Phthalates (PAEs) are endocrine-disrupting chemicals widely used in industrial applications, with significant implications for human health. Growing evidence highlights epigenetic and epitranscriptomic mechanisms, specifically DNA methylation, histone modification, RNA modification and non-coding RNAs, as pivotal mediators of PAE toxicity. This review synthesizes current knowledge on how PAEs disrupt these regulatory layers, linking their dysregulation to diseases such as psoriasis, diabetes, atherosclerosis, reproductive disorders, and cancer. We recapitulate PAE-induced alterations in global and gene-specific DNA methylation patterns, chromatin remodeling via histone acetylation and methylation, and dynamic RNA modifications, alongside the aberrant expression of miRNAs and lncRNAs, which collectively drive pathological outcomes. Additionally, we discuss the potential of epigenetic and epitranscriptomic markers as diagnostic tools and therapeutic targets for PAE-associated diseases. By integrating these dual regulatory perspectives, our work bridges a gap in understanding PAE toxicity and underscores the need for interdisciplinary research to mitigate exposure risks. Finally, we outline future directions to unravel long-term epigenetic/epitranscriptomic impacts, offering novel insights into molecular mechanisms and intervention strategies.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy characterized by a poor prognosis, mainly caused by late diagnosis and the absence of effective treatment options. Malignant transformation of B-cells emphasizes the necessity of novel biomarkers for early diagnosis and prognosis. Dysregulation of long non-coding RNAs (lncRNAs), fundamental regulators in biological pathways, is linked to the development of different cancer types, including DLBCL. In this study, we assessed lncRNA HOTAIR expression in DLBCL and its association with clinicopathological features while investigating the HOTAIR knockdown effects on DLBCL cell lines. RNA extraction, cDNA synthesis, and qRT-PCR were performed on tumor tissue samples from DLBCL patients and non-tumorous lymph nodes. HOTAIR knockdown was performed using short hairpin RNAs (shRNA) integrated into pmiRZip vectors, transfected into SU-DHL6 and OCI-LY10 cells through lentivirus. Then, cells were treated with doxorubicin to determine the effect of HOTAIR on drug sensitivity via apoptosis and cell cycle assays. The expression of HOTAIR was upregulated in DLBCL samples (p = 0.0001) and showed diagnostic potential with an area under the curve (AUC) of 0.85. No significant correlation was found between patients' clinicopathological characteristics and HOTAIR expression levels. HOTAIR knockdown induced apoptosis by a 34-40 % increase in cell death and led to G2 phase arrest, enhancing sensitivity to doxorubicin in HOTAIR-knocked down cells. Targeting HOTAIR may improve treatment outcomes by promoting apoptosis and enhancing doxorubicin sensitivity in DLBCL cells.

Macrophages are key cells in the pathogenesis of chronic inflammatory diseases. Interleukin (IL)-27 is a pleiotropic cytokine with mostly immunoregulatory functions and associated with a wide array of diseases. There is little knowledge on the effects of IL-27 on human macrophages. Here, we characterise the effect of IL-27 on human blood derived CD14+ monocyte derived macrophages (MDMs), in resting state and under inflammatory stimulation (+LPS/PepG), through targeted transcriptomic expression profile, phagocytosis of E. coli bioparticles and expression of intracellular and secreted proteins by DIA mass spectrometry and multiplex ELISA, respectively. There was no change in pro-inflammatory cytokine gene expression with IL-27. IL-27 led to changes in the chemokine secretome, inducing a significant upregulation of the chemokines CXCL9 and CXCL10 and reduced expression of CCL2, CCL7, CCL13, CCL18, CCL24, CXCL13, IL-10 and Midkine. Macrophage phagocytosis was not affected by IL-27. IL-27 effects on intracellular proteome were subtle overall. Using unadjusted p values, changes were most pronounced in the resting state, with a significant (p < 0.05) increase in 106 and decrease in 11 proteins. Enrichment analysis suggested regulation of several biological processes by IL-27, including cellular response to type II interferon. Overall, we demonstrate novel biology of IL-27 mediated effects in human macrophages.

Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, posing a severe threat to female health. Previous research indicates that cuproptosis is a copper-dependent form of regulated cell death, holding potential as a therapeutic avenue. This study aimed to identify and validate Cuproptosis-Related Genes (CRGs) as biomarkers and therapeutic targets in cervical cancer. Transcriptomic data from TCGA and GTEx databases were analysed alongside curated literature data, leading to the identification of 67 pivotal CRGs. Diagnostic and prognostic models were constructed using machine learning algorithms and LASSO-Cox regression, respectively. Glutathione synthetase (GSS) was selected for subsequent functional validation in cellular assays. Drug sensitivity analysis, mechanistic investigations and in vivo experiments were conducted to evaluate therapeutic potential. Statistical analyses were performed using R and GraphPad Prism. Our analysis identified GSS as a core gene. Functional experiments showed that GSS promotes cervical cancer cell proliferation and invasion under cuproptosis-inducing conditions. Drug sensitivity analysis linked GSS to vorinostat, which inhibits tumour growth by suppressing the PI3K/Akt pathway and downregulating GSS. These findings were confirmed in both in vitro and in vivo studies. This study identifies GSS as a key cuproptosis regulator and a promising therapeutic target in cervical cancer, suggesting a novel precision medicine strategy.

This study explored the impact of vaginal microbes, metabolites, and METTL1-mediated m7G modification of BRCA1 mRNA on High-Grade Serous Ovarian Cancer (HGSOC).

Salvianolic acid B (Sal B), a polyphenolic compound with potential anti-cancer properties, possesses mechanisms of action that remain incompletely understood. This study aimed to elucidate the effects of Sal B on the A549 cell line and to investigate the underlying molecular mechanisms. In this study, A549 cells were co-cultured with varying concentrations of Sal B for 48 h. We utilized MTT, wound healing, and transwell assays to evaluate cell proliferation, migration, and invasion, respectively. The expression levels of miR-23a-3p, E-cadherin, N-cadherin, Snail, PTEN, and p-AKT were analyzed using western blotting and RT-PCR. Additionally, a xenograft model of transplanted A549 tumors was employed to assess the in vivo antitumor effects of Sal B. Immunohistochemistry (IHC) was utilized to measure the expression of cleaved PARP, E-cadherin, N-cadherin and Snail. Our findings demonstrated that Sal B inhibited A549 cell proliferation, migration, and invasion in a dose-dependent manner. Furthermore, in vivo experiments revealed that Sal B significantly suppressed the growth and metastasis of A549 tumors, as evidenced by elevated levels of cleaved PARP and E-cadherin, along with a marked reduction in N-cadherin and Snail compared with the control group. Importantly, we observed that Sal B significantly downregulated miR-23a-3p expression, whereas the overexpression of miR-23a-3p via transfection attenuated the inhibitory effects of Sal B on A549 cell proliferation and metastasis. Western blot results indicated that the downregulation of miR-23a-3p led to the upregulation of PTEN and the downregulation of p-AKT. Collectively, these findings suggest that Sal B's mechanism of action in NSCLC may involve the modulation of the miR-23a/PTEN/AKT signaling pathway, thereby highlighting its potential as a therapeutic candidate for NSCLC.

The persistent issues of drug resistance and tumor recurrence remain major challenges in bladder cancer (BCa) treatment, severely impacting patient outcomes. In this study, we found that Triosephosphate isomerase 1 (TPI1) plays a crucial role in influencing gemcitabine (Gem) resistance in BCa. TPI1 is significantly upregulated in Gem-resistant BCa tissues, and the knockdown of TPI1 markedly increases Gem sensitivity and chemotherapy-induced apoptosis both in vivo and in vitro. Meanwhile, the same was validated in Gem-resistant strains. Mechanistically, transcriptome sequencing and transmission electron microscopy, among others, revealed that TPI1 promoted Gem-associated autophagy. Furthermore, mass spectrometry and co-immunoprecipitation assays demonstrated that TPI1 directly binds to the BH3 domain of Beclin-1. This interaction competitively disrupts the binding between Bcl-2 and Beclin-1, thereby relieving Bcl-2-mediated inhibition of Beclin-1. Furthermore, the interaction between TPI1 and Beclin-1 promotes the formation of PIK3C3-C1, which in turn enhances the interaction between PIK3C3-C1 and the ULK1 complex, thereby increasing the phosphorylation of Beclin-1 at Ser15. In addition, TPI1 also enhanced mitochondrial autophagy induced by Gem in BCa cells and tissues. Importantly, a transcription factor, c-Myc, that regulates TPI1 expression was also identified, and dual luciferase and Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) analysis showed that c-Myc binds primarily to the promoter region of TPI1. Our results suggest that TPI1 plays an important role in regulating the formation of autophagic complexes, and that promoting autophagy significantly increased Gem resistance in BCa.

