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PubMed2026

Crotonylome profiling identifies MLKL crotonylation in lupus nephritis associated with RAB1A-mTOR signalling and autophagy changes in tubular epithelial cells.

OBJECTIVE: To investigate whether MLKL crotonylation is associated with tubular autophagy-lysosome pathway homeostasis in lupus nephritis (LN) and to explore its relationship with RAB1A-mechanistic target of rapamycin (mTOR) signalling. METHODS: Crotonylome proteomics was performed in peripheral blood mononuclear cells from patients with LN, patients with systemic lupus erythematosus without nephritis and healthy controls. Renal biopsy tissues were evaluated for tubulointerstitial fibrosis and autophagy-lysosome pathway-related markers. Mechanistic studies were conducted in lipopolysaccharide-stimulated HK-2 cells. Autophagic flux was assessed using bafilomycin A1. The dependency of mTOR/autophagy changes on RAB1A was tested by siRNA-mediated knockdown. RESULTS: MLKL was identified as a differentially crotonylated protein in LN, with increased crotonylation at K95 and K219. Kidney tissues from patients with LN showed increased fibronectin and collagen III deposition compared with controls, whereas no significant difference was observed between class IV and class V LN. LC3 signal did not differ significantly between groups, whereas LAMP1 expression and LC3-LAMP1 co-localisation were reduced in LN. In HK-2 cells, crotonylation-deficient MLKL mutants were associated with increased LC3-II and reduced p62, whereas K219Q showed the opposite pattern. Autophagic flux assays using bafilomycin A1 showed that K219R-expressing cells had higher LC3-II levels than WT cells both before and after lysosomal inhibition, with comparable BafA1-induced LC3-II accumulation, consistent with increased autophagosome formation rather than impaired lysosomal degradation. HDAC1 knockdown increased MLKL crotonylation and was accompanied by mTOR activation. MLKL crotonylation enhanced RAB1A guanriphosphat osphate (GTP) binding without altering total RAB1A abundance. RAB1A knockdown in MLKL WT-expressing cells attenuated mTOR phosphorylation and partly reversed the autophagy-suppressive marker profile. Sodium crotonate induced an autophagy-suppressive marker profile that was partly reversed by rapamycin. CONCLUSION: MLKL crotonylation is associated with activation of the RAB1A-mTOR axis and altered tubular autophagy-lysosome pathway homeostasis in LN. These findings suggest that tubular injury-related changes in LN may not be fully reflected by glomerulus-based classification alone.

Humans↗

PubMed2026

Puerarin Attenuates Binge Ethanol-Induced Cortical Neurotoxicity in Association with AKT/mTOR Signaling and Autophagy-Related Responses.

Puerarin (Pue), a major isoflavone derived from Pueraria lobata, has demonstrated neuroprotective potential in multiple neurological disorders; however, its effects on ethanol (EtOH)-induced cortical injury and the associated molecular responses remain incompletely understood. In the present study, network pharmacology was combined with in vivo and in vitro experiments to investigate molecular responses associated with the effects of Pue on EtOH-induced neurotoxicity. Public databases were used to predict targets of Pue and alcohol-related brain injury, followed by protein-protein interaction analysis, Gene Ontology annotation, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. A total of 101 overlapping targets were identified, among which TNF, AKT1, EGFR, TP53, and PPARG emerged as major hub targets, and PI3K-Akt signaling pathway was among the pathways that remained significantly enriched after FDR correction. In a 4-day binge EtOH rat model, Pue attenuated EtOH-associated increases in oxidative stress, neuronal degeneration, and apoptotic markers in cortical tissue. This was accompanied by attenuation of the EtOH-associated reductions in the p-AKT/AKT and p-mTOR/mTOR ratios, as well as an attenuation of EtOH-associated changes in LC3, ATG5, and Beclin-1 expression. In primary cortical neurons, Pue partially attenuated the EtOH-associated loss of neuronal viability and preserved neurite morphology. Bafilomycin A1 (BafA1)-based analysis of LC3-II and p62/SQSTM1 showed an overall BafA1-sensitive increase in LC3-II without a significant treatment-dependent difference in the BafA1 response. Collectively, these findings suggest that Pue attenuates binge EtOH-induced cortical neurotoxicity in association with changes in AKT/mTOR phosphorylation and autophagy-related responses.

