The aim was to study the inhibitory effect of berberine (BBR) on intestinal senescence induced by radiation and explore its mechanism. Male C57BL/6J mice and SD rats were randomly divided into three groups: Control, irradiation (IR), and IR + BBR. Except for the normal control group, which received sham irradiation, the other two groups were subjected to abdominal X-ray irradiation (12Gy for mice and 15Gy for rats). Mesenteric blood flow was detected using laser speckle blood flow contrast imaging. Senescence markers were evaluated using RT-qPCR, Western blot analysis, and SA-β-Gal staining. 16S rRNA sequencing technology was used to study the changes in the intestinal microbiota. MRI was used to evaluate the efficacy of BBR on intestinal injury. Our results showed that BBR can alleviate radiation-induced DNA damage and senescence in mouse intestines, mitigate both acute and chronic radiation-induced intestinal damage, and is accompanied by an improvement in intestinal flora imbalance. In addition, BBR enhances the survival and proliferative capacity of irradiated intestinal epithelial cells, inhibits radiation-induced cellular senescence and SASP in vitro, and prevents cells from entering senescence. The underlying mechanism may involve the activation of the Nrf2-related pathway. Our findings suggest that BBR can effectively alleviate the intestinal cellular senescence caused by radiation, concomitant with the remodeling of gut microbiota, which provides potential implications for using BBR as a drug against radiation-induced intestinal injury.

The development of compounds triggering intestinal stem cells (ISCs) proliferation represents a promising strategy to alleviate irradiation (IR)-induced gastrointestinal syndrome. Here, cannabidiol (CBD)-a nonpsychotomimetic phytocannabinoid derived from the Cannabis sativa plant-was found to dramatically improve body weight loss of mice and stimulate Lgr5+ ISCs proliferation upon a lethal dose of IR. Using absolute quantitative lipidomics, we found that the dysregulation of fatty acids in crypts induced by IR was rescued by CBD, which was indispensable for ISCs regeneration. Integrative analysis of transcriptome and lipidomics unveiled the critical role of PPARα in regulating fatty acid β-oxidation (FAO) by transcriptionally upregulating Slc27a2 and Acox1. Further experiments showed that CBD could trigger the enrichment of Stat2 on the promoter region of Pparα, ultimately facilitating the FAO program and subsequent ISCs proliferation following IR exposure. In addition,THOC3 was identified as a direct target of CBD, which stabilized the THOC3 protein and substantially alleviated the IR-induced blockade of Stat2 mRNA nuclear export. This study reveals a connection between CBD-driven ISCs proliferation and the FAO program during IR damage, providing a promising avenue for IR-induced gastrointestinal syndrome treatment. The binding of CBD to THOC3 maintains its radiation stability, which then supports the nuclear export of Stat2 mRNA for the subsequent transactivation of Pparα. The upregulation of PPARα will ultimately stimulate the FAO program, thereby facilitating ISCs regeneration during IR exposure.

The OH+ (X3Σ-) radical cation has been investigated by combining a 4 K 22-pole ion trap apparatus with high-resolution IR and THz radiation sources. Applying different types of action spectroscopic methods, the fundamental vibrational band in the 3 µm range and the spin manifold of the N = 1 ← 0 rotational transition around 1 THz have been extended and refined. Additionally, the spin manifold of the N = 2 ← 1 rotational transition, scattered around 2 THz, has been measured for the first time with microwave accuracy. Although all hyperfine components of the pure rotational transitions are affected by considerable Zeeman splittings, a simulation of their contours allowed us to extract the field-free center frequencies with high accuracy. A global fit combining rovibrational and pure rotational transitions from the literature with those newly obtained in this work was performed, leading to improvements in the spectroscopic constants of OH+, particularly those in the ground vibrational state.

