DNA double-strand breaks (DSBs) are among the most cytotoxic forms of chromosomal lesions and are primarily repaired through homologous recombination (HR) or non-homologous end joining (NHEJ). The precise repair of DSBs via HR necessitates 5'-3' end resection to generate 3'-single-stranded DNA (ssDNA) overhangs, which function as templates for repair synthesis. However, the proteins involved in HR, particularly those acting in the critical early stages preceding DNA end resection, and their regulatory mechanisms in response to ionizing radiation (IR), remain incompletely characterized. In this study, we identify the nuclear receptor co-activator NCOA4 as a novel DNA damage responsive protein. We demonstrate that this protein is recruited to sites of DNA damage and is enriched during the S/G2 phase of the cell cycle. Immunofluorescence and reporter gene assays demonstrate that depletion of NCOA4 reduces the IR-induced foci formation of RAD51 and RPA2 and impairs HR efficiency. Mechanistically, NCOA4 interacts with the AAA + ATPases RUVBL1/2, and depletion of RUVBL1/2 has been shown to reduce the recruitment of NCOA4 at DNA damage sites. The knockdown of RUVBL1 or RUVBL2 phenocopies NCOA4 deficiency, and simultaneous knockdown of RUVBL1/2 and NCOA4 does not further reduce the RPA2 RIF, confirming that the entire NCOA4-RUVBL1/2 complex acts together to promote HR. Furthermore, depletion of NCOA4 has been shown to sensitize cancer cells to radiotherapy in tumor-bearing nude mouse models. Consequently, the present findings indicate that the NCOA4-RUVBL1/2 axis is capable of recognizing DNA double-strand breaks and promoting the homologous recombination repair pathway, thereby contributing to the maintenance of genomic integrity. This process may potentially play a role in modulating radioresistance in malignant tumors and expanding the landscape of therapeutic targets.

Ionizing radiation (IR) causes severe vascular damage, yet the dynamic functional states and regulatory mechanisms of vascular endothelial cells (VECs) after irradiation remain poorly understood. To elucidate the underlying processes, we analyzed single-cell RNA sequencing data from mouse dorsal skin collected at multiple post-irradiation (p.i.) time points using trajectory inference, pathway enrichment, transcription factor activity inference, and cell-cell communication analyses. Our results showed that VECs exhibited marked temporal dynamics after irradiation, transitioning from early-stage stress responses to middle-stage angiogenic remodeling and late-stage restoration of homeostasis. A transient Gpihbp1+ capillary endothelial subpopulation (capVEC2) emerged predominantly during the middle stage (2-3 days p.i.) and was enriched for angiogenesis- and migration-related programs. Enhanced Sp1 regulatory activity was associated with its pro-angiogenic phenotype. At 2 days p.i., capVEC2 engaged in pro-angiogenic and pro-repair signaling with keratinocytes, whereas by 3 days p.i. these interactions shifted toward immune surveillance and tissue homeostasis, accompanied by increased pro-inflammatory and pro-apoptotic signaling and a decline in capVEC2 abundance. Collectively, our findings identify a radiation-induced, transient functional endothelial subpopulation that is associated with vascular-epidermal communication during skin repair post irradiation.

Ovarian cancer (OV) is a highly metastatic and recurrent malignancy with limited therapeutic options. NIMA-related kinase 1 (NEK1), a serine/threonine kinase implicated in cell cycle regulation and DNA damage response, has been associated with tumorigenesis in various cancers, yet its specific role in OV pathogenesis remains elusive. This study systematically investigates the oncogenic function and underlying mechanisms of NEK1 in ovarian cancer. Our findings demonstrate that NEK1 promotes tumor progression both in vitro and in vivo. Mechanistically, bioinformatic and biochemical analyses reveal that NEK1 suppresses p53 signaling activity, resulting in downregulation of downstream targets p21 and PUMA, consequently attenuating cell cycle arrest and apoptosis. Importantly, NEK1-driven oncogenicity is dependent on the presence of p53 protein. Clinically, elevated NEK1 expression significantly correlates with poorer prognosis across multiple independent OV cohorts. Paradoxically, high NEK1 expression enhances radiosensitivity by impairing p53-mediated DNA damage repair. Collectively, these findings establish NEK1 as a promising prognostic biomarker and therapeutic target, with potential utility in guiding genotoxic therapy strategies for ovarian cancer patients.