AKT/mTOR signaling↗

PubMed2025

Peri-mitochondrial actin filaments inhibit Parkin assembly by disrupting ER-mitochondria contacts.

Mitochondrial damage represents a dramatic change in cellular homeostasis, necessitating metabolic adaptation and clearance of the damaged organelle. One rapid response to mitochondrial damage is peri-mitochondrial actin polymerization within 2 min, which we term ADA (Acute Damage-induced Actin). ADA is vital for a metabolic shift from oxidative phosphorylation to glycolysis upon mitochondrial dysfunction. In the current study, we investigated the effect of ADA on Pink1/Parkin mediated mitochondrial quality control. We show that inhibition of proteins involved in the ADA pathway significantly accelerates Parkin recruitment onto depolarized mitochondria. Addressing the mechanism by which ADA resists Parkin recruitment onto depolarized mitochondria, we found that ADA disrupts ER-mitochondria contacts in an Arp2/3 complex-dependent manner. Interestingly, overexpression of ER-mitochondria tethers overrides the effect of ADA, allowing rapid recruitment of not only Parkin but also LC3 after mitochondrial depolarization. During chronic mitochondrial dysfunction, Parkin and LC3 recruitment are completely blocked, which is reversed rapidly by inhibiting ADA. Taken together we show that ADA acts as a protective mechanism, delaying mitophagy following acute damage, and blocking mitophagy during chronic mitochondrial damage.

Ubiquitin-Protein Ligases↗

PubMed2026

Enoxaparin induces apoptosis and autophagy, modulates inflammatory signaling, and reduces oxidative DNA damage in breast and liver cancer cells.

Cancer progression involves intricate interactions between inflammatory signaling, programmed cell death mechanisms, and oxidative stress. Although enoxaparin is widely used for managing cancer-associated thrombosis, its direct cellular effects on tumor biology remain insufficiently characterized. This study aimed to evaluate the impact of enoxaparin on apoptosis, autophagy, inflammatory mediators, and oxidative DNA damage in breast (MDA-MB-231) and liver (HepG2) cancer cell lines. MDA-MB-231, HepG2, and non-cancerous HEK-293 cells were treated with varying concentrations (5, 10, 20, 40, and 80 mg/mL) of enoxaparin for 24 and 48 h. Cell viability was assessed using the MTT assay, while apoptosis was quantified by TUNEL analysis. Immunofluorescence staining was employed to evaluate the expression of NF-κB, IL-6, TNF-α, LC3, and p62. Oxidative DNA damage was determined by measuring extracellular 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels using a competitive ELISA. Statistical analyses were conducted to compare the treated and control groups. Enoxaparin significantly reduced cell viability in MDA-MB-231 and HepG2 cells without inducing cytotoxicity in HEK-293 cells. Apoptosis was markedly increased in both cancer cell lines following treatment. Enoxaparin differentially modulated inflammatory signaling; NF-κB expression was significantly increased in MDA-MB-231 cells, accompanied by suppression of IL-6 and TNF-α, whereas no significant inflammatory changes were observed in HepG2 cells. Enoxaparin treatment was observed to increase LC3 and p62 expression in both MDA-MB-231 and HepG2 cells, triggering autophagy-related pathways. Moreover, enoxaparin significantly reduced extracellular 8-OHdG levels, suggesting a reduction in oxidative DNA damage. Enoxaparin exhibits multifaceted anticancer effects by promoting apoptosis and autophagy, selectively modulating inflammatory pathways, and reducing oxidative DNA damage in breast and liver cancer cells.

Humans↗

PubMed2026

RPLP0 drives diffuse large B-cell lymphoma cell proliferation through reactive oxygen species-dependent AKT/mTOR activation and inhibition of stress-induced autophagy.

