Chapter 110: Heart-Stopping (Requesting Subscription)

At this moment, Fang Ziye also felt slightly nervous; he hadn't expected that the inhuman question Jie Han had raised would actually be brought up.

At this moment, Fang Ziye immediately recited the absolute mantra for thesis defense silently in his heart.

Defense, defense. Only answer, don't argue. Point out the problem, first acknowledge then argue. Offer suggestions, thank endlessly...

The defense session is no child's play; it's impromptu Q&A. Once a question is asked, it's already on camera and cannot be interrupted or stalled; therefore, Fang Ziye could only rack his brains searching for a solution.

Yuan Weihong was Fang Ziye's supervisor; it wasn't his turn to speak yet, so he could only fret anxiously.

At the same time, he felt a secret resentment; if Teacher Deng were sitting here right now, would Professor Zheng Tonghui from Hubei Province Provincial Third People's Hospital dare to ask such a question?

"Does this pathway have any practical significance? Are you questioning the research project I applied for or my student's defense thesis? Did you eat your fill and have nothing better to do?"

Professor Zhang Fangping from Zhongnan Hospital's Spine Surgery department stretched his neck at this moment, seemingly moving his joints, but actually easing the current awkward situation.

This kind of problem, if it escalates, might lead to disputes later.

"Indeed, this time, you might be able to make our hospital's student prepare for a second defense, yes. You raised the issue, the student couldn't answer, a second defense is fine, no problem, follow this procedure."

"But I clearly explained to you in advance, this student's workload is sufficient even for a doctoral defense, yet you still ask like this — are you brain-damaged or what?"

"Just say, will all your school's students in the future have to benchmark against Fang Ziye's workload and question difficulty during their master's defenses?"

Naturally, as the questioner, Professor Zheng Tonghui also felt secretly bitter at this moment; he had just been focused on examining the thesis and forgotten this was a master's thesis defense.

And precisely because Fang Ziye's workload and basic research depth were not small, he directly forgot the occasion, treating it as peer exchange — equivalent to a scene of mutual banter — and threw out this question.

Finally, after falling silent for nearly half a minute, Fang Ziye gave his answer: "Thank you for Professor Zheng's question. Regarding this issue, I would like to offer the following explanation."

"As early as the 1930s, the Warburg team observed that cancer cells undergo glycolysis even in high-oxygen environments, thereby producing high lactate levels. This phenomenon is called aerobic glycolysis or the 'Warburg effect.'"

"Although the aerobic glycolysis process produces less ATP than oxidative phosphorylation, it can rapidly provide sufficient energy and biosynthetic precursors for cell proliferation. Therefore, aerobic glycolysis has been established as the seventh hallmark of cancer."

Fang Ziye was explaining that all behaviors of tumor cells require energy, and the energy source of tumor cells is mainly glycolysis, not the oxidative phosphorylation of normal cells.

The vast majority of normal cells' energy source is aerobic respiration!

This is, from the root, first answering why the team sought HK2 as a target, as a node for studying tumor cells.

Although the question was difficult to answer, he could only answer it.

Fang Ziye continued: "Although the glycolysis rate can be regulated by various metabolic enzymes in the glycolysis pathway, most studies indicate that in glycolysis, the flux control of glucose mainly depends on the upregulation of glucose transporters and hexokinase (HK)."

"And the phosphorylation of glucose catalyzed by HK, as a key irreversible step in the glycolysis pathway, plays a critical role in aerobic glycolysis."

This sentence, Fang Ziye was explaining that since tumor cells' energy mainly comes from glycolysis, then if a relatively key metabolic regulatory step can be found as a target, it is the most suitable.

If we liken the glycolysis process to a person eating a meal, then eating more or less might still depend on the seasoning of the side dishes; good seasoning lets one eat more rice, bad seasoning — say using pig slop to eat rice — might make most people unable to eat it.