Age-related hearing loss (ARHL) is the most common type of hearing loss. Genetic factors are considered to play important roles in the development of ARHL. To identify novel susceptibility genes and cell types relevant to ARHL, we performed a two-stage single-cell transcriptome-wide association study (scTWAS) on ARHL in 96,372 cases and 141,590 controls of European descent. In the discovery stage, we identified 1034 gene-cell pairs that showed suggestive associations with ARHL (P < 1.0 × 10-5), representing 450 genes across various cell types. These genes were enriched in multiple pathways, including the immune-related, estrogen signaling, and oxidative damage response pathways. Besides, we provided prominent genetic evidence for putative drug repurposing, highlighting several genes as potential targets, including NR3C2, CHRM4 and SHBG. Further, we validated the significant association of 41 genes with ARHL in the replication stage of scTWAS, including previously reported genes such as HLA-DRA, as well as novel candidates such as TNF, ZC3HAV1, and SLC44A4. Among these novel candidates, several are highly biologically plausible in the development of ARHL. In conclusion, this scTWAS broadens our understanding of the genetic susceptibility to ARHL, which might be helpful in developing new strategies for the treatment and prevention of ARHL.

BACKGROUND:Our previous genome-wide association study (GWAS) identified that chromosome 1p36.22 locus contributes to the risk of hepatocellular carcinoma (HCC). OBJECTIVE:We aimed to identify the functional causative variant(s) and target gene(s) at this locus. DESIGN:Two independent HCC case-control populations, totally consisting of 1934 cases and 1446 controls, were used to validate the association between 1p36.22 locus and HCC risk. The expression quantitative trait locus (eQTL) and eQTL-GWAS co-localisation analyses were used to identify the target gene at 1p36.22. The effects of the target gene on tumourigenesis were assessed in HCC cells, nude mouse models and conditional knockout mouse models. RESULTS:We confirmed the association between 1p36.22 locus and HCC risk (p=4.99×10-24), and revealed that this locus is an eQTL of the kinesin family member 1B isoform β (KIF1Bβ) gene. Further, we demonstrated that KIF1Bβ plays a tumour suppressive role in HCC in vitro and in vivo. Mechanistically, KIF1Bβ interacts with the cargo Fibulin-5 and mediates its intracellular anterograde transport and extracellular secretion, therefore, reducing the activation of the integrin pathway. We further identified the functional causative variant rs61784580 at 1p36.22, which is located in the promoter of KIF1Bβ and regulates its expression in an allele-specific manner. Finally, we observed that downregulation of KIF1Bβ sensitises HCC cells to integrin αv inhibitor cilengitide. CONCLUSIONS:Our findings shed light on the genetic and molecular mechanisms of the HCC-associated susceptibility locus at 1p36.22 and provide potential new strategies for the treatment of HCC.

Cathepsin C (CTSC) is a major lysosomal cysteine protease characterized by its involvement in multiple essential pathological processes associated with various viral infections and pathogenesis, such as influenza virus and coronavirus. However, the antiviral spectrum of CTSC and the molecular mechanisms underlying its activity remain to be fully elucidated. In this study, we demonstrate that CTSC significantly inhibits the infection of influenza A virus (IAV) H1N1 both in vitro and in vivo. Mechanistically, the antiviral function of CTSC is associated with attenuation of the PI3K-AKT signaling pathway, thereby inducing cell apoptosis and reducing inflammation, which ultimately limits the virus’s ability to hijack host resources. Taken together, our findings highlight the crucial role of CTSC in defense against H1N1 by targeting PI3K-AKT pathway and suggest a prospective antiviral target against the infection of H1N1.

Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are highly vulnerable to radiation-induced damage. Systematic delineation of lineage-specific transcription factor (TF) programs, together with in silico perturbation analyses, provides a valuable approach for identifying regulators capable of accelerating hematopoietic reconstruction after irradiation. Here, using single-cell RNA sequencing (scRNA-seq), we characterized the dynamics of HSPCs at both cellular abundance and transcriptional regulation levels following irradiation and used in silico TF perturbation to predict their effects on lineage commitment. We found that granulocyte-macrophage progenitor (GMP) differentiation is consistently prioritized after irradiation, accompanied by enhanced activity of proliferation-associated drivers. Network-based TF profiling identified Tcf7l2 as a previously unrecognized regulator of early lymphoid differentiation. In silico perturbation further functionally predicted TFs driving differentiation in HSPCs after irradiation, and Hsf1, a factor with pharmacological activation potential, was selected for validation via in vivo celastrol treatment and in vitro knockdown. Collectively, our findings uncover the transcriptional programs governing HSPC lineage biases after radiation exposure and highlight the utility of in silico TF perturbation as a strategy for guiding the therapeutic interventions for radiation-induced hematopoietic injury.

