Into Unscientific

"Native donkey?"

In the ward.

Hearing the word that came out of Xu Yun's mouth.

Lao Guo, who was sitting upright in his seat, suddenly showed a look that was so true.

It really is a donkey.

Xu Yun was squeezed like a donkey in the capital, and Xu Yun was squeezed like a donkey like a donkey. Why do you feel a little happy?

Then he paused, pulled his mind back to reality, and asked Xu Yun again:

"Xiao Han, it's true that donkey cells are easier to obtain than human cells, but can this thing really detect DNA differences?"

"...Could it be that you usually eat too much donkey hair and feel resentful, so you want to get revenge?"

At the end, Lao Guo's expression was slightly strange.

Xu Yun has often persecuted the local donkeys in the base in the past few days. The typical one is the donkey pulp film produced by the previous "Zhu Xianjian" project.

As far as Lao Guo knows, the hundreds of donkeys in the base can't even make up twenty hairs

But opposite him, Xu Yun seriously shook his head and explained:

"Guo Gong, I didn't lie to you, the genes of local donkeys are really different from those of foreign donkeys."

"Otherwise, why can the apical secretion of our local donkeys produce that kind of film, but foreign donkeys can't?"

Xu Yun really didn't intend to take revenge this time.

When talking about the expansion and cultivation of Yi'an bacteria, Xu Yun and his good friend Qiu Sheng once talked about two papers.

That is 10.13881/j.cnki.hljxmsy.2021.02.0100 and 10.28502/n.cnki.nkjrb.2014.007254.

The topic of the dissertation took place in 2014.

At that time, under the leadership of Huaxia Gene Bank, Academician Yang Huanming of the Chinese Academy of Sciences once organized a gene sequencing of donkeys, which was also the world's first large-scale donkey genome project.

In the subsequent detection process, the detection team has discovered many very strange situations.

For example.

Native donkeys produce small amounts of calcium thioglycolate, which is an ingredient in hair loss agents, in their bodies.

Another example is that they found that in native donkeys, there will be a Light Point phenotype, referred to as LP phenotype.

under this phenotype.

Mutants of the MC1R gene not only affect the hair, but also affect the amplification of the CDS sequence of the PepT1 gene.

This directly leads to a very strange ratio of Young's modulus of elasticity in donkey hair, and it is quite obvious.

For example, when the relative humidity increased from 0 to 100%, the axial swelling of donkey hair was only 1%.

However, the ratio of Young's modulus to shear modulus decreased from 217:1 to 15:1.

In addition,

A pentose phosphate pathway product with 225 differential metabolites from the high tenderness group was also detected on the hair of the native donkey. The results of this study were also published in the sub-journal of Nature.

Therefore, these phenotypes can be used as test points in the DNA sequencing process.

In a sense.

It is even easier for native and foreign donkeys to detect this phenotype than normal humans and tumors.

"."

After hearing Xu Yun's words.

The expression on Lao Guo's face also became hesitant.

seem

Does it make sense?

After all, in order to ensure the "exclusive agency rights" of the donkey pulp film, the rabbits did experiment with various types of foreign donkeys.

Such as Pakistani donkeys, Neon donkeys, Egyptian donkeys, etc.

But after rounds of experiments, it is true that only local donkeys can produce the donkey pulp film that meets the requirements—otherwise, the rabbits would not have the confidence to trade it.

If it is explained from a genetic point of view, it seems that it can indeed be explained?

Then he pondered for a moment, decided to put the matter aside, and looked at Xu Yun again:

"Xiao Han, since the problem of DNA testing can be solved with a local donkey, then you can finish the rest of the things you need."

"If the conditions and equipment at the base meet the requirements, then we will start researching immediately. If there is still something missing, then contact the capital as soon as possible to supplement it."

Xu Yun hummed immediately when he heard the words, thought for a moment, and explained:

"In addition to the structure and target, the rest of the targeted drug is the enzymes and reagents in each link, which involves a lot of chemical steps."