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive subtype of non-Hodgkin lymphoma with poor outcomes. Identifying the primary molecular causes of DLBCL remains key. The present study examined the function of ribosomal protein lateral stalk subunit P0 (RPLP0) in DLBCL pathogenesis. The Cancer Genome Atlas-DLBCL and GSE12453 datasets overlapping differentially expressed genes were identified. Hub genes were identified via protein-protein interaction network analysis. DLBCL cells were subjected to functional tests following RPLP0 overexpression or knockdown. Reverse transcription-quantitative PCR, western blotting, flow cytometry, transmission electron microscopy, colony formation assay and biochemical analysis were among the tests performed. N-acetylcysteine (NAC), rapamycin (RAPA) and 3-MA were among the medication therapies. In the DLBCL datasets, six ribosome-associated genes were differentially expressed. RPLP0 knockdown inhibited the proliferation of DLBCL cells and caused G2-phase arrest, without impacting apoptosis. Thioredoxin, heat shock protein family A member 1A and heat shock protein family B member 1 expression was downregulated by RPLP0 knockdown, which also increased the NAD+/NADH ratio, promoted reactive oxygen species (ROS) accumulation and caused mitochondrial membrane potential depolarization. Meanwhile, 3-MA reversed the effects of RPLP0 knockdown, which encouraged LC3-II accumulation, autophagy-related gene 5 (ATG5) overexpression and an increase in autophagic vesicles. Autophagy-related indicators were decreased, and AKT/mTOR phosphorylation was increased by RPLP0 overexpression, which RAPA inhibited. NAC therapy preserved the viability of RPLP0-silenced cells, restored p-AKT/p-mTOR levels and restored normal LC3 and ATG5 expression. These findings suggest that RPLP0 regulates stress-induced autophagy through ROS-dependent AKT/mTOR signaling and may represent a potential therapeutic target for DLBCL.

AKT/mTOR signaling pathway↗

PubMed2026

Genome mining and metabolomics unveil new napyradiomycin antibiotics from Streptomyces sp. 0H2M.

Napyradiomycins are a family of meroterpenoid natural products known for their promising antibiotic activities. In this study, four new napyradiomycins derivatives were identified, SF2415B4 (1), SF2415B5 (2), SF2415B6 (3), and SF2415B7 (4) from Streptomyces sp. 0H2M, alongside a known molecule, A80915A (5) through the synergy between genome mining and metabolomics analysis. Their structures were elucidated through a combination of spectroscopic and spectrometric analyses, including HRMS-ESI, NMR, and DP4+. Genome sequencing identified a putative biosynthetic gene cluster, and subsequent analyses revealed a distinct biosynthetic pathway with an unprecedented tailoring mechanism mediated by novel hydroxylases and halogenases. Biological assays demonstrated significant activity against Bacillus subtilis, Bacillus cereus and methicillin-resistant Staphylococcus aureus due to perturbation of cell membrane integrity, and minimum inhibitory concentration (MIC) values ranged from 0.24 to 30.7 μM. Additionally, in vitro cytotoxicity experiments indicated that compounds 2-5 very mildly inhibited the viability of human non-small cell lung cancer (NSCLC) cell line A549 in a concentration-dependent manner, with IC50 values of 16.7, 39.1, 65.0, and 32.8 μM, respectively. Moreover, they were shown to induce apoptosis and autophagy in A549 cells, evidenced by increased levels of cleaved PARP, decreased expression of anti-apoptotic proteins (Bcl-2, Bcl-xL, and Survivin), and accumulation of LC3-II. These findings offer new insights into the natural product chemistry in Streptomyces and the pharmacology of napyradiomycin class antibiotics.

Streptomyces↗

PubMed2026

A combined stimulus of acute fasting and exercise modulates hippocampal mitochondrial quality control in healthy mice.

