total of 164 patients with relapsed sensitive SCLC, 20 of whom were administered temozolomide (TMZ). Categorical clinical variables were compared between subgroups with the chi-square test or Fisher's exact test, continuous clinical variables were compared with the t-test or one-way ANOVA, and the impact on overall survival (OS) was assessed using Kaplan-Meier analysis with the log-rank test. In general, TMZ prolonged the OS of patients with SCLC with brain metastasis from 12.0 to 19.0 months [P=0.0109, hazard ratio (HR): 0.4789, 95% CI: 0.2470-0.9287]. Furthermore, the administration of PCI improved the effects of TMZ on patients with SCLC with brain metastasis, with an increase in OS from 16.0 to 36.5 months (P=0.0017, HR: 3.634, 95% CI: 1.083-12.20); additionally, no difference was observed on the basis of the history of chemotherapy or state of brain metastasis. For the local response evaluation, the overall response rate reached 75.0% for both brain metastasis and extracranial lesions in the two-cycle evaluation, remained at 30.0 and 25.0% in the four-cycle and more-cycle evaluations, respectively, and was minimally influenced by the history of chemotherapy or PCI. In conclusion, the results of this study suggest that PCI may be valuable for patients with relapsed sensitive SCLC with brain metastasis who are receiving TMZ treatment, and it may also serve as an effective regimen to prevent local progression of extracranial lesions; however, more evidence is needed.

Background:Radiation-induced skin injury (RISI) is a common complication of radiotherapy, affecting up to 95% of cancer patients. It manifests as acute erythema and ulceration or chronic fibrosis and telangiectasia, severely compromising patients' quality of life. The pathogenesis of RISI involves oxidative stress, inflammation, DNA damage, and cellular senescence. However, current treatments are largely supportive and fail to address underlying mechanisms. Berberine (BBR), a natural isoquinoline alkaloid, exhibits anti-inflammatory, antioxidant, and wound-healing properties, making it a promising candidate for managing RISI. Methods:Single-cell RNA sequencing and proteomic analyses were employed to characterize the molecular and cellular changes in patient, rats and cells exposed to ionizing radiation. Differentially expressed genes (DEGs) and proteins were identified, and functional enrichment analyses were performed. Key senescence markers were validated using molecular docking and in vitro assays. The therapeutic effect of BBR was validated in skin cells and in mouse models of radiation-induced skin injury, focusing on wound healing and systemic health. Results:Transcriptomic analysis identified 217 DEGs in RISI, highlighting pathways such as TNF, p53, and NF-kappa B signaling. Key senescence markers, including CDKN1A, IGFBP7, and CTSL, were overexpressed, correlating with impaired wound healing. Proteomic analysis revealed that BBR modulated 684 proteins, enhancing keratinocyte migration and reducing oxidative damage. BBR treatment promoted the proliferation and migration of skin cells, alleviated radiation-induced cellular senescence, and downregulated inflammatory pathways including p53, ROS, and JAK-STAT. BBR-treated mice exhibited significantly reduced skin injury scores, improved body weight retention, and enhanced wound healing. Conclusion:Radiation injury leads to persistent senescence, inflammation, and impaired wound healing in skin tissues. CDKN1A, IGFBP7, and CTSL are core senescence markers in RISI. By downregulating the expression of senescence markers and suppressing inflammatory pathways (including p53, ROS, and JAK-STAT), BBR accelerates radiation-induced wound healing, offering a novel therapeutic strategy for managing RISI.

We present a nitrogen-targeting Proton-Carbon-Alpha-Therapy method, abbreviated as Proton-CAT. It produces carbon ions ( C-12) and alpha particles through nuclear reactions between protons and nitrogen-15 ( 15N), thus incorporating the benefits of carbon ion therapy into conventional proton therapy. Monte Carlo simulations validated the effectiveness of Proton-CAT, and the study specifically focused on the distribution of relative energy deposition. The results indicated that the presence of N-15 enhanced the maximum dose level of protons, resulting in more effective damage confined to tumor cells. Statistical analysis of secondary ions has shown that the Proton-CAT significantly increases the production efficiencies of C-12 and alpha particles. Furthermore, it has been revealed that elevating the N-15 concentration significantly boosts the dose of C-12 and alpha particles within the tumor region. The present work would contribute to the future development of proton therapy.