"After all, if the drug and the target want to be combined, some specific enzymes must be needed for recognition and binding. Also, if PCR technology wants to complete the amplification, it also needs DNA polymerase."

As soon as Xu Yun finished speaking.

Lao Guo nodded, expressing his understanding.

Although he has never been exposed to the concept of targeted drugs before, he still knows about enzymes.

The discovery of enzymes can be traced back to 1897, when German chemist Buschner extracted brewing enzymes that can ferment alcohol from ground yeast cells.

From then on.

The concept of enzymes has entered the field of vision of biology.

Then in 1930.

The biochemist Northrup and others across the sea isolated and purified pepsin, which proved that the essence of the enzyme is protein.

Follow the normal historical trajectory.

In three years, Northrup would be awarded the Nobel Prize for this discovery.

Today, the enzyme production technology in the chemical industry has developed to a level that is barely self-contained, even in China.

So when Lao Guo heard Xu Yun mention the targeted enzyme, he quickly followed his rhythm.

Then Xu Yun paused, then raised his index finger again:

"First of all, let's talk about the enzymes needed for PCR. In fact, there is already a precedent for the extraction of this enzyme in Europe, mainly from Escherichia coli."

"The enzyme can be obtained by culturing, centrifuging and extracting E. coli."

well known.

The basic principle of PCR technology is through the complementary pairing of primers and DNA template strands.

Then, in the PCR reaction system, the catalysis of the enzyme is used to amplify the template DNA to a specified multiple.

The first step of the PCR reaction is to separate the double-stranded DNA into two single strands, and then pair the two ends of the DNA with primers to form a starting structure of double-stranded DNA.

next.

The auxiliary enzyme starts to synthesize the DNA strand down from the starting structure of the double-stranded DNA through DNA polymerization.

Taq enzyme is commonly used in later generations. It is extracted from Thermus aquaticus, and its protein has a strong ability to resist high temperature.

But on the other hand.

Its extraction technology requirements are very high, and a relatively complete extraction process will not appear until the end of the 1980s.

It's a coincidence.

In his previous life, when Xu Yun was writing a novel called "The Empire of Science and Technology Starts from Local Donkeys", he happened to write about hand rubbing PCR technology.

As a result, I met a reader at that time. Xu Yun hadn't finished writing the plot yet, and kept asking Taq enzyme how to solve it.

This is very typical talking from the perspective of God, because Xu Yun tmd didn't plan to use Taq enzyme at all.

Compared with Taq enzyme, the Klenow enzyme isolated from E. coli can have the same effect.

Actually.

At the beginning of the birth of PCR technology, it was Klenow enzyme that was used.

The extraction technology of this enzyme is very simple, as long as there is a centrifuge, the rest of the steps can be easily done.

It’s just that compared with Taq enzyme, Klenow enzyme is not so resistant to high temperature and is prone to denaturation.

That is to say, in the experiment, the enzyme must be added again in each cycle, which seriously hinders the popularization and promotion of PCR technology.

But the problem is that Xu Yun doesn't plan to promote PCR technology immediately, what he needs is to use this technology to produce targeted drugs for Yang Kaiqu to treat diseases.

Just like Xu Yun's hand rubbing generator in the Northern Song Dynasty copy.

At that time, Xu Yun only needed to ensure that he could provide electricity that could complete electrolysis, and he didn't want to rub his hands on a nuclear power plant.

At that time in the Northern Song Dynasty, Lao Su, a local rich man, distributed coins, but now Xu Yun is relying on a huge country.

Although rabbits are still poor these days, there is still some money and ability to add Klenow enzymes to every cycle.

"Extract enzymes from E. coli?"

Old Guo Wenyan blinked and asked subconsciously:

"Xiao Han, centrifugation in the field of microbiology should require high-precision instruments, right?"

"It may not be a problem in Europe, but based on the current situation in our country, can we get it together in a while?"

"sure."

Xu Yun nodded very easily, his brows were not furrowed at all, and he explained confidently:

"Guo Gong, although in terms of process, it requires a shaker and a high-precision filter membrane, it may indeed be difficult to find equipment of the same standard in China."

