Beijing Radiation Center

Radiation-responsive promoters represent a functionally distinct class of transcriptional regulatory elements that translate genotoxic stress signals into quantifiable gene expression outputs. These promoters occupy a unique mechanistic position within the broader radiation biomarker landscape: rather than directly measuring molecular damage products, they report the cellular interpretation of radiation-induced stress through coordinated gene regulatory networks. This review provides a systematic analysis of five major classes of radiation-responsive promoters-microRNA (miRNA) promoters, tRNA-derived small RNA (tsRNA) promoters, acute-phase protein gene promoters, DNA repair gene promoters, and long non-coding RNA (lncRNA) promoters-with emphasis on their regulatory logic, dose-response characteristics, and current evidence for clinical deployment. We further describe four complementary screening strategies: homology-based conservation analysis, functional genomics and transcriptomics, epigenetic modification profiling, and synthetic biology promoter engineering. Applications spanning biosensor development, biological dosimetry, treatment response prediction, and radiation-guided gene therapy are evaluated within a two-track framework that distinguishes biomarker-oriented applications (Track A) from tool-oriented reporter gene systems (Track B). Critical appraisal of current limitations-including insufficient clinical-grade validation, absence of standardized dose-response curves, and reproducibility deficits-is integrated throughout. Future priorities include multi-center prospective validation studies, FAIR-compliant data infrastructure, AI-driven multi-omics integration, and point-of-care detection platforms. Radiation-responsive promoter biology holds significant potential for advancing precision radiotherapy and nuclear emergency medical response, contingent upon systematic closure of the current evidence gap relative to established gold-standard cytogenetic methods.

Radiation-induced brain injury (RBI) is a severe complication of cranial radiotherapy that poses a significant clinical challenge due to a lack of effective treatments. Ferroptosis, an oxidative stress-driven cell death pathway, has been implicated in its pathogenesis. Here, we report that 75% ethanol (GBF-8), a novel subfraction isolated from male Ginkgo biloba flowers, confers significant protection against RBI. In a murine RBI model, GBF-8 administration restored cognitive function and alleviated neuroinflammation. We demonstrated that this neuroprotective effect is mechanistically linked to ferroptosis inhibition. Integrated proteomic and metabolomic profiling identified the Solute carrier family 7 member 11 (Slc7a11)-Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (Eif4ebp1) axis as the primary target of GBF-8. This work not only establishes GBF-8 as a promising therapeutic candidate but also delineates a previously unrecognized regulatory axis for combating ferroptosis in RBI.

IntroductionHigh-power microwave (HPM) exposure can produce biological effects in cells, but the specific characteristics and mechanisms of these effects in ocular tissues remain poorly defined. This study aimed to investigate the biological responses of human corneal epithelial cells (HCE-T) to 4.3 GHz HPM exposure, with a focus on moderate-dose effects.MethodsHCE-T cells were exposed to 4.3 GHz HPM at average specific absorption rates (SARs) of 1.64, 3.28, and 8.2 W/kg. Cellular responses were evaluated by measuring cell viability, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and apoptosis at multiple time points. Transcriptomic analysis was performed to identify underlying molecular pathways.ResultsModerate-dose exposure (3.28 W/kg) resulted in the most pronounced cellular effects, including early and significant ROS elevation, marked collapse of mitochondrial membrane potential, the highest apoptosis rate, and sustained inhibition of proliferation. Transcriptomic profiling showed strong suppression of the mTOR signaling pathway, upregulation of TSC2, and activation of Polycomb-mediated chromatin remodeling, suggestive of autophagy induction and irreversible cell cycle arrest. In contrast, low-dose exposure (1.64 W/kg) primarily activated DNA repair and adaptive pathways, while high-dose exposure (8.2 W/kg) predominantly disrupted metabolic and membrane signaling with a trend toward recovery.DiscussionThese findings demonstrate that moderate-dose 4.3 GHz HPM exposure induces a uniquely strong stress response in HCE-T cells, characterized by oxidative stress, mitochondrial dysfunction, and activation of stress-related signaling pathways. These results highlight the importance of considering specific exposure conditions in assessing HPM bioeffects and ocular safety.