Fang Ziye continued: "In the human body, HK is divided into four subtypes: HK1, HK2, HK3, HK4. Among the four subtypes, no literature has reported HK1's correlation with malignant tumors; HK2 is highly expressed in multiple tumor cell types; HK3 is inhibited at physiological glucose concentrations; while HK4 is mostly expressed only in the liver and pancreas."

"Other studies have proven that HK2 is overexpressed in multiple solid tumors such as colorectal cancer, liver cancer, ovarian cancer, and pancreatic cancer, suggesting HK2 plays an important role in tumor occurrence and development. Further research found that in most human tumors, the main hexokinase is HK2, and HK2 is a key component promoting tumor cell survival and energy production pathways."

This sentence, Fang Ziye was elaborating that if HK2 is a delicious seasoning, then the seasoning suitable for humans is certainly our common food.

For example, same food, cats think eating raw mice is not bad, dogs think eating shit is fragrant, dung beetles and maggots think a cesspit is a paradise.

In the human body, HK has multiple subtypes; generally, HK2 is the delicious seasoning suitable for humans. This is to steer the topic toward HK2.

"Additionally, many scholars' research has found that HK2 overexpression is positively correlated with tumor staging, differentiation, and degree of lymph node enlargement, and lowers patient survival rates. In recent years, studies have also found that HK2 levels are elevated in vigorously growing osteosarcoma cells. And research has also confirmed that HK2 expression levels in osteosarcoma affect the prognosis of osteosarcoma patients."

This is also a setup; although the HK2 target has regulatory effects on most tumors, in a portion of tumors it has little regulatory significance.

Moreover, HK2 overexpression indeed affects the survival rate of osteosarcoma patients.

Naturally, answering to this point is still insufficient; it's just citations.

Fang Ziye continued: "If we want to further verify whether HK2 also produces absolute negative effects on normal cells, we would first need to construct survival rates and viability of HK2-knockout nude mice, then move to human-like monkeys and apes to verify survival status after knockout."

"Naturally, if we must go this step, we might also need to knock out or silence HK2 in normal cells of various human organs and observe their functional efficiency. This is an extremely massive workload."

"Currently, worldwide, there are no corresponding papers and studies supporting this. However, by reading previously published literature, we know that the glycolysis pathway can proceed step by step, which means that even if each rate-limiting enzyme is silenced, the corresponding cells still have the possibility of survival."

"Perhaps our research group's next step, for example finding osteosarcoma-specific upstream and downstream elements that can regulate HK2 levels but are absent in normal cells, and by targeting the regulation of these elements' levels to suppress HK2 expression in osteosarcoma without affecting HK2 expression in normal cells, is a key step to better solve the problem you raised, Teacher."

"This requires an extremely massive workload; if the opportunity is suitable, and I have the chance to obtain further advanced study opportunities, I will strive and advance in this direction."

"All current evidence cannot yet prove whether knocking out this target would produce side effects exceeding the range of side effects of chemotherapy drugs currently recognized by humanity."

"Thank you, Teacher."

After Fang Ziye finished speaking, his back was faintly damp with cold sweat.

This question was truly too sharp, so sharp that if his foundation had been even slightly weaker, he might not have been able to answer at all.

But even now, Fang Ziye's answering angle was still not particularly good. But this was already everything Fang Ziye could answer.

Naturally, Fang Ziye also knew that if this question were placed before any tumor medical research group worldwide, they would all find it difficult to answer.

Who dares guarantee that even if a targeted drug for this target is found, it can ensure safety and efficacy?

If that were possible, that research group would long be famous in the industry, belonging to the top-tier big shots. Because they might have solved all problems of an entire tumor system.

Fang Ziye returned to his seat; Associate Professor Xie Jinyuan, as the defense secretary, looked at Professor Zheng Tonghui.

Zheng Tonghui nodded, hurriedly finding a reason to patch things up: "This aspect is indeed something we need to pay attention to when doing research; of course, the scope of this topic is a bit too broad."