Bladder cancer is a common malignancy, and the insensitivity of advanced bladder cancer to cisplatin poses an imminent challenge to treatment. Our study aims to identify novel targets that mediate cisplatin responsiveness in bladder cancer. Accordingly, overexpression of the histone demethylase KDM4A in clinical cohorts was found in association with poor prognosis. Tissue culture and animal tests showed that KDM4A pis ro-proliferative in bladder cancer cells. Using co-immunoprecipitation and mass spectrometry methods, we identified that USP7 is an interacting partners in KDM4A protein complex, in which USP7 catalyzes KDM4A proteins deubiquitination that uncouples the proteasome-dependent degradation. In accordance, a positive correlation between USP7 and KDM4A protein expression was noted in bladder cancer clinical samples. Functional validation tests confirmed that USP7 and KDM4A act complementarily to drive bladder cancer cell proliferation. Importantly, cell and animal assays all evidenced that antagonizing the USP7-KDM4A axis would aggravate cisplatin-induced DNA damage and sensitize cisplatin responsiveness.

Fosfomycin is increasingly used in combination therapies for multidrug-resistant bacterial infections. This study aimed to investigate the effect of sub-minimum inhibitory concentrations (sub-MICs) of fosfomycin on the virulence of Staphylococcus aureus to optimize therapeutic strategies.

Diabetic nephropathy (DN) is a critical complication of diabetes mellitus. Icariside II, a bioactive compound from epimedium, is known for its anti-hyperglycemic properties, but its mechanism in DN remains unclear. Our study aimed to explore Icariside II's protective effects against high-glucose (HG) induced podocytes injury using an in vitro model. We assessed cell viability and proliferation using the CCK8 assay after treating cells with Icariside II. qPCR and Western blot analysis were used to measure the mRNA and protein expressions of DNMT1, α-SMA, fibronectin and collagen IV. Molecular docking studies were performed using DNMT1's 3D structure from the Protein Data Bank. DNMT1 overexpression levels were quantified via qRT-PCR and western blot. Immunofluorescence staining and ELISA assays evaluated TGF-β1, inflammatory cytokines, respectively. GSH, MDA, and intracellular Fe2+ were measured using biochemical assay kits and FerroOrange probes, respectively. Western blot analysis was used to measure the protein expressions of GPX4, SLC7A11, ACSL4 and TFR1. Results showed Icariside II inhibits HG induced proliferation, inflammation and extracellular matrix (ECM) accumulation in MPC-5 cells. Besides, Icariside II also reduced inflammation, ECM accumulation and ferroptosis by downregulating DNMT1. However, the intervention treatment with Ferrostatin-1 could effectively counteract this effect. Icariside II mitigated HG-induced inflammation and ECM accumulation by down-regulating DNMT1 and ferroptosis.

The present study evaluated the effects of dietary selenium (Se) supplementation on growth performance, physiological responses, tissue fatty acid profiles, and the expression of genes related to fatty acid metabolism in juvenile grouper (Epinephelus coioides). A control diet based on soy protein concentrate, replacing 40% of the fish meal protein, was supplemented with graded levels of Se at 0, 0.3, 0.6, and 1.0 mg Se kg-1. A fish meal-based reference diet was also included for comparison. The five test feeds were assigned to three groups of fish with an average weight of 13.14 ± 0.03 g, and cultured in a recirculating aquaculture system for 56 days. No significant differences (p > 0.05) were observed among dietary treatments in terms of weight gain, feed efficiency, survival, and whole-body proximate composition of grouper. Tissue Se concentrations in whole body, liver, and muscle, hepatic glutathione peroxidase activity, and proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increased proportionally with dietary Se levels. Whole-body EPA retention was highest in fish fed the reference diet and 1.0 mg Se kg-1, intermediate in the 0.6 mg Se kg-1 group, and lowest in the 0 and 0.3 mg Se kg-1 groups. Similarly, DHA retention was elevated in fish fed the reference diet and 1.0 mg Se kg-1 diet. Furthermore, hepatic mRNA expression levels of fatty acid desaturase 2 (FAD2), elongase 5 (FAD5), and peroxisome proliferator-activated receptor gamma (PPAR-γ) were upregulated in a dose-dependent manner in response to dietary Se. These findings demonstrate that Se supplementation can enhance antioxidant defense mechanisms, tissue Se deposition, and the hepatic accumulation of EPA and DHA.

