Certainly! Here is the English translation:
Lu Xiaolu stood in front of the cryo-electron microscopy control panel, his eyes fixed on the data streaming continuously on the screen. He had been working for fourteen hours straight, but his mind remained highly focused. The sample preparation went more smoothly than expected, utilizing an improved low-temperature fixation thod that preserved the cell mbrane protein’s natural state to the maximum extent.
On the screen, the initial processed tomography images gradually beca clearer. Among countless organelle contours, so distinct granular structures were distributed on the cell mbrane, which were PANC-ID1 complexes marked with SpyTag.
"Resolution is initially estimated to be around 20 Ångström," Griffin’s voice ca from behind as he walked over with two cups of coffee. "It’s enough to see the general shape and aggregation state, but to clearly view the binding interface, you would need below 10 Ångström at least."
Lu Xiaolu took the coffee and said thank you: "The first round of data collection is complete, next cos the 3D reconstruction and classification. I’ve written a new image alignnt algorithm that might improve the signal-to-noise ratio."
"You can write algorithms?" Griffin was sowhat surprised.
Lu Xiaolu rarely showed a slight smile: "When I was in Germany, I minored in computational biology. Structural biology is now half experintation, half computation."
The two sat side by side at the workstation, Lu Xiaolu brought up his program interface, the code was concise and efficient, with clear annotations, showing a solid grasp of computer science.
"This clustering algorithm is very creative," Griffin comnted after reading carefully. "You’ve categorized not only by shape but also included local mbrane curvature and neighboring protein distribution as features, which better distinguishes true signals from noise."
"The function of mbrane proteins is often influenced by the microenvironnt," Lu Xiaolu explained. "The conformation of the sa protein may differ in flat mbrane regions and in regions with high curvature, and interactions with neighboring proteins can change its accessibility. The K Factor we designed is ant to work in a real tumor environnt, so this information is crucial."
Through the dialogue with Lu Xiaolu, Griffin felt that this young man’s level should be world-class, but as a fellow expert in oncology, Griffin wondered why he had no impression of Lu Xiaolu before; even his several visits to China for academic conferences did not yield any mory of Lu Xiaolu’s presentations. It didn’t fit.
Griffin glanced at Lu Xiaolu: "You’re also engaged in tumor research; why hadn’t I read any of your papers before? I’ve communicated with Chinese academics but never heard of you. It doesn’t make sense."
Lu Xiaolu felt at a loss for words: "I’ve only had so achievents after coming to the Sanbo Research Institute. Before that..." He did not continue, and the laboratory fell silent for a mont.
"I’m sorry," Griffin said.
He realized that Lu Xiaolu might have so hidden troubles or perhaps he was a talent who matured late, without notable achievents in the past.
After a short break and so idle chat, Lu Xiaolu refocused on the screen, starting the 3D reconstruction program. Tens of thousands of 2D projection images were being calculated, aligned, and overlaid, gradually constructing the 3D model of cellular local regions.
Ti passed minute by minute, and at two o’clock in the morning, the preliminary 3D reconstruction was completed.
On the screen, a breathtaking microscopic world unfolded: the cancer cell mbrane was not a smooth plane but was covered with ripples, depressions, and protrusions. Among these dynamic mbrane structures, PANC-ID1 complexes were embedded like tiny locks.
Lu Xiaolu zood into one of the complexes, and at the current resolution, it was noticeable that it consisted of three main subunits: a transmbrane core, a larger extracellular domain, and a smaller, irregularly shaped accessory protein.
"That small one should be the unknown protein you discovered," Griffin pointed to the irregular module. "It seems to be flexibly connected to the core, as if swinging on the mbrane surface."
"This might be the regulation chanism," Lu Xiaolu contemplated. "If the conformation of this accessory protein is variable, then perhaps the lock’s open-close state can be modulated. For the K Factor to work, it may need to be stabilized in the open state."
While the two were absorbed in analysis, the laboratory door was gently pushed open.
