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<?xml version='1.0' encoding='utf-8'?> <svg width="2000" height="1200" viewBox="0 0 2000 1200" xmlns="http://www.w3.org/2000/svg" style="font-family: Arial, sans-serif;"> <rect x="0" y="0" width="2000" height="1200" fill="#ffffff" /> <text x="1000" y="80" font-size="36" text-anchor="middle" font-weight="bold">GK Treatment</text> <text x="1000" y="1120" font-size="36" text-anchor="middle" font-weight="bold" fill="#d32f2f">GSDME-dependent Pyroptosis & Tumor Suppression</text> <line x1="300" y1="400" x2="500" y2="400" stroke="#000000" stroke-width="6" marker-end="url(#arrow)" /> <text x="200" y="380" font-size="20" text-anchor="middle">GK</text> <rect x="100" y="350" width="200" height="80" fill="none" stroke="#000" rx="15" /> <line x1="700" y1="400" x2="900" y2="400" stroke="#000000" stroke-width="6" marker-end="url(#arrow)" /> <text x="600" y="380" font-size="20" text-anchor="middle">FADS2↓ (Ub degradation)</text> <rect x="500" y="350" width="200" height="80" fill="none" stroke="#000" rx="15" /> <line x1="1100" y1="400" x2="1300" y2="400" stroke="#000000" stroke-width="6" marker-end="url(#arrow)" /> <text x="1000" y="380" font-size="20" text-anchor="middle">Lipid remodeling\n(Ceramide↑, Ox-PL↑)</text> <rect x="900" y="350" width="200" height="80" fill="none" stroke="#000" rx="15" /> <line x1="1500" y1="400" x2="1700" y2="400" stroke="#000000" stroke-width="6" marker-end="url(#arrow)" /> <text x="1400" y="380" font-size="20" text-anchor="middle">Lipid peroxidation↑ → ROS burst</text> <rect x="1300" y="350" width="200" height="80" fill="none" stroke="#000" rx="15" /> <text x="1000" y="550" font-size="20" text-anchor="middle">ZBP1-dsRNA activation → Death complex → Casp-8/3 → GSDME-N → Pyroptosis</text> <line x1="1000" y1="600" x2="1000" y2="1080" stroke="#d32f2f" stroke-width="6" marker-end="url(#arrowred)" /> <defs> <marker id="arrow" viewBox="0 0 10 10" refX="8" refY="5" markerWidth="6" markerHeight="6" orient="auto-start-reverse"> <path d="M 0 0 L 10 5 L 0 10 z" fill="#000" /> </marker> <marker id="arrowred" viewBox="0 0 10 10" refX="8" refY="5" markerWidth="6" markerHeight="6" orient="auto-start-reverse"> <path d="M 0 0 L 10 5 L 0 10 z" fill="#d32f2f" /> </marker> </defs> <rect x="150" y="150" width="350" height="500" fill="#a5d6a7" rx="20" opacity="0.3" stroke="#a5d6a7" stroke-width="4" /> <text x="325.0" y="200" font-size="24" text-anchor="middle" font-weight="bold">Part 1: GK-induced FADS2 degradation & pro-death lipid remodeling</text> <text x="325.0" y="300" font-size="18" text-anchor="middle">Key Techniques: CHX-chase, MG132 rescue, Co-IP/IP-MS, LC-MS/MS, C11-BODIPY</text> <text x="325.0" y="400" font-size="18" text-anchor="middle">Key Readouts: FADS2 t1/2↓, Poly-Ub↑, Cer↑, ROS↑</text> <line x1="325.0" y1="650" x2="200" y2="450" stroke="#666" stroke-width="3" stroke-dasharray="5,5" /> <rect x="550" y="150" width="350" height="500" fill="#fff176" rx="20" opacity="0.3" stroke="#fff176" stroke-width="4" /> <text x="725.0" y="200" font-size="24" text-anchor="middle" font-weight="bold">Part 2: ROS-driven Viral Mimicry (ZBP1↑ & dsRNA↑)</text> <text x="725.0" y="300" font-size="18" text-anchor="middle">Key Techniques: WB(p-JNK/p38), ChIP-qPCR, Luciferase, J2 IF, PLA, RIP-seq</text> <text x="725.0" y="400" font-size="18" text-anchor="middle">Key Readouts: ZBP1 mRNA↑, J2+ dots↑, PLA↑</text> <line x1="725.0" y1="650" x2="600" y2="450" stroke="#666" stroke-width="3" stroke-dasharray="5,5" /> <rect x="950" y="150" width="350" height="500" fill="#ef9a9a" rx="20" opacity="0.3" stroke="#ef9a9a" stroke-width="4" /> <text