Blog

  • SLC7A11 as a bridge between ferroptosis and disulfidptosis: a promising target for tumor treatment | Cell Communication and Signaling

    SLC7A11 as a bridge between ferroptosis and disulfidptosis: a promising target for tumor treatment | Cell Communication and Signaling

  • Newton K, Strasser A, Kayagaki N, Dixit VM. Cell death. Cell. 2024;187(2):235–56. https://doi.org/10.1016/j.cell.2023.11.044.

    Article 
    PubMed 

    Google Scholar 

  • Green DR, Victor B. The pantheon of the fallen: why are there so many forms of cell death? Trends Cell Biol. 2012;22(11):555–6. https://doi.org/10.1016/j.tcb.2012.08.008.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–72. https://doi.org/10.1016/j.cell.2012.03.042.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bannai S, Kitamura E. Transport interaction of L-cystine and L-glutamate in human diploid fibroblasts in culture. J Biol Chem. 1980;255(6):2372–6.

    Article 
    PubMed 

    Google Scholar 

  • Fotiadis D, Kanai Y, Palacín M. The SLC3 and SLC7 families of amino acid transporters. Mol Aspects Med. 2013;34(2–3):139–58. https://doi.org/10.1016/j.mam.2012.10.007.

    Article 
    PubMed 

    Google Scholar 

  • Koppula P, Zhang Y, Zhuang L, Gan B. Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer. Cancer Commun (Lond). 2018;38(1):12. https://doi.org/10.1186/s40880-018-0288-x.

    Article 
    PubMed 

    Google Scholar 

  • Mou Y, Wang J, Wu J, He D, Zhang C, Duan C, et al. Ferroptosis, a new form of cell death: opportunities and challenges in cancer. J Hematol Oncol. 2019;12(1):34. https://doi.org/10.1186/s13045-019-0720-y.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu J, Xia X, Huang P, xCT:. A critical molecule that links cancer metabolism to redox signaling. Mol Ther. 2020;28(11):2358–66. https://doi.org/10.1016/j.ymthe.2020.08.021.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Koppula P, Zhuang L, Gan B. Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy. Protein Cell. 2021;12(8):599–620. https://doi.org/10.1007/s13238-020-00789-5.

    Article 
    PubMed 

    Google Scholar 

  • Liu X, Nie L, Zhang Y, et al. Actin cytoskeleton vulnerability to disulfide stress mediates Disulfidptosis. Nat Cell Biol. 2023;25(3):404–14. https://doi.org/10.1038/s41556-023-01091-2.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lee N, Park SJ, Lange M, et al. Selenium reduction of ubiquinone via SQOR suppresses ferroptosis. Nat Metab. 2024;6(2):343–58. https://doi.org/10.1038/s42255-024-00974-4.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 2021;22(4):266–82. https://doi.org/10.1038/s41580-020-00324-8.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lin Q, Zhou H, Zeng J, et al. Bioactive polysaccharides mediate ferroptosis to modulate tumor immunotherapy. Int J Biol Macromol. 2024. https://doi.org/10.1016/j.ijbiomac.2024.135147.

    Article 
    PubMed 

    Google Scholar 

  • Mao C, Wang M, Zhuang L, Gan B. Metabolic cell death in cancer: ferroptosis, cuproptosis, disulfidptosis, and beyond. Protein Cell. 2024;15(9):642–60. https://doi.org/10.1093/procel/pwae003.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen X, Kang R, Kroemer G, Tang D. Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol. 2021;18(5):280–96. https://doi.org/10.1038/s41571-020-00462-0.

    Article 
    PubMed 

    Google Scholar 

  • Tang D, Chen X, Kang R, Kroemer G. Ferroptosis: molecular mechanisms and health implications. Cell Res. 2021;31(2):107–25. https://doi.org/10.1038/s41422-020-00441-1.

    Article 
    PubMed 

    Google Scholar 

  • Tong X, Tang R, Xiao M, et al. Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and Cuproptosis research. J Hematol Oncol. 2022;15(1):174. https://doi.org/10.1186/s13045-022-01392-3.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lang X, Green MD, Wang W, et al. Radiotherapy and immunotherapy promote tumoral lipid oxidation and ferroptosis via synergistic repression of SLC7A11. Cancer Discov. 2019;9(12):1673–85. https://doi.org/10.1158/2159-8290.CD-19-0338.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li Y, Yan J, Zhao Q, Zhang Y, Zhang Y. ATF3 promotes ferroptosis in sorafenib-induced cardiotoxicity by suppressing Slc7a11 expression. Front Pharmacol. 2022;13:904314. https://doi.org/10.3389/fphar.2022.904314.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bassi MT, Gasol E, Manzoni M, et al. Identification and characterisation of human xCT that co-expresses, with 4F2 heavy chain, the amino acid transport activity system Xc-. Pflugers Arch. 2001;442(2):286–96. https://doi.org/10.1007/s004240100537.

    Article 
    PubMed 

    Google Scholar 

  • Bridges CC, Kekuda R, Wang H, et al. Structure, function, and regulation of human cystine/glutamate transporter in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2001;42(1):47–54.

    PubMed 

    Google Scholar 

  • Kim JY, Kanai Y, Chairoungdua A, et al. Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. Biochim Biophys Acta. 2001;1512(2):335–44.

    Article 
    PubMed 

    Google Scholar 

  • Sato H, Tamba M, Kuriyama-Matsumura K, Okuno S, Bannai S. Molecular cloning and expression of human xCT, the light chain of amino acid transport system Xc-. Antioxid Redox Signal. 2000;2(4):665–71. https://doi.org/10.1089/ars.2000.2.4-665.

    Article 
    PubMed 

    Google Scholar 

  • Li S, Lu Z, Sun R, et al. The role of SLC7A11 in cancer: friend or foe? Cancers (Basel). 2022;14(13):3059. https://doi.org/10.3390/cancers14133059.

    Article 
    PubMed 

    Google Scholar 

  • Yang J, Zhou Y, Xie S, et al. Metformin induces ferroptosis by inhibiting ufmylation of SLC7A11 in breast cancer. J Exp Clin Cancer Res. 2021;40(1):206. https://doi.org/10.1186/s13046-021-02012-7.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Badgley MA, Kremer DM, Maurer HC, et al. Cysteine depletion induces pancreatic tumor ferroptosis in mice. Science. 2020;368(6486):85–9. https://doi.org/10.1126/science.aaw9872.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hong T, Lei G, Chen X, et al. PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer. Redox Biol. 2021;42:101928. https://doi.org/10.1016/j.redox.2021.101928.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Park JW, Kilic O, Deo M, et al. CIC reduces xCT/SLC7A11 expression and glutamate release in glioma. Acta Neuropathol Commun. 2023;11(1):13. https://doi.org/10.1186/s40478-023-01507-y.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Long Y, Tao H, Karachi A, et al. Dysregulation of glutamate transport enhances Treg function that promotes VEGF blockade resistance in glioblastoma. Cancer Res. 2020;80(3):499–509. https://doi.org/10.1158/0008-5472.CAN-19-1577.

    Article 
    PubMed 

    Google Scholar 

  • Yuan L, Li S, Chen Q, et al. EBV infection-induced GPX4 promotes chemoresistance and tumor progression in nasopharyngeal carcinoma. Cell Death Differ. 2022;29(8):1513–27. https://doi.org/10.1038/s41418-022-00939-8.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Combs JA, DeNicola GM. The non-essential amino acid cysteine becomes essential for tumor proliferation and survival. Cancers (Basel). 2019;11(5):678. https://doi.org/10.3390/cancers11050678.