The incomplete understanding of the IGFR pathway activation mechanism limits its clinical application in hepatocellular carcinoma (HCC). Here, a transcriptome-wide screening is performed and a novel HCC-associated lncRNA, named IGFR-inducing lncRNA (IGFRIL) is identified. IGFRIL is frequently upregulated in HCC tissues and predicts poor clinical outcomes. It is revealed that IGFRIL plays an oncogenic role in the development of HCC. Mechanistically, IGFRIL serves as a scaffold to recruit PTBP1, destabilizing IGFBP3 mRNA and thereby overactivating the IGF1R-AKT-mTOR signaling in HCC cells. Furthermore, it is observed that the inhibitors against IGF1R or mTOR exhibit suppressive effects on patient-derived tumor xenograft tumors with high IGFRIL expression, through simultaneous blocking of the IGF1R-AKT-mTOR signaling pathway. In summary, this study identifies IGFRIL as a novel non-coding activator of the IGF1R pathway, providing a promising new therapeutic target for HCC patients.

Resistance to anoikis, a crucial factor in cancer cell survival, drives the development and progression of numerous malignancies. Hepatocellular carcinoma (HCC) is a malignant liver tumor characterized by high rates of recurrence and metastasis. However, the role of anoikis in HCC remains poorly understood. In this study, we identify 74 anoikis-related genes (ARGs) differentially expressed in HCC using the transcriptional data from The Cancer Genome Atlas (TCGA). Then, we develop a prognostic model incorporating 9 of these genes through LASSO-Cox regression analysis, and confirm the model's independent prognostic significance for overall survival in HCC patients by using multivariable Cox proportional hazards analysis. Furthermore, we observe significant enrichment of activated proliferation-related pathways, increased infiltration of immunosuppressive cells and resistance to anti-PD-L1 therapy in the high-risk group defined by this model. These findings suggest that the ARG model may serve as a novel prognostic indicator for HCC patients and underscore the critical role of anoikis in HCC progression.

High doses of ionizing radiation (IR) cause severe damage to the hematopoietic system. However, the heterogeneity of hematopoietic stem and progenitor cells (HSPCs) in response to IR stress remains largely uncharacterized. Here, we present a dynamic single cell transcriptomic landscape and elucidate the complex crosstalk between HSPCs and the bone marrow (BM) microenvironment during IR-induced regeneration process. We reveal that BMP4 signaling in HSPCs confers IR resistance, and a single administration of BMP4 or SB4 can rescue mice from the IR-induced mortality. Furthermore, we identify BMPR2+ HSCs as a radiation resistant subset, displaying distinct epigenetic landscapes from BMPR2- HSCs under radiation stress. BMPR2+ HSCs sustain a strong self-renewal capacity primarily by reducing the H3K27me3 modification on the Nrf2 gene in response to radiation stress. In Nrf2 knockout mice, we demonstrate that Nrf2 is a critical downstream functional gene for BMP4-BMPR2 signaling on HSCs to resist IR-induced damage. Collectively, we provide insights into the molecular intricacies underlying HSPC heterogeneity and BM niche after radiation exposure, and we uncover that BMP4-BMPR2 signaling may serve as a promising target for developing innovative and effective intervention strategies to mitigate IR-induced hematopoietic injury.

Liver cancer ranks sixth in cancer incidence and third in cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the primary histological subtype, and hepatitis B virus (HBV) carriers have a higher risk of HCC. Although several susceptibility loci for HCC have been identified in East Asian populations through genome-wide association studies (GWAS), the underlying biological mechanisms of this malignancy remain incompletely understood. Here, we conduct a two-stage GWAS including 2413 cases and 2794 HBV-positive controls from a high-incidence region in Southern China. The function of the susceptibility locus is investigated by bioinformatic and experimental approaches, supported by a xenograft model. We identify a 4p14 locus significantly associated with the risk of HCC (rs55718051, OR [95% CI] = 0.73 [0.67-0.80], Pmeta = 9.14 × 10-11), and 18q23 locus with borderline significance (rs12964643: OR [95% CI] = 0.75 [0.67-0.83], Pmeta = 1.11 × 10-7). Functional experiments indicate the role of rs55718051 in FAM114A1 expression regulation, possibly through the interaction with FOXA1. Knockdown of FAM114A1 significantly promote the oncogenic phenotypes in liver cancer cells, suggesting its potential tumor suppressor role. Our findings expand the understanding of HCC susceptibility and suggest FAM114A1 as a potential suppressor in HBV-related HCC carcinogenesis.