"But on the other hand, although we don't have the same level of equipment, we have more sophisticated instruments than this."

"A more sophisticated instrument?"

Lao Guo was slightly taken aback, not following Xu Yun's train of thought for a while.

But after all, he is a top science and engineering expert, and centrifugation is also his proficiency direction, so he soon realized something:

"You mean the centrifuges and the batch of gas diffusion membranes in Jincheng 504 Factory?"

Snapped!

Xu Yun snapped his fingers again. Since his hands returned to normal, he suddenly fell in love with this gesture:

"bingo!"

That's right.

The extraction equipment that Xu Yun thought of was the centrifuge and gas diffusion membrane used to enrich uranium in Plant 504.

After officially entering the core sequence of the base.

Xu Yun was also finally informed of the [truth] of the gas diffusion membrane—although he already knew about it

This is the centrifuge used to enrich uranium, much better than any shaker.

In addition, only a part of the gas diffusion membrane was used in the Zhuxianjian project, and now there is still a thick stack in the warehouse of the 221 base.

With these two problems solved, the rest is much simpler.

For example, the eluent required for Klenow enzyme can be prepared with methanol, isopropanol, and ammonium acetate. This technology has been mastered by rabbits during the production of tetracycline hydrochloride.

Of course.

Although the growth environment of E. coli bacteria on the petri dish is actually very clean, the word does have some congenital smell.

So if nothing unexpected happens, the ice cream business of Factory 504 may be affected in the future

Then Xu Yun paused and continued:

"In addition to the Klenow enzyme for PCR, there are two sources of targeted enzymes required for targeted drugs."

"One is a synthetic metalloenzyme. I don't know the specific ingredients, but the efficiency is a little higher than the second one."

"The other is a natural enzyme, which comes from marine actinomycetes—although the place where the marine actinomycetes were found in that notebook is in the UK, as long as you spend a little time in the high latitude areas of the country, you should be able to find this kind of enzyme." Bacteria."

"Both of these two enzymes can be used as recognition enzymes for targeted drugs. If these enzymes are added on the basis of the drug structure reference paclitaxel, the remaining problems are only clinical trials."

Students who were cancer cells in their previous lives should know this.

In the development of targeted drugs, metalloenzymes are a very common class of recognition enzymes.

They use active-site metal ions for catalysis, and more strictly speaking, active-site metal ions of metalloenzymes need to form stable coordination with active-site residues and participate in related chemical reactions.

Metal ions often act as Lewis acids or redox partners and facilitate catalytic reactions by increasing the ground-state energy of reaction partners, enhancing substrate binding, or stabilizing reaction intermediates.

In the year 2023 that Xu Yun travels through.

About 70 metalloenzyme small molecule inhibitors have been officially approved for clinical use.

Most of these inhibitors have a direct coordination interaction with the active site metal ion through a specific chemical type, which is usually called a metal-binding pharmacophore. It is the MBP that many people learn to die or live.

Although Xu Yun did not give a specific formula for the sake of avoiding suspicion, there are only two metalloenzymes that can combine with the polyhydric structure of paclitaxel:

boron or zinc.

Among them, boron Xu Yun estimated that domestic technology would not be able to make a breakthrough smoothly, so zinc should be selected with a high probability in the end.

As for the second natural enzyme?

Xu Yun said it was marine actinomycetes, but he was actually referring to marizomib, a cyclic peptide compound extracted from marine sponges.

It is the first compound that can inhibit the combination of ubiquitin-conjugating enzyme UBC13 and UEV1A, and it can probably recognize and inhibit the growth of 60 tumor cell lines.

In fact, there are quite a few places in China where marizomib can be extracted, basically at higher latitudes. Probably take Shanghai as the line, and you can find corresponding targets in the ocean above Shanghai.

At the same time, in addition to marizomib, Flavopiridol that can be extracted in Sange is also a good choice.

However, in this period of time, rabbits must develop in a low-key way, so Xu Yun finally gave up this idea.

