Surgery Godfather

Chapter 2274: Chapter 1472: New World_3

Yang Ping stared at the node encircled in red on the screen, watching it sit like a spider in the network’s center, extending countless tentacles, connecting proliferation modules, differentiation modules, migration modules, communication modules, angiogenesis modules, and inflammation regulation modules. Six modules, six main roads, all converge at this point.

He finally found it. It wasn’t found today; it started a long time ago, by Sisi’s bedside, with the proposition of the three-dimensional guidance theory, with the discovery of the K Factor, with the first line drawn on the repair program map.

"Has the expression distribution of Receptor X within the body been done?" Yang Ping asked.

Weber opened another image. It was a heatmap of mouse whole body tissue expression, with red representing high expression and blue representing low expression. From the image, it was clearly visible that Receptor X was entirely red in embryonic tissue, with very high expression levels. In adult tissue, most areas were blue, with very low expression levels. However, there were a few places that were red, sporadically distributed like a few stars in the night sky.

"What are these red dots representing?" Yang Ping pointed to the red speckles on the image.

Weber zoomed in on the image and moved the mouse to the red speckles. A label box popped up on the screen.

"Liver, bone marrow, and the subventricular zone of the nervous system. These three locations are where stem cells are most concentrated in adult tissue. Liver stem cells are there, hematopoietic stem cells are there, neural stem cells are there. Receptor X is highly expressed in these places not because its distribution is selective, but because stem cells need it. Stem cells are the construction crew for repair programs, Receptor X is the foreman. Wherever the foreman is, the construction crew is. If the foreman doesn’t move, the construction crew doesn’t move. When the foreman gives instructions, the crew starts working."

"What about the upstream regulatory mechanism of Receptor X? Who controls it? What signals activate it?" Yang Ping asked.

Manstein took over: "We did a CRISPR screening and found three transcription factors binding to the promoter region of Receptor X. Upstream of the three transcription factors points to a single signaling pathway—the Hippo pathway. This pathway is famous in developmental biology; it controls the size of organs. Organs stop growing once they’ve reached the appropriate size, and the Hippo pathway is at play. Now we’ve discovered that it also controls the initiation of repair programs. When an organ needs repair, the program starts; when it should stop, it ceases. The same pathway governs both development and repair."

"Hippo pathway?" Yang Ping repeated.

"Yes! And upstream of the Hippo pathway is the hardness of the extracellular matrix. A softer matrix activates the pathway, upregulates Receptor X expression, and initiates the repair program. A harder matrix inhibits the pathway, downregulates Receptor X expression, and shuts down the repair program."

Yang Ping looked at Manstein, Manstein looked at him, and Weber also looked at him. None of the three spoke. The laboratory was quiet for a while.

Weber’s voice broke the silence: "So, the master switch of the repair program is not only under genetic regulation but also under physical environmental control. The softness and hardness around cells determine whether the repair program is on or off. A soft matrix tells the cells: this area is damaged and needs repair. A hard matrix tells the cells: this area is already fixed, you can stop."

Yang Ping leaned against the lab bench, hands tucked into the pockets of his White Gown.

"What does this mean?" he asked.

Weber paused for a moment: "It means we don’t have to use drugs to initiate the repair program. We can use materials. Use a soft, degradable material mimicking the embryonic extracellular matrix, implant it in the injured tissue, and make the cells think they’re in the embryo, then the repair program starts."

Yang Ping nodded slightly, "First, create a monoclonal antibody for Receptor X. I want an antibody that can specifically activate this receptor. Don’t use small molecules, don’t use polypeptides, use antibodies. Antibodies have a long half-life, high specificity, and are less prone to off-target effects. Once created, first validate it in vitro, then in animal models. Liver injury model, myocardium infarction model, spinal cord injury model, lung fibrosis model, renal failure model. Do them one by one. Do each model three times. If it can’t be repeated, find the reason. If can’t be found, give up. If found, do it three times again."

Weber and Manstein simultaneously nodded.

"Do you know what this means?" Yang Ping asked.

Weber and Manstein exchanged glances but said nothing.

Yang Ping looked at them and saw behind them the whiteboard with the enormous repair program map drawn on it, containing five hundred sixty-three nodes, three thousand and two connections, and the Receptor X encircled in red at the network’s center. He saw the wear marks on the edge of Weber’s goggles and saw the small bleached holes in the cuffs of Manstein’s lab coat. He saw the sunlight streaming through the window, falling on the lab bench, and shining on the microscope that had been used for countless years.

"It means we might have really found that door, not just cracked it open a bit, but opened the entire door. What’s behind the door is still unknown. But the door is open."

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