The synergistic suppressive effects of the radioimmunotherapy-induced abscopal effect on distant non-irradiated tumors have recently emerged as a research hotspot. However, studies on its specific regulatory role in adjacent sentinel lymph nodes (SLNs) remain limited. The deep location and small size of SLNs hinder the monitoring of treatment-related changes, underscoring the need for lymphography-based approaches. In this study, we aimed to evaluate the abscopal-like effect of radioimmunotherapy on SLNs in an H22 hepatocellular carcinoma mouse model via dynamic lymphography. H22 murine hepatocarcinoma cells were transplanted into the right hind foot sole of C57BL/6 mice. Fourteen days post-inoculation, mice with SLNs were selected and divided into six groups: control, isotype control Ig, anti-PD-1 alone, irradiation (IR) alone, irradiation + isotype control Ig, and IR + anti-PD-1. The volume and weights of tumors and non-irradiated SLNs were measured. The SLNs were imaged with ¹⁸F-fluorodeoxyglucose (18F-FDG) dynamic lymphography at 14, 21, and 28 days post-inoculation. CD8 immunohistochemistry assays were performed to assess CD8+ T cell infiltration. In this mouse model, the IR + anti-PD-1 combination treatment exerted a marked suppressive effect on the growth of both irradiated tumors and non-irradiated SLNs, demonstrating a robust enhancement of the abscopal-like effect compared with the monotherapy groups. Mechanistic investigations demonstrated elevated CD8⁺ T cell infiltration in non-irradiated SLNs, suggesting that enhanced systemic anti-tumor immunity mediated the effect. Dynamic ¹⁸F-FDG PET lymphography enabled clear visualization of SLNs as early as 30s post-injection, with sustained imaging clarity for over 30min. This method also demonstrated decreased radioactive accumulation in irradiated tumors and non-irradiated SLNs, confirming an enhanced abscopal-like effect with the IR and anti-PD-1 combination approach. Our data demonstrate that the regression of SLNs adjacent to the irradiation field, mediated by the abscopal-like effect of radioimmunotherapy, can be sensitively and effectively tracked via dynamic 18F-FDG lymphography. Furthermore, our findings provide an effective and straightforward lymphographic approach with substantial translational potential for assessing the efficacy of the radioimmunotherapeutic abscopal-like effect against SLNs.

Pressure broadening is commonly observed in the infrared spectrum of gases in the presence of a foreign species. This phenomenon produces a deviation from the Bouguer-Beer-Lambert (BBL) law preventing quantitative analysis. The aim of the present study is to measure its effect over the IR spectra of CH4/CO2 binary gas mixtures at ambient temperature up to 10 bar in the mid and near-infrared frequency ranges and use the enhanced IR signals to quantify the gas pair interdiffusion. The composition is accurately tuned with calibrated thermal mass flow controllers. The infrared absorbance of methane in the range [3025, 3300] cm-1 and of carbon dioxide at 3626 cm-1 is correlated with the molar concentration of each component to elucidate the effect of pressure and composition. The data are described with polynomial functions, and the coefficients' dependence on the gas composition is unveiled. We consider that collision-induced absorption and local field effects produce the absorbance enhancement and show how this phenomenon can be exploited in the analytical technique. The binary gas diffusion of CH4/CO2 at ~1 bar and 298.45 or 308.15 K is successfully investigated with the same IR signals within a closed system: for methane, the absorbance is appropriately corrected accounting for equimolar counter diffusion as a constraint; for carbon dioxide, the absorbance varies linearly with the concentration so that no correction is needed. Homonuclear foreign species transparent to IR radiation can also be indirectly analyzed if the broadening effect is appropriately described, as reported in this article.

Inflammatory injury to the intestine triggers a reprogramming of the intestinal epithelium to a fetal-like state that drives rapid restoration of the epithelial barrier. Although the intestinal microbiota is a key modulator of inflammation, its role in influencing epithelial fetal-like stem cell reprogramming and consequent restitution remains unclear. Using irradiation (IR) injury as a model for small intestinal epithelium injury and repair, we found that the intestinal microbiota accelerated epithelial restitution by amplifying a repair-associated inflammatory response that promoted the emergence of fetal-like intestinal epithelial cells (IECs), marked by Ly6a and Clu. NOD2, the strongest genetic link to the development of Crohn's disease, was found to be expressed in fetal-like IECs following injury. Employing an ileal organoid model, we demonstrated that NOD2 activation by its peptidoglycan ligand potentiated an inflammatory gene signature characterized by interferon signaling, concurrent with enterocyte recovery. NOD2 deficiency exacerbated epithelial apoptosis following IR injury, whereas epithelial-specific NOD2 signaling promoted fetal-like IEC emergence and increased epithelial proliferation. Collectively, these findings reveal a pivotal role for the microbiota and NOD2-mediated microbial sensing in regulating fetal-like IEC fate after injury, thus contributing to the protective function of this microbial sensor during intestinal inflammation.