To identify genomic regions subject to positive selection that might contain genes involved in high-altitude adaptation (HAA), we performed a genome-wide scan by whole-genome sequencing of Tibetan highlanders and Han lowlanders. We revealed a collection of candidate genes located in 30 genomic loci under positive selection. Among them, MCUR1 at 6p23 was a novel pronounced candidate. By single-cell RNA sequencing and comprehensive functional studies, we demonstrated that MCUR1 depletion leads to impairment of erythropoiesis under hypoxia and normoxia. Mechanistically, MCUR1 knockdown reduced mitochondrial Ca2+ uptake and then concomitantly increased cytosolic Ca2+ levels, which thereby reduced erythropoiesis via the CAMKK2-AMPK-mTOR axis. Further, we revealed rs61644582 at 6p23 as an expression quantitative trait locus for MCUR1 and a functional variant that confers an allele-specific transcriptional regulation of MCUR1. Overall, MCUR1-mediated mitochondrial Ca2+ homeostasis is highlighted as a novel regulator of erythropoiesis, deepening our understanding of the genetic mechanism of HAA.

High-altitude hypobaric hypoxia is associated with immune dysregulation, potentially linked to the progression of altitude illnesses such as acute mountain sickness (AMS) in unacclimatized individuals. However, the immune signatures associated with AMS severity remain poorly understood. This study investigated immune dynamics under high-altitude exposure and identified immune signatures associated with AMS severity. In this longitudinal study, 205 lowlanders travelled from Chongqing (∼200 m) to Xizang (∼3600 m) by air. Immune status was comprehensively assessed using multi-parametric flow cytometry, alongside monitoring of clinical features at baseline, 1 day after arrival (acute phase) and after 90 days at high altitude (chronic phase). Results demonstrated that high-altitude exposure induced systemic, sustained immune cell perturbations. Using the high-altitude immune score (HI score), derived from immune cell composition, we revealed immune status was associated with hypoxic conditions and changed concurrently with haematopoietic and liver function. Cross-sectional analysis revealed immune cell alterations associated with AMS severity, including reduced frequencies of eosinophils, basophils, plasmacytoid dendritic cells and CD4+ T cells, which was more evident in severe AMS patients. Among these immune alterations, the reduction in eosinophils mediates the relationship between hypoxia and AMS severity. In vitro experiments further suggested hypoxia-induced eosinophil apoptosis may account for the eosinophil reduction. Through network analysis, we identified two immune features as potential biomarkers for predicting and classifying severe AMS cases. This study provides detailed immune dynamics under high-altitude hypoxia exposure and unveils key immune features associated with AMS severity, offering valuable insights for disease prediction and stratification. KEY POINTS: High-altitude exposure induces systemic perturbations in the immune system. Immune status correlates with haematopoietic and liver function under hypoxia. Immune cell alterations are associated with the severity of acute mountain sickness (AMS). The reduction in eosinophils is likely driven by hypoxia-induced apoptosis. Immune biomarkers can predict and diagnose severe AMS cases.

As two major types of primary liver cancers, the tumor immune microenvironment (TIME) of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have been well studied separately. However, a systemic assessment of the similarities and differences between the TIME of HCC and ICC is still lacking. In this study, we pictured a landscape of combined TIME of HCC and ICC by sequencing and integrating 41 single-cell RNA-seq samples from four different tissue types of both malignancies. We found that T cells in HCC tumors generally exhibit higher levels of immunosuppression and exhaustion than those in ICC tumors. Myeloid cells in HCC and ICC tumors also exhibit distinct phenotypes and may serve as a key factor driving the differences between their TIMEs. Besides, we identified a cluster of EGR1+ macrophages specifically enriched in HCC tumors. Together, our study provides new insights into cellular composition, states and interactions in the TIMEs of HCC and ICC, which could pave the way for the development of future therapeutic targets for liver cancers.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer accounting for 90% of cases. It is a highly invasive and deadly cancer with a gradual onset. Polypyrimidine tract-binding protein 1 (PTBP1) is an important RNA-binding protein involved in RNA metabolism and has been linked to oncogenic splicing events. While the oncogenic role of PTBP1 in HCC cells has been established, the exact mechanism of action remains unclear. This study aimed to investigate the functional connection between PTBP1 and dysregulated splicing events in HCC. Through immunoprecipitation-mass spectrometry analyses, we discovered that the proteins bound to PTBP1 were significantly enriched in the complex responsible for the alternative splicing of FGFR2 (fibroblast growth factor receptor 2). Further RNA immunoprecipitation and quantitative PCR assays confirmed that PTBP1 down-regulated the FGFR2-IIIb isoform levels and up-regulated the FGFR2-IIIc isoform levels in HCC cells, leading to a switch from FGFR2-IIIb to FGFR2-IIIc isoforms. Subsequent functional evaluations using CCK-8, transwell, and plate clone formation assays in HCC cell lines HepG2 and Huh7 demonstrated that FGFR2-IIIb exhibited tumor-suppressive effects, while FGFR2-IIIc displayed tumor-promoting effects. In conclusion, this study provides insights into the PTBP1-mediated alternative splicing mechanism in HCC progression, offering a new theoretical basis for the prevention and treatment of this malignancy. Mechanistically, the isoform switch from FGFR2-IIIb to FGFR2-IIIc promoted epithelial-mesenchymal transformation (EMT) of HCC cells and activated the FGFR cascades ERK and AKT pathways.