    Article 
    PubMed 

    Google Scholar 

  • Carlisle AE, Lee N, Matthew-Onabanjo AN, et al. Selenium detoxification is required for cancer-cell survival. Nat Metab. 2020;2(7):603–11. https://doi.org/10.1038/s42255-020-0224-7.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lee N, Carlisle AE, Kim D. Examining xCT-mediated selenium uptake and Selenoprotein production capacity in cells. Methods Enzymol. 2022;662:1–24. https://doi.org/10.1016/bs.mie.2021.10.002.

    Article 
    PubMed 

    Google Scholar 

  • Goji T, Takahara K, Negishi M, Katoh H. Cystine uptake through the cystine/glutamate antiporter xCT triggers glioblastoma cell death under glucose deprivation. J Biol Chem. 2017;292(48):19721–32. https://doi.org/10.1074/jbc.M117.814392.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Timmerman LA, Holton T, Yuneva M, et al. Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell. 2013;24(4):450–65. https://doi.org/10.1016/j.ccr.2013.08.020.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shin CS, Mishra P, Watrous JD, et al. The glutamate/cystine xCT antiporter antagonizes glutamine metabolism and reduces nutrient flexibility. Nat Commun. 2017;8:15074. https://doi.org/10.1038/ncomms15074.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Romero R, Sayin VI, Davidson SM, et al. Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nat Med. 2017;23(11):1362–8. https://doi.org/10.1038/nm.4407.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bannai S. Induction of cystine and glutamate transport activity in human fibroblasts by diethyl maleate and other electrophilic agents. J Biol Chem. 1984;259(4):2435–40.

    Article 
    PubMed 

    Google Scholar 

  • Bannai S, Kitamura E. Adaptive enhancement of cystine and glutamate uptake in human diploid fibroblasts in culture. Biochim Biophys Acta. 1982;721(1):1–10. https://doi.org/10.1016/0167-4889(82)90017-9.

    Article 
    PubMed 

    Google Scholar 

  • Bannai S, Sato H, Ishii T, Taketani S. Enhancement of glutathione levels in mouse peritoneal macrophages by sodium arsenite, cadmium chloride and glucose/glucose oxidase. Biochim Biophys Acta. 1991;1092(2):175–9. https://doi.org/10.1016/0167-4889(91)90153-o.

    Article 
    PubMed 

    Google Scholar 

  • Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman AM. The integrated stress response. EMBO Rep. 2016;17(10):1374–95. https://doi.org/10.15252/embr.201642195.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ye P, Mimura J, Okada T, et al. Nrf2- and ATF4-dependent upregulation of xCT modulates the sensitivity of T24 bladder carcinoma cells to proteasome inhibition. Mol Cell Biol. 2014;34(18):3421–34. https://doi.org/10.1128/MCB.00221-14.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ye Y, Chen A, Li L, et al. Repression of the antiporter SLC7A11/glutathione/glutathione peroxidase 4 axis drives ferroptosis of vascular smooth muscle cells to facilitate vascular calcification. Kidney Int. 2022;102(6):1259–75. https://doi.org/10.1016/j.kint.2022.07.034.

    Article 
    PubMed 

    Google Scholar 

  • Wang L, Liu Y, Du T, et al. ATF3 promotes erastin-induced ferroptosis by suppressing system Xc. Cell Death Differ. 2020;27(2):662–75. https://doi.org/10.1038/s41418-019-0380-z.

    Article 
    PubMed 

    Google Scholar 

  • Zhao X, Chen C, Qiu H, et al. The landscape of ATF3 in tumors: metabolism, expression regulation, therapy approach, and open concerns. Pharmacol Res. 2025;214:107666. https://doi.org/10.1016/j.phrs.2025.107666.

    Article 
    PubMed 

    Google Scholar 

  • Wang Y, Yang L, Zhang X, et al. Epigenetic regulation of ferroptosis by H2B monoubiquitination and p53. EMBO Rep. 2019;20(7):e47563. https://doi.org/10.15252/embr.201847563.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang Y, Koppula P, Gan B. Regulation of H2A ubiquitination and SLC7A11 expression by BAP1 and PRC1. Cell Cycle. 2019;18(8):773–83. https://doi.org/10.1080/15384101.2019.1597506.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tsuchihashi K, Okazaki S, Ohmura M, et al. The EGF receptor promotes the malignant potential of glioma by regulating amino acid transport system xc(-). Cancer Res. 2016;76(10):2954–63. https://doi.org/10.1158/0008-5472.CAN-15-2121.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu L, He J, Sun G, et al. The N6-methyladenosine modification enhances ferroptosis resistance through inhibiting SLC7A11 mRNA deadenylation in hepatoblastoma. Clin Transl Med. 2022;12(5):e778. https://doi.org/10.1002/ctm2.778.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhu Y, Zhang C, Huang M, Lin J, Fan X, Ni T. TRIM26 induces ferroptosis to inhibit hepatic stellate cell activation and mitigate liver fibrosis through mediating SLC7A11 ubiquitination. Front Cell Dev Biol. 2021;9:644901. https://doi.org/10.3389/fcell.2021.644901.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li S, Lu Z, Sun R, et al. The role of SLC7A11 in cancer: friend or foe? Cancers (Basel). 2022;14(13):3059. https://doi.org/10.3390/cancers14133059.

    Article 
    PubMed 

    Google Scholar 

  • Ishimoto T, Nagano O, Yae T, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell. 2011;19(3):387–400. https://doi.org/10.1016/j.ccr.2011.01.038.

    Article 
    PubMed 

    Google Scholar 

  • Gan W, Dai X, Dai X, et al. LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control. Nat Cell Biol. 2020;22(2):246–56. https://doi.org/10.1038/s41556-020-0463-6.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang W, Feng J, Ni Y, et al. The role of SLC7A11 in diabetic wound healing: novel insights and new therapeutic strategies. Front Immunol. 2024;15:1467531. https://doi.org/10.3389/fimmu.2024.1467531.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gu Y, Albuquerque CP, Braas D, et al. mTORC2 regulates amino acid metabolism in cancer by phosphorylation of the Cystine-Glutamate antiporter xCT. Mol Cell. 2017;67(1):128–e1387. https://doi.org/10.1016/j.molcel.2017.05.030.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171(2):273–85. https://doi.org/10.1016/j.cell.2017.09.021.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Doll S, Proneth B, Tyurina YY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 2017;13(1):91–8. https://doi.org/10.1038/nchembio.2239.

    Article 
    PubMed 

    Google Scholar 

  • Kagan VE, Mao G, Qu F, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol. 2017;13(1):81–90. https://doi.org/10.1038/nchembio.2238.

    Article 
    PubMed 

    Google Scholar 

  • Chu B, Kon N, Chen D, et al. ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway. Nat Cell Biol. 2019;21(5):579–91. https://doi.org/10.1038/s41556-019-0305-6.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jiang L, Kon N, Li T, et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature. 2015;520(7545):57–62. https://doi.org/10.1038/nature14344.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jennis M, Kung CP, Basu S, et al. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev. 2016;30(8):918–30. https://doi.org/10.1101/gad.275891.115.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang Y, Shi J, Liu X, et al. BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat Cell Biol. 2018;20(10):1181–92. https://doi.org/10.1038/s41556-018-0178-0.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu T, Jiang L, Tavana O, Gu W. The deubiquitylase OTUB1 mediates ferroptosis via stabilization of SLC7A11. Cancer Res. 2019;79(8):1913–24. https://doi.org/10.1158/0008-5472.CAN-18-3037.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Reck M, Carbone DP, Garassino M, Barlesi F. Targeting KRAS in non-small-cell lung cancer: recent progress and new approaches. Ann Oncol. 2021;32(9):1101–10. https://doi.org/10.1016/j.annonc.2021.06.001.