BACKGROUND AND AIMS: Exercise and fasting are recognized for their ability to improve brain health and mitigate neurodegeneration. However, little is known about how these interventions acutely impact mitochondrial quality control mechanisms including mitophagy. METHODS: We examined the effects of a single bout of fasting and exercise (FEx) on hippocampal mitochondrial function and proteomic remodeling in male and female mice. To assess in vivo autophagy dynamics, we combined proteomics with chloroquine (CQ) inhibition of autophagic flux. Mice were assigned to sedentary (Sed), fasting (F), exercise (Ex), or combined FEx groups and received unilateral intrahippocampal injections of CQ or PBS following treatments. Four hours later, hippocampi were collected for analysis. RESULTS: LC3-II levels significantly increased in the FEx group only following CQ treatment, indicating enhanced autophagic flux. Proteomic profiling showed sedentary males failed to mount a robust response to FEx however females exhibited upregulation of proteins involved in the TCA cycle, glutathione metabolism, and oxidative phosphorylation, suggesting greater mitochondrial adaptability. Functional assays supported these findings, females showed increased complex IV activity post-FEx. The mitochondrial DNA / nuclear DNA ratio increased after FEx regardless of sex, and upstream regulator analysis predicted activation of mitochondrial biogenesis. CONCLUSIONS: Together, these data reveal sex-specific mitochondrial remodeling in response to acute fasting and exercise. Defining these normative responses is critical for understanding how mitochondrial adaptability shapes resilience or vulnerability to neurological challenges.

Animals↗

PubMed2026

miR-519d-3p inhibits gastric cancer progression by targeting the Beclin-1-dependent autophagy pathway.

Dysregulation of microRNA networks is a hallmark of gastric cancer pathogenesis, but the mechanisms driving early-stage disease remain poorly understood. This study utilized integrative bioinformatics analysis of the Gene Expression Omnibus dataset GSE158315 to identify tumor-suppressive microRNAs in early gastric cancer. We identified hsa-miR-519d-3p as a core downregulated microRNA in early-stage tissues. Functional assays in NUGC-3 and MKN-45 cell lines demonstrated that miR-519d-3p overexpression significantly suppressed cell migration and invasion, whereas its inhibition enhanced these malignant phenotypes. Dual-luciferase reporter assays confirmed that miR-519d-3p directly targets the 3' untranslated region of BECN1 (Beclin-1). Silencing Beclin-1 via siRNA mimicked the effects of miR-519d-3p overexpression, while rescue experiments showed that Beclin-1 knockdown reversed the pro-migratory and pro-invasive effects triggered by miR-519d-3p inhibition. Furthermore, monitoring of autophagic flux using mRFP-GFP-LC3 tandem reporters revealed that miR-519d-3p inhibition enhances autophagy in a Beclin-1-dependent manner. Clinical data analysis from The Cancer Genome Atlas further supported the upregulation of Beclin-1 in gastric cancer and its correlation with aggressive clinicopathological features. In conclusion, our findings establish the miR-519d-3p/Beclin-1 axis as a critical regulator of motility and autophagy in gastric cancer, representing a potential therapeutic target for early intervention.

Autophagy↗

PubMed2024

The scramblases VMP1 and TMEM41B are required for primitive endoderm specification by targeting WNT signaling.

The ER-resident proteins VMP1 and TMEM41B share a conserved DedA domain, which confers lipid scramblase activity. Loss of either gene results in embryonic lethality in mice and defects in autophagy and lipid droplet metabolism. To investigate their role in pluripotency and lineage specification, we generated Vmp1 and Tmem41b mutations in mouse embryonic stem cells (ESCs). We observed that ESCs carrying mutations in Vmp1 and Tmem41b show robust self-renewal and an unperturbed pluripotent expression profile but accumulate LC3-positive autophagosomes and lipid droplets consistent with defects in autophagy and lipid metabolism. ESCs carrying combined mutations in Vmp1 and Tmem41b can differentiate into a wide range of embryonic cell types. However, differentiation into primitive endoderm-like cells in culture is impaired, and the establishment of extra-embryonic endoderm stem (XEN) cells is delayed. Mechanistically, we show the deregulation of genes that are associated with WNT signaling. This is further confirmed by cell surface proteome profiling, which identified a significant reduction of the WNT-receptor FZD2 at the plasma membrane in Vmp1 and Tmem41b double mutant ESCs. Importantly, we show that transgenic expression of Fzd2 rescues XEN differentiation. Our findings identify the role of the lipid scramblases VMP1 and TMEM41B in WNT signaling during extra-embryonic endoderm development and characterize their distinct and overlapping functions.