Genotoxic therapies such as ionizing radiation eliminate cancer cells by inducing extensive DNA damage but often cause normal tissue toxicity, including cutaneous injury. Extrachromosomal circular DNA (eccDNA) refers to circular DNA fragments outside the chromosomal context, with their formation and persistence linked to DNA damage repair and genomic instability. Despite growing recognition of eccDNA in oncogenesis, its role under genotoxic stress in normal tissues remains poorly understood. Here, eccDNA is profiled in irradiated rat skin using Circle-seq, identifying alterations in eccDNA number and composition. Specifically, radiation induced circle17:44148731-48208624, in which vacuolar protein sorting 41 homolog (VPS41) is the sole radiation-induced amplification gene by semiquantitative PCR and gel electrophoresis. The findings show that eccDNA or VPS41 overexpression reduces radiation-induced skin injury (RISI) in vitro and in vivo. Proteomic and interaction analyses identified metastasis suppressor kangai-1 (KAI1) as a VPS41-interacting partner. Notably, VPS41 overexpression promotes KAI1 lysosomal degradation, protecting against radiation-induced apoptotic cell death. Peptide array analysis pinpoints the VPS41-KAI1 interaction through the K263 residue, consistent with AlphaFold prediction. The findings uncover a novel mechanism in which radiation-induced eccDNA, specifically VPS41, mitigates skin injury by modulating KAI1 degradation. This study highlights the role of eccDNA in cellular defense, providing strategies to enhance tissue resilience to genotoxic stress.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, associated with chronic low-grade inflammation and metabolic disorders. The exact pathogenesis of PCOS remains unclear. Adropin, a secreted protein encoded by the energy homeostasis gene (Enho), has immunometabolic regulatory functions. In the present study, the serum levels of adropin were significantly lower (P < 0.001) in PCOS mice than controls, and adropin deficiency exacerbated the obesity and inflammatory phenotypes in letrozole (LTZ)induced PCOS mice. In vitro experiments, it has shown that adropin mediated the phenotypic change of RAW264.7 macrophages to M2 through upregulation of heme oxygenase-1 (HO-1), and then adropin-treated macrophage-conditioned medium (Adr-CM) induced browning of fully differentiated 3T3-L1 adipocytes. Finally, vivo experiments by injecting adropin into PCOS model mice showed that adropin treatment significantly reduced body weight, and promoted macrophage M2 anti-inflammatory phenotypic transformation and browning of white adipose tissue. In summary, the present study reveals a novel mechanism by which adropin indirectly promotes adipose tissue browning by regulating macrophage polarisation, which provides a new perspective and experimental basis for the therapeutic strategy of PCOS and its related metabolic disorders.

Keloids are benign dermal tumors that arise from abnormal wound healing processes following skin lesions. Keloids are present in all human populations but occur most frequently in Africans. A significantly higher incidence is observed in female populations. Consequently, keloid patients not only endure physical burdens caused by symptoms such as pain, pruritus, and burning, but also suffer from psychological distress due to altered appearance, significantly compromising their quality of life. Surgical excision, as one of the various treatment options, demonstrates rapid efficacy but carries an unacceptably high recurrence rate of 40–100 % when used as a standalone therapy. Postoperative radiotherapy (PORT) is a clinically effective measure to reduce recurrence rates of keloid. Nevertheless, studies comparing the effectiveness and underlying mechanisms of distinct radiotherapy modalities for keloid remain absent in the literature. In our study, we performed single-cell RNA sequencing (scRNA-Seq) of primary keloid fibroblasts treated with three kinds of radiotherapy modalities, and unbiased clustering revealed the identification of seven distinct clusters. Among them, the cell proportions of Fib2-CCND1high, Fib3-IGFBP7high and Fib 4-APCDD1high increased significantly in the X-ray group, electron beam group and both 90Sr groups, which are involved in microtubule-associated complex, extracellular matrix organization and oxidative phosphorylation, respectively. In addition, the bioinformatics analysis highlighted the alteration of immune-associated interactions, such as PVR-TNFSF9 and TNFSF9-IL13RA2, and provided a basis for the activation of interferon regulatory factor 1 (IRF1) in all radiotherapy modalities. Then, functional analysis revealed that Ad-IRF1 and pharmacological activation of IRF1 (ATRA and 9-cis-RA) significantly induced apoptosis and suppressed cell viability. Mechanistically, reciprocal regulation between the single-stranded DNA sensors SSBP1 and IRF1 was revealed. Thus, this study illustrates the molecular alterations and driving transcription factors following various radiotherapy modalities at the single-cell resolution. Notably, IRF1 is regulated by SSBP1 and identified as a novel therapeutic target for keloid.