    Article 
    PubMed 

    Google Scholar 

  • Xiong HJ, Yu HQ, Zhang J, et al. Elevated FBXL6 activates both wild-type KRAS and mutant KRASG12D and drives HCC tumorigenesis via the ERK/mTOR/PRELID2/ROS axis in mice. Mil Med Res. 2023;10(1):68. https://doi.org/10.1186/s40779-023-00501-8.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mueller S, Engleitner T, Maresch R, et al. Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes. Nature. 2018;554(7690):62–8. https://doi.org/10.1038/nature25459.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hu K, Li K, Lv J, et al. Suppression of the SLC7A11/glutathione axis causes synthetic lethality in KRAS-mutant lung adenocarcinoma. J Clin Invest. 2020;130(4):1752–66. https://doi.org/10.1172/JCI124049.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lim JKM, Delaidelli A, Minaker SW, et al. Cystine/glutamate antiporter xCT (SLC7A11) facilitates oncogenic RAS transformation by preserving intracellular redox balance. Proc Natl Acad Sci U S A. 2019;116(19):9433–42. https://doi.org/10.1073/pnas.1821323116.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen X, Li J, Kang R, Klionsky DJ, Tang D. Ferroptosis: machinery and regulation. Autophagy. 2021;17(9):2054–81. https://doi.org/10.1080/15548627.2020.1810918.

    Article 
    PubMed 

    Google Scholar 

  • Wang W, Green M, Choi JE, et al. CD8 + T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 2019;569(7755):270–4. https://doi.org/10.1038/s41586-019-1170-y.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kim DH, Kim WD, Kim SK, Moon DH, Lee SJ. TGF-β1-mediated repression of SLC7A11 drives vulnerability to GPX4 Inhibition in hepatocellular carcinoma cells. Cell Death Dis. 2020;11(5):406. https://doi.org/10.1038/s41419-020-2618-6.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dai E, Han L, Liu J, et al. Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein. Autophagy. 2020;16(11):2069–83. https://doi.org/10.1080/15548627.2020.1714209.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bi G, Liang J, Zhao M, et al. MiR-6077 promotes cisplatin/pemetrexed resistance in lung adenocarcinoma via CDKN1A/cell cycle arrest and KEAP1/ferroptosis pathways. Mol Ther. 2022;28:366–86. https://doi.org/10.1016/j.omtn.2022.03.020.

    Article 

    Google Scholar 

  • Qin K, Zhang F, Wang H, et al. CircRNA circSnx12 confers cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis. BMB Rep. 2023;56(2):184–9. https://doi.org/10.5483/BMBRep.2022-0175.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sun C, Liu P, Pei L, Zhao M, Huang Y. Propofol inhibits proliferation and augments the anti-tumor effect of doxorubicin and paclitaxel partly through promoting ferroptosis in triple-negative breast cancer cells. Front Oncol. 2022;12:837974. https://doi.org/10.3389/fonc.2022.837974.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yadav P, Sharma P, Sundaram S, Venkatraman G, Bera AK, Karunagaran D. SLC7A11/ xCT is a target of miR-5096 and its restoration partially rescues miR-5096-mediated ferroptosis and anti-tumor effects in human breast cancer cells. Cancer Lett. 2021;522:211–24. https://doi.org/10.1016/j.canlet.2021.09.033.

    Article 
    PubMed 

    Google Scholar 

  • Chen X, Kang R, Kroemer G, Tang D. Ferroptosis in infection, inflammation, and immunity. J Exp Med. 2021;218(6):e20210518. https://doi.org/10.1084/jem.20210518.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mi T, Kong X, Chen M, Guo P, He D. Inducing disulfidptosis in tumors: potential pathways and significance. MedComm (2020). 2024;5(11):e791. https://doi.org/10.1002/mco2.791

  • Yan Y, Teng H, Hang Q, et al. Slc7a11 expression level dictates differential responses to oxidative stress in cancer cells. Nat Commun. 2023;14(1):3673. https://doi.org/10.1038/s41467-023-39401-9.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Joly JH, Delfarah A, Phung PS, Parrish S, Graham NA. A synthetic lethal drug combination mimics glucose deprivation-induced cancer cell death in the presence of glucose. J Biol Chem. 2020;295(5):1350–65. https://doi.org/10.1074/jbc.RA119.011471.

    Article 
    PubMed 

    Google Scholar 

  • Liu T, Ren Y, Wang Q, et al. Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies. Cancer Cell Int. 2023;23(1):259. https://doi.org/10.1186/s12935-023-03091-6.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhao D, Meng Y, Dian Y, et al. Molecular landmarks of tumor disulfidptosis across cancer types to promote disulfidptosis-target therapy. Redox Biol. 2023;68:102966. https://doi.org/10.1016/j.redox.2023.102966.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li J, Yu T, Sun J, et al. Integrated analysis of disulfidptosis-related immune genes signature to boost the efficacy of prognostic prediction in gastric cancer. Cancer Cell Int. 2024;24(1):112. https://doi.org/10.1186/s12935-024-03294-5.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Xia Q, Yan Q, Wang Z, et al. Disulfidptosis-associated lncRNAs predict breast cancer subtypes. Sci Rep. 2023;13(1):16268. https://doi.org/10.1038/s41598-023-43414-1.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu L, Liu J, Lyu Q, et al. Disulfidptosis-associated lncRNAs index predicts prognosis and chemotherapy drugs sensitivity in cervical cancer. Sci Rep. 2023;13(1):12470. https://doi.org/10.1038/s41598-023-39669-3.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Korangath P, Teo WW, Sadik H, et al. Targeting glutamine metabolism in breast cancer with aminooxyacetate. Clin Cancer Res. 2015;21(14):3263–73. https://doi.org/10.1158/1078-0432.CCR-14-1200.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Stine ZE, Schug ZT, Salvino JM, Dang CV. Targeting cancer metabolism in the era of precision oncology. Nat Rev Drug Discov. 2022;21(2):141-162. doi:10.1038/s41573-021-00339-6

  • Shao N, Qiu H, Liu J, et al. Targeting lipid metabolism of macrophages: a new strategy for tumor therapy. J Adv Res. 2025;68:99–114. https://doi.org/10.1016/j.jare.2024.02.009.

    Article 
    PubMed 

    Google Scholar 

  • Zhao X, Zhao J, Li D, et al. Akkermansia muciniphila: a potential target and pending issues for oncotherapy. Pharmacol Res. 2023;196:106916. https://doi.org/10.1016/j.phrs.2023.106916.

    Article 
    PubMed 

    Google Scholar 

  • Liu X, Zhuang L, Gan B. Disulfidptosis: disulfide stress-induced cell death. Trends Cell Biol. 2024;34(4):327–37. https://doi.org/10.1016/j.tcb.2023.07.009.

    Article 
    PubMed 

    Google Scholar 

  • Qiu H, Shao N, Liu J, et al. Amino acid metabolism in tumor: new shine in the fog? Clin Nutr. 2023;42(8):1521–30. https://doi.org/10.1016/j.clnu.2023.06.011.

    Article 
    PubMed 

    Google Scholar 

  • Liu J, Shao N, Qiu H, et al. Intestinal microbiota: A Bridge between intermittent fasting and tumors. Biomed Pharmacother. 2023;167:115484. https://doi.org/10.1016/j.biopha.2023.115484.

    Article 
    PubMed 

    Google Scholar 

Continue Reading

  • Inserting a venoarterial extracorporeal membrane oxygenation drainage cannula into the inferior vena cava through the internal jugular vein in a patient with an inferior vena cava filter | International Journal of Emergency Medicine

    Inserting a venoarterial extracorporeal membrane oxygenation drainage cannula into the inferior vena cava through the internal jugular vein in a patient with an inferior vena cava filter | International Journal of Emergency Medicine

    An 18-year-old male patient, a Moroccan international student in China, presented to the emergency department of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, with a chief complaint of persistent upper…

    Continue Reading

  • These teams that have qualified for the IFAF Flag Football World Championships 2026

    These teams that have qualified for the IFAF Flag Football World Championships 2026

    The fields are now set for the women’s and men’s competitions at the 2026 IFAF Flag Football World Championships.