"As a professional master's student, you were able to produce this much workload during your master's, and your reading volume is also very extensive."

"As the workload for a graduation thesis, it is definitely completely sufficient; just, I know, an outstanding person like you will definitely go into society in the future..."

Hearing Zheng Tonghui say this, Fang Ziye only then let out a slight breath of relief; he was truly afraid the other party would deliberately pick faults. Good thing the other party stopped midway, steering the question toward a nonsense direction.

Because once someone is determined not to pass you, a second defense definitely needs preparation, and also requires a cooling-off period of about half a year — that would be awkward as hell.

Although his own defense in July wouldn't affect normal doctoral enrollment, but if he ran into another stubborn idiot next time.

Causing him to lack a graduate diploma and master's degree certificate before doctoral enrollment, then doctoral study would have nothing to do with him at all.

Even if, in the future, Hubei Province Provincial Third People's Hospital basically has master's students who can't graduate, that's not what Fang Ziye needs.

The topic having reached this point, Zheng Tonghui asked one more symbolic small question, then hurriedly skipped over it.

He absolutely couldn't go too deep into the topic, treating this master's thesis defense as the kind of peer-exchange questioning — that would lead to problems.

Professor Du from the Provincial People's Hospital, also belonging to Hankou University Affiliated Hospital, therefore didn't make things difficult either, just picked a medium-difficulty question.

This question's difficulty was roughly at the level that would appear in a doctoral defense, but Professor Du had clearly thought it over deeply.

Fang Ziye answered fairly well.

……

Then came Professor Li and Professor Wu from Peking Union Medical College Hospital, and Professor Qi from Tongji Hospital, each asking a standard, by-the-book question.

But when it came to this Professor Wu from Zhongnan University Affiliated Third Hospital, Professor Wu flipped through Fang Ziye's thesis left and right, then asked: "Student, I see in your thesis, the workload for the basic cell experiment part is not small, but in the animal experiment part, you only did a tumor-bearing experiment size comparison — why didn't you think to do a sectioning and classification?"

Upon hearing this, Fang Ziye's back instantly tightened slightly.

The difficulty of this question was a bit high; although not as sharp as the question Professor Zheng Tonghui raised earlier, in reality it was to examine Fang Ziye's depth in animal experiment techniques.

And it just so happened that Fang Ziye was relatively weak in this aspect; Fang Ziye could more or less understand the corresponding meaning.

Fortunately, Fang Ziye had spare Knowledge Points.

He silently thought: Sorry, Knowledge Points, I can't keep you anymore.

Add Points!

Thus, Fang Ziye's Animal Basic Experiment Skill Proficiency instantly rose from Level 1 to Level 3 200/500!

All of Fang Ziye's Knowledge Points were completely cleared.

No matter how slow the Knowledge Point accumulation speed is afterward, graduate defense first.

Some parts about pure animal basic experiments appeared in Fang Ziye's mind, so Fang Ziye understood even more clearly what angle Professor Wu's question was coming from.

A bit tricky, but not difficult.

"Professor Wu, the angle our research group is currently studying is the effect of HK2 on osteosarcoma cells, mainly observing the growth speed of osteosarcoma cells after HK2 molecular overexpression and silence."

"It belongs to the most superficial part of HK2 research."

"Before the experiment, the osteosarcoma cell lines were already classified, belonging to MG63, U2OS, SAOS-2, HOS, all purchased from the Cell Resource Center of the Shanghai Institute of Life Sciences, Chinese Academy of Sciences; therefore, sectioning to classify osteosarcoma cell lines has little reference significance."

"If one were to section and study the mortality of visceral, bone, and brain tissue cells in experimental mice, the significance would also not be great."

"If there is drug intervention, sectioning these tissues is to observe the corresponding toxicity of the drug or implant. Our research group only involves cell-level processing, does not involve other interfering substances entering the nude mouse body, and there are no long-term residual exogenous substances."

"Therefore, the significance of conducting sectioning research is not great; we mainly observe their growth speed."