Most treatments for advanced NSCLC are no longer effective due to drug resistance, causing tumor progression. Cancer stem cells drive tumor development and treatment resistance. Moreover, HDAC1 and ARID1A play a role in tumor progression in EGFR-mutated NSCLC. This study aimed to investigate the role of HDAC1 in propofol-mediated antitumor effects in NSCLC using A549 and HCC827 cell lines and NSCLC nude mouse tumor models. Our results demonstrated that propofol effectively inhibited the stemness, activity, proliferation, migration, and invasion of NSCLC cells and tumor growth in NSCLC nude mice. Propofol also downregulated the levels of CD133, CD44, ABCG2, and ALDH1A1 in NSCLC cells. Moreover, propofol promoted the enrichment of HDAC1 and ARID1A in the ALDH1A1 promoter region by promoting EGFR degradation, leading to H3K27 deacetylation and subsequent transcriptional repression of ALDH1A1. Beyond altering the localization of HDAC1, propofol also inhibited the expression of HDAC1 and the level of miR-21-5p. MG132 eliminated the inhibition of propofol on HDAC1-mediated DGCR8 deacetylation. Furthermore, HDAC1 overexpression reversed the inhibitory effect of propofol on miR-21-5p expression and NSCLC tumor growth. Therefore, propofol inhibited HDAC1 expression to downregulate miR-21-5p, resulting in the inhibition of NSCLC tumors. As a conclusion, propofol inhibited the stem characteristics and growth of NSCLC tumor by regulating the translocation and expression of HDAC1. This study provides potential targets and treatment options for the treatment of advanced NSCLC tumors.

Colorectal cancer (CRC) is a predominant contributor to global cancer-associated mortality worldwide. Oxaliplatin (OXP), a foundational chemotherapeutic agent for CRC, often exhibits limited efficacy due to the emergence of drug resistance. Although endothelin-1 (EDN1) has been implicated in tumor drug resistance, its role in oxaliplatin resistance in CRC remains poorly defined. This work aimed to define how EDN1 contributes to oxaliplatin resistance and to explore its potential as a therapeutic target.

Gastric cancer (GC) is often associated with high invasiveness, epithelial-mesenchymal transition (EMT), and resistance to 5-fluorouracil (5-FU), highlighting the need for novel therapeutic targets. This study explored whether diallyl disulfide (DADS) upregulates retinoic acid-related orphan receptor alpha (RORα) to weaken the protein kinase C alpha (PKCα)/RORα-mediated RORα/β-catenin pathway, thereby inhibiting GC cell invasion, epithelial-mesenchymal transition (EMT), and enhancing 5-FU sensitivity.

Spring wheat is predominantly cultivated in saline-alkaline regions. However, little is known about the mechanisms underlying the salt tolerance of spring wheat. This study explored physiological and gene expression regulation mechanisms by which a salt-tolerant spring wheat variety (QM-1) resists salt stress during the seedling stage. Under salt stress, QM-1 displayed higher root Na+ concentration and root biomass but lower shoot Na+ concentration than the control variety (NCY-4). Increasing root biomass was helpful to reduce Na+ influx into the shoots via Na+ compartmentalization at the roots for QM-1 under salt stress. Metabolomic analysis revealed that NCY-4 had synthesis defects in many flavonoids in the leaves, while high flavonoid accumulation was a specific metabolic characteristic of QM-1 under salt stress. Exogenous application experiments confirmed that exogenous application of quercetin-7-O-glucoside alleviated salt stress damage in NCY-4, whereas application of neither flavonoids nor carbohydrates alone can alleviate damage of salt stress to NCY-4. Transcriptomics showed that many key flavonoid synthesis genes (4CL, CHS, ANR), glycosyltransferase genes (responsible for flavonoid glycosylation), key carbohydrate metabolic synthesis genes, and flavonoid synthesis regulatory genes (R2R3-MYB, bHLH) displayed significantly higher expression levels in the leaves of QM-1 than in those of NCY-4 under salt stress. The above data indicated that flavonoids, like quercetin-7-O-glucoside, may play a critical role in QM-1. In response to salt stress, the salt-tolerant spring wheat variety enhanced whole-plant tolerance by increasing root biomass and root/shoot ratio to improve ionic stress tolerance and by accumulating flavonoids in leaves to facilitate ROS scavenging.