    Following the conclusion of the Asia-Oceania Flag Football Championships on Sunday (26 October), the final continental competition…

    Continue Reading

  • AI Helps Decode The Epigenetic ‘off-switch’ In An Ugly Plant That Lives For 3,000 Years

    AI Helps Decode The Epigenetic ‘off-switch’ In An Ugly Plant That Lives For 3,000 Years

    We all age, and for decades, science has been looking for a way to slow that clock. Much of that research is now focused on epigenetics—a system of “software” that runs on our genetic “hardware,” telling genes when to turn on and off.…

    Continue Reading

  • Sotheby’s Records Surrealist Records in Paris—and More Art News

    Sotheby’s Records Surrealist Records in Paris—and More Art News

    The Headlines

    SUSPECTED LOUVRE THIEVES ARRESTED. Two suspects have been detained in connection with the theft of jewels, including pieces once belonging to Emperor Napoleon III and Empress Eugénie, from the Louvre on October 19….

    Continue Reading

  • Access Denied


    Access Denied

    You don’t have permission to access “http://www.business-standard.com/cricket/news/shreyas-iyer-s-condition-improves-out-of-icu-after-spleen-injury-reports-125102700953_1.html” on this server.

    Reference…

    Continue Reading

  • Eli Lilly buys Adverum in eye disease gene therapy punt

    Eli Lilly buys Adverum in eye disease gene therapy punt

    As part of the deal, Eli Lilly will acquire Adverum’s lead candidate ixo-vec, an intravitreal gene therapy for wAMD treatment. Credit: Tada Images via Shutterstock.com.

    Eli Lilly has agreed to acquire eye disease specialist Adverum Biotechnologies, bucking a recent trend of big pharma companies deciding to steer clear of the cell and gene therapy sector.

    Eli Lilly has offered Adverum $3.56 per share in cash, including an additional $8.91 in milestone payments. The latter depends on US approval of the biotech’s lead gene therapy candidate, ixo-vec, within seven years and achieving more than $1bn in annual global sales within ten years. This brings the total consideration to $12.47 a share, valuing the deal at a possible $261.7m.

    Discover B2B Marketing That Performs

    Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.

    Find out more

    The share offer agreed on 24 October reflects a nearly 15% discount from the $4.18 closing price on 23 October.

    For Adverum, the potential buyout from Eli Lilly provides financial respite. The biotech has been struggling for cash in recent times – holding $44.4m to its name in July 2025. The lack of capital had increased jeopardy for ixo-vec, an intravitreal gene therapy that advanced into a Phase III trial (NCT06856577) for the treatment of wet age-related macular degeneration (wAMD) in March 2025.

    Indeed, Eli Lilly stated that without a $65m loan given to Adverum to continue ongoing clinical trials, the biotech would only be able to finance itself through October before having to wind down operations.

    Despite having to help fund ixo-vec’s development, which has been granted fast track and regenerative medicine advanced therapy (RMAT) designations by the US Food and Drug Administration (FDA), Eli Lilly could use the candidate to enter the lucrative wAMD market. The AMD sector, which also includes the dry form, is expected to reach $27.5bn across 7MM by 2031 (7MM: US, France, Germany, Italy, Spain, UK, and Japan), according to GlobalData analysis.

    There is no gene therapy approved with a wAMD indication, with current treatments working via the anti–vascular endothelial growth factor (VEGF) mechanism, such as Regeneron’s blockbuster Eylea (aflibercept). The therapy is administered every four weeks for the first five months, followed by a single injection every two months. For Eli Lilly’s soon-to-be acquired ixo-vec, this could offer patients a one-and-done treatment.

    Lilly molecule discovery group vice-president Andrew Adams said: “Ixo-vec has the potential to transform wAMD treatment from a paradigm of chronic care with repeated intravitreal injections to a convenient one-time therapy.”

    Adverum CEO Laurent Fischer: “[Lilly’s] scientific depth and global reach offer the opportunity to accelerate our vision to deliver a transformative one-and-done therapy that can potentially restore and preserve vision for millions of patients living with wAMD.”

    Lilly bucks big pharma trend

    This is not the first time in 2025 that Eli Lilly has swooped in to rescue a cash-strapped biotech specialising in gene therapies. In April, the big pharma signed a licensing deal worth up to $1.4bn for Sangamo Therapeutics’ neurology-targeting gene therapy.

    However, Lilly’s recent deals, which includes a $1.3bn acquisition of RNA-based gene therapy developer Rznomics in May 2025, goes against the grain of big pharma generally opting to retreat from the cell and gene therapy sector.  

    Earlier this month, Galapagos wound down its cell and gene therapy division after failing to sell the unit. Japanese pharma Takeda also abandoned its cell therapy research, pivoting instead towards small molecules, biologics and antibody-drug conjugates (ADCs).

    In addition, Gilead Sciences’ Kite Pharma terminated its cell therapy collaboration with Shoreline in September 2025, ending a research partnership valued at $2.3bn.  

    Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva.

    Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content.

    Pharmaceutical Technology Excellence Awards – The Benefits of Entering

    Gain the recognition you deserve! The Pharmaceutical Technology Excellence Awards celebrate innovation, leadership, and impact. By entering, you showcase your achievements, elevate your industry profile, and position yourself among top leaders driving pharmaceutical advancements. Don’t miss your chance to stand out—submit your entry today!

    Nominate Now



    Continue Reading

  • When Neurology Overlaps: Herpes Simplex Virus Encephalitis in a Patient with Progressive Multiple Sclerosis

    When Neurology Overlaps: Herpes Simplex Virus Encephalitis in a Patient with Progressive Multiple Sclerosis

    Continue Reading

  • Bitcoin faces a new civil war over how its blockchain should be used

    Bitcoin faces a new civil war over how its blockchain should be used

    I recently had the pleasure of visiting the lovely mountain town of Lugano, Switzerland, whose appeal lies in that it is basically Italy but administered by the Swiss. That’s according to Tether CEO Paolo Ardoino, one of the prime backers of Plan B, a Bitcoin conference where I hosted a discussion on the growing trend of nation states embracing the original cryptocurrency.

    The event had an upbeat vibe—not surprising since everyone there worshipped Bitcoin—but it was also clear there was trouble in paradise. It turns out there is a growing schism over Bitcoin’s codebase, and whether it should be modified to permit the blockchain to include more non-financial data.

    The notion of including data unrelated to Bitcoin transactions is hardly new and, indeed, the very first block on the blockchain includes a reference to a newspaper headline about bank bailouts. Now, though, Bitcoin’s biggest and most influential group of coders, known as Core, are planning to tweak their software in order to significantly lift the restrictions on how much non-payment information can be included in a block.

    For the Core crowd, this is a simple and pragmatic way to promote new uses for Bitcoin and, in the process, drum up extra fees for miners at a time when the blockchain’s lottery payment is 3.125 Bitcoins, and set to halve again in 2028. A fast-growing rival faction, though, wants nothing to do with the scheme and is promoting a Bitcoin client software of its own called Knots.

    That faction’s software is led by an influential Bitcoin developer, who is a devout Catholic and reportedly named it Knots after the “whip of knots” Jesus used to drive money changers from a temple. According to a lawyer I spoke with on the Knots side, the software is necessary to protect the blockchain from what he decried as spammers and “scam adjacency” projects that promote things like Bitcoin NFTs. 

    If you’ve encountered Bitcoiners in person or online, you’re aware they’re not known for their tact. That is true of prominent figures from Bitcoin’s early days who have been denouncing each other on stage in Lugano and on X. These high profile partisans include Peter Todd and Jameson Lopp for the Core faction, and Nick Szabo and Luke Dashjr for the rival Knots sect.