x="1125.0" y="200" font-size="24" text-anchor="middle" font-weight="bold">Part 3: ZBP1-mediated GSDME Pyroptosis Execution</text> <text x="1125.0" y="300" font-size="18" text-anchor="middle">Key Techniques: RNA-IP, Co-IP, WB(GSDME-N), LDH/PI, SEM/Time-lapse</text> <text x="1125.0" y="400" font-size="18" text-anchor="middle">Key Readouts: GSDME-N↑, LDH↑, Ballooning</text> <line x1="1125.0" y1="650" x2="1000" y2="450" stroke="#666" stroke-width="3" stroke-dasharray="5,5" /> <rect x="1350" y="150" width="350" height="500" fill="#ce93d8" rx="20" opacity="0.3" stroke="#ce93d8" stroke-width="4" /> <text x="1525.0" y="200" font-size="24" text-anchor="middle" font-weight="bold">Part 4: In vivo Validation & Clinical Translation</text> <text x="1525.0" y="300" font-size="18" text-anchor="middle">Key Techniques: Nude mice xenograft, IHC/WB, ssGSEA, KM plot, TIMER</text> <text x="1525.0" y="400" font-size="18" text-anchor="middle">Key Readouts: Tumor volume↓, Survival↑, ICD markers↑</text> <line x1="1525.0" y1="650" x2="1400" y2="450" stroke="#666" stroke-width="3" stroke-dasharray="5,5" /> <rect x="1400" y="800" width="500" height="250" fill="#ffe082" rx="15" stroke="#f57f17" /> <text x="1650" y="850" font-size="22" text-anchor="middle" font-weight="bold">Causal Loop Validation</text> <text x="1450" y="900" font-size="18">⊥ FADS2 K→R rescue</text> <text x="1450" y="940" font-size="18">⊥ NAC / Fer-1 (ROS block)</text> <text x="1450" y="980" font-size="18">⊥ T-5224 (AP-1 inh)</text> <text x="1450" y="1020" font-size="18">⊥ ADAR1-OE</text> <text x="1450" y="1060" font-size="18">⊥ zVAD-fmk</text> <text x="1450" y="1100" font-size="18">⊥ GSDME-KO</text> <text x="800" y="300" font-size="18">ROS → ADAR1↓ → dsRNA↑</text> <line x1="900" y1="350" x2="1100" y2="400" stroke="#000" stroke-width="4" marker-end="url(#arrow)" /> </svg>

GK TreatmentPyroptosisGSDME

$<?xml version='1.0' encoding='utf-8'?> <svg width="2000" height="1200" viewBox="0 0 2000 1200" xmlns="http://www.w3.org/2000/svg" style="font-family: Arial, sans-serif;"> <rect x="0" y="0" width="2000" height="1200" fill="#ffffff" /> <text x="1000" y="80" font-size="36" text-anchor="middle" font-weight="bold">GK Treatment</text> <text x="1000" y="1120" font-size="36" text-anchor="middle" font-weight="bold" fill="#d32f2f">GSDME-dependent Pyroptosis & Tumor Suppression</text> <line x1="300" y1="400" x2="500" y2="400" stroke="#000000" stroke-width="6" marker-end="url(#arrow)" /> <text x="200" y="380" font-size="20" text-anchor="middle">GK</text> <rect x="100" y="350" width="200" height="80" fill="none" stroke="#000" rx="15" /> <line x1="700" y1="400" x2="900" y2="400" stroke="#000000" stroke-width="6" marker-end="url(#arrow)" /> <text x="600" y="380" font-size="20" text-anchor="middle">FADS2↓ (Ub degradation)</text> <rect x="500" y="350" width="200" height="80" fill="none" stroke="#000" rx="15" /> <line x1="1100" y1="400" x2="1300" y2="400" stroke="#000000" stroke-width="6" marker-end="url(#arrow)" /> <text x="1000" y="380" font-size="20" text-anchor="middle">Lipid remodeling\n(Ceramide↑, Ox-PL↑)</text> <rect x="900" y="350" width="200" height="80" fill="none" stroke="#000" rx="15" /> <line x1="1500" y1="400" x2="1700" y2="400" stroke="#000000" stroke-width="6" marker-end="url(#arrow)" /> <text x="1400" y="380" font-size="20" text-anchor="middle">Lipid peroxidation↑ → ROS burst</text> <rect x="1300" y="350" width="200" height="80" fill="none" stroke="#000" rx="15" /> <text x="1000" y="550" font-size="20" text-anchor="middle">ZBP1-dsRNA activation → Death complex → Casp-8/3 → GSDME-N → Pyroptosis</text> <line x1="1000" y1="600" x2="1000" y2="1080" stroke="#d32f2f" stroke-width="6" marker-end="url(#arrowred)" /> <defs> <marker