Fang Ziye replied relatively easily; this was Fang Ziye answering the purpose and significance of the sectioning operation, which was unrelated to our research group's operations.

Of course, the answer angle for this question was not limited to this.

Professor Wu asked again: if one were to section a tumor, what other operations could be done.

Therefore, Fang Ziye continued: "If one were to study tumor internal angiogenesis after sectioning, one might need to use specific markers of vascular endothelial cells."

"But this belongs to the corresponding pathway and topic of HK2 and promotion of tumor cell internal angiogenesis, which has a certain directional deviation from the experiments and research our group is doing, so it is not within the scope of our group's current research."

"It belongs to a deeper level of theoretical research on HK2's growth-promoting factors in the growth process of osteosarcoma cells, which may be the scope of our next step of discussion."

"And if it is to determine the tumor organ source, this experiment……"

Only after finishing his answer did Fang Ziye finally breathe a sigh of relief.

He cast his gaze toward his Master: Master, I held on until here; next it should be your turn to debate the scholars — these professors are all too old and cunning, I really can't hold on anymore.

During the defense stage, the teacher can help supplement; if Yuan Weihong's rank were high enough, he could even have supplemented when Zheng Tonghui raised the question, but to give the professors face, Yuan Weihong didn't speak.

So, for the next ten minutes or so, Yuan Weihong showed everyone his solid skill.

Yuan Weihong, ever since Professor Chu passed away, he became a postdoctoral without a teacher in the department; he knew he had to rely on his own efforts, so Yuan Weihong's theoretical reserve and scientific research operation reserve capability were not bragged into existence.

One who dares apply for Youth Thousand Talents, harboring such ambition, is absolutely not an incapable person.

And with the teacher's participation, Fang Ziye discovered that the other several professors, after hearing Yuan Weihong's words, concealed the various emotions on their faces, and their gazes toward Yuan Weihong also changed slightly.

This inconspicuous young Supervisor is also absolutely not to be underestimated; perhaps in a few more years he can represent Zhongnan Hospital's Senior Professional Title Group, and on the national level, display his brilliance.

And after reaching Chief Physician, the nationwide jianghu status can only be fought for by oneself; workload, work quality, technical level, depth of scientific research, essence of clinical operation — these are the greatest guarantees of whether you can receive true respect in others' eyes, or whether it's just human relations.

……

A speech finished.

Fang Ziye finally left the Demonstration Classroom with Yuan Weihong, leaving only the Defense Secretary and others to meet.

The meeting time was not long, only ten-odd minutes.

After the defense ended, Professor Deng Yong immediately went along with it, and with a group of professors did a small py transaction — that is, commercial mutual flattery.

Eating and drinking would naturally not be missed, but before that, Professor Deng Yong still took them to his office — the hardship fee and labor fee had to be paid……

And when Xie Jinyuan came out, he merely nodded at Yuan Weihong.

Yuan Weihong and Fang Ziye each relaxed a breath.

"Master Master, Senior Brother, come over for a photo." At this moment, Jie Han held up the camera, Lan Tianluo was moving a stool, letting Yuan Weihong sit, Fang Ziye stand at the side, and they properly took a Supervisor-and-student group photo.

The two then just waited for the Defense Committees to come out, and together with Fang Ziye and Yuan Weihong, take a group photo with the defense red-background banner; the defense procedure, at this point, came to a conclusion.

Next, is simply the Teacher Appreciation Banquet.

This Teacher Appreciation Banquet was very simple, paid for by Fang Ziye and Sun Shaoqing together, thanking the Person of Gratitude for the kindness of support, thanking the Person of Gratitude for the care, thanking the past teacher-student relationship, continuing a lifetime of teacher-student bond.

A bit expensive; he and Senior Brother each needed to spend around 6-8k.

But this money is far from making up for the teacher's usual expense of treating guests to meals; it's not deliberately making things difficult.

(Chapter End)