    This latest schism (you can read a helpful breakdown here) hearkens back to the Bitcoin block size wars that raged from 2015 to 2017, and ultimately saw the “small blockers”—who favored keeping Bitcoin blocks at 1MB—prevail over rivals who claimed boosting the blocks to 2MB or more would be more commercially viable. That fight produced bad blood that has lasted to this day.

    In the current fight, Knots is still the smaller faction, but has already become the client of choice for over 20% of Bitcoin node operators. Its growing popularity lies not only in Knots’ position on expanding the blockchain, but from a perception that the Core crowd has grown arrogant and out-of-touch with Bitcoin’s core values. The Core folks, meanwhile, dismiss the Knots faction as lying trouble-makers.

    I lack the authority to weigh in on much of this, other than to observe that this latest battle for the soul of Bitcoin reinforces what I’ve said for years: Bitcoin is a marvelous technology, but also a religion. And with any religion, there will be divisions between old-line believers and more modern adherents. Happily for the crowd in Lugano, there was a moment of unity that came with the unveiling of a restored Satoshi Nakamoto statue on the city’s beautiful lakefront. Bitcoin’s factions may be at war but there’s no doubt they still worship a common god.

    Jeff John Roberts
    jeff.roberts@fortune.com
    @jeffjohnroberts

    DECENTRALIZED NEWS

    If you can’t beat ‘em, join ‘em: JPMorgan Chase’s CEO continues to soften his longtime anti-crypto stance as his bank announced that it will let borrowers use Bitcoin and Ethereum for loan collateral by the end of year. (Bloomberg)

    COIN upgrade: Coinbase’s forthcoming crypto token could be worth $12 billion to $34 billion, said a JPM analyst, who cited the token and the slowing growth of DEXes as reasons to upgrade the stock ahead of third-quarter earnings this week. (DL News)

    Here we ICO again? In assessing Coinbase’s $375 million acquisition of Echo, which was founded by crypto influencer Cobie and helps token projects raise funds, one journalist speculated it could inaugurate the return of 2016-style initial coin offerings. (Bloomberg) 

    DAT doesn’t add up: Following a Fortune exposé pointing to potential insider trading ahead of public company pivots to digital asset treasuries, a new report provides evidence that insiders tied to some popular DATs are using share sales to circumvent token lockups. (Unchained)

    Trump picks a CFTC chair: The White House selected longtime lawyer and crypto guy Mike Selig to lead the agency. The choice of Selig, which came after the Winklevii helped torpedo the original frontrunner, was hailed by industry vets who are eager to finalize a key bill that will divide responsibilities between the SEC and CFTC. (Politico)

    MAIN CHARACTER OF THE WEEK

    Changpeng Zhao, cofounder of Binance.

    Samsul Said—Bloomberg/Getty Images

    CZ was the easy choice for main character of the week after finally securing a Presidential pardon. Critics, pointing to a $2 billion deal involving the Trump family’s stablecoin and Binance, blasted the pardon as massively corrupt while many on Crypto Twitter claimed it was fair since CZ—who pleaded guilty—had allegedly been the target of a political prosecution.

    MEME O’ THE MOMENT

    A screenshot of a twitter post that juxtaposes two Bitcoin statues.
    In Lugano, Switzerland, Bitcoiners unveiled a refurbished statue of Satoshi Nakamoto.

    @Globalstats11

    Bitcoin devotees seeking to make a pilgrimage have a growing number of options. In addition to the refurbished Satoshi statue unveiled in Lugano, there is one in Budapest as well. Can a formal shrine—or perhaps a Bitcoin theme park—be far behind?

    Continue Reading

  • Mitigation of alkaline stress and iron deficiency in Petunia hybrida through resveratrol-induced physiological and nutrient responses | BMC Plant Biology

    Mitigation of alkaline stress and iron deficiency in Petunia hybrida through resveratrol-induced physiological and nutrient responses | BMC Plant Biology

  • Chatterjee S. Petunia. Commercial flowers, vol. 4. New Delhi: Daya Publishing House, A Division of Astral International Pvt. Ltd.; 2022. p. 55.

    Google Scholar 

  • Guo G, Xiao J, Jeong BR. Iron source and medium pH affect nutrient uptake and pigment content in Petunia hybrida ‘madness red’ cultured in vitro. Int J Mol Sci. 2022;23:8943. https://doi.org/10.3390/ijms23168943.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Velez Bermudez IC, Schmidt W. Iron sensing in plant. Front Plant Sci. 2023;14:1145510. https://doi.org/10.3389/fpls.2023.1145510.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ansari A, Amiri J, Norouzi P, Fattahi M, Easouli-Sadaghiani MH, Alipour H. Assessing the efficacy of different nano-iron sources for alleviating alkaline soil challenges in Goji berry trees (Lycium barbarum L). BMC Plant Biol. 2024;24:1153. https://doi.org/10.1186/s12870-024-05870-3.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang S, Xu Y, Tang Z, Jin S, Yang S. The impact of alkaline stress on plant growth and its alkaline resistance mechanisms. Int J Mol Sci. 2024;25(24):13719. https://doi.org/10.3390/ijms252413719.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Savchenko T, Tikhonov K. Oxidative stress-induced alteration of plant central metabolism. Life. 2021;11:304. https://doi.org/10.3390/life11040304.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bontpart T, Weiss A, Vile D, Gérard F, Lacombe B, Reichheld JP, et al. Growing on calcareous soils and facing climate change. Trends Plant Sci. 2024;29(12):1319–30. https://doi.org/10.1016/j.tplants.2024.03.013.

    Article 
    PubMed 

    Google Scholar 

  • Tamir G, Zilkah S, Dai N, Shawahna R, Cohen S, Bar-Tal A. Combined effects of CaCO3 and the proportion of N-NH4+ among the total applied inorganic N on the growth and mineral uptake of rabbiteye blueberry. J Soil Sci Plant Nutr. 2021;21:35–48. https://doi.org/10.1007/s42729-020-00339-2.

    Article 

    Google Scholar 

  • Kumar K, Jaiswal A, Koppolu UMK, Kumar KRR. Alkaline stress disrupts growth, biochemistry, and ion homeostasis of Chickpea (Cicer arietinum L.) roots. Front Agron. 2024;6:1497054. https://doi.org/10.3389/fagro.2024.1497054.

    Article 

    Google Scholar 

  • Zhao Y, Chen Y, Liu S, Li F, Sun M, Liang Z, et al. Bicarbonate rather than high pH in growth medium induced Fe-deficiency chlorosis in dwarfing rootstock quince A (Cydonia oblonga Mill.) but did not impair Fe nutrition of vigorous rootstock Pyrus betulifolia. Front Plant Sci. 2023;14:1237327. https://doi.org/10.3389/fpls.2023.1237327.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Saleem A, Zulfiqar A, Saleem MZ, Ali B, Saleem MH, Ali S, et al. Alkaline and acidic soil constraints on iron accumulation by rice cultivars in relation to several physio-biochemical parameters. BMC Plant Biol. 2023;23(1):397. https://doi.org/10.1186/s12870-023-04400-x.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liang G. Iron uptake, signaling, and sensing in plants. Plant Commun. 2022;3(5):100349. https://doi.org/10.1016/j.xplc.2022.100349.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ning X, Lin M, Huang G, Mao J, Gao Z, Wang X. Research progress on iron absorption, transport, and molecular regulation strategy in plants. Front Plant Sci. 2023;14:1190768. https://doi.org/10.3389/fpls.2023.1190768.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li J, Cao X, Jia X, Liu L, Cao H, Qin W, et al. Iron deficiency leads to chlorosis through impacting chlorophyll synthesis and nitrogen metabolism in Areca catechu L. Front Plant Sci. 2021a;12:710093. https://doi.org/10.3389/fpls.2021.710093.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Trofimov K, Mankotia S, Ngigi M, Baby D, Satbhai SB, Bauer P. Shedding light on iron nutrition: exploring intersections of transcription factor cascades in light and iron deficiency signaling. J Exp Bot. 2025;76:787–802. https://doi.org/10.1093/jxb/erae324.