Functional impairment of T and NK cells following irradiation (IR) undermine anti-tumor immune responses. This study aimed to investigate the characteristics of T-cell and NK-cell reconstitution in mice following low-dose radiation-induced injury and the restorative effects of Rehmanniae Radix Praeparata (RRP). At various time points post-IR, splenic/thymic indices, complete blood count and CD3+ T, CD4+ T, CD8+ T and NK cells, as well as CD80, CD86, MHC-I and MHC-II were assessed. Type 1T helper (Th1), Type 1 cytotoxic (Tc1), Type 1 NK (NK1), regulatory T (Treg) and Th17 cells along with IL-12, IL-15, T-bet and foxP3 were also evaluated with or without RRP treatment. Additionally, a B16 melanoma lung metastasis model in irradiated mice was used to confirm the restorative effects of RRP. CD3+, CD4+, CD8+ T and NK cells decreased significantly on Days 4 to 6 and largely recovered by Days 9 to 11 post-IR. The expression of CD80, CD86 and MHC-II reduced on Day 6 and recovered by Day 11. However, interferon (IFN)-γ production by Th1, Tc1 and NK1 cells remained lower, whereas Tregs were elevated. RRP effectively enhanced IFN-γ production from Th1, Tc1 and NK1 cells and suppressed Tregs by increasing T-bet and decreasing foxP3 expression, thereby significantly reduced the tumor burden. These findings suggest that T-Cell and NK-Cell-mediated inefficient reconstitution following IR was characterized by an decrease of Th1, Tc1 and NK1 cells and an increase of Tregs, RRP effectively promoted the functional reconstitution of T-cell and NK-cell subsets, thereby enhancing anti-tumor immunity after IR.

PGK1/PHGDH axis drives radioresistance in glioblastoma stem cells.

The possibility of obtaining information on the increase in disturbance of geomaterials caused by the intensification of deformation processes occurring in them is investigated by variations in the intensity of concomitant IR radiation. The results of experiments on the registration of thermal radiation from the surface of rock salt samples under conditions of uniaxial compression close to the limit conditions of periodic loading are presented. The qualitative identity of the recordings of mechanical parameters and variations of IR radiation characterizing changes in the stress–strain state of the tested rock samples is shown. It has been established that the recorded changes in the angle of inclination of the dependences of the intensity of thermal radiation from the surface of rock salt samples on longitudinal deformation in areas of load growth under high–amplitude periodic exposure are similar to changes in the values of the deformation modulus E, calculated in the same way in the corresponding sections of the stress-strain diagrams. It is concluded that it is possible to use the results of non-contact thermoradiometric measurements, namely, data on changes in the angle of inclination of these curves as an indicator of the degree of disturbance of geomaterials.

Aqueous microdroplets have fascinated scientists with unique properties that deviate from bulk solutions. Understanding microdroplet chemistry has been limited by few spectroscopic measurements on single well-defined microdroplets. Here we present a new technique to record an IR spectrum of a single droplet called Single Droplet Displacement Infrared Action Spectroscopy (SiDDIRAS) with potential broad applications in physical, analytical, and environmental chemistry. The droplet was trapped in a linear quadrupole electrodynamic balance. When IR radiation at resonant frequency was introduced, mass loss from IR-induced evaporation caused the droplet to displace upwards. Mapping the displacement as a function of IR frequency yields an IR spectrum of a single microdroplet. As a demonstration, the SiDDIRA spectrum of an ~8 µm droplet containing NaCl and NaN3 shows that the azide asymmetric stretch blueshifts by 5 cm-1 relative to bulk with significant peak broadening, evidence that this droplet is supersaturated with salts compared to bulk solutions.

Abstract Flux variability is a fundamental channel of information from Sgr A* because of its direct probe of processes occurring within an accretion disk under strong gravity. We present simultaneous JWST, NuSTAR, and Very Large Array observations of Sgr A* on 2024 April 5. We report the detection of a strong X-ray flare with a duration of about 40 minutes and a luminosity of 5.2 × 10 35 erg s −1 coincident with a bright near-IR (NIR) flare, and a brightening in radio about an hour later. We investigate the candidate physical mechanisms for the X-ray flare emission and conclude that this can best be explained by inverse Compton scattering of NIR flare radiation. We propose a dynamic scenario analogous to a coronal mass ejection in which a magnetic flux rope is ejected from Sgr A*’s inner accretion flow with a current sheet extending down from the rope to the bulk of the accretion flow. The accelerated electrons are continually ejected from the reconnection X-point with a bulk flow at the Alfvén speed of 0.7 c . IR radiation from the approaching energetic electrons is enhanced by beaming and upscattered by thermal electrons in the accretion flow to produce the strong X-ray flare. Meanwhile, the relativistic electrons moving in the opposite direction away from the disk experience weaker magnetic fields and so radiate at longer wavelengths. They feed into the magnetic flux tube explaining the detected delayed radio emission. This physical picture attempts to unify the origin of the variable emission from Sgr A* at IR, X-ray, and radio/submillimeter wavelengths.