Exogenous γ-aminobutyric acid (GABA) alleviates nitrogen (N) deficiency stress in plants; however, its effects on secondary metabolite biosynthesis in medicinal plants under such conditions remain poorly understood. This study investigated the effects of GABA on the growth and andrographolide biosynthesis in Andrographis paniculata (Chuanxinlian) under low N (LN, 1 mmol L-1 NO3-) using soilless culture. Our findings indicated that both 5 mmol L-1 GABA and nitrate-N (NN) treatments enhanced plant N accumulation, upregulated photosynthesis and N metabolism, and downregulated secondary metabolism such as flavonoid and andrographolide biosynthesis, consistent with the protein competition model (PCM) and carbon/nutrient balance hypothesis (CNBH). Nevertheless, compared to NN, GABA attenuated the decline in andrographolide content and maintained levels of 14-deoxyandrographolide and dehydroandrographolide. Consequently, GABA preserved the yield of diterpenoid lactones, whereas NN treatment resulted in a significant reduction. Metabolomic analyses revealed similarities between GABA-treated and control plants in glycolysis and the tricarboxylic acid (TCA) cycle. Additionally, transcriptome analysis revealed that upregulated differentially expressed genes (DEGs) in both control and GABA treatments were enriched in sulfur-related metabolism, extracellular signaling pathways, and cyanoamino acid metabolism, suggesting these processes are closely associated with the regulation of andrographolide biosynthesis. The cytochrome P450 enzymes CYP71D11 and CYP76T24 were identified as promising candidates involved in andrographolide biosynthesis. Collectively, these results demonstrate that exogenous GABA not only alleviates N deficiency stress but also mitigates reductions in andrographolide content in Chuanxinlian, suggesting that GABA presents a promising alternative to nitrate fertilizers for achieving high-yield and high-quality production of Chuanxinlian under N-deficient conditions.

Per- and polyfluoroalkyl substances (PFAS) represent a large class of > 11,000 synthetic organofluorine compounds that are globally distributed and consistently detected in human serum. Recent studies suggest that environmentally relevant exposures to short-chain PFAS can disrupt ATP-binding cassette (ABC) transporters, which regulate xenobiotic disposition and are critical for human health. This study examined the effects of short-term (45 min) and long-term (48 h) exposures to 1 nM or 1 µM of four short-chain PFAS, perfluorobutanesulfonic acid (PFBS), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), and 6:2 fluorotelomer alcohol (6:2 FTOH), using differentiated HepaRG hepatocytes. Functional assays evaluated changes in efflux activity, while gene expression analysis quantified transcriptional responses across 38 ABC transporters. Following 48-h exposures, both 1 nM and 1 µM treatments significantly decreased the retention of fluorescent substrates CMFDA, BODIPY-cholesterol, Hoechst 33342, and Rhodamine 123 relative to controls, indicating enhanced efflux transporter activity. Consistent with these results, transcriptional analysis revealed significant upregulation of multiple ABC genes, including ABCG2 (BCRP), ABCB1 (P-gp/MDR1), and ABCC1 (MRP1). In contrast, short-term exposures produced no measurable effects on efflux activity. Together, these findings demonstrate that environmentally relevant concentrations of short-chain PFAS can alter the expression and activity of key hepatic ABC transporters. Such changes may disrupt the handling of endogenous compounds and pharmaceuticals, raising concerns that low-level PFAS exposure could influence drug disposition and human health outcomes.