    Article 
    PubMed 

    Google Scholar 

  • Khalil S, Strah R, Lodovici A, Vojta P, Ziegler J, Novak MP, Zanin L, Tomasi N, Forneck A, Griesser M. Lime-induced iron deficiency stimulates a stronger response in tolerant grapevine rootstocks compared to low iron availability. Plant Stress. 2025;16:100841. https://doi.org/10.1016/j.stress.2025.100841.

    Article 

    Google Scholar 

  • Martín-Barranco A, Thomine S, Vert G, Zelazny E. A quick journey into the diversity of iron uptake strategies in photosynthetic organisms. Plant Signal Behav. 2021;16(11):1975088. https://doi.org/10.1080/15592324.2021.1975088.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Amooaghaie R, Roohollahi S. Effect of sodium Nitroprusside on responses of Melissa officinalis to bicarbonate exposure and direct Fe deficiency stress. Photosynthetica. 2017;55(1):153–63. https://doi.org/10.1007/s11099-016-0240-8.

    Article 

    Google Scholar 

  • Wang N, Dong X, Chen Y, Ma B, Yao C, Ma F, et al. Direct and bicarbonate-induced iron deficiency differently affect iron translocation in Kiwifruit roots. Plants. 2020;9:1578. https://doi.org/10.3390/plants9111578.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Marschner H, Römheld V. Strategies of plants for acquisition of iron. Plant Soil. 1994;165:375–88. https://doi.org/10.1007/BF00008069.

    Article 

    Google Scholar 

  • Kobayashi T, Nakanishi H, Nishizawa NK. Recent insights into iron homeostasis and their application in graminaceous crops. Proc Jpn Acad Ser B. 2010;86:900–13. https://doi.org/10.2183/pjab.86.900.

    Article 

    Google Scholar 

  • Nozoye T, Nagasaka S, Kobayashi T, Takahashi M, Sato Y, Sato Y, et al. Phytosiderophore efflux transporters are crucial for iron acquisition in graminaceous plants. J Biol Chem. 2011;286:5446–54. https://doi.org/10.1074/jbc.M110.180026.

    Article 
    PubMed 

    Google Scholar 

  • Wagner ALS, Araniti F, Ishii-Iwamoto EL, Abenavoli MR. Resveratrol exerts beneficial effects on the growth and metabolism of Lactuca sativa L. Plant Physiol Biochem. 2022;171:26–37. https://doi.org/10.1016/j.plaphy.2021.12.023.

    Article 

    Google Scholar 

  • Rao MJ, Zheng B. The role of polyphenols in abiotic stress tolerance and their antioxidant properties to scavenge reactive oxygen species and free radicals. Antioxidants. 2025;14(1):74. https://doi.org/10.3390/antiox14010074.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zheng X, Chen H, Su Q, Wang C, Sha G, Ma C, et al. Resveratrol improves the irondeficiency adaptation of Malus baccata seedlings by regulating iron absorption. BMC Plant Biol. 2021;21(1):433. https://doi.org/10.1186/s12870-021-03215-y.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Šamec D, Karalija E, Šola I, Vujčić Bok V, Salopek-Sondi B. The role of polyphenols in abiotic stress response: the influence of molecular structure. Plants. 2021;10(1):118. https://doi.org/10.3390/plants10010118.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jian J, Su W, Liu Y, Wang M, Chen X, Wang E, et al. Effects of saline–alkali composite stress on the growth and soil fixation capacity of four herbaceous plants. Agronomy. 2024;14(7):1556. https://doi.org/10.3390/agronomy14071556.

    Article 

    Google Scholar 

  • López-Pérez M, Acosta J, Pérez-Labrada F. Iron nutrition management in calcisol soils as a tool to mitigate chlorosis and promote crop quality – An overview. J Appl Biol Biotechnol. 2023;12(1):17–29. https://doi.org/10.7324/JABB.2024.157536.

    Article 

    Google Scholar 

  • Mehrotra R, Rajesh KV, Anirban P. Iron deficiency chlorosis in aromatic grasses—A review. Environ Chall. 2022;9:100646. https://doi.org/10.1016/j.envc.2022.100646.

    Article 

    Google Scholar 

  • Liu X, Niu H, Li J, Jiang D, Chen R, Zhang R, et al. Higher endogenous abscisic acid confers greater tolerance to saline-alkaline stress in Petunia hybrida. Environ Exp Bot. 2024;228:106035. https://doi.org/10.1016/j.envexpbot.2024.106035.

    Article 

    Google Scholar 

  • Murata Y, Itoh Y, Iwashita T, Namba K. Transgenic petunia with the iron(III)phytosiderophore transporter gene acquires tolerance to iron deficiency in alkaline environments. PLoS ONE. 2015;10:e0120227. https://doi.org/10.1371/journal.pone.0120227.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jelali N, Wasli H, Youssef RB, Hessini K, Cardoso SM. Iron deficiency modulates secondary metabolite biosynthesis and antioxidant potential in Sulla carnosa L. primed with Salicylic acid. Appl Sci. 2022;12(20):10351. https://doi.org/10.3390/app122010351.

    Article 

    Google Scholar 

  • Sun Z, Wang T, Li J, Zheng X, Ge H, Sha G, et al. Resveratrol enhances the tolerance of Malus hupehensis to potassium deficiency stress. Front Plant Sci. 2024;15:1503463. https://doi.org/10.3389/fpls.2024.1503463.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li T, Li Y, Sun Z, Xi X, Sha G, Ma C, et al. Resveratrol alleviates the KCl salinity stress of Malus hupehensis Rhed. Front Plant Sci. 2021b;12:650485. https://doi.org/10.3389/fpls.2021.650485.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hoagland DR, Arnon DI. The waterculture method for growing plants without soil. Berkeley (CA): California Agricultural Experiment Station; 1950. Circular No. 347. 32.

  • Sonneveld C, Straver N. Nutrient solutions for vegetables and flowers grown in water or substrates. Naaldwijk (Netherlands): Glasshouse Crops Research Station; 1999. p. 43.

    Google Scholar 

  • Poorter H, Niinemets Ü, Poorter L, Wright IJ, Villar R. Causes and consequences of variation in leaf mass per area (LMA): a metaanalysis. New Phytol. 2009;182(3):565–88. https://doi.org/10.1111/j.1469-8137.2009.02830.x.

    Article 
    PubMed 

    Google Scholar 

  • Pang W, Crow WT, Luc JE, McSorley R, GiblinDavis RM, Kenworthy KE, et al. Comparison of water displacement and WinRHIZO software for plant root parameter assessment. Plant Dis. 2011;95(10):1308–10. https://doi.org/10.1094/PDIS-01-11-0026.

    Article 
    PubMed 

    Google Scholar 

  • Markwell J, Osterman JC, Mitchell JL. Calibration of the Minolta SPAD-502 leaf chlorophyll meter. Photosynth Res. 1995;46:467–72. https://doi.org/10.1007/BF00032301.

    Article 
    PubMed 

    Google Scholar 

  • Lichtenthaler HK. Chlorophylls and carotenoids: pigments of photosynthetic biomembranes. Methods Enzymol. 1987;148:350–82. https://doi.org/10.1016/0076-6879(87)48036-1.

    Article 

    Google Scholar 

  • Lutts S, Kinet JM, Bouharmont J. Changes in plant response to NaCl during development of rice (Oryza sativa L.) varieties differing in salinity resistance. J Exp Bot. 1995;46(12):1843–52. https://doi.org/10.1093/jxb/46.12.1843.