Abstract. We investigate the response of space weather events on Earth's upper atmosphere over the polar regions by studying their effect on the drag of the CHAMP and GRACE satellites. Increasing solar activity that results in heating and the expansion of the upper atmosphere threatens low Earth orbit (LEO) satellites. Auroral events are closely related to the stellar energy deposition of solar EUV radiation and precipitating energetic electrons, which influence photochemical processes such as the production of nitric oxide (NO) in the upper atmosphere. To study the production of NO molecules and their influence on the thermospheric structure and satellite drag, we first model Earth's background thermosphere structure with the 1D upper atmosphere model Kompot by considering the incident X-ray, EUV, and IR radiation during selected space weather events. For investigating the effect of electron precipitation in the production of NO molecules in the polar thermosphere, we apply a Monte Carlo model that takes into account the stochastic nature of collisional scattering of auroral electrons in collisions with the surrounding N2-O2 atmosphere, including the production of suprathermal N atoms. The observed effect of the atmospheric drag on the CHAMP and GRACE spacecraft during the two studied events indicates that a sporadic enhancement of NO molecule production in the polar thermosphere and its IR-cooling capability, which counteracts thermospheric expansion and can lead to an “overcooling” with decreased density after the space weather event, can have a protective effect on LEO satellites. Their production efficiency, however, is highly dependent on the energy flux of the precipitating electrons. Our results have direct implications for empirical satellite orbit prediction models, as our simulations highlight the need to consider precipitation-induced NO production to improve the predictive power of these models.

Hematopoietic stem cells (HSCs) are responsible for replenishing blood cells under stress conditions through increasing proliferation and differentiation. After the hematopoietic function has reconstructed, HSCs must re-enter a quiescent state to avoid their depletion, whereas the underlying mechanisms remain to be elucidated. Here, we show that the translocation of nuclear receptor coactivator 2 (NCOA2) into the nucleus is gradually increased in HSCs during the hematopoietic recovery phase after sub-lethal dose irradiation (IR). Although deletion of NCOA2 only slightly affects the steady state hematopoiesis, its deficiency leads to HSC pool exhaustion and delayed hematopoietic recovery after exposure to IR. Further investigations reveal that loss of NCOA2 decreases the quiescence, survival, and long-term reconstituting ability of HSCs following IR due to increased mitochondria-derived oxidative stress. Mechanistically, NCOA2 promotes the clearance of activated or damaged mitochondria by coactivating FOXO3a-dependent transcription of PINK1, which drives HSCs to return to quiescence after being activated by IR stress. Collectively, our findings demonstrate a critical role of NCOA2 in facilitating the restoration of HSC homeostasis after IR via the FOXO3a-PINK1-mediated mitophagy axis and thus provide an additional strategy to prevent hematopoietic failure induced by IR.

Colored and colored-infrared (IR) hybrid laser technologies have recently gained attention as promising alternatives to conventional IR sources for welding highly reflective metals such as aluminum and copper. These emerging technologies are particularly relevant to electric-vehicle battery manufacturing, power-electronic packaging, and high-precision joining of conductive materials, where conventional IR lasers often face absorption and stability limitations. This review summarizes developments in blue (450 nm), green (515-532 nm), and colored-IR hybrid systems, focusing on their welding characteristics and absorption behavior. Blue and green lasers exhibit improved energy coupling, enabling deeper penetration and wider bead formation at reduced power levels, whereas IR lasers often suffer from unstable keyhole behavior and spatter formation that degrade weld quality. Hybrid systems have shown additional benefits in stabilizing keyhole formation by preheating the surface with visible light and maintaining deep penetration with IR radiation. Influence of differences in energy density, beam size, emission mode (pulsed vs. continuous wave), and experimental setup were also discussed in relation to their impact on welding behavior, aiming to clarify why colored lasers exhibit superior performance over IR lasers for highly reflective materials. Although existing studies remain limited in providing quantitative comparisons, this review was intended to enhance understanding of the underlying mechanisms and to offer insights for optimizing future laser welding processes.