Dyslipidemia is a major cardiovascular risk factor; however, disease patterns-particularly lipid profiles-remain understudied in high-altitude populations. On the Pamirs Plateau (> 4000m), no relevant epidemiological studies have been conducted to date. This study investigates the disease patterns in this region, with an emphasis on dyslipidemia epidemiology. We conducted a serial cross-sectional study (2021-2024) using annual health examination data from Tashkurgan County, Pamirs Plateau. Adults aged ≥ 18years residing ≥ 1year were included. We first examined the overall disease patterns, with a focus on dyslipidemia. Age-standardized prevalence was calculated and stratified by sex and ethnicity. Subsequently, lipid profile distributions and temporal trends were analyzed. To place these findings in a global context, LDL-C levels were compared with populations from plains and other high-altitude regions. Finally, potential risk factors were identified using multivariate logistic regression and machine learning models. Among a representative subset (24.37%) of the Pamirs Plateau population, dyslipidemia was the most prevalent condition, followed by hypertension, sinus bradycardia, and fatty liver. The prevalence of dyslipidemia ranged from 25.24% to 37.64%. LDL-C levels were lower than those in plains and other high-altitude regions. Ethnic disparities were evident: the minority population (predominantly Tajik) maintained stable, favorable lipid profiles across ages, while non-minorities exhibited pronounced age-related fluctuations. Age 70 emerged as a potential inflection point at which sex-related differences in LDL-C levels reversed. Male, non-minority, older age, diabetes, frequent alcohol consumption, and higher education were significantly associated with dyslipidemia. Unexpectedly, improved living conditions (range hood use [OR: 1.839, 95% CI: 1.673-2.021], natural gas use [OR: 1.273, 95% CI: 1.152-1.406], tap water access [OR: 1.315, 95% CI: 1.204-1.436]) were linked to a higher risk, a "modernization paradox". Additionally, distinct temporal fluctuations were observed: LDL-C levels sharply declined in 2022 before rebounding, coinciding with the COVID-19 lockdown period. This first comprehensive analysis from "the roof of the world" reveals unique lipid patterns, including low LDL-C levels, pandemic-era fluctuations, ethnic disparities, unique age-sex patterns, and a paradoxical association between improved living conditions and increased dyslipidemia risk. These insights should inform context-specific lipid management strategies for this and similar vulnerable high-altitude populations globally.

Effective therapies for primary sclerosing cholangitis (PSC), a progressive cholestatic liver disease characterized by biliary inflammation and fibrotic damage, remain limited due to an incomplete elucidation of its underlying molecular mechanisms. Although N6-methyladenosine (m6A) RNA methylation has been implicated in hepatic pathophysiology, its role in PSC remains undefined. Here, we demonstrate that hepatocyte-specific deletion of Mettl3, a critical m6A methyltransferase, induces spontaneous PSC-like pathology characterized by ductular reaction and peribiliary fibrosis. Therapeutic restoration of Mettl3 through genetic knock-in or AAV8-mediated hepatocyte-specific overexpression significantly attenuated 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced PSC progression. Integrated single-cell and bulk transcriptomic profiles revealed an expansion of Trem2+ macrophages that interact with Spp1high cholangiocytes via the Cd44-Spp1 axis. Genetic ablation of Trem2 or cholangiocyte-specific deletion of Spp1 significantly suppressed DDC-induced biliary injury. Mechanistically, Mettl3-deficient hepatocytes secreted higher levels of macrophage-recruiting cytokines (such as Mif and Csf1), facilitating the recruitment of Trem2+ macrophage, which subsequently activated cholangiocytes through Cd44-Spp1 signaling, exacerbated biliary inflammation and fibrosis. Notably, pharmacological activation of Mettl3 in adult hepatocytes substantially mitigated PSC progression and liver fibrosis. Collectively, our findings establish hepatocyte Mettl3 deficiency as a pivotal driver of PSC pathogenesis and highlight the therapeutic potential of targeting the m6A epitranscriptome in cholestatic liver diseases.

A systematic literature review of the PubMed database, filtering for publication dates up to and including October 2025, was conducted to identify relevant studies on glucose metabolism and radiotherapy. Radioresistance poses a major therapeutic challenge, in which tumor-associated glucose metabolic reprogramming, characterized by the Warburg effect, supports cellular energy requirements and contributes to radioresistance by facilitating DNA repair and promoting survival pathways. Targeting pivotal glycolytic enzymes, such as hexokinase (HK) and pyruvate kinase M2 (PKM2), and integrating radiotherapy with metabolic modulators have been shown to improve radiosensitivity. Special emphasis is placed on how these interventions remodel the tumor microenvironment and modulate antitumor immunity—emerging factors that influence therapeutic efficacy. This review highlights mechanistic insights and potential therapeutic targets for the development of effective radiosensitization strategies.