id="arrow" viewBox="0 0 10 10" refX="8" refY="5" markerWidth="6" markerHeight="6" orient="auto-start-reverse"> <path d="M 0 0 L 10 5 L 0 10 z" fill="#000" /> </marker> <marker id="arrowred" viewBox="0 0 10 10" refX="8" refY="5" markerWidth="6" markerHeight="6" orient="auto-start-reverse"> <path d="M 0 0 L 10 5 L 0 10 z" fill="#d32f2f" /> </marker> </defs> <rect x="150" y="150" width="350" height="500" fill="#a5d6a7" rx="20" opacity="0.3" stroke="#a5d6a7" stroke-width="4" /> <text x="325.0" y="200" font-size="24" text-anchor="middle" font-weight="bold">Part 1: GK-induced FADS2 degradation & pro-death lipid remodeling</text> <text x="325.0" y="300" font-size="18" text-anchor="middle">Key Techniques: CHX-chase, MG132 rescue, Co-IP/IP-MS, LC-MS/MS, C11-BODIPY</text> <text x="325.0" y="400" font-size="18" text-anchor="middle">Key Readouts: FADS2 t1/2↓, Poly-Ub↑, Cer↑, ROS↑</text> <line x1="325.0" y1="650" x2="200" y2="450" stroke="#666" stroke-width="3" stroke-dasharray="5,5" /> <rect x="550" y="150" width="350" height="500" fill="#fff176" rx="20" opacity="0.3" stroke="#fff176" stroke-width="4" /> <text x="725.0" y="200" font-size="24" text-anchor="middle" font-weight="bold">Part 2: ROS-driven Viral Mimicry (ZBP1↑ & dsRNA↑)</text> <text x="725.0" y="300" font-size="18" text-anchor="middle">Key Techniques: WB(p-JNK/p38), ChIP-qPCR, Luciferase, J2 IF, PLA, RIP-seq</text> <text x="725.0" y="400" font-size="18" text-anchor="middle">Key Readouts: ZBP1 mRNA↑, J2+ dots↑, PLA↑</text> <line x1="725.0" y1="650" x2="600" y2="450" stroke="#666" stroke-width="3" stroke-dasharray="5,5" /> <rect x="950" y="150" width="350" height="500" fill="#ef9a9a" rx="20" opacity="0.3" stroke="#ef9a9a" stroke-width="4" /> <text x="1125.0" y="200" font-size="24" text-anchor="middle" font-weight="bold">Part 3: ZBP1-mediated GSDME Pyroptosis Execution</text> <text x="1125.0" y="300" font-size="18" text-anchor="middle">Key Techniques: RNA-IP, Co-IP, WB(GSDME-N), LDH/PI, SEM/Time-lapse</text> <text x="1125.0" y="400" font-size="18" text-anchor="middle">Key Readouts: GSDME-N↑, LDH↑, Ballooning</text> <line x1="1125.0" y1="650" x2="1000" y2="450" stroke="#666" stroke-width="3" stroke-dasharray="5,5" /> <rect x="1350" y="150" width="350" height="500" fill="#ce93d8" rx="20" opacity="0.3" stroke="#ce93d8" stroke-width="4" /> <text x="1525.0" y="200" font-size="24" text-anchor="middle" font-weight="bold">Part 4: In vivo Validation & Clinical Translation</text> <text x="1525.0" y="300" font-size="18" text-anchor="middle">Key Techniques: Nude mice xenograft, IHC/WB, ssGSEA, KM plot, TIMER</text> <text x="1525.0" y="400" font-size="18" text-anchor="middle">Key Readouts: Tumor volume↓, Survival↑, ICD markers↑</text> <line x1="1525.0" y1="650" x2="1400" y2="450" stroke="#666" stroke-width="3" stroke-dasharray="5,5" /> <rect x="1400" y="800" width="500" height="250" fill="#ffe082" rx="15" stroke="#f57f17" /> <text x="1650" y="850" font-size="22" text-anchor="middle" font-weight="bold">Causal Loop Validation</text> <text x="1450" y="900" font-size="18">⊥ FADS2 K→R rescue</text> <text x="1450" y="940" font-size="18">⊥ NAC / Fer-1 (ROS block)</text> <text x="1450" y="980" font-size="18">⊥ T-5224 (AP-1 inh)</text> <text x="1450" y="1020" font-size="18">⊥ ADAR1-OE</text> <text x="1450" y="1060" font-size="18">⊥ zVAD-fmk</text> <text x="1450" y="1100" font-size="18">⊥ GSDME-KO</text> <text x="800" y="300" font-size="18">ROS → ADAR1↓ → dsRNA↑</text> <line x1="900" y1="350" x2="1100" y2="400" stroke="#000" stroke-width="4" marker-end="url(#arrow)" /> </svg>$

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