To further explore relative biological effectiveness (RBE) variability, the RBE of different intracerebral cells at various irradiation (IR) dosages and time were determined in this study. A total of 120 rabbits were randomly divided into proton groups (0, 10, 20, 30, 40 Gy, RBE) (n = 3) and photon groups (0, 10, 20, 30, 40 Gy) (n = 3). The rabbits were sacrificed at 2, 4, 6, 8 weeks after brain IR. Neuronal survival, identified via Hematoxylin and Eosin (H&E) staining, and immunohistochemical detection of neurofilament (NF), Olig2, and CD68 in the hippocampus and thalamus, were analyzed. Dose- and time-dependent RBE curves were fitted using the LQ model. Proton IR showed higher neuronal survival at 4-, 6-, and 8-weeks post 10 Gy, 20 Gy, 30 Gy IR (p < 0.05) compared to photon IR. Oligodendrocyte populations in photon group at 4-, 6-, and 8-weeks post 10 Gy IR and 6-, 8-weeks post 20 Gy were consistently higher than proton subgroups (p < 0.05). While proton IR showed higher microglial activation which was observed only at 4-weeks post 30y IR. Proton RBE for neurons and oligodendrocytes remained below 1.1 but exceeded 1.1 for microglial activation. These findings demonstrate the dose- and time- dependent nature of proton RBE and suggest brain tissue tolerates higher proton IR doses compared to photon IR, which fully confirmed the biological advantages of proton IR. These will help clinicians more precisely set the organ limit at risk and tailor radiotherapy plans.

Stereotactic arrhythmia radiotherapy (STAR) is emerging as a highly effective treatment for ventricular tachycardia (VT). Growing evidence indicates that STAR favorably reprograms the electrical substrate by speeding conduction and/or prolonging repolarization via modulation of ion channel expression, although the mechanisms by which single-fraction radiation mediates durable changes in gene expression are incompletely understood. Here, we identify dynamic changes in the cardiomyocyte epigenome and transcriptome after irradiation (IR) in vivo and in vitro, including durably increased expression and chromatin accessibility of Scn5a (encodes the α subunit of the sodium channel, NaV1.5), demonstrating a role for epigenetic memory in conduction velocity (CV) increases observed after STAR. Transcriptomic and epigenetic sequencing further identified dynamic changes in gene expression and regulatory regions involved in cellular repolarization, calcium handling, and metabolism after IR. These changes were mirrored by dose-dependent and cell-autonomous changes in repolarization, calcium flux, and mitochondrial respiration, highlighting important cellular processes that may mediate the therapeutic effects of STAR. Overall, we found that cardiomyocytes exposed to a single fraction of high-dose IR exhibited epigenetic reprogramming that mediated broad and dynamic physiologic responses.

With the evolution of dietary habits and the widespread application of radiation therapy, high-salt diet (HSD) and irradiation (IR) have become significant public health concerns. This study aims to investigate the protective effects of melatonin (MLT) against multi-organ damage induced by HSD combined with whole-abdominal irradiation (WAI), with a focus on its gender-specific mechanisms. Using a C57BL/6 J mouse model of HSD and IR injury, we employed a multi-omics approach to evaluate MLT's therapeutic effects. Results demonstrated that both oral and intraperitoneal administration of MLT significantly mitigated HSD and WAI-induced damage to renal and intestinal tissues while restoring expression of intestinal tight junction proteins and mucin-2 (MUC2), which is the main intestinal mucin forming the mucus barrier. Further investigations revealed that MLT showed sex-dependent associations with the gut microbiota-metabolite axis. Under HSD conditions, it primarily regulates microbial balance via the tryptophan metabolic pathway, whereas post-IR exposure, its regulation shifts toward specific metabolites. Additionally, MLT alleviates cognitive impairment. These findings provide crucial experimental evidence for developing personalized radiation protection strategies.