Trichostatin A (TSA) is a strong epigenetic tool that promises to have the future in the field of immune reprogramming, but its mechanisms of action in patient-derived immune cells in colorectal cancer (CRC) are still poorly studied. We examined in this current study the molecular and functional immune phenotype of lymphocytes of CRC patients and healthy donors in response to low-dose (0.1 nM), short-term (12 h) treatment with TSA, which aims at narrowing cytotoxicity and retaining epigenetic regulation. The TSA potentiated pro-inflammatory cytokines (IFN-gamma, IL-12, TNF-alpha) and inhibited immunoregulatory interleukins (IL-4, IL-10, IL-17, CCL5, Granzyme B in CRC-derived immune cells). At the transcriptional level, TSA induced TBX21 and TP53 and repressed GATA3, FOXP3, RORC, and MYC. Epigenetic profiling showed H3K14ac and H3K4me3 markups, H3K27me3 and HDAC1 downregulation, promoter hypermethylation of immune territory, less R-loop formation, and higher methylation of m6A RNA-partaking in the recommendation that TSA promotes chromatin and transcriptome multilayered modification. The TSA pretreated lymphocytes elicited cytotoxic effect in HT-29 CRC cells and also showed redox disproportion via depletion of glutathione and increase in nitric oxide. Although previous research focuses on the direct impact of TSA on tumor cells, in our study, we exclusively highlight TSA ability to reprogram the immune cells epigenetically in a more inflammatory tumor-reactive phenotype. The findings justify the possibility of TSA as an epigenetic adjunct of low toxicity in immuno-oncology and form a basis to continue in vivo and translational study in CRC immunotherapy.

N6-methyladenosine (m6A) modification of mRNAs is a predominant epigenetic regulatory mechanism in tumor initiation and progression. Cancer stem cells (CSCs) are the key drivers of colorectal cancer (CRC) initiation and chemotherapy resistance. Here, we found that the m6A reader YT521-B homologous domain family, member 1 (YTHDF1), promotes CRC stemness, tumorigenesis, and chemotherapy resistance. YTHDF1 protein expression was positively correlated with CD133 and LGR5 expression in human CRC tissues (N = 184, P < 0.001 for both markers). YTHDF1 promoted m6A-dependent self-renewal in CSCs and patient-derived organoids and increased the tumor-initiating potential in vivo. Lgr5-specific Ythdf1-KI mice presented accelerated ApcMin/+ (P < 0.05) and AOM/DSS (P < 0.05)-induced colorectal tumorigenesis, whereas Lgr5-specific Ythdf1 knockout in ApcMin/+ mice inhibited tumorigenesis (P < 0.01). Integrative multiomic profiling revealed NOTCH1 as a downstream target. YTHDF1 binds m6A-modified NOTCH1, promoting its translation and enhancing NOTCH signaling. NOTCH1 knockdown or blockade by the γ-secretase inhibitor DAPT abolished YTHDF1-mediated tumorigenesis in Ythdf1 knock-in mice (P < 0.01). YTHDF1 promoted resistance to oxaliplatin and 5-fluorouracil in CSCs by inhibiting apoptosis and DNA damage. AOM/DSS-treated Ythdf1 knock-in mice presented increased resistance to oxaliplatin (P < 0.001) and 5-fluorouracil (P < 0.05). Translationally, in vivo targeting of YTHDF1 via VNP-encapsulated siYTHDF1 or salvianolic acid C inhibited tumor growth (P < 0.05 for both treatments) and increased treatment efficacy when VNP was combined with oxaliplatin (P < 0.05, SAC: P < 0.01) or 5-fluorouracil (P < 0.05 for both treatments). In conclusion, YTHDF1 promotes stemness and chemoresistance in CRC via NOTCH1 activation. Targeting YTHDF1 is a promising strategy to improve the outcome of chemotherapy in CRC.

Immunomodulatory agents (IMiDs) are a cornerstone in the successful management of multiple myeloma (MM). However, acquired IMiD resistance leading to disease relapses remains a major barrier. Hydrogen peroxide generation and oxidative stress are key mediators that determine IMiD's effectiveness in MM. Iron plays a key role in the generation of oxidative stress; therefore, cellular iron levels are tightly governed. FTH1 is the major iron storage protein that tightly regulates cellular iron availability. Hence, the present study is targeted to investigate the role of FTH1 in MM and IMiD resistance.