Cancer remains one of the leading health threats globally, with therapeutic resistance being a long-standing challenge across chemotherapy, radiotherapy, targeted therapy, and immunotherapy. In recent years, the association between epigenetic modification abnormalities and therapeutic resistance in tumors has garnered widespread attention, spurring interest in the development of approaches to target epigenetic factors. In this review, we explore the widespread dysregulation and crosstalk of various types of epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNA changes, which interact through complex regulatory networks in tumors. Clinically, single-targeted therapy based on epigenetic modification usually has its limited effect against cancer. However, the combination of epigenetic drugs with other treatment modalities, such as chemotherapy, targeted therapy, or immunotherapy, shows potential for synergistically enhancing efficacy and reducing drug resistance. Therefore, we evaluate the possibility and potential mechanisms of targeting epigenetic modifications to overcome resistance in cancer therapy, and discuss the challenges and opportunities in moving epigenetic therapy into clinical practice. Moreover, the application of multi-omics technologies will aid in identifying core epigenetic factors from complex epigenetic networks, enabling precision treatment and overcoming therapeutic resistance in tumors. Furthermore, the development of spatial multi-omics technologies, by providing spatial coordinates of cellular and molecular heterogeneity, revolutionizes our understanding of the tumor microenvironment, offering new perspectives for precision therapy. In summary, the combined application of epigenetic therapies and the integration of multi-omics technologies herald a new direction for cancer treatment, holding the potential to achieve more effective personalized treatment strategies.

The radiolysis of water molecules by ionizing radiation leads to the production of various reactive species, which play a critical role in the indirect killing of cancer cells. In radiotherapy (RT) techniques involving nuclear reactions, both radiolysis-induced radical generation and nuclear reaction processes are present within the irradiated environment. However, the interaction between these two mechanisms remains poorly understood, limiting further optimization of RT. In this work, the effect of the 15N(p, alpha) 12C reaction on the kinetic energy release of water fragmentation and on the kinetic energy (KE) of the generated radicals is investigated using a point-charge model. It is found that the charge state q and flight velocity v of the nuclear reaction products are the primary influencing factors. Additionally, lighter and more distant radicals produced by the nuclear reaction are observed to obtain higher KEs. These radicals may influence the local spatial distribution of reactive species and their interaction with nearby biomolecules. A feasibility analysis indicates that such effects can be experimentally measured using a cold target recoil ion momentum spectroscopy. The primary motivation of this study is to provide atomic-and molecular-level insights into how nuclear reactions influence water fragmentation in RT, laying a foundation for future experimental and biological investigations.

The widespread application of nuclear technology has markedly heightened the risk of extensive, uncontrolled exposure to radiation. Nevertheless, in contrast to external irradiation, the biological impacts and countermeasures against internal irradiation from radionuclides remain inadequately characterized. Mice were administered yttrium-90 (Y90) carbon microspheres via gavage at different dosages (0–5.0 mCi) to establish a radionuclides exposure model. A multi-omics analysis was employed to access alterations in gut microbiota, fecal and colonic metabolites profiles, and intestinal mRNA expression post-irradiation. The function of significant metabolite was validated at both cellular levels and organismal levels. Additionally, ChIP-Seq and RNA-Seq techniques were utilized to investigate the molecular mechanism underlying the actions of key metabolite. Exposure to Y90 resulted in intestinal damage and hematological impairment. Multi-omics analysis revealed significant alternations of gut microbiota, fecal metabolites, colonic metabolites, and intestinal mRNA expression following internal radiation exposure. Notably, L-citrulline was identified as a metabolite with changes observed in both fecal and colonic tissues, demonstrating radioprotective properties in vitro and in vivo. Mechanistically, L-citrulline facilitated the citrullination of histone H3 at the 17th site (H3Cit17), and multiple mRNAs including C-X-C motif chemokine ligand 3 (Cxcl3), were transcriptionally regulated by H3Cit17 post L-citrulline treatment. Furthermore, Cxcl3 conferred protective effects for intestinal epithelial cells against ionizing radiation. The research offers critical perspectives on the intestinal and gut microbiota’s reaction to radionuclides exposure. It underscores the promise of L-citrulline as a radioprotective compound, which may have substantial ramifications for the formulation of strategies to mitigate radiation exposure.