Animals↗

PubMed2026

A CRISPR-Cas9 screen identifies LAPTM4A (lysosomal protein transmembrane 4 alpha) as a key host barrier against PRRSV infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) manipulates host intracellular processes, particularly macroautophagy/autophagy and lysosomal function, to facilitate its replication and spread. However, the precise host factors and molecular mechanisms by which PRRSV remodels the autophagy-lysosome axis remain poorly defined. Here, we performed a CRISPR-Cas9 knockout screen targeting 1,332 genes involved in protein degradation, metabolism, and vesicular trafficking, and identified LAPTM4A (lysosomal protein transmembrane 4 alpha) as a critical antiviral factor involved in the lysosomal pathway. A yeast two-hybrid screen identified LAPTM4A as an interactor of PRRSV GP5 (glycoprotein 5). Mechanistically, GP5 recruits the E3 ubiquitin ligase NEDD4 and the autophagy receptor SQSTM1/p62 to promote K63-linked polyubiquitination of LAPTM4A, leading to its autophagic degradation. This selective degradation activates the AMPK-ULK1-MAP1LC3/LC3 signaling cascade, initiating autophagy while facilitating MTOR-lysosome colocalization, thereby suppressing TFEB nuclear translocation and transcription of lysosome-related genes. The resulting incomplete autophagic flux enhances viral replication. Additionally, in terms of host defense, LAPTM4A maintains lysosomal homeostasis by restraining excessive autophagy through AMPK-ULK1-LC3 signaling and promoting TFEB-dependent lysosomal gene expression by impairing the binding of RPTOR/raptor to MTOR, thus providing broad antiviral protection against multiple RNA viruses. Collectively, our findings identify LAPTM4A as a central regulator of lysosome-autophagy homeostasis and reveal a viral strategy that dismantles this defense axis to facilitate infection.Abbreviations: ATG5: autophagy related 5; AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; Baf A1: bafilomycin A1; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DMVT library: protein degradation, metabolism, and vesicular trafficking library; LAPTM4A: lysosomal protein transmembrane 4 alpha; MAGeCK: model-based analysis of genome-wide CRISPR-Cas9 knockout; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; NC: negative control; PAMs: porcine alveolar macrophages; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PRRSV: porcine reproductive and respiratory syndrome virus; qRT-PCR: quantitative real-time PCR; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID50: 50% tissue culture infective dose; TFEB: transcription factor EB; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; WT: wild type.

Animals↗

PubMed2025

Panduratin A Induces Autophagy Through AMPK Activation Independent of mTOR Inhibition and Restricts Mycobacterium tuberculosis in Host Macrophages.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health burden, especially with the increasing prevalence of drug-resistant strains. There is an urgent need for new therapeutics that act via alternative mechanisms. Autophagy, a vital cell-autonomous defense process, allows macrophages to degrade intracellular pathogens such as Mtb and has gained attention as a potential target for host-directed therapy. In this study, we conducted a high-content imaging screen of herb-derived compounds to identify autophagy inducers in RAW264.7 macrophages. Panduratin A (NPA), a natural compound from Boesenbergia rotunda, was found to potently induce autophagy. NPA promoted autophagic vacuole formation in a dose-dependent fashion at low micromolar levels. Its autophagy-inducing effect was validated using RFP-GFP-LC3 dual fluorescence assays and immunoblotting in the presence of bafilomycin A1. Further mechanistic analysis revealed that NPA activates autophagy through AMPK activation, independent of mTOR inhibition. Importantly, NPA significantly promoted intracellular Mtb clearance and increased colocalization of Mtb with autophagosomes and lysosomes, in a manner dependent on Beclin-1. These findings highlight NPA as a potent enhancer of macrophage antimicrobial responses via autophagy, supporting its potential as a candidate for host-directed adjunctive therapy against TB.

Autophagy↗

PubMed2024

Deciphering the molecular nexus of BTG2 in periodontitis and diabetic kidney disease.