Of course.

In the development of targeted drugs, some Xu Yun can find a way to solve, and some need to bear the risk.

For example, diagnostic kits for targeted drugs, which are tools used to detect people who benefit from drugs, involve nanotechnology and CTC, and Xu Yun is really helpless in this regard.

At that time, he will at most use a specific antibody to do an enrichment test, and the accuracy will not exceed 80%.

In other words.

Even if the targeted drug is successfully produced, whether Yang Kaiqu can take it at that time and how effective it will be depends only on his own physique.

But what Xu Yun didn't know was.

In the Pharmacy Institute of the Academy of Medical Sciences far away in the capital, a few small pills have been mastered a long time ago.

That's the fourth generation quinolone

"."

After Xu Yun introduced the information.

Lao Guo glanced at Lin Yu subconsciously. Among the few people present, this one is a well-deserved expert in medicine:

"Doctor Lin, what do you think?"

This moment.

Lin Yu's expression is still a little shocked.

Although in the past period of time he had heard a lot about Xu Yun's oddly familiar story, this was the first time he had personally experienced it.

As expected of the legendary Mr. Lying Deaf

Fortunately, after all, he is also a big brother who has seen a lot of troubles, so he quickly regained his senses.

I saw him pondering for a moment, and finally a flash of determination flashed in his eyes, and said:

"Director Guo, I agree with Comrade Han Li's plan, you can give it a try!"

Although what Xu Yun said was beyond his cognition, he couldn't find any rebuttal or questionable points for the specific principles.

In addition, Yang Kaiqu's body is already extremely bad. If he doesn't try, he will definitely not be able to survive. If he tries, there may be miracles.

To put it bluntly

A dead horse is treated as a live horse doctor.

Then Lao Guo looked at Yang Kaiqu again, and said to the client:

"Comrade Kaiqu, what do you think?"

Yang Kaiqu's answer was as open-minded and calm as ever:

"Youlai, to tell you the truth, before I came to the base, I would definitely not agree to the country wasting these resources for me."

"But now that I have obsessions, I'll have the audacity to enjoy the preferential treatment for a while."

"Didn't Xiaohan just say that there will be some human clinical trials after the drug is ready? Don't look for other people or donkeys at that time, just experiment and observe on me."

"If it works, I will try my best to live on. If it doesn't work or has any side effects, it can also serve as a reference for drug development."

"Anyway, I have already written in my suicide note. After my death, my body will be donated to Southwest Medical University. The country gave me the treatment of a member of the academic department, but I haven't made many contributions. I can only repay the country in this way."

The scene was suddenly silent, and Xu Yun was filled with emotions.

Yang Kaiqu in history also said the same, and even more so. In this era, there are indeed quite a few people who have a kind of sincerity and awareness that will move future generations.

About a minute passed.

Li Jue opened his mouth to break the silence in the ward, and saw him solemnly addressing Yang Kai:

"Alright, since Comrade Kaiqu has no objections, I will start drafting the report after I return to the office."

"Comrade Kaiqu, believe me, you will definitely see the scene of the atomic bomb explosion!"

Yang Kaiqu laughed out loud:

"In that case, I'll just wait and see!"

After more than ten minutes.

Yang Kaiqu's strong body entered a sleepy state again, Li Jue and old Guo Xuyun took the initiative to leave.

Then Li Jue brought Lao Guo and Xu Yun to the factory office, and sent someone to invite Liu Youcheng from the chemical laboratory, and began to draw up the relevant report content.

Two hours later.

A telegram was transmitted to the capital.

Another hour passed.

A reply came from the capital:

[Agreed in principle to the targeted drug preparation plan, and the relevant equipment and personnel will be delivered to the base in the near future].

Targeted drug development plan.

So far on the horse!

Note:

I didn’t update it yesterday, because I drove to a laboratory to observe the reproduction of room temperature superconductivity, which is the synthesis route of the stick. I won’t talk about the specific laboratory. I will try to see if I can make a video or something.