    Article 

    Google Scholar 

  • Horst JH, Cakmak I. Effects of aluminum on lipid peroxidation, superoxide dismutase, catalase, and peroxidase activities in root tips of soybean (Glycine max). Physiol Plant. 1991;83:463–8. https://doi.org/10.1111/j.1399-3054.1991.tb00121.x.

    Article 

    Google Scholar 

  • Velikova V, Yordanov I, Edreva A. Oxidative stress and some antioxidant systems in acid rain-treated bean plants: protective role of exogenous polyamines. Plant Sci. 2000;151(1):59–66. https://doi.org/10.1016/S0168-9452(99)00197-1.

    Article 

    Google Scholar 

  • Ojeda M, Schaffer B, Davies FS. Root and leaf ferric chelate reductase activity in pond Apple and soursop. J Plant Nutr. 2004;27:1381–93. https://doi.org/10.1081/PLN-200025836.

    Article 

    Google Scholar 

  • Grieve CM, Grattan SR. Rapid assay for determination of water-soluble quaternary ammonium compounds. Plant Soil. 1983;70(3):303–7. https://doi.org/10.1007/BF02374789.

    Article 

    Google Scholar 

  • Ohayama T, Ito M, Kobayashi K, Araki S, Yasuyoshi S, Sasaki O, et al. Analytical procedures of N, P and K content in plant and manure materials using H₂SO₄–H₂O₂ Kjeldahl digestion method. Bull Fac Agric Niigata Univ. 1991;43:111–20.

    Google Scholar 

  • Ryan J, Estefan G, Rashid A. Soil and plant analysis: laboratory manual. Aleppo (Syria): ICARDA; 2001.

    Google Scholar 

  • Mizukoshi K, Nishiwaki T, Ohtake N, Minagawa R, Kobayashi K, Ikarashi T, et al. Determination of tungstate concentration in plant materials by HNO₃–HClO₄ digestion and colorimetric method using thiocyanate. Plant Anal Methods. 1994;46:51–6.

    Google Scholar 

  • Ghazanshahi J. Soil and plant analysis. Tehran (Iran): Motarjem; 2006. p. 311.

    Google Scholar 

  • Ahmed N, Zhang B, Chachar Z, Li J, Xiao G, Wang Q, et al. Micronutrients and their effects on horticultural crop quality, productivity and sustainability. Sci Hortic. 2024;323:112512. https://doi.org/10.1016/j.scienta.2023.112512.

    Article 

    Google Scholar 

  • Khan F, Siddique AB, Shabala S, Zhou M, Zhao C. Phosphorus plays key roles in regulating plants’ physiological responses to abiotic stresses. Plants. 2023;12(15):2861. https://doi.org/10.3390/plants12152861.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Therby-Vale R, Lacombe B, Rhee SY, Nussaume L, Rouached H. Mineral nutrient signaling controls photosynthesis: focus on iron deficiency-induced chlorosis. Trends Plant Sci. 2022;27(5):502–9. https://doi.org/10.1016/j.tplants.2021.11.005.

    Article 
    PubMed 

    Google Scholar 

  • Hasanuzzaman M, Bhuyan MHMB, Parvin K, Bhuiyan TF, Anee TI, Nahar K, et al. Regulation of ROS metabolism in plants under environmental stress: a review of recent experimental evidence. Int J Mol Sci. 2020a;21(22):8695. https://doi.org/10.3390/ijms21228695.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hong Y, Boiti A, Vallone D, Foulkes NS. Reactive oxygen species signaling and oxidative stress: transcriptional regulation and evolution. Antioxidants. 2024;13(3):312. https://doi.org/10.3390/antiox13030312.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Saito A, Shinjo S, Ito D, Doi Y, Sato A, Wakabayashi Y, et al. Enhancement of photosynthetic iron-use efficiency is an important trait of Hordeum vulgare for adaptation of photosystems to iron deficiency. Plants. 2021;10(2):234. https://doi.org/10.3390/plants10020234.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Marschner P. Marschner’s mineral nutrition of higher plants. 3rd ed. San Diego: Academic; 2012. https://doi.org/10.1016/C2009-0-63043-9.

    Book 

    Google Scholar 

  • Zheng L, Yamaji N, Ma JF. Iron transport and distribution in plants: research progress and future perspectives. Plant Cell Physiol. 2022;63(2):185–93. https://doi.org/10.1093/pcp/pcab164.

    Article 

    Google Scholar 

  • Giehl RF, Lima JE, von Wirén N. Localized iron supply triggers lateral root elongation in Arabidopsis by altering the AUX1-mediated auxin distribution. Plant Cell. 2012;24(1):33–49. https://doi.org/10.1105/tpc.111.092973.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang C, Shi D, Wang D. Comparative effects of salt and alkali stresses on growth, osmotic adjustment and ionic balance of an alkali-resistant halophyte Suaeda glauca (Bge). Plant Growth Regul. 2008;56:179–90. https://doi.org/10.1007/s10725-008-9299-y.

    Article 

    Google Scholar 

  • Sun X, Zhu C, Li B, Ning W, Yin J. Combining physiology and transcriptome to reveal mechanisms of Hosta ‘golden cadet’ in response to alkali stress. Plants. 2025;14(4):593. https://doi.org/10.3390/plants14040593.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang Y, Ian J, Qiu X, Wang G, Zong J. Effects of combined saline-alkali stress on physiological and biochemical characteristics of OT hybrid Lily. J Nanjing Univ. 2022;46(4):117. https://doi.org/10.12302/j.issn.1000-2006.202105041.

    Article 

    Google Scholar 

  • Gao Q, Zheng R, Lu J, Li X, Wang D, Cai X, et al. Trends in the potential of stilbenes to improve plant stress tolerance: insights of plant defense mechanisms in response to biotic and abiotic stressors. J Agric Food Chem. 2024;72(14):7655–71. https://doi.org/10.1021/acs.jafc.4c00326.

    Article 
    PubMed 

    Google Scholar 

  • Vélez-Bermúdez IC, Schmidt W. Plant strategies to mine iron from alkaline substrates. Plant Soil. 2023;483:1–25. https://doi.org/10.1007/s11104-022-05746-1.

    Article 

    Google Scholar 

  • Rottet S, Förster B, Hee WY, Rourke LM, Price GD, Long BM. Engineered accumulation of bicarbonate in plant chloroplasts: known knowns and known unknowns. Front Plant Sci. 2021;12:727118. https://doi.org/10.3389/fpls.2021.727118.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bhat MA, Mishra AK, Shah SN, Bhat MA, Jan S, Rahman S, et al. Soil and mineral nutrients in plant health: a prospective study of iron and phosphorus in the growth and development of plants. Curr Issues Mol Biol. 2024;46(6):5194–222. https://doi.org/10.3390/cimb46060312.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rengasamy P, Lacerda C, Gheyi H. Salinity, sodicity and alkalinity. Subsoil constraints for crop production. Cham: Springer; 2022. pp. 75–94. https://doi.org/10.1007/978-3-031-00317-2_4.

    Chapter 

    Google Scholar 

  • Zagoskina NV, Zubova MY, Nechaeva TL, Kazantseva VV, Goncharuk EA, Katanskaya VM, et al. Polyphenols in plants: structure, biosynthesis, abiotic stress regulation, and practical applications. Int J Mol Sci. 2023;24(18):13874. https://doi.org/10.3390/ijms241813874.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chauhan J, Prathibha MD, Singh P, Choyal P, Mishra UN, Saha D, et al. Plant photosynthesis under abiotic stresses: damages, adaptive, and signaling mechanisms. Plant Stress. 2023;10:100296. https://doi.org/10.1016/j.stress.2023.100296.

    Article 

    Google Scholar 

  • Graziano M, Lamattina L. Nitric oxide and iron in plants: an emerging and converging story. Trends Plant Sci. 2005;10:4–8. https://doi.org/10.1016/j.tplants.2004.12.004.