OBJECTIVE: To investigate the role of BTG2 in periodontitis and diabetic kidney disease (DKD) and its potential underlying mechanism. METHODS: Gene expression data for periodontitis and DKD were acquired from the Gene Expression Omnibus (GEO) database. Differential expression analysis identified co-expressed genes between these conditions. The Nephroseq V5 online nephropathy database validated the role of these genes in DKD. Pearson correlation analysis identified genes associated with our target gene. We employed Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) networks to elucidate potential mechanisms. Expression levels of BTG2 mRNA were examined using quantitative polymerase Chain Reaction (qPCR) and immunofluorescence assays. Western blotting quantified proteins involved in epithelial-to-mesenchymal transition (EMT), apoptosis, mTORC1 signaling, and autophagy. Additionally, wound healing and flow cytometric apoptosis assays evaluated podocyte migration and apoptosis, respectively. RESULTS: Analysis of GEO database data revealed BTG2 as a commonly differentially expressed gene in both DKD and periodontitis. BTG2 expression was reduced in DKD compared to normal conditions and correlated with proteinuria. GSEA indicated enrichment of BTG2 in the EMT and mTORC1 signaling pathways. The PPI network highlighted BTG2's relevance to S100A9, S100A12, and FPR1. Immunofluorescence assays demonstrated significantly lower BTG2 expression in podocytes under high glucose (HG) conditions. Reduced BTG2 expression in HG-treated podocytes led to increased levels of EMT markers (α-SMA, vimentin) and the apoptotic protein Bim, alongside a decrease in nephrin. Lower BTG2 levels were associated with increased podocyte mobility and apoptosis, as well as elevated RPS6KB1 and mTOR levels, but reduced autophagy marker LC3. CONCLUSION: Our findings suggest that BTG2 is a crucial intermediary gene linking DKD and periodontitis. Modulating autophagy via inhibition of the mTORC1 signaling pathway, and consequently suppressing EMT, may be pivotal in the interplay between periodontitis and DKD.

Periodontitis↗

PubMed2026

lncRNA JPX promotes radioresistance in nasopharyngeal carcinoma via the miR-1301-3p/PIK3R2-mediated autophagy pathway.

BACKGROUND: Nasopharyngeal carcinoma (NPC) represents an aggressive head and neck malignancy with high metastatic potential. Radioresistance remains a major therapeutic obstacle associated with poor prognosis. Although the long non-coding RNA (lncRNA) JPX has been implicated in various cancers, its specific role in NPC radioresistance requires further elucidation. This study aimed to investigate whether JPX modulates radiosensitivity through autophagy regulation and to delineate the underlying molecular mechanisms. METHODS: JPX expression was analyzed in NPC cell lines and The Cancer Genome Atlas (TCGA) datasets, with subcellular localization determined through cellular fractionation. Functional characterization was performed using short hairpin RNA (shRNA)-mediated knockdown in CNE-2 and HONE-1 cell lines. Radiosensitivity was evaluated by clonogenic survival assays at a clinically relevant radiation dose, with cell viability assessed by MTT as a screening measure. while autophagy activity was assessed through Western blot analysis of LC3-II and p62. Molecular interactions were validated using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: JPX was significantly upregulated in head and neck squamous cell carcinoma (HNSCC) tissues and NPC cell lines, showing predominant cytoplasmic localization. Clinical association analysis in the TCGA-HNSCC cohort revealed that elevated JPX expression correlated with advanced tumor stage and poor overall survival, although NPC-specific clinical validation remains to be established. Genetic silencing of JPX attenuated autophagic flux and enhanced radiosensitivity. Mechanistic investigations revealed that JPX functions as a competitive endogenous RNA (ceRNA) functionally associating with miR-1301-3p, thereby alleviating miR-1301-3p-mediated repression of PIK3R2 and subsequently activating pro-survival autophagy pathways. CONCLUSIONS: The findings demonstrate that JPX promotes radioresistance in NPC through a ceRNA mechanism involving the miR-1301-3p/PIK3R2/autophagy regulatory axis. The JPX/miR-1301-3p/PIK3R2 axis thus emerges as a potential mechanistic candidate for radiosensitization; however, this notion remains strictly provisional and requires rigorous validation in authenticated NPC models, in vivo systems, and patient-derived samples before any translational consideration can be justified. Despite the cell line limitations acknowledged herein, our findings provide a mechanistic framework for understanding JPX-mediated radioresistance that warrants further investigation in more physiologically relevant models.

JPX↗