ObjectiveThis study investigates the protective effects of citraconic acid (CA) on radiation-induced intestinal injury (RIII) and elucidates its relationship with the interleukin-17 (IL-17) signaling pathway.MethodsA mouse model of whole-abdominal irradiation (IR) was established, and CA (10, 20, 40 mg/kg) was administered intraperitoneally as an intervention. Assessments included body weight, Disease Activity Index (DAI), and colon length measurements. Serum and tissue inflammatory markers were quantified using enzyme-linked immunosorbent assay. Histological analysis was performed using Hematoxylin and Eosin (HE) staining, Ki67 and Lgr5 immunohistochemistry, Alcian Blue-Periodic Acid-Schiff (AB-PAS) staining, and immunofluorescence for Zonula Occludens-1 (ZO-1) and Occludin. Transcriptomic sequencing with functional enrichment analyses was conducted, followed by Western blot validation of IL-17 A, CCL7, CXCL2, and MMP13 protein expression. IL-17 inhibitor experiments were performed to validate the causal relationship.ResultsCA administration attenuated body weight loss and reduced DAI scores in a dose-dependent manner while preserving colon length. CA treatment suppressed the elevation of IL-6 and TNF-α levels induced by irradiation. Furthermore, CA enhanced the abundance of Ki67-positive and Lgr5-positive cells, increased goblet cell numbers and mucus secretion, and restored the expression of tight junction proteins ZO-1 and Occludin, thereby improving histological damage. Transcriptomic analysis revealed significant enrichment of IL-17 signaling pathways associated with regeneration and inflammation. Protein levels of IL-17 A, CCL7, CXCL2, and MMP13 were upregulated following CA treatment. Importantly, IL-17 inhibition abolished the protective effects of CA, confirming the dependence on IL-17 signaling.ConclusionCA exerts protective effects against radiation-induced intestinal injury by modulating the IL-17-related signaling network, thereby promoting intestinal epithelial regeneration and barrier repair. These findings suggest that CA may represent a potential metabolic intervention strategy for the prevention and treatment of radiation-induced gastrointestinal damage.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s12876-026-04689-6.

Carcinoma (PTC) is the most common malignant tumor derived from thyroid follicular cells and represents the most common pathological type of thyroid malignancy. Cancer metastasis and radiosensitivity are important factors that limit the treatment of PTC. This study aimed to investigate the regulatory effects of transient receptor potential channel C5 (TrpC5) on the proliferation, invasion, migration, and radiosensitivity of PTC. Human papillary thyroid carcinoma cell lines TPC-1 and B-CPAP were transfected with TrpC5 siRNA, pcDNA-TrpC5, or their corresponding negative control. PTC cells were stimulated by radiotherapy. The results showed that TrpC5 silencing weakened the proliferation, invasion, and migration of PTC cells, whereas TrpC5 overexpression promoted these cellular behaviors. Moreover, TrpC5 expression was progressively upregulated in PTC cells following exposure to irradiation (IR). TrpC5 silencing enhanced radiosensitivity of TPC-1 and B-CPAP cells. In addition, TrpC5 silencing enhanced the expression of DNA damage-related proteins p-ATM, p-CHK, and γH2AX in PTC cells under IR treatment. Overall, TrpC5 silencing weakened cell invasion and migration and enhanced the radiosensitivity of PTC cells. These findings suggest that TrpC5 may serve as a potential therapeutic target for PTC and warrant further investigation in vivo.

BackgroundTo date, no robust, non-invasive biomarker for breast cancer (BC) diagnosis has been identified. The study aimed to develop a circulating microRNA (miRNA or miR)-based diagnostic model and explore potential mechanisms of miRNA regulating DNA damage sensitivity.MethodsA differential analysis was performed on The Cancer Gene Atlas (TCGA)-Breast Invasive Carcinoma (BRCA) and Gene Expression Omnibus (GEO) datasets. Three machine-learning algorithms were employed to screen key circulating miRNAs. The serum miRNA levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). The effect of miR-139-3p on sensitivity to DNA damage and the underlying mechanisms were investigated in vivo and in vitro.ResultsOur diagnostic model was based on the identification of four miRNAs (i.e., miR-139-3p, miR-134-3p, miR-629-3p, and miR-191-3p). The model achieved high diagnostic performance in two external datasets and a clinical cohort, which had area under the curve (AUC) values of 0.952, 0.847, and 0.869, respectively. The survival analysis showed that high levels of miR-139-3p were only linked with a better prognosis in the subgroups of patients that underwent chemotherapy [hazard ratio (HR) =0.6, P<0.001]. The overexpression of miR-139-3p in BC cells enhanced cisplatin, olaparib, and irradiation (IR) sensitivity. MiR-139-3p was found to target RPA2 directly, and the overexpression of RPA2 counteracted the effect of miR-139-3p on homologous recombination (HR) repair and DNA damage sensitivity.ConclusionsThe diagnostic model based on the four circulating miRNAs could serve as a tool for the liquid biopsy of BC. Targeting the miR-139-3p/RPA2 axis may have potential in modulating the DNA damage pathway in BC.