Background The global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized. Methods Based on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell–cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors. Results Our analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings. Conclusions This study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.

To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10-9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.

Hepatocellular carcinomas (HCCs) are characterized by a vast spectrum of somatic copy number alterations (CNAs); however, their functional relevance is largely unknown. By performing a genome-wide survey on prognosis-associated focal CNAs in 814 HCC patients by an integrative computational framework based on transcriptomic data, genomic amplification is identified at 8q24.13 as a promising candidate. Further evidence is provided that the 8q24.13 amplification-driven overexpression of Rab GTPase activating protein TBC1D31 exacerbates HCC growth and metastasis both in vitro and in vivo through activating Epidermal growth factor receptor (EGFR) signaling. Mechanistically, TBC1D31 acts as a Rab GTPase activating protein to catalyze GTP hydrolysis for Rab22A and then reduces the Rab22A-mediated endolysosomal trafficking and degradation of EGFR. Notably, overexpression of TBC1D31 markedly increases the resistance of HCC cells to lenvatinib, whereas inhibition of the TBC1D31-EGFR axis can reverse this resistance phenotype. This study highlights that TBC1D31 at 8q24.13 is a new critical oncogene, uncovers a novel mechanism of EGFR activation in HCC, and proposes the potential strategies for treating HCC patients with TBC1D31 amplification or overexpression.

Background: Hepatitis B virus (HBV) is a DNA virus known to induce hepatitis and liver dysfunction, and is one of the main causes of liver cirrhosis and liver cancer. At present, there lacks a satisfactory optimal treatment plan for HBV in clinical practice, promoting the development of a novel Chinese formula, QingReJieDu Formula (QRJDF), as a potential solution. Purpose: This study aims to explore the underlying mechanisms of QRJDF in the treatment of Hepatitis B virus (HBV) through a combination of network pharmacology and experimental validation. Methods/study design: HepG2.2.15 cells were used to study the efficacy of QRJDF against HBV in vitro. Entecavir (ETV) was used as a positive control. Additionally, HBV transgenic mice served as subjects to study the in vivo efficacy of QRJDF against HBV, with serum and tissue samples analyzed post-euthanasia at 12 weeks to observe relevant indicators. UPLC-Q-TOF-MS technology was utilized to obtain the main ingredients in QRJDF. Network pharmacology was used to explore the potential ingredients and targets of QRJDF against HBV. Transcriptome sequencing was used to further explore the potential targets of QRJDF against HBV. Finally, integration of network pharmacology and transcriptomics results facilitated the screening of potential key targets and identification of potential pathways. Results: QRJDF demonstrated anti-HBV effects in HepG2.2.15 cells, compared to ETV control, QRJDF was more efficient in inhibiting HBV antigen levels, although it was less efficient in inhibiting HBV DNA level. In addition, the antiviral effect was verified in HBV transgenic mice. Network pharmacology results found three major active anti-HBV ingredients from QRJDF. Network pharmacology and transcriptomics revealed that QRJDF could act on the TGF beta 1/Smad4 signaling pathway. Conclusion: The study comprehensively evaluated the efficacy in vivo and in vitro, and fully confirmed that QRJDF was a potential therapeutic agent for HBV. In addition, the transcriptome technology was verified, and the key targets and approaches of QRJDF against hepatitis B were screened in combination with network pharmacology, which provided research ideas for the follow-up research of antiviral Chinese medicine.

>As the first barrier of the body, the skin is inevitably damaged by radiation during clinical radiotherapy (typically administered at 2–3 Gy per session, for a total of approximately 50–80 Gy to eradicate tumors) or nuclear accidents. Currently,the primary clinical methods for protecting against radiation are limited, and some have serious side effects. 1,2-Propanediol (PPD) is a low-toxicity smallmolecule compound that is typically used as a humectant in drug solvents, food additives,pharmaceutical excipients, cosmetics, and electronic cigarettes.