    Article 
    PubMed 

    Google Scholar 

  • Tripathy BC, Oelmüller R. Reactive oxygen species generation and signaling in plants. Plant Signal Behav. 2012;7(12):1621–33. https://doi.org/10.4161/psb.22455.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Apel K, Hirt H. Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol. 2004;55:373–99. https://doi.org/10.1146/annurev.arplant.55.031903.141701.

    Article 
    PubMed 

    Google Scholar 

  • Ahuja I, Kissen R, Bones AM. Phytoalexins in defense against pathogens. Trends Plant Sci. 2012;17(2):73–90. https://doi.org/10.1016/j.tplants.2011.11.002.

    Article 
    PubMed 

    Google Scholar 

  • Jeandet P, Douillet-Breuil AC, Bessis R, Debord S, Sbaghi M, Adrian M. Phytoalexins from the vitaceae: biosynthesis, phytoalexin gene expression in Transgenic plants, antifungal activity, and metabolism. J Agric Food Chem. 2013;51(20):6109–15. https://doi.org/10.1021/jf011429s.

    Article 

    Google Scholar 

  • Kong Q, Zheng S, Li W, Liang H, Zhou L, Yang H, et al. Performance of Camellia oleifera seedlings under alkali stress improved by spraying with types of exogenous biostimulants. Agriculture. 2025;15(3):274. https://doi.org/10.3390/agriculture15030274.

    Article 

    Google Scholar 

  • Arcas A, López-Rayo S, Gárate A, Lucena JJ. A critical review of methodologies for evaluating iron fertilizers based on iron reduction and uptake by strategy i plants. Plants. 2024;13(6):819. https://doi.org/10.3390/plants13060819.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kobayashi T, Nishizawa NK. Iron uptake, translocation, and regulation in higher plants. Annu Rev Plant Biol. 2012;63:131–52. https://doi.org/10.1146/annurev-arplant-042811-105522.

    Article 
    PubMed 

    Google Scholar 

  • Santi S, Schmidt W. Dissecting iron deficiency-induced proton extrusion in Arabidopsis roots. New Phytol. 2009;183(4):1072–84. https://doi.org/10.1111/j.1469-8137.2009.02901.x.

    Article 
    PubMed 

    Google Scholar 

  • Hsieh EJ, Waters BM. Alkaline stress and iron deficiency regulate iron uptake and riboflavin synthesis gene expression differently in root and leaf tissue: implications for iron deficiency chlorosis. J Exp Bot. 2016;67(19):5671–85. https://doi.org/10.1093/jxb/erw328.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ashraf M, Foolad MR. Roles of glycine betaine and proline in improving plant abiotic stress resistance. Environ Exp Bot. 2007;59(2):206–16. https://doi.org/10.1016/j.envexpbot.2005.12.006.

    Article 

    Google Scholar 

  • Zhu XG, Long SP, Ort DR. Improving photosynthetic efficiency for greater yield. Annu Rev Plant Biol. 2016;61:235–61. https://doi.org/10.1146/annurev-arplant-042809-112206.

    Article 

    Google Scholar 

  • Truong VL, Jun M, Jeong WS. Role of resveratrol in regulation of cellular defense systems against oxidative stress. Biofactors. 2018;44(1):36–49. https://doi.org/10.1002/biof.1399.

    Article 
    PubMed 

    Google Scholar 

  • D’Introno A, Paradiso A, Scoditti E, D’Amico L, De Paolis A, Carluccio MA, et al. Antioxidant and anti-inflammatory properties of tomato fruits synthesizing different amounts of Stilbenes. Plant Biotechnol J. 2009;7(5):422–9. https://doi.org/10.1111/j.1467-7652.2009.00409.x.

    Article 
    PubMed 

    Google Scholar 

  • Shi Y, Guo S, Zhao X, Xu M, Xu J, Xing G, Ahammed GJ. Comparative physiological and transcriptomics analysis revealed crucial mechanisms of silicon-mediated tolerance to iron deficiency in tomato. Front Plant Sci. 2022;13:1094451. https://doi.org/10.3389/fpls.2022.1094451.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Johan PD, Ahmed OH, Omar L, Hasbullah NA. Phosphorus transformation in soils following co-application of charcoal and wood ash. Agronomy. 2021;11(10):2010. https://doi.org/10.3390/agronomy11102010.

    Article 

    Google Scholar 

  • Santoro V, Schiavon M, Celi L. Role of soil abiotic processes on phosphorus availability and plant responses with a focus on Strigolactones in tomato plants. Plant Soil. 2024;494:1–49. https://doi.org/10.1007/s11104-023-06266-2.

    Article 

    Google Scholar 

  • Zhao H, Zhang W, Zhang L. Interactive effects of iron deficiency and other mineral nutrients on plants. Plant Soil. 2014;382(1–2):1–19. https://doi.org/10.1007/s11104-014-2152-1.

    Article 

    Google Scholar 

  • Wdowiak A, Podgórska A, Szal B. Calcium in plants: an important element of cell physiology and structure, signaling, and stress responses. Acta Physiol Plant. 2024;46:108. https://doi.org/10.1007/s11738-024-03733-w.

    Article 

    Google Scholar 

  • Zhang X, Zhang D, Sun W, Wang T. The adaptive mechanism of plants to iron deficiency via iron uptake, transport, and homeostasis. Int J Mol Sci. 2019;20(10):2424. https://doi.org/10.3390/ijms20102424.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ahmed N, Zhang B, Bozdar B, Chachar S, Rai M, Li J, et al. The power of magnesium: unlocking the potential for increased yield, quality, and stress tolerance of horticultural crops. Front Plant Sci. 2023;14:1285512. https://doi.org/10.3389/fpls.2023.1285512.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cakmak I. Enrichment of cereal grains with zinc: agronomic or genetic biofortification? Plant Soil. 2008;302(1–2):1–17. https://doi.org/10.1007/s11104-007-9466-3.

    Article 

    Google Scholar 

  • Rai S, Singh PK, Mankotia S, Swain J, Satbhai SB. Iron homeostasis in plants and its crosstalk with copper, zinc, and manganese. Plant Stress. 2021;1:100008. https://doi.org/10.1016/j.stress.2021.100008.

    Article 

    Google Scholar 

  • Shaver TM, Westfall D, Ronaghi M. Zinc fertilizer solubility and its effects on zinc bioavailability over time. J Plant Nutr. 2007;30:123–33. https://doi.org/10.1080/01904160601055145.

    Article 

    Google Scholar 

  • Garcia-Caparros P, Ciriello M, Rouphael Y, Giordano M. The role of organic extracts and inorganic compounds as alleviators of drought stress in plants. Horticulturae. 2025;11(1):91. https://doi.org/10.3390/horticulturae11010091.

    Article 

    Google Scholar 

  • Jeandet P. Phytoalexins. Current progress and future prospects. Mol. 2015;20(2):2770–4. https://doi.org/10.3390/molecules20022770.

    Article 

    Google Scholar 

  • Chang X, Heene E, Qiao F, Nick P. The phytoalexin Resveratrol regulates the initiation of hypersensitive cell death in Vitis cell. PLoS ONE. 2011;6(10):e26405. https://doi.org/10.1371/journal.pone.0026405.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Stanton C, Sanders D, Kraemer U, Podar D. Zinc in plants: integrating homeostasis and biofortification. Mol Plant. 2022;15(1):65–85. https://doi.org/10.1016/j.molp.2021.12.008.

    Article 
    PubMed 

    Google Scholar 

  • Xu L, Wang X. A comprehensive review of phenolic compounds in horticultural plants. Int J Mol Sci. 2025;26:5767. https://doi.org/10.3390/ijms26125767.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

    • Continue Reading