Zhang Lin peeked in, paused seeing soone there: "Dr. Lu, Doctor Griffin, you’re still here?"
"What are you here for again?" Lu Xiaolu asked.
"I... I couldn’t sleep, took a stroll and saw the light was on here. Thought whoever left after work didn’t turn it off." Zhang Lin scratched his head awkwardly. "Since the light’s on, I used a new machine learning thod to re-analyze the data from the breathing experint during the day, found an interesting correlation, wanted to check on the big screen."
"You sleep in the lab?" Lu Xiaolu was quite surprised.
Zhang Lin nodded: "Both Little Five and I sleep in the lab. How can one do experints without sleeping in the lab? A slow bird flies first."
Lu Xiaolu couldn’t help but feel a bit of admiration; they were quite serious, not just saying it for fun.
"What correlation?" Lu Xiaolu asked.
"When changing hand postures, not only does the breathing pattern change, but heart rate variability changes concurrently." Zhang Lin entered, opened his laptop, "Look, this is the frequency domain analysis when thumb and index finger pinched together, low-frequency power increases, high-frequency power decreases, indicating relative enhancent of sympathetic nerve activity. In contrast, pinching thumb and ring finger shows a pattern more akin to parasympathetic nerve activation."
Lu Xiaolu and Griffin exchanged a glance; this indeed surpassed the simple explanation of ’attention shift.’
"Are you suggesting specific hand gestures can directly regulate the autonomic nerve balance?" Lu Xiaolu assud a serious tone.
"The data suggests such a possibility, but I’m unsure of the chanism," Zhang Lin said. "It might be through so unclear somatosensory-autonomic nerve reflex, or... Hang on, what are you guys looking at?"
His attention was drawn to the 3D structural model on the main screen: "Is this the pancreatic cancer target? Wow, so clear!"
"Preliminary model, resolution is still low," Lu Xiaolu comnted.
Zhang Lin moved closer to the screen, examining it for a while, suddenly saying: "This swinging small protein... doesn’t it seem to have so areas rich with positive charges on its surface?"
Lu Xiaolu was taken aback: "How did you notice that? The current resolution can’t show charge distribution."
"It wasn’t noticed, it’s guessed," Zhang Lin pointed to several slightly protruding regions in the structural model. "Look at these areas; they form a kind of recess-protrusion-recess pattern in 3D space. If I were a naturally evolved lock, wanting specific binding with other molecules would likely use charge complentarity, as positive and negative charge attraction is one of the simplest and direct interactions."
Griffin mused: "Computational chemistry can predict surface electrostatic potential; Professor Lu, shall we give it a try?"
Lu Xiaolu nodded, pulled up another program, and, based on the existing low-resolution structure, predicted the full atomic model of the complex with AlphaFold2, then calculated the surface electrostatic potential distribution.
The result was surprising; just as Zhang Lin guessed, the swinging small protein surface indeed had three distinct regions rich in positive charges, arranged in a triangular pattern.
"This is most likely the binding interface," Lu Xiaolu’s voice carried excitent. "If the K Factor is to recognize this target, its binding surface should have corresponding negative charge complentary regions. Your guess was quite spot-on."
Zhang Lin chuckled: "Seems my offhand observational skills occasionally co in handy."
Lu Xiaolu patted his shoulder: "Scientific discovery sotis requires perspectives from different angles. Oh, and your finding on the hand gestures affecting autonomic nerves might be explained through neuroanatomy. The palm and fingers have rich chanoreceptors and proprioceptors; their afferent nerves have extensive projections in the spinal cord and brainstem, which theoretically could affect autonomic nerve nuclei."
"Really?" Zhang Lin’s eyes lit up. "Dr. Lu, can you guide through so literature?"
"Tomorrow, it’s too late now," Lu Xiaolu glanced at the ti; it was already 3 a.m. "Everyone should go rest."
Griffin then said: "If you need, I can introduce you to experts in neurosciences from the United States."
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